Comprehensive Physiology最新文献

Complement factor D (CFD, also known as adipsin) is a secreted serine protease classically known for activating the alternative complement pathway and regulating systemic metabolism. Although CFD is highly expressed in adipocytes, its roles in adipogenesis remain to be elucidated. Here, we show that intracellularly localized CFD promoted lipid droplet (LD) formation in its catalytic activity-independent manner. Using mammary adipose tissue-derived stem cells (mADSCs) isolated from wild-type (WT) and Cfd-knockout (Cfd-KO) mice, we demonstrated that the lack of CFD significantly reduced LD number in mature adipocytes. Lentiviral expression of the secretion signal sequence-deficient (SD) or catalytically inactive CFD mutant, as well as the cytosolic CFD3 splice variant, rescued LD formation to WT levels in Cfd-KO adipocytes. In contrast, exogenously supplemented CFD proteins were unable to restore LD formation in our culture system. These findings uncover a previously unrecognized intracellular function for CFD, revealing its regulatory role in LD biogenesis during adipocyte differentiation.

Rheumatoid arthritis (RA), a chronic autoimmune disorder driven by genetic-environmental interplay, manifests as progressive synovitis and irreversible joint damage. Despite mechanistic advances in disease-modifying antirheumatic drugs (DMARDs) and biologics, upstream mucosal triggers of autoimmunity remain elusive. Mounting evidence implicates gut microbiota dysbiosis as a pivotal environmental factor in RA pathogenesis through multifaceted mechanisms: (1) compromising intestinal barrier integrity, (2) facilitating molecular mimicry via cross-reactive microbial antigens, (3) skewing mucosal immunity toward pro-inflammatory T helper 17 (Th17)/T follicular helper (Tfh) cell responses, and (4) generating bioactive metabolites with dual roles in regulating osteoclastogenesis and synovial inflammation. This review synthesizes recent advances in gut microbiome profiling, mechanistic studies, and preclinical models, elucidating microbial-host crosstalk in autoimmune cascades. Furthermore, we critically evaluate microbiota-directed strategies, including dietary and probiotic modulation, microbiome-informed optimization of conventional DMARDs and biologics, and investigational approaches like fecal microbiota transplantation and Chinese herbal medicine, that may offer promising adjunctive approaches to complement conventional RA management.

Metabolic Associated Fatty Liver Disease (MAFLD) is a prevalent chronic condition with limited therapeutic options, making lifestyle interventions a primary strategy. This study investigated whether exercise, alone or with dietary modifications, mitigates HFD-induced alterations in rats of both sexes. The motor coordination, plasma glucose and irisin levels, oxidative stress and inflammatory biomarkers (catalase, superoxide dismutase, glutathione peroxidase, malondialdehyde and myeloperoxidase) in liver and muscle, and hepatic Nrf2, NF-κB, and UCP-2 expression were evaluated. Rats were fed a HFD for 3 months, followed by 2 months of interventions consisting of exercise and a shift to a standard diet (SD) or antioxidant-rich diet. Control and HFD groups received pellet and HFD, respectively, for the full 5 months. The results showed improvements in weight gain, motor performance, and antioxidant profiles in tissues when exercise was combined with dietary changes in both sexes. Exercise alone was enough to improve motor coordination in males. Plasma glucose and irisin recovered control values, especially when exercise was combined with a healthier diet in both sexes. Nrf2, NF-κB and UCP-2 expression, altered by the HFD, were also restored after interventions. Overall, the combination of exercise and an antioxidant-rich diet produced the most pronounced improvements across all parameters. In conclusion, combining exercise and a healthier diet, especially rich in antioxidants, led to marked improvements in motor function and plasma and tissue biomarkers with slight differences between females and males.

Background: The pace of physiological deterioration is variable among living beings. Vitamin D is proven to be one of the crucial yet deficient vitamins. Hypovitaminosis D is often marked by aging, but young adults are also not exempt. Thus, to identify the lacunae and bridge the gap between aging and vitamin D, this study selected the middle-aged age group and their phenotypic aging markers. Physiological changes are gradual and measurable using non-invasive methods, and they contribute to the phenotypic aging markers like BMI, WHR, F%, WS, and HGS. This study hypothesizes that the minute changes in phenotypic markers in young adults, which are prominent during middle age and potentially cause early aging, are influenced by Vitamin D.

Methods: The study is based on a cross-sectional design. Healthy individuals were recruited from the OPD following convenience sampling, and anthropometric and physical assessments were performed. Then, the blood samples were assessed for vitamin D levels. After segregating deficient (< 20 ng/dL), insufficient (20-30 ng/mL), and sufficient (> 20 ng/dL), the comparison was drawn.

Result: A frequency analysis of three groups and comparisons among them was made. Association of phenotypic markers with vitamin D was shown.

Conclusion: The present study population attempted to establish the hypothesis; however, chronological age can have multicollinearity with all variables, and sample size is a limitation of this study.

