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1.
目的分析慢性心力衰竭患者血清氨基末端B型脑钠肽前体(NT-proBNP)、超敏C反应蛋白(hypersensitive C-reactive protein, hs-CRP)和糖类抗原-125(carbohydrate antigen-125, CA-125)水平特征。方法选取2019年1月-2020年12月沈阳医学院附属第二医院心血管内科收治的82例慢性心力衰竭患者纳入观察组,选取同期进行健康体检的82例健康者纳入对照组。对比分析两组患者血清NT-pro BNP、hs-CRP和CA-125水平,以及观察组治疗前后和不同心功能分级患者血清NT-pro BNP、hs-CRP和CA125水平的差异,分析心功能分级与血清NT-pro BNP、hs-CRP和CA-125水平的关系。结果观察组治疗前血清NT-pro BNP、hs-CRP和CA-125水平高于对照组,差异均具有统计学意义(P<0.05)。观察组治疗后血清NT-pro BNP、hs-CRP和CA-125水平较治疗前降低,差异均具有统计学意义(P<0.05)。观察组心功能Ⅲ级和Ⅳ级患者的血清NT-pro BNP、hs-CRP和CA-125水平高于心功能Ⅰ级和Ⅱ级患者,差异均具有统计学意义(P<0.05)。Spearman相关性分析显示,NT-pro BNP、hs-CRP和CA-125水平与患者的心功能分级呈正相关。结论慢性心力衰竭患者血清NT-pro BNP、hs-CRP和CA-125表达水平高于健康人群,且这3项指标与患者心功能分级呈正相关,可作为慢性心力衰竭患者病情评估的潜在指标。  相似文献   
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《Saudi Pharmaceutical Journal》2022,30(11):1572-1588
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.  相似文献   
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目的:研究鱼藤素(De)诱导SGC-7901胃癌细胞凋亡的其作用机制。方法:运用CCK-8细胞活力检测法考察不同浓度(10、20、40、60、80、100 mol/L)鱼藤素作用24、48 h对SGC-7901胃癌细胞的细胞毒性;将SGC-7901胃癌细胞分为对照组及20、40 mol/L鱼藤素药物组,给药作用24 h后,蛋白质印迹法检测p-AKTThr308、叉头框蛋白O1(FoxO1)、B淋巴细胞瘤-2基因(Bcl-2)等蛋白的表达水平;运用蛋白激酶B(AKT)基因转染使SGC-7901胃癌细胞中AKT过表达,然后给予20、40 mol/L鱼藤素给药作用24 h,以未用AKT基因转染的SGC-7901胃癌细胞作为对照组蛋白质印迹法检测p-AKTThr308、FoxO1、Bcl-2等蛋白的表达水平,实时荧光定量PCR(RT-qPCR)检测FoxO1、Bcl-2、Bax mRNA的表达水平。结果:不同浓度的鱼藤素对SGC-7901胃癌细胞均具有一定的细胞毒性;20、40 mol/L鱼藤素给药作用24 h能够显著降低SGC-7901胃癌细胞中p-AKTThr308、Bcl-2等蛋白的表达水平,升高FoxO1的表达水平;与对照组比较,AKT基因转染后,SGC-7901胃癌细胞中p-AKTThr308、Bcl-2等蛋白表达水平升高,FoxO1蛋白表达降低,与模型组比较,20、40 mol/L鱼藤素给药作用后能够降低p-AKTThr308、Bcl-2等蛋白的表达水平,降低Bcl-2 mRNA的表达水平,升高FoxO1及Bax的表达水平。结论:鱼藤素能够通过作用于AKT/FoxO1信号通路诱导胃癌细胞SGC-7901凋亡。  相似文献   
5.
