Life

12 pages, 1448 KiB

Open AccessSystematic Review

Comparison of Effectiveness Between Ultrasound-Guided and Blind Corticosteroid Injections in Plantar Fasciitis: A Systematic Review and Meta-Analysis

by Hoa Ngan Doan, Yoo Jin Choo and Min Cheol Chang

Life 2025, 15(7), 1107; https://doi.org/10.3390/life15071107 (registering DOI) - 15 Jul 2025

Abstract

The effectiveness of ultrasound (US)-guided compared with blind corticosteroid injections for the treatment of plantar fasciitis (PF) remains uncertain. This meta-analysis aimed to evaluate the clinical benefits of US-guided over blind injections in patients with PF. A systematic search of PubMed, Embase, Web [...] Read more.

The effectiveness of ultrasound (US)-guided compared with blind corticosteroid injections for the treatment of plantar fasciitis (PF) remains uncertain. This meta-analysis aimed to evaluate the clinical benefits of US-guided over blind injections in patients with PF. A systematic search of PubMed, Embase, Web of Science, and Scopus was conducted, collecting articles published up to 20 April 2025. Randomized controlled trials comparing US-guided and blind corticosteroid injections for PF were included. The extracted outcome measures, i.e., visual analog scale (VAS), heel tenderness index (HTI), tenderness threshold (TT), and plantar fascia thickness, were assessed at short- (2–6 weeks) and long-term (≥12 weeks) follow-ups. Compared with the blind injection group, the US-guided group showed significantly greater improvement in TT at both short- and long-term follow-ups, as well as a greater reduction in plantar fascia thickness. However, no significant differences were found between the two groups in VAS and HTI scores. US-guided corticosteroid injections provide superior clinical benefits compared with blind injections in patients with PF, particularly in enhancing mechanical pain tolerance and reducing plantar fascia thickness. Nevertheless, these findings should be interpreted with caution due to the limited methodological quality of the included studies. Full article

(This article belongs to the Special Issue Musculoskeletal Pain and Disorders: Diagnosis, Treatment and Management)

13 pages, 1230 KiB

Open AccessSystematic Review

Assessing Efficacy of Interleukin-1 Blockade in Patients with Alcoholic Hepatitis: A Comprehensive Systematic Review of Emerging Evidence

by Shree Rath, Mary Girgis, Ishita Gupta, Anchit Chauhan, Zahir Ud Din, Hema Hotchandani, Ali Hasan, Raheel Ahmed and Raheel Qureshi

Life 2025, 15(7), 1106; https://doi.org/10.3390/life15071106 (registering DOI) - 15 Jul 2025

Abstract

Background and Objectives: Alcoholic hepatitis (AH) is a growing public health concern with its rising incidence and its contribution to nearly half of all cirrhosis-related deaths in the United States. In this systematic review, we aimed to comprehensively evaluate the current evidence [...] Read more.

Background and Objectives: Alcoholic hepatitis (AH) is a growing public health concern with its rising incidence and its contribution to nearly half of all cirrhosis-related deaths in the United States. In this systematic review, we aimed to comprehensively evaluate the current evidence and trials on the use of anti-interleukin-1 (anti-IL-1) drugs in patients with AH, assessing their efficacy and adverse events compared to routinely prescribed drugs like corticosteroids. Materials and Methods: A comprehensive literature search was conducted across five databases to identify randomized controlled trials (RCTs) evaluating the role of anti-IL-1 agents like canakinumab and anakinra among patients diagnosed with AH. Data was extracted and pooled in the form of mean and standard deviation for continuous variables and event and total for dichotomous variables. Results: Three RCTs were included for quantitative synthesis, encompassing 307 patients. Using canakinumab, 58% of patients showed improvement in histology. Prednisolone was associated with higher 90-day survival (90% vs. 70%; hazard ratio for death = 0.34, 95% CI 0.14–0.83, p = 0.018) and transplant-free survival. Overall, a higher incidence of acute kidney injury and new-onset cardiac disorders was noted in the anti-IL-1 arm when compared to placebo. Conclusions: This study concludes the lack of efficacy of anti-IL-1 agents in causing improvement in patient outcomes when compared to standard therapies. A higher incidence of adverse events was also noted in the anti-IL-1 arm. These results emphasize the need for future clinical trials to evaluate the use of anti-IL-1 agents in AH objectively. Full article

(This article belongs to the Special Issue New Insights into Diagnosis and Therapeutic Strategies for Chronic Liver Diseases)

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16 pages, 548 KiB

Open AccessReview

Auditory Steady-State Responses for Detecting Mild Hearing Loss in Babies, Infants, and Children: Literature Review

by Mariana Ferreira Pires Martins, Caroline Donadon, Piotr Henryk Skarzynski, Ana Júlia Tashiro de Souza, Adriana Neves de Andrade, Daniela Gil and Milaine Dominici Sanfins

Life 2025, 15(7), 1105; https://doi.org/10.3390/life15071105 (registering DOI) - 15 Jul 2025

Abstract

The assessment of hearing in children is important, as hearing deficits can impair child development. The Auditory Steady-State Response (ASSR) is an electrophysiological technique that is able to simultaneously evaluate both ears at four frequencies, making it advantageous for testing children where the [...] Read more.

