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Life, Volume 15, Issue 7 (July 2025) – 118 articles

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13 pages, 2203 KiB  
Article
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  
Review
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  
Article
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
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32 pages, 1397 KiB  
Review
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  
Article
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  
Review
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
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22 pages, 1137 KiB  
Review
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  
Article
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
Viewed by 23
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  
Review
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
Viewed by 13
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
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21 pages, 3463 KiB  
Article
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
Viewed by 14
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
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22 pages, 637 KiB  
Article
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
Viewed by 33
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
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14 pages, 2729 KiB  
Review
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
Viewed by 27
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  
Article
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
Viewed by 16
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
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27 pages, 2356 KiB  
Article
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
Viewed by 40
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
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11 pages, 862 KiB  
Article
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
Viewed by 41
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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17 pages, 1609 KiB  
Article
Meta-Analysis of Wild Relatives and Domesticated Species of Rice, Tomato, and Soybean Using Publicly Available Transcriptome Data
by Makoto Yumiya and Hidemasa Bono
Life 2025, 15(7), 1088; https://doi.org/10.3390/life15071088 - 11 Jul 2025
Viewed by 57
Abstract
The domesticated species currently available in the market have been developed through the breeding of wild relatives. Breeding strategies using wild relatives with high genetic diversity are attracting attention as an important approach for addressing climate change and ensuring sustainable food supply. However, [...] Read more.
The domesticated species currently available in the market have been developed through the breeding of wild relatives. Breeding strategies using wild relatives with high genetic diversity are attracting attention as an important approach for addressing climate change and ensuring sustainable food supply. However, studies examining gene expression variation in multiple wild and domesticated species are limited. Therefore, we aimed to investigate the changes in gene expression associated with domestication. We performed a meta-analysis of public gene expression data of domesticated species of rice, tomato, and soybean and their presumed ancestral species using 21 pairs for rice, 36 pairs for tomato, and 56 pairs for soybean. In wild relatives, the expression of genes involved in osmotic, drought, and wound stress tolerance was upregulated, with 18 genes included in the top 5% of DW scores. In domesticated species, upregulated expression was observed in genes related to auxin and those involved in the efflux of heavy metals and harmful substances, with 36 genes included in the top 5% of DW scores. These findings provide insights into how domestication influences changes in crop traits. Thus, our findings may contribute to rapid breeding and the development of new varieties capable of growing in harsh natural environments. Hence, a new cultivation method called “de novo domestication” has been proposed, which combines the genetic diversity of currently unused wild relatives and wild relatives with genome editing technologies that enable rapid breeding. Full article
(This article belongs to the Special Issue Recent Advances in Crop Genetics and Breeding)
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14 pages, 429 KiB  
Article
Effects of a Self-Management Telehealth Program on Improving Strength and Hand Function in Systemic Sclerosis Patients: A Randomized Controlled Trial
by Orathai Wantha, Ajanee Mahakkanukrauh, Siraphop Suwannaroj, Kwankaew Tuydaung, Nonglak Methakanjanasak, Kannika Srichomphu, Jinnaphat Kraipoj and Chingching Foocharoen
Life 2025, 15(7), 1087; https://doi.org/10.3390/life15071087 - 10 Jul 2025
Viewed by 151
Abstract
Objective: A self-management telehealth program to improve hand strength and function in systemic sclerosis (SSc) patients may improve their quality of life, so we investigated its efficacy. Methods: A 6-week prospective randomized controlled study was conducted in adults with SSc with a hand [...] Read more.
