Search Results (1,864)

Mesenchymal stem cells (MSCs) are multipotent cells capable of self-renewal and differentiation into specialized cell types, which play an important role in maintaining homeostasis and tissue regeneration in humans. The effectiveness of MSCs depends largely on their immunomodulatory properties and ability to regenerate damaged tissues. Biological activity of MSCs is modulated by environmental factors, including dietary components such as vitamins, minerals, and phytochemicals which influence their proliferation, aging, inflammatory response and resistance to oxidative stress. The article aims to highlight the importance of micronutrients and phytochemicals in modulating the MSCs’ performance and therapeutic potential, with a focus on the role of bioactive food components in regulating metabolism, regenerative efficacy and protective mechanisms of stem cells. Vitamins and trace elements are essential for antioxidant protection by eliminating reactive oxygen species, maintaining mitochondrial function and preserving cell viability under stressful conditions. Micronutrients and phytochemicals can modulate the immunomodulatory activity of MSCs by altering the cytokine secretion profile, reducing pro-inflammatory mediators while enhancing anti-inflammatory factors. However, both deficiency and excessively high concentrations of natural compounds can impair stem cell function. Interdisciplinary knowledge about the impact of micronutrients on the functioning of mesenchymal stem cells creates new opportunities in personalized medicine and nutrition. Understanding the mechanisms regulating MSCs activity under the influence of diet components may contribute to the development of individualized therapeutic strategies aimed at supporting tissue regeneration, delaying aging processes, and improving the prevention and treatment of chronic diseases. This knowledge is applicable in the design of functional foods and dietary supplements, making it particularly valuable for specialists in personalized nutrition and functional food development. Full article

Aflatoxin B₁ (AFB₁) is a common contaminant in canine diets that can cause significant damage to metabolic organs with prolonged exposure. Dihydromyricetin (DMY), a flavonoid compound abundant in Ampelopsis grossedentata, is widely used in functional foods due to its diverse biological activities. This study aimed to investigate the mechanism by which DMY alleviates AFB1-induced damage in MDCK cells. Four experimental groups were established: a control group with culture medium only (CON group), a group treated with 5 μg/mL AFB1 (AFB1 group), and two treatment groups treated with 5 μg/mL AFB1 combined with either 25 mmol/L or 50 mmol/L DMY—concentrations with more robust and stable protective effects than 100 mmol/L DMY, as confirmed by experimental screening. The results showed that AFB₁ significantly reduced MDCK cell viability at concentrations of 5–30 μg/mL (p < 0.01), while DMY at 25–100 mmol/L markedly improved cell viability (p < 0.01). AFB₁ treatment led to a significant increase in reactive oxygen species (ROS), malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) levels, along with a reduction in superoxide dismutase (SOD) and catalase (CAT) activities (p < 0.01). 25 mmol/L and 50 mmol/L DMY treatment reversed these effects, decreasing ROS, MDA, TNF-α, IL-6, and IL-1β levels while increasing SOD and CAT activities (p < 0.01). Furthermore, 25 mmol/L and 50 mmol/L DMY improved mitochondrial membrane potential (p < 0.01), counteracting AFB₁’s inhibitory effects on autophagy-related proteins by promoting p-AMPK and Beclin-1 expression while inhibiting p-mTOR, p53, and p62 expression (p < 0.05). In conclusion, DMY mitigates AFB₁-induced damage in MDCK cells by enhancing anti-inflammatory and antioxidant defenses and promoting autophagy, providing a theoretical foundation for future treatment strategies for canine kidney damage. Full article

Biosynthesis of ribose-5-phosphate (R5P) underlies all biosynthetic processes associated with biomass growth. Actively dividing cells continuously require building blocks for genome replication, synthesis of ribosomes and other derivatives containing R5P as a carbohydrate backbone. The main source of R5P in the cell is the pentose phosphate pathway (PPP), which is an anabolic sensor designed to coordinate the level of pentose phosphates and reduced NADPH required for anabolic processes. This review is devoted to a comparative analysis of R5P biosynthesis pathways among different domains of microorganisms, the features of PPP regulation in bacterial cells depending on physiological conditions, as well as genetic modifications of PPP and their effect on cell viability. We emphasize that ribose metabolism is a factor in the consolidation of cellular homeostasis under conditions of intensive biomass growth and the discrepancy between the processes of ribose synthesis and consumption is marked by spontaneous cell death. Full article

