黄芪注射液对腹膜透析相关腹膜间皮细胞TGF-β1分泌与表达的影响

目的: 探讨黄芪对腹膜透析相关性腹膜纤维化的作用。方法: 人腹膜间皮细胞(HPMC) 做体外培养,第三代细胞用于实验。分5 组观察, 对照组为RPMI1640;PDS (peritoneal dialysis solution, 腹膜透析液) 组为加入PDS; 黄芪1、2、3 组为加入含黄芪注射液的PDS,黄芪终浓度分别为10、20、40 mg·ml^-1 。分别在24 h 采用ELISA 法检测细胞上清液中转移生长因子-β₁ (TGF-β₁) 的含量, 采用逆转录多聚酶链式反应(RT-PCR) 检测TGF-β₁ mRNA 表达。结果: 腹膜间皮细胞在PDS 干预下分泌TGF-β₁明显增加(P <0.05) 。腹膜间皮细胞经含不同浓度黄芪注射液的PDS 干预后, TGF-β₁分泌与PDS 组比较有显著下降(P <0.05) 。不同浓度黄芪注射液组之间比较无显著差异(P >0.05) 。腹膜间皮细胞在PDS 干预下TGF-β₁ mRNA 表达明显升高, 比对照组上升62.43%, 腹膜间皮细胞经含不同浓度黄芪注射液的PDS 干预后, TGF-β₁ mRNA 表达显著低于PDS 组(P <0.01) 。结论: 商业性腹膜透析液可促进腹膜间皮细胞分泌和表达TGF-β₁, 黄芪可以部分抵消这一作用所致的腹膜透析相关性腹膜纤维化。     

Encapsulated Cellular Implants for Recombinant Protein Delivery and Therapeutic Modulation of the Immune System

Ex vivo gene therapy using retrievable encapsulated cellular implants is an effective strategy for the local and/or chronic delivery of therapeutic proteins. In particular, it is considered an innovative approach to modulate the activity of the immune system. Two recently proposed therapeutic schemes using genetically engineered encapsulated cells are discussed here: the chronic administration of monoclonal antibodies for passive immunization against neurodegenerative diseases and the local delivery of a cytokine as an adjuvant for anti-cancer vaccines.     

Comparative Anti-Inflammatory Effects of Salix Cortex Extracts and Acetylsalicylic Acid in SARS-CoV-2 Peptide and LPS-Activated Human In Vitro Systems

The usefulness of anti-inflammatory drugs as an adjunct therapy to improve outcomes in COVID-19 patients is intensely discussed in this paper. Willow bark (Salix cortex) has been used for centuries to relieve pain, inflammation, and fever. Its main active ingredient, salicin, is metabolized in the human body into salicylic acid, the precursor of the commonly used pain drug acetylsalicylic acid (ASA). Here, we report on the in vitro anti-inflammatory efficacy of two methanolic Salix extracts, standardized to phenolic compounds, in comparison to ASA in the context of a SARS-CoV-2 peptide challenge. Using SARS-CoV-2 peptide/IL-1β- or LPS-activated human PBMCs and an inflammatory intestinal Caco-2/HT29-MTX co-culture, Salix extracts, and ASA concentration-dependently suppressed prostaglandin E2 (PGE₂), a principal mediator of inflammation. The inhibition of COX-2 enzyme activity, but not protein expression was observed for ASA and one Salix extract. In activated PBMCs, the suppression of relevant cytokines (i.e., IL-6, IL-1β, and IL-10) was seen for both Salix extracts. The anti-inflammatory capacity of Salix extracts was still retained after transepithelial passage and liver cell metabolism in an advanced co-culture model system consisting of intestinal Caco-2/HT29-MTX cells and differentiated hepatocyte-like HepaRG cells. Taken together, our in vitro data suggest that Salix extracts might present an additional anti-inflammatory treatment option in the context of SARS-CoV-2 peptides challenge; however, more confirmatory data are needed.     

肝素与细胞因子

综述了由Th2 型细胞产生的细胞因子IL-4、IL-5,IgE和NF-κB在支气管哮喘发病过程中的作用,阐述肝素在哮喘炎症过程中细胞因子的调节作用和抗哮喘的分子作用机制。     

