Association of serum Nrf2 protein levels with disease activity and renal impairment in lupus nephritis.

Introduction: We aimed to investigate the relationship between nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression levels, lupus nephritis (LN) disease activity, and the degree of renal injury (based on the estimated glomerular filtration rate [eGFR]) in patients with LN. Methods: We selected 40 healthy control participants and 102 patients with LN who were treated in the Second Hospital of Jilin University, China, for inclusion in this study. Patients with LN were classified into LN with high-eGFR and LN with low-eGFR groups. Nrf2 protein levels were measured in the serum and renal tissues of the participants in both groups to assess the correlation between Nrf2 protein levels and different LN disease states. Results: There was a significantly positive correlation between serum Nrf2 protein levels, the degree of renal injury, and systemic lupus erythematosus disease activity index (SLEDAI) scores in patients with LN. Nrf2 protein levels were higher in the LN with high-eGFR group than in the healthy control and LN with low-eGFR groups. In follow-up patients in the LN high eGFR group, Nrf2 protein levels decreased significantly after remission of disease activity. Conclusion: Nrf2 protein expression has a dual role in patients with LN. Nrf2 protein levels not only correlate with disease activity in patients with LN, but also with the degree of kidney injury. Before implementing targeted therapy for Nrf2, evaluating both Nrf2 protein expression and the disease state in patients with LN is necessary to better identify and place each patient in an appropriate patient group.

Rituximab alleviates pediatric systemic lupus erythematosus associated refractory immune thrombocytopenia: a case-based review.

A complication of pediatric systemic lupus erythematosus (pSLE) is immune thrombocytopenia (ITP). Although corticosteroids and immunoglobulins are frequently used as preliminary treatments, some patients do not respond to them. Rituximab has been reported to be safe and effective in the treatment of pSLE complicated with refractory ITP. Research is currently underway to determine the optimal rituximab dose for these individuals. We report a case of a child with SLE-associated ITP (SLE-ITP) who was successfully treated with rituximab. Rituximab is likely the most viable therapeutic option for refractory SLE-ITP. Furthermore, a comprehensive review of the relevant literature was performed and a concise overview of the pathogenesis and available treatment modalities for pediatric patients diagnosed with SLE and concurrent ITP was provided.

An overlap of IgG4-related tubulointerstitial nephritis and microscopic polyangiitis-associated glomerulonephritis: a case-based review.

Because of some similarities in organ involvement, clinical manifestations, and histopathological features, IgG4-related disease (IgG4-RD) may occur concurrently with some clinicopathologic variants of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). An overlap syndrome of IgG4-RD and AAV has recently been proposed in clinical and/or histopathological studies, indicating that there may be some potential pathophysiological associations between the two disease entities; however, the mechanisms underlying these are incompletely understood. Here, we describe a rare case of a 63-year-old man with IgG4-related tubulointerstitial nephritis (IgG4-TIN) and microscopic polyangiitis-associated glomerulonephritis (MPA-GN) overlap syndrome. The clinical diagnosis of MPA was based on the 2022 American College of Rheumatology (ACR)/European League Against Rheumatology (EULAR) classification criteria. Remission induction therapy with intravenous methylprednisolone was initiated, followed by oral prednisone maintenance therapy with gradual tapering. The patient remained asymptomatic and his renal function was essentially normalized within 3.5 months of follow-up. The serum IgG4 levels decreased to 5 g/L. We also conducted a literature review to identify clinical findings, treatment options, and outcomes of patients with concurrent IgG4-RD and MPA and briefly discussed the potential pathophysiological association between IgG4-RD and MPA. Our findings enrich the database of this rare overlap syndrome and provide a basis for the diagnosis and early intervention in both diseases. These results provide some insights for clinicians to recognize and treat this overlap syndrome.

Influence of zinc levels and Nrf2 expression in the clinical and pathological changes in patients with diabetic nephropathy.