This study characterized leaf extracts of Cymbopogon flexuosus (Ryukyu Lemongrass Corporation, Okinawa, Japan) and evaluated the bioaccessibility and bioactivities of phenolic compounds following a simulated in vitro gastrointestinal model of digestion (in vitro GID) of plant material. Undigested (controls, AqC, EtC) and digested aqueous (AqD) and ethanolic (EtD) extracts were analyzed. Control extracts contained higher total phenolics and flavonoids than digested ones, with EtC showing the highest values. UHPLC-QToF-MS (ultra-high-performance liquid chromatography system coupled to a quadrupole time-of-flight mass spectrometer) identified 32 compounds, including phenolic acids, flavone aglycones, C-glycosides, and derivatives. Hydroxybenzoic acids, coumaric acid, caffeic esters, flavones, tricin derivatives, vitexin, and isoorientin exhibited reduced recovery, while coumaric acid hexoside, ferulic acid hexoside, and isoschaftoside/schaftoside exceeded 100% recovery, suggesting release from the matrix. Some compounds were absent from AqD, and many were found in the pellet, indicating potential colonic metabolism. Antioxidant activity (DPPH, reducing power, β-carotene/linoleic acid) was stronger in controls but always weaker than BHT/ascorbic acid. Extracts mildly inhibited α-amylase but more strongly inhibited α-glucosidase as shown with applied enzyme inhibition assays, especially EtD (76.93% at a concentration of 10 mg/mL), which showed stronger activity than controls but remained below acarbose (87.74% at 1 mg/mL). All extracts promoted HaCaT keratinocyte growth and reduced HCT-116 colon cancer cell viability at 250 µg/mL, with the strongest effects in AqC and AqD. Overall, GID decreased antioxidant activity but enhanced antidiabetic potential, confirming the safety and selective anticancer effects of C. flexuosus extracts. Full article

Tetracenomycins are anticancer polyketides that arrest cancer cell proliferation via binding to the large mammalian ribosomal subunit near the polypeptide exit channel. The tetracenomycins are natural products that many members of the actinomycete family produce. The first goal of this study was to improve the biosynthesis of tetracenomycin analogs via metabolic engineering. The second goal was to probe more deeply into the antiproliferative activity of tetracenomycin aglycones. The tetracenomycins were assessed via several assays, including cell viability assays, clonogenic assays, and flow cytometry apoptosis assays. The data suggest that tetracenomycins C and X inhibit cell proliferation and arrest cell growth, supporting their cytostatic action mechanism. In addition, tetracenomycins C and X induced degeneration of 3D spheroid cultures and exhibited concentration-dependent inhibition of cell survival and colony formation in clonogenic assays. This work demonstrates that tetracenomycins act mainly as cytostatic rather than apoptotic agents. Full article

This study aimed to investigate the role and underlying mechanism of apolipoprotein C2 (APOC2) in the progression of clear cell renal cell carcinoma (ccRCC). Analysis of The Cancer Genome Atlas (TCGA) datasets, combined with validation in ccRCC cell lines, revealed that APOC2 was markedly upregulated in ccRCC tissues and cells and was associated with poor patient prognosis. Functional assays demonstrated that APOC2 knockdown significantly suppressed cell proliferation, colony formation, migration, and invasion, while promoting apoptosis. Mechanistic studies showed that silencing APOC2 reduced the phosphorylation levels of key components of the JAK-STAT signaling pathway, including Jak1/2 and STAT3, without affecting their total protein expression. Gene enrichment analysis further indicated the involvement of JAK-STAT signaling, and functional rescue experiments using the STAT3 agonist Colivelin partially reversed the decreased cell viability and increased apoptosis caused by APOC2 knockdown, confirming the pathway’s mediating role. Collectively, these findings suggest that APOC2 promotes ccRCC cell proliferation and inhibits apoptosis, at least in part, through activation of the JAK-STAT signaling pathway, highlighting APOC2 as a novel oncogenic regulator and potential therapeutic target, and providing new insight into the metabolic–inflammatory axis in ccRCC progression. Clinically, APOC2 may serve as a biomarker to identify ccRCC patients with hyperactivated JAK-STAT signaling and could potentially guide combination therapies involving JAK/STAT inhibitors or metabolic-targeted agents. Full article

