Phase 1/2 clinical trial of COVID-19 vaccine in Japanese participants: A report of interim findings

We initiated a randomized, placebo-controlled, phase 1/2 trial to evaluate the safety and immunogenicity of the S-268019-b recombinant protein vaccine, scheduled as 2 intramuscular injections given 21 days apart, in 60 randomized healthy Japanese adults. We evaluated 2 regimens of the S-910823 antigen (5 μg [n = 24] and 10 μg [n = 24]) with an oil-in-water emulsion formulation and compared against placebo (n = 12). Reactogenicity was mild in most participants. No serious adverse events were noted. For both regimens, vaccination resulted in robust IgG and neutralizing antibody production at days 36 and 50 and predominant T-helper 1-mediated immune reaction, as evident through antigen-specific polyfunctional CD4+ T-cell responses with IFN-γ, IL-2, and IL-4 production on spike protein peptides stimulation. Based on the interim analysis, the S-268019-b vaccine is safe, produces neutralizing antibodies titer comparable with that in convalescent serum from COVID-19-recovered patients. However, further evaluation of the vaccine in a large clinical trial is warranted.     

Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

Medication Adherence App for Food Pantry Clients With Diabetes: A Feasibility Study

Low-income food pantry clients are unable to adhere to the diet and physical activity recommendations of the American Diabetes Association. The aim of the study is to test the feasibility of using a mobile phone app to improve diabetes medication adherence. Clients with uncontrolled type 2 diabetes were enrolled in a mobile phone app featuring 70 days of text message reminders and incentives. The app and the 4-item Morisky Medication Adherence Scale evaluated medication adherence. Clinically significant medication adherence of 93% was achieved with use of the app. Phone app use is feasible among urban low-income clients to improve medication adherence.     

五色培元固本膏对维持性血液透析患者细胞免疫功能的影响

目的:探讨五色培元固本膏对维持性血液透析(MHD)患者细胞免疫功能的影响。方法:90例MHD患者随机分为对照组和治疗组,两组血透方法相同。对照组给予一般治疗及血透治疗,治疗组在对照组基础上口服五色培元固本膏,连续治疗3个月; 20例健康志愿者作为正常组,三组观察时间均为3个月。治疗前后用流式细胞技术检测各组T细胞亚群表达水平,酶联免疫吸附法检测各组白介素-2(IL-2)和可溶性白介素-2受体(sIL-2R)蛋白表达水平。结果:治疗前与正常组比较,对照组与治疗组CD₄⁺、CD₄⁺/CD₈⁺和IL-2表达水平均明显下降,CD₈⁺和sIL-2表达水平均上升,差异有统计学意义(P<0.05)。治疗后,与对照组相比较,治疗组CD₄⁺、CD₄⁺/CD₈⁺、IL-2表达水平明显升高,CD₈⁺和sIL-2表达水平均降低,差异有统计学意义(P<0.05)。治疗组相较正常组CD₄⁺T淋巴细胞、CD₄⁺/CD₈⁺、IL-2表达水平,差异无统计学意义(P>0.05),CD₈⁺、sIL-2表达水平升高。结论:五色培元固本膏调节T淋巴细胞和IL-2表达改善MHD的细胞免疫功能。     

Cellular immunotherapy in breast cancer: The quest for consistent biomarkers

Breast cancer is the most common malignancy in women worldwide, with a relatively high proportion of patients experiencing resistance to standard treatments. Cellular immunotherapy (CI), which is based on the extraction, modification, and re-infusion of the patient’s immune cells, is showing promising results in these patients. Among CI possible approaches, adoptive cell therapy (ACT) and dendritic cell (DC) vaccination are the most comprehensively explored in both primary/translational research studies and clinical trials. ACT may include the use of tumor-infiltrating lymphocytes (TILs), T cell receptor (TCR)-, or chimeric antigen receptor (CAR)-engineered T-cells. There are indications suggesting that a biomarker-based approach might be beneficial in effectively selecting breast cancer patients for CI. Here, we sought to provide the current knowledge of CI in breast cancer, focusing on candidate biomarkers, ongoing clinical trials, limitations, and immediate future perspectives.     

体液免疫和细胞免疫在不同巴塞罗那分期肝细胞癌患者中的差异及临床意义

目的 分析体液免疫和细胞免疫与肝细胞癌（hepatocellular carcinoma，HCC）患者巴塞罗那（Barcelona clinic liver cancer，BCLC）分期的相关性。方法 回顾性分析2014年1月至2017年12月在广西医科大学附属肿瘤医院入院治疗的1 164例HCC初治患者的体液免疫状况。采用免疫透射比浊法测定体液免疫因子的水平，采用流式细胞术检测患者细胞免疫因子的水平。结果 HCC患者体液免疫中IgG、IgA、C3、C4和C-反应蛋白（c-reaction protein，CRP）在不同BCLC分期中的水平差异有统计学意义（均P<0.05），其中C/D期患者中IgG、IgA、C3、C4和CRP水平均高于A期或B期。总T淋巴细胞在不同BCLC分期患者中的水平差异有统计学意义（P=0.040），其中C/D期患者中的总T淋巴细胞水平低于B期（P<0.05）。Spearman相关分析显示，IgG、IgA、C3、C4和CRP水平与BCLC分期均呈正相关（均P<0.05）。进一步分层分析发现IgG、IgA水平与BCLC分期的相关性受到性别因素的影响，而T淋巴细胞总数与BCLC的相关性受到性别和肝硬化背景的影响。结论 随着BCLC分期的增加，HCC患者的体液免疫功能增强，而细胞免疫功能受到抑制，尤其是男性和有肝硬化的患者。 【关键词】 肝细胞癌；细胞免疫；体液免疫；BCLC分期