OBJECTIVE: We investigated the correlation between zinc levels and Nrf2 expression and potential effects on the clinicopathology of patients with diabetic nephropathy (DN). METHODS: We selected 30 patients with DN, diagnosed via renal biopsy at our hospital from March 2018 to November 2019, and enrolled 30 healthy individuals from a medical examination center as the control group. Patients with DN were divided into normal-zinc and low-zinc groups. We detected the levels of zinc, copper, and Nrf2 mRNA in their serum, and collected the clinical and pathological data of DN patients. RESULTS: Serum zinc level and Nrf2 mRNA expression were significantly decreased in patients with DN compared to those of healthy people (P < 0.05). Of the 30 patients, 16 had low zinc (53.3%) and 14 had normal zinc levels (46.7%). There was no significant difference in the blood Nrf2 mRNA expression between the two groups (P > 0.05). However, the expression of Nrf2 in the kidney tissue of the low-zinc group was significantly lower compared to the normal-zinc group (P < 0.05). Diastolic blood pressure and copper levels were significantly higher in the low-zinc group (P < 0.05). In contrast, body mass index, red blood cell count, Hb level, and the ratio of zinc to copper were significantly lower in the low-zinc group (P < 0.05). The pathological classifications of the low-zinc group were more severe (P < 0.05). CONCLUSION: Patients with DN were more likely to have zinc deficiency and lower expression of Nrf2. Additionally, DN patients with zinc deficiency were prone to have more severe clinical and pathological manifestations.

SPRR3, a novel miR-338-3p target, regulates the malignant progression of clear cell renal cell carcinoma in vitro via the PI3K/Akt signaling pathway.

Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma and has a poor prognosis. However, its underlying mechanisms remain unclear. The present study aimed to evaluate the role of small proline-rich repeat protein 3 (SPRR3) in the proliferation, migration and invasion of ccRCC cells and to investigate its upstream and downstream regulatory mechanisms. Survival analysis was performed using the UALCAN website based on the The Cancer Genome Atlas database. Normal renal cell line HK-2 and ccRCC cell lines (786-O, CaKi-1 and UMRC-2) were used. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect mRNA and microRNA (miRNA) levels. Western blotting was used to detect protein levels. Cell Counting Kit-8 and colony formation assays, a wound healing assay and a Transwell invasion assay were used to assess the proliferation, migration and invasion of ccRCC cells, respectively. Transfection of overexpression plasmids and small interfering RNAs were used to upregulate and knockdown SPRR3 expression, respectively. Transfection of miRNA-mimics was used to overexpress miR-338-3p. A luciferase reporter gene assay was used to verify the predicted binding relationship between SPRR3 mRNA and miR-338-3p. The results indicated the following: i) SPRR3 was a risk factor for the survival of patients with ccRCC, and was upregulated in ccRCC cell lines; ii) SPRR3 promoted the proliferation, migration and invasion of ccRCC cells; iii) SPRR3 regulated the tumor phenotypes of ccRCC cells via the PI3K/Akt pathway; iv) miR-338-3p directly targeted SPRR3 mRNA and negatively regulated SPRR3 expression; and v) miR-338-3p inhibited the PI3K/Akt pathway and the tumor phenotypes of ccRCC cells by downregulating SPRR3. In conclusion, SPRR3, as a novel target of miR-338-3p, regulated the proliferation, migration and invasion of ccRCC cells via the PI3K/Akt pathway; this finding not only enriches our understanding of the mechanism underlying ccRCC development, but also demonstrates a potential novel therapeutic target for this disease.

Efficacy of Atorvastatin Plus Conventional Disease-Modifying Antirheumatic Drugs on Disease Activity in Rheumatoid Arthritis: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

METHODS: We queried the PubMed, Embase, Web of Science, and the CENTRAL (Cochrane Central Register of Controlled Trials) databases for this study. The pooled efficacy was evaluated using standardized mean differences. The inverse of the variance model was used for data pooling. RESULTS: Based on the search, we identified 9 randomized controlled trials. The trials included 258 patients in the atorvastatin plus DMARD groups and 246 patients in the DMARD alone groups. The primary outcome was the change from baseline in the 2018 (209:228 Disease Activity Score in 28 Joints). Based on the Disease Activity Score in 28 Joints, disease activity in RA patients decreased significantly in patients given atorvastatin plus DMARD compared with patients given DMARD alone (standardized mean difference, -2.46; 95% confidence interval, -3.98 to -0.95; p = 0.0015; I2 = 97%; p < 0.01). Subgroup analysis did not identify any confounding factors, and no publication bias was detected in the meta-analysis. CONCLUSIONS: The result supports that atorvastatin could be added to DMARDs to treat patients with RA.