Nitric oxide (NO), a reactive nitrogen species (RNS), plays a role in multiple biological functions and signal transduction. However, the mechanisms by which NO counteracts stress tolerance in microbes have been poorly explored. In addition, the decomposition of salty food waste poses a significant challenge for food-degrading microbes. Therefore, we investigated how S-nitrosocysteine (CysNO) affects the cellular salt stress response of Burkholderia vietnamiensis TVV75, a strain isolated from a commercial food waste composite. Under the additional 2% NaCl treatment, increased reactive oxygen species (ROS) inhibited bacterial cell growth and viability. In contrast, CysNO treatment alleviated the cellular ROS levels and growth inhibition by augmenting the superoxide dismutase (SOD) and catalase (CAT) activities. CysNO supplementation also promotes the nitrate reduction pathway in B. vietnamiensis TVV75 under salt stress, suggesting NO-mediated nitrogen metabolism for microbial adaptation to salt stress. Furthermore, CysNO restored the intracellular lipid-degrading lipase enzyme activities, which were compromised by salt stress alone. This restoration was accompanied by a concentration-dependent increase in the relative expression of the lipA (lipase A) and ELFPP (esterase lipase family protein) genes. These results suggest that external NO supplementation can regulate redox balance, nitrate reduction, and lipase activity to maintain microbial cell growth in high-salt environments, pinpointing a NO-dependent salt stress adaptation strategy for salt-sensitive microbes involved in food waste decomposition. Full article

The heart’s relentless contractile activity depends critically on mitochondrial function to meet its extraordinary bioenergetic demands. Mitochondria, through oxidative phosphorylation, not only supply ATP but also regulate metabolism, calcium homeostasis, and apoptotic signaling, ensuring cardiomyocyte viability and cardiac function. Mitochondrial dysfunction is a hallmark of cardiomyopathies and heart failure, characterized by impaired oxidative phosphorylation, excessive production of reactive oxygen species (ROS), dysregulated calcium handling, and disturbances in mitochondrial dynamics and mitophagy. These defects culminate in energetic insufficiency, cellular injury, and cardiomyocyte death, driving heart disease progression. Diverse cardiomyopathy phenotypes exhibit distinct mitochondrial pathologies, from acute ischemia-induced mitochondrial collapse to chronic remodeling seen in dilated, hypertrophic, restrictive, and primary mitochondrial cardiomyopathies. Mitochondria also orchestrate cell death and inflammatory pathways that worsen cardiac dysfunction. Therapeutic strategies targeting mitochondrial dysfunction, including antioxidants, modulators of mitochondrial biogenesis, metabolic therapies, and innovative approaches such as mitochondrial transplantation, show promise but face challenges in clinical translation. Advances in biomarker discovery and personalized medicine approaches hold promise for optimizing mitochondrial-targeted therapies. Unlike previous reviews that examined these pathways or interventions individually, this work summarizes insights into mechanisms with emerging therapeutic strategies, such as SGLT2 inhibition in HFpEF, NAD⁺ repletion, mitochondrial transplantation, and biomarker-driven precision medicine, into a unified synthesis. This framework underscores the novel contribution of linking basic mitochondrial biology to translational and clinical opportunities in cardiomyopathy and heart failure. This review synthesizes the current understanding of mitochondrial biology in cardiac health and disease, delineates the molecular mechanisms underpinning mitochondrial dysfunction in cardiomyopathy and heart failure, and explores emerging therapeutic avenues aimed at restoring mitochondrial integrity and improving clinical outcomes in cardiac patients. Full article