Objective: A self-management telehealth program to improve hand strength and function in systemic sclerosis (SSc) patients may improve their quality of life, so we investigated its efficacy. Methods: A 6-week prospective randomized controlled study was conducted in adults with SSc with a hand mobility in scleroderma (HAMIS) score > 1 or a limited range of motion in at least one hand joint. Participants were randomly allocated into three groups for six weeks of health education: (a) typical education, (b) watching video guides as needed, in addition to typical education, and (c) watching video guides and receiving weekly telephone notifications, in addition to typical education. The endpoints were the differences in self-management behavior, HAMIS scores, hand grip strength (HGS), and quality of life (QoL) using the European Quality of Life-5 Dimensions between groups, as well as the changes in these parameters compared to baseline. Results: A total of 24 patients per group were enrolled, with the majority diagnosed with diffuse cutaneous SSc (79.2%). Six weeks post-intervention, HGS improved significantly in both the video guide and telephone notification groups compared to typical education in both hands (p = 0.028, p = 0.044). Pincer grip differed between the groups in the non-dominant hand. Household modifications were more frequent in the video guide and telephone notification groups than in the typical education group (p = 0.023). All groups showed significant improvements in HGS and HAMIS scores in both hands, as well as in self-management behaviors, compared to baseline. QoL, as measured using a visual analog scale, improved significantly after the intervention in both the video guide and telephone notification groups, but not in the typical education group. Conclusions: Self-management telehealth programs effectively enhance hand strength, function, and self-management behaviors in patients with SSc with limited hand function. Weekly telephone notifications further reinforced continuity and engagement in these patients. Full article
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13 pages, 2262 KiB  
Systematic Review
The Role of Gut Microbiota in Insomnia: A Systematic Review of Case–Control Studies
by Yun Wang, Suyi Xie, Sizhe Chen, Chenyu Li, Yeuk Lam Chan, Ngan Yin Chan, Yun Kwok Wing, Francis K. L. Chan, Qi Su and Siew C. Ng
Life 2025, 15(7), 1086; https://doi.org/10.3390/life15071086 - 10 Jul 2025
Viewed by 168
Abstract
Background: Insomnia is one of the most prevalent health concerns and has a major impact on human health and quality of life. Increasing evidence indicates the gut microbiota’s role in sleep regulation through the gut–brain axis. This systematic review aims to summarise current [...] Read more.
Background: Insomnia is one of the most prevalent health concerns and has a major impact on human health and quality of life. Increasing evidence indicates the gut microbiota’s role in sleep regulation through the gut–brain axis. This systematic review aims to summarise current evidence on the role of gut microbiota alterations in insomnia. Methods: We searched PubMed, Embase, and Cochrane Library through November 2024 for case–control studies comparing gut microbiota in insomnia subjects and controls. The primary outcome was changes in microbiota diversity and bacteria taxonomy. Results: We included 15 case–control studies from 14 articles, consisting of 1321 subjects (603 insomnia; 718 controls). Eight studies showed reduced alpha diversity and eleven showed altered beta diversity in insomnia subjects. Depletions of specific taxa such as Lactobacillales (class Bacilli), Faecalibacterium, and Lachnospira and the enrichment of Actinobacteria, Bacteroidales (class Bacteroidia), and several genera, including Streptococcus, Blautia, Lactobacillus, Clostridium, Holdemanella, and Eubacterium hallii, were observed in insomnia subjects. There was a negative association between insomnia severity and abundance of Faecalibacterium and Lachnospira, and positive associations with Blautia. Conclusions: This systematic review identifies specific alterations in gut microbiota among insomnia subjects characterised by taxonomic changes that may serve as promising therapeutic targets for sleep disorders. Full article
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22 pages, 3914 KiB  
Article
The Enigmatic Schizoglyphid Mite Oriboglyphus maorianus gen. and sp. n. and Its Implications for Astigmatid Life Cycle Evolution
by Pavel B. Klimov, Vasiliy B. Kolesnikov, Matt Shaw, Qing-Hai Fan, Zhi-Qiang Zhang and Barry OConnor
Life 2025, 15(7), 1085; https://doi.org/10.3390/life15071085 - 10 Jul 2025
Viewed by 181
Abstract
A detailed morphological characterization is presented for Oriboglyphus maorianus gen. et sp. nov., a newly discovered modern representative of the relict family Schizoglyphidae, found in a nest of the termite Stolotermes ruficeps in New Zealand. This is the second extant schizoglyphid species known [...] Read more.
