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Search Results (12,147)

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Keywords = physiologic mechanisms

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11 pages, 359 KiB  
Article
Assessing Pain and Anxiety Impact in Smokers with Spine Fractures Managed Without Surgery: A Retrospective Cohort Study
by Jose Castillo, James Zhou, Gabriel Urreola, Michael Nhien Le, Omar Ortuno, Matthew Kercher, Kee Kim, Richard L. Price and Allan R. Martin
J. Clin. Med. 2025, 14(15), 5332; https://doi.org/10.3390/jcm14155332 - 28 Jul 2025
Abstract
Background/Objective: Smoking is known to impair fracture healing and worsen surgical outcomes, but its effect on psychological recovery in spine trauma patients remains unclear. The purpose of this study is to assess how smoking affects pain and anxiety in patients with spine fractures [...] Read more.
Background/Objective: Smoking is known to impair fracture healing and worsen surgical outcomes, but its effect on psychological recovery in spine trauma patients remains unclear. The purpose of this study is to assess how smoking affects pain and anxiety in patients with spine fractures treated either conservatively or surgically. Methods: We conducted a retrospective analysis looking at spine fracture patients > 18 years old seen at a single institution between 11/2015 and 9/2019. Patient variables such as age, sex, race, ethnicity, mechanism of injury, fracture location, presence of spinal cord injury, surgical intervention, hospital and ICU LOS, disposition, and EQ-5D-3L at 3 and 12 months were collected and analyzed. Results: Non-operative management was selected for 403 patients, of which 304 never smoked and 99 were smokers. Surgical management was utilized for 126 patients, of which 90 never smoked and 36 were smokers. Studying non-smokers and current smokers, higher levels of extreme pain and anxiety at 3 and 12 months were reported in smokers managed conservatively. Smokers managed surgically reported higher levels of pain and anxiety than non-smokers at 3 months but not at 12 months. No significant differences were seen with regards to changes in pain or anxiety between the 3- and 12-month follow-up. Conclusions: Smoking is independently associated with higher levels of pain and anxiety in conservatively managed spine fracture patients. These findings suggest a need for early intervention and cessation efforts in the trauma setting. Further investigation is warranted to clarify whether underlying psychological or physiological phenomena are impacting patient outcomes. Full article
(This article belongs to the Special Issue Spine Surgery: Clinical Advances and Future Directions)
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27 pages, 900 KiB  
Review
Seed Priming Beyond Stress Adaptation: Broadening the Agronomic Horizon
by Mujo Hasanović, Adaleta Durmić-Pašić and Erna Karalija
Agronomy 2025, 15(8), 1829; https://doi.org/10.3390/agronomy15081829 - 28 Jul 2025
Abstract
Seed priming, traditionally viewed as a method for enhancing crop resilience to abiotic stress, has evolved into a multifaceted agronomic strategy. This review synthesizes the current findings demonstrating that priming influences plant development, metabolic regulation, and yield enhancement even under optimal conditions. By [...] Read more.
Seed priming, traditionally viewed as a method for enhancing crop resilience to abiotic stress, has evolved into a multifaceted agronomic strategy. This review synthesizes the current findings demonstrating that priming influences plant development, metabolic regulation, and yield enhancement even under optimal conditions. By covering a wide range of crops, including cereals (e.g., wheat, maize, rice, and barley) as well as vegetables and horticultural species (e.g., tomato, carrot, spinach, and lettuce), we highlight the broad applicability of priming across agricultural systems. The underlying mechanisms include hormonal modulation, altered source–sink dynamics, accelerated phenology, and epigenetic memory. Various priming techniques are discussed, including hydropriming, osmopriming, biopriming, chemopriming, and nanopriming, with attention to their physiological and molecular effects. Special focus is given to the role of seed priming in advancing climate-smart and precision agriculture. By shifting the narrative from stress mitigation to holistic crop performance optimization, seed priming emerges as a key tool for sustainable agriculture in the face of global challenges. Full article
(This article belongs to the Section Plant-Crop Biology and Biochemistry)
24 pages, 2145 KiB  
Review
A New Perspective on Regenerative Medicine: Plant-Derived Extracellular Vesicles
by Yuan Zuo, Jinying Zhang, Bo Sun, Xinxing Wang, Ruiying Wang, Shuo Tian and Mingsan Miao
Biomolecules 2025, 15(8), 1095; https://doi.org/10.3390/biom15081095 - 28 Jul 2025
Abstract
Plant-derived extracellular vesicles (PDEVs) are nanoscale, phospholipid bilayer-enclosed vesicles secreted by living cells through cytokinesis under physiological and pathological conditions. Owing to their high biocompatibility and stability, PDEVs have attracted considerable interest in regenerative medicine applications. They can exhibit the capacity to enhance [...] Read more.
