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The crosstalk between autophagy and ferroptosis:what can we learn to target drug resistance in cancer?

Cancer Biology & Medicine 2019年第4期16卷 630-646页

作者： Yulu Zhou Yong Shen Cong Chen Xinbing Sui Jingjing Yang Linbo Wang Jichun Zhou Department of Surgical Oncology Sir Run Run Shaw HospitalZhejiang University School of MedicineHangzhou 310016China Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Provinee Hangzhou 310016China Department of Breast Surgery First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310006China Department of Medical Oncology Holistic Integrative Oncology Institutes and Holistic Integrative Cancer Center of Traditional Chinese and Western MedicineThe Affiliated Hospital of Hangzhou Normal UniversityCollege of MedicineHangzhou Normal UniversityHangzhou 310012China Department of Cancer Pharmacology Holistic Integrative Pharmacy InstitutesCollege of MedicineHangzhou Normal UniversityHangzhou 310012China Key Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Provinee and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Provinee Hangzhou Normal UniversityHangzhou 310012China

Autophagy is a conserved intracellular degradation system that plays a dual role in cell death;thus,therapies targeting autophagy in cancer are somewhat *** is a new form of regulated cell death featured with the iron-dependent accumulation of lethal lipid *** pathway is morphologically,biochemically and genetically distinct from other forms of cell *** studies have revealed crosstalk between autophagy and ferroptosis at the molecular *** this review,we summarize the mechanisms of ferroptosis and autophagy,and more importantly,their roles in the drug resistance of *** connections between ferroptosis and autophagy have been revealed,and a strong causal relationship exists wherein one process controls the other and can be utilized as potential therapeutic targets for *** elucidation of when and how to modulate their crosstalk using therapeutic strategies depends on an understanding of the fine-tuned switch between ferroptosis and autophagy,and approaches designed to manipulate the intensity of autophagy might be the key.

关键词： Autophagy ferroptosis crosstalk cancer drug resistance

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自噬抑制剂3-MA增强内质网应激诱导的人鼻咽癌细胞的凋亡（英文）

自噬抑制剂3-MA增强内质网应激诱导的人鼻咽癌细胞的凋亡（英文）

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第十一届全国青年药学工作者最新科研成果交流会

作者：宋乐乐 Faculty of pharmacy Bengbu Medical CollegeAnhui Engineering Technology Research Center of Biochemical Pharmaceuticals

背景:放疗联合顺铂辅助化疗是鼻咽癌治疗的主要手段,能有效地提高预后及减少肿瘤复发。近来,在治疗时比较常见的放化疗抵抗是鼻咽癌治疗失败的关键因素。因此,目前迫切需要新的治疗手段或新的辅助用药。目的:目前,可获得的有关鼻咽癌细... 详细信息

背景:放疗联合顺铂辅助化疗是鼻咽癌治疗的主要手段,能有效地提高预后及减少肿瘤复发。近来,在治疗时比较常见的放化疗抵抗是鼻咽癌治疗失败的关键因素。因此,目前迫切需要新的治疗手段或新的辅助用药。目的:目前,可获得的有关鼻咽癌细胞中自噬的资料很少。在这一研究中,我们探讨了在鼻咽癌细胞中自噬抑制剂对内质网应激诱导的自噬的影响。方法:实验采用两种人鼻咽癌细胞珠 CNE-1 和 CNE-2 进行试验,探讨顺铂、电离辐射、2-脱氧-D-葡萄糖、衣霉素、3-甲基腺嘌呤或联合使用所诱导的内质网应激与自噬之间的关系。通过 MTT 法和集落克隆形成法检测细胞增殖情况,同时,Annexin V-FITC/PI 双染法、JC-1 染色法和 DAPI 染色法观察细胞凋亡。最后,Western blotting 法检测内质网应激标志GRP78、自噬相关蛋白 LC-3和beclin1的表达,Immunocytochemistry 法进一步检测了 beclin1 的表达。结果:MTT 法和集落克隆形成法结果均显示 3-甲基腺嘌呤与顺铂、电离辐射、2-脱氧-D-葡萄糖、衣霉素联用组处理的细胞死亡多于单用组。Annexin V-FITC/PI双染结果显示人鼻咽癌细胞对顺铂、电离辐射诱导的凋亡不敏感。顺铂、电离辐射、2-脱氧-D-葡萄糖、衣霉素均能诱导细胞产生内质网应激和自噬。3-甲基腺嘌呤增强顺铂、电离辐射、2-脱氧-D-葡萄糖、衣霉素诱导的细胞凋亡,同时,抑制顺铂、电离辐射、2-脱氧-D-葡萄糖、衣霉素所诱发的自噬。结论:顺铂、电离辐射、2-脱氧-D-葡萄糖、衣霉素能诱导人鼻咽癌细胞内质网应激和自噬的发生。自噬抑制剂 3-甲基腺嘌呤增强内质网应激诱导的细胞凋亡。结果显示,自噬在顺铂、电离辐射、2-脱氧-D-葡萄糖、衣霉素诱导凋亡中起保护细胞的机制。这些发现可作为鼻咽癌中自噬进一步研究的基础。但是,本实验仅选用了体外培养的细胞株进行观察,进一步的体内和临床试验有待深入研究。

