Search Results (467)

Sarcopenia is a progressive age-related musculoskeletal disorder characterized by loss of muscle mass, strength, and physical performance, contributing to functional decline and increased risk of disability. Emerging evidence suggests that vitamin D (Vit D) plays a pivotal role in skeletal muscle physiology beyond its classical functions in bone metabolism. This review aims to critically analyze the relationship between serum Vit D levels and sarcopenia in older adults, focusing on pathophysiological mechanisms, diagnostic criteria, clinical evidence, and preventive strategies. An integrative narrative review of observational studies, randomized controlled trials, and meta-analyses published in the last decade was conducted. The analysis incorporated international diagnostic criteria for sarcopenia (EWGSOP2, AWGS, FNIH, IWGS), current guidelines for Vit D sufficiency, and molecular mechanisms related to Vit D receptor (VDR) signaling in muscle tissue. Low serum 25-hydroxyvitamin D levels are consistently associated with decreased muscle strength, reduced physical performance, and increased prevalence of sarcopenia. Although interventional trials using Vit D supplementation report variable results, benefits are more evident in individuals with baseline deficiency and when combined with protein intake and resistance training. Mechanistically, Vit D influences muscle health via genomic and non-genomic pathways, regulating calcium homeostasis, mitochondrial function, oxidative stress, and inflammatory signaling. Vit D deficiency represents a modifiable risk factor for sarcopenia and functional impairment in older adults. While current evidence supports its role in muscular health, future high-quality trials are needed to establish optimal serum thresholds and dosing strategies for prevention and treatment. An individualized, multimodal approach involving supplementation, exercise, and nutritional optimization appears most promising. Full article

Lindane, a persistent organochlorine pesticide, exerts toxic effects on the female reproductive system, compromising oocyte quality and maturation. However, the effects of this pesticide on mammalian oocyte morphology and ultrastructure remain unknown. This study investigated the effects of Lindane on mouse oocyte ultrastructure using an in vitro model with Transmission Electron Microscopy (TEM) at concentrations from 1 to 100 μM. The results revealed a progressive dose-related trend of alterations: at 1 μM, mild swelling of smooth endoplasmic reticulum (SER) vesicles; at 10 μM, increased SER dilation and cytoplasmic disorganization; and at 100 μM, pronounced vacuolization, mitochondrial swelling, dense lamellar bodies (dlbs), and multivesicular bodies (MVBs) indicative of autophagic activity. Mitochondrial alterations increased significantly with concentration: 3.2 ± 0.8 (control), 5.7 ± 1.0 (1 μM), 9.4 ± 1.5 (10 μM), and 16.8 ± 2.3 (100 μM) altered mitochondria per oocyte (p < 0.01). Vacuole frequency was notably elevated at 100 μM (4.3 ± 1.1 vs. 0.7 ± 0.5 in controls), and mislocalization of organelles within the ooplasm was observed. In conclusion, Lindane-induced oocyte ultrastructural alterations were observed at all tested concentrations but were more pronounced at 100 μM. These results highlight its impact on female fertility and may guide the search for protective agents, as well as efforts to reduce environmental exposure to endocrine disruptors. Full article

The study of metabolic abnormalities regarding mitochondrial respiration and energy production has significantly advanced our understanding of cell biology and molecular mechanisms underlying cardiovascular diseases (CVDs). Mitochondria provide 90% of the energy required for maintaining normal cardiac function and are central to heart bioenergetics. During the initial phase of heart failure, mitochondrial number and function progressively decline, causing a decrease in oxidative metabolism and increased glucose uptake and glycolysis, leading to ATP depletion and bioenergetic starvation, finally contributing to overt heart failure. Compromised mitochondrial bioenergetics is associated with vascular damage in hypertension, vascular remodeling in pulmonary hypertension and acute cardiovascular events. Thus, mitochondrial dysfunction, leading to impaired ATP production, excessive ROS generation, the opening of mitochondrial permeability transition pores and the activation of apoptotic and necrotic pathways, is revealed as a typical feature of common CVDs. Molecules able to positively modulate cellular metabolism by improving mitochondrial bioenergetics and energy metabolism and inhibiting oxidative stress production are expected to exert beneficial protective effects in the heart and vasculature. This review discusses recent advances in cardiovascular research through the study of cellular bioenergetics in both chronic and acute CVDs. Emerging therapeutic strategies, specifically targeting metabolic modulators, mitochondrial function and quality control, are discussed. Full article