Plant-derived extracellular vesicles (PDEVs) are nanoscale, phospholipid bilayer-enclosed vesicles secreted by living cells through cytokinesis under physiological and pathological conditions. Owing to their high biocompatibility and stability, PDEVs have attracted considerable interest in regenerative medicine applications. They can exhibit the capacity to enhance cellular proliferation, migration, and multi-lineage differentiation through immunomodulation, anti-inflammation effects, antioxidative protection, and tissue regeneration mechanisms. Given their abundant availability, favorable safety profile, and low immunogenicity risks, PDEVs have been successfully employed in therapeutic interventions for skeletal muscle disorders, cardiovascular diseases, neurodegenerative conditions, and tissue regeneration applications. This review mainly provides a comprehensive overview of PDEVs, systematically examining their biological properties, standardized isolation and characterization methodologies, preservation techniques, and current applications in regenerative medicine. Furthermore, we critically discuss future research directions and clinical translation potential, aiming to facilitate the advancement of PDEV-based therapeutic strategies. Full article
(This article belongs to the Section Molecular Medicine)
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14 pages, 676 KiB  
Article
Optimizing Row Spacing and Seeding Rate for Yield and Quality of Alfalfa in Saline–Alkali Soils
by Jiaqi Shi, Nan Xie, Lifeng Zhang, Xuan Pan, Yanling Wang, Zhongkuan Liu, Zhenyu Liu, Jianfei Zhi, Wenli Qin, Wei Feng, Guotong Sun and Hexing Yu
Agronomy 2025, 15(8), 1828; https://doi.org/10.3390/agronomy15081828 - 28 Jul 2025
Abstract
To elucidate the photosynthetic physiological mechanisms influencing alfalfa (Medicago sativa L.) yield and quality under varying planting densities, the cultivar ‘Zhongmu No.1’ was used as experimental material. The effects of different row spacing (R1, R2, R3) and seeding rate (S1, S2, [...] Read more.
To elucidate the photosynthetic physiological mechanisms influencing alfalfa (Medicago sativa L.) yield and quality under varying planting densities, the cultivar ‘Zhongmu No.1’ was used as experimental material. The effects of different row spacing (R1, R2, R3) and seeding rate (S1, S2, S3, S4, S5) combinations on chlorophyll content (ChlM), nitrogen flavonol index (NFI), chlorophyll fluorescence parameters, forage quality, and hay yield were systematically analyzed. Results showed that alfalfa under R1S3 treatment achieved peak values for ChIM, NFI, EE, and hay yield, whereas R1S4 treatment yielded the highest Fv/Fm and CP content. Redundancy analysis further indicated that yield was most strongly associated with ChlM, NFI, Y (II), and qP. Y (II), and qP significantly influenced alfalfa forage quality, exerting negative effects on ADF and NDF, while demonstrating positive effects on CP and EE. In conclusion, narrow row spacing (15 cm) with moderate seeding rates (22.5–30 kg·hm−2) optimizes photosynthetic performance while concurrently enhancing both productivity and forage quality in alfalfa cultivated, establishing a theoretical foundation for photosynthetic regulation in high-quality and high-yield alfalfa cultivation. Full article
34 pages, 1544 KiB  
Review
The Crucial Interplay Between the Lungs, Brain, and Heart to Understand Epilepsy-Linked SUDEP: A Literature Review
by Mohd Yaqub Mir, Bilal A. Seh, Shabab Zahra and Legradi Adam
Brain Sci. 2025, 15(8), 809; https://doi.org/10.3390/brainsci15080809 - 28 Jul 2025
Abstract
Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of mortality among individuals with epilepsy, particularly those with drug-resistant forms. This review explores the complex multisystem mechanisms underpinning SUDEP, integrating recent findings on brain, cardiac, and pulmonary dysfunctions. Background/Objectives: The main objective [...] Read more.
Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of mortality among individuals with epilepsy, particularly those with drug-resistant forms. This review explores the complex multisystem mechanisms underpinning SUDEP, integrating recent findings on brain, cardiac, and pulmonary dysfunctions. Background/Objectives: The main objective of this review is to elucidate how seizures disrupt critical physiological systems, especially the brainstem, heart, and lungs, contributing to SUDEP, with emphasis on respiratory control failure and autonomic instability. Methods: The literature from experimental models, clinical observations, neuroimaging studies, and genetic analyses was systematically examined. Results: SUDEP is frequently preceded by generalized tonic–clonic seizures, which trigger central and obstructive apnea, hypoventilation, and cardiac arrhythmias. Brainstem dysfunction, particularly in areas such as the pre-Bötzinger complex and nucleus tractus solitarius, plays a central role. Genetic mutations affecting ion channels (e.g., SCN1A, KCNQ1) and neurotransmitter imbalances (notably serotonin and GABA) exacerbate autonomic dysregulation. Risk is compounded by a prone sleeping position, reduced arousal capacity, and impaired ventilatory responses. Conclusions: SUDEP arises from a cascade of interrelated failures in respiratory and cardiac regulation initiated by seizure activity. The recognition of modifiable risk factors, implementation of monitoring technologies, and targeted therapies such as serotonergic agents may reduce mortality. Multidisciplinary approaches integrating neurology, cardiology, and respiratory medicine are essential for effective prevention strategies. Full article
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24 pages, 6890 KiB  
Article
Multi-Level Transcriptomic and Physiological Responses of Aconitum kusnezoffii to Different Light Intensities Reveal a Moderate-Light Adaptation Strategy
by Kefan Cao, Yingtong Mu and Xiaoming Zhang
Genes 2025, 16(8), 898; https://doi.org/10.3390/genes16080898 - 28 Jul 2025
Abstract
Objectives: Light intensity is a critical environmental factor regulating plant growth, development, and stress adaptation. However, the physiological and molecular mechanisms underlying light responses in Aconitum kusnezoffii, a valuable alpine medicinal plant, remain poorly understood. This study aimed to elucidate the adaptive [...] Read more.
Objectives: Light intensity is a critical environmental factor regulating plant growth, development, and stress adaptation. However, the physiological and molecular mechanisms underlying light responses in Aconitum kusnezoffii, a valuable alpine medicinal plant, remain poorly understood. This study aimed to elucidate the adaptive strategies of A. kusnezoffii under different light intensities through integrated physiological and transcriptomic analyses. Methods: Two-year-old A. kusnezoffii plants were exposed to three controlled light regimes (790, 620, and 450 lx). Leaf anatomical traits were assessed via histological sectioning and microscopic imaging. Antioxidant enzyme activities (CAT, POD, and SOD), membrane lipid peroxidation (MDA content), osmoregulatory substances, and carbon metabolites were quantified using standard biochemical assays. Transcriptomic profiling was conducted using Illumina RNA-seq, with differentially expressed genes (DEGs) identified through DESeq2 and functionally annotated via GO and KEGG enrichment analyses. Results: Moderate light (620 lx) promoted optimal leaf structure by enhancing palisade tissue development and epidermal thickening, while reducing membrane lipid peroxidation. Antioxidant defense capacity was elevated through higher CAT, POD, and SOD activities, alongside increased accumulation of soluble proteins, sugars, and starch. Transcriptomic analysis revealed DEGs enriched in photosynthesis, monoterpenoid biosynthesis, hormone signaling, and glutathione metabolism pathways. Key positive