Purpose:Acute kidney injury (AKI) is a severe clinical condition with high morbidity and mortality that lacks effective therapies. Carbon dots (CDs) derived from traditional Chinese medicine ingredients have emerged as promising therapeutic agents because of their favorable biosafety profile and potent antioxidant and anti-inflammatory properties. In this study, the therapeutic effects of CDs derived from Ligusticum chuanxiong (LC-CDs) were investigated in an ischemia‑reperfusion injury AKI model, and their underlying molecular mechanisms were elucidated. Methods:LC-CDs were developed through a facile hydrothermal method and were used to treat an ischemia-reperfusion AKI rat model and HK-2 cells with hypoxia/reoxygenation injury. Results:LC-CDs with uniform nanostructures, graphitic carbon structures, and multiple chemical functional groups on the surface were successfully synthesized. The LC-CDs exhibited excellent hydrophilicity, chemical reactivity, and unique optical properties. Treatment with the LC-CDs significantly reduced creatinine and blood urea nitrogen levels and alleviated pathological damage in renal tissue. Additionally, the LC-CDs effectively cleared reactive oxygen species, reduced oxidative stress levels, and mitigated mitochondrial damage. Treatment with the LC-CDs also decreased renal tissue expression of key inflammatory factors (IL-1β, IL-6, and TNF-α). Transcriptome analysis revealed that differentially expressed genes associated with the LC‑CDs were primarily involved in the autophagy, and inflammatory signaling pathways. Further subcellular fractionation and fluorescence localization analyses confirmed that the LC-CDs accumulated in and targeted mitochondria, suggesting that mitochondria are the primary organelle target through which the LC-CDs exert their effects. Autophagy-related signaling pathways likely also played a critical role in mediating the therapeutic efficacy of the LC-CDs. Conclusion:The LC-CDs demonstrated considerable therapeutic potential in an AKI model through their antioxidant, anti-inflammatory, and autophagy regulation. Their outstanding biocompatibility, multifunctional synergistic properties, and well-defined molecular targets provide a crucial foundation for the development of novel nanomedicines and kidney-targeted delivery systems.

Diabetic kidney disease (DKD), a major diabetic complication driving chronic and end-stage renal disease, involves disrupted proximal tubular energy metabolism. This study investigated the pathogenic role ofcarnitine palmitoyltransferase-1A (CPT1A) acetylation—a mitochondrial enzyme governing the rate-limiting step of fatty acid oxidation (FAO)—in DKD progression. Utilizingdb/dbmice to establishin vivoDKD models, we assessed renal fibrosis via histology/Western blotting and performedproteome-wide acetylation profiling. Parallelin vitroanalyses employed high-glucose (30 mM, 48 h)-treated human proximal renal tubular cells. Functional consequences oflysine 584 (K584) acetylationwere evaluated using lentiviral-mediated K584R point mutation. Results demonstrated: (1) Global protein hyperacetylation in DKD mice, with CPT1A identified as the most significantly hyperacetylated mitochondrial protein; (2) Downregulated CPT1A expression in renal tubular epithelia of both murine and human DKD tissues; (3) Association of CPT1A hyperacetylation with elevated α-smooth muscle actin, fibronectin, and reactive oxygen species (ROS), alongside reduced mitochondrial membrane potential, FAO, and fatty acid synthesis; (4) K584R mutation attenuated CPT1A acetylation, enhancing fatty acid synthase activity and FAO while reducing ROS and fibrosis markers. We conclude thatCPT1A acetylation at K584critically drives DKD pathogenesis and represents a promising biomarker/therapeutic target.