The assessment of hearing in children is important, as hearing deficits can impair child development. The Auditory Steady-State Response (ASSR) is an electrophysiological technique that is able to simultaneously evaluate both ears at four frequencies, making it advantageous for testing children where the test time needs to be as short as possible. The objective of this work was to perform a literature review on the effectiveness of ASSR to gauge hearing thresholds in babies, infants, and children, examining its ability to distinguish mild hearing loss from normal cases. This review used PubMed, Web of Science, and Scopus databases from 2014 to 2024. A total of 1226 articles were identified, although only 16 met the previously established inclusion criteria. It was found that ASSR is a reliable diagnostic tool for babies, infants, and children. Recent work appears better able to distinguish mild hearing loss from normal hearing. One unresolved aspect that needs additional attention is the effectiveness of using bone-conducted stimuli. Full article

(This article belongs to the Section Physiology and Pathology)

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17 pages, 900 KiB

Open AccessReview

Watercress (Nasturtium officinale) as a Functional Food for Non-Communicable Diseases Prevention and Management: A Narrative Review

by Chikondi Maluwa, Blecious Zinan’dala, Hataichanok Chuljerm, Wason Parklak and Kanokwan Kulprachakarn

Life 2025, 15(7), 1104; https://doi.org/10.3390/life15071104 (registering DOI) - 15 Jul 2025

Abstract

Non-communicable diseases (NCDs) such as cardiovascular disease, diabetes, cancer, and chronic respiratory conditions are the leading causes of death globally, largely driven by modifiable lifestyle factors. With growing interest in dietary strategies for NCDs prevention and management, functional foods like watercress (Nasturtium [...] Read more.

Non-communicable diseases (NCDs) such as cardiovascular disease, diabetes, cancer, and chronic respiratory conditions are the leading causes of death globally, largely driven by modifiable lifestyle factors. With growing interest in dietary strategies for NCDs prevention and management, functional foods like watercress (Nasturtium officinale) have attracted attention for their rich phytochemical content and potential health benefits. This narrative review synthesizes 88 sources published between 2019 and March 2025, exploring the effects of watercress bioactive compounds on major NCDs. Watercress is abundant in glucosinolates, isothiocyanates (especially phenethyl isothiocyanate), flavonoids, vitamins, and minerals. These compounds contribute to antioxidant, anti-inflammatory, and metabolic regulatory effects. Preclinical and clinical studies show that watercress supplementation may improve lipid profiles, reduce oxidative stress, and modulate inflammation in cardiovascular and respiratory conditions. It also appears to enhance insulin function and reduce blood glucose levels. In cancer models, watercress extracts exhibit antiproliferative, pro-apoptotic, and chemoprotective properties, with selective toxicity towards cancer cells and protective effects on normal cells. These findings highlight the therapeutic potential of watercress as a dietary adjunct in NCDs prevention and management, supporting the need for further clinical research. Full article

(This article belongs to the Special Issue Natural Bioactives: Exploring Their Therapeutic Potential—2nd Edition)

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13 pages, 2203 KiB

Open AccessArticle

Ablation of the Evolutionarily Acquired Functions of the Atp1b4 Gene Increases Metabolic Capacity and Reduces Obesity

by Nikolai N. Modyanov, Lucia Russo, Sumona Ghosh Lester, Tamara R. Castañeda, Himangi G. Marathe, Larisa V. Fedorova, Raymond E. Bourey, Sonia M. Najjar and Ivana L. de la Serna

Life 2025, 15(7), 1103; https://doi.org/10.3390/life15071103 (registering DOI) - 14 Jul 2025

Abstract

In placental mammals, the co-option of vertebrate orthologous ATP1B4 genes has profoundly altered the properties of the encoded BetaM proteins, which function as bona fide β-subunits of Na,K-ATPases in lower vertebrates. Eutherian BetaM acquired an extended Glu-rich N-terminal domain resulting in the complete [...] Read more.

In placental mammals, the co-option of vertebrate orthologous ATP1B4 genes has profoundly altered the properties of the encoded BetaM proteins, which function as bona fide β-subunits of Na,K-ATPases in lower vertebrates. Eutherian BetaM acquired an extended Glu-rich N-terminal domain resulting in the complete loss of its ancestral function and became a skeletal and cardiac muscle-specific component of the inner nuclear membrane. BetaM is expressed at the highest level during perinatal development and is implicated in gene regulation. Here we report the long-term consequences of Atp1b4 ablation on metabolic parameters in adult mice. Male BetaM-deficient (Atp1b4−/Y) mice have remarkably lower body weight and adiposity than their wild-type littermates, despite higher food intake. Indirect calorimetry shows higher energy expenditure (heat production and oxygen consumption) with a greater spontaneous locomotor activity in Atp1b4−/Y males. Their lower respiratory exchange ratio suggests a greater reliance on fat metabolism compared to their wild-type counterparts. Consistently, Atp1b4−/Y KO mice exhibit enhanced β-oxidation in skeletal muscle, along with improved glucose and insulin tolerance. These robust metabolic changes induced by Atp1b4 disruption demonstrate that eutherian BetaM plays an important role in regulating adult mouse metabolism. This demonstrates that bypassing the co-option of Atp1b4 potentially reduces susceptibility to obesity. Thus, Atp1b4 ablation leading to the loss of evolutionarily acquired BetaM functions serves as a model for a potential alternative pathway in mammalian evolution. Full article