Photocatalytic oxidation of microorganisms is a powerful alternative to established disinfection approaches, applicable to a variety of water matrices. Bacterial vegetative cells, spores, fungi, and viruses, represent potential biopathogens and photocatalysis targets. Inactivation efficiency is usually evaluated by assessing viability through culture. However, additional inactivation assessment approaches are needed, as some microbes, despite being unculturable, remain metabolically active and pathogenic. Nucleic acid quantification approaches (qPCR) can assess nucleic acid release and degradation during photocatalysis. We developed a novel multiplex qPCR assay for simultaneous detection/quantification of genomic DNA from different bacterial and fungal species and of MS2 bacteriophage load. Following small-scale solar titanium dioxide photocatalysis on a microbial suspension mixture containing different biopathogen classes, we assessed photocatalytic efficiency by conventional microbiological assays (culture) and our novel molecular assay. Microbiological assays show a significant reduction in microbe viability within one hour of processing, following previously reported patterns of microbial species resistance. Molecular analysis data show that nucleic acids released in solution due to microbial oxidative damage were significantly reduced due to oxidative degradation within six hours. Through targeting different biopathogen classes, our assay could be a useful tool for assessment of photocatalytic microbe inactivation both in laboratory and real-wastewater applications. Full article

Aquaculture faces challenges in reducing feed costs while promoting sustainable use of by-products. This study aimed to evaluate the effects of totally replacing soybean oil (SBO) with fish by-product oil (FBO) in the diet of Colossoma macropomum, focusing on growth performance, physiological and hepatic responses, meat composition, and economic viability. A total of 360 juveniles (9.1 ± 0.59) were distributed in a randomized design with six treatments (0–100% SBO replacement) and six replicates each, and fed to apparent satiation for 91 days. Growth performance did not differ significantly among treatments (p > 0.05), although fish receiving 40% FBO achieved the best feed conversion ratio among treatments. Hematological and biochemical analyses indicated that higher FBO levels (particularly 100%) indicating subtle yet adaptive physiological adjustments, such as moderate modulations in lipid metabolism and erythropoietic activity. Liver weight and hepatosomatic index decreased linearly with increasing FBO levels. In meat composition, FBO inclusion enhanced protein and reduced lipid contents. Although economic indicators were not statistically different (p > 0.05), offered the most favorable trade-off between biological performance and economic efficiency. These findings demonstrate that partial replacement of SBO with FBO, particularly at 40%, represents a sustainable and economically viable alternative for C. macropomum farming. Full article

Background: Human cell lines underpin modern biomedical research, offering reproducibility, standardisation, and unrestricted access to biological material. Among the 1206 human lines documented in the Human Protein Atlas, in vitro systems overcome the ethical and technical constraints of primary tissues. The liver is an organ of intricate structure, diverse physiological roles, and limited in vitro viability. Liver-derived cell lines are increasingly used to address the growing burden of liver disease and to accelerate pharmaceutical development, yet their capacity to replicate native hepatic functions remains uncertain. The mutational profiles and expression patterns of hepatocyte-characteristic genes provide critical benchmarks for their suitability for pharmacology and toxicology. Methods: Here, we systematically compare ten widely used hepatic cell lines (HepG2, Huh7, Hep3B, LX-2, HepaRG, HLF, HLE, MHCC97H, SK-Hep1, PLC/PRF/5) with primary hepatocytes and liver tissue, focusing on drug-metabolizing enzyme (DME) gene expression. Beyond literature synthesis, we analysed pre-processed RNA-seq expression data. Results: Overall, among the models examined, the HepaRG cell line shows the greatest similarity to liver and primary hepatocytes, most faithfully reproducing the expression patterns of DME genes. HepG2, Hep3B, and Huh7 form a cluster that retains only a subset of hepatic characteristics. Other models display more pronounced deviations from the reference profile and are generally used for specialized applications. Thus, no universal cell line exists that can fully substitute for the liver. Each model has its own limitations and biases in the expression profile of DME genes, which must be carefully considered when selecting an appropriate system for specific research objectives. Full article

