Endocrine, Metabolic & Immune Disorders-Drug Targets (Formerly Current Drug Targets - Immune, Endocrine & Metabolic Disorders) - Volume 25, Issue 11, 2025

The involvement of the larynx in many situations can have a substantial impact on a person's voice, breathing, and general health. Individuals with autoimmune thyroid disorders can experience a variety of conditions affecting the larynx. Autoimmune thyroid disorders, such as Hashimoto's thyroiditis (HT) and Graves' disease (GD), are prevalent conditions affecting the thyroid gland. Beyond their established impact on thyroid function, these disorders have been associated with laryngeal involvement. The current study aims to explore the likelihood of laryngeal involvement in patients with Autoimmune Thyroid Disorders (AITD).

This study involved a retrospective analysis of medical records from patients diagnosed with autoimmune thyroid disorders. Inclusion criteria were a confirmed diagnosis through laboratory investigations and clinical assessment. Patients with pre-existing laryngeal pathologies or other conditions affecting the larynx were not considered. We collected data from 4 research articles and 3 clinical trials from Embase, PubMed, and NCBI-Trials portals, focusing on reported laryngeal symptoms. The severity of laryngeal involvement was assessed and categorized based on its extent and impact on vocal function.

Preliminary analysis of the collected data indicated a significant proportion of patients with autoimmune thyroid disorders reporting laryngeal symptoms. Among these patients, various manifestations of laryngeal involvement were observed, including vocal changes, hoarseness, and throat discomfort.

The findings show that laryngeal symptoms may be an underappreciated feature of these diseases, potentially impacting vocal function and quality of life in affected people. Further research is also needed for more precise projections in this direction.

Berberine (BBR) has the characteristics of repressing hyperglycemia, obesity, and inflammation, as well as improving insulin resistance. However, the underlying mechanism remains to be fully understood. This study explores whether BBR regulates inositol requiring enzyme 1 (IRE1)/glycogen synthase kinase 3 beta (GSK-3β) axis to resist obesity-associated inflammation, thereby improving glucolipid metabolism disorders.

Mice were fed a high-fat diet and administrated with BBR, followed by measurement of weight change, biochemical indicators, as well as glucose and insulin tolerance. Insulin-resistant 3T3-L1 adipocyte models were established, and the model cells were treated with BBR and IRE1 inhibitors. Cell viability was detected by cell counting kit-8 assay. Inflammatory factor secretion and glucose consumption were measured via specific kits. Oil red O staining was used to observe lipid droplet formation, and protein expressions in the IRE1/GSK-3β axis were determined via Western blot.

BBR reduced weight, insulin resistance, levels of triglyceride, total cholesterol, free fatty acid, high-density lipoprotein, and low-density lipoprotein but improved glucose tolerance in obese mice. BBR and IRE1 inhibitors demonstrated no cytotoxicity. BBR and IRE1 inhibitors diminished secretion of tumor necrosis factor-alpha, interleukin-6, and monocyte chemoattractant protein 1, lipid droplet formation, and values of p-IRE1/IRE1 and p-GSK-3β/GSK-3β, but elevated glucose consumption in insulin-resistant adipocytes.

BBR improves glucose and lipid metabolism in obese mice through the reduction of IRE1/GSK-3β axis-mediated inflammation, showing the great potential of BBR in reversing insulin resistance in obesity.

Osteoporosis (OP) is a skeletal condition characterized by increased susceptibility to fractures. Programmed cell death (PCD) is the orderly process of cells ending their own life that has not been thoroughly explored in relation to OP.

This study is to investigate PCD-related genes in OP, shedding light on potential mechanisms underlying the disease.

Public datasets (GSE56814 and GSE56815) were analyzed to identify differentially expressed genes (DEGs). We employed the least absolute shrinkage and selection operator (LASSO), Boruta, and random forest (RF) algorithms to pinpoint hub PCD-related genes in OP and construct a predictive nomogram model. The performance of the model was validated through ROC curve analysis, calibration curves, and decision curve analysis. Additionally, transcription factor (TF) interaction analysis and functional enrichment analysis were conducted to explore the regulatory networks and biological pathways involved.

We identified 161 DEGs, with 30 prominently associated with PCD. Five hub genes, PDPK1, MAP1LC3B, ZFP36, DRAM1, and MPO, were highlighted as particularly significant. A predictive nomogram integrating these genes demonstrated high accuracy (AUC) in forecasting OP risk, with an AUC of 0.911 in the GSE56815 dataset. The validation confirmed the gene model efficacy in differentiating OP risk and clinical applicability. The subsequent TF-gene interaction analyses revealed that these hub genes are regulated by multiple TFs, indicating their central role in OP pathology. Functional enrichment analysis of the hub genes indicated significant involvement in apoptosis, autophagy, and immune response pathways.