密生波罗花中神经酰胺类成分的抗炎作用

该研究运用硅胶柱层析法,结合超高效液相色谱-高分辨串联质谱联用技术以及核磁共振氢谱/碳谱等鉴定方法,从密生波罗花中分离鉴定了一组以神经酰胺为主的混合物,其中,神经酰胺类成分含量为81.53%,并对其抗炎作用进行了初步评价。噻唑蓝（MTT）检测结果显示低浓度的密生波罗花神经酰胺（6.25~50 μg/mL）对RAW264.7的细胞活性没有显著影响。密生波罗花神经酰胺能显著减少脂多糖（LPS）诱导RAW264.7细胞一氧化氮（NO）的释放量,且当浓度为100 μg/mL时,对NO释放的抑制率最高,为91.07%±0.11%。密生波罗花神经酰胺能高效抑制LPS诱导RAW264.7细胞中白细胞介素-1β（IL-1β）、肿瘤坏死因子（TNF-α）及一氧化氮合酶（iNOS）等炎症因子的mRNA表达水平,显著降低LPS诱导RAW264.7细胞中核因子κB抑制蛋白α（IκBα）、丙酮酸脱氢酶激酶1（PDK1）及AKT蛋白的表达及磷酸化水平。结果表明密生波罗花神经酰胺具有显著的抗炎活性,并可通过磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/AKT）信号通路发挥其抗炎作用,可为相关保健食品开发和该植物资源的合理利用提供一定的科学依据和数据支撑。     

猴头菌多糖对小鼠H22 肝癌移植瘤的抑制作用

目的：观察猴头菌多糖对小鼠移植性实体瘤H22的影响,并初步探讨其作用机制。方法：将H22瘤株接种于小鼠,制备移植性实体瘤模型。将70只小鼠随机分为正常组、模型组、阳性对照组、猴头菌多糖低、中、高剂量组(50、100、200mg/kg,以体质量计),正常组10只,其余各组12只,连续灌胃10d。阳性对照组以20mg/kg隔日腹腔注射环磷酰胺,末次给药后次日处死,计算肿瘤抑制率、胸腺及脾脏指数,检测荷瘤小鼠血清中肿瘤坏死因子-α(TNF-α)、白介素-2(IL-2)和血管内皮生长因子(VEGF)的水平;测定白细胞数和白蛋白含量。结果：不同剂量的猴头菌多糖抑瘤率均高于26%,显著提高胸腺指数,提高血中TNF-α和IL-2的水平,降低实体瘤组织VEGF的水平;不同程度的提高白蛋白水平;猴头菌多糖组白细胞数与模型组比较无明显差异,显著高于阳性对照组。结论：猴头菌多糖对H22荷瘤小鼠有明显的抑瘤作用,其机制可能是通过调节免疫功能和抑制肿瘤组织血管生成而发挥抗肿瘤作用。     

食品是如何通过细胞因子网络控制人类健康的(Ⅰ)

本文的目的是要有选择性地综述食品和肠粘膜、Toll样受体、细胞因了网络和免疫系统的相互作用。越来越多的研究结果显示，少量的食物蛋白、多肽、脂肪、低聚糖和其他生化物质可以诱导或抑制两种．发炎细胞因子和抗炎细胞因子两者之一，从而进一步地控制先天或后天获得性免疫系统、神经生理和代谢网络。而且越来越充分的证据表明，发炎和抗炎细胞因子之间的平衡和联系与中医中药中所说的“阴”“阳”之间的协调与平衡十分相似。中国人一直用“阴”“阳”来分类食品和药品，而且他们坚信一个人可以通过保持他们的食品和中草药的食入和“阴”“阳”平衡来改善其健康状况，治病防病。所以，本文在这些广泛的实验依据的基础上提出了一个理论模型，用来解释食品是如何通过对细胞因子网络的作用来调控免疫网络，并进而影响人体健康的。     

Could a Lower Toll-like Receptor (TLR) and NF-κB Activation Due to a Changed Charge Distribution in the Spike Protein Be the Reason for the Lower Pathogenicity of Omicron?

The novel SARS-CoV-2 Omicron variant B.1.1.529, which emerged in late 2021, is currently active worldwide, replacing other variants, including the Delta variant, due to an enormously increased infectivity. Multiple substitutions and deletions in the N-terminal domain (NTD) and the receptor binding domain (RBD) in the spike protein collaborate with the observed increased infectivity and evasion from therapeutic monoclonal antibodies and vaccine-induced neutralizing antibodies after primary/secondary immunization. In contrast, although three mutations near the S1/S2 furin cleavage site were predicted to favor cleavage, observed cleavage efficacy is substantially lower than in the Delta variant and also lower compared to the wild-type virus correlating with significantly lower TMPRSS2-dependent replication in the lungs, and lower cellular syncytium formation. In contrast, the Omicron variant shows high TMPRSS2-independent replication in the upper airway organs, but lower pathogenicity in animal studies and clinics. Based on recent data, we present here a hypothesis proposing that the changed charge distribution in the Omicron’s spike protein could lead to lower activation of Toll-like receptors (TLRs) in innate immune cells, resulting in lower NF-κB activation, furin expression, and viral replication in the lungs, and lower immune hyper-activation.