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Rehmanniae Radix Praeparata aqueous extract improves hepatic ischemia/reperfusion injury by restoring intracellular iron homeostasis

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chinese Journal of Natural Medicines 2024年第9期22卷 769-784页

作者： ZHANG Yinhao JIA Kexin LI Yufei MA Zhi FAN Guifang LUO Ranyi LI Yajing YANG Yang LI Fanghong LIU Runping LIU Jia LI Xiaojiaoyang School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China School of chinese materia medica Beijing University of Chinese MedicineBeijing 100029China Available online 20 Sep.2024

Hepatic ischemia/reperfusion injury(HIRI)is a common pathophysiological condition occurring during or after liver resection and transplantation,leading to hepatic viability impairment and functional ***,ferroptosis,a newly recognized form of programmed cell death,has been implicated in *** Radix Praeparata(RRP),extensively used in chinese herbal medicine for its hepatoprotective,anti-inflammatory,and antioxidant properties,presents a potential therapeutic ***,the mechanisms by which RRP mitigates HIRI,particularly through the regulation of ferroptosis,remain *** this study,we developed a HIRI mouse model and monocrotaline(MCT)-and erastin-induced in vitro hepatocyte injury *** conducted whole-genome transcriptome analysis to elucidate the protective effects and mechanisms of RRP on *** RRP aqueous extract was characterized by the presence of acteoside,rehmannioside D,and *** results demonstrate that the RRP aqueous extract ameliorated oxidative stress,reduced intracellular iron accumulation,and attenuated HIRI-induced liver ***,RRP significantly inhibited hepatocyte death by restoring intracellular iron homeostasis both in vivo and in ***,the RRP aqueous extract reduced intrahepatocellular iron accumulation by inhibiting ZIP14-mediated iron uptake,promoting hepcidin-and ferroportin-mediated iron efflux,and ameliorating mitochondrial iron aggregation through upregulation of Cisd1 ***,siRNA-mediated inhibition of hamp synergistically enhanced the RRP aqueous extract's inhibitory effect on *** conclusion,our study elucidates the mechanisms by which RRP aqueous extracts alleviate HIRI,highlighting the restoration of iron metabolic *** findings position RRP as a promising candidate for clinical intervention in HIRI treatment.

关键词： Hepatic ischemia/reperfusion injury Rehmanniae Radix Praeparata Ferroptosis Intracellular iron homeostasis

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TCP-1,a novel peptide to diagnose early colon cancer

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chinese Chemical Letters 2024年第3期35卷 226-233页

作者： Hang Yu Baoying Wen Min Huang Ru Feng Libin Pan Manyi Xu Hao Lin Lin Cong Sen Zhang Yan Li Chi-Hin Cho Chongjing Zhang Xiaoguang Chen Yan Wang State key laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaChinese Academy of Medical SciencesBeijing 100050China School of Biomedical Sciences Faculty of MedicineThe Chinese University of Hong KongHong KongChina

A nine cyclic peptide(TCP-1)showed excellent specificity for colon ***-1 binds with human tumor tissues at early stages and mice tumor with diameters of 1-4 mm,suggesting that TCP-1 may be used for early diagnosis of colon *** mechanism of the targeted binding of TCP-1 to colon cancer was also studied using immunoprecipitation,LC-MS and *** screening and identifying of the possible binding target proteins of TCP-1,keratin,typeⅡcytoskeletal 5 was speculated to be the specific binding target protein of TCP-1 in human tumor *** studies were conducted to investigate the target-mediated drug disposition of the new tumor-specific peptide by LC-MS/*** tissue distribution study showed that TCP-1 was found only in colon tumors(the target site)in tumor mice did not bind to any other *** TCP-1 to tumor markedly increased its removal rate from blood circulation but mildly extended its staying time in *** tumor mice,a lower AUC of TCP-1(reduced by almost 35%)and 2-fold higher clearance were found compared to that of normal *** proposed metabolic pathway of TCP-1 in the kidney was also determined using LC-MS^(n)-*** high specificity and low toxicity of the peptide may be caused by its extremely tight binding to the *** applications for future clinical use,including MRI and PET/CT were also explored,and this research may promote the development of colon cancer diagnostic technology research and provide new ideas and technical routes for tumor diagnostic technology.

