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Roles of endophytic fungi in medicinal plant abiotic stress response and TCM quality development

Chinese Herbal Medicines 2024年第2期16卷 204-213页

作者： Jiahao Zhang Jiemiao Lu Yichun Zhu Xiaoxia Shen Bo Zhu Luping Qin school of pharmaceutical sciences Zhejiang Chinese Medical UniversityHangzhou 310053China Songyang Institute of Zhejiang Chinese Medical University Songyang 323400China

Medicinal plants,as medicinal materials and important drug components,have been used in traditional and folk medicine for ages.However,being sessile organisms,they are seriously affected by extreme environmental conditions and abiotic stresses such as salt,heavy metal,temperature,and water stresses.Medicinal plants usually produce specific secondary metabolites to survive such stresses,and these metabolites can often be used for treating human diseases.Recently,medicinal plants have been found to partner with endophytic fungi to form a long-term,stable,and win-win symbiotic relationship.Endophytic fungi can promote secondary metabolite accumulation in medicinal plants.The close relationship can improve host plant resistance to the abiotic stresses of soil salinity,drought,and extreme temperatures.Their symbiosis also sheds light on plant growth and active compound production.Here,we show that endophytic fungi can improve the host medicinal plant resistance to abiotic stress by regulating active compounds,reducing oxidative stress,and regulating the cell ion balance.We also identify the deficiencies and burning issues of available studies and present promising research topics for the future.This review provides guidance for endophytic fungi research to improve the ability of medicinal plants to resist abiotic stress.It also suggests ideas and methods for active compound accumulation in medicinal plants and medicinal material development during the response to abiotic stress.

关键词： abiotic stress active compounds endophytic fungus medicinal material development medicinal plant

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mIgM-mediated splenic marginal zone B cells targeting of folic acid for immunological evasion

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Acta Pharmaceutica Sinica B 2024年第2期14卷 808-820页

作者： Huan Wang Zhuxuan Jiang Zhiwei Guo Gan Luo Tianhao Ding Changyou Zhan Department of Pharmacology School of Basic Medical Sciences&Department of PharmacyShanghai Pudong HospitalFudan UniversityShanghai 200032China Department of pharmaceutical sciences School of PharmacyNaval Medical UniversityShanghai 200433China Shanghai Engineering Research Center for Synthetic Immunology Fudan UniversityShanghai 200032China

Folic acid is a fully oxidized synthetic folate with high bioavailability and stability which has been extensively prescribed to prevent congenital disabilities.Here we revealed the immunosuppressive effect of folic acid by targeting splenic marginal zone B(MZB)cells.Folic acid demonstrates avid binding with the Fc domain of immunoglobulin M(IgM),targeting IgM positive MZB cells in vivo to destabilize IgM-B cell receptor(BCR)complex and block immune responses.The induced anergy of MZB cells by folic acid provides an immunological escaping window for antigens.Covalent conjugation of folic acid with therapeutic proteins and antibodies induces immunological evasion to mitigate the production of anti-drug antibodies,which is a major obstacle to the long-term treatment of biologics by reducing curative effects and/or causing adverse reactions.Folic acid acts as a safe and effective immunosuppressant via IgM-mediated MZB cells targeting to boost the clinical outcomes of biologics by inhibiting the production of anti-drug antibodies,and also holds the potential to treat other indications that adverse immune responses need to be transiently shut off.

关键词： Membrane-bound IgM Anti-drugantibodies Bcell anergy Folic acid Marginal zoneBcells Bcell receptor Biologics Targeting

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Repurposing diacerein to suppress colorectal cancer growth by inhibiting the DCLK1/STAT3 signaling pathway

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Chinese Journal of Natural Medicines 2024年第4期22卷 318-328页

作者： YE Qiaobei ZHU Yu SHI Meng LV Linxi GONG Yuyan ZHANG Luyao YANG Lehe ZHAO Haiyang ZHAO Chengguang XU Huanhai Affiliated Yueqing Hospital Wenzhou Medical UniversityWenzhou 325600China The Institute of Life sciences Biomedical Collaborative Innovation Center of Zhejiang ProvinceWenzhou UniversityWenzhou 325035China school of pharmaceutical sciences Wenzhou Medical UniversityWenzhou 325035China