Fluorofenidone (AKF-PD) is a novel pyridone agent and has potent anti-NLRP3 inflammasome and anti-fibrotic activities. However, the mechanisms underlying its pharmacological actions are not fully understood. A renal fibrosis rat model was established by the unilateral ureteral obstruction (UUO) procedure and the rats were randomized and treated with, or without, AKF-PD for 3 and 7 days. The levels of renal fibrosis, NLRP3 inflammasome activation, mitochondrial function, and autophagy were tested in rat kidney tissues. Macrophages following lipopolysaccharides (LPS) and adenosine 5′-triphosphate (ATP) stimulation were examined by Western blot, spectrophotometry, and TEM. Compared with the untreated UUO rats, AKF-PD treatment significantly mitigated the UUO procedure-induced renal fibrosis in rats. AKF-PD treatment decreased mitochondrial dysfunction and IL-Iβ and caspase-1 expression in rat kidney tissues and reduced mitochondrial reactive oxygen species production in activated macrophages. Mechanistically, AKF-PD treatment significantly attenuated the PI3K/AKT/mTOR signaling, increased Beclin-1 and LC3 II expression and autophagosome formation, and ameliorated the mitochondrial damage in renal tissues and activated macrophages. The results indicated that AKF-PD treatment inhibited renal interstitial fibrosis by regulating the autophagy-mitochondria-NLRP3 inflammasome pathway.

The aim of the present study was to elucidate the potential diagnostic value of urinary N-glycoprotein in patients with IgA nephropathy (IgAN) using mass spectrometry (MS). All procedures were performed between June 2021 and June 2023 at Guangan People's Hospital (Guangan, China). Fresh mid-morning fasting midstream urine samples were collected from a total of 30 patients with IgAN and 30 sex- and age-matched healthy volunteers. Data acquired from 6 participants are available through ProteomeXchange with the identifier PXD041151. By comparison between the IgAN group (n=3) and healthy controls (n=3) and selection criteria of P<0.05 and |log fold-change|>2, a total of 11 upregulated and 22 downregulated glycoproteins in patients with IgAN were identified. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggested that glycoproteins are involved in various functions, such as the regulation of cell growth, cell adhesion, cellular component organization and protein binding, as well as multiple pathways, including p53, Notch and mTOR signaling pathways. The urine levels of afamin were further measured by ELISA in a validation cohort to assess the diagnostic performance of the single indicator model. In conclusion, MS-based proteomics of urinary glycoproteins may be an alternative option for diagnosing patients with IgAN. Biomarkers of IgAN may include, but are not limited to, CCL25, PD-L1, HLA-DRB1, IL7RD and WDR82. In addition, the levels of urinary AFM indicators are of diagnostic value for IgAN.

Acute kidney injury (AKI) is a serious disorder associated with significant morbidity and mortality. AKI and ischemia/reperfusion (hypoxia/reoxygenation, H/R) injury can be induced due to several reasons. Paeoniflorin (PF) is a traditional herbal medicine derived from Paeonia lactiflora Pall. It exerts diverse therapeutic effects, including anti-inflammatory, antioxidative, antiapoptotic, and immunomodulatory properties; thus, it is considered valuable for treating several diseases. However, the effects of PF on H/R injury-induced AKI remain unknown. In this study, we established an in vitro H/R model using COCL 2 and investigated the functions and underlying mechanisms of PF on H/R injury in HK-2 cells. The cell vitality was evaluated using the cell count kit-8 assay. The DCFH-DA fluorescence probe was used to measure the levels of reactive oxygen species (ROS). Oxidative damage was detected using superoxide dismutase (SOD) and malondialdehyde (MDA) assay kits. Apoptotic relative protein and Keap1/Nrf2/HO-1 signaling were evaluated by Western blotting. Our results indicated that PF increased cell viability and SOD activity and decreased the ROS and MDA levels in HK-2 cells with H/R injury. PF inhibits apoptosis by increasing Bcl-2 and decreasing Bax. Furthermore, PF significantly upregulated the expression of HO-1 and Nrf2, but downregulated the expression of HIF-1α and Keap1. PF considerably increased Nrf2 nuclear translocation and unregulated the HO-1 expression. The Nrf2 inhibitor (ML385) could reverse the abovementioned protective effects of PF, suggesting that Nrf2 can be a critical target of PF. To conclude, we found that PF attenuates H/R injury-induced AKI by decreasing the oxidative damage via the Nrf2/HO-1 pathway and inhibiting apoptosis.

