Risk factors on surgical compliance and its impact on survival outcomes in meningioma patients: a SEER-based retrospective propensity-score matched analysis.

BACKGROUND: This study aimed to analyze the effect of surgical compliance on the survival outcome of patients with meningioma and explore the factors affecting surgical compliance. METHODS: We selected data from the Surveillance, Epidemiology, and End Results database for 122,632 meningioma patients diagnosed between 2004 and 2018. The effect of surgical compliance on patients' overall survival (OS) was analyzed through Cox regression and Kaplan-Meier curves. Independent risk factors for surgical compliance were identified through multifactorial logistic regression analyses to construct diagnostic nomograms, further assessed by receiver operating characteristic curves. Furthermore, we used univariate and multivariate logistic regression analyses to evaluate relevant variables linked to adherence with meningioma surgery. Moreover, 1:1 propensity score matching was applied to assess the validity of the results in patients with favorable and poor surgical compliance. RESULTS: A total of 48,735 were eligible from the initial cohort of 122,632 patients with meningioma. Among them, 45,038 (92.40%) exhibited good surgical compliance, while 3697 (7.60%) had poor surgical compliance. The rate of patients with good surgical compliance was significantly higher than that of patients with inadequate surgical compliance (p < 0.001). Moreover, surgical compliance is an independent prognostic factor for OS in meningioma patients. Univariate Cox regression analysis indicated that individuals with poor surgical compliance demonstrated lower OS rates than those with good surgical compliance (hazard ratio [HR 2.404; 95% confidence interval [CI] 2.276-2.54, p < 0.001], consistent with the observation in the multivariate analysis (HR 1.564; 95% CI 1.471-1.663, p < 0.001). We developed a prediction model using seven variables: age, sex, race, tumor behavior recode, tumor size, family income, and residential setting (p < 0.05). Surgical compliance was associated with patient age, sex, race, tumor behavior recode, tumor size, family income, and residential setting by logistic regression analysis. CONCLUSIONS: Surgical compliance emerged as an independent prognostic factor for survival in patients with meningioma. Poor surgical compliance was associated with older age, black and other races, females, advanced-stage tumors, larger tumor size, lower household income, and rural residence. When patients experienced these conditions, OS was shorter, requiring more aggressive treatment.

The association between constipation and stroke based on the NHANES and Mendelian randomization study.

Background: This study aimed to investigate putative causal effects between constipation and stroke using bidirectional Mendelian randomization (MR) analysis. Methods: Based on the cross-sectional study, logistic regression models were developed to assess the association between constipation and stroke prevalence. Subsequently, genome-wide association studies statistics were employed to perform MR analysis between constipation and stroke, as well as its subtypes. The inverse variance weighting (IVW) method was the primary method, complemented by four additional methods, namely weighted median, weighted mode, simple mode, and MR-Egger regression. Cochran's Q test, MR-Egger intercept test, MR Pleiotropy RESidual Sum and Outlier, and MR Steiger test were performed to assess heterogeneity and pleiotropy effects. Results: Constipation was associated with a greater risk of stroke even after adjusting for all covariates in logistic regression [odds ratio (OR) = 1.46, 95% confidence interval (CI) = 1.01-2.09, p = 0.042]. IVW MR analysis revealed that constipation affected large artery atherosclerosis (LAS; IVW OR = 1.5, 95% CI = 1.07-2.104, p = 0.019). No significant or suggestive association was observed with the risk of stroke or its various subtypes in MR analysis. Meanwhile, reverse MR analysis revealed no significant causal relationship between stroke or other stroke subtypes and constipation. The results of sensitivity analyses revealed no significant horizontal pleiotropy affecting causal estimates. Conclusion: While cross-sectional studies have established that constipation increases the risk of stroke, this two-sample bidirectional MR analysis revealed a positive correlation between constipation and LAS. However, no such correlation was observed between constipation and stroke, including its various subtypes.

Unveiling the role of GAS41 in cancer progression.

GAS41, a member of the human YEATS domain family, plays a pivotal role in human cancer development. It serves as a highly promising epigenetic reader, facilitating precise regulation of cell growth and development by recognizing essential histone modifications, including histone acetylation, benzoylation, succinylation, and crotonylation. Functional readouts of these histone modifications often coincide with cancer progression. In addition, GAS41 functions as a novel oncogene, participating in numerous signaling pathways. Here, we summarize the epigenetic functions of GAS41 and its role in the carcinoma progression. Moving forward, elucidating the downstream target oncogenes regulated by GAS41 and the developing small molecule inhibitors based on the distinctive YEATS recognition properties will be pivotal in advancing this research field.

MiR-145 enriched exosomes derived from bone marrow-derived mesenchymal stem cells protects against cerebral ischemia-reperfusion injury through downregulation of FOXO1.

