[Pathogenesis of ferroptosis on chronic kidney disease and traditional Chinese medicine intervention: a review].

Chronic kidney disease(CKD) is an insidious disease that has become a significant global public health issue due to its high incidence rate, low awareness, low diagnostic rate, poor prognosis, and high medical costs. Recent studies have shown that CKD development is associated with varying degrees of ferroptosis features. Traditional Chinese medicine(TCM) can regulate iron metabolism, lipid peroxidation, antioxidant systems to inhibit ferroptosis and delay the progression of CKD. Consequently, the intervention mechanism of ferroptosis has become one of the focuses of CKD research. TCM has thousands of years of traditional experience and wisdom. It focuses on the overall regulation of human body functions and can stimulate the body's disease resistance and recovery capabilities, which has certain advantages in treating CKD. However, there is currently a lack of comprehensive articles on the application of TCM in intervening ferroptosis to treat CKD and the pathogenesis of ferroptosis in CKD. Therefore, this article summarizes the latest research progress both domestically and internationally, briefly introduces the main mechanisms of ferroptosis, and systematically reviews the relationship between ferroptosis and CKD. The article integrates TCM theories related to ferroptosis in CKD, including "deficiency" "stasis" "phlegm turbidity" and "toxins" and summarizes the research status of active ingredients and herbal formulas in intervening ferroptosis to treat CKD. By considering ferroptosis from a new perspective, this article aims to provide new targets and directions for the application of TCM in treating CKD.

[Electroacupuncture Relieves Visceral Hypersensitivity by Down-regulating Mast Cell Number，PAR-2/TRPV 1 Signaling, etc. in Colonic Tissue of Rats with Irritable Bowel Syndrome].

OBJECTIVE: To observe the effect of electroacupuncture (EA) stimulation of "Shangjuxu" (ST 37, Lower Confluent point) and "Tianshu" (ST 25, Front-Mu point) on visceral pain and expression of colonic tryptase(Try), proteinase-activated receptor 2(PAR-2)，transient receptor potential channel vanilloid subfamily member 1 (TPRV 1)，substance P (SP) and calcitonin gene-related peptide (CGRP) in rats with irritable bowel syndrome (IBS), so as to explore its mechanisms underlying improvement of IBS. METHODS: Forty male Sprague Dawley rats were equally randomized into normal control (control), model, medication and EA groups (n＝10 in each). The IBS model was established by chronic acute combining stress (CACS, water deprivation, fasting, tail clamping, forced swimming in ice water, restraint, etc.) for 21 days. Rats of the medication group were treated by gavage of Pinaverium Bromide (1 mg/mL, 15 mg/kg), once daily for 14 d. EA (10 Hz/50 Hz, 0.2－0.3 mA) was applied to bilateral ST 37 and ST 25 for 30 min, once daily for 14 d. The muscular withdrawal reflex (AWR) of both abdomen and buttock was detected by colorectal distension (CRD) with a water-filled balloon for examining the visceral hypersensitivity. The number of mast cells in the colonic tissue was counted after toluidine blue stain. The immunoactivity of colonic Try was determined by immunochemistry and the expression of colonic PAR-2, TRVP 1, SP and CGRP proteins detected by Western blot. RESULTS: After modeling, the body weight was significantly decreased in IBS rats of the model, medication and EA groups compared with their own individual pre-treatment and with the control group (P<0.01), and markedly higher in both medication and EA groups than in the model group (P<0.05, P<0.01). The intra-colonic volume thresholds for inducing abdominal and hip AWR were significantly lower in the model group than in the normal control group (P<0.01), and obviously higher in both medication and EA groups than in the model group (P<0.05，P<0.01). The AWR scores of intra-colorectal balloon at volumes of 0.5, 1.0 and 1.5 mL of water were significantly higher in the model group than in the control group (P<0.01), and considerably lower in the EA and medication groups than in the model group (P<0.01). The number of colonic MC and the expression levels of colonic Try, PAR-2, TRPV 1, SP and CGRP proteins were significantly higher in the model group than in the control group (P<0.01), and obviously decreased in both medication and EA groups relevant to the model group (P<0.01). Comparison between the medication and EA groups showed that the decreased expression levels of colonic PAR-2, TRPV 1, SP and CGRP proteins were significantly lower in the EA group than in the medication group (P<0.05), but no significant differences were found between the two groups in intra-colonic volumes for inducing AWR, AWR scores, body weight, and colonic MC number and Try immunoactivity levels (P>0.05)．. CONCLUSION: EA of ST 37 and ST 25 can relieve visceral hypersensitivity in IBS rats, which may be associated with its effects in down-regulating the number of MC and the expression of PAR-2, TRVP 1, SP, CGRP and Try proteins in the colonic tissue.

Downregulation of miR-214-3p May Contribute to Pathogenesis of Ulcerative Colitis via Targeting STAT6.

MicroRNAs (miRs) are small noncoding RNA molecules and recently have demonstrated that altered expression and functions are their tight association with ulcerative colitis (UC). Previous microarray study reported that miR-214 was downregulated in the sigmoid colon of patients with active UC, but the roles of miR-214 in the pathogenesis of UC remain to be elucidated. In this study, significant lower level of miR-214-3p and higher level of STAT6 in the intestinal mucosa of active UC patients compared with the health controls were confirmed by quantitative real-time PCR. Results of luciferase reporter assays and western blot demonstrated that miR-214-3p directly targets STAT6 and negatively regulates the expression of STAT6 at the posttranscriptional level. Furthermore, the expression of miR-214-3p was decreased in TNF-α treated HT29 cells and STAT6 protein level was increased in a time-dependent manner. Silenced STAT6 and upregulation of miR-214-3p could decrease the level of INF-γ in TNF-α treated HT29 cells. Additionally, the results of the present study indicate that miR-214-3p and STAT6 axis may be a novel therapeutic target for intestinal inflammation of patients with active UC.