关键词： Colon cancer TCP-1 Peptide Cytokeratin 5 Pharmacokinetics/pharmacodynamics(PK/PD)

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Albizzia chinensis(Osbeck)Merr extract YS ameliorates ethanol-induced acute gastric ulcer injury in rats by regulating NRF2 signaling pathway

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Animal Models and Experimental Medicine 2024年第3期7卷 275-282页

作者： Bo Tang Liangning Li Yuanzhi Yu Guibin Wang Shuanggang Ma Shishan Yu Jianjun Zhang Institute of materia medica Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina State key laboratory of Digestive Health BeijingChina State key laboratory of Bioactive Substance and Function of Natural Medicines BeijingChina

Background:Around the world,there is a high incidence of gastric ***,an extract from the chinese herb Albizzia chinensis(Osbeck)Merr,has potential therapeutic applications for gastrointestinal *** we elucidated the protective effect and underlying mechanism of action of YS on gastric ulcer in rats injured by ***:The ethanol-i nduced gastric ulcer rat model was used to assess the protective effect of YS.A pathological examination of gastric tissue was performed by H&E ***-1 cells damaged by hydrogen peroxide were used to simulate oxidative damage in gastric mucosal epithelial *** NRF2 was knocked down using small interfering *** was used to detect ubiquitination of ***-i mmunoprecipitation was used to detect the NRF2-Keap1 ***:YS(10 and 30 mg/kg,i.g.)significantly reduced the ulcer index,decreased MDA level,and increased SOD and GSH levels in gastric tissues damaged by *** promoted NRF2 translocation from cytoplasm to nucleus and enhanced the NQO1 and HO-1 expression levels in injured rat gastric *** addition,YS regulated NQO1 and HO-1 via NRF2 in H_(2)O_(2)-i nduced oxidative injured GES-1 *** studies on the underlying mechanism indicated that YS reduced the interaction between NRF2 and Keap1 and decreased ubiquitylation of NRF2,thereby increasing its stability and expression of downstream ***2 knockdown abolished the effect of YS on MDA and SOD in GES-1 cells treated with H_(2)O_(2).Conclusion:YS reduced the NRF2-Keap1 interaction,promoting NRF2 translocation into the nucleus,which increasing the transcription and translation of NQO1 and HO-1 and improved the antioxidant capacity of rat stomach.

关键词： antioxidative ethanol gastric ulcer NRF2 YS

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Air purifier or fresh air system?A comparison of energy consumption and cost in urban China residential buildings

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Science China(Technological Sciences) 2024年第9期67卷 2637-2647页

作者： GUO Yong SUN ZhiWei WESCHLER Louise B ZHANG YinPing Department of Building Science Tsinghua UniversityBeijing 100084China beijing key laboratory of Indoor Air quality evaluation and Control Beijing 100084China Independent Researcher Colts Neck 07722NJUSA

chinese urban residential buildings face serious indoor air quality *** purification systems(e.g.,air purifiers,fresh air systems)that supply fresh air or purify indoor air are widely used in residential buildings to improve indoor air *** the challenges of energy conservation and emission reduction,it is urgent to guide residents on choosing appropriate air purification *** key problem is how to identify the best air purification system with the lowest energy consumption or operating *** of air purification systems have rarely been conducted on the premise that they should deliver air such that the main indoor pollutant concentrations all meet air quality *** ignored in comparisons are the increased filtration resistance caused by dust accumulation on the filter and the cost of filter *** this study,we propose a method to compare residential air purification systems based on energy consumption and total cost,and we provide methods to select air purification systems in China's different climatic *** used a standard two-person bedroom as the example,and determined the most suitable(minimum cost or energy consumption)air purification systems for the capital cities of the provinces in chinese mainland.

关键词： IAQ fresh air system air purifier energy consumption cost

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A multi-enzymatic cascade reaction for the synthesis of bioactive C-oligosaccharides

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chinese Chemical Letters 2024年第6期35卷 451-455页

作者： Kebo Xie Qian Zhang Fei Ye Jungui Dai State key laboratory of Bioactive Substance and Function of Natural Medicines CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs and NHC Key Laboratory of Biosynthesis of Natural ProductsInstitute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China

C-Oligosaccharides are rare in nature and possess diverse ***,their chemical synthesis faces many *** this work,enzymatic introduction of C-linked sugar chains to target aglycones was successfully achieved by multi-enzymatic cascade reactions.A C-glycosyltransferase from Aloe barbadensis was employed to introduce the first C-linked glucose and then a cyclomaltodextrin glucanotransferase from Bacillus licheniformis was used to extend the sugar chain.A total of twenty C-oligosaccharides with 2-6 sugars were synthesized from scale-up reactions and exhibited good water solubility and sodium-dependent glucose transporter 2(SGLT2)inhibitory ***,a glucoamylase was used to control the length of the sugar chain and the C-maltosides were efficiently *** findings not only expanded the structural diversity of C-oligosaccharides,but also provided a strategy for the modification of C-glycoside drugs to improve the druggability.

