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Pathophysiological changes of muscle after ischemic stroke:a secondary consequence of stroke injury

Neural Regeneration research 2024年第4期19卷 737-746页

作者： Hu Qi Dan Tian Fei Luan Ruocong Yang Nan Zeng state key laboratory of Southwestern chinese medicine Resources Chengdu University of Traditional Chinese Medicine school of pharmacy Chengdu University of Traditional Chinese Medicine Acupuncture and Tuina school Chengdu University of Traditional Chinese Medicine

Sufficient clinical evidence suggests that the damage caused by ischemic stroke to the body occurs not only in the acute phase but also during the recovery period,and that the latter has a greater impact on the long-term prognosis of the ***,current stroke studies have typically focused only on lesions in the central nervous system,ignoring secondary damage caused by this *** a phenomenon arises from the slow progress of pathophysiological studies examining the central nervous ***,the appropriate therapeutic time window and benefits of thrombolytic therapy are still controversial,leading scholars to explore more pragmatic intervention *** treatment measures targeting limb symptoms can greatly improve a patient’s quality of life,they have become a critical intervention *** the most vital component of the limbs,skeletal muscles have become potential points of *** this,to the best of our knowledge,there are no comprehensive reviews of pathophysiological changes and potential treatments for post-stroke skeletal *** current review seeks to fill a gap in the current understanding of the pathological processes and mechanisms of muscle wasting atrophy,inflammation,neuroregeneration,mitochondrial changes,and nutritional dysregulation in stroke *** addition,the challenges,as well as the optional solutions for individualized rehabilitation programs for stroke patients based on motor function are discussed.

关键词： inflammation ischemic stroke mitochondria muscle atrophy muscle fiber muscle nutrition quality of life rehabilitation ubiquitin

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Triple three-dimensional MS/MS spectrum facilitates quantitative ginsenosides-targeted sub-metabolome characterization in notoginseng

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4045-4058页

作者： Ke Zhang Jinru Jia Ting Li Wenjing Liu Pengfei Tu Jian-Bo Wan Jun Li Yuelin Song Modern research Center for Traditional chinese medicine Beijing Research Institute of Chinese MedicineBeijing University of Chinese MedicineBeijing 100029China SCIEX China Beijing 100015China school of pharmacy Henan University of Chinese MedicineZhengzhou 450046China state key laboratory of quality research in chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoTaip1Macao 999078China

Although serving as the workhorse,MS/MS cannot fully satisfy the analytical requirements of quantitative sub-metabolome *** more information intrinsically correlates to more structural and concentration clues,here,efforts were devoted to comprehensively tracing and deciphering MS/MS behaviors through constructing triple three-dimensional(33D)-MS/MS ***-targeted metabolomics of notoginseng,one of the most famous edible medicinal plants,was employed as a *** authentic ginsenosides were deployed to build the correlations between 33D-MS/MS spectra and structure/concentration *** assaying ginsenosides with progressive concentrations using QTOF-MS to configure 1st 3D spectrum,the generations of MS1 spectral signals,particularly multi-charged multimer anions,e.g.,[2Me2H]2e and[2Mt2HCOO]2e ions,relied on both concentration and the amount of sugar *** programming progressive collision energies to the front collision cell of Qtrap-MS device to gain 2nd 3D spectrum,optimal collision energy(OCE)corresponding to the glycosidic bond fission was primarily correlated with the masses of precursor and fragment ions and partially governed by the glycosidation *** quantitative relationships between OCEs and masses of precursor and fragment ions were utilized to build large-scale quantitative program for *** applying progressive exciting energies to the back collision chamber to build 3rd 3D spectrum,the fragment ion and the decomposition product anion exhibited identical dissociation trajectories when they shared the same molecular *** ginsenosides-focused quantitative metabolomics,significant differences occurred for sub-metabolome amongst different parts of *** differential ginsenosides were confirmatively identified by applying the correlations between 33D-MS/MS spectra and ***,33D-MS/MS spectrum covers all MS/MS behaviors and dramatically faci

关键词： Quantitative submetabolome characterization Ginsenosides Structural identification Notoginseng Full exciting energy ramp-MS3 spectrum

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New perspectives on the therapeutic potential of quercetin in non-communicable diseases:Targeting Nrf2 to counteract oxidative stress and inflammation

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Journal of Pharmaceutical Analysis 2024年第6期14卷 805-822页

作者： Li Zhang Li-Yue Xu Fei Tang Dong Liu Xiao-Lan Zhao Jing-Nan Zhang Jia Xia Jiao-Jiao Wu Yu Yang Cheng Peng Hui Ao state key laboratory of Southwestern chinese medicine Resources School of PharmacyChengdu University of Traditional Chinese MedicineChengdu611137China Innovative Institute of chinese medicine and pharmacy Chengdu University of Traditional Chinese MedicineChengdu611137China