A detailed morphological characterization is presented for Oriboglyphus maorianus gen. et sp. nov., a newly discovered modern representative of the relict family Schizoglyphidae, found in a nest of the termite Stolotermes ruficeps in New Zealand. This is the second extant schizoglyphid species known from modern material, and its discovery provides rare insight into a transitional stage in the evolution of astigmatid life cycles. The phoretic stage appears to be a tritonymph—rather than the typical deutonymph—based on key morphological traits including three-segmented palps, three pairs of genital papillae, and the presence of a pharynx. These features suggest that early astigmatid mites evolved multiple ontogenetic routes to dispersal, including tritonymphal, deutonymphal, and possibly adult phoresy, before the canalization of life cycles around deutonymphal dispersal. The persistence of putatively ancestral traits in schizoglyphids, along with their apparent ecological conservatism in termite nests, indicates the role of environmental stability in preserving modes of life history that otherwise appear extinct. We also provide a key to describe Schizoglyphidae species and discuss the implications of this discovery for understanding the origins of phoresy-related metamorphosis in Astigmata. Full article
(This article belongs to the Special Issue Acari: Biodiversity, Biogeography and Taxonomy Studies)
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10 pages, 1841 KiB  
Case Report
Methadone-Induced Toxicity—An Unexpected Challenge for the Brain and Heart in ICU Settings: Case Report and Review of the Literature
by Cristina Buzatu, Sebastian Isac, Geani-Danut Teodorescu, Teodora Isac, Cristina Martac, Cristian Cobilinschi, Bogdan Pavel, Cristina Veronica Andreescu and Gabriela Droc
Life 2025, 15(7), 1084; https://doi.org/10.3390/life15071084 - 10 Jul 2025
Viewed by 136
Abstract
Introduction: Methadone, a synthetic opioid used for opioid substitution therapy (OST), is typically associated with arrhythmias rather than direct myocardial depression. Neurological complications, especially with concurrent antipsychotic use, have also been reported. Acute left ventricular failure in young adults is uncommon and often [...] Read more.
Introduction: Methadone, a synthetic opioid used for opioid substitution therapy (OST), is typically associated with arrhythmias rather than direct myocardial depression. Neurological complications, especially with concurrent antipsychotic use, have also been reported. Acute left ventricular failure in young adults is uncommon and often linked to genetic or infectious causes. We present a rare case of reversible cardiogenic shock and cerebellar insult due to methadone toxicity. Case Presentation: A 37-year-old man with a history of drug abuse on OST with methadone (130 mg/day) was admitted to the ICU with hemodynamic instability, seizures, and focal neurological deficits. Diagnostic workup revealed low cardiac output syndrome and a right cerebellar insult, attributed to methadone toxicity. The patient received individualized catecholamine support. After 10 days in the ICU, he was transferred to a general ward for ongoing cardiac and neurological rehabilitation and discharged in stable condition seven days later. Conclusions: Methadone-induced reversible left ventricular failure, particularly when accompanied by cerebellar insult, is rare but potentially life-threatening. Early recognition and multidisciplinary management are essential for full recovery in such complex toxicological presentations. Full article
(This article belongs to the Special Issue Critical Issues in Intensive Care Medicine)
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20 pages, 1908 KiB  
Article
Effects of Dietary Calcium and Phosphorus Levels on Growth Performance, Calcium–Phosphorus Homeostasis, and Gut Microbiota in Ningxiang Pigs
by Wenzhi Liu, Cheng Zhang, Xijie Kuang, Xianglin Zeng, Jiaqi Zhang, Qiye Wang and Huansheng Yang
Life 2025, 15(7), 1083; https://doi.org/10.3390/life15071083 - 9 Jul 2025
Viewed by 148
Abstract
Optimal dietary calcium (Ca) and phosphorus (P) requirements remain undetermined for Ningxiang pigs, a valuable indigenous Chinese breed. This study conducted a continuous feeding trial with two growth phases (grower: 30–50 kg; finisher: 50–80 kg) using fixed Ca/P ratios to systematically evaluate the [...] Read more.