(This article belongs to the Section Evolutionary Biology)

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17 pages, 598 KiB

Open AccessReview

Management Strategies for Dry Eye Syndrome in Patients with Obesity—A Literature Review

by Cosmin Victor Ganea, Călina Anda Sandu, Corina Georgiana Bogdănici and Camelia Margareta Bogdănici

Life 2025, 15(7), 1102; https://doi.org/10.3390/life15071102 (registering DOI) - 14 Jul 2025

Abstract

Tear film alterations are commonly associated with ocular pathology. The tear film plays a vital role in maintaining the optical properties of the cornea and contains essential elements required for healing and preserving the integrity of the ocular surface. As a biological fluid, [...] Read more.

Tear film alterations are commonly associated with ocular pathology. The tear film plays a vital role in maintaining the optical properties of the cornea and contains essential elements required for healing and preserving the integrity of the ocular surface. As a biological fluid, the tear film is easily collected using non-invasive techniques, making it a promising candidate for analysis and often referred to as an ideal biofluid. Several studies have attempted to identify biomarkers in the tear film that could be linked to systemic or ocular disorders, with the goal of developing tools for diagnosis or even early prevention. The quality and quantity of the tear film are influenced by hormonal status, emotional experiences related to social and familial events, and the work environment. Systemic disorders are often reflected at the ocular level through alterations in the tear film. Obesity is a well-recognized public health concern, extensively studied and investigated, much like other common systemic conditions. The presence of low-grade, chronic inflammation associated with excess body weight has been validated in several studies. The strategies for preventing obesity induced dry eye disease are based on regular physical activity, maintaining adequate hydration through sufficient fluid intake, weight loss, and the supplementation of essential fatty acids. This narrative literature review aims to highlight the tear film alterations associated with obesity. The article is intended for ophthalmologists, general practitioners, nutritionists, and researchers. Full article

(This article belongs to the Section Medical Research)

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15 pages, 2830 KiB

Open AccessArticle

Postbiotic Intervention in Sarcopenia: The Role of Lactiplantibacillus plantarum HY7715 and Its Extracellular Vesicles

by Kippeum Lee, Soo Dong Park, Joo Yun Kim, Jae Jung Shim and Jae Hwan Lee

Life 2025, 15(7), 1101; https://doi.org/10.3390/life15071101 (registering DOI) - 14 Jul 2025

Abstract

Sarcopenia, the age-related loss of skeletal muscle mass and function, is associated with inflammation, mitochondrial dysfunction, and gut barrier impairment. This study investigates the postbiotic effects of heat-killed Lactiplantibacillus plantarum HY7715 (HY7715) and its extracellular vesicles (EVs) on muscle health and intestinal integrity. [...] Read more.

Sarcopenia, the age-related loss of skeletal muscle mass and function, is associated with inflammation, mitochondrial dysfunction, and gut barrier impairment. This study investigates the postbiotic effects of heat-killed Lactiplantibacillus plantarum HY7715 (HY7715) and its extracellular vesicles (EVs) on muscle health and intestinal integrity. In C2C12 myotubes, both treatments enhanced myogenic differentiation by upregulating Myf5 and MYOG, and improved mitochondrial activity and biogenesis via increased PGC1α and mTOR expression. Under TNFα-induced muscle atrophy, they suppressed expression of atrophy-related markers (Fbox32, MuRF1, and myostatin). EVs showed stronger anti-inflammatory effects by reducing IL6 expression in muscle cells. In intestinal Caco-2 cells, HY7715-derived EVs improved barrier function by upregulating tight junction proteins (ZO-1, occludin, and claudins), and effectively reduced LPS-induced inflammation. These findings suggest that heat-killed HY7715 and its EVs may alleviate sarcopenia by enhancing muscle regeneration and maintaining intestinal homeostasis, highlighting their potential as safe, gut–muscle axis-targeting postbiotic interventions for healthy aging. Full article

(This article belongs to the Special Issue Postbiotics—Bioactive Microbial Compounds as Health-Promoting Agents)

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32 pages, 1397 KiB

Open AccessReview

Prognostic Significance of the Comprehensive Biomarker Analysis in Colorectal Cancer

by Vera Potievskaya, Elizaveta Tyukanova, Marina Sekacheva, Zaki Fashafsha, Anastasia Fatyanova, Mikhail Potievskiy, Elena Kononova, Anna Kholstinina, Ekatherina Polishchuk, Peter Shegai and Andrey Kaprin

Life 2025, 15(7), 1100; https://doi.org/10.3390/life15071100 - 14 Jul 2025

Abstract

Colorectal carcinoma remains one of the primary contributors to cancer deaths; however, it is also considered a preventable type of cancer, because the prognosis of the disease is directly dependent on its timely detection. Developing accurate risk prediction models for colorectal cancer is [...] Read more.