Influence of Early-Onset Peritonitis on Mortality and Clinical Outcomes in ESRD Patients with Diabetes Mellitus on Peritoneal Dialysis: A Retrospective Multicenter Study.

INTRODUCTION: The impact of early-onset peritonitis (EOP) on patients with diabetes undergoing peritoneal dialysis (PD) has not been adequately addressed. We therefore sought to investigate the effects of EOP on the therapeutic response to management and long-term prognostic outcomes in patients with diabetes undergoing PD. METHODS: For this retrospective cohort study, we analyzed the data for patients with end-stage renal disease, who were also suffering from diabetes mellitus and had undergone PD between January 1, 2013, and December 31, 2018. EOP was defined as the first episode of peritoneal dialysis-related peritonitis (PDAP) occurring within 12 months of PD initiation. All patients were divided into an EOP group and a later-onset peritonitis (LOP) group. Clinical data, treatment results, and outcomes were compared between groups. RESULTS: Ultimately, 202 patients were enrolled for the analysis. Compared to the EOP group, the LOP group had more Streptococcus (p = 0.033) and Pseudomonas (p = 0.048). Patients with diabetes in the EOP group were less likely to have PDAP-related death (OR 0.13, CI: 0.02-0.82, p = 0.030). Patients with diabetes in the EOP group were more likely to have multiple episodes of PDAP and had higher rates of technical failure and poorer patient survival than those in the LOP group, as indicated by Kaplan-Meier analysis (p = 0.019, p = 0.004, and p < 0.001). In the multivariate Cox proportional hazards model, EOP was a significant predictor for multiple PDAP (HR 4.20, CI: 1.48-11.96, p = 0.007), technical failure (HR 6.37, CI: 2.21-18.38, p = 0.001), and poorer patient survival (HR 3.09, CI: 1.45-6.58, p = 0.003). CONCLUSIONS: The occurrence of EOP is significantly associated with lower rates of PDAP-related death and poorer clinical outcomes in patients with diabetes undergoing PD.

Poorer clinical outcomes of early-onset peritonitis in elderly peritoneal dialysis patients: A longitudinal and multicenter study.

INTRODUCTION: Early-onset peritonitis (EOP) is a risk factor for mortality in peritoneal dialysis (PD) patients. This study investigates the clinical features and outcomes of EOP in elderly patients. METHODS: This multicenter retrospective study evaluated 433 elderly PD patients with end-stage renal disease. The cohort was divided into nonperitonitis group (n = 239), EOP group (≤12 months, n = 109) and late-onset peritonitis (LOP) group (>12 months, n = 85). Clinical data, treatment results, and outcomes were compared between the groups. RESULTS: Compared with LOP group, there were no significant intergroup differences in the rate of primary recovery, complete cure, relapse, catheter removal, or death from PDAP (p >0.05) in the most recent PDAP episode. However, Kaplan-Meier analysis showed that patients in the EOP group were likely to have multiple episodes of PD-associated peritonitis (PDAP), technique failure, all-cause death, and composite endpoint in the long-term prognostic outcomes (p <0.001). CONCLUSIONS: EOP is significantly associated with poorer clinical outcomes in older PD patients.

Validation of the renal risk score for antineutrophil cytoplasmic antibody-associated glomerulonephritis in a Chinese population.