Metabolic acidosis is a common complication of chronic kidney disease (CKD). Veverimer is an orally administrated, free amine polymer with high capacity and binding selectivity to hydrochloric acid from the gastrointestinal tract. This study pooled the current evidence of the efficacy and safety of veverimer for the treatment of metabolic acidosis associated with CKD. We conducted a systematic literature search on PubMed, Embase, and Cochrane Central for relevant randomized controlled trials (RCTs) in June 2020. In this study, three RCTs with 548 patients were included in our analysis. The analysis revealed that veverimer was associated with increased bicarbonate level of patients (weight mean difference [WMD] 3.08, 95% confidence interval [CI] [2.40, 3.77], p < 0.001) and improved physical function compared with placebo measured by Kidney Disease and Quality of Life Short Form 36, question 3 (physical functioning domain) (KDQoL-PFD) score (WMD 5.25, 95% CI [1.58, 8.92], p = 0.005). For safety outcomes, both groups exhibited similar risks for developing headache, diarrhea, flatulence, and hyperkalemia. In conclusion, current clinical evidence indicates that veverimer is efficacious and safe against metabolic acidosis related to CKD compared with placebo. Further research comparing long-term veverimer use with traditional alkali therapy is needed.

Renal interstitial fibrosis (RIF) is the leading cause of end-stage renal disease, partly because of the lack of effective treatments. Curcumin, the primary active ingredient in turmeric, reportedly exerts potent antifibrotic effects. This study investigated the effects of curcumin on RIF in unilateral ureteral obstruction (UUO) rats and characterized the underlying action mechanism. UUO rats were treated with curcumin for 7 and 14 d. Renal fibrosis was evaluated through haematoxylin-eosin staining, Masson staining, and type I and III collagen expression. Autophagy and mitochondria were observed through scanning electron microscopy. NLRP3 inflammasomes, mitochondria, and autophagy-related proteins were detected through Western blotting. Mitochondrial respiratory enzyme activity was assessed spectrophotometrically. Compared with UUO rats, renal fibrosis was attenuated and NLRP3 inflammasome activation was inhibited in curcumin-treated rats. Furthermore, mitochondrial dysfunction was ameliorated and the LC3B/LC3A ratio and Beclin-1 expression were increased in curcumin-treated rats. Additionally, curcumin inhibited the PI3K/AKT/mTOR pathway. These results indicate that curcumin is a promising treatment agent for RIF, and its antifibrotic effects may be mediated by the inhibition of NLRP3 inflammasome activity through the regulation of autophagy and protection of mitochondrial function in UUO rats.

目的 观察姜黄素治疗糖尿病肾病的疗效,并探讨其对p38MAPK信号通路的影响.方法 12只db/db小鼠,分为模型组和姜黄素治疗组,6只db/m小鼠为对照组.小鼠系膜细胞(MES-13)分为低糖对照组,高糖模型组,高糖+姜黄素处理组.生化检测小鼠血糖、血尿素及血肌酐水平,ELISA法检测db/db小鼠24h尿微量白蛋白,PAS染色行肾小球硬化指数评分,Western blot检测致纤维化因子CTGF和38MAPK在db/db小鼠肾组织和系膜细胞中的表达.结果 db/db小鼠血糖、血尿素及血肌酐明显升高,伴有大量蛋白尿,肾小球硬化,db/db小鼠肾组织和经过高糖处理的系膜细胞中磷酸化的P38以及CTGF的表达均明显增加.姜黄素治疗后降低了血尿素及血肌酐的水平,减少db/db小鼠蛋白尿,减轻了肾小球硬化,抑制了db/db小鼠肾组织和高糖处理的系膜细胞中P38的磷酸化,降低了CTGF的表达.结论 姜黄素对糖尿病肾病的治疗作用,与抑制38MAPK信号通路的磷酸化相关.

