Background Chronic spontaneous urticaria (CSU) is defined by itchy hives, angioedema, or both for at least 6 weeks. Omalizumab, an anti-IgE antibody that affects mast cell and basophil function, is a ...promising new treatment option. As of now, however, the efficacy and safety of different doses of omalizumab used in clinical trials for CSU have not been systematically analyzed and summarized. Objective We sought to assess the efficacy and safety of different doses of omalizumab for the treatment of CSU in a meta-analysis of clinical trial results. Methods Suitable trials were identified by searching PubMed, Medline, Embase, and Web of Science databases and with the help of omalizumab's manufacturers. Only double-blind, randomized, placebo-controlled studies with omalizumab-treated versus placebo-treated patients with CSU were included in this analysis. Results We identified 7 randomized, placebo-controlled studies with 1312 patients with CSU. Patients treated with omalizumab (75-600 mg every 4 weeks) had significantly reduced weekly itch and weekly wheal scores compared with the placebo group. Omalizumab's effects were dose dependent, with the strongest reduction in weekly itch and weekly wheal scores observed with 300 mg. Rates of complete response were significantly higher in the omalizumab group (relative risk, 4.55; P < .00001) and dose dependent, with the highest rates in the 300-mg group. Rates of patients with adverse events were similar in the omalizumab and placebo groups. Conclusion This meta-analysis provides high-quality evidence for the efficacy and safety of omalizumab in patients with CSU and for treating these patients with 300 mg of omalizumab every 4 weeks.
•OSCS with different degree of substitution were synthesized.•The structural properties of OSCS were characterized by FT-IR, XRD, and SEM.•The gelatinization characteristics of starch samples were ...determined by DSC.•In vitro digestibility of OSCS was also measured.
The octenylsuccinylated cassava starch (OSCS) samples with a degree of substitution (DS) in the range of 0.008 to 0.035 were prepared in this study. The structural, physicochemical, and in vitro digestibility properties of OS-starch samples were investigated. Intensities of characteristic peaks at 1724cm−1 and 1572cm−1 increased with increasing DS, which confirmed successful introduction of ester carbonyl groups into starch molecules. The esterification occurred primarily in the amorphous regions and surface of starch granule, and the crystalline pattern did not change. SEM results revealed that the modification had slight effects on the morphological structure of native starch. Differential scanning calorimetry (DSC) thermograms of OS-starch samples showed lower onset temperature, peak temperature, conclusion temperature, and endothermic energy than their native counterpart. This study also showed that esterification with OSA was an effective method for increasing slowly digestible starch and resistant starch contents in starch samples.
Abstract Introduction Trimetazidine (TMZ) is an anti-anginal drug that has been widely used in Europe and Asia. The TMZ can optimize energy metabolism via inhibition of long-chain 3-ketoacyl CoA ...thiolase (3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. However, the mechanism by which TMZ aids in cardioprotection against ischemic injury has not been characterized. AMP-activated protein kinase (AMPK) is an energy sensor that controls ATP supply from substrate metabolism and protects heart from energy stress. TMZ changes the cardiac AMP/ATP ratio by modulating fatty acid oxidation, thereby triggering AMPK signaling cascade that contributes to the protection of the heart from ischemia/reperfusion (I/R) injury. Methods The mouse model of in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery (LAD) was used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead (KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart. Results TMZ treatment significantly stimulates cardiac AMPK and extracellular signal-regulated kinase (ERK) signaling pathways (p < 0.05 vs . vehicle group). The administration of TMZ reduces myocardial infarction size in WT C57BL/6J hearts, the reduction of myocardial infarction size by TMZ in AMPK KD hearts was significantly impaired versus WT hearts (p < 0.05). Intriguingly, the administration of ERK inhibitor, PD98059, to AMPK KD mice abolished the cardioprotection of TMZ against I/R injury. The ex vivo working heart perfusion data demonstrated that TMZ treatment significantly activates AMPK signaling and modulating the substrate metabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in the I/R hearts. Therefore, both AMPK and ERK signaling pathways mediate the cardioprotection of TMZ against ischemic injury. The metabolic benefits of TMZ for angina patients could be due to the activation of energy sensor AMPK in the heart by TMZ administration.
The aim of this study is to explore the roles of circular RNA (circRNA) Cdr1as on cisplatin resistance in ovarian cancer and explore the underlying mechanisms. We investigated the expression of ...circRNAs in five paired cisplatin-sensitive and cisplatin-resistant tissues of ovarian cancer by microarray analysis. The quantitative real-time PCR analysis was to investigate the expression pattern of Cdr1as in cisplatin-resistant ovarian cancer patient tissues and cell lines. Then, the effects of Cdr1as on cisplatin resistance, cell proliferation, and apoptosis were assessed in ovarian cancer cells. In this study, Cdr1as was observed to be downregulated in cisplatin-resistant patient tissues and cell lines. Overexpression of Cdr1as inhibited cell proliferation and promoted the cisplatin-induced cell apoptosis in ovarian cancer cells. Then we demonstrated that repressed Cdr1as promoted the miR-1270 expression, and miR-1270 could bind to the predicted binding site of Cdr1as. Furthermore, we found that miR-1270 displayed its role via modulating the Suppressor of Cancer Cell Invasion (SCAI) expression. Importantly, we demonstrated that Cdr1as was downregulated in serum exosomes from cisplatin-resistant patients. In summary, our study demonstrated that Cdr1as sensitizes ovarian cancer to cisplatin by regulating the miR-1270/SCAI signaling pathway.
