头皮机械刺激通过控制脑水肿减轻2-VO大鼠脑低灌注

目的:探讨头皮机械刺激(SMS),作用机理与头针相似,对脑低灌注大鼠脑水肿的脑保护作用。方法:首先,我们通过测量皮肤温度和脑血流量来筛选SMS的强度。接下来,我们观察了头皮机械刺激对2-VO模型大鼠脑血流量、脑水肿和相关病理学改变的脑保护作用。利用免疫组化和免疫印迹法检测神经凋亡相关蛋白(caspase-3、cleaved-caspase-3)和脑水肿相关蛋白(GFAP和AQP4)的表达差异。随后分析神经细胞凋亡与AQP4蛋白水平的相关性。结果:0.5 N为最适合本研究的刺激强度。与对照组相比,0.5 N、1 N、2 N组均可以维持头皮温度,改善脑血流量(均P<0.05)。SMS干预显著增加了2-VO大鼠脑血流量,降低脑含水量(P<0.001和P=0.0449)。与2-VO组相比,SMS组大鼠海马CA1区caspase-3阳性细胞数(P=0.0086)和cleavedcaspase-3阳性细胞数(P=0.036)显著减少,与caspase-3蛋白表达水平(P=0.019)相似。与sham组比较,2-VO组大鼠GFAP和AQP4表达增高(P=0.0369和P=0.0142),SMS组大鼠GFAP和AQP4表达明显降低(P=0.0484和P=0.0229)。AQP4与caspase-3、cleavedcaspase-3的表达呈正相关(R2=0.6071/R2=0.8500)。结论:本研究揭示了SMS改善脑低灌注的最佳强度及其可能的作用机制。SMS可能是一种简便、有前景的预防缺血性卒中和认知障碍的方法。

Exploring the mechanism of Yishen Daluo decoction in the treatment of multiple sclerosis based on network pharmacology and in vitro experiments

Objective:To explore the mechanism and related active components of Yishen Daluo decoction(YSDLD)in treating multiple sclerosis(MS).Methods:Targets of YSDLD were collected through the TCMSP,Chemistry,and TCMID databases.The MS targets were collected through OMIM,DrugBank,Gencards,TTD,and Pharmgkb databases.We built“componentetarget”network diagrams and proteineprotein interaction(PPI)diagrams and performed topological analysis.The targets were subjected to GO and KEGG enrichment analysis.Molecular docking verification was conducted on selected targets and molecules.Finally,in vitro experiments were con-ducted.BV2 cells were induced by lipopolysaccharide for model establishment.CCK8 experiment was conducted to explore the effect of YSDLD and RT-qPCR technology was used to explore the expression of key targets.Results:There were 184 active components in YSDLD and 898 targets of its action.There were 940 MS targets,and 215 targets were shared by YSDLD and MS.According to the“componentetarget”diagram,the top five key components included quercetin,kaempferol,beta-sitosterol,stigmasterol,and nar-ingenin.IL-6,IL-1 b,TNF-α,AKT1,and VEGFA were the important targets identified by PPI network to-pology analysis.A total of 564 functions were identified by GO enrichment analysis(P<0.01),mainly involving inflammatory response,hypoxia response,plasma membrane,neuronal cell body,protein phosphatase binding,and cytokine activity.KEGG enrichment analysis enriched 98 pathways(P<.01).YSDLD at the concentration of 20 m g/mL had no effect on BV2 cells.RT-qPCR indicated that YSDLD at the concentrations of 15 m g/mL and 20 m g/mL alleviated LPS-induced inflammatory injury and lowered the content of inflammatory factors(P<0.05).Conclusion:In this paper,the network pharmacology and in vitro experiments were used to explore the potential mechanism of YSDLD in treating MS.The research provides a good basis for the development of YSDLD and drugs for MS in future.

