Hormone and Metabolic Research最新文献

The objective of the study was to explore the association between homocysteine (Hcy) levels and the risk of type 2 diabetic nephropathy (T2DN). PubMed, Web of Science, Cochrane Library, and Embase databases were searched to collect literature on the association between Hcy levels and the risk of T2DN. The retrieval period was from the establishment of the database to September 10, 2024. Stata 15.0 statistical software was used for data analysis. Type II diabetes without nephropathy was considered the control group, and microalbuminuria and macroalbuminuria were included in the experimental group. Fourteen articles were included in this meta-analysis. The results of the meta-analysis showed that compared with the control group, the level of Hcy in the T2DN group with microalbuminuria [Weighted mean difference (WMD)=2.50, 95% confidence interval (CI): 1.49-3.51, p<0.001] and the group with macroalbuminuria (WMD=3.38, 95% CI: 1.95-4.82) was significantly increased. Compared with the T2DN microalbuminuria group, the Hcy level in the T2DN macroalbuminuria group was considerably higher (WMD=2.12, 95% CI: 0.80-3.44, p<0.001). High homocysteine levels were associated with an increased risk of T2DN (OR=1.36, 95% CI: 1.20-1.54, p<0.001). In conclusion, circulating Hcy levels are significantly associated with the severity of T2DN. In addition, there was a significant association between high Hcy levels and an increased risk of T2DN.

Radioiodine (RAI) therapy after surgery, is an important component for the treatment of patients with papillary thyroid cancer (PTC), the most common thyroid cancer. In this study we sought to evaluate the cancer-specific survival (CSS) impact of RAI in specific thyroid cancer subgroups. The Surveillance, Epidemiology, and End Results (SEER) database were used to identify patients with PTC who underwent surgery between 2000 and 2019. Patients not treated with RAI were compared to those treated with RAI using propensity score matching (PSM) on the basis of identical inclusion criteria. A total of 106 333 patients were identified from the SEER database. RAI therapy was associated with improved CSS in the matched cohort (HR: 0.83; 95% CI: 0.72-0.96, p=0.01) but not in the unmatched data set (HR: 1.46; 95% CI: 1.30-1.64, p<0.001) among all PTC patients regardless of disease stage. Detailed analyses, however, showed that only patients with high-risk disease (pT3N1, pT4N1) experienced the greatest benefit in CSS. In the lower disease stages, no significant differences were recognized in the group of PTC patients with or without RAI therapy. One exception: in the group of PTC patients in stage pT1bN0, a significant difference was seen towards RAI. This is, however, most likely due to the large number of patients investigated. In summary, RAI therapy should not be used in low-risk PTC patients and might be used to some extent in intermediate-risk PTC patients. The histological suptype of the tumor needs to be considered in this context.

Hepatocellular carcinoma (HCC) is a primary liver cancer with a high mortality rate. The search for a new biomarker could help the prognosis of HCC patients. We identified the glycolytic gene set associated with HCC and the glycolytic lncRNA based on TCGA and MsigDB databases. According to these lncRNAs, K-means clustering, and regression analysis were performed on the patients. Two groups of HCC patients with different lncRNA expression levels were obtained based on K-means clustering results. The results of difference analysis and enrichment analysis showed that DEmRNA in the two HCC populations with significant survival differences was mainly enriched in transmembrane transporter complex, RNA polymerase II specificity, cAMP signaling pathway, and calcium signaling pathway. In addition, a prognostic model of HCC with 4 DElncRNAs was constructed based on regression analysis. ROC curve analysis showed that the model had good predictive performance. Drug predictionresults showed that the efficacy of JQ1, niraparib, and teniposide was higher in the low-risk group than in the high-risk group. In conclusion, this study preliminarily identified glycolytic-related prognostic features of lncRNAs in HCC and constructed a risk assessment model. The results of this study are expected to guide the prognosis assessment of clinical HCC patients.