Colorectal carcinoma remains one of the primary contributors to cancer deaths; however, it is also considered a preventable type of cancer, because the prognosis of the disease is directly dependent on its timely detection. Developing accurate risk prediction models for colorectal cancer is crucial for identifying individuals at both low and high risk, as risk stratification determines the need for additional interventions, which carry their own risks. The development of new non-invasive diagnostic methods based on biomaterial analysis, alongside standard diagnostic techniques such as colonoscopy with biopsy, computed tomography scanning, and magnetic resonance imaging, can address multiple objectives: improving screening accuracy, providing a comprehensive assessment of minimal residual disease, identifying patients at a high risk of colorectal cancer, and evaluating the effectiveness of ongoing treatments. The lack of sensitive diagnostic methods drives contemporary research toward the discovery of new tools for detecting tumor cells, particularly through the examination of biological materials, including blood, exhaled air, and tumor tissue itself. In this article, we analyze current studies regarding biomarkers in colorectal cancer and prognostic significance. Full article

(This article belongs to the Section Physiology and Pathology)

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14 pages, 1595 KiB

Open AccessArticle

PBPK Modeling of Acetaminophen in Pediatric Populations: Incorporation of SULT Enzyme Ontogeny to Predict Age-Dependent Metabolism and Systemic Exposure

by Sonia Sharma and David R. Taft

Life 2025, 15(7), 1099; https://doi.org/10.3390/life15071099 - 13 Jul 2025

Abstract

Sulfotransferase (SULT) enzymes contribute significantly to drug metabolism in pediatric patients. The purpose of this study was to develop a PBPK model for acetaminophen (APAP) in pediatric populations that accounts for the ontogeny of SULT isozymes that play a critical role in APAP [...] Read more.

Sulfotransferase (SULT) enzymes contribute significantly to drug metabolism in pediatric patients. The purpose of this study was to develop a PBPK model for acetaminophen (APAP) in pediatric populations that accounts for the ontogeny of SULT isozymes that play a critical role in APAP metabolism. PBPK modeling and simulation were performed using the Simcyp^® Simulator. The model incorporated the developmental ontogeny of three key hepatic SULT enzymes: SULT1A1, SULT1A3, and SULT2A1 using “best-fit” ontogeny equations for each isozyme as determined by nonlinear regression analysis of enzyme abundance versus age. PBPK model-simulated pharmacokinetic profiles for APAP captured observed clinical data for systemic exposure (Cmax, AUC) in neonates, infants, and children. SULTS accounted for ~60% APAP metabolism in neonates, with decreased contributions to infants and children. Model sensitivity analysis highlighted the potential for APAP metabolic DDIs, primarily through SULT1A1. The study demonstrates that the impact of SULT enzymes on drug metabolism is significant in neonates, which is an important clinical consideration for APAP. A PBPK model that incorporates SULT ontogeny has the potential to help inform dosing decisions in this special patient population. Full article

(This article belongs to the Section Pharmaceutical Science)

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45 pages, 797 KiB

Open AccessReview

Non-Celiac Villous Atrophy—A Problem Still Underestimated

by Katarzyna Napiórkowska-Baran, Paweł Treichel, Adam Wawrzeńczyk, Ewa Alska, Robert Zacniewski, Maciej Szota, Justyna Przybyszewska, Amanda Zoń and Zbigniew Bartuzi

Life 2025, 15(7), 1098; https://doi.org/10.3390/life15071098 - 13 Jul 2025

Abstract

Non-celiac villous atrophy (NCVA) is a multifaceted and under-recognized clinical entity with an etiology beyond celiac disease. This review critically examines the diverse pathophysiological mechanisms underlying NCVA, including autoimmune enteropathies, immune deficiency-related disorders, infectious processes, drug-induced trauma, and metabolic or environmental influences. A [...] Read more.

Non-celiac villous atrophy (NCVA) is a multifaceted and under-recognized clinical entity with an etiology beyond celiac disease. This review critically examines the diverse pathophysiological mechanisms underlying NCVA, including autoimmune enteropathies, immune deficiency-related disorders, infectious processes, drug-induced trauma, and metabolic or environmental influences. A comprehensive synthesis of peer-reviewed literature, clinical studies, and case reports was conducted, adopting a multidisciplinary perspective that integrates immunologic, infectious, metabolic, and pharmacologic insights. The literature search was performed in three phases: identification of relevant studies, critical assessment of selected publications, and synthesis of key findings. Searches were carried out in PubMed, Scopus, Web of Science, and Google Scholar databases. The final search, completed in June 2025, included international, English-language articles, electronic books, and online reports. Studies were included if they addressed NCVA in the context of pathophysiology, clinical manifestations, or management strategies, with priority given to publications from the last ten years (2015–2025). The search strategy used the primary term “non-celiac villous atrophy” combined with supplementary keywords such as autoimmune enteropathy, common variable immunodeficiency, tropical sprue, drug-related enteropathy, pathophysiology, immunological mechanisms, chronic inflammation, genetic factors, environmental influences, and clinical management. Histopathological evaluations reveal that NCVA often manifests with varying degrees of villous blunting, crypt hypertrophy, and intraepithelial lymphocytosis, albeit without the gliadin-specific immune response seen in celiac disease. Various immune pathways are involved, such as autoimmune deregulation and chronic inflammatory responses, while drug-induced and environmental factors further complicate its clinical picture. These findings highlight significant diagnostic challenges and underscore the need to adapt diagnostic algorithms that combine clinical history, serologic evaluations, and histopathologic analysis. In conclusion, an in-depth understanding of the heterogeneous etiology of NCVA is critical to improving diagnostic accuracy and optimizing therapeutic strategies. Future research should prioritize the identification of specific biomarkers and the development of targeted interventions to address the unique mechanisms underlying NCVA, thereby improving patient management and outcomes. Full article

