Melitoxin Inhibits Proliferation, Metastasis, and Invasion of Glioma U251 Cells by Down-regulating F2RL1.

As the principal active component of bee venom, melittin has an anti-cancer effect in different cancers. This study was aimed to investigate the effect of melittin in glioma and explore whether F2RL1 is closely involved in glioblastoma cells proliferation. TCGA and GES databases were used to evaluate the role of F2RL1 in gliomas. The U251 cells were divided into a control lentivirus + PBS group (NC-PBS), F2RL1 intervention lentivirus + PBS group (KD-PBS), control lentivirus + melittin group (NC-melittin), and F2RL1 intervention lentivirus + melittin group (KD-melittin). Cell proliferation was detected by MTT and EDU staining assays. The apoptosis rate was assessed by flow cytometry. Expressions of genes related to apoptosis, cycle arrest, migration, and invasion were detected by qRT-PCR. Cellular LDH concentrations were detected by ELISA. The subcutaneous tumor volume of nude mice was analyzed by xenograft method. F2RL1 was significantly overexpressed in glioma tissues and were reduced in the melittin-treated group compared to the blank group. F2RL1 knockdown and melittin alone or in combination increased the proportion of cells in the G1-phase, and the combination was more pronounced. The KD-melittin group showed a decrease in the number of viable cells at 24, 48, 72, and 96 h compared to the NC-PBS group. The number of cell migration and invasion was decreased in the KD-melittin group compared to the other groups. Moreover, the genes related to cell cycle arrest and apoptosis were significantly changed in the KD-melittin group. At weeks 4, 5, and 6, the tumor volume in the KD-melittin group was smaller than that in the KD-PBS group and NC-melittin group. Interference with the target gene F2RL1 inhibited the proliferation of glioma U251 cells, and melittin treatment inhibited the proliferation of glioma U251 cells. Melittin inhibited the proliferation of glioma U251 cells by suppressing the expression of target gene F2RL1.

Comparison of Anterior Controllable Antedisplacement and Fusion Versus Laminoplasty in the Treatment of Multisegment Ossification of Cervical Posterior Longitudinal Ligament: A Meta-Analysis of Clinical.

OBJECTIVE: This study aims to provide a comprehensive summary of the existing literature and conduct a systematic evaluation of the clinical outcomes associated with anterior controllable antedisplacement and fusion (ACAF) and posterior laminoplasty (LP) for the treatment of multisegment ossification of the cervical posterior longitudinal ligament (OPLL). METHODS: We conducted an electronic search of databases, including PubMed, Embase, Cochrane Library, and CNKI, from the inception of the initial database to March 2023. We analyzed various parameters, including demographic data, operation time, intraoperative blood loss, cervical curvature, Japanese Orthopaedic Association (JOA) scores, Visual Analog Scale (VAS) scores, and postoperative complications. Two independent reviewers screened the literature, extracted data, and assessed the risk of bias in the included studies. Meta-analysis was performed using RevMan 5.4 software. RESULTS: Our evaluation encompassed 7 studies involving a total of 467 patients. The patient cohort was divided into 2 groups: Group A (ACAF) comprised 226 patients, while Group B (LP) comprised 241 patients. Overall, our statistical analysis revealed significant differences between the 2 groups (P < 0.05) in terms of intraoperative blood loss, operative time, JOA score, JOA score improvement rate, postoperative VAS score, postoperative cervical curvature, and the incidence of certain postoperative complications (C5 nerve root paralysis, dysphagia, and axial symptoms). However, there was no statistically significant difference in the incidence of postoperative cerebrospinal fluid leakage and postoperative total complications between the 2 groups (P > 0.05). CONCLUSIONS: The findings of this study suggest that, in the treatment of multilevel cervical OPLL, ACAF yields superior outcomes compared to LP. Specifically, ACAF improves postoperative neurologic function, reduces postoperative pain, lowers intraoperative blood loss, improves postoperative cervical curvature, and decreases the incidence of C5 nerve root paralysis and postoperative axial symptoms. Nonetheless, ACAF is associated with longer operative times and a higher incidence of postoperative dysphagia, though the overall incidence of postoperative complications is similar. It is important to note that these conclusions should be interpreted cautiously due to the limited sample size and the variable quality of the included studies. Further research involving larger, high-quality studies is warranted to validate these findings.