INTRODUCTION: In 2018, a renal risk score of antineutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (AAGN) based on estimated glomerular filtration rate (eGFR), normal glomeruli, and tubular atrophy/interstitial fibrosis (TA/IF) was proposed to predict renal outcomes. We aimed to evaluate this renal risk score in a myeloperoxidase (MPO)-ANCA predominant population in Northeast China. METHODS: We retrospectively analyzed the clinicopathologic data of 65 patients biopsy-proven from a Chinese medical center. Each patient was assessed by eGFR, normal glomeruli, and TA/IF, and the renal outcome was evaluated using the renal risk score. RESULTS: In our study, 95.4% of patients were ANCA positive (78.5% MPO-ANCA positive and 16.9% proteinase 3-ANCA positive). The average follow-up period was 14.3 months. Thirty-four patients (52.3%) reached end-stage renal disease (ESRD). Based on the renal risk score, 8 (12.3%), 31 (47.7%), and 26 (40%) patients were divided into the low-risk, medium-risk, and high-risk groups, respectively. Kaplan-Meier survival curves revealed the high-risk group had worse renal outcomes than the low-risk group (p<0.01) and the medium-risk group (p<0.01), but the renal outcome did not differ between the low-risk and medium-risk groups (p>0.017). Similar results were obtained by the competitive survival analysis. The AUC for 3-year overall ESRD predictions was 0.845. In the regression analysis, the renal risk score was a favorable predictor for the development of ESRD (HR 3.13, 95%CI 1.58-6.19, p=0.001). CONCLUSION: The renal risk score is a preferred index that can predict ESRD in Chinese AAGN patients, especially in the high-risk group with worse renal outcomes. Key Points • The eGFR and percentage of normal glomeruli were valuable predictors of renal outcome, whereas TA/IF was not. • We confirmed the renal risk score is a preferred index that can predict ESRD in Chinese AAGN patients. • Based on the renal risk score, the high-risk group had worse renal outcomes than the low-risk group and the medium-risk group.

Detection of microRNA-33a-5p in serum, urine and renal tissue of patients with IgA nephropathy.

The present study aimed to detect the levels of microRNA (miR)-33a-5p in the renal tissue, serum and urine of patients with primary IgA nephropathy (IgAN), thereby preliminarily exploring the association between the levels of miR-33a-5p and the condition of primary IgAN to provide evidence for the expression of miR-33a-5p in the serum and urine of IgAN patients as a clinical marker. Reverse-transcription quantitative PCR was performed to evaluate the level of miR-33a-5p in IgAN patients according to severity and pathological classification. The results suggested that the levels of miR-33a-5p in the serum, urine and kidney tissues of patients with IgAN were lower than those of the control tissues obtained from cancer patients (0.28±0.25 vs. 1.00±0.45, P<0.05; 0.34±0.28 vs. 1.00±0.53, P<0.05; 0.47±0.27 vs. 1.00±0.38, P<0.05, respectively). Receiver operating characteristic curve analysis suggested that the serum and urine levels of miR-33a-5p may be used as a marker to differentiate renal injury in IgAN patients from healthy individuals. At the same time, according to the estimated glomerular filtration rate (eGFR) and Lee classification of nephropathy, it was determined that with the progression of renal failure and the increase of the pathological grade of kidney tissue, the relative level of miR-33a-5p in kidney tissue also decreased (eGFR <50 ml/min vs. eGFR ≥50 ml/min/1.73 m2 group: 0.38±0.27 vs. 1.00±0.34, P<0.001; Lee grade ≤3 group vs. Lee grade >3: 1.00±0.48 vs. 0.38±0.45, P<0.05). This result suggested that the levels of miR-33a-5p in serum, urine and kidney tissues decreased with the severity of renal injury and the progression of renal failure in patients with IgAN. Hence, miR-33a-5p detected in the serum and urine may be used as a non-invasive biomarker to reflect the progression of renal injury and renal failure in patients with IgAN.

Telmisartan alleviates collagen type III glomerulopathy: A case report with literature review.

Collagen type III is commonly detected in the renal interstitium and vasculature; however, it is absent in healthy glomeruli. Deposition of collagen type III in the glomerular mesangium and capillary basement membranes may arise in two rare diseases, namely collagen type III glomerulopathy (CG) and nail patella syndrome. CG is a rare glomerular disease with no specific treatment, although supportive measures for control of hypertension and edema may help to relieve symptoms. With progression to end-stage renal disease, patients with CG may come to require dialysis and/or renal transplantation. The present study reported on a 59-year-old male who was diagnosed with CG nephrotic syndrome by immunohistochemical and electron microscopic examination of biopsy material. To the best of our knowledge, this is the first case reported in northeastern China. The angiotensin II blocker telmisartan was successfully used to alleviate renal symptoms and a literature review was performed. The present case supports the use of telmisartan as a first choice of treatment for CG.

Myeloid-Derived Suppressor Cells Promote the Progression of Primary Membranous Nephropathy by Enhancing Th17 Response.

