Exploring the causal relationship between gut microbiota and frailty: a two-sample mendelian randomization analysis.

Background: Frailty is a complex geriatric syndrome that seriously affects the quality of life of older adults. Previous observational studies have reported a strong relationship of frailty with the gut microbiota; however, further studies are warranted to establish a causal link. Accordingly, we aimed to conduct a bidirectional Mendelian randomization study to assess the causal relationship between frailty, as measured by the frailty index, and gut microbiota composition. Methods: Instrumental variables for the frailty index (N = 175, 226) and 211 gut bacteria (N = 18,340) were obtained through a genome-wide association study. A two-sample Mendelian randomization analysis was performed to assess the causal relationship of gut microbiota with frailty. Additionally, we performed inverse Mendelian randomization analyses to examine the direction of causality. Inverse variance weighting was used as the primary method in this study, which was supplemented by horizontal pleiotropy and sensitivity analyses to increase confidence in the results. Results: Bacteroidia (b = -0.041, SE = 0.017, p = 0.014) and Eubacterium ruminantium (b = -0.027, SE = 0.012, p = 0.028) were protective against frailty amelioration. Additionally, the following five bacteria types were associated with high frailty: Betaproteobacteria (b = 0.049, SE = 0.024, p = 0.042), Bifidobacterium (b = 0.042, SE = 0.016, p = 0.013), Clostridium innocuum (b = 0.023, SE = 0.011, p = 0.036), E. coprostanoligenes (b = 0.054, SE = 0.018, p = 0.003), and Allisonella (b = 0.032, SE = 0.013, p = 0.012). Contrastingly, frailty affected Butyrivibrio in the gut microbiota (b = 1.225, SE = 0.570, p = 0.031). The results remained stable within sensitivity and validation analyses. Conclusion: Our findings strengthen the evidence of a bidirectional causal link between the gut microbiota and frailty. It is important to elucidate this relationship to optimally enhance the care of older adults and improve their quality of life.

Three Liquid-Liquid Phase Separation-Related Genes Associated with Prognosis in Glioma.

Purpose: Dysregulated liquid-liquid phase separation (LLPS) instigates tumorigenesis through biomolecular condensate dysfunction. However, the association between LLPS-associated genes and glioma remains underexplored. Patients and Methods: Differentially expressed genes (DEGs) of glioma were obtained from the GSE50161 dataset, including 34 glioma and 13 normal samples. We analyzed differentially expressed LLPS-related genes in glioma from public databases. These genes informed refined molecular subtyping on the TCGA-glioma dataset. CIBERSORT assessed immune cell infiltration across three subclusters. A prognostic model was devised using univariate and lasso Cox regressions on intersecting genes. Prognostic gene expression was validated in glioma cells via RT-qPCR. Results: A total of 673 differentially expressed LLPS-associated genes were identified in glioma. Three distinct molecular subtypes (C1, C2, and C3) of glioma were obtained with a marked variance in the expression of immune checkpoint genes PD1 and PDL1. Differences in immune cell infiltration were observed across subtypes. In addition, a tri-gene prognostic signature (TAGLN2, NTNG2, and IGF2BP2) was derived with significant survival differences between high and low-risk groups. The prognostic model displayed impressive AUC values for 1, 3, and 5-year survival in both training and validation sets. Further analysis highlighted a notable correlation between the three prognostic genes and immune cells in glioma samples. Furthermore, we found the upregulation of TAGLN2 and IGF2BP2 and the downregulation of NTNG2 in glioma tumors and cells. Conclusion: This study innovatively uncovers the significant role of LLPS-related genes in glioma tumor grading and prognosis. The constructed tri-gene prognostic model holds promise for enhancing personalized prognosis assessments and optimizing immunotherapy strategies for glioma patients.

Arachidonate lipoxygenases 5 is a novel prognostic biomarker and correlates with high tumor immune infiltration in low-grade glioma.