Objective To investigate the effects of fluorofenidone(AKF-PD)on diabetic kidney disease in db/db mice and its possible mechanisms.Methods(1)Fifty-six mice aged 8 weeks(half male and half female),including 42 db/db mice and 14 wild-type mice were studied.Fortytwo db/db mice randomly were divided into model group(mock-treated diabetic db/db mice),AKF-PD(250 mg· kg-1· d-1)treatment group and losartan(20 mg· kg-1· d-1)treatment group.Wild-type mice and model mice were treated with vehicle(0.5％sodium carboxymethylcellulose),while the treatment groups received either AKF-PD or losartan.After 18 weeks,the blood glucose and urinary albumin were measured,the pathological changes of kidney were observed by PAS staining.The protein expressions of type Ⅳ collagen and fibronectin(FN)in kidney tissue were detected by immunohistochemistry.(2)Mouse glomerular mesangial cells(MES-13 cells)were divided into six groups:normal glucose group(5.5 mmol/L glucose),hypertonic group(5.5 mmol/L glucose+19.5 mmol/L mannitol),high glucose group(25.0 mmol/L glucose),AKF-PD group(25.0 mmol/L glucose+400 mg/L AKF-PD)and losartan group(25.0 mmol/L glucose+2 μmol/L losartan).After 72 h treatment,the expressions of type Ⅰ collagen,type Ⅳ collagen and transforming growth factor-β1(TGF-β1)mRNA were detected by realtime PCR,and the content of TGF-β1 protein in the culture supernatant was detected by ELISA.Results(1)Compared with the wild type mice,model mice had increased weight,blood glucose and glomerulosclerosis index(all P ＜ 0.01),accompanied with heavy albuminuria,glomerular hypertrophy,mesangial area expansion and deposition of collagen type Ⅳ and FN(all P ＜ 0.01).Compared with model mice,in AKF-PD and losartan groups 24 h urinary albumin and glomerulosclerosis index decreased(all P ＜ 0.01),glomerular hypertrophy and mesangial area expansion alleviated,and the protein expressions of collagen type Ⅳ and FN were inhibited(all P ＜ 0.01).(2)Compared with the normal glucose group,the mRNA expressions of type Ⅰ collagen and type Ⅳ collagen increased in high glucose group,meanwhile the mRNA and protein expressions of TGF-β1 increased(all P ＜ 0.01).In AKF-PD and losartan groups the expressions of type Ⅰ collagen,type Ⅳ collagen and TGF-β1 were inhibited as compared with high glucose group(all P ＜ 0.05).Conclusion Fluorofenidone may play an anti-fibrotic effect in db/db mice by reducing the expression of TGF-β1 and inhibiting collagen synthesis in glomerular mesangial cells.

Oxidative stress, inflammation and fibrosis can cause irreversible damage on cell structure and function of kidney and are key pathological factors in Diabetic Nephropathy (DN). Therefore, multi-target agents are urgently need for the clinical treatment of DN. Using Pirfenidone as a lead compound and based on the previous research, two novel series (5-trifluoromethyl)-2(1H)-pyridone analogs were designed and synthesized. SAR of (5-trifluoromethyl)-2(1H)-pyridone derivatives containing nitrogen heterocyclic ring have been established for in vitro potency. In addition, compound 8, a novel agent that act on multiple targets of anti-DN with IC50 of 90μM in NIH3T3 cell lines, t1/2 of 4.89±1.33h in male rats and LD50>2000mg/kg in mice, has been advanced to preclinical studies as an oral treatment for DN.

Objective To investigate effects of pirfenidone（PFD） on diabetic nephropathy model in db/db mice and to explore its possible mechanisms. Methods （1） Wildtype mice were as the normal control group,and db/db mice were divided into model group and PFD group,with6 mice in each group. In the PFD group mice were administered continuously by 250 mg·kg -1 ·d -1 PFD for