Several studies have confirmed that the myeloid-derived suppressor cells (MDSCs) are closely associated with autoimmune diseases, but their exact role in these processes remains largely unclear. Here, we investigated the role MDSCs in patients with primary membranous nephropathy (PMN). Compared to healthy controls (HCs), PMN patients showed significantly increased number of HLA-DR-CD11b+CD33+ MDSCs in the peripheral blood, including both CD14+CD66b- monocytic and CD14-CD66b+ granulocytic MDSCs. The frequency of MDSCs was positively correlated with the level of serum anti-phospholipase A2 receptor (anti-PLA2R), 24-h urine protein quantification, and disease activity in PMN patients. Consistently, enhanced T helper 2 (Th2) and T helper 17 (Th17) immune responses were positively associated with plasma anti-PLA2R levels, 24-h urine protein quantification, and the disease activity in PMN patients. Moreover, compared to HCs, MDSCs from PMN patients exhibited significantly elevated arginase-1 (ARG-1) production and increased potential to promote Th17 differentiation in vitro in an ARG-1-dependent manner. This study directly demonstrates a pathogenic role for MDSCs in human PMN and provides a molecular mechanism for the pathogenesis of PMN. Our data show that MDSCs may promote PMN disease progression mainly by enhancing Th17 response. Therefore, MDSCs may be an important diagnostic, therapeutic, and prognostic marker for PMN diseases.

12-Lipoxygenase as a key pharmacological target in the pathogenesis of diabetic nephropathy.

The characteristic features of diabetic nephropathy include thickening of the glomerular basement membranes, expansion of mesangium, and appearance of albumin in the urine (microalbuminuria and macroalbuminuria). Experimental studies have documented that 12-lipoxygenase (12-LOX) and its metabolite 12(S)-hydroxyeicosatetraenoic acid (HETE) play an important role in the pathogenesis of diabetic nephropathy. 12(S)-HETE may work in association with angiotensin II and transforming growth factor- ß (TGF-ß) reciprocally to induce fibrotic changes in the diabetic kidneys. The fibrotic actions of angiotensin II on the kidneys are mediated indirectly through an increase in the synthesis of 12(S)-HETE. Conversely, 12(S)-HETE may also enhance the actions of angiotensin II by upregulating the expression of AT1 receptors on the glomerulus, mesangium, and podocytes. 12(S)-HETE may also cross-talk with TGF-ß in a reciprocal manner to induce the fibrotic changes in the diabetic kidney. 12(S)-HETE-triggered signaling pathways may involve activation of p38 mitogen-activated protein (p38MAP) kinase, increase in cAMP-responsive element-binding protein (CREB) transcriptional activity, epigenetic changes involving histone methylation through an increase in histone methyltransferase activity along with an upregulation of cyclin-kinase inhibitors including, p16, p21, and p27. The present review discusses the role of 12-LOX in the pathogenesis of diabetic nephropathy along with the possible mechanisms.

How Can I Manage Thrombocytopenia in Hemodialysis Patient? A Review.

Hemodialysis (HD) is the most important treatment for patients with end-stage renal disease (ESRD). Thrombocytopenia is a potential treatment complication related to dialysis. Under normal circumstances, the platelet count would slightly decrease within the first hour of HD, but get restored towards the end of procedure. In most patients, the platelet count can be maintained within the normal range, and the occurrence of thrombocytopenia is relatively rare in clinical practice. Therefore, the possibility of thrombocytopenia in HD patients is often ignored. Moreover, thrombocytopenia might be misdiagnosed and mistreated. At present, almost all articles on the subject, apart from some case reports, focus on pseudothrombocytopenia and heparin-induced thrombocytopenia. In this review, we summarized various underlying causes, mechanisms, and diagnostic approaches to thrombocytopenia in HD patients. The review aims to provide a guide for clinicians interested in the causes and adequate treatment of thrombocytopenia.

Protective or deleterious role of Wnt/beta-catenin signaling in diabetic nephropathy: An unresolved issue.