Optimal dietary calcium (Ca) and phosphorus (P) requirements remain undetermined for Ningxiang pigs, a valuable indigenous Chinese breed. This study conducted a continuous feeding trial with two growth phases (grower: 30–50 kg; finisher: 50–80 kg) using fixed Ca/P ratios to systematically evaluate the effects of Ca/P levels on growth performance and mineral metabolism. A total of 180 pigs per phase were allocated to four Ca/P levels. During the grower phase, a dietary regimen of 0.83% Ca/0.67% P significantly increased the average daily feed intake (ADFI), average daily gain (ADG), and apparent total tract digestibility (ATTD) of energy and P. In the finisher phase, 0.60/0.48% Ca/P showed optimal growth performance, upregulated jejunal mineral transporters (CaSR and SLC34A2), enhanced bone mineralization (metatarsal ash content), and improved intestinal morphology (duodenal and jejunal villus height, jejunal villus surface area). This regimen also selectively enriched Peptostreptococcaceae abundance, indicating improved host–microbe interactions. Based on these findings, stage-specific nutritional strategies were recommended: 0.83% Ca/0.67% P during the grower phase and 0.60% Ca/0.48% P during the finisher phase. These protocols synergistically improve microbial ecology, intestinal function, and bone metabolism, thereby maximizing the growth potential of Ningxiang pigs. Full article
(This article belongs to the Special Issue Pig Microbiota Metabolism and Intestinal Health)
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12 pages, 1832 KiB  
Brief Report
HIV Protein TAT Dysregulates Multiple Pathways in Human iPSCs-Derived Microglia
by Liam Liyang Guo, Robert Jiang, Yan Cheng, Brooke Russell, Sanders Y. Yan and Ming-Lei Guo
Life 2025, 15(7), 1082; https://doi.org/10.3390/life15071082 - 9 Jul 2025
Viewed by 209
Abstract
In the era of combined antiretroviral therapy, around 50% of chronic HIV (+) individuals show varying degrees of memory and cognitive deficiency (NeuroHIV), a phenomenon of accelerated brain aging. HIV protein transactivator of transcription (TAT) has been well-accepted as a risk factor contributing [...] Read more.
In the era of combined antiretroviral therapy, around 50% of chronic HIV (+) individuals show varying degrees of memory and cognitive deficiency (NeuroHIV), a phenomenon of accelerated brain aging. HIV protein transactivator of transcription (TAT) has been well-accepted as a risk factor contributing to NeuroHIV through dysregulating microglia (Mg) functions. Previous studies have demonstrated that HIV-TAT can affect lipid metabolism, immune responses, autophagy, and senescence in rodent Mg. However, due to the significant species differences between rodent and human Mg (hMg), it is essential to take caution when interpreting the results obtained from rodent models into human conditions. For the unanswered questions, we generated hMg from human inducible pluripotent stem cells (iPSCs) and exposed them to HIV-TAT. The results obtained from Flow analysis and immunostaining experiments reveal that TAT can induce LD accumulation and increase perilipin-2 (Plin2) levels in hMg. Meanwhile, HIV-TAT can upregulate autophagosome formation and p53 levels. Through human immune array assay, we showed that TAT can increase the expression of multiple pro-inflammatory mediators, cytokines, and chemokines in hMg. Extensive bioinformatic analysis shows that HIV-TAT can affect multiple neuroimmune signaling pathways and indicates that microRNAs (miRNAs) are coherently involved in such dysregulation. Overall, our findings provide direct evidence showing that HIV-TAT can affect lipid metabolism, autophagy, senescence signaling, and multiple neuroimmune-related pathways in hMg and indicate the roles of novel miRNAs on NeuroHIV pathogenesis, which deserves further investigations. Full article
(This article belongs to the Section Medical Research)
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31 pages, 1909 KiB  
Review
Centella asiatica: Advances in Extraction Technologies, Phytochemistry, and Therapeutic Applications
by Zaw Myo Hein, Prarthana Kalerammana Gopalakrishna, Anil Kumar Kanuri, Warren Thomas, Farida Hussan, Venkatesh R. Naik, Nisha Shantakumari, Muhammad Danial Che Ramli, Mohamad Aris Mohd Moklas, Che Mohd Nasril Che Mohd Nassir and Thirupathirao Vishnumukkala
Life 2025, 15(7), 1081; https://doi.org/10.3390/life15071081 - 9 Jul 2025
Viewed by 323
Abstract
Centella asiatica (C. asiatica) has attracted significant scientific interest due to its extensive medicinal properties and long-established use in traditional medicine. This review synthesizes recent advances in the technological exploitation of C. asiatica, covering the extraction of bioactive constituents to [...] Read more.
