中南大学学报(医学版)最新文献

Objectives: The prevalence of Alzheimer's disease (AD) is increasing globally, however its pathogenesis is still unclear. The evidence showed that the progression of AD was closely related to the apoptosis of nerve cells. This study amis to explore the role and specific mechanism of miR-15a and Bag5 in the apoptosis of nerve cells induced by beta-amyloid protein (Aβ) in AD.

Methods: The AD rat model was constructed by injecting Aβ42 into SD rat brain and the AD cell model was constructed by treating SH-SY5Y cells with Aβ42. The learning and memory ability of rats was detected by Morris Water Maze. Hematoxylin and eosin (HE) staining was used to detect the pathological changes of brain tissues. Nissl staining was used to detect the changes of cell morphology and number in brain tissues. The upstream miRNA that interacted with Bag5 were screened by bioinformatics analysis. Methyl thiazolyl tetrazolium (MTT) assay was used to detect cell proliferation. Flow cytometry was used to detect the apoptosis rate of cells. Real-time reverse transcription PCR (real-time RT-PCR) was used to detect the mRNA levels of miR-15a and Bag5. Western blotting was used to detect the protein expression levels of Bag5, Bax and Caspase-3. MiR-15a knockdown or overexpression vectors or Bag5 knockdown vectors were transfected into AD rat model and AD cell models, respectively. Luciferase reporter assay was used to verify the binding relationship between miR-15a and Bag5.

Results: Morris Water Maze, HE staining and Nissl staining showed that the rat model of AD was established successfully, and Aβ could induce neuronal apoptosis and inhibit the expression of miR-15a in AD rats. Compared with normal cells, Aβ treatment significantly increased apoptosis rate and Bag5 expression, and weakened cell proliferation and miR-15a (all P<0.01). Overexpression of miR-15a further enhanced the effect of Aβ on cell proliferation and apoptosis, while knockdown of miR-15a expression had the opposite effect (all P<0.01). Luciferase reporter assay confirmed that there was a negative targeting relationship between miR-15a and Bag5. Compared with Bag5 knockdown alone, the co-transfection of miR-15a inhibitor and si-Bag5 significantly increased the cell proliferation ability and mRNA and protein levels of Bag5, and significantly reduced the cell apoptosis rate and the expression of Bax and Caspase-3, animal studies have also shown consistent results (all P<0.01).

Conclusions: Aβ can inhibit the expression of miR-15a, thereby inducing the expression of Bag5 and activating the protective mechanism of Bag5 against Aβ induced apoptosis.

Alzheimer's disease (AD) is a progressive central neurodegenerative disorder with an insidious onset. With global aging, the incidence and mortality of AD have been steadily increasing, yet effective treatments remain elusive. Obesity, characterized by excessive or abnormal fat accumulation, is a complex metabolic disorder and a confirmed risk factor for numerous diseases. Both obesity and AD have become major public health concerns, posing significant threats to human health and economic development. Studies have revealed a strong correlation between obesity and AD, with multiple contributing factors, including metabolic abnormalities of endocrine factors, inflammatory responses, and genetic interactions. Exploring the correlation and mechanisms between obesity and AD provides important insights and new strategies for the prevention and treatment of AD.

Objectives: Long non-coding RNAs (lncRNAs) play an essential role in cancer biology. Cervical intraepithelial neoplasia grade 3 (CIN3) is the most severe precancerous lesion of cervical cancer. However, the mechanism of multiple lncRNAs in CIN3 has not been studied in-depth and is worth exploring. This study aims to summarize the lncRNA expression profile in CIN 3 and screen for lncRNAs with potential oncogenic effects.

Methods: To further clarify the role of lncRNAs in the development of CIN3, this study collected cancer tissue and para-cancer tissue specimens from three CIN3 patients. The RNA sequencing (RNA-Seq) analysis was used to construct expression profiles of lncRNAs and confirmed by real-time reverse transcription PCR (real-time RT-PCR) methods. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed with computational methods. We obtained their possible target genes through the cis- and trans-regulatory analysis of the lncRNAs. In addition, this study predicted new transcripts and lncRNAs by Cufflinks analysis and coding potential identification (Coding Potential Calculator) analysis to discover new tumor regulatory molecules.

Results: The differential expressions of 1 555 genes, 1 562 mRNAs, 241 ncRNAs, and 6 616 new predicted-lncRNAs were found. The most prominently up-regulated and down-regulated lncRNAs were NR_145433.1 and ENST00000513672.1, respectively. KEGG analysis revealed that lncRNA-targeted genes were closely related to apoptosis, metabolic, p53 signaling pathway, and other cancer-related pathways. The real-time RT-PCR validation results of 5 apoptosis-related lncRNAs (NR_145433.1, ENST00000510610.2, UC001Kfo, ENST00000602964.1, and NR_123733.1) in cervical cancer were consistent with the sequencing results.

Conclusions: This study provides a comprehensive expression profile of lncRNAs in CIN3 patients, particularly the apoptosis-related expression profile of lncRNAs, and provides direction and clues for the study of cervical cancer and the search for potential therapeutic targets.