regulators (PHY and HY5) were upregulated, whereas negative regulators (COP1 and PIFs) were suppressed, collectively facilitating chloroplast development and photomorphogenesis. Trend analysis indicated a “down–up” gene expression pattern, with early suppression of stress-responsive genes followed by activation of photosynthetic and metabolic processes. Conclusions: A. kusnezoffii employs a coordinated, multi-level adaptation strategy under moderate light (620 lx), integrating leaf structural optimization, enhanced antioxidant defense, and dynamic transcriptomic reprogramming to maintain energy balance, redox homeostasis, and photomorphogenic flexibility. These findings provide a theoretical foundation for optimizing artificial cultivation and light management of alpine medicinal plants. Full article
(This article belongs to the Section Plant Genetics and Genomics)
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21 pages, 1855 KiB  
Review
Crosstalk Between N6-Methyladenosine and Other Epigenetic Mechanisms in Central Nervous System Development and Disorders
by Cuiping Qi, Xiuping Jin, Hui Wang and Dan Xu
Biomolecules 2025, 15(8), 1092; https://doi.org/10.3390/biom15081092 - 28 Jul 2025
Abstract
A variety of epigenetic mechanisms—such as DNA methylation, histone alterations, RNA chemical modifications, and regulatory non-coding RNAs—collectively influence gene regulation and cellular processes. Among these, N6-methyladenosine (m6A) represents the most widespread internal modification in eukaryotic mRNA, exerting significant influence on RNA [...] Read more.
A variety of epigenetic mechanisms—such as DNA methylation, histone alterations, RNA chemical modifications, and regulatory non-coding RNAs—collectively influence gene regulation and cellular processes. Among these, N6-methyladenosine (m6A) represents the most widespread internal modification in eukaryotic mRNA, exerting significant influence on RNA metabolic pathways and modulating mRNA function at multiple levels. Studies have shown that m6A modification is highly enriched in the brain and regulates central nervous system development and various physiological functions. Recent studies have demonstrated that m6A interacts with other epigenetic regulators and triggers epigenetic remodeling, which further affects the development and occurrence of central nervous system diseases. In this review, we provide an up-to-date overview of this emerging research hotspot in biology, with a focus on the interplay between m6A and other epigenetic regulators. We highlight their potential roles and regulatory mechanisms in epigenetic reprogramming during central nervous system development and disease, offering insights into potential novel targets and therapeutic strategies for CNS disorders. Full article
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24 pages, 3590 KiB  
Article
Mesocricetus auratus (Golden Syrian Hamster) Experimental Model of SARS-CoV-2 Infection Reveals That Lung Injury Is Associated with Phenotypic Differences Between SARS-CoV-2 Variants
by Daniela del Rosario Flores Rodrigues, Alexandre dos Santos da Silva, Arthur Daniel Rocha Alves, Bárbara Araujo Rossi, Richard de Almeida Lima, Sarah Beatriz Salvador Castro Faria, Oswaldo Gonçalves Cruz, Rodrigo Muller, Julio Scharfstein, Amanda Roberta Revoredo Vicentino, Aline da Rocha Matos, João Paulo Rodrigues dos Santos, Pedro Paulo Abreu Manso, Milla Bezerra Paiva, Debora Ferreira Barreto-Vieira, Gabriela Cardoso Caldas, Marcelo Pelajo Machado and Marcelo Alves Pinto
Viruses 2025, 17(8), 1048; https://doi.org/10.3390/v17081048 - 28 Jul 2025
Abstract
Despite the current level of public immunity to SARS-CoV-2, the early inflammatory events associated with respiratory distress in COVID-19 patients are not fully elucidated. Syrian golden hamsters, facultative hibernators, recapitulate the phenotype of SARS-CoV-2-induced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—induced severe acute [...] Read more.
