Hormone Molecular Biology and Clinical Investigation最新文献

Objectives: It is well recognized that overt thyroid dysfunction is associated with changes in body mass index (BMI). However, there is ongoing debate regarding the influence of thyroid stimulating hormone (TSH) on BMI, in euthyroid subjects. The aim of this study is to examine the association of TSH with BMI in an outpatient population without evidence of thyroid disease.

Methods: Cross-sectional study conducted in an Endocrinology Department. We identified the latest TSH and BMI measurements in 923 patients from the reference euthyroid population. All patients with positive thyroid autoimmunity and nodules were excluded. We performed a linear regression analysis using SPSSv.025.

Results: 923 adult patients were evaluated. 79.4% were males, with a mean age of 67.6 years old. Mean TSH level was 1.78 mIU/L and mean BMI was 29.2 kg/m². A significant negative correlation between serum TSH concentration and BMI was evident (p=0.04; r=-0.067). Statistical significance was lost when performing subgroup analysis, for males and females (p=0.19 and p=0.075), elderly (≥65 years) and non-elderly (p=0.55 and p=0.32) and also obese (BMI ≥30 kg/m²) and non-obese (p=0.39 and p=0.13).

Conclusions: The relationship between BMI and TSH is not consensual in the literature. This study included a large cohort sample of euthyroid patients, majority men and with negative autoimmunity. Our results support the hypothesis that variation in thyroid status within the normal range, could have a negative effect on BMI, contrary to most published studies.

Objectives: Patients with type 1 diabetes mellitus have been reported to have elevated prolactin levels and a possible relationship between prolactin levels and the development of the disease has been proposed. However, some studies show that prolactin mediates beneficial functions in beta cells. Therefore, we review information on the roles of prolactin in type 1 diabetes mellitus.

Content: Here we summarize the functions of prolactin in the immune system and in pancreatic beta cells, in addition, we describe studies related to PRL levels, its regulation and alterations of secretion in patients with type 1 diabetes mellitus.

Summary: Studies in murine models have shown that prolactin protects beta cells from apoptosis, stimulates their proliferation and promotes pancreatic islet revascularization. In addition, some studies in patients with type 1 diabetes mellitus have shown that elevated prolactin levels correlate with better disease control.

Outlook: Prolactin treatment appears to be a promising strategy to improve beta-cell vascularization and proliferation in transplantation and immunotherapies.

Objectives: Leptin polymorphism (LEP) has been associated with coronary heart disease (CAD), obesity, and high body mass index (BMI). However, we performed a systematic review and meta-analysis to discover the association because previous studies reached different conclusions.

Methods: Review Manager, version 5.3.5, and Stata, version 15.0, were used for statistical analysis. We calculated the effect size of the studies using the OR with the corresponding 95% CI, and two-sided (bilateral) p-values of 0.05 were considered significant. To determine heterogeneity among the selected studies, the Q test and I2 statistics were used. Meta-regression was used to examine the disease (heart disease, obesity, and high BMI) and heterogeneity between these subgroups.

Results: Eleven studies with 18,984 subjects were included in this study. The G-2548A (rs12112075), rs7799039, and A19G (rs2167270) polymorphisms of the leptin gene (but not the Lys656Asn (rs1805094) polymorphism) are associated with an increased risk of cardiovascular disease. Our pooled analysis revealed an association between the G-2548A (rs12112075) polymorphism and heart disease, high BMI, and obesity. This indicates that individuals carrying the AA allele are at an increased risk for heart disease, high BMI, and obesity. People with heart failure and coronary artery disease did not have the rs7799039 polymorphism or its alleles linked to them.

Conclusions: Combined analysis of data from current and published research suggests that the leptin gene polymorphisms G-2548A (rs12112075), rs7799039, and A19G (rs2167270) (but not the Lys656Asn (rs1805094) polymorphism) are associated with an increased risk of cardiovascular disease. Further research is needed to understand this association.