The core objective of racehorse breeding is to enhance the speed and endurance of the horses. The Grassland-Thoroughbred is an emerging horse breed developed in northern China in recent years, characterized by excellent speed performance, enduring stamina, and strong environmental adaptability. However, research on the genetic characteristics within this breed and the genes associated with athletic performance remains relatively limited. We conducted whole-genome resequencing of Grassland-Thoroughbred F1, F2, F3, and the crossbred population (CY) and obtained a total of 4056.23 Gb of high-quality data after quality control. The single nucleotide polymorphisms (SNPs) were primarily distributed in intergenic regions, followed by intronic regions. Principal component analysis (PCA) and STRUCTURE revealed clear distinctions among the generations, with a notable overlap between CY and F3. Using the SNP dataset, we analyzed the number and length distribution patterns of runs of homozygosity (ROHs) in the genomes of different generational groups of Grassland-Thoroughbreds. Short ROHs ranging from 0.5 to 2 Mb were the most abundant, with the following distribution: F1 (85.15%) > F2 (82.92%) > CY (78.75%) > F3 (77.51%). Medium-length ROHs (2–8 Mb) and long ROHs (>8 Mb) together exhibited a similar but opposite trend. The average length of ROHs was 1.57 Mb. The inbreeding coefficients (F_ROH) among different generational groups of Grassland-Thoroughbreds were as follows: F1 (0.0942) < F2 (0.1197) < CY (0.1435) < F3 (0.1497). Through ROH island analysis, 10 high-frequency ROH regions were identified and annotated with 120 genes. Genomic regions and candidate genes associated with athletic traits—ACAD8, OPCML, PRDX2, NTM, NDUFB7, SCL25A15, FOXO1, and SLC4A10—were identified. These genes may play important roles in regulating muscle performance, mitochondrial energy supply, and learning and memory processes in horses and are closely associated with the athletic ability of the Grassland-Thoroughbred population. This study is the first to systematically characterize the genomic diversity and inbreeding dynamics of the Grassland-Thoroughbred during the breeding process. It identifies candidate genes that may influence athletic performance, thereby providing an important molecular foundation and theoretical basis for the genetic improvement and performance-based selection of this emerging breed. Full article

Background: Sarcopenia is a syndrome associated with aging, characterized by a progressive decline in skeletal muscle mass and function. Its onset compromises the health and longevity of older adults by increasing susceptibility to falls, fractures, and various comorbid conditions, thereby diminishing quality of life and capacity for independent living. Accumulating evidence indicates that moderate-intensity aerobic exercise is an effective strategy for promoting overall health in older adults and exerts a beneficial effect that mitigates age-related sarcopenia. However, the underlying molecular mechanisms through which exercise confers these protective effects remain incompletely understood. Methods: In this study, we established a naturally aging mouse model to investigate the effects of a 16-week treadmill-based aerobic exercise regimen on skeletal muscle physiology. Results: Results showed that aerobic exercise mitigated age-related declines in muscle mass and function, enhanced markers associated with protein synthesis, reduced oxidative stress, and modulated the expression of genes and proteins implicated in mitochondrial quality control. Notably, a single session of aerobic exercise acutely elevated circulating levels of β-hydroxybutyrate (β-HB) and upregulated the expression of BDH1, HCAR2, and PPARG in the skeletal muscle, suggesting a possible role of β-HB–related signaling in exercise-induced muscle adaptations. However, although these findings support the beneficial effects of aerobic exercise on skeletal muscle aging, further investigation is warranted to elucidate the causal relationships and to characterize the chronic signaling mechanisms involved. Conclusions: This study offers preliminary insights into how aerobic exercise may modulate mitochondrial quality control and β-HB–associated signaling pathways during aging. Full article

Nitrogen-containing bisphosphonates (N-BPs) are commonly used drugs in the treatment of bone diseases due to their potent inhibition of the mevalonate pathway, leading to disrupted protein prenylation and reduced osteoclast activity. Although N-BPs are effective in reducing bone resorption, increasing evidence indicates their side effects on various non-skeletal cells. The aim of this review is to synthesize the current knowledge on the cellular and molecular effects of N-BPs outside the skeletal system, with particular emphasis on their impact on mitochondrial function and energy metabolism. At the cellular level, N-BPs may reduce viability, modulate inflammatory responses, trigger apoptosis, disrupt cytoskeletal organization, and influence signaling and energy metabolism. N-BPs may also impair the prenylation of proteins essential for mitochondrial dynamics and quality control, and may disrupt Ca²⁺ homeostasis. As we have shown in endothelial cells, by inhibiting the mevalonate pathway, N-BPs may lead to a reduction in key components of the mitochondrial respiratory chain, such as coenzyme Q (CoQ) and a-heme. These effects can contribute to impaired mitochondrial respiratory function, increased oxidative stress, and mitochondria-dependent apoptosis, affecting cellular energy metabolism and viability. These findings underscore the multifaceted impact of N-BPs beyond bone, emphasizing the importance of mitochondrial health and energy metabolism in understanding their broader biological effects and potential adverse outcomes. Full article

