Integrated Analysis of Multiple Microarray Studies to Identify Novel Gene Signatures in Ulcerative Colitis.

Background: Ulcerative colitis (UC) is a chronic, complicated, inflammatory disease with an increasing incidence and prevalence worldwide. However, the intrinsic molecular mechanisms underlying the pathogenesis of UC have not yet been fully elucidated. Methods: All UC datasets published in the GEO database were analyzed and summarized. Subsequently, the robust rank aggregation (RRA) method was used to identify differentially expressed genes (DEGs) between UC patients and controls. Gene functional annotation and PPI network analysis were performed to illustrate the potential functions of the DEGs. Some important functional modules from the protein-protein interaction (PPI) network were identified by molecular complex detection (MCODE), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG), and analyses were performed. The results of CytoHubba, a plug for integrated algorithm for biomolecular interaction networks combined with RRA analysis, were used to identify the hub genes. Finally, a mouse model of UC was established by dextran sulfate sodium salt (DSS) solution to verify the expression of hub genes. Results: A total of 6 datasets met the inclusion criteria (GSE38713, GSE59071, GSE73661, GSE75214, GSE87466, GSE92415). The RRA integrated analysis revealed 208 significant DEGs (132 upregulated genes and 76 downregulated genes). After constructing the PPI network by MCODE plug, modules with the top three scores were listed. The CytoHubba app and RRA identified six hub genes: LCN2, CXCL1, MMP3, IDO1, MMP1, and S100A8. We found through enrichment analysis that these functional modules and hub genes were mainly related to cytokine secretion, immune response, and cancer progression. With the mouse model, we found that the expression of all six hub genes in the UC group was higher than that in the control group (P < 0.05). Conclusion: The hub genes analyzed by the RRA method are highly reliable. These findings improve the understanding of the molecular mechanisms in UC pathogenesis.

Pyk2/MCU Pathway as a New Target for Reversing Atherosclerosis.

Objective: Multiple mechanisms including vascular endothelial cell damage have a critical role in the formation and development of atherosclerosis (AS), but the specific molecular mechanisms are not exactly clarified. This study aims to determine the possible roles of proline-rich tyrosine kinase 2 (Pyk2)/mitochondrial calcium uniporter (MCU) pathway in AS mouse model and H2O2-induced endothelial cell damage model and explore its possible mechanisms. Approach and Results: The AS mouse model was established using apolipoprotein E-knockout (ApoE-/-) mice that were fed with a high-fat diet. It was very interesting to find that Pyk2/MCU expression was significantly increased in the artery wall of atherosclerotic mice and human umbilical vein endothelial cells (HUVECs) attacked by hydrogen peroxide (H2O2). In addition, down-regulation of Pyk2 by short hairpin RNA (shRNA) protected HUVECs from H2O2 insult. Furthermore, treatment with rosuvastatin on AS mouse model and H2O2-induced HUVEC injury model showed a protective effect against AS by inhibiting the Pyk2/MCU pathway, which maintained calcium balance, prevented the mitochondrial damage and reactive oxygen species production, and eventually inhibited cell apoptosis. Conclusion: Our results provide important insight into the initiation of the Pyk2/MCU pathway involved in AS-related endothelial cell damage, which may be a new promising target for atherosclerosis intervention.

Risk factors for intracranial infection after craniotomy: A case-control study.

BACKGROUND: Intracranial infection, serving as a severe postoperative infection after craniotomy, poses significant problems for patients' outcomes. OBJECTIVE: To explore risk factors for intracranial infection after craniotomy. METHODS: A total of 2,174 patients who underwent craniotomy from 1 May 2018 to 30 June 2019 were retrospectively studied. Finally, 196 patients with intracranial infections were classified as case group, and 392 patients randomly selected from patients without intracranial infection were classified as control group. Demographic, clinical, laboratory, microbiological, and antimicrobial data were systemically recorded. The characteristics, pre- and postoperative variables, and other variables were evaluated as risk factors for intracranial infection by univariate analysis and binary logistic regression model. RESULTS: There was no significant difference in terms of demographics between two groups, except for gender, hypertension, length of stay (LOS), intraoperative blood loss, tumor, and trauma surgery. The independent risk factors were male, age ≤45, hypertension, tumor surgery, surgery in autumn (compared with spring), surgical duration ≥4 hr, intraoperative blood loss ≥400 ml, and postoperative oral infection, coma, and serum RBC > normal value. Trauma surgery (p < .001, OR = 0.05, 95% CI: 0.017-0.144) was an independent protective factor (p < .05, OR < 1) for intracranial infection. All 196 patients in the case group submitted specimens for cerebrospinal fluid (CSF) cultures, and 70 (35.71%) patients had positive results. Gram-positive pathogens predominated (59 cases, 84.28%). Staphylococcus were the most common causative pathogens, and fully resistant to aztreonam, cefazolin, and benzylpenicillin, but not resistant to linezolid and minocycline. CONCLUSION: Identifying the risk factors, pathogens, and pathogens' antibiotic resistance for intracranial infection after craniotomy plays an important role in the prognosis of patients.

