Taurine-Upregulated Gene 1 Attenuates Cerebral Angiogenesis following Ischemic Stroke in Rats.

Objective: Angiogenesis is one of the therapeutic targets of cerebral infarction. Long noncoding RNAs (lncRNAs) can regulate the pathological process of angiogenesis following ischemic stroke. Taurine-upregulated gene 1 (TUG1), an lncRNA, is correlated to ischemic stroke. We intended to determine the effect of TUG1 on angiogenesis following an ischemic stroke. Materials and Methods: Middle cerebral artery occlusion (MCAO) was adopted to build a focal ischemic model of the rat brain, and pcDNA-TUG1 and miR-26a mimics were injected into rats. Neurological function was estimated through modified neurological severity scores. The volume of focal brain infarction was calculated through 2,3,5-triphenyltetrazolium chloride staining. The level of TUG1 and miR-26a was measured by PCR. The expression of vascular endothelial growth factor (VEGF) and CD31 was checked using immunohistochemistry and western blot. The correlation between miR-26a and TUG1 was verified through a luciferase reporter assay. Results: TUG1 increased noticeably while miR-26a was markedly reduced in MCAO rats. Overexpression of miR-26a improved neurological function recovery and enhanced cerebral angiogenesis in MCAO rats. TUG1 overexpression aggravated neurological deficits and suppressed cerebral angiogenesis in MCAO rats. Bioinformatics analysis revealed that miR-26a was one of the predicted targets of TUG1. Furthermore, TUG1 combined with miR-26a to regulate angiogenesis. TUG1 overexpression antagonized the role of miR-26a in neurological recovery and angiogenesis in MCAO rats. Conclusions: TUG1/miR-26a, which may act as a regulatory axis in angiogenesis following ischemic stroke, can be considered a potential target for cerebral infarction therapy.

Chronic Obstructive Pulmonary Disease and Its Acute Exacerbation before Colon Adenocarcinoma Treatment Are Associated with Higher Mortality: A Propensity Score-Matched, Nationwide, Population-Based Cohort Study.

PURPOSE: To investigate whether chronic obstructive pulmonary disease (COPD) and COPD severity (acute exacerbation of COPD (AECOPD)) affect the survival outcomes of patients with colon adenocarcinoma receiving standard treatments. METHODS: From the Taiwan Cancer Registry Database, we recruited patients with clinical stage I-III colon adenocarcinoma who had received surgery. The Cox proportional hazards model was used to analyze all-cause mortality. We categorized the patients into COPD and non-COPD (Group 1 and 2) groups through propensity score matching. RESULTS: In total, 1512 patients were eligible for further comparative analysis between non-COPD (1008 patients) and COPD (504 patients) cohorts. In the multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% confidence interval (CI)) for all-cause mortality for Group 1 compared with Group 2 was 1.17 (1.03, 1.29). In patients with colon adenocarcinoma undergoing curative resection, the aHRs (95% CIs) for all-cause mortality in patients with hospitalization frequencies of ≥1 and ≥2 times for AECOPD within 1 year before adenocarcinoma diagnosis were 1.08 (1.03, 1.51) and 1.55 (1.15, 2.09), respectively, compared with those without AECOPD. CONCLUSION: In patients with colon adenocarcinoma undergoing curative resection, COPD was associated with worse survival outcomes. Being hospitalized at least once for AECOPD within 1 year before colon adenocarcinoma diagnosis was an independent risk factor for poor overall survival in these patients, and a higher number of hospitalizations for AECOPD within 1 year before diagnosis was associated with poorer survival. Our study highlights the importance of COPD management, particularly the identification of frequent exacerbators and the prevention of AECOPD before standard colon adenocarcinoma treatments are applied.

Angelica dahurica and Rheum officinale Facilitated Diabetic Wound Healing by Elevating Vascular Endothelial Growth Factor.

Traditional Chinese medicine (TCM) provides alternative treatment choices for diabetic wounds. The aim of this study was to evaluate the effects of Angelica dahurica and Rheum officinale (ARE) on diabetic wounds and its underlying action mechanism. A total of 36 healthy male Sprague-Dawley rats were randomly divided into three groups: diabetes mellitus (DM) rats treated with ARE (DM-ARE), DM rats treated with 0.9% saline (DM-NS), and non-DM rats treated with 0.9% saline (NDM-NS). DM was induced by intraperitoneal administration of 40 mg/kg of streptozotocin after a 2-week high-fat diet feeding. After excisional skin wounds and treatments, the remaining wound area (RWA) in each group was measured. The RWA in the DM-NS group (69.60% ± 2.35%) was greater than that in the DM-ARE (55.70% ± 1.85%) and NDM-NS groups (52.50% ± 2.77%) on day 6. Besides, the DM-ARE group showed higher vascular endothelial growth factor (VEGF), higher inducible nitric oxide synthase (iNOs), higher [Formula: see text]-smooth muscle actin ([Formula: see text]-SMA), and lower nuclear factor kappa-light-chain-enhancer of activated B cell (NF-[Formula: see text]B) expression in the wound skin tissue. These results showed that treatment with ARE shifted the recovery pattern of diabetic rats to the pattern of nondiabetic rats, indicating that ARE may improve wound healing in diabetic conditions.

