Case report of epileptic seizure during awake craniotomy of functional area glioma and literature study.

Intraoperative seizure is the most prevalent and serious complication of awake craniotomy in functional areas, which may not only trigger complications of the surgical procedure or even the failure of awake craniotomy but also may result in adverse consequences to patients. The influencing factors of intraoperative seizures are unclear, and only the possible influencing factors can be acquired from the examination and summary of existing cases to offer guidance for the seizure prevention of intraoperative epilepsy.

[Cangxi Tongbi Capsules promote chondrocyte autophagy by regulating circRNA＿0008365/miR-1271/p38 MAPK pathway to inhibit development of knee osteoarthritis].

To investigate the mechanism by which Cangxi Tongbi Capsules promote chondrocyte autophagy to inhibit knee osteoarthritis(KOA) progression by regulating the circRNA＿0008365/miR-1271/p38 mitogen-activated protein kinase(MAPK) pathway. The cell and animal models of KOA were established and intervened with Cangxi Tongbi Capsules, si-circRNA＿0008365, si-NC, and Cangxi Tongbi Capsules combined with si-circRNA＿0008365. Flow cytometry and transmission electron microscopy were employed to determine the level of apoptosis and observe autophagosomes, respectively. Western blot was employed to reveal the changes in the protein levels of microtubule-associated protein light chain 3(LC3)Ⅱ/Ⅰ, Beclin-1, selective autophagy junction protein p62/sequestosome 1, collagen Ⅱ, a disintegrin and metalloproteinase with thrombospondin motifs 5(ADAMTS-5), and p38 MAPK. The mRNA levels of circRNA＿0008365, miR-1271, collagen Ⅱ, and ADAMTS-5 were determined by qRT-PCR. Hematoxylin-eosin staining was employed to reveal the pathological changes of the cartilage tissue of the knee, and enzyme-linked immunosorbent assay to measure the levels of interleukin-1ß(IL-1ß) and tumor necrosis factor-alpha(TNF-α). The chondrocytes treated with IL-1ß showed down-regulated expression of circRNA＿0008365, up-regulated expression of miR-1271 and p38 MAPK, lowered autophagy level, increased apoptosis rate, and accelerated catabolism of extracellular matrix. The intervention with Cangxi Tongbi Capsules up-regulated the expression of circRNA＿0008365, down-regulated the expression of miR-1271 and p38 MAPK, increased the autophagy level, decreased the apoptosis rate, and weakened the catabolism of extracellular matrix. However, the effect of Cangxi Tongbi Capsules was suppressed after interfering with circRNA＿0008365. The in vivo experiments showed that Cangxi Tongbi Capsules dose-dependently inhibited the p38 MAPK pathway, enhanced chondrocyte autophagy, and mitigated articular cartilage damage and inflammatory response, thereby inhibiting the progression of KOA in rats. This study indicated that Cangxi Tongbi Capsules promoted chondrocyte autophagy by regulating the circRNA＿0008365/miR-1271/p38 MAPK pathway to inhibit the development of KOA.

AI-predicted mpMRI image features for the prediction of clinically significant prostate cancer.

