Endocrine, metabolic & immune disorders drug targets最新文献

Introduction: Traditional Chinese medicine, especially Bushen Huoxue decoction, has demonstrated good therapeutic effects in the treatment of intervertebral disc degeneration and osteoarthritis, but its mechanism of action in osteoporosis remains unclear. This study aimed to explore its potential mechanisms against osteoporosis.

Methods: Active components of Bushen Huoxue decoction were identified through searching the TCM databases. Osteoporosis-related genes were retrieved from three disease databases. Common targets were used to construct a PPI network. Functional enrichment analyses (GO and KEGG), molecular docking, molecular dynamics simulations, and literature validation were performed.

Results: A total of 112 active compounds and 343 potential targets were identified. Key bioactive ingredients included quercetin, luteolin, kaempferol, wogonin, and baicalein. The decoction appeared to act via multiple pathways, such as TNF, NF-κB, MAPK, PI3K/Akt, Wnt/β-catenin, HIF-1, FoxO, AMPK, mTOR, and VEGF, affecting inflammation, metabolism, cell proliferation, survival, and angiogenesis.

Discussion: Bushen Huoxue decoction likely exerted anti-osteoporotic effects through a multi-component, multi-target, and multi-pathway approach, consistent with current understanding of osteoporosis mechanisms. However, as this study was based on network pharmacology and computational analysis, experimental validation is needed.

Conclusion: Bushen Huoxue decoction showed promise as a potential treatment for osteoporosis through complex regulatory mechanisms. The findings provided a theoretical basis for further pharmacological research and TCM-based drug development.

Introduction: To evaluate the effectiveness of selective laser trabeculoplasty (SLT) in lowering intraocular pressure (IOP) in Vietnamese patients with pseudoexfoliation glaucoma (PXG).

Methods: This prospective, comparative study included a total of 64 eyes from PXG patients who had not previously received any antiglaucomatous medication. Patients were categorized into two groups: Group 1 consisted of 32 eyes treated with SLT as the initial therapy, while Group 2 comprised 32 eyes treated with Tafluprost 0.0015%.

Results: The baseline IOP before treatment ranged from 22 to 26 mmHg. There were no significant differences between the two groups in terms of mean cup/disc (C/D) ratio and retinal nerve fiber layer (RNFL) thickness. At the final visit, the mean percentage reduction of IOP was 26.73% in Group 1 and 27.15% in Group 2.

Discussion: SLT significantly reduced IOP in PXG patients, with outcomes comparable to Tafluprost. Treatment was more successful in eyes with higher trabecular pigmentation and early- stage glaucoma. Structural and functional parameters remained stable over 12 months. Side effects, including mild itchiness, IOP spikes, and anterior chamber reactions, were transient and manageable. No vision-threatening complications occurred, confirming SLT as a safe and effective first-line option for PXG in Vietnamese patients.

Conclusion: SLT can be effectively used as a primary treatment for PXG. In cases of recurrent IOP elevation, a second SLT procedure can be administered alone or in combination with other medications.

Introduction: The relationship between uric acid to high-density cholesterol ratio (UHR) and diabetic kidney disease (DKD) is unclear. The aim of this study was to investigate the relationship between UHR and DKD in patients with diabetes mellitus (DM).

Methods: Analyses were conducted based on National Health and Nutrition Examination Survey (NHANES) data from the 2007-2018 cycle. We used multifactorial logistic regression to analyze the association between UHR and DKD. We performed restricted cubic splines (RCS) analyses to explore whether there was a nonlinear relationship between the two. In addition, we explored differences in this association between different subgroups.

Results: A total of 2,674 participants were included in the study. After adjusting for all confounding variables, multivariate logistic regression analysis revealed a significant correlation between UHR and DKD in patients with DM. RCS analysis further revealed a significant nonlinear association between UHR and DKD. Subgroup analysis showed that the association between UHR and DKD was consistent across different subgroups. In addition, the effect of UHR on DKD was significantly influenced by the level of BMI.

Discussion: This study explored the relationship between UHR and DKD, contributing to a better understanding of the significance of UHR in DKD.

Conclusion: Our study found a "J" nonlinear association between UHR and DKD in patients with DM.

Introduction: Achyranthes bidentata Blume (AB), a traditional Chinese medicine, is used to treat Non-alcoholic fatty liver disease (NAFLD), although its precise mechanism of action remains unclear. This study investigated the effects of Achyranthes bidentata water extract (ABW) on NAFLD in mice induced by high-fat-fed.