Centella asiatica (C. asiatica) has attracted significant scientific interest due to its extensive medicinal properties and long-established use in traditional medicine. This review synthesizes recent advances in the technological exploitation of C. asiatica, covering the extraction of bioactive constituents to product development. Modern extraction techniques such as supercritical fluid extraction (SFE) and microwave-assisted extraction (MAE) have substantially improved the yield, selectivity, and preservation of key phytochemicals, particularly triterpenoids, saponins, and flavonoids. These compounds are now routinely characterized using advanced analytical platforms, ensuring product quality, consistency, and standardization. Moreover, the use of innovative formulation technologies and advanced delivery systems has facilitated the development of C. asiatica-based products tailored for various therapeutic areas, including pharmaceuticals, nutraceuticals, and cosmeceuticals targeting neuroprotection, wound healing, skin aging, and stress modulation. Alongside these developments, stringent quality control protocols, toxicological evaluations, and adherence to evolving regulatory standards enhance the safety and efficacy of C. asiatica-derived interventions. This review highlights the integration of traditional knowledge with modern science across the domains of extraction, analysis, formulation, and regulation. It serves as a comprehensive resource for researchers, formulators, and regulatory stakeholders aiming to develop high-quality, evidence-based C. asiatica products with improved bioavailability and therapeutic value. Full article
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15 pages, 979 KiB  
Article
Unveiling the Diagnostic Significance of Calprotectin in Serous Ovarian Carcinoma
by Alkis Matsas, Eleni Stamoula, Konstantinos Kontzoglou, Makarios Eleftheriades, Sophia Tsokkou, Panagiotis Christopoulos, Theodoros Panoskaltsis, Eleni Polydorou, Ioannis Sotiropoulos, Theodore Troupis and Dimitrios C. Iliopoulos
Life 2025, 15(7), 1080; https://doi.org/10.3390/life15071080 - 8 Jul 2025
Viewed by 306
Abstract
Introduction: Ovarian cancer (OC) is one of the most common gynecologic malignancies and has the highest mortality rate among them. OC has a multifactorial pathogenesis and is characterized by silent onset, progression, and late-stage detection. Therefore, accurate and early detection is of [...] Read more.
Introduction: Ovarian cancer (OC) is one of the most common gynecologic malignancies and has the highest mortality rate among them. OC has a multifactorial pathogenesis and is characterized by silent onset, progression, and late-stage detection. Therefore, accurate and early detection is of great importance in order to improve survival rates. Emerging evidence reveals that tumor markers are valuable diagnostic and monitoring tools. In this study, we evaluated the aforementioned potential of three markers CA-125, CA 15-3, and serum Calprotectin. CA-125 is a protein that is found elevated in cases of ovarian, breast, and lung cancer. Cancer Antigen 15-3 (CA 15-3) is a protein detected in high levels in women with breast cancer and ovarian cancer and it is significantly elevated in patients with metastasis and recurrence of OC. Calprotectin is a protein released from activated neutrophils, related to inflammatory conditions and can be a potential immune-mediated marker in OC. Purpose: The purpose of this study was to explore the significance of serum calprotectin, CA-125, and CA 15-3 in women diagnosed with serous OC. Methodology: Thirty-eight (38) women with diagnosed OC were included in this research as the study group and twenty-seven (27) healthy women with no history or current diagnosis of OC were included in the control group. Women in both groups shared similar past histories to avoid any other parameters interfering with the study. Our study group was further subdivided into early stage and advanced stage patients. Blood samples were collected from all women of both groups and were examined using ELISA kits to evaluate the levels of the above markers. Results: When comparing patients versus control patients, those with OC exhibited higher levels of Calprotectin compared to healthy individuals. Additionally, Calprotectin showed a statistically significant elevation between the control group and advanced patients. CA-125 remains the current standard of care biomarker exhibiting 90% sensitivity, whereas sensitivities in Calprotectin and CA 15-3 were 60% and 50%, respectively. Conclusions: Serum CA-125 remains the single most valuable biomarker for ovarian