Life | Editor’s choice Articles

13 pages, 1363 KiB

Open AccessEditor’s ChoiceArticle

The Effects of the COVID-19 Pandemic on Trends and Types of Pediatric Burn Injuries: Lessons from a National Burn Center and the Role of Strategic Resource Allocation

by Raluca Tatar, Dan Mircea Enescu, Doina Iulia Nacea, Gabriela Viorela Nițescu, Andreea Lescaie, Mihaela Pertea, Petruța Mitrache and Laura Sorina Diaconu

Life 2025, 15(4), 544; https://doi.org/10.3390/life15040544 - 26 Mar 2025

Viewed by 386

Abstract

The COVID-19 pandemic had a huge global impact on healthcare systems that affected all medical services, including burn care facilities. This paper analyzes the effects of this medical crisis on pediatric burn injuries by comparing patient data from 2019 (pre-pandemic) and 2020 (during [...] Read more.

The COVID-19 pandemic had a huge global impact on healthcare systems that affected all medical services, including burn care facilities. This paper analyzes the effects of this medical crisis on pediatric burn injuries by comparing patient data from 2019 (pre-pandemic) and 2020 (during the pandemic) at a national burn center in Romania. The study included, overall, 676 patients, out of which 412 were admitted in 2019. In 2020, the admissions decreased by 35.9% (n = 264). However, moderate and severe burns remained constant and burn severity increased in 2020, with a larger total body surface area affected on average. Surgical management rates and hospital stay duration increased in 2020 from 18% to 39% and from 7 days to 11 days, respectively. Admissions to the intensive care unit and mortality rates remained similar between 2019 and 2020. Scalds were the leading cause of burns in both years; however, in 2020, they affected a larger total body surface area. Contact burns decreased significantly in 2020 from 10.9% to 5.2%, likely due to reduced outdoor activities. The concomitant presence of SARS-CoV-2 infection and burn injuries did not have a negative impact on complication rates, surgical management approaches, or duration of hospitalization. These findings emphasize the need to preserve dedicated burn care human and material resources during global health crises in order to offer access to the best quality of care, thus ensuring optimal patient outcomes, regardless of fluctuations in admission rates. Full article

(This article belongs to the Special Issue Human Health Before, During, and After COVID-19)

► Show Figures

Figure 1

17 pages, 2959 KiB

Open AccessEditor’s ChoiceArticle

Non-Invasive Spectroscopic Determination of the Skin and Blood Carotenoids of Term and Preterm Infants in the First Month of Life and the Influence of Free Radical-Mediated Diseases

by Hanne Lademann, Maxim E. Darvin, Anna Häfke, Jürgen Lademann, Laura Wagner, Jan Däbritz and Dirk M. Olbertz

Life 2025, 15(4), 534; https://doi.org/10.3390/life15040534 - 24 Mar 2025

Viewed by 450

Abstract

Postpartum adaptation causes an increased formation of free radicals (FRs) in the organism, which can lead to development of various FR-mediated diseases (FRMDs) in the newborn. The present study investigates the kinetics of skin and blood carotenoid antioxidants in term and preterm infants [...] Read more.

Postpartum adaptation causes an increased formation of free radicals (FRs) in the organism, which can lead to development of various FR-mediated diseases (FRMDs) in the newborn. The present study investigates the kinetics of skin and blood carotenoid antioxidants in term and preterm infants and the influence of FRMD. In the first phase, a diffuse reflectance spectroscopy-based scanner was validated for non-invasive measurements of skin carotenoids in term infants (thenar eminence) by correlation with blood carotenoids via reflection spectroscopy. In the second phase, the skin and blood carotenoids of 22 term and 13 preterm infants with and without FRMD were assessed from birth until discharge. It could be shown that the scanner reliably assessed carotenoids in the infants’ skin. The term and preterm infants showed similar kinetics of skin carotenoids, which increased and entered a plateau after 3–4 days. In our cohort, FRMD did not have a significant influence on skin carotenoid concentration. This was due to immature sweat glands and an insufficient excretion of carotenoids. Skin carotenoids seem to be unavailable, suggesting that they may have to be supplemented in infants with FRMD. Blood carotenoid concentrations tended to be lower in preterm infants and infants with FRMD compared to healthy term infants. Full article

(This article belongs to the Special Issue Current Research on Dermatology: Pathology, Clinical Manifestation, Investigation and Therapy: 2nd Edition)

► Show Figures

Figure 1

15 pages, 3194 KiB

Open AccessEditor’s ChoiceReview

Neural Mechanisms of Cognitive Behavioral Therapy Efficacy in Anxiety Disorders: A Scoping Review of fMRI-Based Studies That Tested the Dual Model

by Judith Domínguez-Pérez, Wenceslao Peñate-Castro and Francisco Luis Rivero-Pérez

Life 2025, 15(3), 493; https://doi.org/10.3390/life15030493 - 18 Mar 2025

Viewed by 1505

Abstract

Anxiety disorders are common mental health conditions characterized by excessive fear and anxiety. Cognitive behavioral therapy (CBT) has demonstrated efficacy, yet the possible neurobiological mechanisms underpinning its effects remain debated. The dual-route model offers a potential explanation by suggesting that CBT increases activation [...] Read more.

Anxiety disorders are common mental health conditions characterized by excessive fear and anxiety. Cognitive behavioral therapy (CBT) has demonstrated efficacy, yet the possible neurobiological mechanisms underpinning its effects remain debated. The dual-route model offers a potential explanation by suggesting that CBT increases activation in the brain areas responsible for emotion regulation while decreasing activation in limbic areas. This scoping review examined possible neurobiological mechanisms supporting CBT’s efficacy in anxiety disorders by exclusively reviewing studies that utilized functional magnetic resonance imaging (fMRI). The included studies published since 2018 focused on adult samples that received CBT for anxiety disorders, with pre- or post-treatment fMRI data. The data extraction followed a standardized process, with key variables, such as the study design, population, and neuroimaging findings, systematically charted. While the dual-route model explains key aspects of CBT’s neurobiological effects, the findings suggest the need for expansion to incorporate areas such as the precuneus, particularly in specific phobias and social anxiety disorder. Further research is required to refine this model and explore additional mechanisms underlying CBT’s efficacy. Full article

(This article belongs to the Special Issue Feature Paper in Physiology and Pathology: 2nd Edition)

► Show Figures

Figure 1

37 pages, 4776 KiB

Open AccessEditor’s ChoiceReview

Neuropsychiatric Manifestations of Long COVID-19: A Narrative Review of Clinical Aspects and Therapeutic Approaches

by Olga Adriana Caliman-Sturdza, Roxana Gheorghita and Andrei Lobiuc

Life 2025, 15(3), 439; https://doi.org/10.3390/life15030439 - 11 Mar 2025

Viewed by 3167

Abstract

The COVID-19 (C-19) pandemic has highlighted the significance of understanding the long-term effects of this disease on the quality of life of those infected. Long COVID-19 (L-C19) presents as persistent symptoms that continue beyond the main illness period, usually lasting weeks to years. [...] Read more.

The COVID-19 (C-19) pandemic has highlighted the significance of understanding the long-term effects of this disease on the quality of life of those infected. Long COVID-19 (L-C19) presents as persistent symptoms that continue beyond the main illness period, usually lasting weeks to years. One of the lesser-known but significant aspects of L-C19 is its impact on neuropsychiatric manifestations, which can have a profound effect on an individual’s quality of life. Research shows that L-C19 creates neuropsychiatric issues such as mental fog, emotional problems, and brain disease symptoms, along with sleep changes, extreme fatigue, severe head pain, tremors with seizures, and pain in nerves. People with cognitive problems plus fatigue and mood disorders experience great difficulty handling everyday activities, personal hygiene, and social interactions. Neuropsychiatric symptoms make people withdraw from social activity and hurt relationships, thus causing feelings of loneliness. The unpredictable state of L-C19 generates heavy psychological pressure through emotional suffering, including depression and anxiety. Neuropsychiatric changes such as cognitive impairment, fatigue, and mood swings make it hard for people to work or study effectively, which decreases their output at school or work and lowers their job contentment. The purpose of this narrative review is to summarize the clinical data present in the literature regarding the neuropsychiatric manifestations of L-C19, to identify current methods of diagnosis and treatment that lead to correct management of the condition, and to highlight the impact of these manifestations on patients’ quality of life. Full article

(This article belongs to the Special Issue Human Health Before, During, and After COVID-19)

► Show Figures

Figure 1

25 pages, 1535 KiB

Open AccessEditor’s ChoiceReview

Traumatic Brain Injury and Artificial Intelligence: Shaping the Future of Neurorehabilitation—A Review

by Seun Orenuga, Philip Jordache, Daniel Mirzai, Tyler Monteros, Ernesto Gonzalez, Ahmed Madkoor, Rahim Hirani, Raj K. Tiwari and Mill Etienne

Life 2025, 15(3), 424; https://doi.org/10.3390/life15030424 - 7 Mar 2025

Cited by 1 | Viewed by 4763

Abstract

Traumatic brain injury (TBI) is a leading cause of disability and death globally, presenting significant challenges for diagnosis, prognosis, and treatment. As healthcare technology advances, artificial intelligence (AI) has emerged as a promising tool in enhancing TBI rehabilitation outcomes. This literature review explores [...] Read more.

Traumatic brain injury (TBI) is a leading cause of disability and death globally, presenting significant challenges for diagnosis, prognosis, and treatment. As healthcare technology advances, artificial intelligence (AI) has emerged as a promising tool in enhancing TBI rehabilitation outcomes. This literature review explores the current and potential applications of AI in TBI management, focusing on AI’s role in diagnostic tools, neuroimaging, prognostic modeling, and rehabilitation programs. AI-driven algorithms have demonstrated high accuracy in predicting mortality, functional outcomes, and personalized rehabilitation strategies based on patient data. AI models have been developed to predict in-hospital mortality of TBI patients up to an accuracy of 95.6%. Furthermore, AI enhances neuroimaging by detecting subtle abnormalities that may be missed by human radiologists, expediting diagnosis and treatment decisions. Despite these advances, ethical considerations, including biases in AI algorithms and data generalizability, pose challenges that must be addressed to optimize AI’s implementation in clinical settings. This review highlights key clinical trials and future research directions, emphasizing AI’s transformative potential in improving patient care, rehabilitation, and long-term outcomes for TBI patients. Full article

(This article belongs to the Special Issue Traumatic Brain Injury (TBI))

► Show Figures

Figure 1

20 pages, 615 KiB

Open AccessEditor’s ChoiceSystematic Review

Factors Associated with Post-COVID Cardiac Conditions and Potential Prognostic Factors: A Systematic Review

by Lidian Franci Batalha Santa Maria, Josicélia Estrela Tuy Batista, Virginia Kagure Wachira, Wenderval Borges Carvalho Junior, Alexandre Anderson de Sousa Munhoz Soares, Isis Polianna Silva Ferreira de Carvalho and Henry Maia Peixoto

Life 2025, 15(3), 388; https://doi.org/10.3390/life15030388 - 28 Feb 2025

Viewed by 1230

Abstract

Cardiac conditions are a significant category of post-COVID conditions. The objective of this study was to synthesise the evidence on the factors associated with the development of post-COVID cardiac conditions, the frequency of clinical outcomes in affected patients, and the potential prognostic factors. [...] Read more.

Cardiac conditions are a significant category of post-COVID conditions. The objective of this study was to synthesise the evidence on the factors associated with the development of post-COVID cardiac conditions, the frequency of clinical outcomes in affected patients, and the potential prognostic factors. A systematic review was conducted using the databases EBSCOhost, MEDLINE via PubMed, BVS, and Embase, covering studies from 2019 to December 2023. A total of 8343 articles were identified, and seven met the eligibility criteria for data extraction. The protective effect of vaccination stood out among the associated factors, showing a reduced risk of developing post-COVID cardiac conditions. Conversely, COVID-19 reinfections were associated with an increased risk of cardiovascular outcomes. Regarding the main outcomes in these patients, most recovered, although some cases persisted beyond 200 days of follow-up. The study included in the analysis of prognostic factors reported that the four children who did not recover by the end of the study were between two and five years old and had gastrointestinal symptoms during the illness. The COVID-19 vaccination regimen reduces the risk of developing post-COVID cardiac conditions. Public health policies promoting immunisation should be encouraged to prevent SARS-CoV-2 infections and reinfections. Full article

(This article belongs to the Collection COVID-19 and Life)

► Show Figures

Figure 1

15 pages, 773 KiB

Open AccessEditor’s ChoiceArticle

The Role of the Subcostal Transversus Abdominis Plane Block in Facilitating Operating Room Extubation After Living Donor Liver Transplantation for Hepatocellular Carcinoma: A Propensity Score-Matching Analysis

by Jaewon Huh and Min Suk Chae

Life 2025, 15(2), 297; https://doi.org/10.3390/life15020297 - 14 Feb 2025

Cited by 1 | Viewed by 733

Abstract

Background: Effective pain management is essential to early extubation and recovery in living donor liver transplantation (LDLT). The subcostal transversus abdominis plane (TAP) block has emerged as a potential strategy to address postoperative pain while reducing opioid consumption. This study evaluated the effectiveness [...] Read more.

