Novel ferroptosis gene biomarkers and immune infiltration profiles in diabetic kidney disease via bioinformatics.

Diabetic kidney disease (DKD) is the primary cause of end-stage renal disease, exhibiting high disability and mortality rates. Ferroptosis is vital for the progression of DKD, but the exact mechanism remains unclear. This study aimed to explore the potential mechanism of ferroptosis-related genes in DKD and their relationship with the immune and to identify new diagnostic biomarkers to help treat and diagnose DKD. GSE30122 and GSE47185 were obtained from the Gene Expression Omnibus database and were integrated into a merged dataset, followed by functional enrichment analysis. Then potential differentially expressed genes were screened. Ferroptosis-related differentially-expressed genes were identified, followed by gene ontology analysis. Protein-protein interaction networks were constructed and hub genes were screened. The immune cell-infiltrating state in the dataset was assessed using appropriate algorithms. Immune signature subtypes were constructed using the consensus clustering analysis. Hub gene expression was validated using qRT-PCR and immunohistochemistry. A total of Eleven screened ferroptosis-related differentially expressed genes were screened. Six potentially diagnostically favorable ferroptosis-related hub genes were identified. Significantly increased expression of γδT cells, resting mast cells, and macrophages infiltration was observed in the DKD group. Additionally, two distinct immune signature subgroups were identified. Ferroptosis-related hub genes were significantly correlated with differentially infiltrated immune cells. Six hub genes were significantly upregulated in HK-2 cells following high glucose treatment and in human kidney tissues of patients with DKD. Six ferroptosis-related hub genes were identified as potential biomarkers of diabetic kidney disease, but further validation is needed.

Significance of pyroptosis-related genes in the diagnosis and classification of diabetic kidney disease.

OBJECTIVE: This study aimed to identify the potential biomarkers associated with pyroptosis in diabetic kidney disease (DKD). METHODS: Three datasets from the Gene Expression Omnibus (GEO) were downloaded and merged into an integrated dataset. Differentially expressed genes (DEGs) were filtered and intersected with pyroptosis-related genes (PRGs). Pyroptosis-related DEGs (PRDEGs) were obtained and analyzed using functional enrichment analysis. Random forest, Least Absolute Shrinkage and Selection Operator, and logistic regression analyses were used to select the features of PRDEGs. These feature genes were used to build a diagnostic prediction model, identify the subtypes of the disease, and analyze their interactions with transcription factors (TFs)/miRNAs/drugs and small molecules. We conducted a comparative analysis of immune cell infiltration at different risk levels of pyroptosis. qRT-PCR was used to validate the expression of the feature genes. RESULTS: A total of 25 PRDEGs were obtained. These genes were coenriched in biological processes and pathways, such as the regulation of inflammatory responses. Five key genes (CASP1, CITED2, HTRA1, PTGS2, S100A12) were identified and verified using qRT-PCR. The diagnostic model based on key genes has a good diagnostic prediction ability. Five key genes interacted with TFs and miRNAs in 67 and 80 pairs, respectively, and interacted with 113 types of drugs or molecules. Immune infiltration of samples with different pyroptosis risk levels showed significant differences. Thus, CASP1, CITED2, HTRA1, PTGS2 and S100A12 are potential DKD biomarkers. CONCLUSION: Genes that regulate pyroptosis can be used as predictors of DKD. Early diagnosis of DKD can aid in its effective treatment.

Association of Circulating Trimethylamine-N Oxide With Malnutrition and the Risk of Coronary Artery Disease in Patients With Maintenance Hemodialysis.

OBJECTIVES: Malnutrition is a serious complication frequently observed in dialysis patients. Therefore, nutrition status evaluation and the early identification of malnutrition are clinically important. Trimethylamine N-oxide (TMAO) is reportedly associated with deteriorating metabolic profiles and cardiovascular diseases. The aim of our study was to investigate correlations between circulating TMAO levels and malnutrition and the risk of major adverse cardiovascular events in patients on maintenance hemodialysis. METHODS: This retrospective observational study involved 228 subjects. Fasting plasma TMAO levels were detected using liquid chromatography-tandem mass spectrometry. RESULTS: TMAO levels were significantly elevated in patients with malnutrition (8728.78 ± 704.12 ng/mL) when compared with those without (6532.1 ± 570.41 ng/mL, P < .01). TMAO levels were positively correlated with Subjective Global Assessment scores (ρ = 0.56, P = .02) and were independent risk factors for malnutrition after adjustment for multiple traditional risk factors (odds ratio = 2.07, 95% confidence interval: 1.41-3.62, P < .01). Furthermore, TMAO levels were good predictors of major adverse cardiovascular events in a 2-year follow-up period (area under the curve = 0.68, P < .01) and accuracy was increased to 74% when TMAO levels were combined with Subjective Global Assessment scores (area under the curve = 0.74, P = .02). CONCLUSIONS: Elevated TMAO levels were independently associated with a risk of malnutrition and cardiovascular disease, and could be a useful predictive biomarker for risk stratification and cardiovascular disease management for patients on dialysis.