Effect of pre-surgery assessments on the prognosis of patients received extracranial-intracranial bypass surgery.

BACKGROUND: Extracranial-intracranial (EC-IC) bypass surgery has been used to improve the conditions of cerebral ischemia symptoms for selected patients resulting from diverse complications such as stroke and atherosclerotic disease. However, several clinical trials showed EC-IC bypass surgery failed to prevent recurrent ischemic stroke in certain patients. OBJECTIVE: Our clinical trial aimed to investigate whether there is a correlation between pre-surgery assessments and prognosis of patients received EC-IC bypass operation. METHODS: We divided all patients into 4 groups according to their compensatory stages of cerebral ischemia. The values of cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and oxygen extraction fraction (OEF) were obtained by computed tomography perfusion (CTP), single photon emission computed tomography (SPECT), and positron emission tomography (PET) at different time points before and after EC-IC bypass surgery. We assessed the correlations between the compensatory stage with modified Rankin scale (mRS) scores, survival rates, stroke and TIA incidences over the 12 months after surgery. RESULTS: Patients with normal CBF, normal or increased CBV, and normal OEF tended to have a better prognosis after the EI-CI bypass operation than patients with abnormal CBF, CBV and OEF. However, patients with abnormal CBF and CBV, and increased OEF showed elevated mRS, less survival rates, and higher stroke and TIA incidences over the 12 months after surgery, compared to the groups with normal CBF, CBV and OEF. CONCLUSIONS: Our results suggest that a defined compensatory stage of cerebral ischemia might be useful for the prognosis of patients receiving EI-CI bypass surgery.

Protective Role of Apocynin via Suppression of Neuronal Autophagy and TLR4/NF-κB Signaling Pathway in a Rat Model of Traumatic Brain Injury.

Neuronal autophagy and inflammatory responses are important in the pathogenesis of traumatic brain injury (TBI), and toll-like receptor 4 (TLR4) may play an important role in the related molecular cascade. The present study investigated the protective effect of apocynin, an inhibitor of NADPH oxidase, in a TBI rat model and further examined neuronal autophagy and the TLR4-mediated pathway. Adult male Sprague-Dawley rats were subjected to controlled cortical impact injury and intraperitoneally injected with apocynin (50 mg/kg) immediately after the trauma. In addition to motor and behavioral studies, brain water content and histology analyses were performed. Expression of autophagy-related proteins as well as TLR4/NF-κB signaling and inflammatory mediators was analyzed. The apocynin treatment significantly attenuated TBI-induced motor and behavioral impairment, brain edema and neuronal damage in rats. Immunohistochemical and Western blot analyses revealed that apocynin treatment significantly reduced the expression of NOX2, LC3 and Beclin1 in the hippocampus at 12-48 h after injury. Double immunolabeling demonstrated that apocynin decreased the co-localization of LC3 or TLR4-positive cells with hippocampal neurons at 24 h following TBI. In addition, CD11b (microglial marker) and GFAP (astrocyte marker)-immunopositive cells were also clearly decreased in hippocampal tissues. Meanwhile, protein levels of TLR4, NF-κB p65, TNF-α and IL-1ß were found to be significantly downregulated by Western blot analysis. In conclusion, our findings indicate that the protective effects of apocynin may be related to modulation of neuronal autophagy and the TLR4/NF-κB signaling pathway.

A novel method to derive and expand mice neural stem cells efficiently without neuro-sphere formation.

Neural stem cells (NSCs) are multi-potent stem cells able to self-renew and generate immature and differentiated cell populations by asymmetric division. The NSCs are of considerable interest for cell replacement in neuro-degenerative diseases. NSCs are usually identified and expanded by their ability to generate free-floating aggregates termed neurospheres. However, neurospheres are not a pure population of NSCs with as little as 1% population in primary spheres. Neurospheres also contain neurons, astrocytes and oligodendrocytes. The heterogeneity of these cells may hinder their repopulation potential when used in cell transplantation. Furthermore, to obtain 1 million NSCs by the neurosphere protocol usually takes one month, which is inconvenient for future clinical trials. In this study, we tried to derive the NSCs from mice embryo neuroepithelium without neurosphere formation. Three different protocols were compared. We generated a direct and efficient NSCs generation, expanding and freezing protocol. This protocol can provide sufficient amount of the NSCs from first a few passages for cell transplantation.