Background: Effective pain management is essential to early extubation and recovery in living donor liver transplantation (LDLT). The subcostal transversus abdominis plane (TAP) block has emerged as a potential strategy to address postoperative pain while reducing opioid consumption. This study evaluated the effectiveness of the TAP block in facilitating early extubation in the OR and examined its impact on re-intubation rates, postoperative fentanyl requirements, and pain intensity upon ICU admission to determine its role in perioperative pain management. Methods: This retrospective cohort study included adult patients who underwent LDLT for hepatocellular carcinoma within the Milan criteria. Propensity score matching was performed to compare outcomes between patients who received the subcostal TAP block and those who did not. The primary outcome was the rate of successful extubation in the operating room (OR). Secondary outcomes included re-intubation rates, postoperative fentanyl requirements, and peak numeric rating scale (NRS) pain scores upon ICU admission. Results: The subcostal TAP block was associated with a significantly higher rate of successful OR extubation compared with no TAP block. Multivariable analysis revealed that the TAP block independently increased the likelihood of successful extubation. Patients receiving the TAP block required less fentanyl for pain management and demonstrated lower peak NRS pain scores upon ICU admission. No complications related to the TAP block were observed, underscoring its safety in this high-risk population. Conclusions: The subcostal TAP block facilitates early OR extubation by effectively managing postoperative pain and reducing opioid requirements, promoting smoother recovery without increasing adverse events. These findings support its inclusion in multimodal analgesia protocols for optimizing perioperative outcomes in LDLT patients. Full article

(This article belongs to the Special Issue Gastrointestinal Health: Clinical Research and Therapeutic Innovations)

► Show Figures

Figure 1

25 pages, 331 KiB

Open AccessEditor’s ChoiceReview

Breaking Barriers to an HIV-1 Cure: Innovations in Gene Editing, Immune Modulation, and Reservoir Eradication

by Ana Borrajo

Life 2025, 15(2), 276; https://doi.org/10.3390/life15020276 - 11 Feb 2025

Cited by 1 | Viewed by 3506

Abstract

Recent advances in virology, particularly in the study of HIV-1, have significantly progressed the pursuit of a definitive cure for the disease. Emerging therapeutic strategies encompass innovative gene-editing technologies, immune-modulatory interventions, and next-generation antiretroviral agents. Efforts to eliminate or control viral reservoirs have [...] Read more.

Recent advances in virology, particularly in the study of HIV-1, have significantly progressed the pursuit of a definitive cure for the disease. Emerging therapeutic strategies encompass innovative gene-editing technologies, immune-modulatory interventions, and next-generation antiretroviral agents. Efforts to eliminate or control viral reservoirs have also gained momentum, with the aim of achieving durable viral remission without the continuous requirement for antiretroviral therapy. Despite these promising developments, critical challenges persist in bridging the gap between laboratory findings and clinical implementation. This review provides a comprehensive analysis of recent breakthroughs, ongoing clinical trials, and the barriers that must be addressed to translate these advancements into effective treatments, emphasizing the multifaceted approaches being pursued to achieve a curative solution for HIV-1 infection. Full article

(This article belongs to the Special Issue Emerging Knowledge on Human Immunodeficiency Virus)

29 pages, 398 KiB

Open AccessEditor’s ChoiceArticle

Extracting Knowledge from Machine Learning Models to Diagnose Breast Cancer

by José Manuel Martínez-Ramírez, Cristobal Carmona, María Jesús Ramírez-Expósito and José Manuel Martínez-Martos

Life 2025, 15(2), 211; https://doi.org/10.3390/life15020211 - 31 Jan 2025

Viewed by 1010

Abstract

This study explored the application of explainable machine learning models to enhance breast cancer diagnosis using serum biomarkers, contrary to many studies that focus on medical images and demographic data. The primary objective was to develop models that are not only accurate but [...] Read more.

This study explored the application of explainable machine learning models to enhance breast cancer diagnosis using serum biomarkers, contrary to many studies that focus on medical images and demographic data. The primary objective was to develop models that are not only accurate but also provide insights into the factors driving predictions, addressing the need for trustworthy AI in healthcare. Several classification models were evaluated, including OneR, JRIP, the FURIA, J48, the ADTree, and the Random Forest, all of which are known for their explainability. The dataset included a variety of biomarkers, such as electrolytes, metal ions, marker proteins, enzymes, lipid profiles, peptide hormones, steroid hormones, and hormone receptors. The Random Forest model achieved the highest accuracy at 99.401%, followed closely by JRIP, the FURIA, and the ADTree at 98.802%. OneR and J48 achieved 98.204% accuracy. Notably, the models identified oxytocin as a key predictive biomarker, with most models featuring it in their rules. Other significant parameters included GnRH,

β

-endorphin, vasopressin, IRAP, and APB, as well as factors like iron, cholinesterase, the total protein, progesterone, 5-nucleotidase, and the BMI, which are considered clinically relevant to breast cancer pathogenesis. This study discusses the roles of the identified parameters in cancer development, thus underscoring the potential of explainable machine learning models for enhancing early breast cancer diagnosis by focusing on explainability and the use of serum biomarkers.The combination of both can lead to improved early detection and personalized treatments, emphasizing the potential of these methods in clinical settings. The identified markers also provide additional research and therapeutic targets for breast cancer pathogenesis and a deep understanding of their interactions, advancing personalized approaches to breast cancer management. Full article

(This article belongs to the Special Issue New Insights into Breast Cancer: Current Controversies and Future Perspectives)

► Show Figures

Figure 1

15 pages, 1153 KiB

Open AccessEditor’s ChoiceReview

Use of Live Biopreservatives and Bacteriophages to Enhance the Safety of Meat Products

by Cristina Rodríguez-Marca, Cristina Domenech-Coca, Miho Nakamura, Nàdia Ortega-Olivé and Pere Puigbò

Life 2025, 15(2), 197; https://doi.org/10.3390/life15020197 - 28 Jan 2025

Cited by 1 | Viewed by 1442

Abstract

Critical health considerations for both raw and processed meats include addressing bacterial spoilage and ensuring safety. Nitrites and nitrates are widely used in the meat industry to enhance color and flavor and extend shelf life. However, health concerns linked to their use make [...] Read more.

Critical health considerations for both raw and processed meats include addressing bacterial spoilage and ensuring safety. Nitrites and nitrates are widely used in the meat industry to enhance color and flavor and extend shelf life. However, health concerns linked to their use make reducing nitrites and nitrates in meat production a significant challenge with potential benefits for both the food industry and consumer health. This challenge has been addressed with the use of biopreservatives, i.e., substances extracted from natural sources or produced by fermentation that can enhance food quality and safety. In this article, we assess the use of live biopreservatives (LBs), defined here as microorganisms that produce antimicrobial substances that can be used to preserve and extend the shelf life of food. Moreover, the potential synergistic effects of LBs with bacteriophages and biodegradable food packaging for meat is also explored. This innovative combination offers a comprehensive approach to meat preservation, enhancing both microbial control and sustainability. Overall, the inclusion of LBs extends the shelf life of meat products through bacteriostatic mechanisms, whereas bacteriophages offer direct (lytic) action against pathogens. Enhancing meat preservation and safety with mixed microbe-mediated strategies requires deeper empirical and theoretical insights and further revision of laws and ethical considerations. Full article

(This article belongs to the Special Issue Antimicrobial Innovations)

► Show Figures

Figure 1

24 pages, 2805 KiB

Open AccessEditor’s ChoiceArticle

Dairy Wastewaters to Promote Mixotrophic Metabolism in Limnospira (Spirulina) platensis: Effect on Biomass Composition, Phycocyanin Content, and Fatty Acid Methyl Ester Profile

by Luca Baraldi, Luca Usai, Serenella Torre, Giacomo Fais, Mattia Casula, Debora Dessi, Paola Nieri, Alessandro Concas and Giovanni Antonio Lutzu

Life 2025, 15(2), 184; https://doi.org/10.3390/life15020184 - 26 Jan 2025

Cited by 2 | Viewed by 1789

Abstract

This study explores the mixotrophic cultivation of Limnospira platensis using dairy byproducts, specifically scotta whey (SW), buttermilk wastewater (BMW), and dairy wastewater (DWW), to promote biomass production and enhance the composition of bioactive compounds. By assessing various concentrations (1%, 2%, and 4% v [...] Read more.

This study explores the mixotrophic cultivation of Limnospira platensis using dairy byproducts, specifically scotta whey (SW), buttermilk wastewater (BMW), and dairy wastewater (DWW), to promote biomass production and enhance the composition of bioactive compounds. By assessing various concentrations (1%, 2%, and 4% v v⁻¹) of these byproducts in a modified growth medium, this study aims to evaluate their effect on L. platensis growth, phycocyanin (C-PC) content, and fatty acid methyl ester (FAME) profiles. The results show that the optimal biomass production was achieved with 2% scotta and dairy wastewater, reaching maximum concentrations of 3.30 g L⁻¹ and 3.19 g L⁻¹, respectively. Mixotrophic cultivation led to increased C-PC yields, especially in buttermilk and dairy wastewater treatments, highlighting the potential for producing valuable pigments. Additionally, the FAME profiles indicated minimal changes compared to the control, with oleic and γ-linolenic acids being dominant in mixotrophic conditions. These findings support the viability of utilizing dairy byproducts for sustainable L. platensis cultivation, contributing to a circular bioeconomy while producing bioactive compounds of nutritional and commercial interest. Full article

(This article belongs to the Special Issue Algae—a Step Forward in the Sustainability of Resources: 2nd Edition)

► Show Figures

Figure 1

13 pages, 1131 KiB

Open AccessEditor’s ChoiceArticle

Divergent Patterns of Metabolite Expression in Red Seaweeds (Devaleraea mollis and Palmaria hecatensis) Following Nitrate and Ammonium Supplementation

by Schery Umanzor, Jae Woo Jung, Muriel Dittrich, Jang K. Kim, Patrick Tomco, Zachary C. Redman and Monica Brandhuber

Life 2025, 15(2), 143; https://doi.org/10.3390/life15020143 - 21 Jan 2025

Viewed by 1192

Abstract

This study explores species-specific metabolic responses to different nitrogen-rich formulations in Devaleraea mollis and Palmaria hecatensis, highlighting distinct adaptive strategies. We evaluated the effects of Von Stosch Enrichment (VSE, nitrate-only), F/2 (nitrate-only), and Jack’s Special (JS, nitrate and ammonium) on metabolic profiles. [...] Read more.

This study explores species-specific metabolic responses to different nitrogen-rich formulations in Devaleraea mollis and Palmaria hecatensis, highlighting distinct adaptive strategies. We evaluated the effects of Von Stosch Enrichment (VSE, nitrate-only), F/2 (nitrate-only), and Jack’s Special (JS, nitrate and ammonium) on metabolic profiles. D. mollis exhibited elevated energy storage and growth-related metabolites, with JS enhancing creatine production for energy storage and regeneration, alongside increased DNA/RNA synthesis and cell division activity. This suggests D. mollis prioritizes rapid growth and energy demands, supporting broader ecological adaptability. Conversely, P. hecatensis showed higher expression of metabolites linked to amino acid metabolism and protein synthesis, indicating a focus on efficient nitrogen use for protein production, likely advantageous in low-light, high-turbidity conditions. Nitrogen sources significantly influence amino acid metabolism, with JS promoting broader amino acid production and VSE and F/2 stimulating specific metabolites. These species-specific metabolic patterns underscore the flexibility of D. mollis in energy use versus adaptations of P. hecatensis to protein synthesis pathways. These findings highlight species-specific nutrient formulations as essential for optimizing seaweed growth and metabolic traits in aquaculture. Full article

(This article belongs to the Special Issue Algae—a Step Forward in the Sustainability of Resources: 2nd Edition)

► Show Figures

Figure 1

27 pages, 856 KiB

Open AccessEditor’s ChoiceReview

Alzheimer’s Disease and Porphyromonas gingivalis: Exploring the Links

by Ivana Shawkatova, Vladimira Durmanova and Juraj Javor

Life 2025, 15(1), 96; https://doi.org/10.3390/life15010096 - 14 Jan 2025

Cited by 1 | Viewed by 3961

Abstract

Recent research highlights compelling links between oral health, particularly periodontitis, and systemic diseases, including Alzheimer’s disease (AD). Although the biological mechanisms underlying these associations remain unclear, the role of periodontal pathogens, particularly Porphyromonas gingivalis, has garnered significant attention. P. gingivalis, a [...] Read more.

Recent research highlights compelling links between oral health, particularly periodontitis, and systemic diseases, including Alzheimer’s disease (AD). Although the biological mechanisms underlying these associations remain unclear, the role of periodontal pathogens, particularly Porphyromonas gingivalis, has garnered significant attention. P. gingivalis, a major driver of periodontitis, is recognized for its potential systemic effects and its putative role in AD pathogenesis. This review examines evidence connecting P. gingivalis to hallmark AD features, such as amyloid β accumulation, tau hyperphosphorylation, neuroinflammation, and other neuropathological features consistent with AD. Virulence factors, such as gingipains and lipopolysaccharides, were shown to be implicated in blood–brain barrier disruption, neuroinflammation, and neuronal damage. P. gingivalis-derived outer membrane vesicles may serve to disseminate virulence factors to brain tissues. Indirect mechanisms, including systemic inflammation triggered by chronic periodontal infections, are also supposed to exacerbate neurodegenerative processes. While the exact pathways remain uncertain, studies detecting P. gingivalis virulence factors and its other components in AD-affected brains support their possible role in disease pathogenesis. This review underscores the need for further investigation into P. gingivalis-mediated mechanisms and their interplay with host responses. Understanding these interactions could provide critical insights into novel strategies for reducing AD risk through periodontal disease management. Full article

(This article belongs to the Special Issue Alzheimer’s Disease: Recent Developments in Pathogenesis, Diagnosis, and Therapy)

► Show Figures

Figure 1

15 pages, 3560 KiB

Open AccessEditor’s ChoiceArticle

Gut Microbiota Regulates the Homeostasis of Dendritic Epidermal T Cells

by Jinwoo Chung, Joo-Chan Lee, Hanna Oh, Yesung Kim, Suin Lim, Chanu Lee, Yoon-Gyu Shim, Eun-Chong Bang and Jea-Hyun Baek

Life 2024, 14(12), 1695; https://doi.org/10.3390/life14121695 - 21 Dec 2024

Viewed by 1156

Abstract

Dendritic epidermal T cells (DETCs) are a γδ T cell subset residing in the skin epidermis. Although they have been known for decades, the fate of DETCs has largely remained enigmatic. Recent studies have highlighted the relationship between the gut microbiome and γδ [...] Read more.

