Purpose: Given the rising prevalence of high fasting plasma glucose (HFPG) over the past three decades, it is crucial to assess its global, national, and regional impact on chronic kidney disease (CKD). This study aims to investigate the burden of CKD attributed to HFPG and its distribution across various levels.Methods and materials: The data for this research was sourced from the Global Burden of Diseases Study 2019. To estimate the burden of CKD attributed to HFPG, we utilized DisMod-MR 2.1, a Bayesian meta-regression tool. The burden was measured using age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years (DALYs) rate. Correlation analysis was performed using the Spearman rank order correlation method. Temporal trends were analyzed by estimating the estimated annual percentage change (EAPC).Results: Globally in 2019, there were a total of 487.97 thousand deaths and 13,093.42 thousand DALYs attributed to CKD attributed to HFPG, which represent a substantial increase of 153.8% and 120%, respectively, compared to 1990. Over the period from 1990 to 2019, the burden of CKD attributable to HFPG increased across all regions, with the highest increases observed in regions with high socio-demographic index (SDI) and middle SDI. Regions with lower SDI exhibited higher ASMR and age-standardized DALYs (ASDR) compared to developed nations at the regional level. Additionally, the EAPC values, which indicate the rate of increase, were significantly higher in these regions compared to developed nations. Notably, high-income North America, belonging to the high SDI regions, experienced the greatest increase in both ASMR and ASDR over the past three decades. Furthermore, throughout the years from 1990 to 2019, males bore a greater burden of CKD attributable to HFPG.Conclusion: With an increasing population and changing dietary patterns, the burden of CKD attributed to HFPG is expected to worsen. From 1990 to 2019, males and developing regions have experienced a more significant burden. Notably, the EAPC values for both ASMR and ASDR were higher in males and regions with lower SDI (excluding high-income North America). This emphasizes the pressing requirement for effective interventions to reduce the burden of CKD attributable to HFPG.

Purpose: Given the increasing occurrence of stroke and high-sodium diets (DHIS) over the past 30 years, it is crucial to assess the global, national, and regional impact of DHIS on the burden of stroke.Methods and materials: The Global Burden of Diseases Study 2019 provided the study's data. We used the Bayesian meta-regression tool DisMod-MR 2.1 to evaluate the burden of stroke attributable to DHIS. Age-standardized disability-adjusted life years (ASDR) and age-standardized mortality rate (ASMR) were used to quantify the burden. We perform correlation analysis utilizing the Spearman rank-order correlation method, and we calculate the estimated annual percentage change (EAPC) to evaluate temporal trends.Results: Globally, DHIS accounts for 17,673.33 thousand disability-adjusted life years (DALYs) and 700.98 thousand deaths of stroke in 2019. The burden of stroke attributable to DHIS has declined between 1990 and 2019 globally and in the majority of regions, with the largest declines seen in regions with high sociodemographic indexes (SDI). Both ASMR and ASDR were higher regionally in regions with moderate SDI than those in developed regions. Furthermore, the absolute values of EAPC, reflecting the rate of decrease, were notably lower in these regions compared to developed nations. High-income North America, categorized within the SDI regions, notably witnessed the smallest decline in ASDR over the last three decades. Additionally, from 1990 to 2019, males consistently bore a larger burden of stroke attributable to DHIS.Conclusion: The burden of stroke attributable to DHIS remained a major concern despite advancements in public knowledge of stroke and their utilization of emergency medical services. Over the past 30 years, more burden has been placed on males and regions with moderate SDI values; in males, higher EAPC values for both ASMR and ASDR have been found. This underscores the urgent need for effective interventions to alleviate the burden of stroke associated with DHIS.

Vascular inflammation is directly responsible for atherosclerosis. 5,2′-Dibromo-2,4′,5′-trihydroxydiphenylmethanone (TDD), a synthetic bromophenol derivative, exhibits anti-atherosclerosis and anti-inflammatory effects. However, the underlying pathways are not yet clear. In this study, we first examined the effects of TDD on toll-like receptor-4 (TLR4) activity, the signaling receptor for lipopolysaccharide (LPS), and found that TDD does not inhibit LPS-induced TLR4 expression in EA.hy926 cells and the vascular wall in vivo. Next, we investigated the global protein alterations and the mechanisms underlying the action of TDD in LPS-treated EA.hy926 cells using an isobaric tag for the relative and absolute quantification technique. Western blot analysis revealed that TDD inhibited NF-κB activation by regulating the phosphorylation and subsequent degradation IκBα. Among the differentially expressed proteins, TDD concentration-dependently inhibited Caveolin 1(Cav1) expression. The interaction between Cav1 and TDD was determined by using biolayer interference assay, UV-vis absorption spectra, fluorescence spectrum, and molecular docking. We found that TDD can directly bind to Cav1 through hydrogen bonds and van der Waals forces. In conclusion, our results showed that TDD inhibited LPS-induced vascular inflammation and the NF-κB signaling pathway by specifically targeting the Cav1 protein. TDD may be a novel anti-inflammatory compound, especially for the treatment of atherosclerosis.