This study identified PDPK1, MAP1LC3B, ZFP36, DRAM1, and MPO as potential biomarkers and proposes a nomogram based on hub genes for predicting osteoporosis risk.

Chronic Kidney Disease (CKD) is a common chronic disease that is a threat to human health. Accumulating evidence showed that long noncoding RNAs (lncRNAs) are associated with various diseases and can function as competing endogenous RNAs (ceRNAs). However, the roles and functions of the lncRNA‒miRNA-mRNA network in CKD are still unclear.

In this study, we performed differential expression analysis of lncRNAs, miRNAs, and mRNAs in CKD using the datasets GSE66494 and GSE80247 from the Gene Expression Omnibus. A total of 33 lncRNAs, 20 miRNAs, and 240 mRNAs were differentially expressed between CKD patients and healthy controls. Two ceRNA interaction modules composed of 11 hub nodes, namely, 2 lncRNAs (LINC01086, LINC01094), 2 miRNAs (hsa-miR-197-3p, hsa-miR-513b-5p) and 7 mRNAs (CENPF, TOP2A, ARHGAP11A, CEP55, MELK, DTL, and ANLN) were constructed. In vitro knockdown of LINC01094 expression in renal tubular epithelial HK2 cells significantly attenuated the phenotype of TGFβ1-induced cell fibrosis.

The results of RNA immunoprecipitation (RIP) experiments and dual-luciferase reporter experiments based on constructed mutants confirmed that LINC01094 could mediate MELK expression by sponging miR-513b-5p.

Our observations indicated that lowering the expression of LINC01094 can significantly attenuate the TGFβ1-induced fibrosis phenotype in HK2 cells and renal inflammation through the miR-513b-5p/MELK/Smad3 signalling axis.

In chronic kidney disease (CKD) patients, elevated parathyroid hormone (PTH) is linked to cardiovascular mortality and morbidity. Levels of PTH are influenced by serum phosphate (P) and calcium (Ca), but little is known about the impact of magnesium (Mg) on PTH. Hence, this study investigated the relationship between PTH and Mg in peritoneal dialysis (PD) patients and non-dialysis patients from three hospitals in China.

This cross-sectional study included 446 chronic kidney disease stage 5 (CKD5) patients from three hospitals in southern China. PTH was naturally transformed to Ln_PTH for analysis. The chi-square test, Pearson correlation analysis, hierarchical regression analysis, and t-test were used to explore the relationships between Ln_PTH and gender, diabetes history, Mg, P, Ca, albumin (Alb), red blood cells (RBC), hemoglobin (Hb), white blood cells (WBC), and platelet (Plt).

Patients with diabetes mellitus (DM) had lower levels of Ln_PTH in PD (P<0.05) and non-dialysis (P>0.05) patients. Ln_PTH levels were negatively associated with Mg and Ca but positively associated with P and Alb in PD patients (all P<0.05). Ln_PTH levels were negatively associated with age but positively associated with P in non-dialysis patients (all P<0.05).

This study demonstrates the negative effect of Mg and diabetes on Ln_PTH levels in CKD5 patients.

The coexistence of primary glomerulonephritis and autoimmune thyroid disease has not been investigated.

This study aimed to assess thyroid morphology using sonography, determine the prevalence of autoimmune thyroid disorders, and evaluate thyroid function status in patients diagnosed with primary glomerulonephritis.

This single-center cross-sectional and observational study included 58 consecutive patients with primary glomerulonephritis and 58 healthy controls (HC). All participants underwent thyroid examination through laboratory tests and thyroid ultrasonography. The findings were subsequently compared between the two groups.

Among the patients, 17.2% (n = 10) exhibited subclinical hypothyroidism, while 8.6% (n = 5) had overt hypothyroidism. None of the HCs showed overt hypothyroidism, whereas 3.4% (n = 2) of them exhibited subclinical hypothyroidism. Patients displayed significantly lower free triiodothyronine (FT3) levels than HCs (p < 0.001). A linear correlation was observed between patients' thyroid-stimulating hormone (TSH) levels and the degree of proteinuria (p = 0.044). Furthermore, thyroid volume (p < 0.001), hypoechogenicity (p < 0.001), heterogeneous structure (p < 0.001), pseudonodular hypoechoic infiltration (p = 0.05), and the presence of nodules (p < 0.001) were notably higher in patients compared to HCs.

The prevalence of both overt and subclinical hypothyroidism, along with the frequency of nodular goiter, was found to be elevated in patients with primary glomerulonephritis. Considering that primary glomerulonephritis predominantly afflicts young individuals, and these patients bear the lifelong burden of chronic kidney disease, we underscore the significance of routine thyroid function tests and sonographic examinations for the early detection of thyroid disorders.