Dendritic epidermal T cells (DETCs) are a γδ T cell subset residing in the skin epidermis. Although they have been known for decades, the fate of DETCs has largely remained enigmatic. Recent studies have highlighted the relationship between the gut microbiome and γδ T cells in various epithelial and non-epithelial tissues, such as the small intestine, lung, liver, gingiva, and testis. While the skin microbiota has been shown to impact skin γδ T cells, a direct relationship between the gut microbiota and DETCs remains unexplored. In this study, we investigated whether DETCs are regulated by the gut microbiota in the steady-state skin epidermis. We examined the occurrence of DETCs in Balb/c mice, which have a skin epidermis barely populated with DETCs, compared to C57BL/6 mice, under different housing conditions. Our findings reveal that local skin inflammation markedly increases DETC numbers in the ear epidermis of Balb/c mice and that DETCs are activated by environmental factors. Furthermore, an investigation of the gut microbiota under different housing conditions revealed distinct microbial compositions and functional profiles. Taken together, these results suggest a strong connection between DETCs and gut microbiota. Full article

(This article belongs to the Special Issue Microbiota in Health and Disease)

► Show Figures

Figure 1

12 pages, 2269 KiB

Open AccessEditor’s ChoiceArticle

Immunomodulatory Properties of Multi-Strain Postbiotics on Human CD14⁺ Monocytes

by Kyle D. Roberts, Sadia Ahmed, Erin San Valentin, Luca Di Martino, Thomas S. McCormick and Mahmoud A. Ghannoum

Life 2024, 14(12), 1673; https://doi.org/10.3390/life14121673 - 17 Dec 2024

Cited by 1 | Viewed by 1512

Abstract

The ability of probiotics, comprising live microbiota, to modulate the composition of intestinal microbiomes has been connected to modulation of the central nervous system (Gut–Brain axis), neuroendocrine system (Gut–Skin axis), and immune response (Gut–Immune axis). Less information is known regarding the ability of [...] Read more.

The ability of probiotics, comprising live microbiota, to modulate the composition of intestinal microbiomes has been connected to modulation of the central nervous system (Gut–Brain axis), neuroendocrine system (Gut–Skin axis), and immune response (Gut–Immune axis). Less information is known regarding the ability of postbiotics (cell wall components and secreted metabolites derived from live organisms) to regulate host immunity. In the present study, we tested postbiotics comprising single strains of bacteria and yeast (Lactobacillus acidophilus 16axg, Lacticaseibacillus rhamnosus 18fx, Saccharomyces cerevisiae var. boulardii 16mxg) as well as combinations of multiple strains for their ability to stimulate cytokine production by human CD14⁺ monocytes. We quantified cytokine gene and protein expression levels in monocytes following stimulation with postbiotics. Both heat-killed L. acidophilus and L. rhamnosus stimulated naïve monocytes without significant differences between them. Heat-killed S. boulardii stimulated less cytokine production compared to postbiotic bacteria at the same concentration. Interestingly, the addition of heat-killed yeast to heat-killed L. acidophilus and L. rhamnosus resulted in an enhancement of immune stimulation. Thus, heat-killed postbiotics have immune-modulating potential, particularly when bacteria and yeast are combined. This approach may hold promise for developing targeted interventions that can be fine-tuned to modulate host immune response with beneficial health impact. Full article

(This article belongs to the Section Microbiology)

► Show Figures

Figure 1

14 pages, 261 KiB

Open AccessEditor’s ChoiceArticle

Learning Curve of First-Trimester Detailed Cardiovascular Ultrasound Screening by Moderately Experienced Obstetricians in 3509 Consecutive Unselected Pregnancies with Fetal Follow-Up

by Tibor Elekes, Gyula Csermely, Krisztina Kádár, László Molnár, Gábor Keszthelyi, Andrea Hozsdora, Miklós Vizer, Marianna Török, Petra Merkely and Szabolcs Várbíró

Life 2024, 14(12), 1632; https://doi.org/10.3390/life14121632 - 9 Dec 2024

Viewed by 1150

Abstract

Our primary objective was to assess the effectiveness of detailed cardiovascular ultrasound screening during the first trimester, which was performed by obstetricians with intermediate experience. We collected first-trimester fetal cardiac screening data from an unselected pregnant population at RMC-Fetal Medicine Center during a [...] Read more.

Our primary objective was to assess the effectiveness of detailed cardiovascular ultrasound screening during the first trimester, which was performed by obstetricians with intermediate experience. We collected first-trimester fetal cardiac screening data from an unselected pregnant population at RMC-Fetal Medicine Center during a study period spanning from 1 January 2010, to 31 January 2015, in order to analyze our learning curve. A pediatric cardiologist performed a follow-up assessment in cases where the examining obstetrician determined that the fetal cardiac screening results were abnormal or high-risk. Overall, 42 (0.88%) congenital heart abnormalities were discovered prenatally out of 4769 fetuses from 4602 pregnant women who had at least one first-trimester cardiac ultrasonography screening. In total, 89.2% of the major congenital heart abnormalities (27 of 28) in the following fetuses were discovered (or at least highly suspected) at the first-trimester screening and subsequent fetal echocardiography by the pediatric cardiology specialist. Of these, 96.4% were diagnosed prenatally. According to our results, the effectiveness of first-trimester fetal cardiovascular ultrasound screening conducted by moderately experienced obstetricians in an unselected (’routine’) pregnant population may reach as high as 90% in terms of major congenital heart defects, provided that equipment, quality assurance, and motivation are appropriate. Full article

(This article belongs to the Special Issue Obstetrics and Gynecology Medicine: Go From Bench to Bedside)

15 pages, 5384 KiB

Open AccessEditor’s ChoiceArticle

Intrauterine Growth Restriction Alters Postnatal Hippocampal Dentate Gyrus Neuron and Microglia Morphology and Cytokine/Chemokine Milieu in Mice

by Frank A. Strnad, Ashley S. Brown, Matthew Wieben, Emilio Cortes-Sanchez, Megan E. Williams and Camille M. Fung

Life 2024, 14(12), 1627; https://doi.org/10.3390/life14121627 - 9 Dec 2024

Viewed by 1138

Abstract

Infants born with intrauterine growth restriction (IUGR) have up to a five-fold higher risk of learning and memory impairment than those with normal growth. Using a mouse model of hypertensive diseases of pregnancy (HDP) to replicate uteroplacental insufficiency (UPI), we have previously shown [...] Read more.

Infants born with intrauterine growth restriction (IUGR) have up to a five-fold higher risk of learning and memory impairment than those with normal growth. Using a mouse model of hypertensive diseases of pregnancy (HDP) to replicate uteroplacental insufficiency (UPI), we have previously shown that UPI causes premature embryonic hippocampal dentate gyrus (DG) neurogenesis in IUGR offspring. The DG is a brain region that receives the first cortical information for memory formation. In the current study, we examined the postnatal DG neuron morphology one month after delivery (P28) using recombinant adeno-associated viral labeling of neurons. We also examined DG microglia’s morphology using immunofluorescent histochemistry and defined the hippocampal cytokine/chemokine milieu using Luminex xMAP technology. We found that IUGR preserved the principal dendrite lengths but decreased the dendritic branching and volume of DG neurons. IUGR augmented DG microglial number and cell size. Lastly, IUGR altered the hippocampal cytokine/chemokine profile in a sex-specific manner. We conclude that the prematurely-generated neuronal progenitors develop abnormal morphologies postnatally in a cell-autonomous manner. Microglia appear to modulate neuronal morphology by interacting with dendrites amidst a complex cytokine/chemokine environment that could ultimately lead to adult learning and memory deficits in our mouse model. Full article

(This article belongs to the Special Issue Feature Paper in Physiology and Pathology: 2nd Edition)

► Show Figures

Figure 1

14 pages, 1412 KiB

Open AccessEditor’s ChoiceReview

Regulation of Plant Growth and Development by Melatonin

by Dawei Shi, Lejia Zhao, Ruijia Zhang and Qiaofeng Song

Life 2024, 14(12), 1606; https://doi.org/10.3390/life14121606 - 4 Dec 2024

Cited by 3 | Viewed by 1587

Abstract

Melatonin is a naturally occurring chemical with pleiotropic effects in various species. In plants, melatonin is associated with a variety of plant physiological processes, including plant growth and development, stress responses, etc. Thus, melatonin may hold promise for improving crop yields and agricultural [...] Read more.

Melatonin is a naturally occurring chemical with pleiotropic effects in various species. In plants, melatonin is associated with a variety of plant physiological processes, including plant growth and development, stress responses, etc. Thus, melatonin may hold promise for improving crop yields and agricultural sustainability. This review describes the biosynthetic mode of melatonin and its properties and summarizes its functions in growth, development, and reproduction. In addition, the role of melatonin in plants facing various stressful environments is elaborated upon, and its relationship with other phytohormones is summarized. Through this review, we recognize the problems and challenges facing melatonin research and propose some feasible solutions. Full article

(This article belongs to the Special Issue Plant Adaptation Mechanisms to Abiotic Stresses)

► Show Figures

Figure 1

9 pages, 438 KiB

Open AccessEditor’s ChoiceArticle

Effect of Continuous Intake of Lactobacillus salivarius WB21 on Tissues Surrounding Implants: A Double-Blind Randomized Clinical Trial

by Yusuke Taniguchi, Nao Suzuki, Kae Kakura, Kazunari Tanabe, Ryutaro Ito, Tadahiro Kashiwamura, Akie Fujimoto, Marie Naito, Masahiro Yoneda, Takashi Hanioka and Hirofumi Kido

Life 2024, 14(12), 1532; https://doi.org/10.3390/life14121532 - 22 Nov 2024

Viewed by 2253

Abstract

Objective: This study aimed to improve the health of peri-implant tissues through continuous intake of Lactobacillus salivarius WB21 (LSWB21) tablets. Methods: A double-blind, randomized controlled trial was conducted with 23 maintenance patients who had generally healthy oral peri-implant tissues. Participants were divided into [...] Read more.

Objective: This study aimed to improve the health of peri-implant tissues through continuous intake of Lactobacillus salivarius WB21 (LSWB21) tablets. Methods: A double-blind, randomized controlled trial was conducted with 23 maintenance patients who had generally healthy oral peri-implant tissues. Participants were divided into a test group (n = 12) receiving LSWB21 tablets and a control group (n = 11) receiving placebos. All patients took one tablet three times daily for 2 months. Evaluation measures included modified Gingival Index (mGI), modified Plaque Index (mPI), modified Bleeding Index (mBI), salivary secretory IgA, and oral symptoms assessed at baseline, 1 month, and 2 months. Results: After 2 months, significant improvements in the mGI, mPI, and mBI were observed in the test group; significant improvement in the mPI was observed in the control group. Changes in the mGI over 2 months significantly differed between the groups (p = 0.038), and multiple regression analysis confirmed the effectiveness of LSWB21 in reducing the mGI (p = 0.034). Subjective symptoms such as bad breath in the test group and tongue symptoms in the control group also significantly improved. Conclusion: Continuous intake of LSWB21 may be beneficial for stabilizing peri-implant tissue. Trial registration: UMIN000039392 (UMIN-CTR). Full article

(This article belongs to the Section Medical Research)

► Show Figures

Figure 1

14 pages, 603 KiB

Open AccessEditor’s ChoiceReview

Extremophiles and Extremophilic Behaviour—New Insights and Perspectives

by George N. Angelakis, Chrysianna Psarologaki, Stergios Pirintsos and Kiriakos Kotzabasis

Life 2024, 14(11), 1425; https://doi.org/10.3390/life14111425 - 5 Nov 2024

Cited by 3 | Viewed by 3893

Abstract

Extremophiles, throughout evolutionary time, have evolved a plethora of unique strategies to overcome hardships associated with the environments they are found in. Modifying their genome, showing a bias towards certain amino acids, redesigning their proteins, and enhancing their membranes and other organelles with [...] Read more.

Extremophiles, throughout evolutionary time, have evolved a plethora of unique strategies to overcome hardships associated with the environments they are found in. Modifying their genome, showing a bias towards certain amino acids, redesigning their proteins, and enhancing their membranes and other organelles with specialised chemical compounds are only some of those strategies. Scientists can utilise such attributes of theirs for a plethora of biotechnological and astrobiological applications. Moreover, the rigorous study of such microorganisms regarding their evolution and ecological niche can offer deep insight into science’s most paramount inquiries such as how life originated on Earth and whether we are alone in the universe. The intensification of studies involving extremophiles in the future can prove to be highly beneficial for humanity, even potentially ameliorating modern problems such as those related to climate change while also expanding our knowledge about the complex biochemical reactions that ultimately resulted in life as we know it today. Full article

(This article belongs to the Special Issue Extremophiles Breakthrough: Hot Topics and Current Issues in Their Isolation, Identification and Biotechnological Applications)

► Show Figures

Figure 1

19 pages, 1172 KiB

Open AccessEditor’s ChoiceReview

Unlocking the Potential of Circulating miRNAs as Biomarkers in Glioblastoma

by Sanika Suvarnapathaki, Antolin Serrano-Farias, Jonathan C. Dudley, Chetan Bettegowda and Jordina Rincon-Torroella

Life 2024, 14(10), 1312; https://doi.org/10.3390/life14101312 - 16 Oct 2024

Viewed by 3853

Abstract

Using microRNAs (miRNAs) as potential circulating biomarkers in diagnosing and treating glioblastoma (GBM) has garnered a lot of scientific and clinical impetus in the past decade. As an aggressive primary brain tumor, GBM poses challenges in early detection and effective treatment with significant [...] Read more.