目的 观察姜黄素对糖尿病肾病(db/db)小鼠肾组织及人近端肾小管上皮细胞(HK-2细胞)中NLRP3炎性体活化的影响,并探讨其作用机制.方法 12只db/db小鼠,分为模型组和姜黄素治疗组,6只db/m小鼠为对照组.HK-2细胞分为对照组,高糖模型组,姜黄素处理组.ELISA法检测db/db小鼠尿蛋白,计算尿蛋白/尿肌酐比值;PAS染色行肾小球硬化指数评分;Western blot方法检测NLRP3、caspase-1和IL-1β在db/db小鼠肾组织和HK-2细胞中的表达;流式细胞仪检测HK-2细胞中线粒体活性氧(reactive oxygen species,ROS)的水平.结果 db/db小鼠血糖明显升高,伴有大量蛋白尿,肾小球硬化;db/db小鼠肾组织和高糖处理的HK-2细胞中NLRP3、caspase-1和IL-1β的表达增加;姜黄素治疗显著降低了db/db小鼠尿蛋白,减轻了肾小球硬化,抑制了db/db小鼠肾组织和高糖处理的HK-2细胞中NLRP3炎性体的活化;同时发现,高糖处理的HK-2细胞中线粒体ROS的水平明显增加,经过姜黄素处理后,ROS的水平明显减少.结论 姜黄素可以抑制db/db小鼠肾组织和高糖处理的HK-2细胞中NLRP3炎性体的活化,其作用机制可能与抑制线粒体ROS的产生有关.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, partly because of the lack of effective treatments for DN. Curcumin has been shown to exert strong antifibrotic effects in DN, but the underlying mechanisms are not well characterized. In this study, we sought to determine the effects of curcumin on diabetic renal disease in db/db mice and characterize the underlying mechanism of action. We administered curcumin to db/db mice for 16 weeks. In comparison to mock-treated db/db mice, curcumin-treated mice showed diminished renal hypertrophy, reduced mesangial matrix expansion, and a lower level of albuminuria. Furthermore, the upregulated protein and mRNA expressions of collagen IV and fibronectin in the renal cortices of the db/db mice were inhibited by curcumin treatment. Additionally, curcumin treatment was associated with significant reductions in mature interleukin-1β, cleaved caspase-1, and NLRP3 protein levels in the renal cortices of db/db mice as well as in HK-2 cells exposed to high glucose concentration. In summary, curcumin, a potent antifibrotic agent, is a promising treatment for DN, and its renoprotective effects appear to be mediated by the inhibition of NLRP3 inflammasome activity.

Objective To investigate the effect of Jingui Shenqi pill on unilateral ureteral obstruction (UUO) rats with renal interstitial fibrosis and the expression of p-STAT3 protein. Methods 30 male SD rats were randomly divided into sham operation group, UUO model group, low dose of Jingui Shenqi pill group, high dose of Jinguishenqi pill group, enalapril treatment group as positive control. After intragastric administration on the 14 days, the rats were sacrificed. The obstructive kidney tissues were stained with HE and Masson to observe the pathologic changes. The protein or mRNA expression of type I and III collagen in renal tissue was detected by immunohistochemistry staining or Real-time PCR. The phosphorylation of signal transducer and activator of transcription 3 (STAT3) in renal tissue was detected by Western blot. Results Compared with UUO model group, after treatment with Jingui Shenqi pill, the renal interstitial damage index and collagen positive area were decreased, the expression of type I and type III collagen protein and mRNA were also decreased and the phosphorylation of STAT3 protein was inhibited (P<0.05). Conclusion Jingui Shenqi pill can obviously improve renal interstitial injury and reduce interstitial collagen deposition in UUO rats which may be related to the inhibition of STAT3 phosphorylation.

目的:探讨金匮肾气丸对单侧输尿管梗阻(UUO)大鼠肾间质炎症反应及核转录因子-κB(NF-κB)信号通路的影响.方法:雄性SD大鼠48只,随机分为假手术组、UUO模型组、金匮肾气丸治疗组、阳性对照药依那普利治疗组,UUO术后第1天开始灌胃,连续灌胃3d或7d后处死大鼠,取梗阻肾组织,免疫组织化学法检测CD68和CD3在肾组织的表达,组织匀浆EHSA法检测单核细胞趋化蛋白-1(MCP-1)和肿瘤坏死因子-α(TNF-α)在肾组织的蛋白水平,Western印迹检测磷酸化核因子-κB (P-IκB)和IκB在肾组织的表达.结果:与假手术组比较,模型组在3d、7d时肾间质损伤指数均明显增高,CD68阳性巨噬细胞、CD3阳性淋巴细胞增多,肾组织中MCP-1、TNF-α和p-IκB-α蛋白表达水平显著增加,IκB-α表达水平明显降低(P＜0.05或＜0.01);金匮肾气丸和依那普利治疗后,两药物组较模型组的肾间质损伤指数均明显降低,CD68阳性巨噬细胞、CD3阳性淋巴细胞明显减少,肾组织中MCP-1、TNF-α和p-IκB-α蛋白表达水平显著下降,IκB-α表达水平明显上调(P＜0.05).结论:金匮肾气丸可以改善UUO梗阻肾组织的炎症反应,其作用机制可能与抑制NF-κB信号通路的活性有关.