关键词：鼻咽癌顺铂电离辐射凋亡内质网应激自噬 GRP78 beclin1 LC3 3-甲基腺嘌呤 2-脱氧-D-葡萄糖衣霉素

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Development of an orally bioavailable selective inhibitor of the menin-MLL

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Genes & Diseases 2023年第5期10卷 1735-1738页

作者： Hai-Jing Zhong Wanhe Wang Wei Zhou Jia-Xin Liang Yung-Chi Cheng Dik-Lung Ma Chung-Hang Leung State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina Department of Chemistry Hong Kong Baptist UniversityKowloon TongHong Kong SARChina Department of Pharmacology Yale University School of MedicineNew HavenCT 06520USA Department of Biomedical Sciences Faculty of Health SciencesUniversity of MacaoMacao SARChina International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE) College of PharmacyJinan UniversityGuangzhouGuangdong 510632China

The protein–protein interaction between menin and mixed lineage leukemia(MLL)plays an important role in the development of human hepatocellular carcinogenesis(HCC)and is associated with poor prognosis of HCC patients.1,2 Hence,interrupting the menin-MLL interaction is an attractive strategy in cancer treatment,particularly for liver cancer.3,4 In this study,we identified complex C1 as the first rhodium(III)-based orally bioavailable selective inhibitor of the menin-MLL interaction for HCC.

关键词： MLL prognosis carcinogenesis

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Dogs: Active Role Model for Cancer Studies—A Review

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Journal of Cancer Therapy 2013年第5期4卷 989-995页

作者： Sana Munaf Hawai M. Al-Zayer Mohammed M. Ali Yuanjie Niu A. Alawad M. Aljofan A. Aljarbou S. Altuwaijri college of Applied Medical Science Qassim University Qassim Saudi Arabia college of pharmacy Qassim University Qassim Saudi Arabia King Abdulaziz City of Science and Technology Riyadh Saudi Arabia Saad Research and Development Center Clinical Research Laboratory SAAD Specialist Hospital Al Khobar Saudi Arabia Tianjin Institute of Urological Surgery Tianjin Medical Univer- sity Tianjin China

Many studies have been done and many results have been established for studying cancers in human and the ways of treating it. However, one thing that remains relevant is the study model that is used to diagnose, cure or conclude treatment methods for human cancers. The scientists have tried some ways to link the data and tried to analyze the malicious disease in various animal models in order to solve the problem for humans. Out of all the models, scientists have preferred dogs as the most suitable model and conducted studies on them. Our article will review the reason for preferences given to dog as a study model and what the previous studies have tried to conclude by considering the dreaded disease in dogs. Our article has focused on most of the recent observations and tried to elucidate the reasons/preferences for studying cancer disease in dogs (scientific name;Canis Lupus familiaris). We will also talk about the idea of comparative oncology programs that many centers adapt in order to study the disease called cancer.

关键词： Cancer Models Dogs Comparative Oncology

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Antioxidant,antimicrobial,and α-glucosidase inhibitory activities of saponin extracts from walnut(Juglans regia L.) leaves

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Asian Pacific Journal of Tropical Biomedicine 2023年第2期13卷 60-69页