Objectives: Secreted by white adipose tissue, asprosin is a newly recognized adipokine whose physiological function is not well comprehended. This study intended to determine the effect of spinning and stationary cycling on serum asprosin levels in overweight women.

Methods: Forty-five overweight women with BMI>25 kg/m² in the age range of 30-40 years were assigned randomly to three groups of 15 participants: control, spinning (group cycling with music), and stationary bike (individual pedaling on a stationary bike). The participants performed the exercises three sessions per week for six weeks. Lipid profile and asprosin levels were measured by enzymatic and ELISA methods, respectively. Moreover, the paired t-test and one-way ANOVA were employed to make within-group and between-group comparisons, respectively.

Results: The stationary cycling and spinning exercise groups experienced significant reductions in weight, BMI, serum triglyceride, and asprosin levels from the pretest to the posttest. The control group showed no statistically significant differences. Serum concentrations of total cholesterol and low-density lipoprotein only declined in the spinning group. In this regard, neither the control group nor the stationary bicycle exhibited no significant change over time. The spinning group demonstrated a significant rise in high-density lipoprotein levels, which was not observed in the control group. In addition, there was no significant difference in WHR index between the intervention groups.

Conclusions: By lowering the serum asprosin level, a spinning exercise program appears to be effective in reducing disorders linked to metabolic diseases in overweight women.

Objectives: To report a rare case of a metastatic adrenocortical carcinoma (ACC) that achieve a complete and a long-term remission.

Case presentation: AAC is a rare and aggressive tumor, with a high risk of recurrence and that present metastases in 21% of cases at diagnosis. Treatment of advanced ACC is challenging, mitotane is the only available adrenolytic treatment, with modest and unpredictable responses. Response rates to systemic chemotherapy are not encouraging. We describe the case of a 39-year-old woman with a metastatic ACC, that achieve a complete and long-term remission after chemotherapy, mitotane treatment and surgery of primary tumor and liver metastases.

Conclusions: A complete remission of a metastatic adrenocortical carcinoma is possible in some rare cases after a multimodal treatment.

On November 24th, 2021 a case of a new viral variant of SARS-CoV-2 was reported by South Africa and Botswana to WHO, which later was designated as the variant of concern on 26th November 2021. It has around 60 mutations (50 non synonymous, 8 synonymous, and 2 non coding) as compared to the original parent strain of Wuhan. Different hypotheses have been put forward as an explanation for the origin like reverse zoonosis i.e. animal to human transmission, origin from an immune compromised patient or use of highly mutagenic drug like molnupiravir as treatment. A huge spike in cases around the globe is suggestive of a high rate of infectivity and transmissivity as compared to the previous known variants. With whatever cases have been documented so far, it is said that omicron causes mostly mild clinical illnesses and there is a less chance of hospitalization according to the clinicians. Among the reported cases, there were already vaccinated patients also. So there is a possibility that omicron might be able to evade the vaccine induced immunity due to a huge number of mutations (especially in the spike protein sequences). Until new vaccines specific to the pathogen are being developed, the coverage of the currently acceptable vaccines should be increased so that none is deprived of the mandatory doses and a third booster dose might help to reduce the chances of serious complications of this new strain beforehand. So an equal focus on the host and environment is required along with the pathogen.

Objectives: Type 2 diabetes (T2D) is known to be associated with chronic inflammation, but the inflammatory regulators/markers are not exactly defined and the link between them remains undetermined. The objective of this study is to identify these markers by testing traditional (IL6 & IL8) and non-traditional (TREM1 & uPAR) inflammatory markers.

Methods: Data and blood samples were obtained from 114 T2D and 74 non-diabetic Kuwaiti subjects attending health facilities in Kuwait. Chemical analyzers were used to measure glycemic and lipid profiles, while ELISA was used to measure plasma levels of insulin and several inflammatory markers.