Background Tuberculosis (TB) may facilitate carcinogenesis. We performed a case-control study of the association between TB and cancer in Xinjiang, a high TB endemic area of China. Methods From ...January 2016 to December 2018, a total of 45,455 patients hospitalized in Xinjiang Cancer Hospital were consecutively enrolled and divided into a malignant tumor group (n = 32,539) and a benign tumor group (n = 12,916). Patients with active and previous TB before the diagnosis of cancer were retrospectively identified in the two groups. Results A significantly higher proportion of TB was found in the malignant tumor group (n = 1776, 5.46%) than in the control (benign tumor) group (n = 175, 1.35%) (p < 0.0001). The highest and lowest proportions of TB in the malignant group were in patients with non-Hodgkin's lymphoma (16.74%) and thyroid cancer (0.77%), respectively. In multivariate analysis adjusting for age, sex, and ethnicity, TB remained an independent risk factor for all cancers (odds ratio (OR) 1.68; 95% confidence interval (CI) 1.43-1.97). Furthermore, TB was associated with a significantly higher risk of non-Hodgkin's lymphoma, cervical cancer, esophageal cancer, "other" cancers, ovarian cancer, and breast cancer. Moreover, females with TB were more likely to develop cancer than males (p < 0.0001), except for esophageal cancer and lymphoma. Conclusion TB patients have an elevated cancer risk. A screening strategy for TB should be taken into consideration before treatment in patients with some cancer types that are associated with a high proportion of TB. Keywords: Tuberculosis, Malignant Cancer, Case-control study
In the paper, we search for some analytical solutions for a new (3 + 1)‐dimension Boiti–Leon–Manna–Pempinelli (BLMP) equation. Based on the Hirota bilinear method, bilinear neural network framework ...expands to more than one hidden layer to construct test functions. By using the symbolic computation software Maple, periodic‐type I, II, and III solutions of the new (3 + 1)‐dimension BLMP equation are obtained. Besides, the evolution and dynamical characteristics of these solutions derived via the appropriate real values are also exhibited.
MicroRNAs have been appreciated in various cellular functions, including the regulation of angiogenesis. Mesenchymal-stem-cells (MSCs) transplanted to the MI heart improve cardiac function through ...paracrine-mediated angiogenesis. However, whether microRNAs regulate MSC induced angiogenesis remains to be clarified. Using microRNA microarray analysis, we identified a microRNA expression profile in hypoxia-treated MSCs and observed that among all dysregulated microRNAs, microRNA-377 was decreased the most significantly. We also validated that vascular endothelial growth factor (VEGF) is a target of microRNA-377 using dual-luciferase reporter assay and Western-blotting. Knockdown of endogenous microRNA-377 promoted tube formation in human umbilical vein endothelial cells. We then engineered rat MSCs with lentiviral vectors to either overexpress microRNA-377 (MSC miR-377) or knockdown microRNA-377 (MSC Anti-377) to investigate whether microRNA-377 regulated MSC-induced myocardial angiogenesis, using MSCs infected with lentiviral empty vector to serve as controls (MSC Null). Four weeks after implantation of the microRNA-engineered MSCs into the infarcted rat hearts, the vessel density was significantly increased in MSC Anti-377-hearts, and this was accompanied by reduced fibrosis and improved myocardial function as compared to controls. Adverse effects were observed in MSC miR-377-treated hearts, including reduced vessel density, impaired myocardial function, and increased fibrosis in comparison with MSC Null-group. These findings indicate that hypoxia-responsive microRNA-377 directly targets VEGF in MSCs, and knockdown of endogenous microRNA-377 promotes MSC-induced angiogenesis in the infarcted myocardium. Thus, microRNA-377 may serve as a novel therapeutic target for stem cell-based treatment of ischemic heart disease.
•Grouting pressure has a greater impact on settlement rather than face pressure.•Numerical computed volume loss is comparable with some measured results.•Volume loss below 0.2% required to ensure ...surface settlement less than 10mm.•Trough width parameter is in the range of 0.31–0.37 for large tunnels in Shanghai.
There is an ever-growing demand of construction of large-diameter tunnel in Shanghai, China. How to minimize the environmental impact induced by the tunnel construction has been a hot topic of research over the recent years. The Yingbin San Road tunnel with an external diameter of 13.95m has been taken as an example to elaborate the controlling of ground surface deformation induced by shield-driven tunneling, in the case of tunnel passing through the settlement sensitive area and adverse geological conditions. Tunneling process of the EPB shield machine was simulated using a three-dimensional finite difference method. Parametric study was performed to optimize the construction parameters. Field measurement was also carried out to validate the numerical model and its applicability in the case of large-diameter tunnels. Both the numerical prediction and field test data show that grouting pressure and quality appear to determine the surface settlement rather than the supporting pressure at workface on the premise of guaranteeing the safety of tunneling process. Both the empirical correlations and field observations demonstrate that the volume loss Vi should be controlled below 0.2% to guarantee the maximum surface settlement no more than 10mm in the airport area. However, the empirical predictions of trough width parameter i do not match the field measurement very well except for the case where such a high volume loss as 0.81% was obtained.
PDF