In recent years, the Wnt/ß-catenin signaling has gained tremendous attention due to its ability to modulate a number of diseases including diabetic nephropathy. Studies have shown that there is decrease in the secretion of Wnt proteins including Wnt4, 5a and Wnt 6 during high glucose concentration or diabetic conditions, which leads to decreased translocation of ß-catenin to nucleus. The down-regulation of Wnt/ß-catenin signaling leads to detrimental effects on kidney including increased apoptosis of mesangial cells and increased deposition of fibrous tissue in mesangium. The pharmacological modulators such as spironolactone, NO donor and antioxidant are shown to produce beneficial effects in diabetic nephropathy by up regulating the expression of Wnt proteins and activation of diabetes-induced suppressed Wnt/ß-catenin signaling. On the other hand, it is documented that diabetes leads to overactivation of Wnt1/ß-catenin signaling, which promotes podocyte injury, induce epithelial-mesenchymal transition of podocytes along with renal injury and fibrosis. Accordingly, different interventions aimed to suppress overactivated Wnt/ß-catenin signaling are reported to improve the condition and symptoms associated with diabetic nephropathy. The present review discusses the dual role of Wnt/beta-catenin signaling in the pathogenesis of diabetic nephropathy.

Hepatitis C virus-associated cryoglobulinemia with membrano-proliferative glomerulonephritis treated with prednisolone and interferon: A case report.

Hepatitis C virus (HCV) is a major cause of liver-associated morbidity and has an increasing prevalence worldwide. Hepatitis C virus infection may lead to chronic hepatitis, cirrhosis and liver failure. However, it is also associated with a wide range of extra-hepatic complications, such as cryoglobulinemia, an immune complex disease associated with cryoglobulin leading to multiple organ damage and, while the major symptom is vasculitis. The present study reported on a-58-year-old woman who was diagnosed with HCV-associated cryoglobulinemia with skin, kidney and blood system damage and biopsy-proven cryoglobulinemia membrano-proliferative glomerulonephritis. HCV RNA clearance occurred within a few weeks of interferon treatment and the patient was then treated by prednisolone and sustained interferon. While the therapeutic effect was obvious at first, the disease reappeared in combination with refractory infection and multiple organ failure, and the patient finally died. HCV-associated cryoglobulinemia is uncommon in developing countries such as China, while treatment guidelines remain to be established, particularly if complex complications are present.

Involvement of Histone Lysine Methylation in p21 Gene Expression in Rat Kidney In Vivo and Rat Mesangial Cells In Vitro under Diabetic Conditions.

Diabetic nephropathy (DN), a common complication associated with type 1 and type 2 diabetes mellitus (DM), characterized by glomerular mesangial expansion, inflammation, accumulation of extracellular matrix (ECM) protein, and hypertrophy, is the major cause of end-stage renal disease (ESRD). Increasing evidence suggested that p21-dependent glomerular and mesangial cell (MC) hypertrophy play key roles in the pathogenesis of DN. Recently, posttranscriptional modifications (PTMs) have uncovered novel molecular mechanisms involved in DN. However, precise regulatory mechanism of histone lysine methylation (HKme) mediating p21 related hypertrophy associated with DN is not clear. We evaluated the roles of HKme and histone methyltransferase (HMT) SET7/9 in p21 gene expression in glomeruli of diabetic rats and in high glucose- (HG-) treated rat mesangial cells (RMCs). p21 gene expression was upregulated in diabetic rats glomeruli; chromatin immunoprecipitation (ChIP) assays showed decreased histone H3-lysine9-dimethylation (H3K9me2) accompanied with enhanced histone H3-lysine4-methylation (H3K4me1/3) and SET7/9 occupancies at the p21 promoter. HG-treated RMCs exhibited increased p21 mRNA, H3K4me level, SET7/9 recruitment, and inverse H3K9me, which were reversed by TGF-ß1 antibody. These data uncovered key roles of H3Kme and SET7/9 responsible for p21 gene expression in vivo and in vitro under diabetic conditions and confirmed preventive effect of TGF-ß1 antibody on DN.

Clinicopathological characteristics of non-diabetic renal disease in patients with type 2 diabetes mellitus in a northeastern Chinese medical center: a retrospective analysis of 273 cases.