作者： Youssef Elouafy Adil El Yadini Salma Mortada Mohamed Hnini Hicham Harhar Asaad Khalid Ashraf NAbdalla Abdelhakim Bouyahya Khang Wen Goh Long Chiau Ming My El Abbes Faouzi Mohamed Tabyaoui Laboratory of Materials Nanotechnology and EnvironmentFaculty of SciencesMohammed V University in RabatRabatMorocco Laboratories of Pharmacology and Toxicology Pharmaceutical and Toxicological Analysis Research TeamFaculty of Medicine and PharmacyMohammed V University in RabatRabatMorocco Center of Plant and Microbial Biotechnology Biodiversity and EnvironmentMicrobiology and Molecular Biology TeamFaculty of SciencesMohammed V University in RabatRabatMorocco Substance Abuse and Toxicology Research Center Jazan UniversityJazan 45142Saudi Arabia Medicinal and Aromatic Plants and Traditional Medicine Research Institute National Center for ResearchKhartoumSudan Department of Pharmacology and Toxicology College of PharmacyUmm Al-Qura UniversityMakkahSaudi Arabia Laboratory of Human Pathologies Biology Faculty of SciencesMohammed V University in RabatMorocco Faculty of Data Science and Information Technology INTI International UniversityNilaiMalaysia School of Medical and Life Sciences Sunway UniversitySunway CityMalaysia

Objective:To investigate the relationship between triterpenoid saponin content and antioxidant,antimicrobial,and α-glucosidase inhibitory activities of 70%ethanolic,butanolic,aqueous,supernate and precipitate extracts of Juglans regia ***:Triterpenoid saponins of different Juglans regia leaf extracts were measured by the vanillin *** activity was evaluated against DPPH and ABTS free *** also assessed α-glucosidase inhibitory and antimicrobial activities of the leaf ***’s correlation coefficient was evaluated to determine the correlation between the saponin content and biological ***:The butanolic extract was most effective against DPPH with an IC50of 6.63μg/mL,while the aqueous extract showed the highest scavenging activity against ABTS free radical with an IC50of 42.27μg/***’s correlation analysis indicated a strong negative correlation (r=-0.956) between DPPH radical scavenging activity (IC50) and the saponin content in the samples *** addition,the aqueous extract showed the best α-glucosidase inhibitory activity compared with other *** the extracts had fair antibacterial activity against Bacillus subtilis,Escherichia coli,and Klebsiella pneumoniae except for the aqueous ***:Juglans regia extracts show potent antioxidant,antimicrobial,and α-glucosidase inhibitory *** is a correlation between saponin levels in Juglans regia leaf extracts and the studied ***,additional research is required to establish these relationships by identifying the specific saponin molecules responsible for these activities and elucidating their mechanisms of action.

关键词： Juglans regia leaves Triterpenoid saponin Antioxidant activity DPPH ABTS Antidiabetic activity α-Glucosidase Antimicrobial activity

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Inhibition of Rac1-dependent forgetting alleviates memory deficits in animal models of Alzheimer's disease

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Protein & Cell 2019年第10期10卷 745-759页

作者： Wenjuan Wu Shuwen Du Wei Shi Yunlong Liu Ying Hu Zuolei Xie Xinsheng Yao Zhenyu Liu Weiwei Ma Lin Xu Chao Ma Yi Zhong Tsinghua-Peking Center for Life Science IDG/McGovem Institutes for Brain ResearchMOE Key Laboratory of Protein ScienceSchool of Life SciencesTsinghua UniversityBeijing 100084China Life Science Division Graduate school at ShenzhenTsinghua UniversityShenzhen 518055China JoeKai Biotech.LLC LianQiang International BuildingYongfeng BaseBeijing 100084China Institute of Traditional Chinese Medicine and Natural Products College of PharmacyJinan UniversityGuangzhou 510632China Key Lab of Animal Models and Human Disease Mechanisms Kunming Institute of ZoologyChinese Academy of SciencesKunming 650223China Institute of Basic Medical Sciences Chinese Academy of Medical SciencesDepartment of Human AnatomyHistology and EmbryologyNeuroscienee CenterJoint Laboratory of Anesthesia and PainSchool of Basic MedicinePeking Union Medical CollegeBeijing 100005China

Accelerated forgetting has been identified as a feature of Alzheimer's disease(AD),but the therapeutic efficacy of the manipulation of biological mechanisms of forgetting has not been assessed in AD animal ***-re-lated C3 botulinum toxin substrate 1(Rac1),a small GTPase,has been shown to regulate active forgetting in Drosophila and mice?Here,we showed that Rac1 activity is aberrantly elevated in the hippocampal tissues of AD patients and AD animal ***,amyloid-beta 42 could induce Rac1 activation in cultured *** elevation of Rac1 activity not only accelerated 6-hour spatial memory decay in 3-month-old APP/PS1 mice,but also significantly contributed to severe memory loss in aged APP/PS1 mice.A similar age-dependent Rac1 activity-based memory loss was also observed in an AD fly ***,inhibition of Rac1 activity could ameliorate cognitive defects and synaptic plasticity in AD animal ***,two novel compounds,identified through behavioral screening of a randomly selected pool of brain permeable small molecules for their positive effect in rescuing memory loss in both fly and mouse models,were found to be capable of inhibiting Rac1 ***,multiple lines of evidence corroborate in supporting the idea that inhibition of Rac1 activity is effective for treating AD-related memory loss.

