Liaoning University of Traditional Chinese Medicine

The Objective is to explore the mechanism by which Buzhong Yiqi decoction improves inflammatory damage in autoimmune thyroiditis (AIT) mice based on the Wnt5a/ β-catenin signaling pathway. Sixty 8-week-old NOD.H-2h4 mice of SPF grade were selected and randomly divided into six groups: control group, model group, Buzhong Yiqi decoction low, middle, and high-dose groups (4.78, 9.56, 19.12 g·kg-1), and Western medicine group (selenium yeast tablets, 3.033×10-5 g·kg-1), with ten mice in each group. All groups of AIT model mice were allowed to drink a 0.05% sodium iodide solution freely for 8 weeks to establish the AIT model, while the control group drank distilled water freely. ELISA, HE staining, Real-time PCR, and Western Blot were used to assess serum antibodies, thyroid pathology, and expression levels of Wnt5a, β-catenin, PPAR, GSK-3β, IL-1β, and IL-6. The model group showed increased TgAb and TPOAb levels (P<0.01), lymphocyte infiltration, and altered expression of Wnt5a, β-catenin, PPAR, GSK-3β, IL-1β, and IL-6 (P<0.01). Buzhong Yiqi decoction groups and Western medicine groups significantly reduced these effects, indicating improved thyroid function and inflammation reduction. Buzhong Yiqi decoction modulates the Wnt5a/β-catenin pathway, suggesting a potential therapeutic approach for AIT by reducing inflammation and restoring thyroid function. Buzhong Yiqi decoction can effectively improve AIT inflammatory damage, and the modulation of the Wnt/β-catenin signaling pathway may be one of its intervention mechanisms.

The circadian rhythm syndrome (CircS) is closely linked to metabolism; however, its association with nonalcoholic fatty liver disease (NAFLD) and liver fibrosis remains inadequately explored. This study aims to explore the association of CircS with NAFLD and liver fibrosis. A cross-sectional analysis was performed using data from the National Health and Nutrition Examination Survey, and 3 multivariable logistic regression models were constructed to examine the association of CircS with NAFLD and liver fibrosis. Additionally, subgroup and interaction analyses were conducted to identify potential influencing factors. The study enrolled a total of 2597 participants. In models adjusted for all covariates, the odds ratios (OR) of CircS for NAFLD and liver fibrosis were (OR = 4.85, 95% CI: 3.99–5.89) and (OR = 1.73, 95% CI: 1.29–2.34), respectively. Subgroup and interaction analyses revealed a stronger positive association of CircS with NAFLD and liver fibrosis in younger age groups (<60 years) (P = .049, P = .004). Furthermore, CircS participants with diabetes showed a stronger positive correlation with NAFLD (P = .002). This indicates that in U.S. adults, CircS is significantly associated with the prevalence of both NAFLD and liver fibrosis. The association between CircS and NAFLD is stronger in individuals under 60 years of age and those with diabetes, while the association of CircS with liver fibrosis is more pronounced in individuals under 60 years of age.

BackgroundA substantial association has been established between diabetes and an elevated risk of lung cancer. This study aimed to elucidate the prognosis and characterize alterations in the immune microenvironment linked to the protein kinase C substrate 80K-H (PRKCSH) gene in the context of diabetic lung cancer.MethodsThe expression profile of receptor for advanced glycation end products (RAGE) genes in lung adenocarcinoma (LUAD) and diabetic cohorts was analyzed utilizing data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO). The methodological framework included single-sample gene set enrichment analysis (ssGSEA), hallmark pathway enrichment analysis, Pearson’s correlation, and Wilcoxon tests, employing data from the Cancer Single Cell State Atlas (CancerSEA), tracking tumor immunophenotype (TIP) meta-server, and the Genomics of Drug Sensitivity in Cancer (GDSC) platform. PRKCSH-targeting small interfering RNA (siRNA) was synthesized and transfected into A549 cells. Functional validation of PRKCSH was conducted using real-time quantitative polymerase chain reaction (RT-qPCR), Western blotting, methylthiazolyldiphenyl-tetrazolium bromide (MTT) assays and flow cytometry.ResultsThe analysis identified five RAGE genes with dysregulated expression in both diabetic and LUAD conditions, which were significantly associated with the activation of signaling pathways and patterns of immune cell enrichment in diabetes. PRKCSH has been identified as an independent prognostic marker in LUAD, with associations with key biological processes such as cell cycle regulation, genomic instability responses, inflammatory mediation, and stem cell characteristics. Comprehensive pathway analysis revealed inverse relationships between PRKCSH expression and immune-related molecular mechanisms. Detailed immune profiling indicated reduced infiltration levels of various immune cell populations in association with elevated PRKCSH expression. Notably, increased PRKCSH activity in LUAD was linked to enhanced enzymatic pathway responses and greater therapeutic sensitivity to specific enzyme inhibitors. Experimental validation via gene silencing demonstrated that suppression of PRKCSH effectively reduced malignant cell proliferation while promoting apoptotic mechanisms in lung cancer models.ConclusionsThis extensive investigation positioned PRKCSH as a critical prognostic biomarker and a promising therapeutic target for personalized immunotherapeutic strategies in the management of LUAD.