Non-communicable diseases(NCDs),including cardiovascular diseases,cancer,metabolic diseases,and skeletal diseases,pose significant challenges to public health *** complex pathogenesis of these diseases is closely linked to oxidative stress and inflammatory *** factor erythroid 2-related factor 2(Nrf2),a critical transcription factor,plays an important role in regulating antioxidant and anti-inflammatory responses to protect the cells from oxidative damage and inflammation-mediated ***,Nrf2-targeting therapies hold promise for preventing and treating ***(Que)is a widely available flavonoid that has significant antioxidant and anti-inflammatory *** modulates the Nrf2 signaling pathway to ameliorate oxidative stress and *** modulates mitochondrial function,apoptosis,autophagy,and cell damage biomarkers to regulate oxidative stress and inflammation,highlighting its efficacy as a therapeutic agent against ***,we discussed,for the first time,the close association between NCD pathogenesis and the Nrf2 signaling pathway,involved in neurodegenerative diseases(NDDs),cardiovascular disease,cancers,organ damage,and bone ***,we reviewed the availability,pharmacokinetics,pharmaceutics,and therapeutic applications of Que in treating *** addition,we focused on the challenges and prospects for its clinical *** represents a promising candidate for the treatment of NCDs due to its Nrf2-targeting properties.

关键词： Quercetin Nrf2 Non-communicable diseases Antioxidant Anti-inflammatory Availability

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Ganoderma lucidum:a comprehensive review of phytochemistry,efficacy,safety and clinical study

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Food Science and Human Wellness 2024年第2期13卷 568-596页

作者： Sijia Wu Siyuan Zhang Bo Peng Dechao Tan Mingyue Wu Jinchao Wei Yitao Wang Hua Luo Macao Centre for research and Development in chinese medicine State Key Laboratory of Quality Research in Chinese MedicineInstitute of Chinese Medical SciencesUniversity of MacaoMacao SAR 999078China College of pharmacy Guangxi Medical UniversityNanning 530021China Guangxi University of chinese medicine Nanning 530001China

Ganoderma lucidum,one of the most well-known edible fungi,is believed to be very beneficial for longevity and vitality.A long usage history suggests that *** has various clinical therapeutic *** experimental studies have confirmed that *** has multiple pharmacological effects,including antitumor,anti-microbial,anti-HIV protease,and antidiabetic activity and so *** the deepening of research,more than 300 compounds have been isolated from *** is an increasing population of ***-based products,and its international development is ***,*** has drawn much attention to its chemical composition,therapeutic effect,clinical value,and *** paper provides a comprehensive review of these aspects to enhance the global promotion of ***.

关键词： Ganoderma lucidum Phytochemistry Efficacy Safety Clinical study

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Protective Effect of Silibinin on Lipopolysaccharide-Induced Endotoxemia by Inhibiting Caspase-11-Dependent Cell Pyroptosis

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chinese Journal of Integrative medicine 2024年第10期30卷 917-926页

作者： OU Jin-ying LIU Shan-hong TANG Dong-kai SHI Ling-zhu YAN Li-jun HUANG Jing-yan ZOU Li-fang QUAN Jing-yu YOU Yan-ting CHEN Yu-yao YU Lin-zhong LU Zi-bin Third Level research laboratory of state Administration of Traditional chinese medicine School of Traditional Chinese Medicine Southern Medical University Guangdong Provincial key laboratory of chinese medicine Pharmaceutics school of Traditional chinese medicine Southern Medical University

Objective: To explore the protective effect and the underlying mechanism of silibinin(SIB), one of the active compounds from Silybum marianum(L.) Gaertn in endotoxemia. Methods: Mouse peritoneal macrophage were isolated via intraperitoneally injection of BALB/c mice with thioglycolate medium. Cell viability was assessed using the cell counting kit-8, while cytotoxicity was determined through lactate dehydrogenase cytotoxicity assay. The protein expressions of interleukin(IL)-1α, IL-1β, and IL-18 were determined by enzyme-linked immunosorbent assay. Intracellular lipopolysaccharide(LPS) levels were measured by employing both the limulus amoebocyte lysate assay and flow cytometry. Additionally, proximity ligation assay was employed for the LPS and caspase-11 interaction. Mice were divided into 4 groups: the control, LPS, high-dose-SIB(100 mg/kg), and low-dose-SIB(100 mg/kg) groups(n=8). Zebrafish were divided into 4 groups: the control, LPS, high-dose-SIB(200 μmol/L), and low-dose-SIB(100 μmol/L) groups(n=30 for survival experiment and n=10 for gene expression analysis). The expression of caspase-11, gasdermin D(GSDMD), and N-GSDMD was determined by Western blot and the expressions of caspy2, gsdmeb, and IL-1β were detected using quantitative real-time PCR. Histopathological observation was performed through hematoxylineosin staining, and protein levels in bronchoalveolar lavage fluid were quantified using the bicinchoninicacid protein assay. Results: SIB noticeably decreased caspase-11 and GSDMD-mediated pyroptosis and suppressed the secretion of IL-1α, IL-1β, and IL-18 induced by LPS(P<0.05). Moreover, SIB inhibited the translocation of LPS into the cytoplasm and the binding of caspase-11 and intracellular LPS(P<0.05). SIB also attenuated the expression of caspase-11 and N-terminal fragments of GSDMD, inhibited the relative cytokines, prolonged the survival time, and up-regulated the survival rate in the endotoxemia models(P<0.05). Conclusions: SIB can inhibit pyrop