(This article belongs to the Special Issue From Physiology and Pathology Research to Clinical Insights in Gastrointestinal Disorders)

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22 pages, 1137 KiB

Open AccessReview

Mycobacterium Ulcerans Ulcer: Current Trends in Antimicrobial Management and Reconstructive Surgical Strategies

by Bryan Lim, Omar Shadid, Jennifer Novo, Yi Mon, Ishith Seth, Gianluca Marcaccini, Roberto Cuomo, Daniel P. O’Brien and Warren M. Rozen

Life 2025, 15(7), 1096; https://doi.org/10.3390/life15071096 - 13 Jul 2025

Abstract

Background: Mycobacterium ulcerans causes Buruli ulcer (BU), a necrotizing skin disease endemic in over 30 countries. Its toxin, mycolactone, drives tissue destruction, and the infection is transmitted via environmental reservoirs or vectors. Disease patterns vary globally, and an improved understanding of their [...] Read more.

Background: Mycobacterium ulcerans causes Buruli ulcer (BU), a necrotizing skin disease endemic in over 30 countries. Its toxin, mycolactone, drives tissue destruction, and the infection is transmitted via environmental reservoirs or vectors. Disease patterns vary globally, and an improved understanding of their pathogenesis may enhance current antimicrobial and surgical treatments. Methods: A comprehensive literature search from 1901 to 2025 was conducted across major databases to explore antimicrobial and reconstructive surgical strategies for Mycobacterium ulcerans. Search terms included BU, key antibiotics, and surgical interventions. Relevant English-language studies on treatment outcomes were reviewed to summarize evolving management trends and emerging therapeutic approaches. Results and Discussion: This review highlights the importance of early diagnosis and timely antimicrobial therapy in preventing disease progression and limb loss. It reviews WHO-recommended antibiotic regimens and discusses the theoretical risk of drug resistance, although clinical resistance remains rare and unreported in Australia. Surgical interventions in select cases are crucial, with timing being a significant factor in functional outcomes. The review also covers pediatric-specific challenges, including growth preservation and psychosocial support for young patients. Reconstructive options focus on limb salvage and staged reconstructions, with multidisciplinary care essential for optimal outcomes. The paper advocates for RCTs to refine treatment protocols, surgical guidelines, and explore emerging antibiotic therapies such as telacebec. Conclusions: BU remains a global health challenge, requiring early diagnosis, timely antimicrobial therapy, and surgery in selected cases. Future research will refine treatment and reduce long-term impacts. Full article

(This article belongs to the Section Medical Research)

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29 pages, 4862 KiB

Open AccessArticle

Repurposed Antipsychotics as Potential Anticancer Agents: Clozapine Efficacy and Dopaminergic Pathways in Neuroblastoma and Glioblastoma

by Catarina Moura, Maria João Gouveia and Nuno Vale

Life 2025, 15(7), 1097; https://doi.org/10.3390/life15071097 - 12 Jul 2025

Abstract

Neuro-oncology focuses on the diagnosis and treatment of brain tumors, which, despite their rarity, are associated with high mortality due to their invasiveness and limited treatment options. Emerging evidence suggests that dopamine (DA), a neurotransmitter crucial for cognitive and emotional processes, and its [...] Read more.

Neuro-oncology focuses on the diagnosis and treatment of brain tumors, which, despite their rarity, are associated with high mortality due to their invasiveness and limited treatment options. Emerging evidence suggests that dopamine (DA), a neurotransmitter crucial for cognitive and emotional processes, and its receptors may influence tumor growth and the tumor microenvironment. This study aimed to evaluate the potential anticancer effects of repurposed antipsychotic dopamine-targeting drugs (Clozapine, CLZ; Pimozide, PIM; Olanzapine, OLZ; and Risperidone, RIS) and antiemetic drugs (Domperidone, DOM; Droperidol, DRO) on neuroblastoma (SH-SY5Y) and glioblastoma (A172) cell lines, and to assess whether their efficacy is modulated by oxidative stress and DA synthesis. The drugs were first tested individually, followed by co-treatment with tyrosine (Tyr), a dopamine precursor, and hydrogen peroxide (H₂O₂), an inducer of oxidative stress. Additionally, drug activity was evaluated in the simultaneous presence of H₂O₂ and Tyr. CLZ exhibited the highest cytotoxicity in both cell lines, suggesting strong anticancer potential and also synergism among the different combinations, particularly in SH-SY5Y. Liquid chromatography of the extracellular medium showed greater Tyr consumption in SH-SY5Y compared to A172 cells, indicating a higher dependence on extracellular Tyr to mitigate drug- and/or stress-induced cytotoxicity. In summary, several of the repurposed antipsychotics demonstrated cytotoxic effects on central nervous system tumor cells, with CLZ showing the most promising activity, even under oxidative stress conditions. These findings support further investigation into dopamine-targeting drugs as potential therapeutic agents in neuro-oncology. Full article

(This article belongs to the Section Pharmaceutical Science)

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16 pages, 1361 KiB

Open AccessReview

Cardiovascular Remodeling and Potential Controversies in Master Endurance Athletes—A Narrative Review

by Othmar Moser, Stefan J. Schunk, Volker Schöffl, Janis Schierbauer and Paul Zimmermann

Life 2025, 15(7), 1095; https://doi.org/10.3390/life15071095 - 12 Jul 2025

Abstract

While the interest and participation in general endurance training and recreational sports competitions have continuously increased in recent decades, the number of recreational master-level endurance athletes has additionally multiplied. Athletes, active men and women older than 40 years of age, who participate in [...] Read more.