Autoimmune thyroiditis (AIT) is one of the most common autoimmune diseases and often causes hypothyroidism in patients. As a traditional formulation in my country, Buzhong Yiqi decoction (BZYQD) has significant effects in improving clinical symptoms of AIT and reducing autoantibody titers, but its specific mechanism of action needs to be further explored. The purpose of this study was to explore the effective targets and related mechanisms of Buzhong Yiqi decoction in AIT mice based on transcriptome sequencing technology. Forty NOD.H-2h4 mice were selected and 0.05% NaI was drinking ad libitum for 8 weeks to establish AIT mice, and drug intervention was performed according to groups for 8 weeks. The groups were as follows: control group, Model Group, Buzhong Yiqi Decoction group (9.56 gÅEkg-1) and Positive control group (Se yeast tablets, 3.033Å~10-5 gÅEkg-1), of which Buzhong Yiqi Decoction was the clinical equivalent dose. Thyroid tissues of the Model Group, blank group and Buzhong Yiqi Decoction group were subjected to transcriptome sequencing to analyze the expression of differential genes, and enrichment analysis was carried out. Hematoxylin and eosin staining (HE staining) was used to detect the pathological changes in thyroid tissues, and enzymelinked immunosorbent assay (ELISA) was used to detect the content of serum thyroglobulin antibody (TGAb) to determine the intervention effect of Buzhong Yiqi Decoction; Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was performed based on the transcriptome sequencing results to detect the expression of TLR8, JUN, TICAM2, TIRAP, and IL-1β mRNA in thyroid tissue. According to the transcriptome results, compared with the blank group, there were 327 significantly up-regulated genes and 440 significantly down-regulated genes in the Model Group; compared with the Model Group, there were 502 significantly up-regulated genes and 380 significantly down-regulated genes in the Buzhong Yiqi Decoction group, mainly enriched in immune inflammation and other related pathways including Toll-like receptors. Animal experiments showed that compared with the control group, the model group had obvious lymphocyte infiltration in thyroid tissue under light microscope, a significant increase in inflammatory cells, a significant increase in TGAb content in serum, and a significant increase in TLR8, JUN, TICAM2, TIRAP, IL-1β mRNA expression was observed (P<0.05 or P<0.01). Compared with the Model Group, Buzhong Yiqi Decoction could significantly improve the inflammatory damage of thyroid tissue in AIT mice, reduce the content of TGAb in serum, and down-regulate the expression of TLR8, JUN, TICAM2, TIRAP, IL-1β mRNA (P<0.05 or P<0.01). Buzhong Yiqi Decoction can effectively improve the inflammatory damage of AIT, and inhibiting the abnormal activation of the Toll-like receptor pathway may be one of its intervention mechanisms.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder, with some studies suggesting that obesity may increase the risk of developing RA. However, the relationship between obesity and RA is complex, involving both epidemiological associations and, paradoxically, protective effects. The exact role of obesity in RA pathophysiology remains controversial. In this study, we investigated the impact of obesity on RA progression, focusing on the molecular mechanisms of immune regulation mediated by the adipokine leptin. We examined obese RA patients and employed high-fat diet (HFD)-induced obesity models along with leptin gene-deficient (ob) mice to explore the influence of obesity on RA progression. Our findings revealed elevated serum leptin levels in obese RA patients, which were positively correlated with disease severity. Furthermore, HFD-induced obesity exacerbated arthritis severity in collagen-induced arthritis (CIA) mice, leading to increased joint pathology and bone destruction. To further assess the role of leptin, we utilized ob mice and exogenous leptin supplementation models to investigate its effects on CIA and Th17 polarization. Our results emphasize that leptin, rather than obesity per se, plays a critical role in RA progression by interacting with peroxisome proliferator-activated receptor gamma (PPARγ), thereby promoting Th17 cell differentiation. These findings provide valuable insights into the role of leptin in RA pathogenesis and suggest that leptin may serve as a potential therapeutic target for managing RA in obese individuals.