Despite the current level of public immunity to SARS-CoV-2, the early inflammatory events associated with respiratory distress in COVID-19 patients are not fully elucidated. Syrian golden hamsters, facultative hibernators, recapitulate the phenotype of SARS-CoV-2-induced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—induced severe acute lung injury seen in patients. In this study, we describe the predominance of the innate immune response in hamsters inoculated with four different SARS-CoV-2 variants, underscoring phenotypic differences among them. Severe inflammatory lung injury was chronologically associated with acute and significant weight loss, mainly in animals inoculated with A.2 and Delta variants. Omicron-infected animals had lower overall histopathology scores compared to other variants. We highlight the central role of endothelial injury and activation in the pathogenesis of experimental SARS-CoV-2 infection in hamsters, characterised by the presence of proliferative type I and type II pneumocytes with abundant surfactant expression, thereby maintaining hyperinflated alveolar fields. Additionally, there was evidence of intrapulmonary lymphatic vessel proliferation, which was accompanied by a lack of detectable microthrombosis in the lung parenchyma. However, white microthrombi were observed in lymphatic vessels. Our findings suggest that the physiological compensatory mechanisms that maintain respiratory homeostasis in Golden Syrian hamsters prevent severe respiratory distress and death after SARS-CoV-2 infection. Full article
(This article belongs to the Special Issue Emerging Concepts in SARS-CoV-2 Biology and Pathology, 3rd Edition)
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14 pages, 2268 KiB  
Article
CD1d-Restricted NKT Cells Promote Central Memory CD8+ T Cell Formation via an IL-15-pSTAT5-Eomes Axis in a Pathogen-Exposed Environment
by Yingyu Qin, Yilin Qian, Jingli Zhang and Shengqiu Liu
Int. J. Mol. Sci. 2025, 26(15), 7272; https://doi.org/10.3390/ijms26157272 - 28 Jul 2025
Abstract
The generation of memory CD8+ T cells is essential for establishing protective T cell immunity against pathogens and cancers. However, the cellular and molecular mechanisms underlying memory CD8+ T cell formation remain incompletely understood. Reliance on specific pathogen-free (SPF) models, characterized [...] Read more.
The generation of memory CD8+ T cells is essential for establishing protective T cell immunity against pathogens and cancers. However, the cellular and molecular mechanisms underlying memory CD8+ T cell formation remain incompletely understood. Reliance on specific pathogen-free (SPF) models, characterized by restricted microbial exposure, may limit our understanding of physiologically relevant immune memory development. This study reveals that CD1d-restricted NKT cells regulate central memory T cell (TCM) generation exclusively in a microbe-rich (“dirty”) environment. Under non-SPF housing, CD1d+/ and Ja18+/ mice exhibited enhanced TCM formation compared to NKT-deficient controls (CD1d//Ja18/), demonstrating that microbial experience is required for NKT-mediated TCM regulation. Mechanistically, CD1d-restricted NKT cells increased IL-15Rα expression on CD4+ T cells in CD1d+/ mice, potentiating IL-15 trans-presentation and thereby activating the IL-15/pSTAT5/Eomes axis critical for TCM maintenance. Functional validation through adoptive transfer of CFSE-labeled OT-1 memory cells revealed an NKT cell-dependent survival advantage in CD1d+/ hosts. This provides direct evidence that microbiota-experienced niches shape immune memory. Collectively, these findings establish CD1d-restricted NKT cells as physiological regulators of TCM generation and suggest their potential utility as vaccine adjuvants to enhance protective immunity. Full article
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22 pages, 4495 KiB  
Article
Physiological and Transcriptomic Analyses Reveal Regulatory Mechanisms of Adventitious Root Formation in In Vitro Culture of Cinnamomum camphora
by Yuntong Zhang, Ting Zhang, Yongjie Zheng, Jun Wang, Chenglin Luo, Yuhua Li and Xinliang Liu
Int. J. Mol. Sci. 2025, 26(15), 7264; https://doi.org/10.3390/ijms26157264 - 27 Jul 2025
Abstract
Cinnamomum camphora is an ecologically and economically significant species, highly valued for its essential oil production and environmental benefits. Although a tissue culture system has been established for C. camphora, large-scale propagation remains limited due to the inconsistent formation of adventitious roots [...] Read more.