The prevalence of stroke in patients with migraine is higher than in the general population, suggesting certain shared mechanisms of pathogenesis. Migrainous infarction is a pronounced example of the migraine–stroke connection. Some cases of migraine with aura may be misdiagnosed as stroke, with subsequent mistreatment. Therefore, it is important to identify these shared mechanisms of pathogenesis contributing to the migraine–stroke connection to improve diagnosis and treatment. Sirtuins (SIRTs) are a seven-member family of NAD⁺-dependent histone deacetylases that can epigenetically regulate gene expression. Sirtuins possess antioxidant properties, making them a first-line defense against oxidative stress, which is important in the pathogenesis of migraine and stroke. Mitochondrial localization of SIRT2, SIRT3, and SIRT4 supports this function, as most reactive oxygen and nitrogen species are produced in mitochondria. In this narrative review, we present arguments that sirtuins may link migraine with stroke through their involvement in antioxidant defense, mitochondrial quality control, neuroinflammation, and autophagy. We also indicate mediators of this involvement that can be, along with sirtuins, therapeutic targets to ameliorate migraine and prevent stroke. Full article

Oocyte maturation represents a fundamental biological process in bovine reproduction, establishing the physiological basis for fertilization and early embryonic development while critically determining the propagation of improved varieties and breeding efficiency. The roles of MQC in reproduction have gained substantial scientific attention. The proper maturation of oocytes fundamentally depends on adequate mitochondrial functionality. However, the intrinsic regulatory mechanisms governing MQC during bovine oocyte maturation remain incompletely characterized. Here, we discuss the most recent progress on the molecular mechanisms and roles of mitochondrial fission/fusion, biogenesis, and mitophagy in MQC. Building upon the mechanistic foundations of MQC in bovine oocyte maturation, this review identifies key mitochondrial-targeted supplements with potential applications in enhancing oocyte quality. Furthermore, we evaluate epigenetic influences on mitochondrial regulatory networks through mitochondrial–nuclear communication. Finally, we discuss the challenges in elucidating mitochondrial quality control mechanisms during oocyte maturation and propose corresponding strategies to address these obstacles. Integrating mechanistic insights, this review proposes strategies to enhance in vitro culture systems and identify oocyte quality markers, providing valuable insights for optimizing in vitro production (IVP) of bovine embryos and enhancing reproductive efficiency. Full article

Breast cancer is the leading threat to the health of women, with a rising global incidence linked to social and psychological factors. Among its subtypes, triple-negative breast cancer (TNBC), which lacks estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, is highly heterogeneous with early metastasis and a poor prognosis, making it the most challenging subtype. Mounting evidence shows that the mitochondrial quality control (MQC) system is vital for maintaining cellular homeostasis. Dysfunction of the MQC is tied to tumor cell invasiveness, metastasis, and chemoresistance. This paper comprehensively reviews the molecular link between MQC and TNBC development. We focused on how abnormal MQC affects TNBC progression by influencing chemoresistance, immune evasion, metastasis, and cancer stemness. On the basis of current studies, new TNBC treatment strategies targeting key MQC nodes have been proposed. These findings increase the understanding of TNBC pathogenesis and offer a theoretical basis for overcoming treatment challenges, providing new research angles and intervention targets for effective precision therapy for TNBC. Full article

Obesity and metabolic disorders remain major global health concerns, traditionally attributed to excessive caloric intake and poor diet quality. Recent studies emphasize that the timing of meals plays a crucial role in determining metabolic health. This review explores chrononutrition, a growing field that examines how food intake patterns interact with endogenous circadian rhythms to influence energy balance, glucose and lipid metabolism, and cardiometabolic risk. The circadian system, which includes a central clock in the suprachiasmatic nucleus and peripheral clocks in metabolic tissues, regulates physiological functions on a 24 h cycle. While light entrains the central clock, feeding schedules act as key synchronizers for peripheral clocks. Disrupting this alignment—common in modern lifestyles involving shift work or late-night eating—can impair hormonal rhythms, reduce insulin sensitivity, and promote adiposity. Evidence from clinical and preclinical studies suggests that early time-restricted eating, where food intake is confined to the morning or early afternoon, offers significant benefits for weight control, glycemic regulation, lipid profiles, and mitochondrial efficiency, even in the absence of caloric restriction. These effects are particularly relevant for populations vulnerable to circadian disruption, such as adolescents, older adults, and night-shift workers. In conclusion, aligning food intake with circadian biology represents a promising, low-cost, and modifiable strategy to improve metabolic outcomes. Integrating chrononutrition into clinical and public health strategies may enhance dietary adherence and treatment efficacy. Future large-scale studies are needed to define optimal eating windows, assess long-term sustainability, and establish population-specific chrononutritional guidelines. Full article