PURPOSE: To evaluate the feasibility of using mpMRI image features predicted by AI algorithms in the prediction of clinically significant prostate cancer (csPCa). MATERIALS AND METHODS: This study analyzed patients who underwent prostate mpMRI and radical prostatectomy (RP) at the Affiliated Hospital of Jiaxing University between November 2017 and December 2022. The clinical data collected included age, serum prostate-specific antigen (PSA), and biopsy pathology. The reference standard was the prostatectomy pathology, and a Gleason Score (GS) of 3 + 3 = 6 was considered non-clinically significant prostate cancer (non-csPCa), while a GS ≥ 3 + 4 was considered csPCa. A pre-trained AI algorithm was used to extract the lesion on mpMRI, and the image features of the lesion and the prostate gland were analyzed. Two logistic regression models were developed to predict csPCa: an MR model and a combined model. The MR model used age, PSA, PSA density (PSAD), and the AI-predicted MR image features as predictor variables. The combined model used biopsy pathology and the aforementioned variables as predictor variables. The model's effectiveness was evaluated by comparing it to biopsy pathology using the area under the curve (AUC) of receiver operation characteristic (ROC) analysis. RESULTS: A total of 315 eligible patients were enrolled with an average age of 70.8 ± 5.9. Based on RP pathology, 18 had non-csPCa, and 297 had csPCa. PSA, PSAD, biopsy pathology, and ADC value of the prostate outside the lesion (ADCprostate) varied significantly across different ISUP grade groups of RP pathology (P < 0.001). Other clinical variables and image features did not vary significantly across different ISUP grade groups (P > 0.05). The MR model included PSAD, the ratio of ADC value between the lesion and the prostate outside the lesion (ADClesion/prostate), the signal intensity ratio of DWI between the lesion and the prostate outside the lesion (DWIlesion/prostate), and the ratio of DWIlesion/prostate to ADClesion/prostate. The combined model included biopsy pathology, ADClesion/prostate, mean signal intensity of the lesion on DWI (DWIlesion), DWI signal intensity of the prostate outside the lesion (DWIprostate), and signal intensity ratio of DWI between the lesion and the prostate outside the lesion (DWIlesion/prostate). The AUC of the MR model (0.830, 95% CI 0.743, 0.916) was not significantly different from that of biopsy pathology (0.820, 95% CI 0.728, 0.912, P = 0.884). The AUC of the combined model (0.915, 95% CI 0.849, 0.980) was higher than that of the biopsy pathology (P = 0.042) and MR model (P = 0.031). CONCLUSION: The aggressiveness of prostate cancer can be effectively predicted using AI-extracted image features from mpMRI images, similar to biopsy pathology. The prediction accuracy was improved by combining the AI-extracted mpMRI image features with biopsy pathology, surpassing the performance of biopsy pathology alone.

Cox15 is a novel oncogene that required for lung cancer cell proliferation.

Lung cancer is one of the most malignant and prevalent tumors and accounts for the vast majority of cancer death worldwide. However, the molecular mechanisms underlying lung cancer progression are poorly understood. Here, we reveal that both transcription and protein expression levels of Cox15 were increased in lung cancer. Nrf2 specifically binds to the Cox15 promoter and triggers Cox15 expression at the transcriptional level. Cox15 functions as a novel oncogene that facilitates lung cancer cell proliferation. Additionally, Aripiprazole, a potent inhibitor of Cox15, executives profoundly suppressive effects on lung cancers cells growth and tumor progression in vivo and in vitro through exerting therapeutic effects. Taken together, our results unravel that Cox15 holds great potential to act as a prognostic molecule for lung cancer patients' prognosis in the future.

SH2B3, Transcribed by STAT1, Promotes Glioblastoma Progression Through Transducing IL-6/gp130 Signaling to Activate STAT3 Signaling.

Glioblastoma (GBM) is the most common and aggressive brain tumor in adults. The aberrant activation of STAT3 commonly occurs in GBM and is a key player in GBM tumorigenesis. Yet, the aberrant activation of STAT3 signaling is not fully understood. Here, we report that SH2B adaptor protein 3 (SH2B3) is highly expressed in GBM and preferentially expressed in GBM stem cells (GSCs). Moreover, SH2B3 high expression predicts worse survival of GBM patients. Targeting SH2B3 considerably impairs GBM cell proliferation, migration, and GSCs' self-renewal in vitro as well as xenograft tumors growth in vivo. Additionally, we provide evidence suggesting that STAT1 directly binds to the promoter of SH2B3 and activates SH2B3 expression in the transcriptional level. Functionally, SH2B3 facilitates GBM progression via physically interacting with gp130 and acting as an adaptor protein to transduce IL-6/gp130/STAT3 signaling. Together, our work firstly uncovers that the STAT1/SH2B3/gp130/STAT3 signaling axis plays critical roles in promoting GBM progression and provides insight into new prognosis marker and therapeutic target in GBM.

Quercetin suppresses apoptosis of chondrocytes induced by IL-1ß via inactivation of p38 MAPK signaling pathway.

The objective of the present study was to investigate the effect of quercetin and evaluate its protective effect on articular cartilage in patients with osteoarthritis (OA), by intervening the p38 pathway. The target factors of quercetin protecting articular cartilage in patients with OA were predicted scientifically and analyzed to predict the possible pathways by using network pharmacology. A pathway predicted to be closely associated with osteoarthritis was chosen for experimental verification in in vitro cells. The optimal intervention drug concentrations were selected by the of Cell Cycle Kit-8 assay, osteoarthritis and inflammatory factors relevant to osteoarthritis, interleukin-1ß and tumor necrosis factor-α, were tested by of enzyme-linked immunosorbent assay, and the expression of relevant proteins and mRNA of the p38 signaling pathway was tested by reverse transcription-quantitative PCR and western blotting, following quercetin intervention. It was found that quercetin, at the concentration of 100 umol/l, can decrease inflammatory factors relevant to OA, inhibit the expression of p38, matrix metalloprotease 13 and ADAMTS in the pathway, and promote the expression of collagen Ⅱ. Therefore, it is postulated that quercetin can lower the expression of inflammatory factors in cartilage for the prevention and treatment of OA, and the expression level of relevant factors can be changed positively by blocking the p38 MAPK signaling pathway. Thus, quercetin can promote the repair of degenerative chondrocytes and protect articular chondrocytes.

miR­124­3p inhibits the viability and motility of glioblastoma multiforme by targeting RhoG.