Methods: The chemical components of Achyranthes bidentata Blume water extract (ABW) were analyzed using ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). After 12 weeks of ABW treatment, liver histopathology and hepatic lipid levels, including total cholesterol (TC) and triglycerides (TG), were evaluated in NAFLD mice. Enzyme-linked immunosorbent assay, quantitative PCR, western blotting, and immunofluorescence were employed to assess changes in the PPARγ/LXRα signaling pathway and macrophage efferocytosis in vivo and in vitro.

Results: In vivo, ABW treatment significantly reduced hepatic lipid accumulation (TC and TG) and alleviated hepatic lesions compared with the model group. ABW also upregulated genes associated with lipid metabolism and macrophage efferocytosis, while reducing the hepatic levels of inflammatory cytokines and the number of apoptotic cells. In vitro, ABW suppressed the expression of pro-inflammatory genes (Il1b, Il6, Tnf, and Nos2) and enhanced the expression of macrophage efferocytosis-related genes (Pparγ, Gas6, Tyro3, and Axl) in ox-LDL-induced Raw 264.7 cells. UHPLC-MS identified 501 compounds in ABW. Auto-docking analysis suggested that 4-dodecylbenzenesulfonic acid, isovanilic acid, and oleanolic acid are potential PPARγ activators present in ABW.

Discussion: This study demonstrates that ABW ameliorates NAFLD by activating the PPARγ/LXRα signaling pathway and promoting macrophage efferocytosis.

Conclusion: These findings provide a novel mechanistic insight into the therapeutic effects of multi- component herbal medicines for NAFLD.

Introduction: Valproic acid (VPA), a widely used antiepileptic drug, is associated with pancreatic toxicity. Silibinin, the active component of silymarin, exhibits antioxidant/anti-inflammatory properties. This study investigated silibinin's protective effects against VPA-induced pancreatitis.

Methods: 48 male Wistar rats (250-280 g) were divided into 8 groups (n=6): control, VPA-only (150,300 and 450 mg/kg), silibinin-only (150 mg/kg), and co-treatment groups. After 3 weeks, biochemical markers (amylase, lipase, SOD, CAT, TNF-α, IL-6) and histopathology (H&E staining) were analyzed. Data were compared using ANOVA/Tukey's test (p<0.05 significant).

Results: VPA dose-dependently increased pancreatic enzymes and inflammatory markers, while reducing antioxidants. Silibinin co-treatment significantly attenuated these effects: Reduced amylase (642.8→375.6 U/L at 450 mg/kg VPA) and TNF-α (61.0→31.6 pg/mL) and restored SOD (10.9→18.3 U/mg) and CAT (5.3→366.2 U/mg). Histopathology confirmed reduced inflammation/ necrosis in co-treatment groups (p<0.01).

Discussion: Silibinin mitigated VPA-induced pancreatitis via antioxidant (SOD/CAT upregulation) and anti-inflammatory (TNF-α/IL-6 reduction) mechanisms. The effect was dose-dependent, with optimal protection at lower VPA doses (150 and 300 mg/kg).

Conclusion: Silibinin shows promise as an adjunct therapy to reduce VPA-associated pancreatic damage. Further clinical studies are warranted.

Introduction: To examine the relationship between mercury exposure and serum sex steroid hormones among children aged 6-18 years.

Methods: Data were collected from the NHANES 2013-2016. A cohort of 2,637 Children with available information on mercury exposure, serum sex steroid hormones, and covariates was enrolled. Generalized linear models were applied to explore the association of mercury exposure with sex steroid hormones. Finally, we adopted the Bayesian kernel machine regression (BKMR) model to investigate the effect of mixture exposure to mercury on hormone levels.

Results: Methyl mercury (MeHg) and total mercury (Hg) were associated with all sex steroid hormones except E2 (P <0.05). After adjusting for covariates, MeHg and Hg were related to sex hormone- binding globulin (SHBG) and free androgen index (FAI) (P <0.05). Stratified analysis by sex-puberty revealed a negative relationship between Hg and SHBG, while a positive association of MeHg with FAI in prepubertal girls (P <0.05). Their associations were confirmed by the BKMR model analysis, in which the mixture exposure was positively linked to FAI but inversely related to SHBG, particularly among prepubertal girls.

Discussion: These findings suggest that mercury may disrupt sex hormone homeostasis during critical developmental windows. Appropriate measures should be implemented to mitigate the adverse effects of mercury on sex hormones in the young population. However, future longitudinal large-scale studies are required for validation.

Conclusion: Exposure to MeHg and Hg is associated with increased FAI levels, but decreased levels of SHBG, which are more pronounced in girls. The heightened susceptibility of prepubertal girls underscores the need for targeted public health interventions, including dietary guidance on seafood consumption and early biomonitoring of mercury levels in high-risk populations, to mitigate potential health impacts.