Central precocious puberty (CPP) is an endocrine disorder in children caused by the early activation of the hypothalamic-pituitary-gonadal axis (HPGA), leading to elevated gonadotropin-releasing hormone (GnRH), which triggers the development of gonads and the secretion of sex hormones. This eventually results in the development of internal and external genitalia and secondary sexual characteristics. CPP significantly affects the physical and mental health of children and may increase the risk of various adult diseases. The influencing factors and mechanisms of CPP are a central focus of research, and its prevention and treatment remain challenging. Childhood obesity is an important risk factor for CPP, with a complex relationship influenced by endocrine-disrupting chemicals, genetic factors, and epigenetic regulation. The link between the two is primarily related to the regulation of HPGA function by nutritional and metabolic signals. Exploring the relationship between childhood obesity and CPP, along with the potential mechanisms by which obesity induces CPP, can provide theoretical references for identifying new therapeutic targets.

Obesity, as a global health crisis, is increasingly linked to intestinal microecology. Probiotics colonise the body, effectively regulating the balance of intestinal flora, while strengthening the intestinal barrier, activating the immune response, releasing beneficial substances, and maintaining micro-ecological balance. This process not only enhances the defence against pathogens, but also reduces the production of inflammatory factors and lowers the level of chronic inflammation. However, the specific process and mechanism by which probiotics influence the intestinal microecology through the immune response, improve metabolic disorders caused by obesity, and participate in weight management are not clear. Through multiple neural pathways including the 'gut-brain axis' and their direct interaction with the intestine, probiotics increase the number of beneficial bacteria in the intestine and inhibit the growth of harmful bacteria, thus effectively restructuring the balance of the intestinal flora. This restructuring of the balance can optimise the intestinal environment and enhance the efficiency of food digestion and nutrient absorption. Probiotics show positive effects on obesity management by regulating the metabolic process and reducing fat accumulation, providing individuals with a new way to control body weight and prevent obesity. Therefore, the application of probiotics is of great significance in promoting gut health and weight management.

Although body mass index (BMI) is widely used as a simple tool to assess obesity, it has certain limitations and inaccuracies. It is known that visceral adipose tissue is closely related to cardiometabolic risks and all-cause mortality; however, precise measurement methods for visceral fat (magnetic resonance imaging and computed tomography) cannot be widely used. Thus, simple but accurate alternatives are valuable. Studies have shown that waist circumference-to-height ratio (WHtR) might be a superior and more accurate variable in assessing central or visceral adiposity as well as predicting risks of diabetes and other cardiometabolic diseases. Furthermore, WHtR cutoff values can be consistent across different races, age, and genders, making it a universal metric worth promoting and applying.

Nesfatin-1 is a neuropeptide hormone known for its biological functions, including inhibiting food intake, regulating glucose and lipid metabolism, promoting apoptosis, and providing anti-inflammatory and anti-tumor effects. Glucose metabolism is a crucial pathway for the body's energy supply. Current research has demonstrated that Nesfatin-1 can affect glucose metabolism through various mechanisms, such as inhibiting food intake, regulating enzyme activity, and improving insulin resistance, though the findings are not entirely consistent. Investigating the relationship between Nesfatin-1 and glucose metabolism may offer new insights into the diagnosis and treatment of diseases related to glucose metabolism disorders.

Objectives: The causal relationship between eczema and autoimmune diseases has not been previously reported. This study aims to evaluate the causal relationship between eczema and autoimmune diseases.

Methods: The two-sample Mendelian randomization (MR) method was used to assess the causal effect of eczema on autoimmune diseases. Summary data from the Genome-Wide Association Study Catalog (GWAS) were obtained from the Integrative Epidemiology Unit (IEU) database. For eczema and autoimmune diseases, genetic instrument variants (GIVs) were identified according to the significant difference (P<5×10^-8). Causal effect estimates were generated using the inverse-variance weighted (IVW) method. MR Egger, maximum likelihood, MR-PRESSO, and MR-RAPS methods were used for alternative analyses. Sensitivity tests, including heterogeneity, horizontal pleiotropy, and leave-one-out analyses, were performed. Finally, reverse causality was assessed.

Results: Genetic susceptibility to eczema was associated with an increased risk of Crohn's disease (OR=1.444, 95% CI 1.199 to 1.738, P<0.001) and ulcerative colitis (OR=1.002, 95% CI 1.001 to 1.003, P=0.002). However, no causal relationship was found for the other 6 autoimmune diseases, including systemic lupus erythematosus (SLE) (OR=0.932, P=0.401), bullous pemphigoid (BP) (OR=1.191, P=0.642), vitiligo (OR=1.000, P=0.327), multiple sclerosis (MS) (OR=1.000, P=0.965), ankylosing spondylitis (AS) (OR=1.001, P=0.121), rheumatoid arthritis (RA) (OR=1.000, P=0.460). Additionally, no reverse causal relationship was found between autoimmune diseases and eczema.

Conclusions: Eczema is associated with an increased risk of Crohn's disease and ulcerative colitis. No causal relationship is found between eczema and SLE, MS, AS, RA, BP, or vitiligo.