The mortality rate of patients with glioma is increasing worldwide per annum. This is attributed to the poor disease prognosis, most notably for high­grade gliomas (grade III and IV), which does not improve the overall patient survival. The dysregulation of microRNA (miRNA/miR)­124­3p is found in a variety of tumors. However, the association between miR­124­3p expression and its target genes in glioma has not been thoroughly elucidated. The present study aimed to explore the possible effects of miR­124­3p and its proved target, Ras homology Growth­related (RhoG), on the oncogenic events associated with glioblastoma multiforme (GBM) development. The data demonstrated an inverse association between miR­124­3p and RhoG expression levels during GBM progression in GBM tissues and cells. U87 and U251 cells were employed for the in vitro assays. Luciferase reporter assays revealed that miR­124­3p interacted with RhoG at the RhoG 3' untranslated region and inhibited RhoG expression in GBM cells. Functionally, enriched miR­124­3p repressed RhoG transcription and suppressed GBM cell proliferation and migration, promoting apoptosis and altering the expression or activity of the apoptosis­related proteins of GBM cells. By contrast, the inhibition of miR­124­3p in GBM cells upregulated RhoG levels and promoted the proliferation of GBM cells. The knock down of RhoG expression by specific small interfering RNA sequences partially neutralized the effects induced by the miR­124­3p inhibitor. In conclusion, the present study demonstrated the crucial effects of miR­124­3p on the development and deterioration of GBM by targeting RhoG.

Nurr1 promotes neurogenesis of dopaminergic neuron and represses inflammatory factors in the transwell coculture system of neural stem cells and microglia.

INTRODUCTION: Neural stem cells (NSCs) are the most promising cells for cell replacement therapy for Parkinson's disease (PD). However, a majority of the transplanted NSCs differentiated into glial cells, thereby limiting the clinical application. Previous studies indicated that chronic neuroinflammation plays a vital role in the degeneration of midbrain DA (mDA) neurons, which suggested the developing potential of therapies for PD by targeting the inflammatory processes. Thus, Nurr1 (nuclear receptor-related factor 1), a transcription factor, has been referred to play a pivotal role in both the differentiation of dopaminergic neurons in embryonic stages and the maintenance of the dopaminergic phenotype throughout life. AIM: This study investigated the effect of Nurr1 on neuroinflammation and differentiation of NSCs cocultured with primary microglia in the transwell coculture system. RESULTS: The results showed that Nurr1 exerted anti-inflammatory effects and promoted the differentiation of NSCs into dopaminergic neurons. CONCLUSIONS: The results suggested that Nurr1 protects dopaminergic neurons from neuroinflammation insults by limiting the production of neurotoxic mediators by microglia and maintain the survival of transplanted NSCs. These phenomena provided a new theoretical and experimental foundation for the transplantation of Nurr1-overexpressed NSCs as a potential treatment of PD.

[Protective effect of Ginkgo biloba extract on paracetamol-induced acute hepatic injury in mice].

