The Marine-Derived Oligosaccharide Sulfate (MdOS), a Novel Multiple Tyrosine Kinase Inhibitor, Combats Tumor Angiogenesis both In Vitro and In Vivo

Despite the emerging success of multi-targeted protein tyrosine kinase (PTK) inhibitors in cancer therapy, significant side effects and resistance concerns seems to be avoided unlikely. The aim of the present study was to identify novel multi-targeting PTK inhibitors. The kinase enzymatic activities were measured by enzyme-linked immunosorbent assay (ELISA). The antiproliferative activities in human microvascular endothelial cells (HMECs) were evaluated by sulforhodamine (SRB) assay. The phosphorylation of kinases and their downstream molecules was probed by western blot analysis. The binding mode between MdOS and PTKs was profiled by surface plasmon resonance (SPR) approach and molecular simulation. Tube formation assay, rat aortic ring method and chicken chorioallantoic membrane assay were combined to illustrate the in vitro and in vivo anti-angiogenic effects. Results indicated that MdOS, a novel marine-derived oligosaccharide sulfate, exhibited a broad-spectrum PTK inhibitory action. At an enzymatic level, MdOS inhibited HER2, EGFR, VEGFR, PDGFR, c-Kit, FGFR1 and c-Src, with little impact on FGFR2. In cellular settings, MdOS inhibited phosphorylation of PTKs, exemplified by HER2, EGFR and VEGFR2, and downstream molecules of Erk1/2 and AKT. Further studies demonstrated that MdOS acted as an ATP-competitive inhibitor via directly binding to the residues of entrance rather than those of the ATP-binding pocket. Furthermore, MdOS inhibited proliferation and tube formation of HMECs, arrested microvessel outgrowth of rat aortic rings and hindered the neovascularization of chick allantoic membrane. Taken together, results presented here indicated that MdOS exhibited anti-angiogenic activity in a PTK-dependent manner and make it a promising agent for further evaluation in PTK-associated cancer therapy

Size-Controlled Large-Diameter and Few-Walled Carbon Nanotube Catalysts for Oxygen Reduction

We demonstrate a new strategy for tuning the size of large-diameter and few-walled nitrogen-doped carbon nanotubes (N-CNTs) from 50 to 150 nm by varying the transition metal (TM = Fe, Co, Ni or Mn) used to catalyze graphitization of dicyandiamide. Fe yielded the largest tubes, followed by Co and Ni, while Mn produced a clot-like carbon morphology. We show that morphology is correlated with electrocatalytic activity for the oxygen reduction reaction (ORR). A clear trend of Fe \u3e Co \u3e Ni \u3e Mn for the ORR catalytic activity was observed, in both alkaline media and more demanding acidic media. The Fe-derived N-CNTs exhibited the highest BET (∼870 m2 g−1) and electrochemically accessible (∼450 m2 g−1) surface areas and, more importantly, the highest concentration of nitrogen incorporated into the carbon planes. Thus, in addition to the intrinsic high activity of Fe-derived catalysts, the high surface area and nitrogen doping contribute to high ORR activity. This work, for the first time, demonstrates size-controlled synthesis of large-diameter N-doped carbon tube electrocatalysts by varying the metal used in N-CNT generation. Electrocatalytic activity of the Fe-derived catalyst is already the best among studied metals, due to the high intrinsic activity of possible Fe–N coordination. This work further provides a promising route to advanced Fe–N–C nonprecious metal catalysts by generating favorable morphology with more active sites and improved mass transfer

Optical Fiber LSPR Biosensor Prepared by Gold Nanoparticle Assembly on Polyelectrolyte Multilayer

This article provides a novel method of constructing an optical fiber localized surface plasmon resonance (LSPR) biosensor. A gold nanoparticle (NP) assembled film as the sensing layer was built on the polyelectrolyte (PE) multilayer modified sidewall of an unclad optical fiber. By using a trilayer PE structure, we obtained a monodisperse gold NP assembled film. The preparation procedure for this LSPR sensor is simple and time saving. The optical fiber LSPR sensor has higher sensitivity and outstanding reproducibility. The higher anti-interference ability for response to an antibody makes it a promising method in application as a portable immuno-sensor

Study on the evaluation of the clinical effects of traditional chinese medicine in heart failure by complex intervention: protocol of SECETCM-HF

<p>Abstract</p> <p>Background</p> <p>Experts in Traditional Chinese Medicine (TCM) have studied the TCM subject of the pathogenesis of heart failure (HF) for several decades. As a result, the general idea is <it>ben </it>deficiency and <it>biao </it>excess. However, the clinical evaluation system which combined the TCM and western medicine in HF has not been developed yet. The objective is to establish the evaluation index system for the integration of TCM and western medicine. The evaluation indexes which include TCM items will specify the research design and methods.</p> <p>Methods</p> <p>Nine medical centers in different cities in China will participate in the trial. A population of 340 patients with HF will be enrolled through a central randomized system for different test groups. Group A will be treated with only western medicine, while group B with western and Chinese medicine together. The study will last for 12 months from the date of enrollment. The cardiovascular death will be the primary outcome.</p> <p>Discussion</p> <p>By putting the protocol into practice, the clinical effects of TCM for HF will be identified scientifically, objectively as well as rationally. The proper index system which built in the study will be helpful for the clinical effect expression of HF by integrated medicine in future.</p> <p>Trial Registration</p> <p>ChiCTR-TRC-00000059</p