Using microRNAs (miRNAs) as potential circulating biomarkers in diagnosing and treating glioblastoma (GBM) has garnered a lot of scientific and clinical impetus in the past decade. As an aggressive primary brain tumor, GBM poses challenges in early detection and effective treatment with significant current diagnostic constraints and limited therapeutic strategies. MiRNA dysregulation is present in GBM. The intricate involvement of miRNAs in altering cell proliferation, invasion, and immune escape makes them prospective candidates for identifying and monitoring GBM diagnosis and response to treatment. These miRNAs could play a dual role, acting as both potential diagnostic markers and targets for therapy. By modulating the activity of various oncogenic and tumor-suppressive proteins, miRNAs create opportunities for precision medicine and targeted therapies in GBM. This review centers on the critical role and function of circulating miRNA biomarkers in GBM diagnosis and treatment. It highlights their significance in providing insights into disease progression, aiding in early diagnosis, and potential use as targets for novel therapeutic interventions. Ultimately, the study of miRNA would contribute to improving patient outcomes in the challenging landscape of GBM management. Full article

(This article belongs to the Special Issue Novel Approaches to Early Cancer Detection)

► Show Figures

Graphical abstract

12 pages, 1598 KiB

Open AccessEditor’s ChoiceArticle

Therapy for Dupuytren’s Disease: Collagenase Therapy—A Long-Term Follow-Up Study

by Nikolaus Wachtel, Francesca Romana Dingler, Tim Nürnberger, Felix Hubertus Vollbach, Nicholas Moellhoff, Riccardo Giunta and Wolfram Demmer

Life 2024, 14(10), 1275; https://doi.org/10.3390/life14101275 - 8 Oct 2024

Cited by 1 | Viewed by 1555

Abstract

Background: Dupuytren’s disease (DD) is a systemic connective tissue disorder of the palm. It particularly affects men of Northern European or Caucasian origin over the age of 55. In addition to the classical surgical therapy via limited fasciectomy, Dupuytren’s contracture can also be [...] Read more.

Background: Dupuytren’s disease (DD) is a systemic connective tissue disorder of the palm. It particularly affects men of Northern European or Caucasian origin over the age of 55. In addition to the classical surgical therapy via limited fasciectomy, Dupuytren’s contracture can also be treated minimally invasively. A relatively new treatment method is the use of collagenase injections (Xiapex) to reduce the contracture of the fingers. The data regarding the long-term success of this therapy are currently limited. Methods: In this monocentric retrospective study, we examined 35 patients who were treated with collagenase (Xiapex) for Dupuytren’s contracture in the long fingers. Following the manufacturer’s recommendations, the injection was administered intralesionally, and the cord was ruptured through the passive extension of the finger under local anesthesia with Mepivacain the following day. The clinical follow-up examination was conducted after an average of 5.7 years. The stages of Dupuytren’s disease were documented using the Tubiana classification. Additionally, parameters of finger extension ability, differentiated by metacarpophalangeal (MCP), and proximal interphalangeal (PIP) joints, as well as patient-specific risk parameters, were evaluated Results: The long-term results of collagenase therapy after an average of 5.7 years showed a significant improvement in the contracture of the affected fingers. In the MCP joints, the flexion contracture decreased from 42° to 17° (p ≤ 0.001), and in the PIP joints, it decreased from 56° to 33° (p ≤ 0.001). The primary recurrence rate was 11% for the MCP joints and 19% for the PIP joints, respectively. The analysis of risk factors showed a significant risk for worse long-term outcomes in patients with diabetes and those with nicotine abuse. Conclusions: Collagenase therapy for Dupuytren’s disease achieved significant long-term improvements in contracture in both MCP and PIP joints. In accordance with general risk factors for DD, patients with diabetes and those with nicotine abuse are at risk of worse long-term outcomes. Overall, it is a time-saving, low-risk, and straightforward technique for treating the disabling contracture component of this disease. Full article

(This article belongs to the Special Issue Novel Approaches in Plastic and Reconstructive Surgery to Improve Quality of Life)

► Show Figures

Figure 1

12 pages, 965 KiB

Open AccessEditor’s ChoiceArticle

Different ECLS Pump Configurations for Temporary Right Ventricular Assist Device in LVAD Patients: A Retrospective Case–Control Study

by Dragan Opacic, Christian Klüß, Darko Radakovic, Georges El-Hachem, Tobias Becker, Markus Rudloff, Volker Lauenroth, Marcus-André Deutsch, Claudio Velasquez-Silva, Henrik Fox, René Schramm, Michiel Morshuis, Jan F. Gummert and Sebastian V. Rojas

Life 2024, 14(10), 1274; https://doi.org/10.3390/life14101274 - 7 Oct 2024

Cited by 1 | Viewed by 1898

Abstract

Background: Acute right ventricular failure is a critical complication after left ventricular assist device (LVAD) implantation, often managed with a temporary paracorporeal right ventricular assist device (RVAD). This study examined three extracorporeal life support (ECLS) systems regarding mortality, bleeding complications, and intensive care [...] Read more.

Background: Acute right ventricular failure is a critical complication after left ventricular assist device (LVAD) implantation, often managed with a temporary paracorporeal right ventricular assist device (RVAD). This study examined three extracorporeal life support (ECLS) systems regarding mortality, bleeding complications, and intensive care unit (ICU) stay duration. Methods: This monocentric, retrospective case–control study included all patients receiving LVAD with paracorporeal RVAD between 2009 and 2020. Three patient groups were formed: Centrimag^TM (A), Cardiohelp^TM (B), and Deltastream^TM (C). Results: A total of 245 patients were included. Preoperative parameters were similar between the Centrimag^TM and Deltastream^TM groups, but Cardiohelp^TM patients had worse Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Scores (A: 1.7 ± 0.8, B: 1.36 ± 0.5, C: 1.9 ± 0.9; p < 0.05). In-hospital death rates were A: 61 (41.8%), B: 15 (32.6%), C: 29 (54.7%); p < 0.05, and reoperation due to bleeding rates were A: 32 (21.9%), B: 8 (17.4%), C: 25 (47.2%); p < 0.05, with the Deltastream^TM group showing the highest rates. This group also had increased thrombocyte consumption and prolonged ICU stays. Conclusions: Temporary RVADs lead to bleeding complications, affecting patient outcomes. The Deltastream^TM group had significantly higher bleeding complications, likely due to high pump revolution rates and thrombocyte decline. Due to the study’s retrospective nature and complex patient profiles, these interesting findings should be validated in future studies. Full article

(This article belongs to the Section Medical Research)

► Show Figures

Figure 1

11 pages, 246 KiB

Open AccessEditor’s ChoiceArticle

Association of Loneliness with Functional and Cognitive Status in Minor and Major Neurocognitive Disorders

by Maria Claudia Moretti, Iris Bonfitto, Luciano Nieddu, Ivana Leccisotti, Savino Dimalta, Giovanni Moniello, Madia Lozupone, Antonello Bellomo, Francesco Panza, Carlo Avolio and Mario Altamura

Life 2024, 14(10), 1216; https://doi.org/10.3390/life14101216 - 24 Sep 2024

Cited by 1 | Viewed by 1842

Abstract

Background: Neurocognitive disorders (NCDs) have a variable decline in cognitive function, while loneliness was associated with cognitive impairment and increased dementia risk. In the present study, we examined the associations of loneliness with functional and cognitive status in patients with minor (mild cognitive [...] Read more.

Background: Neurocognitive disorders (NCDs) have a variable decline in cognitive function, while loneliness was associated with cognitive impairment and increased dementia risk. In the present study, we examined the associations of loneliness with functional and cognitive status in patients with minor (mild cognitive impairment) and major NCDs (dementia). Methods: We diagnosed mild NCD (n = 42) and major NCD (n = 164) through DSM-5 criteria on 206 participants aged > 65 years using the UCLA 3-Item Loneliness Scale (UCLA-3) to evaluate loneliness, the activities of daily living (ADL) and the instrumental activities of daily living (IADL) scales to measure functional status, and Mini-Mental State Examination (MMSE) to assess cognitive functions. Results: In a multivariate regression model, the effect of loneliness on cognitive functions was negative in major (β = −1.05, p < 0.0001) and minor NCD (β = −0.06, p < 0.01). In the fully adjusted multivariate regression model (sex–age–education–multimorbidity–depressive symptoms–antidementia drug treatment), the effect of loneliness remained negative for major NCD and became positive for minor NCD (β = 0.09, p < 0.001). The effect of loneliness on IADL (β = −0.26, p < 0.0001) and ADL (β = −0.24, p < 0.001) showed a negative effect for major NCD across the different models, while for minor NCD, the effect was positive (IADL: β = 0.26, p < 0.0001; ADL: β = 0.05, p = 0.01). Minor NCD displayed different levels of MMSE (β = 6.68, p < 0.001) but not ADL or IADL, compared to major NCD for the same levels of loneliness. MANOVA pill test suggested a statistically significant and different interactive effect of loneliness on functional and cognitive variables between minor and major NCDs. Conclusions: We confirmed the relationships between loneliness and cognitive and functional status in major NCD, observing a novel trend in minor NCD. Full article

(This article belongs to the Special Issue Alzheimer's Disease: From Pathogenesis to Therapy)

22 pages, 10840 KiB

Open AccessEditor’s ChoiceArticle

Murine Retina Outer Plexiform Layer Development and Transcriptome Analysis of Pre-Synapses in Photoreceptors

by Soo-Young Kim, Christine Haewon Park, Bo-Hyun Moon and Gail K. Seabold

Life 2024, 14(9), 1103; https://doi.org/10.3390/life14091103 - 2 Sep 2024

Cited by 1 | Viewed by 2185

Abstract

Photoreceptors in the mammalian retina convert light signals into electrical and molecular signals through phototransduction and transfer the visual inputs to second-order neurons via specialized ribbon synapses. Two kinds of photoreceptors, rods and cones, possess distinct morphology and function. Currently, we have limited [...] Read more.

Photoreceptors in the mammalian retina convert light signals into electrical and molecular signals through phototransduction and transfer the visual inputs to second-order neurons via specialized ribbon synapses. Two kinds of photoreceptors, rods and cones, possess distinct morphology and function. Currently, we have limited knowledge about rod versus (vs.) cone synapse development and the associated genes. The transcription factor neural retina leucine zipper (NRL) determines the rod vs. cone photoreceptor cell fate and is critical for rod differentiation. Nrl knockout mice fail to form rods, generating all cone or S-cone-like (SCL) photoreceptors in the retina, whereas ectopic expression of Nrl using a cone-rod homeobox (Crx) promoter (CrxpNrl) forms all rods. Here, we examined rod and cone pre-synapse development, including axonal elongation, terminal shaping, and synaptic lamination in the outer plexiform layer (OPL) in the presence or absence of Nrl. We show that NRL loss and knockdown result in delayed OPL maturation and plasticity with aberrant dendrites of bipolar neurons. The integrated analyses of the transcriptome in developing rods and SCLs with NRL CUT&RUN and synaptic gene ontology analyses identified G protein subunit beta (Gnb) 1 and p21 (RAC1) activated kinase 5 (Pak5 or Pak7) transcripts were upregulated in developing rods and down-regulated in developing SCLs. Notably, Gnb1 and Gnb5 are rod dominant, and Gnb3 is enriched in cones. NRL binds to the genes of Gnb1, Gnb3, and Gnb5. NRL also regulates pre-synapse ribbon genes, and their expression is altered in rods and SCLs. Our study of histological and gene analyses provides new insights into the morphogenesis of photoreceptor pre-synapse development and regulation of associated genes in the developing retina. Full article

(This article belongs to the Special Issue Retinal Diseases: From Molecular Mechanisms to Therapeutics)

► Show Figures

Figure 1

10 pages, 3046 KiB

Open AccessEditor’s ChoiceArticle

Screening and Validation of Leaf Width-Related Genes in Inbred Maize Lines

by Shi Lu, Qi Wang, Junqi Yin, Shubo Zheng, Tingting Gao, Xudong Zhou, Jianxin Zhang, Yuexian Xing, Yingjie Ma, Min Wang, Delong Zhou, Ming Lu, Wenguo Liu, Piwu Wang and Zhijun Zhang

Life 2024, 14(9), 1057; https://doi.org/10.3390/life14091057 - 23 Aug 2024

Viewed by 1241

Abstract

Leaf width is a key determinant of planting density and photosynthetic efficiency. In an effort to determine which genes regulate maize plant leaf width, we performed a genome-wide association study (GWAS) of 1.49 × 106 single nucleotide polymorphisms (SNPs) in 80 sequenced backbone [...] Read more.