关键词： Alzheimer's disease Rac1 forgetting memory loss hippocampus

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The interplay between inflammation,immunity and commensal microflora in glaucomatous neurodegeneration

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Annals of Eye Science 2019年第1期4卷 37-40页

作者： Christin Henein Peng T.Khaw National Institute for Health Research Biomedical Research Centre for Ophthalmology Moorfields Eye Hospital and UCL Institute of OphthalmologyLondonUK School of pharmacy University College LondonLondonUK

The immensely diverse and rich human gut microbiome has a huge potential to impact health and disease(1).Gut microbiome dysbiosis has been associated with gastro-intestinal inflammatory conditions and extra-intestinal disorders;such as stroke,depression,neurodegenerative,cardiovascular and metabolic disorders(2-6).In the September 2018 issue of nature communications,Chen and colleagues report the findings from a study that found commensal microflora-induced T cell responses mediate progressive neurodegeneration in glaucoma,in mouse glaucoma models(7).

关键词： glaucoma immunity inflammation

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Human β-defensin-2 Enhances Anti-tumor Efficacy of Survivin-based Broad-spectrum DNA Vaccine in Mouse Tumor Model

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Chinese Journal of Biomedical Engineering(English Edition) 2021年第4期30卷 139-151,171页

作者： LUO Yan-xi WANG Ming-long WANG Shi-bing SUN Ting XIE Tian YAN Hui Institute of Materia Medica Hangzhou Medical CollegeHangzhou 310013China Department of Surgical Oncology the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China Molecular Diagnosis Laboratory Zhejiang Provincial People's HospitalPeople's Hospital of Hangzhou Medical CollegeHangzhou 310013China Holistic Integrative pharmacy Institutes Hangzhou Normal UniversityHangzhou 310013China

Objective:Malignant tumors greatly endanger and affect the quality of human *** antitumor biotherapy strategies,DNA vaccines hold promise in part because of their unique *** this study,an effective broad-spectrum antitumor DNA vaccine expressing human survivin T34A dominant-negative mutant fused with humanβ-defensin-2(HBD2)was ***:The expression profiles of genes of interest were examined using western blotting,reverse transcription-polymerase chain reaction(RT-PCR),and enzyme-linked immunosorbent assay(ELISA)in *** immune function of the fusion gene vaccine(FGV)was assessed in BALB/c mice,which included detection of serum antibody,spleen lymphocyte proliferation,interferon-gamma(IFN-γ)secretion,and lactate dehydrogenase(LDH)*** vivo antitumor effects of FGV were examined in a mouse breast cancer(4T1)model,whereas in vitro effects were assessed using tumor cells derived from different ***-3activity in tumor cells was also assessed after vaccine ***:The FGV triggered humoral as well as cellular immune responses against *** exhibited more potent inhibition of tumor growth as well as prolonged the survival of immunized mice compared to mice immunized with only either survivin T34A or HBD2 *** addition,FGV displayed stronger cytotoxicity against tumor cells derived from different origins compared to the other vaccines and facilitated increased caspase-3 activity in transfected tumor ***:The novel DNA vaccine consisting of a fusion of the universal tumor antigen survivin T34A mutant with molecular adjuvant HBD2generates enhanced broad-spectrum antitumor efficacy against cancers derived from various origins.

关键词： survivin T34A β-defensin 2 molecular adjuvant antitumor DNA vaccine

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The Chrysanthemum nankingense Genome Provides Insights into the Evolution and Diversification of Chrysanthemum Flowers and Medicinal Traits

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Molecular Plant 2018年第12期11卷 1482-1491页

作者： Chi Song Yifei Liu Aiping Song Gangqiang Dong Hongbo Zhao Wei Sun Shyam Ramakrishnan Ying Wang Shuaibin Wang Tingzhao Li Yan Niu Jiafu Jiang Bin Dong Ye Xia Sumei Chen Zhigang Hu Fadi Chen Shilin Chen Key Laboratory of Beijing for Identification and Safety Evaluation of Chinese Medicine Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences Beijing 100700 China college of pharmacy Hubei University of Chinese Medicine Wuhan 430065 China college of Horticulture Nanjing Agricultural University Key Laboratory of Landscape Agriculture Ministry of Agriculture Nanjing 210095 China Amway (China) Botanical R&D Center Wuxi 214115 China Department of Ornamental Horticulture School of Landscape Architecture Zhejiang Agriculture and Forestry University Hangzhou 311300 China Amway Corporation Buena Park CA 90622-5940 USA Wuhan Benagen Tech Solutions Company Limited Wuhan 430070 China Key Laboratory of Plant Resources Conservation and Sustainable Utilization South China Botanical Garden The Chinese Academy of Sciences Guangzhou 510650 China These authors contributed equally to this article