关键词： caspase-11 endotoxemia inflammation pyroptosis silibinin

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Progress in approved drugs from natural product resources

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chinese Journal of Natural medicines 2024年第3期22卷 195-211页

作者： LUO Zhongwen YIN Fucheng WANG Xiaobing KONG Lingyi state key laboratory of Natural medicines and Jiangsu key laboratory of Bioactive Natural Product research School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 211198China

Natural products (NPs) have consistently played a pivotal role in pharmaceutical research, exerting profound impactson the treatment of human diseases. A significant proportion of approved molecular entity drugs are either directly derived from NPs orindirectly through modifications of NPs. This review presents an overview of NP drugs recently approved in China, the United states,and other countries, spanning various disease categories, including cancers, cardiovascular and cerebrovascular diseases, centralnervous system disorders, and infectious diseases. The article provides a succinct introduction to the origin, activity, development process, approval details, and mechanism of action of these NP drugs.

关键词： New drugs Natural products Structural modification

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Exosomes derived from pulmonary metastatic sites enhance osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2039-2056页

作者： Pei Yu Yubao Han Lulu Meng Yanyuan Tian Zhiwei Jin Jun Luo Chao Han Wenjun Xu Lingyi Kong Chao Zhang state key laboratory of Natural medicines Jiangsu Key Laboratory of Bioactive Natural Product ResearchSchool of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 211198China

Osteosarcoma,a prevalent primary malignant bone tumor,often presents with lung metastases,severely impacting patient survival *** vesicles,particularly exosomes,play a pivotal role in the formation and progression of osteosarcoma-related pulmonary ***,the communication between primary osteosarcoma and exosome-mediated pulmonary lesions remains obscure,with the potential impact of pulmonary metastatic foci on osteosarcoma progression largely *** study unveils an innovative mechanism by which exosomes originating from osteosarcoma pulmonary metastatic sites transport the miR-194/215 cluster to the primary tumor *** transportation enhances lung metastatic capability by downregulating myristoylated alanine-rich C-kinase substrate(MARCKS)*** this phenomenon,in this study we employ cationic bovine serum albumin(CBSA)to form nanoparticles(CBSA-anta-194/215)via electrostatic interaction with antagomir-miR-194/*** nanoparticles are loaded into nucleic acid-depleted exosomal membrane vesicles(anta-194/215@Exo)targeting osteosarcoma lung metastatic *** with bioengineered exosome mimetics(anta-194/215@Exo)not only impedes osteosarcoma progression but also significantly prolongs the lifespan of tumor-bearing *** findings suggest that pulmonary metastatic foci-derived exosomes initiate primary osteosarcoma lung metastasis by transferring the miR-194/215 cluster targeting MARCKS,making the miR-194/215 cluster a promising therapeutic target for inhibiting the progression of patients with osteosarcoma lung metastases.

关键词： Lung–bone transmission miR-194/215 cluster Exosome Lung metastasis Epithelial–mesenchymal transition Vasculogenic mimicry Bioengineered exosome mimetics Osteosarcoma

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Rapid Simultaneous Determination of Four Ganoderic Acids in Ganoderma(chinese Name:Lingzhi)by Direct Infusion-Multiple Reaction Monitoring Cubed

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Journal of Analysis and Testing 2024年第1期8卷 52-62页

作者： Nian Wu Bo Peng Ting Li Pengfei Tu Shengpeng Wang Bo Li Wenjing Liu Yuelin Song Modern research Center for Traditional chinese medicine Beijing Research Institute of Chinese MedicineBeijing University of Chinese MedicineBeijing 100029China Amway(China)Botanical research Center Wuxi 214011China state key laboratory of quality research in chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipa 999078China Amway(Shanghai)Innovation&Science Co. LtdShanghai 201508China school of pharmacy Henan University of Chinese MedicineZhengzhou 450046China