Cinnamomum camphora is an ecologically and economically significant species, highly valued for its essential oil production and environmental benefits. Although a tissue culture system has been established for C. camphora, large-scale propagation remains limited due to the inconsistent formation of adventitious roots (ARs). This study investigated AR formation from callus tissue, focusing on associated physiological changes and gene expression dynamics. During AR induction, contents of soluble sugars and proteins decreased, alongside reduced activities of antioxidant enzymes, including superoxide dismutase (SOD), peroxidase (POD), and polyphenol oxidase (PPO). Levels of indole-3-acetic acid (IAA) and abscisic acid (ABA) decreased significantly throughout AR formation. Zeatin riboside (ZR) levels initially declined and then rose, whereas gibberellic acid (GA) levels displayed the opposite trend. Comparative transcriptomic and temporal expression analyses identified differentially expressed genes (DEGs), which were grouped into four distinct expression patterns. KEGG pathway enrichment indicated that 67 DEGs are involved in plant hormone signaling pathways and that 38 DEGs are involved in the starch and sucrose metabolism pathway. Additionally, protein–protein interaction network (PPI) analysis revealed ten key regulatory genes, which are mainly involved in auxin, cytokinin, GA, ABA, and ethylene signaling pathways. The reliability of the transcriptome data was further validated by quantitative real-time PCR. Overall, this study provides new insights into the physiological and molecular mechanisms underlying AR formation in C. camphora and offers valuable guidance for optimizing tissue culture systems. Full article
(This article belongs to the Special Issue Emerging Insights into Phytohormone Signaling in Plants)
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17 pages, 564 KiB  
Review
Gut Feelings: Linking Dysbiosis to Depression—A Narrative Literature Review
by Anca C. Bibolar, Vlad I. Nechita, Florin C. Lung, Bianca D. Crecan-Suciu and Ramona L. Păunescu
Medicina 2025, 61(8), 1360; https://doi.org/10.3390/medicina61081360 - 27 Jul 2025
Abstract
The balance between physiological, psychological, and environmental factors often shapes human experience. In recent years, research has drawn attention to the gut microbiota as a significant contributor to brain function and emotional regulation. This narrative review examines how changes in gut microbiota may [...] Read more.
The balance between physiological, psychological, and environmental factors often shapes human experience. In recent years, research has drawn attention to the gut microbiota as a significant contributor to brain function and emotional regulation. This narrative review examines how changes in gut microbiota may relate to depression. We selected studies that explore the link between intestinal dysbiosis and mood, focusing on mechanisms such as inflammation, vagus nerve signaling, HPA axis activation, gut permeability, and neurotransmitter balance. Most of the available data come from animal models, but findings from human studies suggest similar patterns. Findings are somewhat difficult to compare due to differences in measurement procedures and patient groups. However, several microbial shifts have been observed in people with depressive symptoms, and trials with probiotics or fecal microbiota transplant show potential. These results remain limited. We argue that these interventions deserve more attention, especially in cases of treatment-resistant or inflammation-driven depression. Understanding how the gut and brain interact could help define clearer subtypes of depression and guide new treatment approaches. Full article
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15 pages, 1961 KiB  
Article
Age-Dependent Immune Defense Against Beauveria bassiana in Long- and Short-Lived Drosophila Populations
by Elnaz Bagheri, Han Yin, Arnie Lynn C. Bengo, Kshama Ekanath Rai, Taryn Conyers, Robert Courville, Mansour Abdoli, Molly K. Burke and Parvin Shahrestani
J. Fungi 2025, 11(8), 556; https://doi.org/10.3390/jof11080556 - 27 Jul 2025
Abstract
Aging in sexually reproducing organisms is shaped by the declining force of natural selection after reproduction begins. In Drosophila melanogaster, experimental evolution shows that altering the age of reproduction shifts the timing of aging. Using the Drosophila experimental evolution population (DEEP) resource, [...] Read more.