OBJECTIVE: To investigate the clinical and histopathological features of non-diabetic renal disease (NDRD) superimposed on diabetic nephropathy (DN) in northeastern Chinese patients with type 2 diabetes mellitus (T2D), and compare the changes with those of pure DN and isolated NDRD. METHODS: Single-center retrospective analysis based on medical records of 273 patients (172 men, mean age: 51.1 ± 12.4 years) with T2D who underwent renal biopsy between February 2000 and October 2015. All patients were diagnosed as cases of pure DN, isolated NDRD or NDRD superimposed on DN. RESULTS: Out of the 273 T2D patients, 68 (24.9 %) had DN, 175 (64.1 %) had NDRD, and 30 (11.0 %) had NDRD superimposed on DN. Idiopathic membranous nephropathy (IMN, 29.7 %) was the most common NDRD followed by IgA nephropathy (IgAN, 22.9 %), and hypertensive renal arteriolar sclerosis was the most common lesion in patients diagnosed as NDRD superimposed on DN. Patients with NDRD had a shorter duration of diabetes and lower frequencies of diabetic retinopathy (DR, 6.9 %) and renal failure (28.0 %), which is consistent with higher estimated glomerular filtration rates (eGFR) and lower systolic blood pressure (SBP). No significant between-group differences were observed with respect to proteinuria and hematuria. CONCLUSION: Renal biopsy is strongly recommended for T2D patients to distinguish DN, NDRD and NDRD superimposed on DN, especially in patients with no signs of DR. This approach may help in early diagnosis and treatment of NDRD and improve renal outcomes in northeastern Chinese T2D patients.

Histone Lysine Methylation in TGF-ß1 Mediated p21 Gene Expression in Rat Mesangial Cells.

Transforming growth factor beta1- (TGF-ß1-) induced p21-dependent mesangial cell (MC) hypertrophy plays a key role in the pathogenesis of chronic renal diseases including diabetic nephropathy (DN). Increasing evidence demonstrated the role of posttranscriptional modifications (PTMs) in the event; however, the precise regulatory mechanism of histone lysine methylation remains largely unknown. Here, we examined the roles of both histone H3 lysine 4 and lysine 9 methylations (H3K4me/H3K9me) in TGF-ß1 induced p21 gene expression in rat mesangial cells (RMCs). Our results indicated that TGF-ß1 upregulated the expression of p21 gene in RMCs, which was positively correlated with the increased chromatin marks associated with active genes (H3K4me1/H3K4me2/H3K4me3) and negatively correlated with the decreased levels of repressive marks (H3K9me2/H3K9me3) at p21 gene promoter. TGF-ß1 also elevated the recruitment of the H3K4 methyltransferase (HMT) SET7/9 to the p21 gene promoter. SET7/9 gene silencing with small interfering RNAs (siRNAs) significantly abolished the TGF-ß1 induced p21 gene expression. Taken together, these results reveal the key role of histone H3Kme in TGF-ß1 mediated p21 gene expression in RMC, partly through HMT SET7/9 occupancy, suggesting H3Kme and SET7/9 may be potential renoprotective agents in managing chronic renal diseases.

Engineering phosphopeptide-decorated magnetic nanoparticles as efficient photothermal agents for solid tumor therapy.

Due to the high therapeutic efficiency and minimum damage towards normal tissues, phototherapy has drawn a great deal of attention in recent decades. Herein, we reported the synthesis of novel phosphopeptide-decorated magnetic nanoparticles (peptide-Fe3O4 nanoparticles), and their usages in photothermal therapy against solid tumor. By using a classical coprecipitation method and a facile ligand exchange route, these peptide-Fe3O4 nanoparticles were prepared with inexpensive inhesion. Upon the irradiation of a near-infrared (NIR) light, these nanoagents exhibited great photothermal effect with high photo-stability. In vitro biocompatibility studies of these peptide-Fe3O4 nanoparticles indicated their low cytotoxicity, negligible hemolysis, and no effect on blood coagulation. As expected, 4T1 murine breast cancer cells could be effectively damaged by these light-mediated nanoagents. Significantly, animal experiments demonstrated that these nanoagents held great solid tumor ablation effect with the assistance of a NIR laser irradiation. Additional studies focused on the long-term toxicity of these nanoagents indicated their high bio-compatibility. Thus, these peptide-Fe3O4 nanoparticles could bring more opportunities to a new generation of photothermal agents in the field of biomedicine.