Results: Showed that the IL-6 and TREM1 were significantly higher in T2D compared to non-diabetic controls, and the uPAR level was borderline higher in T2D but significantly correlated with IL-6 levels. Unexpectedly, IL8 was significantly below normal in T2D and IL6/IL8 ratio was significantly higher in T2D patients. Unlike other tested markers, uPAR was in addition strongly correlated with insulin levels and HOMA-IR index.

Conclusions: Raised levels of IL6, TREMI, IL6/IL8 ratio, and the strong positive correlation of plasma levels of uPAR with IL-6, insulin, and HOMA-IR index, are reliable spectators of chronic inflammation in T2D patients. The reduced level of IL-8 in T2D was a peculiar observation that needs further explanation. Finally, the consequences and impact of the sustained rise of these inflammatory regulators in diabetic tissues need to be meticulously explored.

Objectives: MicroRNA expression disruptions play an important function in the expansion of gastric cancer. Previous investigation has indicated that miR-372-5p doing as an oncogene in several malignancies. CDX1 and CDX2, as target genes of miR-372-5p, play the role of tumor suppressors and oncogenes in gastric cancer cells, respectively. The current investigation explored the effects of miR-372-5p regulation on CDX2 and CDX1 in AGS cell lines and studied their molecular mechanism.

Methods: hsa-miR-372-5p miRCURY LNA miRNA Inhibitors and Mimic were transfected into AGS cell line. The cell viability and cell cycle calculation were defined by MTT assay and flow cytometry, respectively. The Expression levels of miR-372-5p, CDX1, CDX2 and transfection efficiency were measured using Real-time PCR. Statistical investigation p values <0.05 were considered to be meaningful.

Results: miR-372-5p particularly was upregulated in control cells and also after transfection by mimic. While its expression was reduced by the inhibitor. Upregulation of miR-372-5p remarkably increased cell growth and led to accumulation in the G2/M phase, although the inhibitor decreased cell growth and accumulation in the S phase. Accordingly, upregulation of miR-372-5p increased CDX2 and decreased CDX1 expression. By inhibition of miR-372-5p, expression of CDX2 was decreased and expression of CDX1 was increased.

Conclusions: Up and down-regulation of miR-372-5P has a potential effect on the expression levels of its target genes, CDX1 and CDX22. Accordingly, the downregulation of miR-372-5p may be assumed as a possible therapeutic target in treating gastric cancer.

DNA methylation is the most important epigenetic element that activates the inhibition of gene transcription and is included in the pathogenesis of all types of malignancies. Remarkably, the effectors of DNA methylation are DNMTs (DNA methyltransferases) that catalyze de novo or keep methylation of hemimethylated DNA after the DNA replication process. DNA methylation structures in cancer are altered, with three procedures by which DNA methylation helps cancer development which are including direct mutagenesis, hypomethylation of the cancer genome, and also focal hypermethylation of the promoters of TSGs (tumor suppressor genes). Conspicuously, DNA methylation, nucleosome remodeling, RNA-mediated targeting, and histone modification balance modulate many biological activities that are essential and indispensable to the genesis of cancer and also can impact many epigenetic changes including DNA methylation and histone modifications as well as adjusting of non-coding miRNAs expression in prevention and treatment of many cancers. Epigenetics points to heritable modifications in gene expression that do not comprise alterations in the DNA sequence. The nucleosome is the basic unit of chromatin, consisting of 147 base pairs (bp) of DNA bound around a histone octamer comprised of one H3/H4 tetramer and two H2A/H2B dimers. DNA methylation is preferentially distributed over nucleosome regions and is less increased over flanking nucleosome-depleted DNA, implying a connection between nucleosome positioning and DNA methylation. In carcinogenesis, aberrations in the epigenome may also include in the progression of drug resistance. In this report, we report the rudimentary notes behind these epigenetic signaling pathways and emphasize the proofs recommending that their misregulation can conclude in cancer. These findings in conjunction with the promising preclinical and clinical consequences observed with epigenetic drugs against chromatin regulators, confirm the important role of epigenetics in cancer therapy.