The Asteraceae (Compositae),a large plant family of approximately 24 000-35 000 species,accounts for^10% of all angiosperm species and contributes a lot to plant *** most representative members of the Asteraceae are the economically important chrysanthemums (Chrysanthemum L.)that diversified through reticulate *** is typically created by multiple evolutionary mechanisms such as wholegenome duplication 0NGD)or polyploidization and locally repetitive genome ***,the lack of genomic data from chrysanthemum species has prevented an in-depth analysis of the evolutionary mechanisms involved in their ***,we used Oxford Nanopore long-read technologyto sequence the diploid Chrysanthemum nankingense genome,which represents one of the progenitor genomes of domesticated *** analysis revealed that the evolution of the *** genome was driven by bursts of repetitive element expansion and WGD events including a recentWGD that distinguishes chrysanthemum from sunflower,which diverged from chrysanthemum approximately 38.8 million years *** of ornamental and medicinal traits in chrysanthemums are linked to the expansion of candidate gene families by duplication events including paralogous gene ***,our study of the assembled reference genome offers new knowledge and resources to dissect the history and pattern of evolution and diversification of chrysanthemum plants,and also to accelerate their breeding and improvement.

关键词： Chrysanthemum genome evolution whole-genome duplication nanopore sequencing flower evolution medicinal plant

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3D-printed gelatin methacrylate (GelMA)/ silanated silica scaffold assisted by two-stage cooling system for hard tissue regeneration

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Regenerative Biomaterials 2021年第2期8卷 50-63页

作者： Eunjeong Choi Dongyun Kim Donggu Kang Gi Hoon Yang Bongsu Jung MyungGu Yeo Min-Jeong Park SangHyun An KyoungHo Lee Jun Sik Kim Jong Chul Kim Woonhyeok Jeong Hye Hyun Yoo Hojun Jeon Research Institute of Additive Manufacturing and Regenerative Medicine Baobab Healthcare Inc55 Hanyangdaehak-RoAnsanGyeonggi-do 15588South Korea Department of Mechanical Engineering Korea Polytechnic UniversitySangidaehak-roSiheungGyeonggi-do 15073South Korea Medical Device Development Center Daegu-Gyeongbuk Medical Innovation Foundation(DGMIF)80Cheombok-roDong-guDaegu 41061South Korea Laboratory Animal Center Daegu-Gyeongbuk Medical Innovation Foundation(DGMIF)80 Cheombok-roDong-guDaegu 41061South Korea Department of Plastic and Reconstructive Surgery Dongsan Medical CenterKeimyung University College of Medicine1035 Dalgubeol-daeroDalseo-guDaegu 42601South Korea Institute of Pharmaceutical Science and Technology College of PharmacyHanyang University55 Hanyangdaehak-RoAnsanGyeonggi-Do 15588South Korea

Among many biomaterials,gelatin methacrylate(GelMA),a photocurable protein,has been widely used in 3D bioprinting process owing to its excellent cellular responses,biocompatibility and ***,GelMA still shows a low processability due to the severe temperature dependence of *** overcome this obstacle,we propose a two-stage temperature control system to effectively control the viscosity of *** optimize the process conditions,we evaluated the temperature of the cooling system(jacket and stage).Using the established system,three GelMA scaffolds were fabricated in which different concentrations(0,3 and 10 wt%)of silanated silica particles were *** evaluate the performances of the prepared scaffolds suitable for hard tissue regeneration,we analyzed the physical(viscoelasticity,surface roughness,compressive modulus and wettability)and biological(human mesenchymal stem cells growth,western blotting and osteogenic differentiation)***,the composite scaffold with greater silica contents(10 wt%)showed enhanced physical and biological performances including mechanical strength,cell initial attachment,cell proliferation and osteogenic differentiation compared with those of the *** results indicate that the GelMA/silanated silica composite scaffold can be potentially used for hard tissue regeneration.

关键词： 3D bioprinting gelatin methacrylate silanated silica cooling system human mesenchymal stem cells

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