Double cortin-like kinase 1(DCLK1)exhibits high expression levels across various cancers,notably in human colorectal cancer(CRC).Diacerein,a clinically approved interleukin(IL)-1βinhibitor for osteoarthritis treatment,was evaluated for its impact on CRC proliferation and migration,alongside its underlying mechanisms,through both in vitro and in vivo analyses.The study employed MTT assay,colony formation,wound healing,transwell assays,flow cytometry,and Hoechst 33342 staining to assess cell proliferation,migration,and apoptosis.Additionally,proteome microarray assay and western blotting analyses were conducted to elucidate diacerein’s specific mechanism of action.Our findings indicate that diacerein significantly inhibits DCLK1-dependent CRC growth in vitro and in vivo.Through high-throughput proteomics microarray and molecular docking studies,we identified that diacerein directly interacts with DCLK1.Mechanistically,the suppression of p-STAT3 expression following DCLK1 inhibition by diacerein or specific DCLK1 siRNA was observed.Furthermore,diacerein effectively disrupted the DCLK1/STAT3 signaling pathway and its downstream targets,including MCL-1,VEGF,and survivin,thereby inhibiting CRC progression in a mouse model,thereby inhibiting CRC progression in a mouse model.

关键词： DCLK1 Diacerein Rhein STAT3 Colorectal cancer

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Ternary-phase layered cathodes toward ultra-stable and highrate sodium ion storage

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Rare Metals 2024年第4期43卷 1589-1598页

作者： Wen-Ji Yin Pei-Dan Su Qi Lu Xiao-Qiong Li Ji-Ming Peng Teng-Fei Zhou Ge-Meng Liang Yu-Liang Cao Hong-Qiang Wang Qing-Yu Li Si-Jiang Hu Guangxi Key Laboratory of Low Carbon Energy Materials School of Chemistry and Pharmaceutical SciencesGuangxi Normal University Institutes of Physical Science and Information Technology Anhui University Department of Chemistry and pharmaceutical sciences Guilin Normal College College of Chemistry and Chemical Engineering Huanggang Normal University school of Chemical Engineering and Advanced Materials The University of Adelaide Engineering Research Center of Organosilicon Compounds and Materials of Ministry of Education College of Chemistry and Molecular SciencesWuhan University

With the shortage of lithium resources,sodiumion batteries（SIBs） are considered one of the most promising candidates for lithium-ion batteries.P2-type and O3-type layered oxides are one of the few cathodes that can access high energy density.However,they usually exhibit structural change,capacity decay,and slow Na ion kinetic.Herein,we present layered ternary-phase cathodes with P2,P3 and O3 phases by a lattice doping strategy,which is demonstrated by X-ray diffraction（XRD） refinement.Combining the characteristics of P2,P3 and O3 phases,the layered composites show performance improvement during long-term battery cycling.In particular,Na0.7Li0.1Co0.3-Fe0.3Mn0.3O2（NLCFM） delivers a reversible capacity of120.1 mAh·g-1at 0.1C(1.0C=175 mA·g-1) with a superior capacity retention of 72.5% after 1000 cycles at10.0C.This work offers insights into the development of advanced cathode materials for SIBs.

关键词： Sodium-ion battery Cathode material Layered oxides Lattice doping Mixed phase

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Ferroptosis:a critical mechanism of N^(6)-methyladenosine modification involved in carcinogenesis and tumor progression

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Science China(Life sciences) 2024年第6期67卷 1119-1132页

作者： Qingqing Wei Changning Xue Mengna Li Jianxia Wei Lemei Zheng Shipeng Chen Yumei Duan Hongyu Deng Faqing Tang Wei Xiong Ming Zhou NHC Key Laboratory of Carcinogenesis Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China Cancer Research Institute and school of Basic Medical sciences Central South UniversityChangsha 410078China The Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education Central South UniversityChangsha 410078China Hunan Key Laboratory of Oncotarget Gene Hunan Key Laboratory of Cancer MetabolismHunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of MedicineCentral South UniversityChangsha 410013China

