Silymarin and MSC-exosomes ameliorate thioacetamide-evoked renal fibrosis by inhibiting TGF-ß/SMAD pathway in rats.

BACKGROUND: TGF-ß1 and SMAD3 are particularly pathogenic in the progression of renal fibrosis. AIM: This study aimed to evaluate the kidney protective potentials of silymarin (SM) and exosomes of mesenchymal stem cells against the nephrotoxin thioacetamide (TAA) in rats. METHODS: 32 female rats were randomly assigned into four groups: the control group, the TAA group, the TAA + SM group, and the TAA + Exosomes group. The kidney homogenates from all groups were examined for expression levels of TGF-ß receptors I and II using real-time PCR, expression levels of collagen type I and CTGF proteins using ELISA, and the expression levels of nuclear SMAD2/3/4, cytoplasmic SMAD2/3, and cytoplasmic SMAD4 proteins using the western blot technique. RESULTS: Compared to the control group, the injection of TAA resulted in a significant increase in serum levels of urea and creatinine, gene expression levels of TßRI and TßRII, protein expression levels of both collagen I and CTGF proteins, cytoplasmic SMAD2/3 complex, and nuclear SMAD2/3/4 (p-value < 0.0001), with significantly decreased levels of the co-SMAD partner, SMAD4 (p-value < 0.0001). Those effects were reversed considerably in both treatment groups, with the superiority of the exosomal treatment regarding the SMAD proteins and the expression levels of the TßRI gene, collagen I, and CTGF proteins returning to near-control values (p-value > 0.05). CONCLUSION: Using in vitro and in vivo experimental approaches, the research discovered a reno-protective role of silymarin and exosomes of BM-MSCs after thioacetamide-induced renal fibrosis in rats, with the advantage of exosomes.

Serum long noncoding RNA H19/micro RNA-675-5p axis as a probable diagnostic biomarker in inflammatory bowel disease.

BACKGROUND: A significant body of research strengthens the starring role of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the pathogenesis of inflammatory bowel disease (IBD). Here, we investigated the diagnostic utility of lncRNA H19 and miRNA-675-5p in IBD. METHODS: This study included 97 participants, thirty-five ulcerative colitis patients, thirty-two Crohn's disease patients, and thirty IBD-free controls. History, staging, laboratory investigations, and colonoscopy were performed. Also, quantitative real-time PCR (qPCR) for revealing of lncRNA H19 and miRNA-675-5p was done. RESULTS: The estimated serum levels for H19 and miRNA-675-5p in the UC and CD groups in comparison to the control group showed a high statistical difference (P = 0.0001 for each parameter). Based upon the severity of UC patients, both biomarkers showed significantly higher values between remission and moderate cases, with p-values 0.022 and 0.02, respectively. Meanwhile, in CD patients, both biomarkers revealed no statistical significance between remission and any active stage of the disease. Additionally, ROC analysis revealed that H19 could discriminate between UC and control subjects with 94.3% sensitivity and 90.0% specificity, and with 87.5% sensitivity, and 88.5% specificity in the CD group. Furthermore, miR-675-5p was able to discriminate between UC and control subjects with 85.7% sensitivity and 97.3% specificity and with 88.4% sensitivity, 95.2% specificity in the CD group. Logistic regression found a significant predictive utility of using miR-675-5p and H19 in IBD. CONCLUSION: H19 and miRNA-675-5p can be used as diagnostic biomarkers in IBD, with superiority in UC patients with moderate activity.