Hormone and Metabolic Research最新文献

ETV5 has been described to be involved in the epithelial to mesenchymal transition (EMT) mainly in cancer. It is known that EMT provokes cytoskeleton remodeling, improving cellular migratory, and invasive capabilities. Moreover, overexpression of ETV5 has been correlated to cancer development and this gene has been implicated in cell proliferation. However, little is known about the downregulation of ETV5 expression in a pancreatic cell line and the inverse mesenchymal to epithelial transition (MET). Therefore, we studied the implications of ETV5 silencing over the phenotype of the insulinoma INS-1 (832/13) cell line and described the MET by partial ETV5 silencing in the INS-1 (832/13) cell line. The downregulation of ETV5 expression was obtained by using ETV5 siRNA in the insulinoma rat cell line, INS-1 (832/13). Then, ETV5 knockdown provoked a MET phenotype observed by crystal violet staining and verified by immunohistochemistry against E-cadherin. Wound healing assay showed no migration, and F-actin stain revealed rearrangement of actin microfilaments. In addition, TGFβ1 and TGFβ3 were downregulated in the absence of ETV5. ETV5 silencing induces epithelial phenotype by downregulating TGFβ1 and TGFβ3 in INS-1 (832/13) cell line.

Wilms' tumor is a malignant renal cancer that arises within the pediatric urinary system. This study intended to investigate how a novel long non-coding RNA LINC01339 functions in the pathogenesis of Wilms' tumor. An elevated miR-135b-3p expression as well as reduced levels of LINC01339 and ADH1C were observed in Wilms' tumor. LINC01339 mediated ADH1C expression by directly binding to miR-135b-3p. The enforced LINC01339 or ADH1C markedly hindered cell growth and migration in Wilms' tumor. The LINC01339 overexpression also repressed the growth of Wilms' tumors in vivo, whereas miR-135b-3p overexpression exerted the opposite effects on Wilms' tumor cells in vitro. Additionally, upregulating miR-135b-3p reversed LINC01339's effects on the cellular processes of Wilms' tumor cells, whereas ADH1C overexpression offset the cancer-promoting influence of miR-135b-3p upregulation on Wilms' tumor progression. Therefore, LINC01339 prevents Wilms' tumor progression by modulating the miR-135b-3p/ADH1C axis. Our findings substantiate that the LINC01339/miR-135 b-3p/ADH1C regulatory axis has potential to be a target for the treatment of Wilms' tumor.

Central diabetes insipidus is a rare disorder characterized by a deficiency of vasopressin. The first line drug to treat this disorder is a synthetic analogue of vasopressin, desmopressin.The primary aim of this retrospective register study was to compare desmopressin dose requirements in patients with acquired and congenital DI, and secondly to assess the influence of BMI on dose requirement and risk of hyponatremia with different drug administrations. We included all patients with suspected DI attending the endocrine department at Rigshospitalet, Copenhagen, Denmark in 2022. We identified 222 patients who were included whereof 130/222 (58.6%) were females and median age was 53 years (IQR 35 to 63). The etiology included 7/222 (3.2%) congenital and 215/222 (96.8%) acquired. After converting nasal and sublingual doses to equivalent oral doses, the median daily dose requirement was 600 μg in patients with congenital etiology compared to 200 μg in patients with acquired etiology (p=0.005). We found no association between BMI and desmopressin dose requirements (p=0.6). During the past 12 months, 66/215 (30.7%) had sodium levels<136 mmol/l including 20/215 (9.3%) with sodium levels<131 mmol/l. No increased risk of hyponatremia was found, when nasal and oral were compared (p=0.9). Daily desmopressin dose requirements were higher in patients with congenital DI compared to patients with acquired DI. However, this result was associated with uncertainty due to the small congenital group. BMI did not influence daily dose requirements and nor did type of administration influence the risk of hyponatremia.

