Biological Research最新文献

Background: The complex interaction between the immune system and metabolic homeostasis is becoming recognized, as immune sensors affect key metabolic tissues, including the liver and adipose tissue. The cGAS-cGAMP-STING pathway, previously recognized as a cytosolic DNA-sensing pathway, is currently associated with lipid metabolism in addition to its inflammatory function. Although STING is acknowledged for its connection to cholesterol, the metabolic functions of its upstream component molecules-the DNA sensor cGAS and the resulting product cGAMP-are largely unexplored. We propose that cGAS and cGAMP serve as crucial, previously unidentified regulators of systemic lipid homeostasis throughout the lifetime.

Results: We investigated the long-term metabolic consequences of intrinsic cGAS deficiency, leading to the absence of cGAMP, in male mice fed on a standard chow diet. cGAS knockout (cGASKO) mice demonstrated a consistent increase in body weight across their lifespan, primarily attributed to adipocyte hypertrophy and increased adipose tissue mass. Increased weight correlated with elevated adiposity. This condition was associated with reduced weight-bearing strength, despite unchanged general locomotor activity and food intake during young age. Liver histology revealed modest cellular infiltration and absent steatosis, suggesting potential low-grade inflammation. Circulating triglyceride and glucose levels exhibited transient, age-dependent variations-decreased glucose and increased triglycerides in young age, which stabilized in adult and old ages, reflecting a possible compensatory metabolic adaptation with time. Conversely, total cholesterol levels were consistently and significantly elevated across all age groups, underscoring the importance of the cGAS-cGAMP axis in cholesterol homeostasis throughout life.

Conclusions: Our study identified the cGAS-cGAMP axis as an interesting regulator of cholesterol homeostasis and fat accumulation in aging, independent of STING activation. The persistent deficiency of cGAS and cGAMP leads to lifelong hypercholesterolemia and adipose hypertrophy. This research highlights an unexpected metabolic function of the cGAS-cGAMP pathway and indicates the necessity of evaluating this axis in relation to physiological aging and metabolic disorders.

Background: Premature ovarian insufficiency (POI) is a fertility disorder impacting women under 40, characterized by an early deterioration of ovarian function, and is one of the major side effects caused by chemotherapy. Cyclophosphamide is a powerful chemotherapeutic agent used in various cancers; however, it inflicts substantial harm on other tissues, particularly the gonads, leading to temporary or permanent infertility.

Materials and methods: Forty female albino rats (Rattus norvegicus) were divided into four groups. Group I (control group) received normal saline, then premature ovarian insufficiency was induced in the remaining groups by intraperitoneal injections of cyclophosphamide (CLP). After that, Group II received no treatment. Group III was administered a daily oral dose of pomegranate (Punica granatum) nanoparticles for one month. Group IV received a daily oral dose of pomegranates, as did group III, plus ovarian stem cell-derived exosomes via intraperitoneal injection twice weekly for one month. Rats were euthanized 30 days post-POI induction; blood was then collected to evaluate hormone levels, and sections of the ovaries were collected for histopathological analysis. Frozen sections were procured for gene expression and oxidative stress studies.

Results: The hormonal assessment of groups indicated a notable reduction in estrogen (E2) level and an elevation of follicle-stimulating hormone (FSH) in group II compared to the control and treated groups. Additionally, the ovaries of group II exhibited pronounced degeneration of ovarian follicles, accompanied by the desquamation of granulosa cells. Gene expression study indicated a downregulation of FSHR, CYP19A1, and AMH in the same group. Rats in both groups III and IV exhibited an increased number of follicles, improved ovarian shape, a considerable elevation in blood E2, a marked decrease in serum FSH levels, and an up-regulation of the three examined genes.

Aim of work: The study aimed to assess the therapeutic efficacy of pomegranate (Punica granatum) peel extract nanoparticles alone and their synergistic effect with ovarian stem cell exosomes in reversing premature ovarian insufficiency (POI) caused by cyclophosphamide.

Conclusion: Treatment with (Punica granatum) nanoparticles and exosomes partially enhanced the structure and function of the ovaries, thereby alleviating the adverse effects of Cyclophosphamide.

Diabetic macrovascular complications, as one of the leading causes of mortality in diabetic patients, are characterized by insidious onset and high residual risk. Effective prevention and treatment of diabetic macrovascular injury remain critical clinical challenges, necessitating the development of novel therapeutic strategies targeting this complication. Although recent studies have demonstrated that vascular remodeling driven by the phenotypic transition of vascular smooth muscle cells (VSMCs) plays a pivotal role in this process, and increasing attention has been paid to the metabolic pathways and mechanosensitive signaling pathways of VSMCs, the underlying molecular mechanisms remain incompletely elucidated. This review summarizes metabolic reprogramming in VSMCs in diabetes and its impact on vascular remodeling systematically, with a focus on elucidating the core mechanisms of endothelial-VSMC crosstalk, pathological characteristics of VSMCs phenotypic transition during different stages of atherosclerosis (AS), and potential diversified strategies such as the application of microRNAs, extracellular vesicle targeting techniques, and targeted protein regulation. Current evidence indicates that precise modulation of the metabolic-mechanical coupling network in VSMCs can significantly attenuate the progression of atherosclerotic plaques and enhance plaque stability. However, clinical translation remains challenged by insufficient targeting specificity and mechanistic complexity. Future studies should integrate multi-omics technologies with biomimetic models to further optimize therapeutic strategies.

Background: Previous studies have demonstrated that oxidative stress and melanogenesis are regulated by the Wnt/β-catenin signaling pathway. However, the precise mechanism by which the PEDF/Wnt/β-catenin axis modulates apoptosis and melanogenesis remains unclear.

Methods: Cell viability and mortality rates were assessed using CCK-8 assays and lactate dehydrogenase (LDH) release assays. Mitochondrial ultrastructural changes were analyzed by transmission electron microscopy (TEM). Changes in the mitochondrial membrane potential (ΔΨm) were assessed using the JC-1 fluorescent probe. The effects of PEDF on protein and gene expression were evaluated by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR).

Results: As the concentration of H₂O₂ increased, the cell survival rate decreased, which activated the Wnt/β-catenin signaling pathway and increased the apoptosis rate and melanin production. PEDF reversed the H₂O₂-induced decrease in cell viability and increase in mortality rate in Melan-a cells while ameliorating the impairment of the mitochondrial membrane potential. PEDF ameliorated H₂O₂-induced protein damage and lipid peroxidation and reduced apoptosis in Melan-a cells. PEDF treatment significantly decreased the protein expression levels of β-catenin, Wnt3a, and Dvl2 (P < 0.05) and reduced the protein levels of Bax and Caspase-3 (P < 0.01) in H₂O₂- and BML-284-treated Melan-a cells. Furthermore, PEDF significantly reduced the H₂O₂- and BML-284-induced increases in the MITF and TYR protein levels (P < 0.01).

Conclusions: These results suggest that PEDF can reduce H₂O₂-induced oxidative damage and melanin production in Melan-a cells by inhibiting the activation of Wnt/β-catenin signaling pathway activation. These findings provide a theoretical basis for human oxidative stress and pigment deposition-related diseases.