While the interest and participation in general endurance training and recreational sports competitions have continuously increased in recent decades, the number of recreational master-level endurance athletes has additionally multiplied. Athletes, active men and women older than 40 years of age, who participate in competitive athletics are usually referred to by the term master athletes (MAs). Previous research revealed the significant benefits of regular moderate physical activity, i.e., its positive influence on cardiovascular risk factors and cardiovascular health; however, recent data have raised concerns that long-term endurance exercise participation is associated with cardiac remodeling and potential adverse cardiovascular outcomes. Previous research also indicated potential structural, functional, and electrical remodeling in MAs due to prolonged and repeated exposure to high-intensity endurance exercise—a condition known as athlete’s heart. In this review, we focus on the association between extreme levels of endurance exercise and potential cardiovascular controversies, such as arrhythmogenesis due to new-onset atrial fibrillation, accelerated coronary artery atherosclerosis, and exercise-induced cardiac remodeling. Additionally, the exercise-dependent modulation of immunological response, such as proteomic response and cytokine alterations, is discussed. Furthermore, we discuss the impact of nutritional supplements in MAs and their potential benefits and harmful interactions. We aim to provide sports medicine practitioners with knowledge of these contemporary longevity controversies in sports cardiology and to highlight the importance of shared decision making in situations of clinical uncertainty. Full article

(This article belongs to the Special Issue Nutritional Supplements and Cardiovascular Function in Athletes and Sedentary People)

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21 pages, 3463 KiB

Open AccessArticle

Hybrid Genome and Clinical Impact of Emerging Extensively Drug-Resistant Priority Bacterial Pathogen Acinetobacter baumannii in Saudi Arabia

by J. Francis Borgio

Life 2025, 15(7), 1094; https://doi.org/10.3390/life15071094 - 12 Jul 2025

Abstract

Acinetobacter baumannii is listed by the World Health Organization as an emerging bacterial priority pathogen, the prevalence and multidrug resistance of which have been increasing. This functional genomics study aimed to understand the drug-resistance mechanisms of an extensively drug-resistant (XDR) A. baumannii strain [...] Read more.

Acinetobacter baumannii is listed by the World Health Organization as an emerging bacterial priority pathogen, the prevalence and multidrug resistance of which have been increasing. This functional genomics study aimed to understand the drug-resistance mechanisms of an extensively drug-resistant (XDR) A. baumannii strain (IRMCBCU95U) isolated from a transtracheal aspirate sample from a female patient with end-stage renal disease in Saudi Arabia. The whole genome of IRMCBCU95U (4.3 Mbp) was sequenced using Oxford Nanopore long-read sequencing to identify and compare the antibiotic-resistance profile and genomic features of A. baumannii IRMCBCU95U. The antibiogram of A. baumannii IRMCBCU95U revealed resistance to multiple antibiotics, including cefepime, ceftazidime, ciprofloxacin, imipenem, meropenem and piperacillin/tazobactam. A comparative genomic analysis between IRMCBCU95U and A. baumannii K09-14 and ATCC 19606 identified significant genetic heterogeneity and mosaicism among the strains. This analysis also demonstrated the hybrid nature of the genome of IRMCBCU95U and indicates that horizontal gene transfer may have occurred between these strains. The IRMCBCU95U genome has a diverse range of genes associated with antimicrobial resistance and mobile genetic elements (ISAba1 and IS26) associated with the spread of multidrug resistance. The presence of virulence-associated genes that are linked to iron acquisition, motility and transcriptional regulation confirmed that IRMCBCU95U is a priority human pathogen. The plasmid fragment IncFIB(pNDM-Mar) observed in the strain is homologous to the plasmid in Klebsiella pneumoniae (439 bp; similarity: 99.09%), which supports its antimicrobial resistance. From these observations, it can be concluded that the clinical A. baumannii IRMCBCU95U isolate is an emerging extensively drug-resistant human pathogen with a novel combination of resistance genes and a plasmid fragment. The complex resistome of IRMCBCU95U highlights the urgent need for genomic surveillance in hospital settings in Saudi Arabia to fight against the spread of extensively drug-resistant A. baumannii. Full article

(This article belongs to the Special Issue Latest Updates on Clinical Microbiology and Antimicrobial Resistant Infection)

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22 pages, 637 KiB

Open AccessArticle

Congee Containing Carotenoids-Enriched Functional Ingredient from Tomato Improves Cognition, Serum α-Synuclein, Monoaminergic Function, and Gut-Brain Axis Functions in the Elderly Volunteers

by Jintanaporn Wattanathorn, Supaporn Muchimapura, Wipawee Thukham-mee and Terdthai Tong-un

Life 2025, 15(7), 1093; https://doi.org/10.3390/life15071093 - 11 Jul 2025

Abstract

Owing to the need for a brain supplement targeting neuroprotection against age-related brain disorders and the known effect of carotenoids on brain function, we aimed to assess the effect of consuming carotenoid-rich functional congee for 8 weeks on cognitive function and age-related serum [...] Read more.