Leaf width is a key determinant of planting density and photosynthetic efficiency. In an effort to determine which genes regulate maize plant leaf width, we performed a genome-wide association study (GWAS) of 1.49 × 106 single nucleotide polymorphisms (SNPs) in 80 sequenced backbone inbred maize lines in Jilin Province, China, based upon phenotypic leaf width data from two years. In total, 14 SNPs were identified as being significantly related to leaf width (p < 0.000001), with these SNPs being located on chromosomes 1, 2, 3, 5, 6, 7, 8, and 9. A total of five candidate genes were identified within a mean linkage disequilibrium (LD) distance of 9.7 kb, with a significant SNP being identified within the Zm00001d044327 candidate gene. RNA was then isolated from 12 different inbred maize lines from this GWAS study cohort and was used to conduct qPCR analyses which revealed significant differences in Zm00001d044327 expression among strains exhibiting significant differences in leaf width. Based on an assessment of EMS mutant lines harboring a conserved amino acid stop mutation and two non-synonymous mutations in Zm00001d044327 that exhibited a narrow leaf width, these data suggested that Zm00001d044327 is a key regulator of maize leaf width. Full article

(This article belongs to the Section Plant Science)

► Show Figures

Figure 1

17 pages, 4891 KiB

Open AccessEditor’s ChoiceArticle

TMEM9B Regulates Endosomal ClC-3 and ClC-4 Transporters

by Margherita Festa, Maria Antonietta Coppola, Elena Angeli, Abraham Tettey-Matey, Alice Giusto, Irene Mazza, Elena Gatta, Raffaella Barbieri, Alessandra Picollo, Paola Gavazzo, Michael Pusch, Cristiana Picco and Francesca Sbrana

Life 2024, 14(8), 1034; https://doi.org/10.3390/life14081034 - 20 Aug 2024

Cited by 2 | Viewed by 4489

Abstract

The nine-member CLC gene family of Cl⁻ chloride-transporting membrane proteins is divided into plasma membrane-localized Cl⁻ channels and endo-/lysosomal Cl⁻/H⁺ antiporters. Accessory proteins have been identified for ClC-K and ClC-2 channels and for the lysosomal ClC-7, but not [...] Read more.

The nine-member CLC gene family of Cl⁻ chloride-transporting membrane proteins is divided into plasma membrane-localized Cl⁻ channels and endo-/lysosomal Cl⁻/H⁺ antiporters. Accessory proteins have been identified for ClC-K and ClC-2 channels and for the lysosomal ClC-7, but not the other CLCs. Here, we identified TMEM9 Domain Family Member B (TMEM9B), a single-span type I transmembrane protein of unknown function, to strongly interact with the neuronal endosomal ClC-3 and ClC-4 transporters. Co-expression of TMEM9B with ClC-3 or ClC-4 dramatically reduced transporter activity in Xenopus oocytes and transfected HEK cells. For ClC-3, TMEM9B also induced a slow component in the kinetics of the activation time course, suggesting direct interaction. Currents mediated by ClC-7 were hardly affected by TMEM9B, and ClC-1 currents were only slightly reduced, demonstrating specific interaction with ClC-3 and ClC-4. We obtained strong evidence for direct interaction by detecting significant Förster Resonance Energy Transfer (FRET), exploiting fluorescence lifetime microscopy-based (FLIM-FRET) techniques between TMEM9B and ClC-3 and ClC-4, but hardly any FRET with ClC-1 or ClC-7. The discovery of TMEM9B as a novel interaction partner of ClC-3 and ClC-4 might have important implications for the physiological role of these transporters in neuronal endosomal homeostasis and for a better understanding of the pathological mechanisms in CLCN3- and CLCN4-related pathological conditions. Full article

(This article belongs to the Special Issue Ion Channels and Neurological Disease: 2nd Edition)

► Show Figures

Figure 1

14 pages, 1032 KiB

Open AccessEditor’s ChoiceReview

The Role of Brassinosteroids in Plant Cold Stress Response

by Zhiqi He, Mengdi Zhou, Xiaojie Feng, Qinghua Di, Di Meng, Xianchang Yu, Yan Yan, Mintao Sun and Yansu Li

Life 2024, 14(8), 1015; https://doi.org/10.3390/life14081015 - 15 Aug 2024

Cited by 2 | Viewed by 1857

Abstract

Temperature affects plant growth and geographical distribution. Cold stress occurs when temperatures fall below the physiologically optimal range for plants, causing permanent and irreversible damage to plant growth, development, and production. Brassinosteroids (BRs) are steroid hormones that play an important role in plant [...] Read more.

Temperature affects plant growth and geographical distribution. Cold stress occurs when temperatures fall below the physiologically optimal range for plants, causing permanent and irreversible damage to plant growth, development, and production. Brassinosteroids (BRs) are steroid hormones that play an important role in plant growth and various stress responses. Recent studies have shown that low temperatures affect BR biosynthesis in many plant species and that BR signaling is involved in the regulation of plant tolerance to low temperatures, both in the CBF-dependent and CBF-independent pathways. These two regulatory pathways correspond to transient and acclimation responses of low temperature, respectively. The crosstalk between BRs and other hormones is a significant factor in low-temperature tolerance. We provide an overview of recent developments in our knowledge of BRs’ function in plant responses to cold stress and how they interact with other plant hormones in this review. Full article

(This article belongs to the Special Issue Plant Biotic and Abiotic Stresses 2024)

► Show Figures

Figure 1

25 pages, 444 KiB

Open AccessEditor’s ChoiceReview

Chemotherapy-Induced Peripheral Neuropathy: A Recent Update on Pathophysiology and Treatment

by Marina Mattar, Florence Umutoni, Marwa A. Hassan, M. Wambui Wamburu, Reagan Turner, James S. Patton, Xin Chen and Wei Lei

Life 2024, 14(8), 991; https://doi.org/10.3390/life14080991 - 9 Aug 2024

Cited by 9 | Viewed by 8317

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a major long-lasting side effect of some chemotherapy drugs, which threatens cancer survival rate. CIPN mostly affects sensory neurons and occasionally motor neurons, causing numbness, tingling, discomfort, and burning pain in the upper and lower extremities. The pathophysiology [...] Read more.

Chemotherapy-induced peripheral neuropathy (CIPN) is a major long-lasting side effect of some chemotherapy drugs, which threatens cancer survival rate. CIPN mostly affects sensory neurons and occasionally motor neurons, causing numbness, tingling, discomfort, and burning pain in the upper and lower extremities. The pathophysiology of CIPN is not completely understood; however, it is believed that chemotherapies induce peripheral neuropathy via directly damaging mitochondria, impairing the function of ion channels, triggering immunological mechanisms, and disrupting microtubules. The treatment of CIPN is a medical challenge, and there are no approved pharmacological options. Currently, duloxetine and other antidepressants, antioxidant, anti-inflammatory, and ion-channel targeted therapies are commonly used in clinics to relieve the symptoms of CIPN. Several other types of drugs, such as cannabinoids, sigma−1 receptor antagonists, and nicotinamides ribose, are being evaluated in preclinical and clinical studies. This paper summarizes the information related to the physiology of CIPN and medicines that could be used for treating this condition. Full article

(This article belongs to the Special Issue Conservative Management of Chronic Disease)

13 pages, 1051 KiB

Open AccessEditor’s ChoiceArticle

Leveraging Electronic Health Records to Predict the Risk of Acute Kidney Injury after Allogeneic Hematopoietic Cell Transplantation

by Elena Bischoff and Nikola Kirilov

Life 2024, 14(8), 987; https://doi.org/10.3390/life14080987 - 8 Aug 2024

Viewed by 1017

Abstract

Background: The objective of this study is to assess the electronic health records (EHRs), which are potential risk factors for acute kidney injury (AKI) after allogenic hematopoietic cell transplantation (allo-HCT), and to propose a basic dataset and score for the calculation of HCT-acute [...] Read more.

Background: The objective of this study is to assess the electronic health records (EHRs), which are potential risk factors for acute kidney injury (AKI) after allogenic hematopoietic cell transplantation (allo-HCT), and to propose a basic dataset and score for the calculation of HCT-acute kidney injury risk (HCT-AKIR). Methods: We undertook a retrospective analysis of the EHRs of 312 patients. Pre- and post-transplant factors were assessed, recognizing the following structured entries: laboratory data, encounters, medication, imaging studies, diagnoses, and procedures. Composite variables were used to create patient groups by combining two or more multivariate significant risk factors for AKI. The EHRs dataset and HCT-AKIR score were created based on the multivariate analysis of the composite variables. Results: A multivariate analysis showed that previous CKD and once-impaired pre-transplant kidney function, sepsis, imaging procedures with contrast media, and cumulative length of intensive care unit stay after transplantation were significant risk factors. A new unit-weighted composite score based on the combination of significant risk factors contained in common EHR resources was proposed. Conclusions: Using our novel HCT-AKIR score calculated from the basic EHR dataset could be an easy way to increase awareness of post-transplant AKI and provide risk stratification. Full article

(This article belongs to the Section Epidemiology)

► Show Figures

Figure 1

12 pages, 3309 KiB

Open AccessEditor’s ChoiceArticle

A Cross-Sectional Analysis of Interventional Clinical Trials in High-Grade Glioma Therapy

by Angelo Angione, Jonathan Patterson, Ebrar Akca, Jessica Xu, Emily Xu, Vanessa Raab, Omar Elghawy, Adam A. Barsouk and Jonathan H. Sussman

Life 2024, 14(8), 926; https://doi.org/10.3390/life14080926 - 24 Jul 2024

Cited by 1 | Viewed by 1426

Abstract

High-grade glioma is the most frequent and lethal primary tumor of the central nervous system. Despite advances in surgical, pharmacological, and cell-directed therapies, there have been no updates to the standard of care in over a decade. This cross-sectional study analyzes patient and [...] Read more.

High-grade glioma is the most frequent and lethal primary tumor of the central nervous system. Despite advances in surgical, pharmacological, and cell-directed therapies, there have been no updates to the standard of care in over a decade. This cross-sectional study analyzes patient and trial data from 201 interventional trials completed between 2010 and 2023, encompassing 18,563 participants. Although we found that all trials reported participant age and sex, only 52% of trials reported participant demographics, resulting in 51% of total participant demographics being unreported. The majority of studies did not report ethnicity, with approximately 60% of participants unreported. Additionally, males were significantly underrepresented in trials, comprising 60% of participants despite representing 75% of glioblastoma patients. Improved demographic reporting has been observed since 2011; however, it is inconsistent. Furthermore, we cataloged the geographic diversity of trials across the United States and found significant coverage deserts in relatively rural, but highly affected, areas such as Montana and Maine. We found a wider distribution of trials in both urban and wealthier regions, which indicates extensive coverage gaps and decreased access to participation for patients of a lower socioeconomic status. Full article

(This article belongs to the Special Issue Cancer Epidemiology, Survival, and Disparities: Past, Present, and Future)

► Show Figures

Figure 1

15 pages, 768 KiB

Open AccessEditor’s ChoiceArticle

Sensitization to Lanolin in North-Eastern Italy, 1997–2021: Prevalence, Risk Factors and the Impact of Occupation

by Luca Cegolon, Francesca Larese Filon and on behalf of the North-East Research Group on Contact Dermatitis

Life 2024, 14(8), 916; https://doi.org/10.3390/life14080916 - 23 Jul 2024

Cited by 3 | Viewed by 1747

Abstract

Background: Direct skin contact with items containing lanolin can induce sensitization and development of contact dermatitis (CD). This multi-centric study investigated prevalence of lanolin sensitization among 30,269 outpatients from North-Eastern Italy patch tested during 1997–2021. Methods: European baseline and extended Triveneto [...] Read more.

Background: Direct skin contact with items containing lanolin can induce sensitization and development of contact dermatitis (CD). This multi-centric study investigated prevalence of lanolin sensitization among 30,269 outpatients from North-Eastern Italy patch tested during 1997–2021. Methods: European baseline and extended Triveneto series were applied on the upper part of patients’ back and removed after 48 h. Risk factors for lanolin sensitization were investigated by multiple logistic regression analysis, reporting adjusted odds ratios (aOR) with 95% confidence interval (95%CI). Results. Overall lanolin patch test positive ratio (PTPR) was 1.64% (=501/30,629), with variability over time and by research center. The body area most frequently affected by CD were hands (36.32%), followed by face (19.52%) and legs (8.09%), with a lanolin PTPR of 1.68%, 1.37% and 3.07%, respectively. Prevalence of occupational CD was 8.24%, and 1.83% patients with occupational CD patch tested positive against lanolin. Lanolin sensitization was significantly higher in males (aOR = 1.34; 95%CI: 1.08; 1.65) and among patients with leg CD aged 49–60 years (aOR = 2.34; 95%CI: 1.20; 4.57) or older than 60 (aOR = 4.21; 95%CI: 2.59; 6.85). Sub-group analysis confirmed the significantly higher sensitization rate of older patients with leg CD, with much stronger effect size in females 61+ years old (aOR = 5.33; 95%CI 2.87; 9.89) than males in the same age group (aOR = 2.92; 95%CI: 1.34; 6.39). Moreover, female house painters were more likely to test positive to lanolin. Conclusions: The variability of lanolin PTPR over time and by research center endorsed the ongoing debate on the relevance of the respective skin reaction. Clinicians assessing patients with dermatitis should collect information on potential risk factors for lanolin sensitization, particularly use of skin care products containing the hapten. Occupational exposure to lanolin-containing varnishes should also be considered. Full article

(This article belongs to the Section Epidemiology)

► Show Figures

Figure 1

20 pages, 2787 KiB

Open AccessEditor’s ChoiceArticle

Evaluating the Role of Susceptibility Inducing Cofactors and of Acetaminophen in the Etiology of Autism Spectrum Disorder

by John P. Jones III, Lauren Williamson, Zacharoula Konsoula, Rachel Anderson, Kathryn J. Reissner and William Parker

Life 2024, 14(8), 918; https://doi.org/10.3390/life14080918 - 23 Jul 2024

Cited by 1 | Viewed by 1957

Abstract

More than 20 previously reported lines of independent evidence from clinical observations, studies in laboratory animal models, pharmacokinetic considerations, and numerous temporal and spatial associations indicate that numerous genetic and environmental factors leading to inflammation and oxidative stress confer vulnerability to the aberrant [...] Read more.

