Circular RNA ITCH promotes extracellular matrix degradation via activating Wnt/ß-catenin signaling in intervertebral disc degeneration.

Intervertebral disc degeneration (IDD) is the prevailing spine disorder and is associated with musculoskeletal disease. The extracellular matrix (ECM) degradation is an essential hallmark of IDD progression. Circular RNAs (circRNAs), as crucial cellular regulators, participate in multiple pathological processes including IDD. Here, we tried to explore the effect of circITCH on the ECM degradation of IDD and the underlying mechanism. Significantly, the expression levels of circITCH were elevated in the IDD patients' nucleus pulposus (NP) tissues relative to that of normal cases. CircITCH promoted apoptosis and decreased proliferation of NP cells. CircITCH contributed to ECM degradation, as demonstrated by increased ADAMTS4 and MMP13 expression and decreased aggrecan and collagen II expression. Mechanically, miR-17-5p could be sponged by circITCH and miR-17-5p inhibited ECM degradation by repressing SOX4 in degenerative NP cells. CircITCH could activate Wnt/ß-catenin pathway by targeting miR-17-5p/SOX4 signaling. SOX4 overexpression, miR-17-5p inhibitor, or Wnt/ß-catenin signaling activator LiCl was able to reverse circITCH knockdown-inhibited apoptosis and ECM degradation, and circITCH knockdown-enhanced proliferation in NP cells. Thus, we conclude that circITCH promotes ECM degradation in IDD by activating Wnt/ß-catenin through miR-17-5p/SOX4 signaling. Our finding presents novel insight into the mechanism that circITCH modulates the IDD progression. CircITCH and SOX4 may serve as potential targets for IDD therapy.

The effectiveness of financial intervention strategies for reducing caesarean section rates: a systematic review.

BACKGROUND: The increasing trend of Caesarean section (CS) in childbirth has become a global public health challenge. Previous studies have proposed financial intervention strategies for reducing CS rates by limiting caesarean delivery on maternal request (CDMR). This study synthesizes such strategies while evaluating their effectiveness. METHODS: The sources of data for this study are Cochrane Library, PubMed, EMBASE, and CINAHL. The publication period included in this study is from January 1991 to November 2018. The financial intervention strategies are divide into two categories: healthcare provider interventions and patient interventions. Risk of Bias in Non-randomized Studies - of Interventions (ROBINS-I) was employed to assess the risk of bias of included studies. The outcome of each study was evaluated with Grades of Recommendation, Assessment, Development and Evaluation (GRADE) through the GRADEpro Guideline Development Tool software. RESULTS: Nine studies were included in this systematic review: five with high certainty evidence (HCE), three with moderate certainty evidence (MCE), and one with low certainty evidence (LCE). Of the nine studies, seven are centered on the effect of provider-side interventions. Three of the HCE studies found that the diagnosis-related group payment system, risk-adjusted capitation, and equalizing fee for both facilities and physicians were effective intervention strategies. One HCE and one MCE study showed that only equalizing facility fees between vaginal and CS deliveries in healthcare service settings had no significant effect on reducing the CS rate. The MCE study showed that case payment had a negative effect on reducing the CS rates. One LCE study revealed that the effect of a global budget system was uncertain, and one HCE and one MCE study focused on combining both provider and patient-side interventions. However, equalizing fees for vaginal and CS deliveries and a co-payment policy for CDMRs failed to reduce the CS rate. CONCLUSIONS: The effectiveness of risk-adjusted payment methods appears promising and should be the subject of further research. Financial interventions should consider stakeholders' characteristics, especially the personal interests of doctors. Finally, high-quality randomized control trials and comparative studies on different financial intervention methods are needed to confirm or refute previous studies' outcomes.

[Effect of coicis semen oil on renal interstitial fibrosis in rats with unilateral urethral obstruction].

OBJECTIVE: To study the effect and mechanism of Coicis Semen oil (Kanglaite injection, KLT) on renal interstitial fibrosis induced by unilateral ureteral obstruction (UUO). METHOD: Fifty-four male SD rats were randomly divided into 3 groups, 6 in each group, the sham operated group, the model group, and the KLT group. Renal interstitial fibrosis model was established in rats by UUO. After administration of KLT (15 mL x kg(-1) x d(-1)) for 3, 7 and 14 days, the dynamic histological changes of renal interstitial tissues were observed and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The expression of alpha-smooth muscle actin (alpha-SMA) and transforming growth factor-beta1 (TGF-beta1) were measured by immunohistochemistry staining sections. The protein expression of p-Smad2 and Smad7 were detected by Western blot respectively. RESULT: The degree of tubular damage in KLT group was much lower than that in UUO group (P < 0.05). The expression of alpha-SMA and TGF-beta1 was decreased in both UUO group and KLT group, while it was significantly lower in KLT group at every time point. The protein expression of p-Smad2 was obviously decreased while the protein expressions of Smad7 was obviously increased in KLT group, compared with the UUO group (P < 0.05). CONCLUSION: Coicis Semen oil could attenuate the tubulo-interstitial fibrosis, probable by intervening the TGF-beta/Smads signal transduction pathway of UUO rats.