As an increased body of COVID-19 related research is now available, it becomes apparent that the effects of COVID-19 extend beyond that of the respiratory system. Among others, the endocrine system is particularly vulnerable to perturbation from the COVID-19 infection. The present scoping review summarizes the bidirectional relationship between COVID-19 and endocrine system in children and adolescents, by describing both the possible susceptibility of children and adolescents without endocrinopathies to endocrine disorders following COVID-19 infection, but also the potential susceptibility to COVID-19 infection and severe infection, or the aggravation of endocrine dysfunction in patients with pre-existing endocrine diseases. Data suggest increased obesity and diabetes rates, as well as increased severity and frequency of diabetic ketoacidosis following COVID-19 infection. Conversely, patients with diabetes and obesity may experience a more severe course of COVID-19 infection. However, in the majority of cases, children and adolescents with well-managed and regulated endocrine disorders do not appear to be at increased risk of infection or severe infection from COVID-19. Thus, adhering to the appropriate "sick day management rules", maintaining adequate supply of medications and supplies, keeping close contact with the therapeutic team and seeking medical help without delay when needed, are the main recommendations for a safe outcome. Additional lessons learnt during the pandemic include the risk for mental health diseases caused by children's disrupted routine due to COVID-19 related protective measures and the importance of adopting alternative communication options, such as telehealth visits, in order to ensure uninterrupted endocrine care.

Recent studies have confirmed that tumor immune cell infiltration (ICI) is associated with sensitivity of ovarian cancer (OC) immunotherapy and disease progression of OC patients. However, studies related to immune infiltration in OC, has not been elucidated. Two algorithms are used to analyze the OC data in the TCGA and GEO databases. After combining the two data sets, the immune cell content of the sample was estimated by Cell-type Identification By Estimate Relative Subsets of RNA Transcripts (CIBERSORT method). An unsupervised consistent clustering algorithm was used to analyze ICI subtypes and their differentially expressed genes (DEGs). Two subgroups and three ICI gene clusters were identified by unsupervised consensus clustering algorithm. The ICI score was obtained by analyzing the gene characteristics through principal component analysis (PCA). The ICI score ranged from -15.8132 to 18.7211, which was associated with the prognosis of OC patients with immunotherapy. The Toll-like receptor pathway, B-cell receptor pathway, antigen processing and presentation pathway, NK-cell-mediated cytotoxicity pathway, and arginine-proline metabolism pathway were activated in the high ICI score group, suggesting that immune cells in the high ICI score group were activated, thus leading to a better prognosis in this group of patients. Patients with G3-G4 in the high ICI rating group were more sensitive to immunotherapy and had a better prognosis in patients with high tumor mutation burden (TMB). This study suggests that ICI scores can be used as a feasible auxiliary indicator for predicting the prognosis of patients with OC.

Ferroptosis is an iron-dependent death mode mediated by the aggregation of lipid peroxides and lipid-reactive oxygen species. It is characterized by iron-dependent lipid peroxide accumulation accompanied by oxidoreductase deficiency. Pancreatic beta cell dysfunction and insulin resistance are two major causes of type 2 diabetes mellitus (T2DM). Iron accumulation and metabolism may play a role in the development of T2DM. The molecular mechanism of β cell apoptosis and iron death in T2DM were reviewed. In addition, we discuss recent insights on the relationship between the trace element iron and apoptosis of β cells in T2DM.

The aim of the study was to investigate the relationship between VEGF-460C/T polymorphism and susceptibility to diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) by meta-analysis. A comprehensive search was conducted across six databases until September 2023 to identify studies examining the association between VEGF-460C/T polymorphism and susceptibility to DR. Data process was performed by Stata 15.0 software. Eight studies were included, involving 1463 patients with DR. In the overall analysis, the difference was statistically significant only in the homozygous model (CC vs. TT: OR=1.86, p=0.048). A subgroup analysis of 6 papers with genotype frequency satisfying HWE in the control group indicated significant differences among the allele (C vs. T: OR=1.34, p=0.037), recessive (CC vs. CT+TT: OR=1.96, p=0.022) and homozygous (CC vs. TT: OR=2.28, p=0.015) models. However, in the dominant and heterozygous models, the difference was not statistically significant. The sensitivity of the HWE-based subgroup analysis showed that the conclusions in other gene models except the heterozygote model were not robust. This meta-analysis indicated that VEGF-460C/T gene polymorphism is associated with susceptibility to DR in T2DM. Allele C and genotype CC at the VEGF-460C/T locus are associated with an increased risk of DR in T2DM. However, considering that the results are not robust, more trials involving more rigorous design are needed to verify the findings of this review in the future.