Objective: To investigate the prognostic value of arachidonate lipoxygenases 5 (ALOX5) expression and methylation, and explore the immune functions of arachidonate lipoxygenases 5 expression in low-grade glioma (LGG). Materials and Methods: Using efficient bioinformatics approaches, the differential expression of arachidonate lipoxygenases 5 and the association of its expression with clinicopathological characteristics were evaluated. Then, we analyzed the prognostic significance of arachidonate lipoxygenases 5 expression and its methylation level followed by immune cell infiltration analysis. The functional enrichment analysis was conducted to determine the possible regulatory pathways of arachidonate lipoxygenases 5 in low-grade glioma. Finally, the drug sensitivity analysis was performed to explore the correlation between arachidonate lipoxygenases 5 expression and chemotherapeutic drugs. Results: arachidonate lipoxygenases 5 mRNA expression was increased in low-grade glioma and its expression had a notable relation with age and subtype (p < 0.05). The elevated mRNA level of arachidonate lipoxygenases 5 could independently predict the disease-specific survival (DSS), overall survival (OS), and progression-free interval (PFI) (p < 0.05). Besides, arachidonate lipoxygenases 5 expression was negatively correlated with its methylation level and the arachidonate lipoxygenases 5 hypomethylation led to a worse prognosis (p < 0.05). The arachidonate lipoxygenases 5 expression also showed a positive connection with immune cells, while low-grade glioma patients with higher immune cell infiltration had poor survival probability (p < 0.05). Further, arachidonate lipoxygenases 5 might be involved in immune- and inflammation-related pathways. Importantly, arachidonate lipoxygenases 5 expression was negatively related to drug sensitivity. Conclusion: arachidonate lipoxygenases 5 might be a promising biomarker, and it probably occupies a vital role in immune cell infiltration in low-grade glioma.

Research on the Relationship Between Meckel's Cavity Shape, Balloon Shape, and Intracapsular Pressure During Percutaneous Balloon Compression.

OBJECTIVE: Percutaneous balloon compression is a safe, effective, and minimally invasive therapeutic method for trigeminal neuralgia. Intraoperatively precise compression after the formation of the pear-shaped balloon is the key to the expected effect. In this study, we assessed the relationship between the structure of Meckel's cavity and the shape and intracapsular pressure of the balloon by preoperative magnetic resonance. METHODS: We respectively analyzed 58 patients with typical trigeminal neuralgia who underwent percutaneous balloon compression surgery in our department. Reconstruction of magnetic resonance imaging 3-dimensional fast imaging employing steady-state acquisition thin-layer scanning sequence was also performed before the operation to analyze the sagittal features of Meckel's cavity. The pressure was recorded continuously when a pear-shaped balloon was forming during the operation. Meanwhile, the balloon height/length (h/l) ratio was measured. The relationship between Meckel's cavity shape, balloon shape, and pressure was analyzed by mentioned parameters. RESULTS: The pain of 57 patients was relieved immediately after the operation, and the effective rate was 98.27% (57 of 58); Recurrence in 2 cases within the median follow-up time (7.5 months). Meckel's cavity classification on magnetic resonance showed that the clubbing type, oval type, and flat type accounted for 31.1% (18 of 58), 58.6% (34 of 58), and 10.3% (6 of 58), respectively. The results demonstrated that the intracapsular pressure was low, while the h/l ratio of Meckel's cavity was relatively high. We also found the corresponding pressure results when the ratio was low. However, no significant difference was found between the balloon h/l ratio and Meckel's cavity h/l ratio. CONCLUSIONS: Intracapsular pressure of balloon is negatively correlated with the h/l ratio of Meckel's cavity. The individually differentiated formation of the pear-shaped balloon has little correlation with the sagittal shape of Meckel's cavity.

Applications of diffusion tensor imaging integrated with neuronavigation to prevent visual damage during tumor resection in the optic radiation area.