[Effects of simvastatin on expression of CTGF and α-SMA in renal tubulointerstitium of rats with diabetic nephropathy].

OBJECTIVE: To investigate the effects of low-dose simvastatin on the expression of connective tissue growth factor (CTGF) and α-smooth muscle actin (α-SMA) in the renal tubulointerstitium of rats with diabetic nephropathy. METHODS: Sixty male SD rats were randomly divided into three groups: Group C (control group), Group D, in which diabetes was induced by stroptozotocin (STZ) and Group DS, in which STZ-induced diabetic rats were treated with low-dose (no cholesterol-lowering effect) simvastatin. The following parameters were measured after 6 weeks and 12 weeks in each groups, respectively: body weight and kidney weight, 24-h urinary albumin excretion (UAE), biochemical indexes including blood glucose (GLU), low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides (TG) and serum creatinine (SCr). The expression of CTGF and α-SMA in renal tubulointerstitium was assessed by immunohistochemical method. RESULT: After 6 and 12 weeks, there were no significant differences in SCr, LDL, HDL and TG levels among all three groups. The expression levels of CTGF and α-SMA in the tubulointerstitium of Group DS were significantly decreased compared with those of Group D at week 6 (P<0.05); there were no significant differences compared with Group C (P>0.05). After 12 weeks, CTGF and α-SMA expressions in Group DS were also lower than those in Group D (P<0.05); while higher than those in Group C (P<0.05). CONCLUSION: Simvastatin with a under cholesterol-lowering dose, can decrease the expression levels of CTGF and α-SMA in renal tubulointerstitium of rats with diabetic nephropathy, by which the progression of the tubulointerstitial fibrosis would be delayed.

Increased ERCC1 protein expression is associated with suboptimal debulking in advanced epithelial ovarian cancer.

UNLABELLED: Some biological features, such as amount of ascites and molecular tissue markers, have been found to correlate with debulking outcome in advanced epithelial ovarian cancer (EOC). This study investigated whether proteins involved in nucleotide excision repair of EOC affected the debulking outcome. PATIENTS AND METHODS: The relationship between dichotomised clinical characteristics, ERCC1 and XPD protein expression levels in 78 patients were tested by univariate and multivariate analysis to determine the independent significance of factors for debulking outcome. Receiver operating characteristic (ROC) curves were constructed to determine their predictive value. RESULTS: Pre- and postoperative CA125, ascites, menopause, and ERCC1 protein all significantly correlated with debulking outcome. However, only ERCC1 was the only independent factor, with the area under the ROC curve being 0.724. CONCLUSION: ERCC1 protein is an independent prognostic indicator for debulking outcome in advanced EOC.

Effects of simvastatin on oxidative stress in streptozotocin-induced diabetic rats: a role for glomeruli protection.

AIMS: To study the effects of simvastatin on oxidative stress in rats with early stage diabetic nephropathy. METHODS: 60 male Sprague-Dawley rats were divided into three groups: control group (CN), streptozotocin (STZ)-induced diabetic rats group (DM) and STZ-induced diabetic rats group treated with simvastatin (DM+S). The following parameters were measured at weeks 6 and 12 in similar rats chosen randomly from each group: body and kidney weight, 24-hour urinary albumin excretion (UAE), biochemical indexes including blood glucose (GLU), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG), serum creatinine (SCr), antioxidant enzymes including superoxide dismutase (SOD), glutathione S-transferase (GST), catalase (CAT) in plasma, lipid peroxidation production as malondialdehyde in plasma (MDAp) and erythrocytes (MDAe), morphology parameters such as glomerular volume (GV) and mesangial area/total glomerular area (M/T). RESULTS: At weeks 6 and 12, GLU and kidney weight to body weight ratio were notably increased in both of the diabetic groups compared with those in the CN group without significant differences between the two diabetic groups. There were no significant differences of SCr, LDL, HDL and TG among all groups within all the experimental time. MDAp and MDAe were significantly increased in both of the diabetic groups, especially at week 12, while SOD, GST and CAT were significantly decreased compared with those in the CN group. At week 12, GV, M/T and UAE were also increased in the two diabetic groups. However, in the DM+S group, changes of lipid peroxidation production, antioxidant enzymes, UAE and GV were less pronounced than those in the DM group. Pearson's correlation analysis and regression analysis shown that MDAp was increased while SOD, GST and CAT in plasma were decreased with elevation of UAE, GV and M/T. CONCLUSION: Increased lipid peroxidation and decreased antioxidant enzymes in plasma may play a role in the progression of diabetic nephropathy. Simvastatin may ameliorate these changes to protect kidney from oxidative lesion in diabetes even in the absence of lipid abnormalities.