Background: Renal involvement resulting from hyperuricemia, known as hyperuricemia nephropathy (HN), is characterized by chronic tubulointerstitial inflammation caused by extensive urate crystal deposition. Managing this condition requires straightforward preventive or therapeutic interventions, primarily through dietary measures.Methods: In this study, the mouse model of HN was established using yeast extract combined with potassium oxonate. The effect and potential mechanism of β‐sitosterol in treating HN were investigated through biochemical indexes, pathological changes, untargeted metabolomics, and network pharmacology.Results: β‐Sitosterol reduced the levels of four biomarkers of HN: uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), and xanthine oxidase (XOD). It also mitigated inflammatory injury in renal tissues and reversed the abnormal expression of four key urate transporter proteins: glucose transporter protein 9 (GLUT9), organic anion transporter 1 (OAT1), ATP‐binding cassette transporter G2 (ABCG2), and urate transporter 1 (URAT1). To explore the mechanism of β‐sitosterol in treating HN, this study employed network pharmacology and metabolomics to analyze 27 intersecting gene targets and 14 differential metabolites. The findings indicated that glutathione (GSH) metabolism might be a crucial pathway. Treatment with β‐sitosterol increased the levels of reduced GSH as well as the activity and expression of 6‐phosphogluconate dehydrogenase (G6PDH) in mice, thereby effectively modulating GSH metabolism. This study proposes a novel strategy using β‐sitosterol for treating HN, providing a promising approach for addressing this condition.

Sepsis-related brain injury (SRBI) refers to brain dysfunction and structural damage caused by sepsis, which is characterized by inflammation, oxidative stress, and destruction of the blood-brain barrier. Pioglitazone is a PPAR-gamma agonist in which PPAR-gamma acts as an inflammatory modulator, determining the relationship between PPAR-gamma and SRBI and inflammatory state is critical for the disease. This study aimed to construct a drug-targetdisease network for SRBI and Pioglitazone based on network pharmacology, and to investigate the therapeutic effect and potential mechanism of Pioglitazone in SRBI induced by lipopolysaccharide (LPS) in rats through transcriptomics. To establish a rat Model of SRBI by intraperitoneal injection of LPS (10 mg/kg): SD rats were divided into Control, Model (LPS), Pioglitazone, (LPS + Pioglitazone) and GW9662 group (LPS+GW9662). The effects and potential mechanisms of Pioglitazone in the treatment of SRBI were studied using biochemical indexes, pathological changes and transcriptome-sequencing (RNA-seq). RNA-seq results showed 620 DEGs between the Model and the Pioglitazone groups. Enrichment analysis involved multiple inflammatory response processes and chemokine receptor binding functions. TLR4 and CXCL10 in the Toll signaling pathway may play an important role in SRBI as important targets. Pioglitazone may ameliorate SRBI through the PPAR-gamma/TLR4/ CXCL10 pathway.

Renal fibrosis, a terminal manifestation of chronic kidney disease, is characterized by uncontrolled inflammatory responses, increased oxidative stress, tubular cell death, and imbalanced deposition of extracellular matrix. 5,2′‐Dibromo‐2,4′,5′‐trihydroxydiphenylmethanone (LM49), a polyphenol derivative synthesized by our group with excellent anti‐inflammatory pharmacological properties, has been identified as a small‐molecule inducer of extracellular matrix degradation. Nonetheless, the protective effects and mechanisms of LM49 on renal fibrosis remain unknown. Here, we report LM49 could effectively alleviate renal fibrosis and improve filtration function. Furthermore, LM49 significantly inhibited macrophage infiltration, pro‐inflammatory cytokine production and oxidative stress. Interestingly, in HK‐2 cells induced by tumour necrosis factor alpha under oxygen–glucose‐serum deprivation conditions, LM49 treatment similarly yielded a reduced inflammatory response, elevated cellular viability and suppressed cell necrosis and epithelial‐to‐mesenchymal transition. Notably, LM49 prominently suppressed the high‐mobility group box 1 (HMGB1) expression, nucleocytoplasmic translocation and activation. Mechanistically, drug affinity responsive target stability and cellular thermal shift assay confirmed that LM49 could interact with the target heat shock protein 90 alpha family class A member 1 (Hsp90α), disrupting the direct binding of Hsp90α to HMGB1 and inhibiting the nuclear export of HMGB1, thereby suppressing the inflammatory response, cell necrosis and fibrogenesis. Furthermore, molecular docking and molecular dynamic simulation revealed that LM49 occupied the N‐terminal ATP pocket of Hsp90α. Collectively, our findings show that LM49 treatment can ameliorate renal fibrosis through inhibition of HMGB1‐mediated inflammation and necrosis via binding to Hsp90α, providing strong evidence for its anti‐inflammatory and anti‐fibrotic actions.