关键词： C-Oligosaccharides C-Glycosyltransferase Cyclomaltodextrin glucanotransferase Glucoamylase Enzymatic synthesis SGLT2 inhibitory activity

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Si-Wu-Tang attenuates liver fibrosis via regulating lncRNA H19-dependent pathways involving cytoskeleton remodeling and ECM deposition

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chinese Journal of Natural Medicines 2024年第1期22卷 31-46页

作者： QU Jiaorong XUE Xiaoyong WANG Zhixing MA Zhi JIA Kexin LI Fanghong ZHANG Yinhao WU Ruiyu ZHOU Fei ZHAO Piwen LI Xiaojiaoyang School of Life Sciences Beijing University of Chinese MedicineBeijing 100029China School of chinese materia medica Beijing University of Chinese MedicineBeijing 100029China State key laboratory of medical Molecular Biology Department of Molecular Biology and BiochemistryInstitute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China

Liver fibrosis is a dynamic wound-healing response characterized by the agglutination of the extracellular matrix(ECM).Si-Wu-Tang(SWT),a traditional chinese medicine(TCM)formula,is known for treating gynecological diseases and liver *** previous studies demonstrated that long non-coding RNA H19(H19)was markedly upregulated in fibrotic livers while its deficiency markedly reversed ***,the mechanisms by which SWT influences H19 remain ***,we established a bile duct ligation(BDL)-induced liver fibrosis model to evaluate the hepatoprotective effects of SWT on various cells in the *** results showed that SWT markedly improved ECM deposition and bile duct reactions in the ***,SWT relieved liver fibrosis by regulating the transcription of genes involved in the cytoskeleton remodeling,primarily in hepatic stellate cells(HSCs),and influencing cytoskeleton-related angiogenesis and hepatocellular *** modulation collectively led to reduced ECM *** extensive bioinformatics analyses,we determined that H19 acted as a miRNA sponge and mainly inhibited miR-200,miR-211,and let7b,thereby regulating the above cellular regulatory ***,SWT reversed H19-related miRNAs and signaling pathways,diminishing ECM deposition and liver ***,these protective effects of SWT were diminished with the overexpression of H19 in *** conclusion,our study elucidates the underlying mechanisms of SWT from the perspective of H19-related signal networks and proposes a potential SWT-based therapeutic strategy for the treatment of liver fibrosis.

关键词： Liver fibrosis LncRNA H19 Si-Wu-Tang miRNAs Cytoskeleton ECM deposition

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Hydroxysafflor Yellow A Inhibits Pyroptosis and Protecting HUVECs from OGD/R via NLRP3/Caspase-1/GSDMD Pathway

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chinese Journal of Integrative Medicine 2024年第11期30卷 1027-1034页

作者： GUO Fan HAN Xiao YOU Yue XU Shu-juan ZHANG Ye-hao CHEN Yuan-yuan XIN Gao-jie LIU Zi-xin REN Jun-guo CAO Ce LI Ling-mei FU Jian-hua Institute of Basic medical Sciences of Xiyuan Hospital China Academy of Chinese Medical Sciences beijing key laboratory of chinese materia Pharmacology Department of Central laboratory Kunshan Hospital of Chinese Medicine

Objective: To observe the protective effect and mechanism of hydroxyl safflower yellow A(HSYA)from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells(HUVECs). Methods:HUVECs were treated with oxygen-glucose deprivation reperfusion(OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations(1.25–160 μmol/L)of HSYA on HUVECs after OGD/R. HSYA 80 μmol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin(IL)-18, IL-1β, monocyte chemotactic protein 1(MCP-1), tumor necrosis factor α(TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3(NLRP3), gasdermin D(GSDMD) and GSDMD-N-terminal domain(GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt(CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1(Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot. Results: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18,IL-1β, MCP-1, TNF-α and IL-6(P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3,Caspase-1, GSDMD and GSDMD-N proteins(P<0.01). Conclusions: The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis.

关键词： chinese medicine NLRP3 inflammasome human umbilical vein endothelial cells hydroxysafflor yellow A myocardial reperfusion injury oxygen-glucose deprivation reperfusion pyroptosis

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A fungal CYP from Beauveria bassiana with promiscuous steroid hydroxylation capabilities

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chinese Chemical Letters 2024年第5期35卷 218-222页

