解毒通络方通过TGF-β1/Smad和ROCK通路对大鼠心肌纤维化的改善作用

目的:探讨解毒通络方在大鼠心肌纤维化进程中的作用,并阐明其作用机制.方法:30只SPF级Wistar大鼠随机分为正常对照组、模型组、卡托普利组、低剂量解毒通络方组和高剂量解毒通络方组(n=6),以5 mg·kg-1盐酸异丙肾上腺素皮下注射法复制大鼠心肌纤维化模型,卡托普利组、低剂量解毒通络方组和高剂量解毒通络方组大鼠分...     

Identification of Inhibitors and Drug Targets for Human Adenovirus Infections

Adenoviruses can cause infections in people of all ages at all seasons of the year. Adenovirus infections cause mild to severe illnesses. Children, immunocompromised patients, or those with existing respiratory or cardiac disease are at higher risk. Unfortunately, there are no commercial drugs or vaccines available on the market for adenovirus infections. Therefore, there is an urgent need to discover new antiviral drugs or drug targets for adenovirus infections. To identify potential antiviral agents for adenovirus infections, we screened a drug library containing 2138 compounds, most of which are drugs with known targets and past phase I clinical trials. On a cell-based assay, we identified 131 hits that inhibit adenoviruses type 3 and 5. A secondary screen confirmed the antiviral effects of 59 inhibitors that inhibit the replication of adenoviruses type 3 or 5. Most of the inhibitors target heat shock protein, protein tyrosine kinase, the mTOR signaling pathway, and other host factors, suggesting that these host factors may be essential for replicating adenoviruses. Through this study, the newly identified adenovirus inhibitors may provide a start point for developing new antiviral drugs to treat adenovirus infections. Further validation of the identified drug targets can help the development of new therapeutics against adenovirus infections.     

Dietary Vitamin B1 Intake Influences Gut Microbial Community and the Consequent Production of Short-Chain Fatty Acids

The gut microbiota is closely related to good health; thus, there have been extensive efforts dedicated to improving health by controlling the gut microbial environment. Probiotics and prebiotics are being developed to support a healthier intestinal environment. However, much work remains to be performed to provide effective solutions to overcome individual differences in the gut microbial community. This study examined the importance of nutrients, other than dietary fiber, on the survival of gut bacteria in high-health-conscious populations. We found that vitamin B1, which is an essential nutrient for humans, had a significant effect on the survival and competition of bacteria in the symbiotic gut microbiota. In particular, sufficient dietary vitamin B1 intake affects the relative abundance of Ruminococcaceae, and these bacteria have proven to require dietary vitamin B1 because they lack the de novo vitamin B1 synthetic pathway. Moreover, we demonstrated that vitamin B1 is involved in the production of butyrate, along with the amount of acetate in the intestinal environment. We established the causality of possible associations and obtained mechanical insight, through in vivo murine experiments and in silico pathway analyses. These findings serve as a reference to support the development of methods to establish optimal intestinal environment conditions for healthy lifestyles.     

博落回中生物碱质谱裂解规律研究进展

博落回中生物碱的代谢途径可简化为：氨基酸→苄基异喹啉类生物碱→四氢原小檗碱型生物碱（或者转化成阿朴芬类生物碱）→N-甲基-四氢原小檗碱型生物碱（或者转化成原小檗碱型生物碱）→普罗托品类生物碱→二氢苯并菲啶类生物碱→苯并菲啶类生物碱→苯并菲啶类生物碱二聚体。对博落回代谢途径中9类生物碱质谱裂解规律的总结,为利用质谱裂解方式初步确定生物碱的结构类型;利用LC-MS鉴定不同产地、不同时期、不同部位博落回中标识性生物碱;以博落回中生物碱为原料而开发的中兽药药动学以及药物残留的研究;解析博落回中微量生物碱的结构式以及对其他天然药物中同类生物碱的质谱研究提供参考。     

mTOR信号通路与支气管肺发育不良

mTOR信号通路是在进化上高度保守的细胞内信号通路,参与多条信号通路的传导,主要包括 PI3K/AKT/mTOR 通路、AKT/TSC1-TSC2/Rheb/mTOR 通路、LKB1-AMPK-TSC-mTOR 通路和 FGF-10-Spry2-mTORC1-STAT3/HIF-1α-VEGF-A通路。该信号通路从多个水平多个方面参与肺发育及肺部多种疾病的调控过程,可能与支气管肺发育不良( bronchopulmonary dysplasia,BPD)有关。 BPD是早产儿十分常见的一种慢性肺疾病( chronic lung disease,CLD),是各种理化因素对发育不成熟肺造成急性肺损伤及损伤后异常修复、肺纤维化的过程。该文总结了mTOR信号通路与肺发育、急性肺损伤及肺纤维化可能存在的关系,探索mTOR信号通路在BPD形成过程中的作用,以期为BPD的防治提供新的切入点。     

Qiangli Wuhu mixture alleviates LPS-induced pneumonia by inhibiting the TLR4/NF-κB/NLRP3 pathway: a study based on network pharmacology