Owing to the need for a brain supplement targeting neuroprotection against age-related brain disorders and the known effect of carotenoids on brain function, we aimed to assess the effect of consuming carotenoid-rich functional congee for 8 weeks on cognitive function and age-related serum biomarkers. Both males and females (60–70 years old) were randomly assigned to consume either placebo or carotenoid-rich functional congee containing dried tomato powder at doses of 200 and 400 mg per day. Cognitive function, working memory, and serum biomarkers including alpha-synuclein and PARK7, together with serum oxidative stress parameters and neurotransmitters, were assessed prior to consumption and every 4 weeks throughout the study period. The contents of Lactobacillus and Bifidobacterium spp. in feces were also determined. Both doses of carotenoid-enriched congee enhanced cognitive function (P300), but only low doses improved working memory and decreased the activity of MAO-A and serum alpha-synuclein. The high-dose congee-treated group exhibited an increase in the density of Lactobacillus spp. in feces. Taking all data together, the carotenoid-enriched congee enhances cognitive function and working memory. The mechanisms may partly involve the increase in monoaminergic function, while the modulation of the gut–brain axis may require further confirmation. Full article

(This article belongs to the Special Issue Therapeutic Effects of Natural Products on Human Diseases: 2nd Edition)

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14 pages, 2729 KiB

Open AccessReview

Review on the Clinical, Imaging, and Therapeutic Aspects of Cardiac Masses in Dog

by Nicoleta Andreea Mincă, Ionuț Cătălin Dumbravă, Niculae Tudor, Alina Ștefănescu, Alexandru Bogdan Vițălaru, Lucian Ioniță and Dorin Țogoe

Life 2025, 15(7), 1092; https://doi.org/10.3390/life15071092 - 11 Jul 2025

Abstract

Cardiac tumors in dogs, although rare in the past, have shown an increasing incidence due to advances in veterinary imaging, especially echocardiography, CT, and MRI with contrast agents. Right atrial hemangiosarcoma is the most common form of tumor associated with pericardial effusion and [...] Read more.

Cardiac tumors in dogs, although rare in the past, have shown an increasing incidence due to advances in veterinary imaging, especially echocardiography, CT, and MRI with contrast agents. Right atrial hemangiosarcoma is the most common form of tumor associated with pericardial effusion and cardiac tamponade, followed by chemodectoma, which is more common in brachycephalic breeds. The diagnosis is based on echocardiographic examination, supplemented by advanced methods and possibly biopsy. Clinical signs are often non-specific, requiring an integrated approach. Treatment includes pericardiocentesis, chemotherapy, and, in some cases, surgery, but the prognosis remains reserved. Full article

(This article belongs to the Special Issue Veterinary Pathology and Veterinary Anatomy: 3rd Edition)

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12 pages, 4125 KiB

Open AccessArticle

New Perspectives of Underlying Cardiomyopathy in Pediatric SMA Patients—An Age Matched Control Study

by Georgiana Nicolae, Andrei Capitanescu, Madalina Cristina Leanca, Elena Neagu, Daniela Vasile, Cristina Filip, Eliza Cinteza, Amelia Aria, Bianka Maria Pavlov, Gabriela Uscoiu, Cristiana Ioana Raita and Andrada Mirea

Life 2025, 15(7), 1091; https://doi.org/10.3390/life15071091 - 11 Jul 2025

Abstract

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder primarily affecting motor neurons. Emerging evidence suggests it also involves multiple organs, including potential cardiac manifestations. This study aimed to evaluate cardiac abnormalities in pediatric SMA patients compared to age-matched healthy controls, providing insight [...] Read more.

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder primarily affecting motor neurons. Emerging evidence suggests it also involves multiple organs, including potential cardiac manifestations. This study aimed to evaluate cardiac abnormalities in pediatric SMA patients compared to age-matched healthy controls, providing insight into underlying cardiomyopathy in this population. A total of 126 children were included in the study, with 63 SMA patients and 63 age-matched controls. We conducted clinical examinations, standard electrocardiography (ECG), and cardiac ultrasound (CUS) in all patients. Electrocardiographic analysis revealed a higher prevalence of sinus tachycardia in the SMA group and significantly deeper Q waves, indicating possible myocardial involvement. Echocardiographic findings demonstrated a significant reduction in left ventricular mass and left ventricular mass index in SMA patients compared to controls, despite normal systolic function. Statistical analysis confirmed that SMA diagnosis was an independent predictor of reduced myocardial mass, suggesting a distinct cardiac phenotype in SMA patients. This study provides new evidence of subclinical cardiac involvement in SMA, characterized by reduced myocardial mass, altered electrocardiographic parameters, and increased sinus tachycardia. These findings suggest a previously unrecognized form of cardiomyopathy in SMA that differs from cardiac manifestations typically seen in other neuromuscular disorders. Full article