More than 20 previously reported lines of independent evidence from clinical observations, studies in laboratory animal models, pharmacokinetic considerations, and numerous temporal and spatial associations indicate that numerous genetic and environmental factors leading to inflammation and oxidative stress confer vulnerability to the aberrant metabolism of acetaminophen during early development, leading to autism spectrum disorder (ASD). Contrary to this conclusion, multivariate analyses of cohort data adjusting for inflammation-associated factors have tended to show little to no risk of acetaminophen use for neurodevelopment. To resolve this discrepancy, here we use in silico methods to create an ideal (virtual) population of 120,000 individuals in which 50% of all cases of virtual ASD are induced by oxidative stress-associated cofactors and acetaminophen use. We demonstrate that Cox regression analysis of this ideal dataset shows little to no risk of acetaminophen use if the cofactors that create aberrant metabolism of acetaminophen are adjusted for in the analysis. Further, under-reporting of acetaminophen use is shown to be a considerable problem for this analysis, leading to large and erroneously low calculated risks of acetaminophen use. In addition, we argue that factors that impart susceptibility to acetaminophen-induced injury, and propensity for acetaminophen use itself, can be shared between the prepartum, peripartum, and postpartum periods, creating additional difficulty in the analysis of existing datasets to determine risks of acetaminophen exposure for neurodevelopment during a specific time frame. It is concluded that risks of acetaminophen use for neurodevelopment obtained from multivariate analysis of cohort data depend on underlying assumptions in the analyses, and that other evidence, both abundant and robust, demonstrate the critical role of acetaminophen in the etiology of ASD. Full article

(This article belongs to the Section Pharmaceutical Science)

► Show Figures

Figure 1

25 pages, 501 KiB

Open AccessEditor’s ChoiceSystematic Review

Mobile Application Applied for Cognitive Rehabilitation: A Systematic Review

by Su-Min Cha

Life 2024, 14(7), 891; https://doi.org/10.3390/life14070891 - 18 Jul 2024

Cited by 1 | Viewed by 3335

Abstract

The COVID-19 pandemic has increased the demand for home rehabilitation services, leading to the development and rising demand for cognitive rehabilitation apps. However, a comprehensive analysis of the content and effectiveness of these apps is needed. This study systematically reviewed and analyzed the [...] Read more.

The COVID-19 pandemic has increased the demand for home rehabilitation services, leading to the development and rising demand for cognitive rehabilitation apps. However, a comprehensive analysis of the content and effectiveness of these apps is needed. This study systematically reviewed and analyzed the literature on mobile apps for cognitive rehabilitation. One researcher and an external expert conducted the study selection, data extraction, and quality assessment following the PRISMA Checklist 2020 guidelines. Our review of 18 studies identified 8 randomized controlled trials (RCTs) (44.44%) of high quality and 10 non-RCT studies (55.56%) of moderate quality. Overall, 16 of the 18 studies (88.88%) demonstrated positive clinical implications for cognitive function after using cognitive rehabilitation apps. Eight studies showed a correlation between app use and improved cognitive function, and four highlighted the potential for cognitive function evaluation through apps. All studies employed various occupational therapy (OT) intervention approaches, with prevention being the most common (100%), followed by establishment and restoration (83.33%), maintenance (77.77%), and creation and promotion (38.88%). This study clinically validates the effectiveness of cognitive rehabilitation mobile applications from an occupational therapy perspective. Full article

(This article belongs to the Section Medical Research)

► Show Figures

Figure 1

13 pages, 1883 KiB

Open AccessEditor’s ChoiceArticle

Comparative Proteomic Analysis of Type 2 Diabetic versus Non-Diabetic Vitreous Fluids

by Abdulaziz H. Alanazi, Shengshuai Shan, S. Priya Narayanan and Payaningal R. Somanath

Life 2024, 14(7), 883; https://doi.org/10.3390/life14070883 - 16 Jul 2024

Cited by 2 | Viewed by 1724

Abstract

Background: Diabetic retinopathy (DR) is a leading cause of vision loss, with complex mechanisms. The study aimed to comprehensively explore vitreous humor of diabetic and non-diabetic individuals, paving the way for identifying the potential molecular mechanisms underlying DR. Methods: Vitreous samples from type [...] Read more.

Background: Diabetic retinopathy (DR) is a leading cause of vision loss, with complex mechanisms. The study aimed to comprehensively explore vitreous humor of diabetic and non-diabetic individuals, paving the way for identifying the potential molecular mechanisms underlying DR. Methods: Vitreous samples from type 2 diabetic and non-diabetic subjects, collected post-mortem, were analyzed using liquid chromatography–mass spectrometry. Pathway enrichment and gene ontology analyses were conducted to identify dysregulated pathways and characterize protein functions. Results: Pathway analysis revealed dysregulation in multiple metabolic and signaling pathways associated with diabetes, including glycerolipid metabolism, histidine metabolism, and Wnt signaling. Gene ontology analysis identified proteins involved in inflammation, immune response dysregulation, and calcium signaling. Notably, proteins such as Inositol 1,4,5-trisphosphate receptor type 2 (ITPR2), Calcium homeostasis endoplasmic reticulum protein (CHERP), and Coronin-1A (CORO1A) were markedly upregulated in diabetic vitreous, implicating aberrant calcium signaling, inflammatory responses, and cytoskeletal reorganization in DR. Conclusions: Our study provides valuable insights into the intricate mechanisms underlying DR and highlights the significance of inflammation, immune dysregulation, and metabolic disturbances in disease progression. Identification of specific proteins as potential biomarkers underscores the multifactorial nature of DR. Future research in this area is vital for advancing therapeutic interventions and translating findings into clinical practice. Full article

(This article belongs to the Special Issue Retinal Disease: Diagnosis and Treatment)

► Show Figures

Figure 1

12 pages, 668 KiB

Open AccessEditor’s ChoiceReview

New Daily Persistent Headache in the Pediatric and Adolescent Population: An Updated Review

by Paige Kalika and Teshamae S. Monteith

Life 2024, 14(6), 724; https://doi.org/10.3390/life14060724 - 3 Jun 2024

Cited by 2 | Viewed by 3587

Abstract

Purpose of review: New daily persistent headache (NDPH) is a primary headache disorder characterized by the sudden onset of continuous pain and its intractability to treatment. It is more prevalent in the pediatric population than the adult population, but remains understudied and underdiagnosed. [...] Read more.

Purpose of review: New daily persistent headache (NDPH) is a primary headache disorder characterized by the sudden onset of continuous pain and its intractability to treatment. It is more prevalent in the pediatric population than the adult population, but remains understudied and underdiagnosed. The purpose of the current article is to provide a current overview of new daily persistent headache in the pediatric and adolescent population, including history, pathophysiology, clinical findings, current and emerging treatment options, and the results of recent studies and meta-analyses. Recent findings: Despite recent studies and meta-analyses showing significant phenotypic overlap between chronic migraine and NDPH in the pediatric population, multiple recent studies have come to conflicting conclusions about the overlap of medication overuse in headache and pediatric NDPH. Recent studies reveal alterations in neuroimaging, particularly in functional connectivity, in patients with NDPH. Patients frequently remain treatment-refractory even to medications that have historically proven helpful in this population; however, new treatment options, including calcitonin gene-related peptide (CGRP) monoclonal antibodies, may be more effective. Summary: NPDH remains a perplexing and difficult-to-manage condition for both children and adults. Despite a higher prevalence in the pediatric population, there are relatively few studies to guide the evaluation and treatment of NDPH in pediatric and adolescent patients. Early treatment, both pharmacological and non-pharmacological, should be employed to reduce disability. Overall, further studies are needed to better understand pathogenesis and to identify more effective therapeutic strategies, both pharmacological and non-pharmacological. Full article

(This article belongs to the Special Issue The Other Pediatric Primary Headaches)

► Show Figures

Figure 1

11 pages, 3217 KiB

Open AccessEditor’s ChoiceArticle

Beyond the Bile: Exploring the Microbiome and Metabolites in Cholangiocarcinoma

by Jungnam Lee, Hanul Kim and Jin-Seok Park

Life 2024, 14(6), 698; https://doi.org/10.3390/life14060698 - 29 May 2024

Cited by 1 | Viewed by 1525

Abstract

Introduction: Cholangiocarcinoma (CCC) still has a high mortality rate despite improvements in diagnostic and therapeutic techniques. The role of the human microbiome in CCC is poorly understood, and a recent metagenomic analysis demonstrated a significant correlation between microbiome-associated carcinogenesis and CCC. This study [...] Read more.

Introduction: Cholangiocarcinoma (CCC) still has a high mortality rate despite improvements in diagnostic and therapeutic techniques. The role of the human microbiome in CCC is poorly understood, and a recent metagenomic analysis demonstrated a significant correlation between microbiome-associated carcinogenesis and CCC. This study aimed to investigate changes in microbiome composition associated with CCC and its metabolic signature by integrating taxonomic and functional information with metabolomics data and in vitro experimental results. Methods: From February 2019 to January 2021, this study included patients who underwent endoscopic retrograde cholangiopancreatography (ERCP), both with and without a diagnosis of CCC. Bile samples were collected via endoscopic nasobiliary drainages (ENBD) and subjected to DNA extraction, PCR amplification of the bacterial 16S rRNA gene V3-V4 region, and data analysis using QIIME2. In vitro Carboxyfluorescein succinimidyl ester (CFSE) proliferation and Annexin V/PI apoptosis assays were performed to investigate the effects of metabolites on CCC cells. Results: A total of 24 patients were included in the study. Bile fluid analysis revealed a significantly higher abundance of Escherichia coli in the CCC group. Alpha diversity analyses exhibited significant differences between the CCC and non-CCC groups, and Nuclear Magnetic Resonance (NMR) spectroscopy metabolic profiling identified 15 metabolites with significant concentration differences; isoleucine showed the most notable difference. In vitro experiments demonstrated that isoleucine suppressed CCC cell proliferation but did not induce apoptosis. Conclusions: This research underlines the significance of biliary dysbiosis and specific bile metabolites, such as isoleucine, in influencing the development and progression of CCC. Full article

(This article belongs to the Special Issue Microbiota in Health and Disease)

► Show Figures

Figure 1

20 pages, 1121 KiB

Open AccessEditor’s ChoiceReview

Evolving Concepts of the SCORE System: Subtracting Cholesterol from Risk Estimation: A Way for a Healthy Longevity?

by Francesco Natale, Rosa Franzese, Luigi Marotta, Noemi Mollo, Achille Solimene, Ettore Luisi, Carmine Gentile, Francesco S. Loffredo, Paolo Golino and Giovanni Cimmino

Life 2024, 14(6), 679; https://doi.org/10.3390/life14060679 - 24 May 2024

Cited by 1 | Viewed by 1712

Abstract

The role of cholesterol, mainly low-density lipoproteins (LDL-C), as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) is now established and accepted by the international scientific community. Based on this evidence, the European and American guidelines recommend early risk stratification and “rapid” [...] Read more.

The role of cholesterol, mainly low-density lipoproteins (LDL-C), as a causal risk factor for atherosclerotic cardiovascular disease (ASCVD) is now established and accepted by the international scientific community. Based on this evidence, the European and American guidelines recommend early risk stratification and “rapid” achievement of the suggested target according to the risk estimation to reduce the number of major cardiovascular events. Prolonged exposure over the years to high levels of LDL-C is one of the determining factors in the development and progression of atherosclerotic plaque, on which the action of conventional risk factors (cigarette smoking, excess weight, sedentary lifestyle, arterial hypertension, diabetes mellitus) as well as non-conventional risk factors (gut microbiota, hyperuricemia, inflammation), alone or in combination, favors the destabilization of the atherosclerotic lesion with rupture/fissuration/ulceration and consequent formation of intravascular thrombosis, which leads to the acute clinical manifestations of acute coronary syndromes. In the current clinical practice, there is a growing number of cases that, although extremely common, are emblematic of the concept of long-term exposure to the risk factor (LDL hypercholesterolemia), which, not adequately controlled and in combination with other risk factors, has favored the onset of major cardiovascular events. The triple concept of “go lower, start earlier and keep longer!” should be applied in current clinical practice at any level of prevention. In the present manuscript, we will review the current evidence and documents supporting the causal role of LDL-C in determining ASCVD and whether it is time to remove it from any score. Full article

(This article belongs to the Special Issue Beyond Atherosclerosis: Between Unresolved Questions, Ongoing Studies, and Future Perspectives—2nd Edition)

► Show Figures

Figure 1

14 pages, 681 KiB

Open AccessEditor’s ChoiceReview

The Impact of Lifestyle on the Secondary Sex Ratio: A Review

by Iasonas Dermitzakis, Paschalis Theotokis, Evangelos Axarloglou, Efthymia Delilampou, Dimosthenis Miliaras, Soultana Meditskou and Maria Eleni Manthou

Life 2024, 14(6), 662; https://doi.org/10.3390/life14060662 - 22 May 2024

Cited by 1 | Viewed by 1532

Abstract

The secondary sex ratio (SSR), indicating the ratio of male to female live births, has garnered considerable attention within the realms of reproductive biology and public health. Numerous factors have been posited as potential trendsetters of the SSR. Given the extensive research on [...] Read more.

