线粒体代谢微环境与心肌纤维化的研究进展

心肌纤维化主要包括修复性纤维化和适应性纤维化,适应性心肌纤维化是不良心肌重构和心力衰竭的主要病理生理变化,以广泛的胶原增生和细胞外基质过度沉积为主要特征。活化的成纤维细胞和肌成纤维细胞是心肌纤维化的最主要效应细胞,抑制成纤维细胞激活并拮抗肌成纤维细胞的胶原分泌成为改善心肌纤维化的重要策略。应激条件下,成纤维细胞的线粒体代谢微环境改变是导致心肌纤维化病变的重要驱动因素,近年来针对线粒体代谢微环境的靶向治疗成为心肌纤维化和心力衰竭的研究热点。该文重点讨论了心肌纤维化病变过程中成纤维细胞的代谢底物或中间产物和线粒体信号调控网络变化,以期为心肌纤维化和心肌重构患者的临床治疗提供新思路。

基于微环境代谢的“开玄充络”治法干预放射性肺纤维化探析

放射性肺纤维化是由于肺脏微环境代谢紊乱所致,中医药防治放射性肺纤维化的疗效已被广泛认可,但其理论内涵不甚系统,基于"开玄充络"理论,结合微环境概念,以改善微环境代谢为治法思路,提出干预肺纤维化新理论,丰富中医理论对于该病的防治方法。

多发性骨髓瘤细胞与骨髓微环境互作机制研究进展

多发性骨髓瘤(multiple myeloma,MM)是浆细胞来源的血液系统恶性肿瘤,其发生发展机制主要包括肿瘤细胞遗传学异常和细胞与骨髓微环境(bone marrow microenvironment,BMME)互作。MM细胞在BMME内恶性增殖,通过细胞与细胞外基质的直接或间接互作,促进MM的发生发展。探讨MM细胞与微环境的互作机制,对阐明MM发生发展机制及早诊和治疗有着重要意义。肿瘤的代谢重编程是肿瘤学研究的重点之一。本文总结出微环境中MM的代谢重编程改变和MM代谢与微生物互作的特征,以便于深入了解MM的发生发展及耐药性机制,最终达到挖掘MM治疗的新策略之目的。

Protective effects of Fufang Ejiao Jiang against aplastic anemia assessed by network pharmacology and metabolomics strategy

Objective To elucidate the mechanisms underlying the therapeutic effects of Fufang Ejiao Jiang(复方阿胶浆,FFEJJ)on aplastic anemia(AA)using integrated network pharmacology and serum metabolomics.Methods Traditional Chinese Medicine Systems Pharmacology(TCMSP),Pubmed,integrative pharmacology-based research platform of traditional Chinese medicine(TCMIP),and Bioinformatics Analysis Tool for Molecular mech ANism of Traditional Chinese Medicine(BATMAN-TCM)were used to identify the constituents and putative targets of FFEJJ.Gene Cards and DisGeNET databases were used to identify AA-associated targets.We constructed a herb-component-target network and analyzed the protein-protein interaction(PPI)network.Potential mechanisms were determined using Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.In addition,an AA model was established using acetylphenylhydrazine(APH)and cetylphenylhydrazine(CTX).Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOF/MS)-based serum metabolomics was applied to screen potential metabolites and the related pathways associated with AA and the potential anti-anemic effects of FFEJJ.Results A total of 30 active components of FFEJJ and 24 targets were related to AA.PPI network analysis showed that VEGFA,AKT1,IL-6,CASP3,and ICAM1 were key nodes overlapping with proteins known to be related to AA.KEGG pathway enrichment analysis revealed that the presumed targets of FFEJJ were mainly associated with pathways linked to the promotion of hematopoiesis and improvement of the hematopoietic microenvironment.A total of 423 metabolite biomarkers were identified between the control and AA models,which are involved in the development of AA.In contrast,FFEJJ reversed the 79 differential metabolites altered by AA.Pathway analysis suggested that the synergistic effects of FFEJJ were mainly enriched in 24 metabolic pathways.Among them,sphingolipid metabolism,glycerophospholipid metabolism,and arachidonic acid metabolism were related to promoting hematopoiesis and improving the hematopoietic microenvironment,which partially conforms with network pharmacology.The interaction network formed by three key differential metabolites,including hydroxy-eicosatetraenoic acid(HETE),sphingosine 1-phosphate(S1 P),and lysophosphatidylcholine(lyso PC),and three predicted network targets(VEGFA,CASP3,and ICAM1)may be the potential mechanism underlying the anti-AA action of the multi-component of FFEJJ.Conclusion FFEJJ could be an alternative treatment option for AA.It acts by promoting hematopoiesis and improving the hematopoietic microenvironment.Network pharmacology-integrated metabolomics makes it possible to analyze TCMs from a systems perspective and at the molecular level.

磷酸戊糖途径重编程与肿瘤生长策略

磷酸戊糖途径(pentose phosphate pathway,PPP)是葡萄糖分解代谢的重要途径之一。PPP不仅向细胞提供核糖-5-磷酸(Ribose-5-phosphate,R5P),还提供NADPH,后者在消除细胞内的活性氧、还原生物合成中起关键作用。有鉴于此,PPP的改变直接关系到细胞的生长状态。肿瘤微环境对肿瘤细胞代谢表型的影响起着至关重要的作用。研究发现,低氧、乳酸化会促使实体肿瘤细胞增加PPP的流量,为肿瘤细胞高速增殖提供物质基础。本文结合本实验室及科学界最新研究成果,对肿瘤细胞PPP重编程以及肿瘤微环境通过PPP促导生物合成的机制进行探讨。