ContextQiangli Wuhu (QLWH) mixture is a concoction approved and registered by Ningxia Medical Products Administration. It has therapeutic effects on various types of pneumonia.ObjectiveTo clarify the mechanisms of QLWH in treating pneumonia.Materials and methodsThe potential targets of QLWH in the treatment of pneumonia were predicted by network pharmacology. Male, Institute of Cancer Research (ICR) mice were randomly divided into five groups of 12 mice, control, vehicle, QLWH (10 and 20 mg/kg) and dexamethasone (DXM), and orally treated twice daily with normal saline, QLWH or DXM. The pneumonia model was established by tracheal instillation of lipopolysaccharide (LPS). After treatment five days, ELISA, H&E staining and Western blot were used to investigate protective effects of QLWH.ResultsNine hundred and ninety-four active ingredients were found through network pharmacology, corresponding to 135 targets for the treatment of pneumonia; compared to the vehicle group, QLWH (10 and 20 mg/kg) significantly decreased the levels of TNF-α (14.3% and 28.8%), IL-1β (23.9% and 42.8%) and IL-6 (13.2% and 16.1%), increased the levels of IL-10 (134.3% and 172.9%); in terms of mechanism, QLWH down-regulated TLR4/NF-κB/NLRP3 axis related proteins in lung tissue of pneumonia model mice (p < 0.05).Discussion and conclusionsThis study combined network pharmacology and animal experiments, providing effective evidence for the clinical promotion of QLWH. Meanwhile, it is of significance for further development.     

蛋氨酸限制提高内源性H2S活性延缓衰老的机制研究进展

蛋氨酸限制(Methionine restriction,MetR)作为饮食限制的方法之一,能够改善多种无脊椎动物、啮齿类动物及包括人类灵长类动物的衰老及其相关疾病.但MetR对衰老的具体调节作用机制尚未完全明确,目前除了与饮食限制的共有机制以外,越来越多的研究表明内源性硫化氢(Endogenous hydrogen ...     

敲低着丝粒蛋白U对顺铂耐药卵巢癌细胞自我更新、顺铂耐药和Wnt/β-catenin信号活性的抑制作用

目的:探讨下调着丝粒蛋白U(CENPU)对卵巢癌(OC)细胞顺铂耐药的影响,并分析其作用机制.方法:采用Western blotting法检测OC细胞(OVCAR3和SKOV3细胞)和顺铂耐药OC细胞(OVCAR3/DDP和SKOV3/DDP细胞)中CENPU蛋白表达水平.将OVCAR3/DDP和SKOV3/DDP细胞...     

五味沙棘散对卵清蛋白诱导的过敏性支气管哮喘大鼠的保护作用及机制

目的 探究五味沙棘散对卵清蛋白（ovalbumin,OVA）诱导的过敏性哮喘大鼠的保护作用及机制。方法 SD大鼠随机分为对照组、模型组、地塞米松（0.5 mg/kg）组和五味沙棘散（0.5、2.0 g/kg）组,建立OVA诱导的大鼠早期支气管哮喘模型,苏木素-伊红（HE）和Masson染色观察支气管病理情况及纤维化程度;免疫组化检测支气管间隙连接蛋白43（connexin 43,Cx43）的表达和分布;ELISA检测血清中免疫球蛋白E（immunoglobulin E,IgE）和白细胞介素-13（interleukin-13,IL-13）水平;亚甲基蓝法和WSP-1荧光探针法测定血清中硫化氢（hydrogen sulfide,H₂S）水平。建立CdCl₂诱导的支气管上皮BEAS-2B细胞损伤模型,MTT法检测细胞活性;Hoechest 33342染色法观察细胞核形态变化;MitoSOX染色检测细胞线粒体活性氧（mitochondrial reactive oxygen species,mtROS）水平;Western blotting检测半胱氨酸天冬氨酸蛋白酶-3（cystein-asparate protease-3,Caspase-3）、核因子红细胞系2相关因子（nuclear factor erythroid 2-related factor,Nrf2）和Kelch样ECH关联蛋白1（Kelch like ECH associated protein 1,Keap1）蛋白表达。结果 五味沙棘散能够减少支气管黏膜上皮细胞脱落和黏液分泌（P＜0.001）,降低胶原纤维的沉积和Cx43的表达及分布（P＜0.05、0.01、0.001）,降低血清中IgE、IL-13水平（P＜0.05）,升高血清中H₂S水平（P＜0.05、0.01）。五味沙棘散含药血清呈剂量相关性地抑制CdCl₂诱导的BEAS-2B细胞凋亡及mtROS水平（P＜0.01、0.001）,上调Caspase-3和Nrf2蛋白表达（P＜0.05、0.01）,下调Keap1蛋白表达（P＜0.01）。结论 五味沙棘散对OVA诱导的哮喘大鼠和CdCl₂诱导的支气管上皮细胞凋亡均具有保护作用,其机制可能与调控Nrf2/Keap1信号通路有关。