Streptococcus pneumoniae is a major opportunistic pathogen and a leading cause of severe infections in infants under two years of age. Human milk oligosaccharides (HMOs), key bioactive components of breast milk, possess immunomodulatory and antimicrobial properties. In this study, the antipneumococcal effects of HMOs are investigated across multiple S. pneumoniae serotypes, focusing on concentration-dependent activity and underlying mechanisms. Growth inhibition and bacterial viability were evaluated using growth curve analysis and colony-forming unit (CFU) assays. HMOs inhibited pneumococcal growth in a concentration-dependent manner, with suppression observed at 1.5–2.5 mg/mL and complete killing at 5 mg/mL for all serotypes. Nonencapsulated strains were more sensitive, with inhibition at 1 mg/mL. In the CFU assays, killing occurred at 1.25–5 mg/mL depending on the strain. At physiologically relevant colostrum concentrations (20–25 mg/mL), HMOs achieved complete bactericidal effects across all the tested strains. In contrast, lactose at equivalent doses showed no measurable antimicrobial activity, confirming the specificity of the observed effects. Overall, HMOs exhibit serotype-independent antipneumococcal activity, possibly through interference with bacterial adhesion or metabolic disruption. These findings suggest a potential role for HMOs as adjunctive agents in the prevention of pneumococcal infections in vulnerable populations, such as infants, and warrant further in vivo studies to validate these effects and explore clinical applications. Full article

Eragrostis nindensis is a resurrection grass capable of surviving near-complete desiccation. We compared non-senescent leaf tissue (NST) and senescent leaf tissue (ST) to investigate the cellular and molecular basis of desiccation tolerance and senescence. NST recovered fully after drying, while ST failed to regain viability. Integrated transcriptomic (using RNA-Seq), lipidomic (using LC-MS), and ultrastructural (Transmission Electron Microscopical) analyses revealed that NST maintain RNA processing, protein folding, and translational activity during desiccation. Lipidomic data and ultrastructure showed preferential accumulation of polyunsaturated triacylglycerols (TAGs) and lipid droplets in NST, supporting membrane protection and energy buffering. In contrast, ST showed cellular collapse, reduced oleosin protein accumulation, and signatures of senescence. These findings highlight the importance of post-transcriptional and post-translational regulation, as well as lipid metabolism, in preserving cellular integrity during desiccation in this species. Full article

The cryopreservation and transplantation of germline stem cells (GSCs) have become the key to conserving fish genetic resources and safeguarding species diversity. This study aimed to investigate the effects of post-mortem temperature and time on the preservation of oogonial stem cells (OSCs) in the marine fish Paralichthys olivaceus. OSCs remained viable after fish death, and they remained viable and could be cultured after storage at 19 °C for 15 h and at 4 °C for 24 h. Combined transcriptomic and metabolomic analysis was used to identify the pathways leading to OSC death. Several genes were differentially expressed in the ovarian tissue post-mortem, with the most enriched pathways being ferroptosis, fatty acid metabolism/biosynthesis, glutathione metabolism, citric acid cycle (TCA cycle), and arachidonic acid metabolism signaling pathways. Genes related to ferroptosis, such as vdac2, p53, and slc7a11, as well as metabolites such as adrenic acid and arachidic acid, can serve as reliable biomarkers for evaluating the viability of post-mortem OSCs. These findings provide valuable insights and theoretical support for the effective use of post-mortem GSCs and enhance strategies for germplasm resource conservation in fish. Full article

Background: Developing clinically relevant experimental models of the human airway can significantly advance our understanding of the mechanisms underlying airway diseases and aid in translating potential therapies to clinical settings. The aim of this study is to establish an ex vivo human airway tissue culture model. Methods: Human donor airway tissues were obtained from clinical cases of lung transplantation. Our established method is based on the concept of scavenging metabolic activity and controlling bacterial growth and includes increased media volume, frequent media exchange, and antifungal additives to efficiently maintain the homeostatic culture environment. After a 3-day culture period, the airway was investigated, and its viability and function were compared with a standard cell culture method. Results: Control tissue exhibited significant acidosis after 3 days, suggesting high metabolic activity of airway tissue and bacterial contamination. The airway epithelial viability—after culturing in our established method for 3 days—was better than that of the controls. We only performed an acute but early investigation of the cultures as airway complications have been known to start early at the proximal bronchus after transplantation. H&E and alcian blue staining showed intact morphology of the epithelium of airway tissue and mucus layers after 3 days in our model, while controls showed remarkable damage to the epithelial layer. Newly synthesized glycoproteins were detected in the epithelial layer using metabolic labeling and the click chemistry technique, suggesting cellular protein synthesis of the airway tissue in our established ex vivo model. Conclusions: We successfully established a reproducible model of human ex vivo airway tissue culture (n = 3 independent biological samples) that may be useful for investigating airway complications and developing their therapies. Full article