Molecular and Cellular Biochemistry最新文献

In-stent restenosis (ISR) is the main risk for the failure of vascular stent implantation. Arctigenin (ARCG) as the active principle of Arctium lappa, possesses the ability to regulate proliferation and inflammation. This study was conducted to illuminate the role and mechanism of ARCG in ISR. The effects of ARCG on the inflammation and proliferation of vascular smooth muscle cells (VSMC) were detected. Then we profiled RNA transcript expression in the femoral arteries of restenosis patients and healthy donors along with the SwissTargetPrediction to identify the target of ARCG. VSMCs were stimulated with IL-6 to assess the effect and mechanism of ARCG in vitro, and the restenosis mouse models generated by the wire injury of the femoral arteries were used to explore the effect of ARCG on restenosis in vivo. We reported significantly increased levels of inflammation and IL-6/JAK/STAT3 pathway in tissue samples from patients with restenosis and restenosis mouse models. And ARCG inactivated the IL-6/JAK2/STAT3 pathway, inhibiting proliferation and inflammation in a dose-dependent manner. Moreover, ARCG treatment was found to inhibit intimal hyperplasia in restenosis mouse models. ARCG inhibits ISR by inhibiting proinflammatory response and proliferation of VSMCs via IL-6/JAK2/STAT3 pathway, providing a promising drug candidate for ISR.

Diabetes mellitus and inflammatory bowel disease are chronic inflammatory disorders characterized by immune dysregulation and rising global prevalence. Epidemiological studies increasingly suggest a bidirectional association between the two conditions, linked through shared mechanisms of intestinal barrier dysfunction, microbial dysbiosis, and sustained innate immune activation. Activated macrophages play a central role in driving mucosal inflammation through polarization toward a pro-inflammatory M1 phenotype, accompanied by increased production of inflammatory cytokines. These mediators disrupt tight junctions, induce epithelial apoptosis, and perpetuate cycles of immune activation and tissue injury. This macrophage-cytokine axis not only amplifies local inflammation but also sustains chronic barrier dysfunction, creating a pathogenic overlap between diabetes mellitus-associated intestinal injury and intestinal bowel disease. In this study, we used a low dose streptozotocin and high-fat diet-induced diabetic Sprague-Dawley rat model in both sexes to investigate the effects of chronic hyperglycemia on intestinal inflammation, with particular emphasis on macrophage activation and pro-inflammatory cytokine responses. We found inflammation in both small and large intestines with mucosal injury and barrier disruption, and immune activation involving macrophages and enhanced expression of CD68, iNOS, TNF-α, and IL-6. Female rats were more susceptible to gut-related inflammatory changes due to diabetes. These findings suggest a complex interplay between epithelial stress, immune signaling, and microbial factors supporting the role of intestinal inflammation in the immune-metabolic interaction in diabetes-associated intestinal changes, which may contribute to the pathogenesis of inflammatory bowel disease.

Diabetes mellitus (DM) is associated with gastrointestinal complications, including structural and functional changes in both small and large intestine. CDC42, a Rho GTPase, plays a critical role in maintaining epithelial integrity through regulation of tight junctions and cytoskeletal organization. Moreover, CDC42 expression has been reported in inflammatory bowel disease (IBD). However, its expression patterns and regulatory mechanisms in the diabetic gut remain poorly defined, particularly in the context of DM - IBD comorbidity. Our study aimed to evaluate histological changes and CDC42 gene and protein expression in the small intestine (ileum) and large intestine (colon) of streptozotocin-induced female and male Sprague-Dawley rats. Rats were divided in control (n = 10) and diabetic (n = 12) group. Histological analysis was based on hematoxylin-eosin staining sections. CDC42 gene and protein expression were quantified using RT-qPCR, western blotting, and immunofluorescence. Correlation analyses were performed to examine the relationship between CDC42 gene expression and clinical parameters, including blood glucose levels and weight gain, stratified by gender. Histological examination revealed marked inflammatory cell infiltration in both intestinal segments (ileum and colon). CDC42 gene expression was significantly increased in the small and large intestine of diabetic rats, particularly in females (for small intestine p < 0.001; for large intestine p < 0.01), suggesting a gender-specific response potentially mediated by hormonal regulation. Reduced expression of CDC42 was detected at protein level in the colon (p < 0.001). These findings highlight a differential expression of CDC42 in the small and large intestine under diabetic conditions. Since CDC42 expression in our study has been found to be related to the intestinal changes under diabetic conditions, future research should be directed towards CDC42 modulation to reduce the pathological changes in the intestine. Getting better insight in CDC42 molecular pattern related to IBD and DM, and development of strategies for its modulation, could be beneficial in clinical setting to control both IBD and DM disease progression.

N-hexane is a widely used aliphatic hydrocarbon solvent that can cause central-peripheral neuropathy. Compared to peripheral nerve tissue, spinal nerve tissue is more vulnerable and typically non-regenerable. However, no effective treatments are currently available. Stem cells are attractive therapeutic cells because of their extensive self-renewal and pluripotent differentiation abilities. Accordingly, numerous studies are focused on their restorative potential. In the present study, we investigated the effects and mechanisms of stem cell therapy on spinal nerves damaged by 2,5-HD (a proximate toxic metabolite of n-hexane). Our results showed that spinal axonopathy induced by 2,5-HD was alleviated by bone mesenchymal stem cell (BMSC) transplantation. Further, by examining the expression of molecules associated with axonal outgrowth, NGF signaling was found to be involved in the regeneration of spinal axons. Moreover, intervention experiments showed that PTEN was also an essential component of BMSC therapy. Conclusively, our data suggested that BMSC transplantation can alleviate spinal injury induced by 2,5-HD through AKT/mTOR/CREB by NGF-dependent and -independent pathways.