Aging in sexually reproducing organisms is shaped by the declining force of natural selection after reproduction begins. In Drosophila melanogaster, experimental evolution shows that altering the age of reproduction shifts the timing of aging. Using the Drosophila experimental evolution population (DEEP) resource, which includes long- and short- lived populations evolved under distinct reproductive schedules, we investigated how immune defense against Beauveria bassiana changes with age and evolved lifespan. We tested survival post-infection at multiple ages and examined genomic differentiation for immune-related genes. Both population types showed age-related declines in immune defense. Long-lived populations consistently exhibited age-specific defense when both long- and short-lived populations were tested. Genomic comparisons revealed thousands of differentiated loci, yet no enrichment for canonical immune genes or overlap with gene sets from studies of direct selection for immunity. These results suggest that enhanced immune defense can evolve alongside extended lifespan, likely via general physiological robustness rather than traditional immune pathways. A more detailed analysis may reveal that selection for lifespan favors tolerance-based mechanisms that reduce infection damage without triggering immune activation, in contrast to direct selection for resistance. Our findings demonstrate the utility of experimentally evolved populations for dissecting the genetic architecture of aging and immune defense to inform strategies to mitigate age-related costs associated with immune activation. Full article
(This article belongs to the Special Issue Advances in Research on Entomopathogenic Fungi)
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16 pages, 3978 KiB  
Article
Cepharanthine Promotes Ca2+-Independent Premature Red Blood Cell Death Through Metabolic Insufficiency and p38 MAPK/CK1α/COX/MLKL/PKC/iNOS Signaling
by Shaymah H. Alruwaili, Jawaher Alsughayyir and Mohammad A. Alfhili
Int. J. Mol. Sci. 2025, 26(15), 7250; https://doi.org/10.3390/ijms26157250 - 27 Jul 2025
Abstract
Nonspecific toxicity to normal and malignant cells restricts the clinical utility of many anticancer drugs. In particular, anemia in cancer patients develops due to drug-induced toxicity to red blood cells (RBCs). The anticancer alkaloid, cepharanthine (CEP), elicits distinct forms of cell death including [...] Read more.
Nonspecific toxicity to normal and malignant cells restricts the clinical utility of many anticancer drugs. In particular, anemia in cancer patients develops due to drug-induced toxicity to red blood cells (RBCs). The anticancer alkaloid, cepharanthine (CEP), elicits distinct forms of cell death including apoptosis and autophagy, but its cytotoxicity to RBCs has not been investigated. Colorimetric and fluorometric techniques were used to assess eryptosis and hemolysis in control and CEP-treated RBCs. Cells were labeled with Fluo4/AM and annexin-V-FITC to measure Ca2+ and phosphatidylserine (PS) exposure, respectively. Forward scatter (FSC) was detected to estimate cell size, and extracellular hemoglobin along with lactate dehydrogenase and aspartate transaminase activities were assayed to quantify hemolysis. Physiological manipulation of the extracellular milieu and various signaling inhibitors were tested to dissect the underlying mechanisms of CEP-induced RBC death. CEP increased PS exposure and hemolysis indices and decreased FSC in a concentration-dependent manner with prominent membrane blebbing. Although no Ca2+ elevation was detected, chelation of intracellular Ca2+ by BAPTA-AM reduced hemolysis. Whereas SB203580, D4476, acetylsalicylic acid, necrosulfonamide, and melatonin inhibited both PS exposure and hemolysis, staurosporin, L-NAME, ascorbate, caffeine, adenine, and guanosine only prevented hemolysis. Interestingly, sucrose had a unique dual effect by exacerbating PS exposure and reversing hemolysis. Of note, blocking KCl efflux augmented PS exposure while aggravating hemolysis only under Ca2+-depleted conditions. CEP activates Ca2+-independent pathways to promote eryptosis and hemolysis. The complex cytotoxic profile of CEP can be mitigated by targeting the identified modulatory pathways to potentiate its anticancer efficacy. Full article
(This article belongs to the Special Issue Blood Cells in Human Health and Disease)
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33 pages, 1777 KiB  
Review
Immunomodulatory Natural Products in Cancer Organoid-Immune Co-Cultures: Bridging the Research Gap for Precision Immunotherapy
by Chang-Eui Hong and Su-Yun Lyu
Int. J. Mol. Sci. 2025, 26(15), 7247; https://doi.org/10.3390/ijms26157247 - 26 Jul 2025
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Abstract
Natural products demonstrate potent immunomodulatory properties through checkpoint modulation, macrophage polarization, and T cell/natural killer (NK) cell activation. While cancer organoid-immune co-culture platforms enable physiologically relevant modeling of tumor–immune interactions, systematic investigation of natural product immunomodulation in these systems remains entirely unexplored. We [...] Read more.