This study attempted to build a prostate cancer (PC) prognostic risk model with mitochondrial feature genes. PC-related MTGs were screened for Cox regression analyses, followed by establishing a prognostic model. Model validity was analyzed via survival analysis and receiver operating characteristic (ROC) curves, and model accuracy was validated in the GEO dataset. Combining risk score with clinical factors, the independence of the risk score was verified by using Cox analysis, followed by generating a nomogram. The Gleason score, microsatellite instability (MSI), immune microenvironment, and tumor mutation burden were analyzed in two risk groups. Finally, the prognostic feature genes were verified through a q-PCR test. Ten PC-associated MTGs were screened, and a prognostic model was built. Survival analysis and ROC curves illustrated that the model was a good predictor for the risk of PC. Cox regression analysis revealed that risk score acted as an independent prognostic factor. The Gleason score and MSI in the high-risk group were substantially higher than in the low-risk group. Levels of ESTIMATE Score, Immune Score, Stromal Score, immune cells, immune function, immune checkpoint, and immunopheno score of partial immune checkpoints in the high-risk group were significantly lower than in the low-risk group. Genes with the highest mutation frequencies in the two groups were SPOP, TTN, and TP53. The q-PCR results of the feature genes were consistent with the gene expression results in the database. The 10-gene model based on MTGs could accurately predict the prognosis of PC patients and their responses to immunotherapy.

Intracellular levels of NAD ⁺  regulate metabolism, among other ways, through enzymes that use NAD ⁺  as a substrate, capable of inducing catabolic processes, such as lipid oxidation, glucose uptake, and mitochondrial activity. In several model organisms, administering precursor compounds for NAD ⁺ synthesis increases its levels, improves lipid and glucose homeostasis, and reduces weight gain. However, evidence of the effects of these precursors on human patients needs to be better evaluated. Therefore, we carried out a systematic review and meta-analysis of randomized clinical trials that assessed the effects of NAD ⁺  precursors on Metabolic Syndrome parameters in humans. We based our methods on PRISMA 2020. Our search retrieved 429 articles, and 19 randomized controlled trials were included in the meta-analysis. We assessed the risk of bias with the Rob 2 algorithm and summarized the quality of evidence with the GRADE algorithm. Supplementation with NAD ⁺  precursors reduced plasma levels of total cholesterol and triglycerides in volunteers, but the intervention did not significantly affect the other outcomes analyzed. Three of the included articles presented a high risk of bias. The quality of evidence varied between very low and low due to the risk of bias, imprecision, and indirectness. The number of participants in outcomes other than lipidemia is still generally tiny; therefore, more clinical trials evaluating these parameters will increase the quality of the evidence. On the other hand, quality randomized studies are essential to assess better the effects of NAD ⁺  precursors on lipidemia.

Osteoarthritis (OA), a chronic joint disease characterized by primary or secondary degeneration of articular cartilage and bone dysplasia, is associated with various risk factors and is the leading cause of musculoskeletal pain and disability, severely impacting the quality of life. Growth hormone (GH), secreted by the anterior pituitary gland, is essential in mediating the growth and development of bone and cartilage. Reportedly, osteoarthritis increases, and the growth hormone decreases with age. A negative correlation between GH and OA suggests that GH may be related to the occurrence and development of OA. Considering that abnormal growth hormone levels can lead to many diseases related to bone growth, we focus on the relationship between GH and OA. In this review, we will explain the effects of GH on the growth and deficiency of bone and cartilage based on the local pathological changes of osteoarthritis. In addition, the potential feasibility of treating OA with GH will be further explored and summarized.

The mitochondrial protein NAD(P)⁺ transhydrogenase (NNT) has been implicated in the metabolic derangements observed in obesity. Mice with the C57BL/6J genetic background bear a spontaneous mutation in the Nnt gene and are known to exhibit increased susceptibility to diet-induced metabolic disorders. Most of the studies on NNT in the context of diet-induced obesity have compared C57BL/6J mice with other mouse strains, where differences in genetic background can serve as confounding factors. Moreover, these studies have predominantly employed a high-fat diet (HFD) consisting of approximately 60% of calories from fat, which may not accurately mimic real-world fat-rich diets. In this study, we sought to examine the role of NNT in diet-induced hypothalamic inflammation and metabolic syndrome by using a congenic mice model lacking NNT, along with a HFD providing approximately 45% of calories from fat. Our findings indicate that mice lacking NNT were more protected from HFD-induced weight gain but presented a worse performance on glucose tolerance test, albeit not in insulin tolerance test. Interestingly, the brown adipose tissue of HFD-fed Nnt ^+/+ mice presented a greater mass and a higher whole-tissue ex-vivo oxygen consumption rate. Also, HFD increased the expression of the inflammatory markers Il1β, Tlr4 and Iba1 in the hypothalamus of Nnt ^-/- mice. In conclusion, our study highlights the importance of NNT in the context of diet-induced obesity and metabolic syndrome, indicating its contribution to mitigate hypothalamic inflammation and suggesting its role in the brown adipose tissue increased mass.