Ferroptosis is an iron-dependent regulatory cell necrosis induced by iron overload and lipid peroxidation.It occurs when multiple redoxactive enzymes are ectopically expressed or show abnormal function.Hence,the precise regulation of ferroptosis-related molecules is mediated across multiple levels,including transcriptional,posttranscriptional,translational,and epigenetic levels.N^(6)-methyladenosine(m^(6)A)is a highly evolutionarily conserved epigenetic modification in mammals.The m^(6)A modification is commonly linked to tumor proliferation,progression,and therapy resistance because it is involved in RNA metabolic processes.Intriguingly,accumulating evidence suggests that dysregulated ferroptosis caused by the m^(6)A modification drives tumor development.In this review,we summarized the roles of m^(6)A regulators in ferroptosis-mediated malignant tumor progression and outlined the m^(6)A regulatory mechanism involved in ferroptosis pathways.We also analyzed the potential value and application strategies of targeting m^(6)A/ferroptosis pathway in the clinical diagnosis and therapy of tumors.

关键词： ferroptosis m6A modification RNA methylation m^(6)A regulator tumor progression

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Functional Changes in Astrocytes Lead to Cognitive Deficits After Social Deprivation

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Neuroscience Bulletin 2024年第4期40卷 547-549页

作者： Yulan Li Lixuan Li Yibei Wang Yi Wang Zhong Chen Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province School of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou310053China Department of Neurology Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou310009ZhejiangChina

Social experience has a far-reaching impact on the brain and behavior.In humans,lacking social experience during childhood is associated with a faster decline in later-life cognitive function[l],while social isolation in the elderly is an independent risk factor for dementia[2].The lack of social experience at different stages of life has significant adverse effects on cognitive development and mental health.Studies have largely been focused on the neuronal activity and synaptic plasticity changes after social deprivation.Two recent studies separately reported increased expression of an astrocyte marker,glial fibrillary acidic protein,in socially isolated perinatal or adult mice demonstrating structural changes in astrocytes after social deprivation[3,4].However,it is still unknown whether and how astrocyte function is impacted by social deprivation.

关键词： faster function Functional

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STING signaling in islet macrophages impairs insulin secretion in obesity

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Science China(Life sciences) 2024年第2期67卷 345-359页

作者： Ze Hong Saihua Chen Jing Sun Dan Cheng Hanli Guo Jiahao Mei Xiang Zhang Munire Maimaiti Haiping Hao Peng Cao Haiyang Hu Chen Wang school of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China State Key Laboratory of Natural Medicines Department of Life Science and TechnologyChina Pharmaceutical UniversityNanjing 211198China school of Life sciences Westlake UniversityHangzhou 310012China

The innate immune regulator stimulator of interferon genes(STING)mediates self-DNA sensing and leads to the induction of type I interferons and inflammatory cytokines,which promotes the progression of various inflammatory and autoimmune diseases.Innate immune system plays a critical role in regulating obesity-induced islet dysfunction,whereas the potential effect of STING signaling is not fully understood.Here,we demonstrate that STING is mainly expressed and activated in islet macrophages upon high-fat diet(HFD)feeding.Sting^(-/-)alleviates HFD-induced islet inflammation by inhibiting the expression of pro-inflammatory cytokines and the infiltration of macrophages.Mechanically,palmitic acid incubation promotes mitochondrial DNA leakage into the cytosol and subsequently activates STING pathway in macrophages.Additionally,STING activation in macrophages impairs glucose-stimulated insulin secretion by mediating the engulfment ofβcell insulin secretory granules.Pharmacologically inhibiting STING activation enhances insulin secretion to control hyperglycemia.Together,our results reveal a regulatory mechanism in controlling the islet inflammation and insulin secretion in dietinduced obesity and suggest that selective blocking of the STING activation may be a promising strategy for treating type 2 diabetes.

关键词： STING obesity type 2 diabetes insulin macrophages islet

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Cellular interplay to 3D in vitro microphysiological disease model:cell patterning microbiota-gut-brain axis

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Bio-Design and Manufacturing 2024年第3期7卷 320-357页

作者： Kamare Alam Lakshmi Nair Souvik Mukherjee Kulwinder Kaur Manjari Singh Santanu Kaity Velayutham Ravichandiran Sugato Banerjee Subhadeep Roy Department of Pharmacology and Toxicology National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India Department of pharmaceutical sciences Assam UniversitySilchar 788011India Department of pharmaceutical sciences Guru Ghasidas UniversityKoniBilaspur 495009C.G.India school of Pharmacy and Biomolecular sciences RCSI University of Medicine and Health SciencesDublin D02 YN77Ireland Tissue Engineering Research Group Department of Anatomy and Regenerative MedicineRCSI University of Medicine and Health SciencesDublin D02 YN77Ireland Department of Pharmaceutics National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India Department of Natural Products National Institute of Pharmaceutical Education and ResearchKolkataWest Bengal 700054India