目的 免疫检查点抑制剂中的程序性细胞死亡蛋白受体1(programmed cell death protein1,PD-1)抑制剂已被用于多种晚期肿瘤的治疗中,该研究旨在识别恶性黑色素瘤术后PD-1抑制剂单药辅助治疗患者早期疲劳发展轨迹及其影响因素。 方法 采用便利抽样法,选取2020年4月—2021年12月于河南省某三级肿瘤医院和吉林省某三级甲等医院肿瘤科住院的患者作为调查对象,采用癌症疲乏量表调查患者首次PD-1抑制剂治疗后1、2、3、4周后的疲乏现状,利用组基轨迹模型识别106例PD-1抑制剂单药辅助治疗患者早期疲劳症状发展轨迹,运用多元Logistic回归分析患者早期疲劳症状发展轨迹的影响因素。 结果 识别出“疲劳缓解组”和“疲劳升高组” 2种早期疲劳发展轨迹。单因素分析结果显示,各亚组在肿瘤部位、自理能力、休息后是否缓解、伴有其他免疫相关不良事件个数方面的差异均具有统计学意义(P<0.05)。多元Logistic回归分析结果显示,早期疲劳症状休息后缓解[RR=0.026,95%CI(0.004,0.179)]、不伴有其他免疫相关不良事件[RR=0.255,95%CI(0.181,0.361)]被归属为类型2“疲劳升高组”的可能性较小。 结论 恶性黑色素瘤术后患者PD-1抑制剂辅助治疗早期疲劳发展呈现不同的变化轨迹,护士应重视疲劳症状休息后不缓解、伴有其他免疫相关不良事件患者早期疲劳症状的评估和干预。  相似文献   
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BackgroundTo study the effect of WISP1 on lipopolysaccharide (LPS)-induced cell injury in 3T3-L1 adipocytes.MethodLentivirus was transiently transfected into log phase 3T3-L1 adipocytes, which were then treated with LPS at a concentration of 10 μg/mL for 24 h. The cells were divided into the following groups: group A (control, untreated cells); group B (LPS-treated cells); group C (GFP), cells transfected with lentivirus-containing GFP; group D (GFP+LPS), group C treated with LPS;group E (WISP1OE), cells transfected with lentivirus, group F (shNC+LPS), cells transfected with lentivirus-containing nshRNA treated with LPS; group G (shWISP1 +LPS), cells transfected with lentivirus-containing shRNA treated with LPS; group H (WISP1OE+LPS), group E treated with LPS; group I (WISP1OE+LPS+LY294002), group E treated with LPS followed by LY294002 for 24 h.ResultsWISP1 overexpression notably ameliorated cell apoptosis, accompanied with the increased expression of bcl-2, the decreased expressions of bax and cleaved-caspase-3, and promoted the release of inflammatory factors, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in LPS-treated 3T3-L1 adipocytes. WISP1 knockdown exhibited the opposite results. In addition, WISP1 stimulated Akt phosphorylation and reduced nuclear translocation of Fork head box protein O3 (FoxO3a) in 3T3-L1 adipocytes treated by LPS. The inhibition of the PI3K/Akt signaling pathway diminished the protective effect of WISP1.ConclusionWISP1 prevents 3T3-L1 adipocytes from being injured by LPS by regulating the PI3K/Akt pathway.  相似文献   
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In lysosomal diseases, enzyme deficiency is caused by misfolding of mutant enzyme protein with abnormal steric structure that is expressed by gene mutation. Chaperone therapy is a new molecular therapeutic approach primarily for lysosomal diseases. The misfolded mutant enzyme is digested rapidly or aggregated to induce endoplasmic reticulum stress. As a result, the catalytic activity is lost. The following sequence of events results in chaperone therapy to achieve correction of molecular pathology. An orally administered low molecular competitive inhibitor (chaperone) is absorbed into the bloodstream and reaches the target cells and tissues. The mutant enzyme is stabilized by the chaperone and subjected to normal enzyme protein folding (proteostasis). The first chaperone drug was developed for Fabry disease and is currently available in medical practice. At present three types of chaperones are available: competitive chaperone with enzyme inhibitory bioactivity (exogenous), non-competitive (or allosteric) chaperone without inhibitory bioactivity (exogenous), and molecular chaperone (heat shock protein; endogenous). The third endogenous chaperone would be directed to overexpression or activated by an exogenous low-molecular inducer. This new molecular therapeutic approach, utilizing the three types of chaperone, is expected to apply to a variety of diseases, genetic or non-genetic, and neurological or non-neurological, in addition to lysosomal diseases.  相似文献   
10.
《Vaccine》2021,39(45):6601-6613
AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.  相似文献   
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