The physiological functions of mammalian sperm, such as motility, hyperactivation, and capacitation, require substantial energy. This study investigates the effects of two classic cryopreservation extenders—TCG (tris-citrate-glucose) and LEY (lactose-egg yolk)—on the energy metabolism of frozen–thawed boar semen. By comparing the quality indicators, key metabolite levels, and the activities of critical enzymes involved in glycolysis and the tricarboxylic acid cycle, we aim to understand how these different semen extenders influence the spermatozoa vitality of frozen–thawed boar semen. Following thawing, the LEY-cryopreserved sperm demonstrated significantly elevated motility parameters (viability, VCL, VSL, and VAP) and enhanced plasma membrane and acrosomal integrity compared with the TCG group (p < 0.05), though both cryopreserved groups exhibited significantly reduced performance relative to fresh semen controls. Cryopreservation markedly reduced intracellular adenosine triphosphate (ATP), pyruvate, and acetyl coenzyme A (A-CoA) levels (fresh > LEY > TCG; p < 0.05). The LEY-preserved spermatozoa retained higher activities of glycolysis-related enzymes (phosphofructokinase, PFK; pyruvate kinase, PK) compared with the TCG group, which, in turn, showed elevated lactate dehydrogenase (LDH) activity. Critically, TCG-suppressed pyruvate dehydrogenase (PDH) activity (p < 0.05) coincided with diminished A-CoA, indicating impaired mitochondrial oxidative phosphorylation. These results demonstrate LEY’s superior preservation of motility and membrane stability but highlight cryodamage-induced energy metabolism dysregulation, particularly TCG’s disruption of the glycolysis–TCA cycle coordination essential for spermatozoa function. In conclusion, the choice of semen extender has a significant impact on the energy metabolism and overall quality of frozen–thawed semen, highlighting the importance of optimizing cryopreservation protocols for improved spermatozoa viability and functionality. Full article

Aflatoxin contamination poses a significant food safety risk, particularly during the storage of dried chili peppers. This study evaluated the efficacy of formic acid treatment, ultraviolet (UV) treatment, and combined UV-formic acid treatment in both preventing and controlling Aspergillus flavus in dried red chili powder. Efficacy was assessed by measuring the growth diameter of A. flavus colonies on un-colonized and already colonized dried red chili powder. The optimal treatment conditions for the UV-formic acid combination were determined through single-factor experiments, orthogonal experiments, and quality assessment. Finally, the effects of the UV-formic acid combination on the cell membrane, antioxidant system, and energy metabolism of A. flavus were investigated. The results revealed that fumigation of un-colonized dried red chili powder with 5% formic acid for 24 h inhibited A. flavus growth by 93.29% and toxin synthesis by 99.41%. In contrast, treatment of already colonized chili powder with 10% formic acid inhibited A. flavus colony growth by 50%. Through a three-factor, three-level orthogonal experiment followed by quality testing, the optimal conditions were determined to be 8% formic acid concentration, a UV irradiation distance of 15 cm, and a treatment time of 75 min. This optimized combined treatment reduced the required fumigation time from 24 h to 1.25 h. This technique achieved complete suppression of aflatoxin B₁ synthesis on un-colonized dried red chili powder. On already colonized chili powder, the mycelial growth inhibition rate was 48.05 ± 6.68%, and aflatoxin B₁ synthesis was inhibited by 91.32 ± 3.15%. Quality assessment revealed that the UV-formic acid co-treatment parameters did not significantly affect key quality indicators including color, capsaicin content, total phenolic content (p > 0.05). Furthermore, UV-formic acid treatment disrupt the cell membrane structure of A. flavus, impairs its antioxidant and energy metabolism systems, and induces mitochondrial dysfunction. The study confirmed the synergistic antifungal effect of formic acid and UV, providing a potential industrialized solution for enhancing the safety and storage stability of dried chili products. Full article

