Mesenchymal stem cell-derived exosomes ameliorate diabetic kidney disease through NOD2 signaling pathway.

BACKGROUND AND AIMS: Diabetic kidney disease (DKD) is one of the most common complications of diabetes. It is reported that mesenchymal stem cells (MSCs) derived exosomes (MSCs-Exo) may have great clinical application potential for the treatment of DKD, but the underlying mechanism has not been illustrated. To clarify the effect of MSC-Exo on NOD2 signaling pathway in podocytes under high glucose (HG) and DKD, we conduct this study. METHODS: We co-cultured podocytes and MSCs-Exo under 30 mM HG and injected MSCs-Exo into DKD mice, then we detected the NOD2 signaling pathway by western blot, qRT-PCT, immunofluorescence, transmission electron microscopy and immunohistochemistry both in vitro and in vivo. RESULTS: In vitro, HG lead to the apoptosis, increased the ROS level and activated the NOD2 signaling pathway in podocytes, while MSCs-Exo protected podocytes from injury reduced the expression of inflammatory factors including TNF-α, IL-6, IL-1ß, and IL-18 and alleviated the inflammatory response, inhibited the activation of NOD2 signaling pathway and the expression of it's downstream protein p-P65, p-RIP2, prevented apoptosis, increased cell viability in podocytes caused by HG. In vivo, MSCs-Exo alleviated renal injury in DKD mice, protected renal function, decreased urinary albumin excretion and inhibited the activation of NOD2 signaling pathway as well as the inflammation in renal tissue. CONCLUSION: MSCs-Exo protected the podocytes and DKD mice from inflammation by mediating NOD2 pathway, MSCs-Exo may provide a new target for the treatment of DKD.

Syntaxin 6 Enhances the Progression of Epithelial Ovarian Cancer by Promoting Cancer Cell Proliferation.

OBJECTIVES: The aim of this study is to evaluate the expression of syntaxin 6 (STX6) in epithelial ovarian cancer (EOC) and assess the effects of STX6 on the prognosis of patient. METHODS: Using information from the Kaplan-Meier Plotter database, the effects of STX6 expression on overall survival (OS) and progression-free survival (PFS) in ovarian cancer patients were examined. The clinical information of 147 patients with epithelial ovarian cancer was evaluated, and immunohistochemical staining was used to identify STX6 expression in postoperative tumor specimens, and the affection of STX6 expression on patient prognosis was assessed. In addition, the expression of STX6 in tumor tissue, peritoneal metastases (PM) derived from 13 patients with epithelial ovarian cancer and 6 normal ovarian specimens was detected by PCR and Western blot. In order to investigate how STX6 affects the proliferation of tumor cells, STX6 was also over expressed and knock down in ovarian cancer cell lines. Then colony formation assay was used to explore the effect of STX6 regulating on cell proliferation. RESULTS: Kaplan-Meier Plotter enrollment data analysis revealed that patients with overexpressed STX6 had substantially worse OS and PFS than individuals with low STX6 expression. Retrospective study revealed a significant (P<0.05) correlation between the STX6 expression and tumor classifications, tumor stage, peritoneal carcinomatosis index (PCI), and PFS survival of patients. Western blot and PCR findings for fresh samples showed that STX6 was overexpressed in both primary lesions and PM nodules of OC. SKOV3 cell proliferation was shown to be dramatically reduced by STX6 knockdown and promoted by STX6 overexpression, according to the in vitro experiments. CONCLUSION: STX6 may increase the progression of epithelial OC by encouraging the proliferation of cancer cells, indicating that STX6 was a viable therapeutic target of epithelial OC.

Life-threatening complications after microvascular decompression procedure: Lessons from a consecutive series of 596 patients.

The microvascular decompression procedure (MVD) is widely utilized on patients with neurovascular compression syndromes, such as trigeminal neuralgia, hemifacial spasm and glossopharyngeal neuralgia, which have failed medical therapy. However, surgical complications are an ongoing problem. We retrospectively reviewed a total of 596 patients undergoing MVD in the Affiliated Hospital of Qingdao University from January 2008 to December 2018. Furthermore, we discussed the cases with life-threatening complications to determine the potential causes, aiming to achieve the goal of safer microvascular decompression. There were seven cases with life-threatening complications. Of those complications, one was cerebellar infarction with acute hydrocephalus, one was infarction of the cerebellum and the brain stem with acute hydrocephalus and serious intracranial infection, two were cerebellar haematoma, one was multiple haemorrhage with acute hydrocephalus, one was supratentorial subdural haematoma, and one was cerebellar swelling with acute hydrocephalus. After therapy, one patient died, one was in a persistent vegetative state, and five were discharged from the hospital upon recovery. In brief, MVD is a safe operation, and life-threatening complications accompanying MVD are rare, but require attention. The causes of some life-threatening complications are still not completely clear. Surgeons should continuously improve surgical techniques and perioperative care to reduce potential risks.