Introduction: Quan-du-zhong capsule (QDZ), derived from Eucommia ulmoides Oliv, is clinically utilized for diabetic kidney disease (DKD) management due to its renoprotective effects. Recent studies have demonstrated that QDZ ameliorates proteinuria and attenuates the decline in glomerular filtration rate (GFR) in DKD patients; however, the underlying mechanisms remain unclear.

Methods: To elucidate the active components of QDZ and their potential association with immune cell modulation, we conducted bioinformatics analyses using GEO datasets and CIBERSORT to assess immune cell infiltration. Furthermore, molecular docking experiments and experimental validation were performed to verify the interactions between QDZ and potential immunotherapeutic targets.

Results: Network pharmacology analysis identified the main active components of QDZ, including Quercetin, Kaempferol, β-carotene, β-sitosterol, and Syringetin. Furthermore, bioinformatics and molecular docking studies demonstrated that the FOS gene and the MAPK signaling pathway exhibit differential expression in DKD patients and were significantly correlated with immune cell activity. Notably, the active components-particularly Quercetin, Kaempferol, and Syringetin- displayed strong binding affinities to key targets. In addition, QDZ significantly upregulated FOS and MAPK expression and enhanced glucose uptake in HG-induced HEK-293 cells, suggesting its role in improving insulin sensitivity.

Conclusions: This study illustrates the mechanism by which QDZ upregulates FOS expression and modulates the MAPK signaling pathway, thereby regulating immune cell function in DKD. These findings provide novel insights to inform future research and development of QDZ-based DKD therapies.

Introduction: This study aimed to identify key genes and potential therapeutic targets involved in the progression of osteoarthritis (OA) through an integrated multi-omics approach.

Methods: We performed single-cell RNA sequencing (scRNA-seq) analysis on OA and control samples to define cell types and differentially expressed genes (DEGs). Bulk RNA-seq data from 7 public OA datasets were analyzed to identify DEGs, and Weighted Gene Co-expression Network Analysis (WGCNA) identified key co-expressed modules. An Integrated analysis of scRNA- seq DEGs, bulk RNA-seq DEGs, and WGCNA module genes pinpointed overlapping candidates. Functional enrichment analysis of these genes was then conducted. Mendelian randomization (MR) analysis was used to assess causal relationships between candidate genes and OA risk. The top candidate gene, CDO1, was functionally validated using siRNA-mediated knockdown in a rat OA model, assessed by histology and immunohistochemistry.

Results: scRNA-seq identified 11 distinct cell types and 4,316 DEGs. Bulk RNA-seq meta-analysis revealed 3,664 DEGs, with WGCNA highlighting a key module significantly associated with OA. Integration identified 932 overlapping DEGs. Enrichment analysis implicated pathways including ferroptosis, PI3K-Akt signaling, and ECM-receptor interaction. MR analysis established CDO1 as the top causal OA risk gene (OR [95% CI] = 0.998 [0.996-0.999], P = 0.003).

Discussion: In vivo, CDO1 knockdown significantly delayed OA progression in rats. Compared to controls, the si-CDO1 group showed improved cartilage structure, increased chondrocyte numbers, and enhanced type II collagen expression.

Conclusion: CDO1 is a novel OA risk gene and therapeutic target. Its inhibition protects against OA progression, as supported by integrated multi-omics analysis and in vivo validation.

Introduction: Irisin is a hormone synthesized by skeletal muscle cells in response to physical exercise. It has been linked to various health benefits, including improved insulin sensitivity, fat burning, reduced inflammation, and potential protection against metabolic diseases, such as obesity and type 2 diabetes. This review explores the role of irisin, stimulated by physical exercise, in kidney diseases.

Methods: A comprehensive review was conducted using SciELO, PubMed, Scopus, Web of Science, and EMBASE. Five articles were selected based on pre-established eligibility criteria. These studies used animal experiments, assessing irisin predominantly through Western blotting or ELISA, with aerobic exercise protocols, mainly treadmill running.

Results: The results consistently showed an increase in irisin levels in response to physical exercise in animal models with kidney diseases.

Discussion: Aerobic exercise increased plasma irisin expression, with better outcomes observed with low to medium-intensity training. Irisin demonstrated therapeutic potential by reducing renal cysts, inhibiting epithelial-mesenchymal transition, decreasing markers of diabetic nephropathy, and restoring autophagy in podocytes. Additionally, it activated the AMPK-Sirt1-PGC-1α pathway, suggesting antioxidant and antiapoptotic effects.

Conclusion: The studies reviewed suggested that aerobic exercise increased irisin levels in animal models of kidney diseases, showing potential therapeutic effects for renal health.