Activation of GSDME by Lithospermum erythrorhizon drives pyroptotic cell death

Objective:To reveal GSDME-executed pyroptosis in cancer cells induced by the Chinese traditional herbal medicine plant Lithospermum erythrorhizon(L.erythrorhizon,Zi Cao)and to investigate the potential mechanism.Methods:L.erythrorhizon was extracted by ultrasonication in 95%ethanol,and determined using high-performance liquid chromatography(HPLC).He La,A549,SW620,HEK-293 T,THP-1,K562,Raw264.7 and MDA-MB-231 cell lines were used to investigate the morphology and mechanism of pyroptosis induced by L.erythrorhizon.The lactate dehydrogenase(LDH)release,propidium iodide(PI)/Hoechst double-staining,and pyroptosis reconstitution experiments were performed to study L.erythrorhizon-induced cell pyroptosis.Results:Compared with the death inhibitor,PI/Hoechst and LDH release experiments,we found that L.erythrorhizon induced pyroptosis.Recombination and western blot experiments confired that L.erythrorhizon induced GSDME cleavage,which drives pyroptosis.This phenomenon is conserved in several cancer cell lines that might be triggered by caspase family proteases.The mechanism of L.erythrorhizon inducing pyroptosis is widely found in tumor cells.Conclusion:Our findings not only explain how L.erythrorhizon triggers cancer cell pyroptosis,but also provide mechanistic insights to guide its clinical application in the future.

Assessment of traditional Chinese medicine pattern in a bleomycininduced pulmonary fibrosis mouse model: A pilot study

Objective:To initially explore traditional Chinese medicine patterns in a bleomycin-induced pulmonary fibrosis mouse model.Methods:Thirty-six C57BL/6 mice were divided by the random number table method(with 12 rats per group)into three groups:a blank group,a model group,and a number 2 Feibi recipe(FBR-2)group.The pulmonary fibrosis mouse model was established by intratracheal instillation of bleomycin.The FBR-2 group was treated with FBR-2 for 4 weeks.Symptoms in the mice such as mental behavior,food/water intake,body weight,body temperature,respiratory rate,and tongue image were observed.The samples were collected on the 14th day and 28th day after modeling,and lung tissues were visually assessed and microscopically evaluated by staining with hematoxylin-eosin and Masson.The expression levels of hydroxyproline,interleukin(IL)-33,IL-37,tissue plasminogen activator,and plasminogen activator inhibitor-1 were determined by enzyme-linked immunosorbent assay.Results:Mice in the model group were poor in spirit,less active,slow in response,showed reduced food/water intake,body temperature,and body weight,increased respiratory rate,and their tongue color had changed from light red to dark red.However,treatment with FBR-2 significantly improved these symptoms.Extensive inflammatory cell infiltration and collagen fiber deposition were observed in the lung tissues of the model group.Compared with the blank group,the levels of hydroxyproline,IL-33,and plasminogen activator inhibitor-1 in the model group significantly increased(all P<.05),whereas that of tissue plasminogen activator significantly decreased on the 14th day and 28th day(P=.036 and P=.005,respectively).Moreover,FBR-2 improved lung inflammation and fibrinolysis imbalance and reduced collagen fiber deposition.Conclusion:To some extent,our bleomycin-induced pulmonary fibrosis mouse model exhibited traditional Chinese medicine patterns of qi deficiency,blood stasis,and heat retention.

Multiple-Objective Optimization and Design of Series-Parallel Systems Using Novel Hybrid Genetic Algorithm Meta-Heuristic Approach

In this study, we develop a new meta-heuristic-based approach to solve a multi-objective optimization problem, namely the reliability-redundancy allocation problem (RRAP). Further, we develop a new simulation process to generate practical tools for designing reliable series-parallel systems. Because the?RRAP is an NP-hard problem, conventional techniques or heuristics cannot be used to find the optimal solution. We propose a genetic algorithm (GA)-based hybrid meta-heuristic algorithm, namely the hybrid genetic algorithm (HGA), to find the optimal solution. A simulation process based on the HGA is developed to obtain different alternative solutions that are required to generate application tools for optimal design of reliable series-parallel systems. Finally, a practical case study regarding security control of a gas turbine in the overspeed state is presented to validate the proposed algorithm.