Microsurgical Treatment of 86 Anterior Choroidal Artery Aneurysms: Analysis of Factors Influencing the Prognosis.

PURPOSE: To explore factors affecting the prognosis of choroidal anterior artery aneurysm (AChAA) and provide a reference for improving the postoperative outcome. METHODS: The clinical data of 86 patients with AChAA who underwent treatment by a single surgeon were collected and analyzed retrospectively. Univariate analysis and multivariate logistic regression analysis were conducted to examine 12 factors that possibly affected outcome. RESULTS: The five factors that affected the patient outcomes were times of subarachnoid hemorrhage (SAH), characteristics of SAH on computed tomography (CT), Hunt-Hess grade, aneurysm size, and presence or absence of postoperative complications. Characteristics of SAH on CT (odds ratio [OR]: 3.727; p = 0.000; 95% confidence interval [CI], 1.850-7.508), aneurysm size (OR: 6.335; p = 0.000; 95% CI, 2.564-15.647), and presence or absence of postoperative complications (OR: 4.141; p = 0.000; 95% CI, 1.995-8.599) were independent risk factors influencing the prognosis. In addition, the incidence of postoperative ischemia (caused by anterior choroidal artery syndrome) is related to the aneurysm emitting part and presence or absence of intraoperative rupture. CONCLUSIONS: The analysis of characteristics of SAH on CT, aneurysm size, and presence or absence of postoperative complications can roughly determine the outcome of patients with AChAAs.

Levetiracetam Reduces Early Inflammatory Response After Experimental Intracerebral Hemorrhage by Regulating the Janus Kinase 2 (JAK2)-Signal Transducer and Activator of Transcription 3 (STAT3) Signaling Pathway.

BACKGROUND Levetiracetam (LEV) is an antiepileptic drug that promotes recovery of neurological function by alleviating inflammatory reactions. However, it is not known whether it can improve secondary brain injury after intracerebral hemorrhage (ICH). The aim of this study was to determine whether LEV can reduce early inflammatory response after ICH in rats. MATERIAL AND METHODS An in vitro model of early inflammation was created by treating microglia cells with lipopolysaccharide (LPS). After exposure to various concentrations of LEV, the expression levels of NF-kappaB and STAT3 and inflammatory factors such as interleukin (IL)-1ß and tumor necrosis factor (TNF)-alpha in microglia were detected. In vivo, autologous blood was used to induce the rat ICH model. The effects of LEV on post-cerebral hemorrhagic inflammatory response were examined using neurobehavioral tests, FJC staining, brain water content testing, and analysis of protein expression levels of NF-kappaB, JAK2, STAT3, and inflammatory factors. RESULTS LEV treatment significantly reduced the expression of inflammatory factors and protein expression levels of NF-kappaB and STAT3 in LPS-treated microglia cells (P<0.05). In male Sprague-Dawley (SD) rats, LEV treatment markedly decreased the volume of hematoma and the number of degenerative neurons (P<0.05). It also improved the neurological function and relieved brain edema. The protein expression levels of NF-kappaB, JAK2, and STAT3 were significantly lower in the ICH+LEV group than in the control group (P<0.05). CONCLUSIONS Our study suggests that treatment with LEV alleviates early inflammatory responses induced by ICH. Mechanistically, LEV inhibited the JAK2-STAT3 signaling pathway and reduced neuronal injury around the hematoma, and ameliorated brain edema, all of which promoted recovery of nerve function after hemorrhage.

Identification of 2 Potential Core Genes for Influence of Gut Probiotics on Formation of Intracranial Aneurysms by Bioinformatics Analysis.