Sarcopenia is a syndrome characterized by progressive decline in skeletal muscle mass, strength, and physical performance. It has become a common pathological manifestation of aging, physical inactivity, and multiple chronic diseases. The α-Klotho protein, a well-established anti-aging factor, exists in both membrane-bound and soluble forms. Soluble α-Klotho (s-α-Klotho) circulates systemically and performs a wide range of physiological functions. Studies indicate that α-Klotho is closely associated with multiple age-related disorders, including diabetes, osteoporosis, chronic kidney disease, and neurodegenerative diseases such as Alzheimer's and Parkinson's. Notably, recent studies have revealed reduced expression of α-Klotho in sarcopenia, implicating it in the disease pathogenesis through the regulation of multiple signaling pathways. Given its anti-aging properties, α-Klotho has emerged as a promising therapeutic target for sarcopenia. This review summarizes current evidence supporting the role of α-Klotho in sarcopenia, with a focus on its mechanisms of action in determining skeletal muscle cell fate. Furthermore, it evaluates the potential of various α-Klotho-targeted interventions to ameliorate sarcopenia and discusses challenges and future directions in this evolving field.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating illness marked by persistent fatigue, yet its mechanisms remain unclear. Growing evidence implicates immunosenescence-the age-related decline in immune function-in the onset and persistence of fatigue.

Methods: This review synthesizes clinical and experimental data to examine how immunosenescence contributes to ME/CFS. We focus on chronic inflammation, senescent immune phenotypes, mitochondrial dysfunction, and neuroendocrine imbalance, with emphasis on maladaptive crosstalk among immune, muscular, neuroendocrine, and vascular systems.

Results: Aging immune cells drive chronic inflammation that impairs mitochondrial ATP production and promotes muscle catabolism. Concurrently, HPA-axis suppression and β₂-adrenergic dysfunction amplify immune dysregulation and energy imbalance. Together, these processes illustrate how immunosenescence sustains pathological cross-organ signaling underlying systemic fatigue.

Conclusion: Immunosenescence provides a unifying framework linking immune, metabolic, and neuroendocrine dysfunction in ME/CFS. Recognizing cross-organ communication highlights its clinical relevance, suggesting biomarkers such as cytokines and exhaustion markers, and supports integrated therapeutic strategies targeting immune and metabolic networks.

Background: Irritable Bowel Syndrome (IBS) is a common functional gastrointestinal disorder affecting 5%-10% of the global population and is characterized by recurrent abdominal pain and dysregulation of bowel movements. Many patients do not benefit from full remission of symptoms by conventional treatments. Recently, yoga has demonstrated its potential benefits in various medical conditions including IBS, as a result of its effect on the gut-brain axis. This systematic review evaluates the effectiveness of yoga for the management of IBS.

Methods: We conducted a comprehensive literature search in PubMed and Scopus until March 2025 to identify studies on yogic posture, pranayama, and meditation in IBS. After excluding reviews, case reports, and studies not meeting age or design criteria, 10 studies were included. These were evaluated for methodological quality and classified as randomized controlled trials (RCTs) or non-controlled trials. We analyzed outcomes related to gastrointestinal symptoms, quality of life, and psychological symptoms and examined the type of yoga administered.

Results: Yoga interventions led to amelioration of gastrointestinal symptoms, decreased anxiety and depression, and enhanced quality of life compared to usual care or wait-list controls. Of note, the studies that fixed the change in the IBS Symptom Severity Scale scores as the primary outcome showed a moderate-large effect of yoga on the improvement of symptoms compared to controls (Cohen's d range: 0.37-3.60).

Conclusion: These preliminary findings suggest that yoga could favorably influence both the physical and psychological aspects of IBS. However, high-quality larger sample studies are needed to confirm the findings reported in the review.

Recurrent pregnancy loss (RPL), defined as the loss of two or more pregnancies, is a significant health issue in obstetrics. As a chronic stressor, RPL exerts numerous uncertain effects on pregnancy outcomes. While prior research has recognized psychological contributors, the comprehensive investigation of psychobiological mechanisms remains incomplete. During early pregnancy, the HPA axis continues to respond to chronic stress. Chronic stress leads to a prolonged elevation of glucocorticoids (GCs) by reducing the protective function of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), resulting in sustained GC exposure. Hallmarks of RPL include progesterone deficiency and inflammation, both of which exhibit intricate associations with the effects of chronic stress and GCs. In this review, we integrate the key mechanisms of progesterone deficiency caused by chronic stress and GCs, including precursor competition, reactive oxygen species (ROS) overproduction, and FK506-binding protein 51 (FKBP51) overexpression. Specifically, we discuss the effects of chronic stress and GCs on inflammatory amplification, including glucocorticoid resistance (GCR) and M1 macrophage polarization. Mediators including transcription factor nuclear factor kappa B (NF-κB), ROS, lactic acid (LA) and FKBP51 are central to the link between stress-induced inflammation and RPL. We further incorporated the potential role of the endoplasmic reticulum stress-related unfolded protein response (UPR) in progesterone deficiency and inflammatory amplification. By integrating these pathways, this review offers a more comprehensive framework for understanding how chronic stress contributes to the pathogenesis of RPL.

Alcohol misuse is a leading modifiable risk factor for disease burden across the lifespan. Alcohol-mediated end organ injury results from a combination of pathophysiological processes including oxidative stress, mitochondrial dysfunction, cell death, endoplasmic reticulum stress, extracellular matrix remodeling, and epigenomic adaptations. Alcohol's multi-systemic physiological impact causes direct cellular damage and impairs an individual's capacity to adapt or recover from additional health insults, thereby amplifying overall disease burden. While the impact of alcohol on liver and brain physiological mechanisms is the most studied, the adverse effects of alcohol extend to multiple other organ systems, and though frequently underappreciated, contribute to several comorbidities. This review focuses on alcohol-associated pathophysiological effects on the gastrointestinal, cardiovascular, immune systems, and energy metabolism that contribute to multiorgan injury and disease burden. Understanding the pathophysiological effects of alcohol on the different organ systems will significantly help inform therapeutic modalities to help reduce alcohol-associated comorbidities.