Hormone and Metabolic Research最新文献

Denosumab is a completely human monoclonal high-affinity antibody that binds to the nuclear factor kappa-B ligand (RANKL) and is widely used to treat osteoporosis. Furthermore, it can potentially lower serum calcium levels by inhibiting osteoclast activation and preventing bone calcium from being released into the blood. This review aimed to provide evidence of the efficacy and safety of denosumab in treating hypercalcemia in primary hyperparathyroidism (PHPT). PubMed and the Cochrane Library were searched for published studies that described denosumab for hypercalcemia management in PHPT. Data were extracted by two independent investigators and analyzed using SPSS 23. The risk of bias was assessed by NIH Quality Assessment Tool. In total, 161 patients with PHPT from 18 studies were included in this review. The average age was 61 (47-72) years and the highest serum calcium was 3.76 (3.11-4.20) mmol/l. We found that denosumab can effectively reduce the serum calcium level by a median reduction of 0.5 mmol/l within 3 days. Significant reduction was maintained for 14 days. The serum calcium-lowering effect weakened after one month. In conclusion, denosumab has a potential clinical value in treating hypercalcemia in patients with PHPT.

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.

Type 2 diabetes (T2D) has a pathophysiological component that includes inflammation. Inflammation-sensitive marker measurement may be helpful in determining the risk of complications for both older T2D patients and the public. This study aimed to investigate the association between blood pro-inflammatory mediators and the characteristics of elderly patients with T2D using meta and network analyses. The Web of Science, Scopus, PubMed, and Cochrane Library databases were selected as study methodology. The Quality in Prognosis Studies (QUIPS) tool in the meta-analysis assessed the studies' methodological quality. The selected studies were statistically analyzed using the META-MAR tool based on the standardized mean difference (SMD). The selected studies included nine examinations involving 6399 old people [+>+55 years old, 65.9+±+4.09 (mean+±+SD)]. The meta-analysis showed that pro-inflammatory mediators (SMD 0.82) and patient-related variables [risk factors (SMD 0.71)] were significantly associated with T2D (p+<+0.05). Subgroup analysis revealed that tumor necrosis factor alpha (TNF-α; SMD 1.08), body mass index (SMD 0.64), high-density lipoprotein (HDL; SMD -0.61), body weight (SMD 0.50), and blood pressure (SMD 1.11) were factors significantly associated with T2D (p+<+0.05). Network analysis revealed that among patient characteristics, diastolic blood pressure and, among inflammatory mediators, leptin were the most closely associated factors with T2D in older adults. Moreover, network analysis showed that TNF-α and systolic blood pressure were most closely associated with leptin. Overall, alternate techniques, such as meta-analysis and network analysis, might identify different markers for T2D in older people. A therapeutic decision-making process needs to consider these differences in advance.

The aim of the study was to assess glucocorticoid sensitivity in survivors of childhood acute lymphoblastic leukemia using in vivo and in vitro tests. Thirty leukemia survivors of both sexes aged ≥18 years participated in the study and at least two years after therapy withdrawal. In vivo tests comprised: a) a very low dose intravenous dexamethasone suppression test for measurement of serum cortisol before, after, and % suppression, compared with 32 age-matched controls; and b) 0.25 mg overnight oral dexamethasone suppression test for assessment of salivary cortisol before, after, and % suppression. In vitro methods comprised: c) glucocorticoid receptor polymorphisms: BcI1-NR3C1 and A3669G; and d) splicing variant of glucocorticoid receptor GR-α mRNA by real-time quantitative polymerase chain reaction, compared with 32 controls. There was a reduction in salivary cortisol, and 73.3% of leukemia survivors showed high sensitivity according to % suppression after oral dexamethasone (p<0.05). Serum cortisol at baseline, after the test, % suppression after intravenous dexamethasone, and the percentage of high sensitivity were reduced in the leukemia group (%F=36.7; p<0.05). The BcI1-NR3C1 and A3669G polymorphisms were present in 11/30 (36.7%) and 5/30 (16.7%) patients, respectively. GR-α mRNA levels were lower in the leukemia group than in the controls (p<0.05). Survivors of acute lymphoblastic leukemia presented with reduced glucocorticoid sensitivity. Glucocorticoid sensitivity allows individualized treatment to avoid adverse effects and may be involved in cardiovascular disease risk among this particular group of cancer survivors.

The medical community acknowledges the presence of thyroid disorders and nonalcoholic fatty liver disease (NAFLD). Nevertheless, the interconnection between these two circumstances is complex. Thyroid hormones (THs), including triiodothyronine (T3) and thyroxine (T4), and thyroid-stimulating hormone (TSH), are essential for maintaining metabolic balance and controlling the metabolism of lipids and carbohydrates. The therapeutic potential of THs, especially those that target the TRβ receptor isoform, is generating increasing interest. The review explores the pathophysiology of these disorders, specifically examining the impact of THs on the metabolism of lipids in the liver. The purpose of this review is to offer a thorough analysis of the correlation between thyroid disorders and NAFLD, as well as suggest potential therapeutic approaches for the future.

The aim of the study was to explore the effect of low dose glucocorticoid on bronchopulmonary dysplasia in premature infants, to provide new ideas for clinical prevention and cure of bronchopulmonary dysplasia in premature infants. The 144 cases of premature infants were divided into 72 each: control group and experimental group. Control group received routine clinical prevention and cure, while experimental group was received low dose glucocorticoid on the basis of control group. The serum interleukin-10 (IL-10) , interleukin-8 (IL-8), and transforming growth factor-1 (TGF-β1) before and after treatment were compared between two groups. The incidence and severity of bronchopulmonary dysplasia was compared between two groups. The mechanical ventilation time, oxygen inhalation time and hospitalization time in two groups were recorded, and the body mass, head circumference and body length at 30 days after birth were assessed in both groups. After treatment, the serum IL-10 level in experimental group was increased and IL-8, TGF-β1 levels were decreased compared with control group (p <0.05). The incidence rate of bronchopulmonary dysplasia in experimental group was 13.89% and the disease severity in experimental group was significantly reduced (p<0.05). Both groups exhibited no notable adverse reactions (p>0.05). Low-dose glucocorticoids have a significant preventive and therapeutic effect on bronchopulmonary dysplasia in preterm infants, and have a high safety, showing high clinical application value for bronchopulmonary dysplasia in preterm infants.

Glucagon-like peptide-1 (GLP-1) receptor agonists are effective hypoglycemic agents for type 2 diabetes mellitus (T2DM). It was reported that T2DM was implicated in pancreatic β-cell senescence. Whether loxenatide regulates cellular senescence of pancreatic β-cells is to be investigated. Our results revealed that high glucose (HG)-induced cellular senescence and elevated expression of SASP factors inhibited cell proliferation and stimulated DNA damage, which were reversed by loxenatide treatment. In addition, HG induction resulted in promoted insulin secretion and insulin synthesis of pancreatic β-cells and loxenatide treatment further strengthened these influences. In addition, loxenatide could inactivate the PERK/eIF2α signaling pathway via decreasing the levels of p-PERK and p-eIF2α in HG-induced pancreatic β-cells. Furthermore, CCT020312, an activator of the PERK/eIF2α signaling pathway, abolished loxenatide-mediated inhibiting cellular senescence, elevating cell proliferation and improving DNA damage and enhancing insulin secretion of HG-induced pancreatic β-cells. In conclusion, our results indicated that loxenatide impeded cellular senescence, promoted cell proliferation, improved DNA damage, enhanced insulin secretion and insulin synthesis of HG-induced pancreatic β-cells through modulating the PERK/eIF2α signaling pathway.

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.