Exosomal OIP5-AS1 attenuates cerebral ischemia-reperfusion injury by negatively regulating TXNIP protein stability and inhibiting neuronal pyroptosis.

BACKGROUND: Cerebral ischemia-reperfusion injury (CIRI) can cause neuronal apoptosis and lead to irreversible brain injury. Numerous lncRNAs have been reported to play important roles in CIRI, but it is unclear whether these lncRNAs can function through exosomes. METHODS: In this study, we utilized the middle cerebral artery occlusion/reperfusion (MCAO/R) animal model and the oxygen-glucose deprivation/ reoxygenation (OGD/R) cell model. RNA sequencing was performed to screen for differentially expressed lncRNAs in M2 microglia-derived exosomes (M2-Exos). RNA pull-down, RNA immunoprecipitation, co-immunoprecipitation and ubiquitination assays were used to explore the molecular mechanism of OIP5-AS1 in alleviating CIRI. RESULTS: M2-Exos could alleviate nerve injury and pyroptosis after CIRI in vitro and in vivo. OIP5-AS1 was found to be significantly up-regulated in M2-Exos and down-regulated in OGD/R neurons, MCAO/R mice and ischemic stroke patients. In MCAO/R mice, OIP5-AS1 could reduce cerebral infarct size, cerebral edema and mNSS scores, and inhibit the expression levels of pyroptosis-related proteins in brain tissue. TXNIP was confirmed to be a reliable binding protein of OIP5-AS1. OIP5-AS1 overexpression significantly attenuated MCAO/R-induced upregulation of TXNIP at the protein level, but not at the mRNA level. OIP5-AS1 promoted the TXNIP degradation process and increased the ubiquitination of TXNIP. ITCH could bind to TXNIP. ITCH overexpression or knockdown did not alter the mRNA level of TXNIP, but negatively regulated TXNIP expression at the protein level. ITCH accelerated the degradation and ubiquitination of TXNIP, which could be attenuated by OIP5-AS1 knockdown. OIP5-AS1 could improve neuronal damage and inhibit neuronal pyroptosis through TXNIP. CONCLUSIONS: M2-Exo-derived OIP5-AS1 can induce TXNIP ubiquitination and degradation by recruiting ITCH, negatively regulate TXNIP protein stability, inhibit neuronal pyroptosis, and attenuate CIRI.

Verification of expression of LINC00648 in the serum of lung cancer patients by TCGA database.

TCGA data were used to verify the expression of LINC00648 in lung cancer patients to provide a reference for clinical practice.  Lung cancer transcriptome data were downloaded by the TCGA database and LINC00648 data were extracted for analysis. Fifty-two patients with lung cancer diagnosed in our hospital from May 2014 to March 2016 were collected as the patient group and 30 normal people as the control group. RT-qPCR was used to detect the expression of LINC00648 in serum, follow up of patients was carried out, and bioinformatics was used to analyze the potential mechanism of LINC00648. LINC00648 was highly expressed in lung cancer. Lymphatic metastasis and probability of low differentiation were significantly increased, and the overall survival rate of highly expressed patients with lung cancer was reduced and the prognosis was poor. LINC00648 had 17 potential miR-targeted and 78 miR-targeted mRNAs. LINC00648 was found to have participated in SMAD binding, transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific DNA binding, PDZ domain binding, cytokine binding, activin binding, RNA polymerase II activating transcription factor binding, transforming growth factor-beta receptor binding, etc. LINC00648 participated in the signal pathways of the Hippo signaling pathway, Transcriptional misregulation in cancer, MAPK signaling pathway, Proteoglycans in cancer. There were 55 co-expression pairs in PPI protein co-expression analysis, of which KIF11 was the most common.  High expression of LINC00648 in lung cancer patients indicates poor prognosis of patients and is expected to become a potential diagnostic marker for lung cancer.