Attributing to the rapid demand expansion for the edible medicinal materials in the market,the limited throughput of highperformance liquid chromatography-multiple reaction monitoring(HPLC-MRM)cannot fully address the measurement workload for a huge number of testing ***,it is urgent to pursue more efficient approaches for the quality *** of the greater selectivity of MRM cubed(MRM^(3))over MRM,there might be a chance to omit the time-intensive LC *** current study,we attempted to develop a direct infusion(DI)-MRM^(3) program,and the applicability was thereafter assessed through simultaneous determination of four ganoderic acids(GAs)in one of the most famous tonic herbal medicines namely Ganoderma(chinese name:Lingzhi).Primary parameters such as Q1>Q3>QLIT ion transitions,collision energy(CE),and excitation energy were optimized by programming online energy-resolved mass spectrometry with authentic compounds.A single DI-MRM measurement merely costed four minutes,and in spite of the wide occurrences of isomers,satisfactory selectivity was *** validation assays demonstrated the method to be sensitive,precise,accurate,and *** quantitative results from DI-MRM^(3) were also justified by conducting LC-MRM measurements in *** differences occurred for the content patterns between the two original sources namely Ganoderma lucidum and ***,and,moreover,either cultivar or harvest time showed dramatical influence on the quantitative features of the four targeted *** importantly,DI-MRM3 is a meaningful analytical option for rapid quantitative analysis of herbal medicines,because of the comparable reliability,nonetheless,less consumptions of both measurement time and solvent,compared with LC-MRM.

关键词： Direct infusion Multiple reaction monitoring cubed High-throughput quantitative analysis Ganoderic acids Ganoderma

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Supramolecular Manipulation of Intracellular Acidic Vesicles to Improve Cellular Self-Repair and Self-Defense

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CCS Chemistry 2024年第6期6卷 1487-1498页

作者： Ziyi Wang Chen Sun Yu Dong Yuan-Fu Ding Chen Zhao Ian Wa Ho Jiahong Lu Ruibing Wang state key laboratory of quality research in chinese medicine Institute of Chinese Medical SciencesUniversity of MacaoTaipaMacao 999078China

Lysosomes are the“cell stomach”that digests various species including macromolecules and pathogens for self-repair and self-defense upon fusion with endosomes,autophagosomes,and ***,artificially manipulating intracellular vesicles could potentially promote lysosome-mediated intracellular digestion for disease prevention and ***,a supramolecular strategy to efficiently tether and fuse acidic vesicles(i.e.,lysosomes,late endosomes,autolysosomes,and phagosomes)has been developed for the first time to enhance the digestion of cellular wastes and foreign matter,including pathogens.A linear polyethylene glycol(PEG)derivative dually tagged with morpholine(MOR)and adamantane(ADA)on the opposite side,namely,MOR-PEG-ADA,was designed to target intracellular acidic vesicles via MOR and to decorate their surfaces with ***,the addition of cucurbit[7]uril(CB[7])grafted hyaluronic acid(HA)induced supramolecular tethering and fusion of acidic vesicles via strong host-guest interactions between CB[7]of CB[7]-HA and ADA residing on the surface of acidic *** a proof-ofconcept,the overall cellular metabolism,including endogenous autophagy and the exogenous endocytosis and phagocytosis,was effectively upregulated,demonstrating that supramolecular regulation of the dynamics of intracellular acidic vesicles may promote the lysosome’s digestion to significantly improve cellular self-repair and self-defense.

关键词： supramolecular chemistry organelle regulation intracellular acidic vesicles lysosomes selfdefense self-repair

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Feasible Synthesis of N,O-Bidentate Difluoroboron Chromophores through Direct Functionalization of Quinoxalin-2(1H)-ones with Ketones in One Shot

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chinese Journal of Chemistry 2024年第13期42卷 1481-1486页

作者： Shuaichen Zhang Jing Zhang Xiang Ling Yifan Zhao Yue Ma Peng Sun state key laboratory for quality Ensurance and Sustainable Use of Dao-di Herbs Artemisinin Research Center and Institute of Chinese Materia MedicaChina Academy of Chinese Medical SciencesBeijing 100700China Department of Pharmaceutics School of PharmacyChina Pharmaceutical UniversityState Key Laboratory of Natural MedicinesNanjingJiangsu 210009China

Organic difluoroboron complexes are a kind of potential platforms for a wide range of applications owing to their excellent photophysical ***,we have explored a simple and direct synthesis methodology for a library of N,O-bidentate difluoroboron complexes from quinoxalin-2(1H)-ones and ketones in one *** photophysical properties of the generated complexes were evaluated and the application potential of these compounds on subcellular imaging was also explored.

关键词： N,O-Bidentate difluoroboron Chromophores Quinoxalin-2(1H)-ones Ketones/Green chemistry Synthetic method C-CcouplingI Boron

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