Objective: Keloids are pathological scars characterized by excessive collagen deposition that occurs during wound healing after skin injury. Keloid fibroblasts (KF) and keloid keratinocytes (KK) are key contributors to keloid pathogenesis. Although adipose-derived mesenchymal stromal cells (ASCs) have been investigated for keloid therapy, their therapeutic potential and underlying mechanisms require further elucidation. This study aimed to characterize the therapeutic potential of ASCs for human keloid management.

Methods: Molecular profiles associated with keloid pathogenesis were characterized through integrative analyses, including gene expression profiling, functional annotation, protein-protein interaction mapping, and hub gene identification. Single-cell RNA sequencing (scRNA-seq) was used to identify ASC subpopulations with inhibitory effects on keloid development. The therapeutic efficacy of these subpopulations was subsequently assessed in a miniature pig model of hypertrophic scar.

Results: Upregulation of hub genes such as NOG and IL6 was strongly associated with KF formation, whereas increased expression of APP and NOTCH1 was implicated in KK development. Functional scRNA-seq analysis identified ASC subpopulations capable of inhibiting the development of KF, KK, or both through molecular interactions with these hub genes. Administration of porcine ASCs enriched in the identified inhibitory subpopulations effectively prevented hypertrophic scar formation in the miniature pig model.

Conclusion: This study delineated key molecular signatures underlying keloid formation and identified ASC subpopulations with targeted inhibitory activity against pathological cell types involved in keloid development. These findings support the potential application of ASC-based interventions for prophylaxis and treatment of hypertrophic scarring in humans.

Heart failure (HF) represents the terminal stage of multiple cardiovascular disorders and is characterized by substantial morbidity, disability, and mortality. Although standard pharmacotherapies offer partial symptomatic relief, their capacity to halt or reverse disease progression remains limited. In recent years, autophagy-an essential intracellular degradation and recycling process that safeguards cardiomyocyte homeostasis-has emerged as a critical determinant in the onset and progression of HF. In this review, we systematically examined approximately 170 research articles related to "natural compounds-autophagy-HF" published up to 2025, and synthesized major advances reported over the past five years. Based on chemical structure and natural source, representative bioactive compounds were categorized into five major classes: flavonoids, polyphenols, alkaloids, terpenoids, and marine-derived molecules. We then integrated evidence on the principal autophagy-regulatory signaling cascades influenced by these compounds, including the AMP-activated protein kinase (AMPK)/mechanistic target of rapamycin (mTOR) axis, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), sirtuin 1 (SIRT1)/forkhead box O (FOXO), BCL2/adenovirus E1B 19 kDa-interacting protein 3 (BNIP3)/NIP3-like protein X (NIX), and Beclin-1 pathways. Moreover, this review summarizes how these natural compounds modulate autophagy to attenuate key pathological processes associated with HF, including cardiac hypertrophy, adverse ventricular remodeling, mitochondrial dysfunction, and cardiomyocyte apoptosis. By comparing convergent mechanisms and compound-specific differences in autophagy-mediated cardioprotection, we highlight emerging mechanistic patterns and therapeutic implications. Collectively, through structured classification of compounds, integration of autophagy signaling pathways, and assessment of translational potential, this review provides a systematic framework to guide the rational application and further development of natural products for the prevention and treatment of HF.

T-cell acute lymphocytic leukemia (T-ALL) is a malignant transformation of immature precursor T-cells that is highly aggressive. The disruption of SETD2 is thought to be a unique epigenetic mechanism for leukemia. This study aimed to investigate the role and possible mechanism of SETD2 in T-ALL. The expression of SETD2 in T-ALL tissues and cells was detected by RT-PCR, and siRNA (si-NC/si-SETD2) and overexpressed plasmids (ov-NC/ov-SETD2) were used to transfected T-ALL cell lines JURKAT and MOLT-4, and cell proliferation, migration/invasion and cell cycle were detected by CCK8, Transwell, flow cytometry, respectively. WB was used to detect the changes in the JAK/STAT pathway. The JAK/STAT inhibitor AG490 was further used to demonstrate the role of JAK/STAT in SETD2 regulation of T-ALL. Then, the effects of SETD2 on T-ALL tissue infiltration were verified in vivo. Results showed that SETD2 was significantly lowly expressed in T-ALL, and si-SETD2 promoted the proliferation, migration, invasion, cell cycle, and activation of the JAK/STAT pathway of T-ALL cells, while overexpression of SETD2 showed the opposite inhibitory effect. The use of AG490 inhibited the promoting effect of si-SETD2 on T-ALL, suggesting that JAK/STAT was involved in the regulation of SETD2 on T-ALL. In vivo experiments further confirmed that silencing SETD2 decreased the body weight of mice and increased the infiltration of JURKAT cells in the liver, kidney, spleen, lung, and brain, while overexpression of SETD2 showed inhibitory effects. In conclusion, SETD2 played an important role in T-ALL by inhibiting the JAK/STAT pathway to inhibit T-ALL proliferation, invasion, and transfection.