NADPH oxidase inhibitor regulates microRNAs with improved outcome after mechanical reperfusion.

BACKGROUND: Inhibition of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) pathway improves the neurological outcome in the transient middle cerebral artery occlusion (tMCAO) animal model. In this study we analyzed the microRNAs profile targeting NOX2 and NOX4 genes and its response to NOX2/4 inhibitor VAS2870 to understand the mechanisms of this protective effect. METHODS: The intraluminal filament tMCAO model was established in hyperglycemic rats (n=106) with 5 hours ischemia followed by 19 hours reperfusion. NOX inhibitor VAS2870 was delivered intravenously before reperfusion. Infarct volume, hemorrhagic transformation, and mortality were determined at 24 hours after cerebral ischemia. MicroRNAs profile targeting NOX2 and NOX4 genes were predicted by microRNA databases and further evaluated by microRNA microarray and quantitative RT-PCR. RESULTS: Ten microRNAs potentially targeting NOX2 and NOX4 genes (including microRNA-29a, microRNA-29c, microRNA-126a, microRNA-132, microRNA-136, microRNA-138, microRNA-139, microRNA-153, microRNA-337, and microRNA-376a) were significantly downregulated in the ischemic hemisphere in the tMCAO group compared with the sham-operated group, as shown by microRNA microarray and quantitative RT-PCR (all p<0.05). Intravenous treatment with NOX inhibitor VAS2870 before reperfusion increased the expression of microRNA-29a, microRNA-29c, microRNA-126a, and microRNA-132 compared with the tMCAO group (all p<0.05). CONCLUSIONS: Several microRNAs potentially targeting NOX2 and NOX4 genes displayed altered levels in hyperglycemic rats with the tMCAO model, suggesting their regulatory roles and targeting potentials for acute ischemic stroke treatment. Targeting specific microRNAs may represent a novel intervention opportunity to improve outcome and reduce hemorrhagic transformation after mechanical reperfusion for acute ischemic stroke.

NADPH oxidase inhibitor improves outcome of mechanical reperfusion by suppressing hemorrhagic transformation.

BACKGROUND: Severe hemorrhagic transformation (HT) after mechanical thrombectomy predicts a poor clinical outcome in acute ischemic stroke. To better understand the mechanism of HT, we investigated the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in HT after reperfusion during acute stroke and whether NOX2/4 inhibitor VAS2870 reduces reperfusion-induced HT after mechanical recanalization. METHODS: A model of reperfusion-induced HT was established in rats (n=182) with hyperglycemic challenge and 5 h middle cerebral artery occlusion followed by 19 h reperfusion. NOX inhibitor VAS2870 was delivered intravenously 30 min before reperfusion. Infarct volume, brain water content, HT, neurological score, mortality rate, blood-brain barrier (BBB) damage, neuronal apoptosis, and reactive oxygen species were determined at 24 h after cerebral ischemia. The expressions of NOX1, NOX2, NOX4, and BBB-associated proteins were measured. RESULTS: NOX2 and NOX4 upregulation and severe HT were observed in hyperglycemic rats after cerebral ischemia/reperfusion. VAS2870 suppressed oxidative stress, neuronal apoptosis, and NOX2/4 upregulation in the ischemic hemisphere. VAS2870 reduced infarct volume (17.2±5.3% vs 37.4±9.2%, p<0.01) and the frequency of reperfusion-induced parenchymal hematoma (29.7% vs 59.5%, p<0.05) at 24 h after ischemia compared with the ischemia/reperfusion group. VAS2870 attenuated brain edema and reduced reperfusion-induced BBB breakdown, resulting in improved neurological outcome (neurological deficit score 1.43±0.50 vs 2.43±0.93, p<0.001) and reduced mortality (11.9% vs 64.1%, p<0.001). CONCLUSIONS: NOX2 and NOX4 may mediate HT in rats with large vessel stroke after mechanical reperfusion. Infusion of NOX inhibitor VAS2870 before mechanical thrombectomy represents a novel adjunctive therapeutic strategy to prevent reperfusion-induced HT and improve outcome of acute stroke treatment.

Effective synthetic peptide vaccine for foot-and-mouth disease in swine.

We have designed a peptide-based vaccine for foot-and-mouth disease (FMD) effective in swine. The peptide immunogen has a G-H loop domain from the VP1 capsid protein of foot-and-mouth disease virus (FMDV) and a novel promiscuous T helper (Th) site for broad immunogenicity in multiple species. The G-H loop VP1 site was optimised for cross-reactivity to FMDV by the inclusion into the peptide of cyclic constraint and adjoining sequences. The incorporation of consensus residues into the hypervariable positions of the VP1 site provided for broad immunogenicity. The vaccine protected 20 out of 21 immunised pigs from infectious challenge by FMDV O1 Taiwan using peptide doses as low as 12.5 microg, and a mild adjuvant that caused no lesions. A safe chemically-defined product would have considerable advantages for vaccination against FMD.