Inhibition of Sema4D/PlexinB1 signaling alleviates vascular dysfunction in diabetic retinopathy.

Diabetic retinopathy (DR) is a common complication of diabetes and leads to blindness. Anti-VEGF is a primary treatment for DR. Its therapeutic effect is limited in non- or poor responders despite frequent injections.

Sema3E/PlexinD1 signaling inhibits postischemic angiogenesis by regulating endothelial DLL4 and filopodia formation in a rat model of ischemic stroke.

Angiogenesis is a crucial defense response to hypoxia that regulates the process of raising the promise of long-term neurologic recovery during the management of stroke. A high expression of antiangiogenic factors leads to the loss of neovascularization capacity in pathologic conditions. We have previously documented an impairment of the cerebral vessel perfusion and neovascularization in the cortex neighboring the stroke-induced lesion, which was accompanied by an activation of semaphorin 3E (Sema3E)/PlexinD1 after ischemic stroke.

Coding mutations in contribute to Parkinson's disease.

Whole-exome sequencing has been successful in identifying genetic factors contributing to familial or sporadic Parkinson's disease (PD). However, this approach has not been applied to explore the impact of de novo mutations on PD pathogenesis. Here, we sequenced the exomes of 39 early onset patients, their parents, and 20 unaffected siblings to investigate the effects of de novo mutations on PD.

Sema3E/PlexinD1 inhibition is a therapeutic strategy for improving cerebral perfusion and restoring functional loss after stroke in aged rats.

Brain tissue survival and functional recovery after ischemic stroke greatly depend on cerebral vessel perfusion and functional collateral circulation in the ischemic area. Semaphorin 3E (Sema3E), one of the class 3 secreted semaphorins, has been demonstrated to be a critical regulator in embryonic and postnatal vascular formation via binding to its receptor PlexinD1. However, whether Sema3E/PlexinD1 signaling is involved in poststroke neovascularization remains unknown.

Alleviative effects of fluoxetine on depressive-like behaviors by epigenetic regulation of BDNF gene transcription in mouse model of post-stroke depression.

Fluoxetine, one of the selective serotonin reuptake inhibitor (SSRI) antidepressants, has been thought to be effective for treating post-stroke depression (PSD). Recent work has shown that fluoxetine may exert an antidepressive effect through increasing the level of brain-derived neurotrophic factor (BDNF), but the underlying mechanism still remains unclear. In the present study, we successfully established the PSD model using male C57BL/6 J mice by photothrombosis of the left anterior cortex combined with isolatied-housing conditions.

MicroRNA-130a regulates cerebral ischemia-induced blood-brain barrier permeability by targeting Homeobox A5.

Blood-brain barrier (BBB) disruption plays a critical role in brain injury induced by cerebral ischemia, and preserving BBB integrity during ischemia could alleviate cerebral injury. We examined the role of miR-130a in ischemic BBB disruption by using models of rat middle cerebral artery occlusion and cell oxygen-glucose deprivation. We found that ischemia significantly increased microRNA-130a (miR-130a) level and that miR-130a was predominantly from brain microvascular endothelial cells.

Effects of LRRK2 Inhibitors on Nigrostriatal Dopaminergic Neurotransmission.

Introduction: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most prevalent cause of familial and sporadic Parkinson's disease (PD). Because most pathogenic LRRK2 mutations result in enhanced kinase activity, it suggests that LRRK2 inhibitors may serve as a potential treatment for PD. To evaluate whether LRRK2 inhibitors are effective therapies for PD, it is crucial to know whether LRRK2 inhibitors will affect dopaminergic (DAergic) neurotransmission.

Autophagy in ageing and ageing-associated diseases.

Autophagy is a cell self-digestion process via lysosomes that clears "cellular waste", including aberrantly modified proteins or protein aggregates and damaged organelles. Therefore, autophagy is considered a protein and organelle quality control mechanism that maintains normal cellular homeostasis. Dysfunctional autophagy has been observed in ageing tissues and several ageing-associated diseases.

Which is a more accurate predictor in colorectal survival analysis? Nine data mining algorithms vs. the TNM staging system.

Objective: Over the past decades, many studies have used data mining technology to predict the 5-year survival rate of colorectal cancer, but there have been few reports that compared multiple data mining algorithms to the TNM classification of malignant tumors (TNM) staging system using a dataset in which the training and testing data were from different sources. Here we compared nine data mining algorithms to the TNM staging system for colorectal survival analysis.

Methods: Two different datasets were used: 1) the National Cancer Institute's Surveillance, Epidemiology, and End Results dataset; and 2) the dataset from a single Chinese institution.

Effect of trehalose on PC12 cells overexpressing wild-type or A53T mutant α-synuclein.

Accumulation of α-synuclein (α-Syn) is a common pathology for both familiar and sporadic Parkinson's disease (PD), enhancing its clearance might be a promising strategy for treating PD. To assess the potential of trehalose in this regard, we investigated its effect on the PC12 cells overexpressing wild type (WT) or A53T mutant α-Syn and the implicated pathway it might mediated. We observed that trehalose promoted the clearance of A53T α-Syn but not WT α-Syn in PC12 cells, and confirmed the increased LC3 and Lysotracker RED positive autolysosomes by using lysotracker and LC3 staining, the enhanced expression of LC3-II in Western blot, and more autophagosomes under Transmission Electron Microscope in a dose dependent manner after the trehalose treatment.

Trehalose inhibits fibrillation of A53T mutant alpha-synuclein and disaggregates existing fibrils.

The aggregation of alpha-synuclein (AS) is pivotally implicated in the development of Parkinson's disease (PD), inhibiting this process might be effective in treating PD. Here, by using circular dichroism spectroscopy, thioflavin T fluorescence, and atomic force microscopy, we found that trehalose at low concentration disaggregates preformed A53T AS protofibrils and fibrils into small aggregates or even random coil structure, while trehalose at high concentration slows down the structural transition into β-sheet structure and completely prevents the formation of mature A53T AS fibrils. Further work in vivo will be needed to evaluate its potential as a novel strategy for treating PD.

Polymorphisms and a haplotype in heparanase gene associations with the progression and prognosis of gastric cancer in a northern Chinese population.

Background: Human heparanase plays an important role in cancer development and single nucleotide polymorphisms (SNPs) in the heparanase gene (HPSE) have been shown to be correlated with gastric cancer. The present study examined the associations between individual SNPs or haplotypes in HPSE and susceptibility, clinicopathological parameters and prognosis of gastric cancer in a large sample of the Han population in northern China.

Methodology/principal Findings: Genomic DNA was extracted from formalin-fixed, paraffin-embedded normal gastric tissue samples from 404 patients and from blood from 404 healthy controls.

MicroRNA-148b is frequently down-regulated in gastric cancer and acts as a tumor suppressor by inhibiting cell proliferation.

Background: MicroRNAs (miRNAs) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Our previous studies have revealed that miR-148a and miR-152 are significantly down-regulated in gastrointestinal cancers. Interestingly, miR-148b has the same "seed sequences" as miR-148a and miR-152.

Is pT2 subclassification feasible to predict patient outcome in colorectal cancer?

Background: This study aimed to evaluate the prognostic impact of pT2 subclassification according to the depth of muscularis propria (MP) invasion and to explore the clinicopathologic factors correlated with lymph node metastasis (LNM) and postoperative hematogenous metastasis in pT2 colorectal cancer.

Methods: A total of 317 patients with pT2 colorectal cancer were reviewed. pT2a represents the infiltration of the inner circumferential layer of the MP, and pT2b represents the infiltration of the outer longitudinal layer of the MP.