The secondary sex ratio (SSR), indicating the ratio of male to female live births, has garnered considerable attention within the realms of reproductive biology and public health. Numerous factors have been posited as potential trendsetters of the SSR. Given the extensive research on the impact of daily behaviors and habits on individuals’ reproductive health, there is a plausible suggestion that lifestyle choices may also influence the SSR. By synthesizing the existing literature on the current research field, this comprehensive review indicates that an elevated SSR has been associated with an increased intake of fatty acids and monosaccharides, proper nutrition, higher educational levels, financial prosperity, and favorable housing conditions. On the other hand, a decreased SSR may be linked to undernutrition, socioeconomic disparities, and psychological distress, aligning with the Trivers–Willard hypothesis. Occupational factors, smoking habits, and cultural beliefs could also contribute to trends in the SSR. Our review underscores the significance of considering the aforementioned factors in studies examining the SSR and emphasizes the necessity for further research to unravel the mechanisms underpinning these connections. A more profound comprehension of SSR alterations due to lifestyle holds the potential to adequately develop public health interventions and healthcare strategies to enhance reproductive health and overall well-being. Full article

(This article belongs to the Section Epidemiology)

► Show Figures

Figure 1

38 pages, 10899 KiB

Open AccessEditor’s ChoiceReview

Compaction and Segregation of DNA in Escherichia coli

by Conrad L. Woldringh

Life 2024, 14(6), 660; https://doi.org/10.3390/life14060660 - 22 May 2024

Cited by 1 | Viewed by 1908

Abstract

Theoretical and experimental approaches have been applied to study the polymer physics underlying the compaction of DNA in the bacterial nucleoid. Knowledge of the compaction mechanism is necessary to obtain a mechanistic understanding of the segregation process of replicating chromosome arms (replichores) during [...] Read more.

Theoretical and experimental approaches have been applied to study the polymer physics underlying the compaction of DNA in the bacterial nucleoid. Knowledge of the compaction mechanism is necessary to obtain a mechanistic understanding of the segregation process of replicating chromosome arms (replichores) during the cell cycle. The first part of this review discusses light microscope observations demonstrating that the nucleoid has a lower refractive index and thus, a lower density than the cytoplasm. A polymer physics explanation for this phenomenon was given by a theory discussed at length in this review. By assuming a phase separation between the nucleoid and the cytoplasm and by imposing equal osmotic pressure and chemical potential between the two phases, a minimal energy situation is obtained, in which soluble proteins are depleted from the nucleoid, thus explaining its lower density. This theory is compared to recent views on DNA compaction that are based on the exclusion of polyribosomes from the nucleoid or on the transcriptional activity of the cell. These new views prompt the question of whether they can still explain the lower refractive index or density of the nucleoid. In the second part of this review, we discuss the question of how DNA segregation occurs in Escherichia coli in the absence of the so-called active ParABS system, which is present in the majority of bacteria. How is the entanglement of nascent chromosome arms generated at the origin in the parental DNA network of the E. coli nucleoid prevented? Microscopic observations of the position of fluorescently-labeled genetic loci have indicated that the four nascent chromosome arms synthesized in the initial replication bubble segregate to opposite halves of the sister nucleoids. This implies that extensive intermingling of daughter strands does not occur. Based on the hypothesis that leading and lagging replichores synthesized in the replication bubble fold into microdomains that do not intermingle, a passive four-excluding-arms model for segregation is proposed. This model suggests that the key for segregation already exists in the structure of the replication bubble at the very start of DNA replication; it explains the different patterns of chromosome arms as well as the segregation distances between replicated loci, as experimentally observed. Full article

(This article belongs to the Collection Feature Papers in Microbiology)

► Show Figures

Figure 1

21 pages, 6387 KiB

Open AccessEditor’s ChoiceArticle

Genistein–Aspirin Combination Exerts Cytotoxic and Anti-Migratory Effects in Human Colorectal Cancer Cells

by Claudia Iftode, Stela Iurciuc, Iasmina Marcovici, Ioana Macasoi, Dorina Coricovac, Cristina Dehelean, Sorin Ursoniu, Andreea Rusu and Simona Ardelean

Life 2024, 14(5), 606; https://doi.org/10.3390/life14050606 - 9 May 2024

Cited by 5 | Viewed by 1909

Abstract

Colorectal cancer (CRC) is a heterogenous pathology with high incidence and mortality rates globally, but it is also preventable so finding the most promising candidates (natural compounds or repurposed drugs) to be chemopreventive alternatives has become a topic of interest in recent years. [...] Read more.

Colorectal cancer (CRC) is a heterogenous pathology with high incidence and mortality rates globally, but it is also preventable so finding the most promising candidates (natural compounds or repurposed drugs) to be chemopreventive alternatives has become a topic of interest in recent years. The present work aims to elucidate the potential effects of a combination between genistein (GEN), an isoflavone of natural origin, and aspirin (ASA) in CRC prevention/treatment by performing an in vitro evaluation in human colorectal cancer cells (HCT-116) and an in ovo analysis using the chick embryo chorioallantoic membrane (CAM) model. Cell viability was verified by an MTT (migratory potential by scratch) assay, and the expressions of MMP-2 and MMP-9 were analyzed using RT-qPCR. Our results indicated a dose-dependent cytotoxic effect of ASA (2.5 mM) + GEN (10–75 µM) combination characterized by reduced cell viability and morphological changes (actin skeleton reorganization and nuclei deterioration), an inhibition of HCT-116 cells’ migratory potential by down-regulating MMP-2 and MMP-9 mRNA expressions, and an antiangiogenic effect by modifying the vascular network. These promising results raise the possibility of future in-depth investigations regarding the chemopreventive/therapeutical potential of ASA+GEN combination. Full article

(This article belongs to the Special Issue Natural Bioactives: Exploring Their Therapeutic Potential)

► Show Figures

Figure 1

11 pages, 1100 KiB

Open AccessEditor’s ChoiceArticle

Comorbidities and Complications in People Admitted for Leprosy in Spain, 1997–2021

by Blanca Figueres-Pesudo, Héctor Pinargote-Celorio, Isabel Belinchón-Romero and José-Manuel Ramos-Rincón

Life 2024, 14(5), 586; https://doi.org/10.3390/life14050586 - 2 May 2024

Cited by 2 | Viewed by 1607

Abstract

This study aims to describe the epidemiological and clinical characteristics and trends of these admissions in Spain. This retrospective study drew data from the Hospital Discharge Records Database of the Spanish National Health System. We used the diagnostic codes for leprosy from the [...] Read more.

This study aims to describe the epidemiological and clinical characteristics and trends of these admissions in Spain. This retrospective study drew data from the Hospital Discharge Records Database of the Spanish National Health System. We used the diagnostic codes for leprosy from the International Classification of Diseases, ninth and tenth revisions, to retrieve leprosy admissions from 1997 to 2021. There were 1387 hospitalizations for leprosy The number of annual cases decreased gradually, from 341 cases in 1997–2001 to 232 in 2017–2021 (p < 0.001). Patients’ median age increased, from 65 years in 1997–2001 to 76 years in 2017–2021 (p < 0.001), as did the prevalence of some comorbidities, such as hypertension (15% in 1997–2001 to 27.6% in 2017–2021; p < 0.001). The mortality rate (6%) and the frequency of leprosy complications remained stable. After Spain (79.1%), the most common country of origin was Paraguay (4.4%). Admissions decreased significantly in Andalusia, from 42% in 1997–2001 to 10.8% in 2017–2021 (p < 0.001), and in the Canary Islands, from 7.9% in 1997–2001 to 2.6% in 2017–2021 (p = 0.001), whereas they increased in Madrid, from 5.9% in 1997–2001 to 12.1% in 2017–2021 (p = 0.005). Overall, leprosy admissions in Spain have declined, even in the regions with the highest prevalence. Patients admitted for leprosy have become older and sicker. Full article

(This article belongs to the Section Epidemiology)

► Show Figures

Figure 1

11 pages, 1260 KiB

Open AccessEditor’s ChoiceArticle

Serum Concentrations of TIM-3, LAG-3, and PD-1 in Patients with Hemorrhagic Fever with Renal Syndrome

by Željka Mačak Šafranko, Lana Jakopec, Karla Svaguša, Lidija Cvetko Krajinović, Domagoj Tomasović, ǈiljana Lukić and Alemka Markotić

Life 2024, 14(5), 551; https://doi.org/10.3390/life14050551 - 25 Apr 2024

Viewed by 1648

Abstract

Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease widespread in Europe and Asia. HFRS is caused by negative-sensed single-stranded RNA orthohantaviruses transmitted to humans through inhaling aerosolized excreta of infected rodents. Symptoms of HFRS include acute kidney injury, thrombocytopenia, hemorrhages, and [...] Read more.

Hemorrhagic fever with renal syndrome (HFRS) is a rodent-borne disease widespread in Europe and Asia. HFRS is caused by negative-sensed single-stranded RNA orthohantaviruses transmitted to humans through inhaling aerosolized excreta of infected rodents. Symptoms of HFRS include acute kidney injury, thrombocytopenia, hemorrhages, and hypotension. The immune response raised against viral antigens plays an important role in the pathogenesis of HFRS. Inhibitory co-receptors are essential in regulating immune responses, mitigating immunopathogenesis, and reducing tissue damage. Our research showed an increased soluble form of inhibitory co-receptors TIM-3, LAG-3, and PD-1 in HFRS patients associated with disease severity. Our study aimed to investigate the impact of HFRS on the concentrations of soluble forms of inhibitory receptors TIM-3, LAG-3, and PD-1 in the patient’s serum and the potential correlation with key clinical parameters. Our study aimed to investigate the impact of HFRS on the concentrations of soluble forms of inhibitory receptors TIM-3, LAG-3, and PD-1 in the patient’s serum and their possible association with relevant clinical parameters. Using multiplex immunoassay, we found elevated levels of TIM-3, LAG-3, and PD-1 proteins in the serum of HFRS patients. Furthermore, increased levels were associated with creatinine, urea, lactate dehydrogenase concentrations, and platelet count. These findings suggest that these proteins play a role in regulating the immune response and disease progression. Full article

(This article belongs to the Special Issue Emerging and Re-emerging Zoonotic Infectious Diseases)

► Show Figures

Figure 1

15 pages, 1364 KiB

Open AccessEditor’s ChoiceArticle

Deciphering the Systemic Impact of Herbal Medicines on Allergic Rhinitis: A Network Pharmacological Approach

by Sa-Yoon Park, Yoon Yeol Lee, Min Hee Kim and Chang-Eop Kim

Life 2024, 14(5), 553; https://doi.org/10.3390/life14050553 - 25 Apr 2024

Cited by 4 | Viewed by 2315

Abstract

Allergic rhinitis (AR) is a systemic allergic disease that has a considerable impact on patients’ quality of life. Current treatments include antihistamines and nasal steroids; however, their long-term use often causes undesirable side effects. In this context, traditional Asian medicine (TAM), with its [...] Read more.

Allergic rhinitis (AR) is a systemic allergic disease that has a considerable impact on patients’ quality of life. Current treatments include antihistamines and nasal steroids; however, their long-term use often causes undesirable side effects. In this context, traditional Asian medicine (TAM), with its multi-compound, multi-target herbal medicines (medicinal plants), offers a promising alternative. However, the complexity of these multi-compound traits poses challenges in understanding the overall mechanisms and efficacy of herbal medicines. Here, we demonstrate the efficacy and underlying mechanisms of these multi-compound herbal medicines specifically used for AR at a systemic level. We utilized a modified term frequency–inverse document frequency method to select AR-specific herbs and constructed an herb–compound–target network using reliable databases and computational methods, such as the Quantitative Estimate of Drug-likeness for compound filtering, STITCH database for compound-target interaction prediction (with a high confidence score threshold of 0.7), and DisGeNET and CTD databases for disease-gene association analysis. Through this network, we conducted AR-related targets and pathway analyses, as well as clustering analysis based on target-level information of the herbs. Gene ontology enrichment analysis was conducted using a protein–protein interaction network. Our research identified 14 AR-specific herbs and analyzed whether AR-specific herbs are highly related to previously known AR-related genes and pathways. AR-specific herbs were found to target several genes related to inflammation and AR pathogenesis, such as PTGS2, HRH1, and TBXA2R. Pathway analysis revealed that AR-specific herbs were associated with multiple AR-related pathways, including cytokine signaling, immune response, and allergic inflammation. Additionally, clustering analysis based on target similarity identified three distinct subgroups of AR-specific herbs, corroborated by a protein–protein interaction network. Group 1 herbs were associated with the regulation of inflammatory responses to antigenic stimuli, while Group 2 herbs were related to the detection of chemical stimuli involved in the sensory perception of bitter taste. Group 3 herbs were distinctly associated with antigen processing and presentation and NIK/NF-kappa B signaling. This study decodes the principles of TAM herbal configurations for AR using a network pharmacological approach, providing a holistic understanding of drug effects beyond specific pathways. Full article

(This article belongs to the Special Issue Advances in the Biomedical Applications of Plants and Plant Extracts)

► Show Figures

Figure 1

16 pages, 323 KiB

Open AccessEditor’s ChoiceReview

Immunological and Clinical Responses to Vaccinations among Adults Living with HIV

by Carlo Bieńkowski, Zuzanna Żak, Filip Fijołek, Martyna Cholewik, Maciej Stępień, Agata Skrzat-Klapaczyńska and Justyna D. Kowalska

Life 2024, 14(5), 540; https://doi.org/10.3390/life14050540 - 24 Apr 2024

Cited by 1 | Viewed by 2509

Abstract

People living with human immunodeficiency virus (HIV) are at higher risk of morbidity and mortality due to vaccine-preventable diseases. At the same time, they are less likely to respond to vaccinations, and might have a higher rate of vaccine adverse event and faster [...] Read more.