AimApoptosis is one of the most important mechanisms underlying renal tubulointerstitial fibrosis. We identified a role of protein Peroxiredoxin 1 (Prx1) in protecting apoptosis occurred in tubular epithelial cells of the rat and human kidney.MethodsImmunohistochemistry (IHC) staining was used to detect Prx1 expression in kidney derived from unilateral-ureteral obstruction (UUO) rats or patients with obstructive nephropathy. Modulation of Prx1 expression by transfecting siRNA and overexpression plasmid approach were carried out in NRK-52E (rat kidney tubular epithelial cell line) cells. UUO-induced apoptosis was determined using TUNEL assay.ResultsImmunohistochemistry staining showed that Prx1 expressed in the cytoplasm of renal tubular epithelial cells, in the kidneys of UUO rats. The reduction was confirmed by both IHC and real-time polymerase chain reaction following a course of renal tubulointerstitial fibrosis in UUO rats and a decrease of Prx1 occurred concomitantly with an elevation of TUNEL-positive cells. Fluorofenidone (AKF-PD), a new anti-tubulointerstitial fibrotic agent, attenuated Prx1 reduction in UUO rats. Furthermore, hydrogen peroxide (H2O2)-derived oxidative stress activated p38 MAPK, and induced apoptosis in NRK-52E cells; knockdown of Prx1 sensitized both events in NRK-52E cells, and overexpression of Prx1 diminished the apoptosis and the phosphorylation of p38ConclusionDownregulation of Prx1 occurred in renal tubular epithelial cells of UUO rats and patients with obstructive nephropathy. Prx1 may alleviate the pathogenesis by inhibiting H2O2-induced apoptosis via inhibiting the p38 MAPK pathway. Prx1 may represent a useful target for a protective therapy towards renal tubulointerstitial fibrosis.Summary at a Glance Mei etal. utilize the standard rat model of unilateral ureteric obstruction model to demonstrate the expression and distribution of the antioxidant enzyme peroxiredoxin 1 (Prx1). Their subsequent studies suggest that fluorofenidone treatment ameliorates progression through maintaining PRx1, and thereby inhibiting apoptosis.

Interleukin-1 beta (IL-1β) is a potent pro-inflammatory and pro-fibrotic cytokine that plays an important role in renal fibrosis. Fluorofenidone (AKF-PD) is a novel pyridone agent that exerts a strong renal anti-fibrotic effect. We previously found that administration of AKF-PD could significantly attenuate IL-1β production in vitro and in vivo. However, the underlying mechanism is not fully understood. Here we show that AKF-PD has no effect on the expression of pro-IL-1β in activated mouse macrophages in vitro. Instead, AKF-PD inhibits the inflammasome, lowering caspase-1 levels and thereby decreasing cleavage of pro-IL-1β into IL-1β. AKF-PD was found to block inflammasome activity induced by various signals, including ATP, alum crystals, and Salmonella typhimurium. These results provide a novel mechanistic insight into how AKF-PD exerts its anti-inflammatory and anti-fibrotic activities, and suggest that AKF-PD might block IL-1β production via suppression of inflammasomes in renal fibrosis. In addition, the results suggest that AKF-PD may be of therapeutic potential in other inflammasome-related diseases.