Identification and functional analysis of a novel phospholipase D2 gene mutation associated with familial systemic lupus erythematosus. / ä¸Žå®¶æ—æ€§ç³»ç»Ÿæ€§çº¢æ–‘ç‹¼ç–®æœ‰å ³çš„PLD2åŸºå› æ–°çªå˜åŠå ¶åŠŸèƒ½åˆ†æž.

OBJECTIVES: Systemic lupus erythematosus (SLE) is a kind of autoimmune inflammatory connective tissue disease which seriously endangers human health. Genetic factors play a key role in the pathogenesis of SLE. This study aims to investigate a novel phospholipase D2 (PLD2) mutation associated with familial SLE, and further explore the underlying mechanism of the mutation in SLE. METHODS: The blood samples from a SLE patient, the patient's parents, and 147 normal controls were collected and DNA was extracted. Whole genome high-throughput sequencing was performed in the patient and her parents and the results were further analyzed by various bioinformatics methods. The wild type (wt), mutant type (mu), and negative control PLD2 plasmids were further constructed and transfected into 293 cells. The expression level of HRAS protein in 293 cells was detected by Western blotting. RESULTS: In this SLE family, the female SLE patient and her mother, 1 in generation II and 1 in generation III had typical clinical manifestations of SLE, and all of them had lupus nephritis at early stage. The genetic characteristics are consistent with autosomal dominant inheritance. A novel PLD2 heterozygous mutation (c.2722C>T) was found in the patient and her mother, but not in her father and other normal controls. Compared with wtPLD2 plasmid and negative control PLD2 plasmid, the expression of HRAS in 293 cells transfected with muPLD2 plasmid was significantly up-regulated (both P<0.05). CONCLUSIONS: PLD2 c.2722C>T mutation may be one of the pathogeny of SLE in this family.

MicroRNA-302c modulates peritoneal dialysis-associated fibrosis by targeting connective tissue growth factor.

Long-term peritoneal dialysis (PD) can lead to the induction of mesothelial/epithelial-mesenchymal transition (MMT/EMT) and fibrosis; these effects eventually result in ultrafiltration failure and the discontinuation of PD. MicroRNA-302c (miR-302c) is believed to be involved in regulating tumour cell growth and metastasis by suppressing MMT, but the effect of miR-302c on MMT in the context of PD is unknown. MiR-302c levels were measured in mesothelial cells isolated from the PD effluents of continuous ambulatory peritoneal dialysis patients. After miR-302c overexpression using lentivirus, human peritoneal mesothelial cell line (HMrSV5) and PD mouse peritoneum were treated with TGF-ß1 or high glucose peritoneal dialysate respectively. MiR-302c expression level and MMT-related factors alteration were observed. In addition, fibrosis of PD mouse peritoneum was alleviated by miR-302c overexpression. Furthermore, the expression of connective tissue growth factor (CTGF) was negatively related by miR-302c, and LV-miR-302c reversed the up-regulation of CTGF induced by TGF-ß1. These data suggest that there is a novel TGF-ß1/miR-302c/CTGF pathway that plays a significant role in the process of MMT and fibrosis during PD. MiR-302c might be a potential biomarker for peritoneal fibrosis and a novel therapeutic target for protection against peritoneal fibrosis in PD patients.

Efficacy of adefovir dipivoxil combined with a corticosteroid in 38 cases of nephrotic syndrome induced by hepatitis B virus-associated glomerulonephritis.

OBJECTIVE: To investigate the treatment efficacy of adefovir dipivoxil combined with a corticosteroid on hepatitis B virus-associated glomerulonephritis (HBV-GN). METHODS: A total of 38 patients with nephrotic syndrome induced by HBV-GN were treated for 36 weeks between 2010 and 2012. RESULTS: The efficacy analysis showed that 11 patients achieved complete remission and 17 patients achieved partial remission, and the effective remission rate was 73.7%. In addition, 10 patients achieved no remission. CONCLUSIONS: Adefovir dipivoxil combined with corticosteroids has a certain efficacy on the HBV-GN and displays few adverse reactions. A large sample, randomized double-blind controlled study and long-term follow-up are needed to verify the efficacy of adefovir dipivoxil combined with corticosteroids.

Exploring the Effect of Dapagliflozin on Alcoholic Kidney Injury and Renal Interstitial Fibrosis in Rats Based on TIMP-1/MMP-24 Pathway.