Traditional Chinese medicine injections for heart failure: a protocol for systematic review and network meta-analysis of randomised controlled trials

Introduction Heart failure (HF) has always been an important issue in global public health. The research and development of traditional Chinese medicine (TCM) provide more possibilities for improving the prognosis of HF patients. Because multiple TCM injections (TCMIs) are being widely applied in clinical work, it is important to choose the right TCMIs for HF patients. The purpose of this study is to assess and compare the effect of different TCMIs for HF using network meta-analysis (NMA) and further provide references for clinical decision-making.Methods and analysis The clinical randomised controlled trials (RCTs) and meta-analyses of TCMIs for treating HF will be searched in the relevant database, including PubMed, EMBASE, Cochrane Library (No. 2 of 2020), Chinese BioMedical Literature Database, China National Knowledge Infrastructure, Wan Fang Database and Chinese Scientific Journal Database from inception to 29 February 2020. The outcomes of interest include all-cause mortality, rehospitalisation rate, left ventricular ejection fraction, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, brain natriuretic peptide (BNP), N-terminal pro-BNP, cardiac output, stroke volume, 6 min walking distance and adverse events. The risk of bias assessment of the included RCTs will be conducted according to the Cochrane Collaboration’s tool for assessing the risk of bias. NMA will be performed in a Bayesian hierarchical framework using R V.3.6.1 with the gemtc package. Finally, we will rank the efficacy of these treatment programmes according to the surface under the cumulative ranking curve, and perform quality assessment and recommendation grading of the evidence according to the Grading of Recommendations Assessment, Development and Evaluation system.Ethics and dissemination This study will extract data from the published literature and will not involve private information from individuals or compromise their rights. Therefore, the study does not require ethical approval. The results will eventually be published in a peer-reviewed journal and disseminated at relevant conferences.PROSPERO registration number CRD42020166900

Association between Chinese visceral adiposity index and risk of stroke incidence in middle-aged and elderly Chinese population: evidence from a large national cohort study

Abstract Background Abdominal obesity has long been considered as a crucial risk factor of stroke. Chinese visceral adiposity index (CVAI), a novel surrogate indicator of abdominal obesity, has been confirmed as a better predictor for coronary heart disease than other indicators in Asian population. However, the data on the relationship of CVAI with stroke is limited. The objective of our study is evaluating the relationship between CVAI and stroke incidence. Methods In the present study, we enrolled 7242 middle-aged and elderly residents from the China Health and Retirement Longitudinal Study (CHARLS) and placed them into groups according to quartile of CVAI. The outcome of interest was stroke. Kaplan–Meier curves were used to estimate the cumulative incidences of stroke. Cox regression analyses and multivariable-adjusted restricted cubic spline (RCS) curves were performed to evaluate the relationship between CVAI and incident stroke. Multiple sensitivity analyses and subgroups analyses were performed to test the robustness of the findings. Results During a median 84 months of follow-up, 612 (8.45%) participants experienced incident stroke, and the incidences of stroke for participants in quartiles (Q) 1–4 of CVAI were 4.42%, 7.29%, 9.06% and 13.04%, respectively. In the fully adjusted model, per 1.0-SD increment in CVAI has a significant increased risk of incident stroke: hazard ratio (HR) [95% confidence interval (CI)] was 1.17 (1.07–1.28); compared with participants in Q1 of CVAI, the HRs (95% CI) of incident stroke among those in Q2–4 were 1.47 (1.10–1.95), 1.62 (1.22–2.15), and 1.70 (1.28–2.27), respectively. Subgroups analyses suggested the positive association was significant in male participants, without diabetes, hypertension and heart disease. The findings were robust in all the sensitivity analyses. Additional, RCS curves showed a significant dose-response relationship of CVAI with risk of incident stroke (P for non-linear trend = 0.319). Conclusion Increased CVAI is significantly associated with higher risk of stroke incidence, especially in male individuals, without hypertension, diabetes and heart disease. The findings suggest that baseline CVAI is a reliable and effective biomarker for risk stratification of stroke, which has far-reaching significance for primary prevention of stroke and public health

Serum total bilirubin and one-year prognosis of patients with coronary artery disease and psoriasis

Summary: To evaluate the potential predictive value of total bilirubin (TBIL) for one-year prognosis in patients with coronary artery disease (CAD) and psoriasis. 278 psoriasis patients who underwent coronary angiography and were diagnosed as CAD were recruited. Baseline TBIL was measured at admission. Patients were divided into three groups according to the third tertiles of TBIL. The coronary angiography showed that lower TBIL was associated with the severity of lesion calcification. After a mean follow-up of 315 days, major adverse cardiac and cerebrovascular events (MACCEs) were reported in 61 patients. Compared with patients with higher TBIL tertiles, the incidence of MACCEs increased significantly in patients with middle and lower TBIL tertiles. The incidence of MACCEs in one-year follow-up was significantly different between higher and lower tertiles. The findings indicate that decreased TBIL is a potential predictor of poor prognosis in patients with psoriasis and CAD