For treatment of type 1 diabetes mellitus, a combination of immune-based interventions and medication to promote beta-cell survival and proliferation has been proposed. Dextromethorphan (DXM) is an N-methyl-D-aspartate receptor antagonist with a good safety profile, and to date, preclinical and clinical evidence for blood glucose-lowering and islet-cell-protective effects of DXM have only been provided for animals and individuals with type 2 diabetes mellitus. Here, we assessed the potential anti-diabetic effects of DXM in the non-obese diabetic mouse model of type 1 diabetes. More specifically, we showed that DXM treatment led to five-fold higher numbers of pancreatic islets and more than two-fold larger alpha- and beta-cell areas compared to untreated mice. Further, DXM treatment improved glucose homeostasis and reduced diabetes incidence by 50%. Our data highlight DXM as a novel candidate for adjunct treatment of preclinical or recent-onset type 1 diabetes.

Reduced bone mass and degeneration of the microarchitecture of bone tissue are the hallmarks of osteoporosis, a bone metabolic disease that increases skeletal fragility and fracture susceptibility. Osteoporosis is primarily caused by unbalanced bone remodeling, in which bone synthesis is outpaced by bone resorption caused by osteoclasts. Along with the bone-building vitamins calcium and vitamin D, typical medications for treating osteoporosis include bisphosphonates and calcitonin. The present therapies effectively stop osteoclast activation that is too high, however they come with varying degrees of negative effects. Numerous factors can contribute to osteoporosis, which is characterized by a loss of bone mass and density due to the deterioration of the bone’s microstructure, which makes the bone more fragile. As a result, it is a systemic bone condition that makes patients more likely to fracture. Interest in the function of ferroptosis in the pathophysiology of osteoporosis is developing. In this review, we go through the shape of the cell, the fundamental mechanisms of ferroptosis, the relationship between osteoclasts and osteoblasts, the association between ferroptosis and diabetic osteoporosis, steroid-induced osteoporosis, and the relationship between ferroptosis and postmenopausal osteoporosis. The functions of ferroptosis and osteoporosis in cellular function, signaling cascades, pharmacological inhibition, and gene silencing have been better understood thanks to recent advances in biomedical research.

Maternal diabetes has been related to an increased risk of congenital heart disease (CHD) in offspring. However, inconsistent results were retrieved for studies evaluating the association between gestational diabetes mellitus (GDM) and CHD in offspring. We therefore performed a systematic review and meta-analysis for comprehensive investigation. Observational studies were identified by searching PubMed, Embase, and Web of Science according to the aim of the meta-analysis. A randomized-effects model was used to pool the data by incorporating the influence of potential heterogeneity. Twenty-three observational studies, involving 46953078 mother-child pairs, were available for the meta-analysis. Among them, 2131800 mothers were diagnosed as GDM and 214379 newborns had CHD. Overall, maternal GDM was associated with a higher incidence of CHD in offspring [odds ratio (OR): 1.32, 95% confidence interval (CI): 1.21 to 1.45, p<0.001; I2=62%]. Sensitivity analysis limited to studies with adjustment of maternal age and other potential confounding factors showed similar results (OR: 1.40, 95% CI: 1.30 to 1.51, p<0.001; I2=47%). Subgroup analysis suggested that the association between maternal GDM and CHD in offspring was not significantly affected by methods for diagnosis of GDM, methods for confirmation of CHD, or study quality scores (p for subgroup difference all>0.05). Subsequent analysis according to types of CHD showed that maternal GDM was associated with higher risks of atrial septal defect, ventricular septal defect, and Tetralogy of Fallot. Maternal GDM may be associated with a higher risk of CHD in offspring.