cancer, having the highest statistical significance, correlation with disease stage, detecting both early or advanced patients, and sensitivity of 90%. It appears to be a promising inflammatory biomarker in the early diagnosis of ovarian cancer, showing an elevation in patients, while CA 15-3 provides moderate complementary information and exhibits inferior sensitivity when compared to both CA-125 and Calprotectin. The latter appears to be a promising marker and further studies could show if its addition to established protocols could improve early detection, disease progression, or risk stratification. Calprotectin enhances the detection range for ovarian cancer when used alongside CA-125, while this combined approach detected a greater proportion of patients than CA-125 alone, indicating improved diagnostic potential. Full article
(This article belongs to the Section Medical Research)
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4 pages, 152 KiB  
Editorial
Implications of Bioactive Compounds in Lifelong Disorders
by Francisco Les and Guillermo Cásedas
Life 2025, 15(7), 1079; https://doi.org/10.3390/life15071079 - 7 Jul 2025
Viewed by 252
Abstract
Over the past decade, there has been a remarkable surge in research focused on bioactive compounds, reflecting their growing importance in fields such as pharmacology, nutrition, and disease prevention [...] Full article
(This article belongs to the Special Issue Implications of Bioactive Compounds in Lifelong Disorders)
13 pages, 5262 KiB  
Article
The Relationship Between Tramadol-Induced Oxidative Testis Injury and Reproductive Function Disorder and Adenosine Triphosphate
by Fevzi Bedir, Hüseyin Kocatürk, Mehmet Sefa Altay, Renad Mammadov, Bahadır Süleyman, Taha Abdulkadir Coban, Gülce Naz Yazici, Seval Bulut and Halis Süleyman
Life 2025, 15(7), 1078; https://doi.org/10.3390/life15071078 - 6 Jul 2025
Viewed by 313
Abstract
Tramadol, a central analgesic drug, is used to treat moderate to severe pain but can cause reproductive disorders. The pathogenesis of tramadol-induced reproductive damage may involve increased oxidative stress, pro-inflammatory cytokines, ATP depletion, and reduced antioxidant levels. In this study, subjects were divided [...] Read more.
Tramadol, a central analgesic drug, is used to treat moderate to severe pain but can cause reproductive disorders. The pathogenesis of tramadol-induced reproductive damage may involve increased oxidative stress, pro-inflammatory cytokines, ATP depletion, and reduced antioxidant levels. In this study, subjects were divided into four groups: healthy control (HC), tramadol only (TM), ATP only (ATP), and ATP + tramadol (ATM). ATP was administered intraperitoneally at 4 mg/kg, and tramadol was administered orally at 50 mg/kg. Distilled water was given to the HC group. This regimen was repeated for three weeks. At the end of the treatment, testicular tissues from six rats in each group were analyzed biochemically and histopathologically after euthanasia. The remaining rats’ reproductive functions were evaluated. Long-term tramadol exposure resulted in oxidative stress, inflammation in testicular tissue, and reduced male reproductive capacity. Thinning of seminiferous tubule walls and thickening of basement membrane, irregularity in germ cells, increase in interstitial connective tissue, congestion in vessels, increase in Leyding cells and hyperplasia were found in the TM group. ATP treatment significantly reduced tramadol-induced increases in oxidants and pro-inflammatory cytokines, reversed the decline in antioxidants, and mitigated infertility in testicular tissue. Furthermore, ATP preserved the morphology of the testicular tissue. These findings suggest that ATP may offer therapeutic potential for tramadol-induced infertility. Full article
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22 pages, 5021 KiB  
Article
Luteolin-Rich Extract from Harrisonia perforata (Blanco) Merr. Root Alleviates SARS-CoV-2 Spike Protein-Stimulated Lung Inflammation via Inhibition of MAPK/NLRP3 Inflammasome Signaling Pathways
by Warathit Semmarath, Punnida Arjsri, Kamonwan Srisawad, Sonthaya Umsumarng and Pornngarm Dejkriengkraikul
Life 2025, 15(7), 1077; https://doi.org/10.3390/life15071077 - 5 Jul 2025
Viewed by 202
Abstract
The COVID-19-related long-standing effect or Post-Acute Sequelae of COVID-19 (PASC) is often associated with NLRP3 inflammasome activation in pulmonary inflammation elicited by SARS-CoV-2 spike proteins. Spike proteins engage toll-like receptors (TLRs) in respiratory epithelial cells, leading to excessive cytokine production. Given the need [...] Read more.