People living with human immunodeficiency virus (HIV) are at higher risk of morbidity and mortality due to vaccine-preventable diseases. At the same time, they are less likely to respond to vaccinations, and might have a higher rate of vaccine adverse event and faster waning of protective effect. International and national guidelines emphasize the importance of vaccinating people living with HIV against respiratory system disease pathogens including seasonal influenza, Streptococcus pneumoniae, and COVID-19, as well as against sexually transmitted infections, i.e., Hepatitis A and B (HAV, HBV) and human papillomavirus (HPV). This narrative review aims to provide a comprehensive examination of the current knowledge regarding the immune and clinical responses elicited by vaccinations in the older adult population living with HIV. Full article

(This article belongs to the Special Issue Exploration of the Unmet Needs of Aging People Living with HIV)

19 pages, 8165 KiB

Open AccessEditor’s ChoiceArticle

Focal Traumatic Brain Injury Impairs the Integrity of the Basement Membrane of Hindlimb Muscle Fibers Revealed by Extracellular Matrix Immunoreactivity

by Mette Albæk Kristensen, Karen Kalhøj Rich, Tobias Christian Mogensen, Andreas Malmquist Damsgaard Jensen, Åsa Fex Svenningsen and Mengliang Zhang

Life 2024, 14(5), 543; https://doi.org/10.3390/life14050543 - 24 Apr 2024

Cited by 1 | Viewed by 1419

Abstract

Traumatic brain injury (TBI) stands as a prominent global cause of disability, with motor deficits being a common consequence. Despite its widespread impact, the precise pathological mechanisms underlying motor deficits after TBI remain elusive. In this study, hindlimb postural asymmetry (HL-PA) development [...] Read more.

Traumatic brain injury (TBI) stands as a prominent global cause of disability, with motor deficits being a common consequence. Despite its widespread impact, the precise pathological mechanisms underlying motor deficits after TBI remain elusive. In this study, hindlimb postural asymmetry (HL-PA) development in rats subjected to focal TBI was investigated to explore the potential roles of collagen IV and laminin within the extracellular matrix (ECM) of selected hindlimb muscles in the emergence of motor deficits following TBI. A focal TBI was induced by ablating the left sensorimotor cortex in rats and motor deficits were assessed by measuring HL-PA. The expression of laminin and collagen IV in eight selected muscles on each side of the hindlimbs from both TBI- and sham-operated rats were studied using immunohistochemistry and semi-quantitatively analyzed. The results indicated that the TBI rats exhibited HL-PA, characterized by flexion of the contralateral (right) hindlimb. In the sham-operated rats, the immunoreactive components of laminin and collagen IV were evenly and smoothly distributed along the border of the muscle fibers in all the investigated muscles. In contrast, in the TBI rats, the pattern was broken into aggregated, granule-like, immunoreactive components. Such a labeling pattern was detected in all the investigated muscles both from the contra- and ipsilateral sides of the TBI rats. However, in TBI rats, most of the muscles from the contralateral hindlimb showed a significantly increased expression of these two proteins in comparison with those from the ipsilateral hindlimb. In comparison to sham-operated rats, there was a significant increase in laminin and collagen IV expression in various contralateral hindlimb muscles in the TBI rats. These findings suggest potential implications of laminin and collagen IV in the development of motor deficits following a focal TBI. Full article

(This article belongs to the Special Issue Motor Deficits Caused by Neurological Disorders: From Mechanism to Treatment)

► Show Figures

Figure 1

18 pages, 1124 KiB

Open AccessEditor’s ChoiceReview

Chrono-Endocrinology in Clinical Practice: A Journey from Pathophysiological to Therapeutic Aspects

by Silvia Mercadante and Antonio Bellastella

Life 2024, 14(5), 546; https://doi.org/10.3390/life14050546 - 24 Apr 2024

Cited by 2 | Viewed by 1974

Abstract

This review was aimed at collecting the knowledge on the pathophysiological and clinical aspects of endocrine rhythms and their implications in clinical practice, derived from the published literature and from some personal experiences on this topic. We chose to review, according to the [...] Read more.

This review was aimed at collecting the knowledge on the pathophysiological and clinical aspects of endocrine rhythms and their implications in clinical practice, derived from the published literature and from some personal experiences on this topic. We chose to review, according to the PRISMA guidelines, the results of original and observational studies, reviews, meta-analyses and case reports published up to March 2024. Thus, after summarizing the general aspects of biological rhythms, we will describe the characteristics of several endocrine rhythms and the consequences of their disruption, paying particular attention to the implications in clinical practice. Rhythmic endocrine secretions, like other physiological rhythms, are genetically determined and regulated by a central hypothalamic CLOCK located in the suprachiasmatic nucleus, which links the timing of the rhythms to independent clocks, in a hierarchical organization for the regulation of physiology and behavior. However, some environmental factors, such as daily cycles of light/darkness, sleep/wake, and timing of food intake, may influence the rhythm characteristics. Endocrine rhythms are involved in important physiological processes and their disruption may cause several disorders and also cancer. Thus, it is very important to prevent disruptions of endocrine rhythms and to restore a previously altered rhythm by an early corrective chronotherapy. Full article

(This article belongs to the Section Physiology and Pathology)

► Show Figures

Figure 1

16 pages, 639 KiB

Open AccessEditor’s ChoiceReview

Organ-Specific Mitochondrial Alterations Following Ischemia–Reperfusion Injury in Post-Cardiac Arrest Syndrome: A Comprehensive Review

by Eriko Nakamura, Tomoaki Aoki, Yusuke Endo, Jacob Kazmi, Jun Hagiwara, Cyrus E. Kuschner, Tai Yin, Junhwan Kim, Lance B. Becker and Kei Hayashida

Life 2024, 14(4), 477; https://doi.org/10.3390/life14040477 - 5 Apr 2024

Cited by 9 | Viewed by 4384

Abstract

Background: Mitochondrial dysfunction, which is triggered by systemic ischemia–reperfusion (IR) injury and affects various organs, is a key factor in the development of post-cardiac arrest syndrome (PCAS). Current research on PCAS primarily addresses generalized mitochondrial responses, resulting in a knowledge gap regarding organ-specific [...] Read more.

Background: Mitochondrial dysfunction, which is triggered by systemic ischemia–reperfusion (IR) injury and affects various organs, is a key factor in the development of post-cardiac arrest syndrome (PCAS). Current research on PCAS primarily addresses generalized mitochondrial responses, resulting in a knowledge gap regarding organ-specific mitochondrial dynamics. This review focuses on the organ-specific mitochondrial responses to IR injury, particularly examining the brain, heart, and kidneys, to highlight potential therapeutic strategies targeting mitochondrial dysfunction to enhance outcomes post-IR injury. Methods and Results: We conducted a narrative review examining recent advancements in mitochondrial research related to IR injury. Mitochondrial responses to IR injury exhibit considerable variation across different organ systems, influenced by unique mitochondrial structures, bioenergetics, and antioxidative capacities. Each organ demonstrates distinct mitochondrial behaviors that have evolved to fulfill specific metabolic and functional needs. For example, cerebral mitochondria display dynamic responses that can be both protective and detrimental to neuronal activity and function during ischemic events. Cardiac mitochondria show vulnerability to IR-induced oxidative stress, while renal mitochondria exhibit a unique pattern of fission and fusion, closely linked to their susceptibility to acute kidney injury. This organ-specific heterogeneity in mitochondrial responses requires the development of tailored interventions. Progress in mitochondrial medicine, especially in the realms of genomics and metabolomics, is paving the way for innovative strategies to combat mitochondrial dysfunction. Emerging techniques such as mitochondrial transplantation hold the potential to revolutionize the management of IR injury in resuscitation science. Conclusions: The investigation into organ-specific mitochondrial responses to IR injury is pivotal in the realm of resuscitation research, particularly within the context of PCAS. This nuanced understanding holds the promise of revolutionizing PCAS management, addressing the unique mitochondrial dysfunctions observed in critical organs affected by IR injury. Full article

(This article belongs to the Special Issue Clinical Advances in Cardiac Arrest: Prognostic Performance and Management)

► Show Figures

Figure 1

18 pages, 1568 KiB

Open AccessEditor’s ChoiceReview

Curcumin as a Multifunctional Spice Ingredient against Mental Disorders in Humans: Current Clinical Studies and Bioavailability Concerns

by Maria Spanoudaki, Sousana K. Papadopoulou, Georgios Antasouras, Konstantinos A. Papadopoulos, Evmorfia Psara, Theofanis Vorvolakos, Evangelos Solovos, Maria Chrysafi, Michalis Psallas, Maria Mentzelou, Despoina Ourda and Constantinos Giaginis

Life 2024, 14(4), 479; https://doi.org/10.3390/life14040479 - 5 Apr 2024

Cited by 3 | Viewed by 5746

Abstract

Background: Mental disorders in terms of depression, anxiety, and stress are one of the major causes of burden globally. Over the last two decades, the use of plant-based substances in the treatment of mental disorders in combination or not with medication has increasingly [...] Read more.

Background: Mental disorders in terms of depression, anxiety, and stress are one of the major causes of burden globally. Over the last two decades, the use of plant-based substances in the treatment of mental disorders in combination or not with medication has increasingly attracted the interest of the scientific research community. However, even if there is a plethora of naturally occurring bioactive compounds, most of them have low bioavailability, rendering them unable to insert into the bloodstream to exert their biological activities. Methods: This is a comprehensive narrative review that critically summarizes and scrutinizes the new approaches to the treatment of mental disorders using curcumin, also highlighting its bioavailability properties. The most accurate were searched using effective and relevant keywords. Results: This narrative review reveals substantial evidence that curcumin can exert significant effects on several mental disorders. However, despite the low cost, the extensive and confirmed potency of curcumin and its involvement in signaling pathways and the scientifically confirmed data regarding its molecular mechanisms of action against mental disorders, this naturally occurring compound presents low oral bioavailability. Pharmaceutical technology has provided solutions to increase the bioavailability of curcumin. Combination with piperine, galactomannosides, liposomal formulation or nanoformulation overcomes the bioavailability and solubility disadvantages. Conclusions: Although curcumin demonstrates anti-anxiety, anti-depressive and anti-stress properties, studies on humans are limited and heterogeneous. Further research is highly recommended to determine the most functional formula, dose, duration, and possible side effects of curcumin on mental disorders in humans. Based on the current knowledge, the curcumin nanoformulation and Theracurmin, a form of colloidal submicroscopic particles, seem to be the most effective bioavailable formulations, which may be examined in future clinical human studies. Full article

(This article belongs to the Section Pharmaceutical Science)

► Show Figures

Figure 1

18 pages, 4076 KiB

Open AccessEditor’s ChoiceArticle

The Putative GATA Transcription Factor SbGATA22 as a Novel Regulator of Dhurrin Biosynthesis

by Viviana C. Rosati, Alicia A. Quinn, Roslyn M. Gleadow and Cecilia K. Blomstedt

Life 2024, 14(4), 470; https://doi.org/10.3390/life14040470 - 3 Apr 2024

Cited by 3 | Viewed by 2244

Abstract

Cyanogenic glucosides are specialized metabolites produced by over 3000 species of higher plants from more than 130 families. The deployment of cyanogenic glucosides is influenced by biotic and abiotic factors in addition to being developmentally regulated, consistent with their roles in plant defense [...] Read more.

Cyanogenic glucosides are specialized metabolites produced by over 3000 species of higher plants from more than 130 families. The deployment of cyanogenic glucosides is influenced by biotic and abiotic factors in addition to being developmentally regulated, consistent with their roles in plant defense and stress mitigation. Despite their ubiquity, very little is known regarding the molecular mechanisms that regulate their biosynthesis. The biosynthetic pathway of dhurrin, the cyanogenic glucoside found in the important cereal crop sorghum (Sorghum bicolor (L.) Moench), was described over 20 years ago, and yet no direct regulator of the biosynthetic genes has been identified. To isolate regulatory proteins that bind to the promoter region of the key dhurrin biosynthetic gene of sorghum, SbCYP79A1, yeast one-hybrid screens were performed. A bait fragment containing 1204 base pairs of the SbCYP79A1 5′ regulatory region was cloned upstream of a reporter gene and introduced into Saccharomyces cerevisiae. Subsequently, the yeast was transformed with library cDNA representing RNA from two different sorghum developmental stages. From these screens, we identified SbGATA22, an LLM domain B-GATA transcription factor that binds to the putative GATA transcription factor binding motifs in the SbCYP79A1 promoter region. Transient assays in Nicotiana benthamiana show that SbGATA22 localizes to the nucleus. The expression of SbGATA22, in comparison with SbCYP79A1 expression and dhurrin concentration, was analyzed over 14 days of sorghum development and in response to nitrogen application, as these conditions are known to affect dhurrin levels. Collectively, these findings suggest that SbGATA22 may act as a negative regulator of SbCYP79A1 expression and provide a preliminary insight into the molecular regulation of dhurrin biosynthesis in sorghum. Full article

(This article belongs to the Special Issue Novel Insights into the Regulation of Plant Specialized Metabolism)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Editor’s Choice Articles

Further Information

Guidelines

MDPI Initiatives

Follow MDPI