BACKGROUND: Mesenchymal stem cells-derived exosomes (MSCs-Exo) were able to exert neuroprotective effects in brain injury after ischemic stroke (IS). In addition, exosomes containing microRNAs (miRNAs) can be transported to recipient cells to mediate intercellular communication. It has been shown that the level of miR-145 was significantly downregulated in brain tissues of rats subjected to middle cerebral artery occlusion (MCAO). However, the role of MSCs-derived exosomal miR-145 in IS progression remains largely unknown. METHODS: Microglial BV2 cell exposed to oxygen-glucose deprivation/reperfusion (OGD/R) was applied to mimic cerebral ischemia/reperfusion (I/R) injury conditions in vitro. In addition, a rat model of MCAO was established to induce I/R injury. Meanwhile, exosomes were isolated from miR-145-transfected bone marrow MSCs, and then these isolated exosomes were used to treat OGD/R-stimulated BV-2 cell and rats subject to MCAO/R. RESULTS: In this study, we found that miR-145 could be transferred from MSCs to BV2 cells via exosomes. In addition, exosomal miR-145-derived from MSCs was able to shift microglia polarization toward anti-inflammatory M2 phenotype in OGD/R-stimulated BV2 cells. Moreover, exosomal miR-145 markedly suppressed the apoptosis, cell cycle arrest and oxidative stress in OGD/R-treated BV2 cells. Additionally, exosomal miR-145 notably decreased the expression of FOXO1 in BV2 cell exposed to OGD/R and in brain tissues of MCAO rats. Furthermore, exosomal miR-145 remarkably decreased infarct area in MCAO rats. CONCLUSION: Collectively, exosomal miR-145-derived from MSCs was able to attenuate cerebral I/R injury through downregulation of FOXO1. These studies may serve as a potential approach for treating of cerebral I/R injury.

Interleukin-35 attenuates blood-brain barrier dysfunction caused by cerebral ischemia-reperfusion injury through inhibiting brain endothelial cell injury.

Background: Interleukin-35 (IL-35), an anti-inflammatory and antioxidant cytokine, plays a potent immunosuppressive role in various diseases. However, the effects of IL-35 on blood-brain barrier (BBB) dysfunction in ischemic stroke are not well characterized. Methods: A total of 150 male C57BL/6 mice (aged 6-8 weeks and weighing 20-25 g) were used in this study. The protective effects of IL-35 against BBB dysfunction were examined using a mouse model of middle cerebral artery occlusion (MCAO) and an in vitro model of oxygen-glucose deprivation/reoxygenation (OGD/R) injury in mouse brain endothelial cells (bEnd.3). Results: Intracerebroventricular administration of IL-35 (10 µg/g) was found to reduce cerebral edema and Evans blue (EB) leakage, and increase the expression of tight junction (TJ) proteins, thereby attenuating MCAO-induced neurological deficit in mice. Moreover, IL-35 (20 ng/mL) treatment upregulated the expression of TJ proteins in OGD/R-induced bEnd.3 cells. IL-35 also markedly suppressed the expression of caspase-1, IL-1ß, and gasdermin D (GSDMD) in vivo and in vitro. In addition, IL-35 decreased the generation of reactive oxygen species (ROS) and inhibited the expression of thioredoxin-interacting protein (TXNIP) in OGD/R-induced bEnd.3 cells. Conclusions: These results indicated that IL-35 exerts a protective effect on the BBB by targeting the ROS/TXNIP/caspase-1 pathway in cerebral ischemia-reperfusion (I/R) injury.

Long non­coding RNA SNHG16 inhibits the oxygen­glucose deprivation and reoxygenation­induced apoptosis in human brain microvascular endothelial cells by regulating miR­15a­5p/bcl­2.

MicroRNA (miR) 15a­5p can promote ischemia/reperfusion (I/R)­induced apoptosis of cerebral vascular endothelial cells, which is inhibited by long non­coding RNAs (lncRNAs). The present study investigated the potential of lncRNAs targeting miR­15a­5p to regulate oxygen­glucose deprivation and reoxygenation (OGD­R)­induced apoptosis of human brain microvascular endothelial cells (hBMECs). hBMECs were transfected with or without miR­15a­5p or its mutant, together with p­small nucleolar RNA host gene 16 (SNHG16) or its mutant. Following OGD­R, proliferation, apoptosis and miR­15a­5p, SNHG16 and Bcl­2 expression levels were determined using MTT, flow cytometry, reverse transcription­quantitative PCR or western blotting. The potential interaction of SNHG16 with miR­15a­5p was analyzed by pull­down, luciferase and immunoprecipitation assays. OGD­R induced apoptosis of hBMECs and increased miR­15a­5p expression levels in a time­dependent manner. miR­15a­5p overexpression decreased the proliferation of hBMECs and promoted apoptosis by decreasing Bcl­2 expression levels. SNHG16 was pulled­down by miR­15a­5p and anti­Ago2. miR­15a­5p overexpression significantly decreased SNHG16­regulated luciferase activity and hBMEC survival by increasing apoptosis. SNHG16 overexpression decreased miR­15a­5p expression levels in hBMECs. SNHG16 gradually decreased following OGD­R and its overexpression decreased miR­15a­5p expression levels and promoted the proliferation of hBMECs by decreasing apoptosis. SNHG16 enhanced Bcl­2 expression levels in hBMECs, which was abrogated by miR­15a­5p. Bioinformatics suggest that SNHG16 may antagonize the binding of miR­15a­5p to the 3'UTR of Bcl­2 mRNA. These findings suggest that SNHG16 may protect hBMECs from OGD­R­induced apoptosis by antagonizing the miR­15a­5p/bcl­2 axis. Thus, targeting SNHG16­based mechanisms may provide novel therapeutic strategies for treatment of ischemic stroke.