The COVID-19-related long-standing effect or Post-Acute Sequelae of COVID-19 (PASC) is often associated with NLRP3 inflammasome activation in pulmonary inflammation elicited by SARS-CoV-2 spike proteins. Spike proteins engage toll-like receptors (TLRs) in respiratory epithelial cells, leading to excessive cytokine production. Given the need for effective therapeutic strategies to mitigate spike protein-stimulated lung inflammation, we examined the anti-inflammatory properties of luteolin and ethanolic extract from Harrisonia perforata (Blanco) Merr. root. The ethanolic extract of H. perforata root (HPEE) contained a high concentration of luteolin flavonoid (143.53 ± 1.58 mg/g extract). Both HPEE (25–100 μg/mL) and luteolin (4.5–36 μM) significantly inhibited inflammation stimulated by the Wuhan (W) and Omicron (O) spike protein S1, as evidenced by a dose-dependent significant decrease in IL-6, IL-1β, and IL-18 secretion in A549 lung epithelial cells (p < 0.05). Furthermore, pretreatment with HPEE or luteolin prior to spike protein exposure (100 ng/mL) significantly, in a dose-dependent manner, repressed the inflammatory mRNA expression (p < 0.05). Mechanistic study revealed that HPEE and luteolin suppressed NLRP3 inflammasome signaling activation by reducing their machinery protein expressions. Additionally, they inhibited the ERK/JNK/p38 MAPK signaling activation, resulting in decreased inflammatory mRNA expression and cytokine release. These findings suggest that H. perforata root extract and its major flavonoid luteolin exert potent anti-inflammatory effects and may offer therapeutic potential against spike protein-induced lung inflammation. Full article
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15 pages, 3976 KiB  
Article
Uncommon but Important: Tertiary Center Experience with Rare Cases of Breast Hamartoma
by Mihaela Camelia Tîrnovanu, Bogdan Florin Toma, Elena Cojocaru, Elena Țarcă, Ștefan Dragoș Tîrnovanu, Vlad Gabriel Tîrnovanu, Cristian Mârțu, Roxana Ana Covali, Anca Irina Gradinariu, Gabriela Ghiga and Ludmila Lozneanu
Life 2025, 15(7), 1076; https://doi.org/10.3390/life15071076 - 5 Jul 2025
Viewed by 201
Abstract
Background: A breast hamartoma or fibroadenolipoma is a rare, benign mass consisting of disorganized mature breast tissue elements. Surgical excision is recommended if the lesion exhibits rapid progressive growth. However, incomplete excision may result in recurrence. The objective of this study is to [...] Read more.
Background: A breast hamartoma or fibroadenolipoma is a rare, benign mass consisting of disorganized mature breast tissue elements. Surgical excision is recommended if the lesion exhibits rapid progressive growth. However, incomplete excision may result in recurrence. The objective of this study is to provide comprehensive insights into the characteristics of breast hamartomas and to conduct a thorough investigation into their clinical presentation, diagnostic procedures, and management strategies. Methods: We report on 13 cases of breast hamartomas treated surgically between January 2018 and June 2023 at the Obstetrics and Gynecology Hospital “Cuza Vodă” in Iași. We analyzed their histological images and immunohistochemical evaluations. Results: The mean age of the patients was 33.35 years, ranging from 22 to 57 years. Clinically, all patients presented with a painless mass. The diagnosis was confirmed through ultrasound examination, which revealed that hamartomas appeared as well-circumscribed, oval, and heterogeneous in echotexture. The tumor sizes ranged from 1 to 17 cm, with an average size of 6.75 cm. Surgical treatment involved lumpectomy with the excision of a small portion of normal tissue surrounding the tumor. The histological variability of these tumors poses diagnostic challenges for pathologists, potentially leading to underdiagnosis. Conclusions: Most hamartomas exhibit characteristic features on ultrasound attributable to their fibrous, glandular, and adipose tissue composition. Accurate identification of hamartomas is crucial due to the potential for recurrence. Notably, none of the women in our study experienced recurrence during the follow-up period. Full article
(This article belongs to the Section Medical Research)
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20 pages, 2843 KiB  
Review
Neural Mechanisms and Alterations of Sweet Sensing: Insights from Functional Magnetic Resonance Imaging Studies
by Tobias Long, Colette C. Milbourn, Alison Smith, Kyaw Linn Su Khin, Amanda J. Page, Iskandar Idris, Qian Yang, Richard L. Young and Sally Eldeghaidy
Life 2025, 15(7), 1075; https://doi.org/10.3390/life15071075 - 5 Jul 2025
Viewed by 365
Abstract
Sweet sensing is a fundamental sensory experience that plays a critical role not only in food preference, reward and dietary behaviour but also in glucose metabolism. Sweet taste receptors (STRs), composed of a heterodimer of taste receptor type 1 member 2 (T1R2) and [...] Read more.