OBJECTIVE: To investigate the protective effects of Ginkgo biloba extract(GBE) on paracetamol(APAP)-induced acute hepatic injury in mice and its mechanism. METHODS: Thirty mice were randomly divided into control group, model group, GBE low, medium and high-dose(50,100,and 200 mg·kg-1)groups,with 6 mice in each group. All mice except control group were administered with APAP(300 mg/kg)for one time by intraperitoneal injection. The mice in GBE low, medium and high-dose groups were intragastric administered with GBE for 2 d consecutively, then samples were harvested for analysis. The appearance and pathology of liver were observed. The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum and the levels of superoxide dismutase (SOD), myeloperoxidase(MPO), glutathione (GSH) and malondialdehyde (MDA) in hepatic tissue were measured. Western blot was used to detect the protein expressions of Nrf2 and HO-1. RESULTS: Compared with control group, in model group, the appearance and pathology of liver were bad, the levels of ALT,AST,TNF-α and IL-6 in serum were increased significantly(P<0.01),the levels of GSH and SOD were decreased while the levels of MDA and MPO were increased in hepatic tissue(P<0.01), the expressions of Nrf2 and HO-1 were increased in hepatic tissue(P<0.05). Compared with model group, in GBE groups, the appearance and pathology of liver were improved, the levels of ALT,AST,TNF-α and IL-6 in serum were decreased significantly(P<0.01), the levels of GSH and SOD were increased while the levels of MDA and MPO were decreased in hepatic tissue(P<0.01), the expression of Nrf2 and HO-1 were increased in hepatic tissue(P<0.05). The high-dose of GBE possessed the most obvious treatment effect among them. CONCLUSIONS: GBE may play a protective role in APAP-induced acute hepatic injury through Nrf2/HO-1 pathway.

Long non-coding RNA PAR5 inhibits the proliferation and progression of glioma through interaction with EZH2.

Emerging evidence suggests that long non-coding RNAs (lncRNAs) may be involved in modulating various aspects of tumor biology and serve as potential therapeutic targets as well as novel biomarkers in the treatment of glioma. The present study investigated the role of lncRNA, Prader Willi/Angelman region RNA 5 (PAR5; also known as PWAR5), in glioma and its clinical significance in glioma cases. The expression levels of PAR5 were determined in clinical samples and U87, U251 cells using real-time reverse transcription quantitative polymerase chain reaction (qRT-PCR) analysis. The effects of PAR5 on cell proliferation, migration and invasion were determined using in vitro assays. RNA immunoprecipitation (RIP) and RNA pull-down assays, as well as the evauation of the expression of various oncogenes were carried out to reveal the underlying mechanisms. We found that PAR5 was significantly downregulated in glioma tissues and cell lines. Furthermore, PAR5 expression was negatively correlated with tumor size, World Health Organization (WHO) grade and Karnofsky performance score (KPS). Patients with low PAR5 expression in tumors had a worse overall survival compared to those with higher expression. Finally, in vitro restoration of PAR5 expression inhibited human glioma cell proliferation, invasion and migration by binding to EZH2 and regulating oncogene expression. This finding may provide a therapeutic approach for the future treatment of glioma.

MicroRNA-584 functions as a tumor suppressor and targets PTTG1IP in glioma.

MicroRNAs (miRNAs) are small noncoding RNA molecules that regulate gene expression at the post transcriptional level. Compelling evidence shows that there are causative links between miRNAs deregulation and cancer development and progression. In this study, we demonstrated that miR-584 was downregulated in human glioma and could suppress growth of the human glioma cell line U87-MG and U251-MG. Bioinformatics analysis indicated that PTTG1IP was a putative target of miR-584. In a Luciferase reporter system, we confirmed that PTTG1IP was a direct target gene of miR-584. These findings indicate that miR-584 suppresses glioma cell growth by negatively regulating the expression of PTTG1IP, suggesting that miR-584 has a tumor suppressive role in human glioma pathogenesis.

Comparison of the protective efficacy of recombinant adenoviruses against classical swine fever.

Classical swine fever (CSF), which is caused by classical swine fever virus (CSFV), is a highly contagious and often fatal swine disease that is responsible for significant losses to the swine industry worldwide. Previously, we demonstrated that pigs immunized with a recombinant adenovirus (rAdV-E2) expressing the E2 glycoprotein of CSFV were protected against virulent CSFV; however, a few pigs showed a short-term fever and occasional pathological changes. To enhance the efficacy of the vaccine, we constructed two recombinant adenoviruses, namely, rAdV-E2UL49, which encodes the CSFV E2 gene fused with the UL49 gene from pseudorabies virus (PRV), and rAdV-optiE2, which expresses the codon-optimized CSFV E2 gene. With these viruses, we performed a comparative immunogenicity trial in rabbits and pigs and compared these recombinant adenovirus vaccines (rAdV-E2UL49 and rAdV-optiE2) with the one containing the wild-type E2 gene (rAdV-E2). In terms of antibody titers, IFN-γ production, lymphocyte proliferation, viral loads and clinical protection from the disease, rAdV-E2UL49 was more immunogenic and protective against C-strain CSFV in rabbits and Shimen strain CSFV in pigs than rAdV-optiE2 and rAdV-E2. Data from this study could assist in making decisions for further development of recombinant adenoviruses as vaccine candidates against CSF.