The study aims to assess the improvement in bone metabolism in prepubertal girls with Turner Syndrome (TS) after long-term polyethylene glycol recombinant human Growth Hormone (PEG-rhGH) treatment. A 12-month longitudinal prospective study was conducted with 28 prepubertal girls diagnosed with TS. Participants were divided into two groups: 18 received PEG-rhGH therapy (0.1-0.25 mg/kg/week) and 10 did not. Anthropometric measurements, bone turnover markers (BTMs), and serum levels of IGF-1, calcium, and phosphate were collected at baseline and after 12 months. BTMs included bone alkaline phosphatase (BAP), Type I collagen propeptide (CICP), Type I collagen telopeptide (CTX), and fibroblast growth factor 23 (FGF23). After 12 months of PEG-rhGH therapy, the treatment group showed significant increases in growth velocity (GV) and height standard deviation scores (HtSDS). Serum IGF-1 levels increased rapidly within one month and remained elevated. BTMs indicated enhanced bone formation, significantly increasing BAP and CICP, while CTX levels remained low. FGF23 levels initially rose slightly but declined below baseline by 12 months. Elevated blood phosphate levels were observed. PEG-rhGH therapy in children with TS significantly improves linear growth and enhances bone formation markers, benefiting bone metabolism.

The epidemic of obesity and metabolic syndrome has become the most serious global public health problem. The part played by microRNA (miRNA) in the onset and progression of obesity and metabolic syndrome has been increasingly focused upon. The goal of this study was to explore miR-335-5p as a potential predictive biomarker or therapeutic target for obesity and metabolic syndrome. The expression level of miR-335-5p was detected by qRT-PCR. The diagnostic value of miR-335-5p was evaluated by ROC curve. The association between serum miR-335-5p levels and various clinical parameters was assessed using the chi-square test. Logistic regression analysis was used to evaluate the risk factors of metabolic syndrome in obese population. The biological processes and molecular mechanisms are studied through GO and KEGG enrichment analysis. The ROC curve analysis revealed that miR-335-5p could serve as a predictive indicator for the development of obesity accompanied by metabolic syndrome. Logistic regression analysis revealed that BMI, TG, FBG, HOMA-IR, and miR-335-5p expression represent independent risk factors of metabolic syndrome occurrence. Chi-square test analysis revealed that patients with higher values of BMI, SBP, DBP, TG, FBG, and HOMA-IR exhibited a more significantly increased expression of miR-335-5p in their serum. In conclusion, miR-335-5p holds predictive and diagnostic value for obesity and metabolic syndrome and has potential to serve as a biomarker for these conditions.

Obesity, non-alcoholic fatty liver disease (NAFLD), and atherosclerotic cardiovascular diseases are common and growing public health concerns. Previous epidemiological studies unfolded the robust correlation between obesity, NAFLD, and atherosclerotic cardiovascular diseases. Obesity is a well-known risk factor for NAFLD, and both of them can markedly increase the odds of atherosclerotic cardiovascular diseases. On the other hand, significant weight loss achieved by lifestyle modification, bariatric surgery, or medications, such as semaglutide, can concomitantly improve NAFLD and atherosclerotic cardiovascular diseases. Therefore, certain pathophysiological links are involved in the development of NAFLD in obesity, and atherosclerotic cardiovascular diseases in obesity and NAFLD. Moreover, recent studies indicated that simultaneously targeting several mechanisms by tirzepatide and retatrutide leads to greater weight loss and markedly improves the complications of metabolic syndrome. These findings remind the importance of a mechanistic viewpoint for breaking the association between obesity, NAFLD, and atherosclerotic cardiovascular diseases. In this review article, we mainly focus on shared pathophysiological mechanisms, including insulin resistance, dyslipidemia, GLP1 signaling, inflammation, oxidative stress, mitochondrial dysfunction, gut dysbiosis, renin-angiotensin-aldosterone system (RAAS) overactivity, and endothelial dysfunction. Most of these pathophysiological alterations are primarily initiated by obesity. The development of NAFLD further exacerbates these molecular and cellular alterations, leading to atherosclerotic cardiovascular disease development or progression as the final manifestation of molecular perturbation. A better insight into these mechanisms makes it feasible to develop new multi-target approaches to simultaneously unhinge the deleterious chain of events linking obesity and NAFLD to atherosclerotic cardiovascular diseases.