Leveraging various extracellular matrix levels to assess prognosis and sensitivity to immunotherapy in patients with ovarian cancer

BackgroundOvarian cancer (OC) is the fifth leading cause of cancer-related deaths among women. Late diagnosis and heterogeneous treatment result in a poor prognosis for patients with OC. Therefore, we aimed to develop new biomarkers to predict accurate prognoses and provide references for individualized treatment strategies.MethodsWe constructed a co-expression network applying the “WGCNA” package and identified the extracellular matrix-associated gene modules. We figured out the best model and generated the extracellular matrix score (ECMS). The ECMS’ ability to predict accurate OC patients’ prognoses and responses to immunotherapy was evaluated.ResultsThe ECMS was an independent prognostic factor in the training [hazard ratio (HR) = 3.132 (2.068–4.744), p< 0.001] and testing sets [HR = 5.514 (2.084–14.586), p< 0.001]. The receiver operating characteristic curve (ROC) analysis showed that the AUC values for 1, 3, and 5 years were 0.528, 0.594, and 0.67 for the training set, respectively, and 0.571, 0.635, and 0.684 for the testing set, respectively. It was found that the high ECMS group had shorter overall survival than the low ECMS group [HR = 2 (1.53–2.61), p< 0.001 in the training set; HR = 1.62 (1.06–2.47), p = 0.021 in the testing set; HR = 1.39 (1.05–1.86), p = 0.022 in the training set]. The ROC values of the ECMS model for predicting immune response were 0.566 (training set) and 0.572 (testing set). The response rate to immunotherapy was higher in patients with low ECMS.ConclusionWe created an ECMS model to predict the prognosis and immunotherapeutic benefits in OC patients and provided references for individualized treatment of OC patients

Assessing the causal associations of different types of statins use and knee/hip osteoarthritis: A Mendelian randomization study.

ObjectiveThis study comprehensively evaluated the causal relationship between different types of statins use and knee/hip osteoarthritis (OA) using a two-sample and multivariate Mendelian randomization (MR) method.MethodsMR analysis was conducted using publicly available summary statistics data from genome-wide association studies (GWAS) to assess the causal associations between total statins use (including specific types) and knee/hip OA. The primary analysis utilized the inverse variance-weighted (IVW) method, with sensitivity analysis conducted to assess robustness. Multivariable MR (MVMR) analysis adjusted for low-density lipoprotein cholesterol (LDL-C), intermediate-density lipoprotein cholesterol (IDL-C), high-density lipoprotein cholesterol (HDL-C), and body mass index (BMI).ResultsThe MR analysis revealed a significant inverse association between genetically predicted total statins use and the risk of knee OA (OR = 0.950, 95%CI: 0.920-0.982, p = 0.002) as well as hip OA (OR = 0.932, 95%CI: 0.899-0.966, p ConclusionThis study provides compelling evidence of the close relationship between statin use and a reduced risk of knee/hip OA, particularly with atorvastatin and simvastatin. LDL-C and IDL-C may mediate these effects. These findings have important implications for the clinical prevention and treatment of knee/hip OA

Protective effect of CDDO-imidazolide against intestinal ischemia/reperfusion injury in mice

Intestinal ischemia/reperfusion (I/R) is life-threatening and challenging in clinical practice. CDDO-imidazolide (CDDO-Im) is therapeutic in alleviating I/R injury. Nevertheless, there is a lack of investigation on the effects of CDDO-Im on intestinal I/R. Mice were randomly divided into four groups: (a) the sham group, (b) the CDDO-Im group, (c) the I/R group, and (d) the I/R + CDDO-Im group. Intestinal I/R was performed by clamping arteria mesenteric anterior for 45 min, followed by 24 h reperfusion. In addition, Kaplan–Meier method and the log-rank test were used to compare the survival rates among groups by observing for 24 h. Intestinal I/R in model group demonstrated severe injury of the intestinal mucosa, lung, kidney, and liver. The intestinal mucosal damage and intestinal barrier dysfunction were obviously attenuated in CDDO-Im-treated group compared with the model group. Also, preconditioning with CDDO-Im reduced pulmonary, hepatic and renal damage, and decreased oxidative stress (malondialdehyde (MDA), superoxide dismutase (SOD), and NO) and pro-inflammatory responses (tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), and interleukin 6 (IL-6)) following I/R injury. Furthermore, we also observed that these protective properties of CDDO-Im were accomplished by the activation of nuclear factor E2-related factor 2 (Nrf2) signaling pathway and upregulation of its downstream antioxidant genes, including heme oxygenase (HO-1), NQO-1, and glutamate–cysteine ligase regulatory subunit (GCLM). Our data suggest that CDDO-Im exerts a beneficial effect on intestinal I/R-associated mucosal barrier dysfunction and distant organ injuries

The potential causal relationships between different types of statins use and knee/hip osteoarthritis were examined using various MR methods, including MR Egger, weighted median, inverse variance weighted.

The potential causal relationships between different types of statins use and knee/hip osteoarthritis were examined using various MR methods, including MR Egger, weighted median, inverse variance weighted.</p

Details of datasets included in analyses.

ObjectiveThis study comprehensively evaluated the causal relationship between different types of statins use and knee/hip osteoarthritis (OA) using a two-sample and multivariate Mendelian randomization (MR) method.MethodsMR analysis was conducted using publicly available summary statistics data from genome-wide association studies (GWAS) to assess the causal associations between total statins use (including specific types) and knee/hip OA. The primary analysis utilized the inverse variance-weighted (IVW) method, with sensitivity analysis conducted to assess robustness. Multivariable MR (MVMR) analysis adjusted for low-density lipoprotein cholesterol (LDL-C), intermediate-density lipoprotein cholesterol (IDL-C), high-density lipoprotein cholesterol (HDL-C), and body mass index (BMI).ResultsThe MR analysis revealed a significant inverse association between genetically predicted total statins use and the risk of knee OA (OR = 0.950, 95%CI: 0.920–0.982, p = 0.002) as well as hip OA (OR = 0.932, 95%CI: 0.899–0.966, p ConclusionThis study provides compelling evidence of the close relationship between statin use and a reduced risk of knee/hip OA, particularly with atorvastatin and simvastatin. LDL-C and IDL-C may mediate these effects. These findings have important implications for the clinical prevention and treatment of knee/hip OA.</div

Causal effects of statins use and three common statins use on the risk of knee/hip osteoarthritis from MVMR.

Causal effects of statins use and three common statins use on the risk of knee/hip osteoarthritis from MVMR.</p

Diagram of Mendelian randomization analysis.

Arrows represent associations. Assumption 1: the IVs correlate strongly with exposures. Assumption 2: the IVs are not associated with confounders. Assumption 3: the IVs influence outcomes only through exposures.</p