Sweet sensing is a fundamental sensory experience that plays a critical role not only in food preference, reward and dietary behaviour but also in glucose metabolism. Sweet taste receptors (STRs), composed of a heterodimer of taste receptor type 1 member 2 (T1R2) and member 3 (T1R3), are now recognised as being widely distributed throughout the body, including the gastrointestinal tract. Preclinical studies suggest these receptors are central to nutrient and glucose sensing, detecting energy availability and triggering metabolic and behavioural responses to maintain energy balance. Both internal and external factors tightly regulate their signalling pathways, and dysfunction within these systems may contribute to the development of metabolic disorders such as obesity and type 2 diabetes (T2D). Functional magnetic resonance imaging (fMRI) has provided valuable insights into the neural mechanisms underlying sweet sensing by mapping brain responses to both lingual/oral and gastrointestinal sweet stimuli. This review highlights key findings from fMRI studies and explores how these neural responses are modulated by metabolic state and individual characteristics such as body mass index, habitual intake and metabolic health. By integrating current evidence, this review advances our understanding of the complex interplay between sweet sensing, brain responses, and health and identifies key gaps and directions for future research in nutritional neuroscience. Full article
(This article belongs to the Special Issue New Advances in Neuroimaging and Brain Functions: 2nd Edition)
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12 pages, 684 KiB  
Article
Age-Related Effects on the Color Discrimination Threshold
by Ali Almustanyir, Mohammed Alhazmi, Amal Aldarwesh, Meznah S. Almutairi, Mohammed Almahubi, Ansam Alateeq, Tahani Alqahtani, Muteb Alanazi, Sultan Alotaibi, Mansour Alghamdi, Essam Almutleb, Basal H. Altoaimi, Balsam Alabdulkader and Mosaad Alhassan
Life 2025, 15(7), 1074; https://doi.org/10.3390/life15071074 - 5 Jul 2025
Viewed by 289
Abstract
Traditional color vision tests lack the sensitivity to detect subtle differences in individuals with normal color vision. The Konan ColorDx Cone Contrast Threshold (CCT) HD test allows the quantitative measurement of color discrimination thresholds for each cone type. This cross-sectional study established normative [...] Read more.
Traditional color vision tests lack the sensitivity to detect subtle differences in individuals with normal color vision. The Konan ColorDx Cone Contrast Threshold (CCT) HD test allows the quantitative measurement of color discrimination thresholds for each cone type. This cross-sectional study established normative values for L-, M-, and S-cone contrast sensitivities and evaluated the effects of age and sex on color discrimination thresholds. Participants aged 15–79 years with normal color vision were included (n = 216; 55% female). CCTs were measured monocularly using the Konan ColorDx CCT HD test under standardized conditions, and the influences of age and sex on L-, M-, and S-cone sensitivities were evaluated. In all groups, L-cone sensitivity was the highest, followed by the M- and S-cone sensitivities. Overall contrast sensitivity was significantly higher in females than in males (mean difference = −0.041), especially for adolescents and young adults (20–24 years). Young adults outperformed middle-aged and older adults, with age-related decline most pronounced for S-cone sensitivity in those over 60. The right and left eye sensitivities did not differ. This study provides age- and sex-stratified normative data for the Konan Color Dx CCT HD test, supporting its use for clinical and occupational assessments. Full article
(This article belongs to the Special Issue Vision Science and Optometry: 2nd Edition)
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