作者： Yu Peng Yue Wang Tian-Jiao Chen Jing-Jing Chen Jin-Ling Yang Ting Gong Ping Zhu State key laboratory of Bioactive Substance and Function of Natural Medicines NHC Key Laboratory of Biosynthesis of Natural ProductsCAMS Key Laboratory of Enzyme and Biocatalysis of Natural DrugsInstitute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Hydroxylation of steroid core is critical to the synthesis of steroid *** sp^(3) C-H hydroxylation is challenging through chemical catalysis,alternatively,fungal biotransformation offers a possible solution to this ***,mining and metabolic engineering of cytochrome P450 monooxygenases(CYPs)is usually regarded as a more eco-friendly and efficient ***,we report the mining and identification of a new steroid CYP(CYP68BE1)from Beauveria bassiana by transcriptomics,heterologous expression,in vivo and in vitro functional *** catalytic promiscuity of CYP68BE1 was explored,and CYP68BE1 showed promiscuously and catalytically versatile,which is qualified for monohydroxylation on C11α,C1α,C6βand dihydroxylation on C1β,11αand C6β,11αof six steroids,leading to the production of key steroid intermediates required in the industrial synthesis of some indispensable steroid *** dynamics simulations were performed,revealing the molecular basis of different binding orientations of CYP68BE1 with different *** discovery of CYP68BE1 offers a promising biocatalyst for enriching the steroid structural and functional diversity,which also can be applied to biosynthesize valuable steroid drug intermediates.

关键词： Fungal CYPs Steroid hydroxylase Beauveria bassiana Promiscuous biocatalyst Molecular dynamics

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Molecular characterization and structure basis of a malonyltransferase with both substrate promiscuity and catalytic regiospecificity from Cistanche tubulosa

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2333-2348页

作者： Xiao Liu Yuyu Liu Xiping Xu Wenqian Huang Yaru Yan Yingxia Wang Weisheng Tian Ting Mo Xiaoxue Cui Jun Li She-Po Shi Pengfei Tu Modern Research Center for Traditional chinese Medicine Beijing Research Institute of Chinese MedicineBeijing University of Chinese MedicineBeijing 100029China Modern Research Center for Traditional chinese Medicine School of Chinese Materia MedicaBeijing University of Chinese MedicineBeijing 100029China

Enzymatic malonylation of natural glycosides provides a promising alternative method for drug-like malonylated glycosides ***,the catalytic potential and structural basis of plant malonyltransferase are far from being fully *** work identified a new malonyltransferase CtMaT1 from Cistanche *** displayed unprecedented mono-and/or di-malonylation activity toward diverse glucosides with different aglycons.A“one-pot”system by CtMaT1 and a malonyl-CoA synthetase was established to biosynthesize nine new malonylated *** investigations revealed that CtMaT1 possesses an adequately spacious acyl-acceptor pocket capable of accommodating diverse ***,it recognizes malonyl-CoA through strong electrotactic and hydrogen ***/MM calculation revealed the H167-mediated SN2 reaction mechanism of CtMaT1,while dynamic simulations detected the formation of stable hydrogen bonds between the glucose-6-OH group and H167,resulting in its high malonylation *** energy profiles of two isomeric glycosides highlighted lower reaction energy barriers towards glucoside substrates,emphasizing CtMaT1's preference for ***,a mutant CtMaT1H36A with notably increased di-malonylation activity was *** underlying molecular mechanism was illuminated through MM/GBSA binding free energy *** study significantly advances the understanding of plant acyltransferases from both functional and protein structural perspectives,while also providing a versatile tool for enzymatic malonylation applications in pharmacology.

关键词： Plant acyltransferase Malonyltransferase Malonylated glycosides Enzymatic catalysis Enzyme promiscuity

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Insights into Euphorbia diversity: Probing the contrasts between Euphorbia fischeriana Steud and Euphorbia ebracteolata Hayata

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Journal of Pharmaceutical Analysis 2024年第5期14卷 775-779页

作者： Kaicheng Du Yi Zhang Lei Sun Muke Tao Tiantian Zuo Yumeng Wang Zhengfeng Zhang Dali Meng School of Traditional chinese materia medica Shenyang Pharmaceutical UniversityShenyang110016China NMPA key laboratory for quality Monitoring of Narcotic Drugs and Psychotropic Substances Chongqing Institute for Food and Drug ControlChongqing401121China National Institutes for Food and Drug Control Beijing100050China

In traditional chinese medicine(TCM),Euphorbia fischeriana Steud(***)and Euphorbia ebracteolata Hayata(***),commonly referred to as“Langdu”,are widely extensively utilized for treating lymphatic tuberculosis and ringworm[1].Both plant species are perennial herbaceous plants mainly distributed in northeastern China,Mongolia,Russia(Siberia),and Republic of Korea[2].There have been many reports on the chemical constituents and pharmacological effects of the two plant species,which has made more and more researchers realize that there may be differences between *** and *** some cases,long-term improper use of herbal medicines can even lead to life-threatening conditions[3,4].Therefore,it is essential to employ an effective technology to differentiate between these two plants based on their chemical constituents and biological activities,so as to reduce the harm caused by the mixing and misuse of medicinal ***,the present paper describes a study of the differences between *** and ***,using untargeted plant metabolomics and biological activity *** study aims to provide valuable insight into their equivalence and potential interchangeability in TCM and clinical medication.

关键词： Euphorbia Siberia northeastern

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