OBJECTIVE: To establish a rat model of alcoholic kidney injury and detect the expression of TIMP-1/MMP-24 in the kidneys of rats with alcoholic kidney injury at the molecular pathological level, so as to explore the mechanism of alcohol abuse leading to kidney injury and renal interstitial fibrosis as well as the alleviation of alcohol-induced kidney injury and inhibition of renal interstitial fibrosis by dapagliflozin. METHODS: 48 male rats were randomly divided into 4 groups: control group, alcohol group, alcohol + dapagliflozin group, and alcohol + losartan group, each with 12 rats. Different drugs were administered by gavage for modeling and treatment. Six days later, the rats were sacrificed, blood was collected from the heart to separate the serum, and the blood creatinine (Scr) and urea nitrogen (BUN) contents were detected biochemically. After blood collection, the kidney tissue was taken and fixed in10% neutral formalin. The expression of renal tissue inflammatory factors (CRP, IL-6, and TNF-α) and renal fibrosis indexes (LN, HA, and TGF-ß1) were detected; MMP-24 and TIMP-1 in the kidney tissue of rats in different treatment groups were detected, and Smad3 expression was also detected. RESULTS: After treatment, the general condition of the alcohol + dapagliflozin group and the alcohol + losartan group improved to different degrees. The weight first decreased and then gradually increased over time. There was no statistical difference in the weight change between the two groups; Compared with the control group, the Scr level, BUN content, renal index, inflammatory factors, and renal fibrosis indexes in the alcohol group were significantly increased (P < 0.05); after 6 weeks of treatment, in the alcohol + dapagliflozin group and alcohol + losartan group, Scr level, BUN content, kidney index, inflammatory factors, and renal fibrosis indexes were significantly decreased (P < 0.05); the expression of MMP-24 in the kidney tissue of the control group was upregulated, and the expression of TIMP-1 and Smad3 was downregulated; MMP-24 expression was downregulated, and TIMP-1 and Smad3 expression was significantly upregulated (P < 0.05) in the rats of the alcohol group. After dapagliflozin and losartan treatment, MMP-24 expression gradually increased and TIMP-1 and Smad3 expression gradually decreased (P < 0.05). CONCLUSION: Long-term large-scale alcohol intake can cause kidney tissue damage and fibrotic lesions. The expression of fibrotic cytokines such as TIMP-1 and Smad3 will increase, and the expression of MMP-24 will be decreased. However, dapagliflozin and losartan have certain therapeutic effects on the abovementioned lesions. The mechanism may be downregulating TIMP-1 and Smad3 and upregulating the expression of MMP-24 and other cytokines in the kidney.

Successful treatment of tuberculosis combined with drug-induced myopathy using corticosteroid therapy: a case report.

A 39-year-old woman was admitted to our hospital on 19 January 2019 because of a 10-day history of intolerance to oils in her food, fatigue, and yellowing of the skin and sclera. In December 2018, the patient had been diagnosed with tuberculous pleurisy at a local hospital and received quadruple anti-tuberculosis treatment. Ten days before presentation to our hospital, she had developed anorexia, fatigue, nausea, loss of appetite, cough, and shortness of breath. She visited a local hospital, where she was considered to have drug-induced hepatitis. She discontinued the anti-tuberculosis drugs and liver protection treatment. After 3 days, her symptoms had not substantially improved. She visited the infection department of our hospital for further diagnosis and treatment. After 6 days of treatment, the patient's symptoms were not significantly improved, her liver and muscle enzyme concentrations were further increased, and her limbs had become weaker and more difficult to move. We considered diagnoses of drug-induced hepatitis and drug-induced myopathy. The patient was treated with intravenous methylprednisolone at 40 mg once a day for 16 days and other symptomatic treatments. Her symptoms significantly improved and she was discharged.

A bibliometric analysis of the 100 most influential papers on peritoneal dialysis.

BACKGROUND: We aimed to identify the 100 most cited articles published on peritoneal dialysis (PD) and analyze their characteristics to provide information on the achievements and developments of PD research over the past decades. METHODS: The Science Citation Index Expanded (SCIE) in the Web of Science Core Collection was comprehensively searched from 2000 to 2018, using the keywords "Peritoneal dialysis" or "Dialyses, Peritoneal" or "Dialysis, Peritoneal" or "Peritoneal Dialyses". The top 100 cited articles were retrieved by reading titles and abstracts. Significant information was further elicited, including the authors, journals, countries, institutions, and publication year. RESULTS: The United States was the most productive country (n = 51), Li Pkt published the highest number of papers (n = 7), the Journal of the American Society of Nephrology produced the highest number of contributions (n = 28), and Baxter International Inc., the University of California System, and the University of Toronto were the institutions with the highest number of articles (n = 10). CONCLUSIONS: This is the first bibliometric study to identify the most influential papers in PD research. This report describes the major changes and advances in research regarding PD as a guide for writing a citable article.