Natural products demonstrate potent immunomodulatory properties through checkpoint modulation, macrophage polarization, and T cell/natural killer (NK) cell activation. While cancer organoid-immune co-culture platforms enable physiologically relevant modeling of tumor–immune interactions, systematic investigation of natural product immunomodulation in these systems remains entirely unexplored. We conducted a comprehensive literature analysis examining natural products tested in cancer organoids, immunomodulatory mechanisms from traditional models, technical advances in organoid-immune co-cultures, and standardization requirements for clinical translation. Our analysis reveals a critical research gap: no published studies have investigated natural product-mediated immunomodulation using organoid-immune co-culture systems. Even though compounds like curcumin, resveratrol, and medicinal mushroom polysaccharides show extensive immunomodulatory effects in two-dimensional (2D) cultures, and organoid technology achieves high clinical correlation for drug response prediction, all existing organoid studies focus exclusively on direct cytotoxicity. Technical challenges include compound stability, limited matrix penetration requiring substantially higher concentrations than 2D cultures, and maintaining functional immune populations in three-dimensional (3D) systems. The convergence of validated organoid-immune co-culture platforms, Food and Drug Administration (FDA) regulatory support through the Modernization Act 2.0, and extensive natural product knowledge creates unprecedented opportunities. Priority research directions include systematic screening of immunomodulatory natural products in organoid-immune co-cultures, development of 3D-optimized delivery systems, and clinical validation trials. Success requires moving beyond cytotoxicity-focused studies to investigate immunomodulatory mechanisms in physiologically relevant 3D systems, potentially unlocking new precision cancer immunotherapy approaches. Full article
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28 pages, 4633 KiB  
Review
Innovative Strategies in Hernia Mesh Design: Materials, Mechanics, and Modeling
by Evangelia Antoniadi, Nuno Miguel Ferreira, Maria Francisca Vaz, Marco Parente, Maria Pia Ferraz and Elisabete Silva
Materials 2025, 18(15), 3509; https://doi.org/10.3390/ma18153509 - 26 Jul 2025
Viewed by 159
Abstract
Hernia is a physiological condition that significantly impacts patients’ quality of life. Surgical treatment for hernias often involves the use of specialized meshes to support the abdominal wall. While this method is highly effective, it frequently leads to complications such as pain, infections, [...] Read more.
Hernia is a physiological condition that significantly impacts patients’ quality of life. Surgical treatment for hernias often involves the use of specialized meshes to support the abdominal wall. While this method is highly effective, it frequently leads to complications such as pain, infections, inflammation, adhesions, and even the need for revision surgeries. According to the Food and Drug Administration (FDA), hernia recurrence rates can reach up to 11%, surgical site infections occur in up to 21% of cases, and chronic pain incidence ranges from 0.3% to 68%. These statistics highlight the urgent need to improve mesh technologies to minimize such complications. The design and material composition of meshes are critical in reducing postoperative complications. Moreover, integrating drug-eluting properties into the meshes could address issues like infections and inflammation by enabling localized delivery of antibiotics and anti-inflammatory agents. Mesh design is equally important, with innovative structures like auxetic designs offering enhanced mechanical properties, flexibility, and tissue integration. These advanced designs can distribute stress more evenly, reduce fatigue, and improve performance in areas subjected to high pressures, such as during intense coughing, sneezing, or heavy lifting. Technological advancements, such as 3D printing, enable the precise fabrication of meshes with tailored designs and properties, providing new opportunities for innovation. By addressing these challenges, the development of next-generation mesh implants has the potential to reduce complications, improve patient outcomes, and significantly enhance quality of life for individuals undergoing hernia repair. Full article
(This article belongs to the Section Biomaterials)
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