The microbiota-gut-brain axis(MGBA)has emerged as a key prospect in the bidirectional communication between two major organ systems:the brain and the gut.Homeostasis between the two organ systems allows the body to function without disease,whereas dysbiosis has long-standing evidence of etiopathological conditions.The most common communication paths are the microbial release of metabolites,soluble neurotransmitters,and immune cells.However,each pathway is intertwined with a complex one.With the emergence of in vitro models and the popularity of three-dimensional(3D)cultures and Transwells,engineering has become easier for the scientific understanding of neurodegenerative diseases.This paper briefly retraces the possible communication pathways between the gut microbiome and the brain.It further elaborates on three major diseases:autism spectrum disorder,Parkinson’s disease,and Alzheimer’s disease,which are prevalent in children and the elderly.These diseases also decrease patients’quality of life.Hence,understanding them more deeply with respect to current advances in in vitro modeling is crucial for understanding the diseases.Remodeling of MGBA in the laboratory uses many molecular technologies and biomaterial advances.Spheroids and organoids provide a more realistic picture of the cell and tissue structure than monolayers.Combining them with the Transwell system offers the advantage of compartmentalizing the two systems(apical and basal)while allowing physical and chemical cues between them.Cutting-edge technologies,such as bioprinting and microfluidic chips,might be the future of in vitro modeling,as they provide dynamicity.

关键词： Microbiota-gut-brain axis Neurodegeneration 3D disease model Organoid Transwell system

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Research progress on natural products against hepatocellular carcinoma

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BIOCELL 2024年第6期48卷 905-922页

作者： LINGLI ZHANG YAN LI JINGXIN MAO Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System Chongqing Medical and Pharmaceutical CollegeChongqing400030China Provincial Key Laboratory of pharmaceutical Bioactive Substances School of Life Sciences and BiopharmaceuticalsGuangdong Pharmaceutical UniversityGuangzhou510006China

Hepatocellular carcinoma(HCC)remains a prevalent and challenging malignancy globally,characterized by its numerous causal factors and generally unfavorable prognosis.In the relentless pursuit of effective treatment modalities,natural products have emerged as a promising and relatively non-toxic alternative,garnering signiﬁcant interest.The integration of natural products with contemporary medical research has yielded encouraging therapeutic outcomes in the management of HCC.This review offers a comprehensive overview of the causal factors underlying HCC,and the diverse treatment options available,and highlights the advancements made by natural products in anti-HCC research.Particularly,we provide an outline of the various types of natural products,their corresponding nomenclature,target molecules,and mechanisms of action that exhibit anti-HCC activities.Natural products are anticipated to play a pivotal role in future comprehensive treatment plans for liver cancer,potentially offering patients improved survival rates and an enhanced quality of life.

关键词： Hepatocellular carcinoma Natural products Targets Research progress Drug

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Combination strategies for first-line treatment of patients with unresectable hepatocellular carcinoma:prospect of natural products

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Chinese Journal of Natural Medicines 2024年第1期22卷 1-3页

作者： ZHANG Lele LU Jinjian school of Basic Medical sciences Chengdu UniversityChengdu 610106China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 999078China Department of pharmaceutical sciences Faculty of Health SciencesUniversity of MacaoMacao 999078China

Liver cancer stands as a significant global health concern,contributing substantially to cancer incidence and mortality,particularly in Asian countries[1].Hepatocellular carcinoma(HCC)accounts for approximately 90%of all liver cancer cases and is characterized by a high-risk profile and a generally poor prognosis[2].To address advanced HCC,systemic therapy has been recommended,leading to the approval of a range of treatment regimens in clinical practice.Traditionally,first-line therapy involved the use of multitargeted tyrosine kinase inhibitors(TKIs)such as sorafenib or lenvatinib,while cabozantinib,ramucirumab.

关键词： Unresectable hepatocellular carcinoma Combination strategies Immunotherapy PD-1/PD-L1 Natural products

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