(This article belongs to the Special Issue Pediatric Cardiology Frontiers: Innovations in Diagnosis and Treatment)

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27 pages, 2356 KiB

Open AccessArticle

Exploring the Anticancer Activity of Artocarpus heterophyllus Leaves: Selective Effects on Triple-Negative Breast Cancer and HPV16-Positive Tumorigenic Cells

by Ariana Cabrera-Licona, Gustavo A. Hernández-Fuentes, Oscar F. Beas-Guzmán, Alejandra E. Hernández-Rangel, Janet Diaz-Martinez, Osval A. Montesinos-López, José Guzmán-Esquivel, Víctor H. Cervantes-Kardasch, Mario Ramírez-Flores, Alejandrina Rodriguez-Hernandez, Erika R. González-Espinosa, Ana B. Castellanos-Gutiérrez, Francisco Orozco-Ramos, Valery Melnikov and Iván Delgado-Enciso

Life 2025, 15(7), 1090; https://doi.org/10.3390/life15071090 - 11 Jul 2025

Abstract

Artocarpus heterophyllus (jackfruit) is widely distributed in subtropical and tropical regions, and some phytochemicals isolated from this species have demonstrated anti-proliferative effects. However, its impact on triple-negative breast cancer (TNBC) and HPV-related cervical cancer models remains unclear. This study evaluated the phytochemical profile [...] Read more.

Artocarpus heterophyllus (jackfruit) is widely distributed in subtropical and tropical regions, and some phytochemicals isolated from this species have demonstrated anti-proliferative effects. However, its impact on triple-negative breast cancer (TNBC) and HPV-related cervical cancer models remains unclear. This study evaluated the phytochemical profile and anticancer activity of an ethanolic extract from A. heterophyllus leaves (AHEE) in the TNBC cell line MDA-MB-231 and in the HPV-16⁺ murine cancer cell line TC-1. Phytochemical screening and spectroscopic analyses (UV-Vis, IR, ¹H, and ¹³C NMR) revealed the presence of tannins, alkaloids, steroids, coumarins, and flavone-type flavonoids, with a total phenolic content of 3.34 µg GAE/mg and flavonoid content of 0.44 mg QE/g extract. In 2D cultures, AHEE reduced cell viability by 49% in TC-1 and 24% in MDA-MB-231 at 300 µg/mL, inhibited colony formation and migration in TC-1, and impaired survival but not migration in MDA-MB-231. In 3D cultures, 250 µg/mL inhibited proliferation, migration, and anchorage-independent growth in both cell lines. Furthermore, the combination of AHEE with one-fifth of the IC₅₀ of doxorubicin or cisplatin produces an effect comparable to that observed with the full IC₅₀ of these drugs. These findings suggest that AHEE possesses anticancer activity with cell-type-specific effects and highlight its potential as an adjuvant therapy. Further studies are warranted to elucidate its mechanisms of action. Full article

(This article belongs to the Special Issue Natural Bioactives: Exploring Their Therapeutic Potential—2nd Edition)

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11 pages, 862 KiB

Open AccessArticle

Level 3 Cardiopulmonary Exercise Testing to Guide Therapeutic Decisions in Non-Severe Pulmonary Hypertension with Lung Disease

by Raj Parikh, Chebly Dagher and Harrison W. Farber

Life 2025, 15(7), 1089; https://doi.org/10.3390/life15071089 - 11 Jul 2025

Abstract

Inhaled treprostinil is approved for the treatment of pulmonary hypertension-associated interstitial lung disease (PH-ILD); however, it has not shown significant benefit in patients with a pulmonary vascular resistance (PVR) < 4 WU. As such, treatment for non-severe PH-ILD remains controversial. A total of [...] Read more.

Inhaled treprostinil is approved for the treatment of pulmonary hypertension-associated interstitial lung disease (PH-ILD); however, it has not shown significant benefit in patients with a pulmonary vascular resistance (PVR) < 4 WU. As such, treatment for non-severe PH-ILD remains controversial. A total of 16 patients with non-severe PH-ILD were divided into two groups based on changes in PVR during exercise: a dynamic PVR group (n = 10), characterized by an increase in PVR with exertion, and a static PVR group (n = 6), with no increase in PVR with exercise. The dynamic PVR group received inhaled treprostinil, while the static PVR group was monitored off therapy. Baseline and 16-week follow-up values were compared within each group. At 16 weeks, the dynamic PVR group demonstrated significant improvements in mean 6 min walk distance (6MWD) (+32.5 m, p < 0.05), resting PVR (−1.04 WU, p < 0.05), resting mean pulmonary arterial pressure (mPAP) (−5.8 mmHg, p < 0.05), exercise PVR (−1.7 WU, p < 0.05), exercise mPAP (−13 mmHg, p < 0.05), and estimated right ventricular systolic pressure (−9.2 mmHg, p < 0.05). In contrast, the static PVR group remained clinically stable. These observations suggest that an exercise-induced increase in PVR, identified through Level 3 CPET, may help select patients with non-severe PH-ILD who are more likely to benefit from early initiation of inhaled treprostinil. Full article

(This article belongs to the Section Physiology and Pathology)

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