Background: Intracranial tumors involving the temporo-occipital lobe often compress or destroy the optic radiation (OpR), resulting in decreased visual function. The aim of this study is to explore the value of diffusion tensor imaging (DTI) tractography integrated with neuronavigation to prevent visual damage when resecting tumors involving the OpR and find potential factors affecting patients' visual function and quality of life (QOL). Methods: Our study is a cross-sectional study that included 28 patients with intracranial tumors in close morphological relationship with the OpR recruited between January 2020 and February 2022. The surgical incision and approach were preoperatively designed and adjusted according to the DTI tractography results and visual function scores. All patients underwent examinations of visual acuity (VA) and visual field index (VFI) and completed visual function and QOL scales at admission and 2 months after discharge. Logistic regression and linear regression analysis were conducted to evaluate clinical factors potentially affecting pre/postoperative OpR morphology, VA, VFI, visual function, and QOL. Results: Lesion size was the main factor found to affect visual function (ß = -0.74, 95%CI: -1.12~-0.36, P = 0.05), VA (left: ß = -0.11, 95%CI: -0.14~-0.08, P < 0.001; right: ß = -0.15, 95%CI: -0.17~-0.13, P < 0.001), and VFI (left: ß = -0.11, 95%CI: -0.14~-0.08, P < 0.001; right: ß = -0.14, 95%CI: -0.16~-0.12, P < 0.001). Lesion size, edema, and involvement of the lateral ventricle temporal horn were factors affecting OpR morphology and QOL. The 28 patients showed significantly improved VA, VFI, visual function, and QOL results (P < 0.05) 2 months after discharge. Conclusions: Combining DTI of OpR mapping and microscopic-based neuronavigation aided precise mapping and thus preservation of visual function in patients undergoing tumor resection. Potential clinical factors affecting patients' visual function and QOL scores were identified which are useful for assessing a patient's condition and predicting prognosis.

Hemangioblastoma in the lateral ventricle: An extremely rare case report.

Hemangioblastoma (HB) is a benign vascular tumor that accounts for approximately 2% of intracranial neoplasms. HB of the lateral ventricles is extremely rare. Only a few reports are present in the literature. This article reports a 27-year-old male patient who arrived at our hospital because of a progressive headache lasting one month. The brain Magnetic Resonance Imaging (MRI) revealed a solid-cystic mass of 3.5×3.0 cm in size located in the left lateral ventricle, the surgery was performed by applying an interhemispheric approach to single frontal craniotomy with coronal incision to remove the tumor. The postoperative CT and MRI showed the successful complete removal of the tumor and a normal ventricle morphology. The differential diagnosis should be considered in case of intraventricular tumors including HB. Angiography should be performed prior to surgery when HB is suspected.

KIF26B Is Overexpressed in Medulloblastoma and Promotes Malignant Progression by Activating the PI3K/AKT Pathway.

Medulloblastoma is one of the most common malignant tumors of the central nervous system in children. Although KIF2B was reported as an oncogene in several malignant tumor types, its role in medulloblastoma has not been studied so far. The PCR results of our study showed that KIF26B is highly expressed in medulloblastoma, and its high expression is associated with a high clinical stage. Knockdown the expression of KIF26B could significantly impair the proliferation and migration of medulloblastoma cells. KIF26B promotes the malignant progression of medulloblastoma by affecting the expression of phosphorylation of key proteins in the PI3K/AKT signaling pathway. With the help of 740 Y-P, activating the pi3k signaling pathway can partially rescue the phenotype. Therefore, our experimental results suggest that KIF26B is a potential target for medulloblastoma.

Identification of Key Biomarkers and Immune Infiltration in Sporadic Vestibular Schwannoma Basing Transcriptome-Wide Profiling.

BACKGROUND: Vestibular schwannoma is a common intracranial tumor, with 95% of the cases being sporadic vestibular schwannoma (SVS). The purpose of this study was identifying genes responsible for inflammation in SVS and clarifying its underlying immune mechanisms. METHODS: Transcriptional sequencing datasets (GSE141801 and GSE108237) from the Gene Expression Omnibus database were used in this study. The candidate modules closely related to SVS and hub genes were screened out by weighted gene coexpression network analysis. Τhe sensitivity and specificity of the hub genes for SVS prediction were evaluated by receiver operating characteristic curve analysis. The CIBERSORT algorithm was subsequently applied to analyze the immune infiltration between SVS and controls. Finally, biological signaling pathways involved in the hub genes were identified via gene set enrichment analysis. RESULTS: A total of 39 significantly enriched in myelination and collagen-containing extracellular matrix DEGs were identified at the screening step. Three hub genes (MAPK8IP1, SLC36A2, and OR2AT4) were identified, which mainly enriched in pathways of melanogenesis, GnRH, and calcium signaling pathways. Compared with normal nerves, SVS tissue contained a higher proportion of T cells, monocytes, and activated dendritic cells, whereas proportions of M2 macrophages were lower. CONCLUSIONS: The integrated analysis revealed the pattern of immune cell infiltration in SVS and provided a crucial molecular foundation to enhance understanding of SVS. Hub genes MAPK8IP1, SLC36A2, and OR2AT4 are potential biomarkers and therapeutic targets to facilitate the accurate diagnosis, prognosis, and therapy of SVS.