Background/Objectives: This study investigated whether enzymatic hydrolysis enhances the cognitive benefits of HongJam (steamed mature silkworms) and explored the underlying mechanisms. A marker compound of enzyme-treated HongJam was also identified to support quality control. Methods and Results: Mice were supplemented with Golden Silk HongJam (GS) or its enzyme hydrolysates (GS-EHS). Behavioral tests showed both improved fear-aggravated memory, with GS-EHS producing similar or greater effects at lower doses. GS-EHS activated the cyclic AMP response element binding protein/brain-derived neurotrophic factor signaling pathway and mitigated scopolamine-induced mitochondrial dysfunction by enhancing mitochondrial complex activity and ATP production. It also increased esterase activity, reduced reactive oxygen species, and modulated programmed cell death by suppressing apoptosis while promoting autophagy and unfolded protein response pathways. These changes led to reduced endoplasmic reticulum stress and neuroinflammation. Mass spectrometry identified glycine-tyrosine dipeptide as a potential bioactive marker. Conclusions: GS-EHS enhances cognitive function by improving mitochondrial activity, reducing oxidative stress, and regulating programmed cell death. Enzymatic hydrolysis appears to increase the bioavailability of active compounds, making GS-EHS effective at lower doses. The glycine–tyrosine dipeptide may serve as a marker compound for standardizing GS-EHS based on its cognitive-enhancing properties. Full article

Objectives: The aim of this study was to evaluate the impact of a novel antioxidant formulation (RE:PAIR, RP-25) containing CoQ10, alpha-lipoic acid, and Chaga extract on mitochondrial dysfunction and oxidative stress. To explore the activity of the formulation on neuronal cells, we explored cell metabolism and its activity as an antioxidant, using a combination of NMR-based metabolomics and UHPLC-HRMS analytical techniques. Methods: SH-SY5Y neuroblastoma cells were treated with RP-25, and cell viability was assessed via CCK-8 assay. Metabolomic profiles of the treated and untreated cells were analyzed by 1D-NMR, providing insights into both intracellular metabolites (endometabolome) and excreted metabolites (exometabolome). Additionally, a UHPLC-HRMS method was developed for quality control and analysis of the RP-25 formulation. Multivariate statistical approaches, including PLS-DA and volcano plot analyses, were used to identify key metabolic changes. Changes in mitochondrial membrane potential were assessed by means of TMRE assay, while radical oxygen species (ROS) were measured by means of the DCHF assay. Results: RP-25 treatment did not affect cell viability but significantly increased metabolic pathways, including amino acid biosynthesis, oxidative phosphorylation, and glycolysis. Higher levels of ATP, glutamate, tyrosine, and proline were observed in treated cells than in control cells, indicating enhanced cellular energy production, as also proved by the increased stability of the mitochondrial membrane after RP-25 treatment, an index of preserved mitochondrial functions. In support, the formulation RP-25 showed antioxidant activity when cells underwent peroxide oxygen stimulation. This effect was mainly due to the combination of Chaga, CoQ10, and ALA, main components of the RP25 formulation. Moreover, the analysis of enriched pathways highlighted that RP formulation influenced mitochondrial energy and oxidative stress response. Conclusions: RP-25 demonstrated biological activity in that it mitigated mitochondrial dysfunction and oxidative stress in neuronal cells, with potential implications in neuronal diseases associated with dysfunctional mitochondria. Full article

Cardiac adaptations induced by aerobic exercise have been shown to reduce the risk of cardiovascular disease, and the autonomic nervous system is closely associated with the development of cardiovascular disease. Aerobic exercise intervention has been shown to enhance cardiac function and mitigate myocardial fibrosis and hypertrophy in heart failure mice. Further insights reveal that cardiomyocytes experiencing chronic heart failure undergo modifications in their lipidomic profile, including remodeling of multiple myocardial membrane phospholipids. Notably, there is a decrease in the total content of cardiolipin, as well as in the levels of total lysolipid CL and the CL (22:6). These alterations disrupt mitochondrial quality control processes, leading to abnormal expressions of proteins such as Drp1, MFN2, OPA1, and BNIP3, thereby resulting in a disrupted mitochondrial dynamic network. Whereas aerobic exercise ameliorated mitochondrial damage to a large extent by activating parasympathetic nerves, this beneficial effect was accomplished by modulating myocardial membrane phospholipid remodeling and restoring the mitochondrial dynamic network. In conclusion, aerobic exercise activated the parasympathetic state in mice and attenuated lipid peroxidation and oxidative stress injury, thereby maintaining mitochondrial dynamic homeostasis and improving cardiac function. Full article