BACKGROUND Rupture of intracranial aneurysms (IA) is associated with high rates of mortality around the world. Use of intestinal probiotics can regulate the pathophysiology of aneurysms, but the details of the mechanism involved have been unclear. MATERIAL AND METHODS The GEO2R analysis website was used to detect the DEGs between IAs, AAAs, samples after supplementation with probiotics, and normal samples. The online tool DAVID provides functional classification and annotation analyses of associated genes, including GO and KEGG pathway. PPI of these DEGs was analyzed based on the STRING database, followed by analysis using Cytoscape software. RESULTS We found 170 intersecting DEGs (contained in GSE75240 and more than 2 of the 4 aneurysms datasets), 5 intersecting DEGs (contained in all datasets) and 1 intersecting DEG (contained in GSE75240 and all IAs datasets). GO analysis results suggested that the DEGs primarily participate in signal transduction, cell adhesion, immune response, response to drug, extracellular matrix organization, cell-cell signaling, and inflammatory response in the BP terms, and the KEGG pathways are mainly enriched in focal adhesion, cytokine-cytokine receptor interaction, ECM-receptor interaction, amoebiasis, chemokine signaling pathway, proteoglycans, and PI3K-Akt signaling pathway in cancer pathways. Through PPI network analysis, we confirmed 2 candidates for further study: CAV1 and MYH11. These downregulated DEGs are associated with the formation of aneurysms, and the change of these DEGs is the opposite in probiotics-treated animals. CONCLUSIONS Our study suggests that MYH11 and CAV1 are potential target genes for prevention of aneurysms. Further experiments are needed to verify these findings.

Intracranial Mirror Aneurysm: Epidemiology, Rupture Risk, New Imaging, Controversies, and Treatment Strategies.

There are some controversies about the surgical treatment strategy of mirror aneurysms. Whether to choose 1-stage or 2-stage surgery, bilateral or unilateral craniotomy, or surgical or interventional treatment are the main points in dispute. In this review, the different surgery strategies faced by patients are discussed. Different surgical methods are adopted based on the patient's individual state and the location and size of the aneurysm. A new imaging method is introduced using 3D Slicer, which clearly recognizes the relationship among aneurysm, brain tissue, skull, and nerve. The 3D Slicer can help surgeons undertake adequate preoperative preparation. In addition, we also introduce some ruptured factors (e.g., age, gender, hypertension, morphologic, and hemodynamic) concerning mirror aneurysm. Systematic discussion of the controversies and methods in surgical treatment of mirror aneurysms may provide new perspectives in future research for the prevention and treatment of mirror aneurysms.

Surgical Treatment Strategy and Perioperative Analysis of Patients With Intracranial Mirror Aneurysms.

OBJECT: Intracranial mirror aneurysm is a type of multiple aneurysms, which is rare in clinical and literature. There is no unified conclusion on the treatment strategy of mirror aneurysms. Therefore, our study evaluated the surgical approach and prognosis of a series of mirror aneurysms, and explored the clinical features and treatment strategies of mirror aneurysms. METHODS: This study retrospectively analyzed the clinical features, imaging data, treatment methods and post-hospital results of 67 cases of mirror aneurysms admitted to our department from December 1997 to April 2018. RESULTS: There were 20 males and 47 females with an average age of 53.6 years. Mirror aneurysms are mainly located in the posterior communicating artery and middle cerebral artery. Of 67 patients, 1-stage unilateral craniotomy with bilateral aneurysms in 18 cases, 1-stage bilateral craniotomy with bilateral aneurysms in 17 cases, staged treatment of bilateral aneurysms in 13 cases, and 19 cases only treated the responsible aneurysms. 57 cases with good recovery; 7 cases were self-care; 1 case was heavy disability; 2 cases were dead. In parallel, 8 cases had different degrees of cerebral infarction, 3 cases of hydrocephalus, 3 cases of oculomotor nerve injury, 2 cases died of cerebral hernia resulted from intracranial hypertension, and the remaining 53 cases were better. CONCLUSIONS: The treatment of the mirror aneurysm should be based on the location, size, shape of the aneurysm, the patient's clinical manifestations and the surgeon's experience to choose a personalized treatment.

A highly sensitive gas sensor employing biomorphic SnO2 with multi-level tubes/pores structure: bio-templated from waste of flax.

Metal oxide gas sensors with porous structures are widely used in numerous applications ranging from health monitoring and medical detection to safety; in this study, we report a highly sensitive SnO2 gas sensor with a multi-level tube/pore structure prepared via biomimetic technology using flax waste as a bio-template and a simple wet chemical process combined with subsequent annealing. Indeed, MLTPS not only maintained and improved the excellence of porous structure gas sensing materials with abundant active sites and large surface-to-volume ratios, but also overcame the deficiency of the lack of gas diffusion channels in porous gas sensing materials. Thus, this novel multi-level tube/pore SnO2 gas sensor exhibited significantly enhanced sensing performance, e.g. an ultra-low response concentration (250 ppb), a high response (87.9), a fast response (9.2 s), a low operating temperature (130 °C) and good stability, for formaldehyde. On the basis of these results, via the reuse of agricultural waste, this study provides a new concept for the low-cost synthesis of environmentally friendly and effective multi-level tube/pore gas sensor materials.