Exosomes derived from mesenchyml stem cells ameliorate oxygen-glucose deprivation/reoxygenation-induced neuronal injury via transferring MicroRNA-194 and targeting Bach1.

The neuroprotective function of miR-194 on neurovascular endothelial cell injury is perceived as a novel method for clinical therapy. So are exosomes (EXs), being attractive in neurofunctional recovery. However, whether EXs derived from mesenchymal stromal cells (MSCs) perform the same efficacy by transferring miR-194 and the underlying mechanism remain vague. This study rooted in oxygen-glucose deprivation/reoxygenation (OGD/R) model. MSCs were isolated by gradient centrifugation and identified by flow cytometry. EXs were obtained through ultracentrifugation, whereas protein levels of specific markers (CD63, TGS101), together with Bach1, Nrf2 and HO-1 were measured by western blot. The relative mRNA expressions of Bach1, NOX1, AGSL4, GPX4 and miR-194 were measured by RT-qPCR assays. Cell viability was measured by cell counting kit-8, and cell migration was detected by wound healing assay. The interaction between miR-194 and Bach1 was predicted by starBase and confirmed by dual luciferase reporter assay. OGD/R dampened cell viability and miR-194 expression. Bach1 could bind with miR-194. miR-194 mimic attenuated the effect of OGD/R on cell viability and protein levels of Nrf2, HO-1 and Bach1, whereas Bach1 overexpression reversed the effect of miR-194 mimics. MSC-EXs could merge with HBMECs. Based on this, MSC-EXs loaded with miR-194 downregulated Bach1 protein level and iron content and the mRNA expressions of NOX1 and ACSL4, yet upregulated miR-194 and GPX4 expressions and Nrf2/HO-1 protein level in OGD/R-injured cells, whereas those carrying ShmiR-194 had the opposite effects. Our study suggested MSC-EXs loaded with miR-194 attenuated OGD/R-induced injury via targeting Bach1, providing a new therapeutic strategy for cerebral injuries.

Reliability and toxicity of bevacizumab for neurofibromatosis type 2-related vestibular schwannomas: A systematic review and meta-analysis.

BACKGROUND: The anti-angiogenic agent bevacizumab is currently the only drug used clinically for neurofibromatosis type 2-related vestibular schwannomas (NF2-VS). Though benefits have been demonstrated in several cases, the standardized dosage remains unclear. OBJECTIVE: Our meta-analysis was performed to systematically and comprehensively investigate the reliability and toxicity of bevacizumab in the treatment of NF2-VS, with particular emphasis on the impact of dosage. METHODS: The literature search was conducted for studies providing data on patients treated with bevacizumab for NF2-VS across PubMed, Embase, and Cochrane Library until December 31, 2020. Two reviewers extracted the incidence rate of results independently. Then we calculated and pooled unadjusted incidence rate with 95% CIs for each study. The subgroups analyzed were conducted. RESULTS: Fourteen citations (prospective or retrospective observational cohort studies) were eligible based on data from a total of 247 patients with NF2 and 332 related VSs. The pooled results showed that the radiographic response rate (RRR) was 30% [95% CI (20%-42%)], the hearing response rate (HRR) was 32% [95% CI (21%-45%)]. The incidence of major complications was: hypertension 29% [95% CI (23%-35%)], proteinuria 30% [95% CI (18%-44%)], menstrual disorders 44% [95% CI (16%-73%)], hemorrhage 14% [95% CI (4%-26%)], grade3/4 events 12% [95% CI (4%-22%)]. CONCLUSIONS: Nearly one-third of NF2-VS patients may benefit significantly from bevacizumab due to hearing improvement and tumor reduction. Menstrual disorders were the most common adverse events. The high-dose regimen didn't show better efficacy, but results varied considerably according to age.