The Fyn related kinase (FRK), a member of intracellular Src-related tyrosine kinases, was recently reported to function as a potent tumor suppressor in several cancer types. However, the expression level and functional significance of FRK in human malignant glioma, which is characterized by high migration and invasion potential, have never been investigated. We reported here that FRK reduced cell migration and invasion via inhibiting the c-Jun N-terminal protein kinase (JNK)/c-Jun signaling pathway in glioma cells. The mRNA and protein levels of FRK were significantly down-regulated in human primary glioma tissues. In addition, over-expression of FRK inhibited migration and invasion of glioma cells and excretion of the matrix metalloprotease 2 (MMP2), an index of migration and invasion. Furthermore, over-expression of FRK inhibited phosphorylation of JNK and c-Jun, which play important role in cell migration and invasion. Finally, the effects of FRK on cell migration and invasion and JNK/c-Jun inhibition were abolished by anisomycin, a JNK specific activator. In summary, these results clearly indicate that FRK may play a protective role against the progression of glioma by suppressing cell migration and invasion, suggesting that FRK needs to be further studied in its detail mechanism and clinical significant.

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Background Adiponectin is an adipocytokine that plays a key regulatory role in glucose and lipid metabolism in obesity. The prevalence of obesity has led to an increase in the incidence of obesity-related glomerulopathy (ORG). This study aimed to identify the protective role of adiponectin in ORG. Methods Small-interfering RNA (siRNA) against the gene encoding adiponectin was transfected into podocytes. The oxidative stress level was determined using a fluorometric assay. Apoptosis was analyzed by flow cytometry. The expressions of podocyte markers and pyrin domain containing protein 3 (NLRP3) inflammasome-related proteins were measured by qRT-PCR, immunohistochemistry, and Western blot. Results Podocytes treated with palmitic acid (PA) showed downregulated expressions of podocyte markers, increased apoptosis, upregulated levels of NLRP3 inflammasome-related proteins, increased production of inflammatory cytokines (IL-18 and IL-1β), and induced activation of NF-κB as compared to the vehicle-treated controls. Decreased adiponectin expression was observed in the serum samples from high fat diet (HFD)-fed mice. Decreased podocin expression and upregulated NLRP3 expression were observed in the kidney samples from high fat diet (HFD)-fed mice. Treatment with adiponectin or the NLRP3 inflammasome inhibitor, MCC950, protected cultured podocytes against podocyte apoptosis and inflammation. Treatment with adiponectin protected mouse kidney tissues against decreased podocin expression and upregulated NLRP3 expression. The knockout of adiponectin gene by siRNA increased ROS production, resulting in the activation of NLRP3 inflammasome and the phosphorylation of NF-κB in podocytes. Pyrrolidine dithiocarbamate, an NF-κB inhibitor, prevented adiponectin from ameliorating FFA-induced podocyte injury and NLRP3 activation. Conclusions Our study showed that adiponectin ameliorated PA-induced podocyte injury in vitro and HFD-induced injury in vivo via inhibiting the ROS/NF-κB/NLRP3 pathway. These data suggest the potential use of adiponectin for the prevention and treatment of ORG.

ObjectivePineal region meningiomas are deeply located and adjacent to critical neurovascular structures, making them one of the most challenging areas to access. The authors presented a combined microscopic and endoscopic surgery and investigated its value in resecting pineal region meningiomas.MethodsTwelve patients with pineal region meningiomas from February 2017 to December 2020 were retrospectively reviewed. All patients underwent combined microscopic and endoscopic surgery using the occipital-parietal transtentorial approach. Perioperative clinical, surgical, and radiographic data were collected.ResultsThe endoscope provided a wider view and increased visualization of residual tumors. All tumors were completely resected, and none of the patients died. Total resection was believed to have been achieved in four patients, but the residual tumor was detected after endoscopic exploration and was completely resected with an endoscope. Only one patient had transient visual field deficits. No recurrence was observed during follow-up.ConclusionsCombined microscopic-endoscopic surgery for pineal region meningiomas eliminates microscopic blind spots, thus compensating for the shortcomings of the traditional occipital transtentorial approach. It is a promising technique for minimally invasive maximal resection of pineal region meningiomas.

Increasing evidence indicates that early brain injury (EBI) can contribute to poor outcomes following subarachnoid hemorrhage (SAH), and is associated with apoptosis. Cyclin-dependent kinase 5 (Cdk5) is a key mediator of neuronal viability. The role of Cdk5 in several neurological disorders has been elucidated; however, its role in EBI after SAH remains unclear. The present study aimed to explore the involvement of Cdk5 in EBI after SAH. The expression levels of Cdk5, Cdk5 phosphorylated at Tyr15 (Cdk5-pTyr15) and p25 (a Cdk5 activator) were assessed by western blotting, and the cell distribution of Cdk5 was demonstrated by double immunofluorescence. The expression levels of caspase-3 and cytochrome c were evaluated by western blotting to assess the severity of neuronal apoptosis. Nissl and TUNEL staining experiments were performed to observe the effects of roscovitine, a Cdk5 inhibitor, on EBI following SAH. The results indicated that the expression levels of Cdk5, p25 and Cdk5-pTyr15 significantly increased in the rat temporal cortex following SAH. Immunofluorescence staining indicated that Cdk5 was expressed in the neurons and astrocytes of the rat cortex after SAH and that Cdk5 underwent nuclear translocation in neurons. Roscovitine administration effectively inhibited Cdk5 activation. In conclusion, roscovitine treatment significantly mitigated EBI and alleviated cerebral edema following SAH. These findings suggest that Cdk5 is an important target in SAH therapy.