Signaling through the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, especially JAK2/STAT3, is involved in renal fibrosis. Fluorofenidone (FD), a novel pyridone agent, exerts anti-fibrotic effects in vitro and in vivo. Herein, we sought to investigate whether FD demonstrates its inhibitory function through preventing JAK2/STAT3 pathway. In this study, we examined the effect of FD on activation of rat renal interstitial fibroblasts, glomerular mesangial cells (GMC), and expression of JAK2/STAT3. Moreover, we explored the histological protection effects of FD in UUO rats, db/db mice, and phosphorylation of JAK2/STAT3 cascade. Our studies found that pretreatment with FD resulted in blockade of activation of fibroblast and GMC manifested by fibronectin (FN) and α-smooth muscle actin (α-SMA) protein expression and decline of STAT3 tyrosine phosphorylation induced by IL-6 or high glucose. In unilateral ureteral obstruction rats and a murine model of spontaneous type 2 diabetes (db/db mice), treatment with FD blocked the expression of FN and α-SMA, prevented renal fibrosis progression, and attenuated STAT3 activation. However, FD administration did not interfere with JAK2 activation both in vivo and in vitro. In summary, the molecular mechanism by which FD exhibits renoprotective effects appears to involve the inhibition of STAT3 phosphorylation.

Background Inflammation has a crucial role in renal interstitial fibrosis, which is the common pathway of chronic kidney diseases. Mefunidone (MFD) is a new compound which could effectively inhibit the proliferation of renal fibroblasts in vitro. However, the overall effect of Mefunidone in renal fibrosis remains unknown. Methods Sprague-Dawley rats were randomly divided intro 6 groups: sham operation, unilateral ureteral obstruction (UUO), UUO/Mefunidone (25, 50, 100mg/kg/day) and UUO/PFD (500mg/kg/day). The rats were sacrificed respectively on days 3, 7, and 14 after the operation. Tubulointerstitial injury index, interstitial collagen deposition, expression of fibronectin (FN), α-smooth muscle actin (α-SMA), type I and III collagen and the number of CD3+ and CD68+ cells were determined. The expressions of proinflammatory cytokines, p-ERK, p-IκB, and p-STAT3 were measured in human renal proximal tubular epithelial cells of HK-2 or macrophages. Results Mefunidone treatment significantly attenuated tubulointerstitial injury, interstitial collagen deposition, expression of FN, α-SMA, type I and III collagen in the obstructive kidneys, which correlated with significantly reduced the number of T cells and macrophages in the obstructive kidneys. Mechanistically, Mefunidone significantly inhibited tumor necrosis factor-α (TNF-α-) or lipopolysaccharide (LPS)-induced production of proinflammatory cytokines. This effect is possibly due to the inhibition of phosphorylation of ERK, IκB, and STAT3. Conclusion Mefunidone treatment attenuated tubulointerstitial fibrosis in a rat model of UUO, at least in part, through inhibition of inflammation.

OBJECTIVETo determine the effect of curcumin on diabetic nephropathy in db/db mice and its possible mechanism.METHODSTen female db/db mice were randomly divided into 2 groups: one was treated with curcumin at 200 mg/(kg.d) and the other was a placebo group. Five age-matched db/m mice were grouped as the controls. In the curcumin group, curcumin was administered to db/db mice for 18 weeks. At the end of the experiment, the blood glucose and albumin were measured, and the kidney tissue sections were stained with PAS to observe the pathological changes. The expression of collagen IV and FN in the kidney was detected by immunohitochemistry staining. Western blot was used to detect the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and IκB in the kidney.RESULTSCompared with db/m mice, the weight and blood glucose of db/db mice were markedly increased, accompanied with heavy proteinuria, glomerulus hypertrophy, mesangial area expansion, thickening of basement membrane and ECM deposition. The phosphorylation of STAT3 was upregulated and the degradation of IκB was increased. Compared with the db/db mice, curcumin significantly decreased the urinary albumin, inhibited the phosphorylation of STAT3 and the degradation of IκB, and reduced the expression of collagen IV and FN in the kidney.CONCLUSIONCurcumin can obviously decrease albuminuria and attenuate glomerular sclerosis in diabetic db/db mice by inhibiting phosphorylation of STAT3 and degradation of IκB.