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Anticancer Activity of Diosgenin and Its molecular mechanism

Chinese Journal of Integrative Medicine 2023年第8期29卷 738-749页

作者： REN Qun-li WANG Qian ZHANG Xin-qun WANG Miao HU Huan TANG Jun-jie YANG Xiong-tong RAN Ying-hui LIU Huan-huan SONG Zhi-xing LIU Jian-guo LI Xiao-lan Special Key Laboratory of Microbial Resources and Drug Development of Guizhou Higher Education Institution Zunyi Medical UniversityZunyiGuizhou Province(563000)China School of Stomatology Zunyi Medical UniversityZunyiGuizhou Province(563000)China Institute of Life Sciences Zunyi Medical UniversityZunyiGuizhou Province(563000)China Zheng'an County People's Hospital ZunyiGuizhou Province(563000)China School of Basic Medicine Zunyi Medical UniversityZunyiGuizhou Province(563000)China

Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati, has shown high potential and interest in the treatment of various cancers, such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro,and clinical studies reporting the diosgenin’s anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin’s deficiencies in clinical application.

关键词： diosgenin steroidal sapogenin anticancer molecular mechanism biological activity

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The molecular mechanism of plasma membrane H^(+)-ATPases in plant responses to abiotic stress

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Journal of Genetics and Genomics 2022年第8期49卷 715-725页

作者： Jing Li Yan Guo Yongqing Yang Beijing Advanced Innovation Center for Tree Breeding by molecular Design College of Bioscience and Resources EnvironmentBeijing University of AgricultureBeijing 102206China State Key Laboratory of Plant Physiology and Biochemistry College of Biological SciencesChina Agricultural UniversityBeijing 100193China

Plasma membrane H^(+)-ATPases(PM H^(+)-ATPases)are critical proton pumps that export protons from the cytoplasm to the apoplast.The resulting proton gradient and difference in electrical potential energize various secondary active transport events.PM H^(+)-ATPases play essential roles in plant growth,development,and stress responses.In this review,we focus on recent studies of the mechanism of PM H^(+)-ATPases in response to abiotic stresses in plants,such as salt and high pH,temperature,drought,light,macronutrient deficiency,acidic soil and aluminum stress,as well as heavy metal toxicity.Moreover,we discuss remaining outstanding questions about how PM H^(+)-ATPases contribute to abiotic stress responses.

关键词： PM H^(+)-ATPases Abiotic stress molecular mechanism

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Saline-Alkali Tolerance in Rice: Physiological Response, molecular mechanism, and QTL Identification and Application to Breeding

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Rice science 2022年第5期29卷 412-434页

作者： Ratan Kumar GANAPATI Shahzad Amir NAVEED Sundus ZAFAR WANG Wensheng XU Jianlong Institute of Crop Sciences National Key Facility for Crop Gene Resources and Genetic ImprovementChinese Academy of Agricultural SciencesBeijing 100081China Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518120China

Salinity-alkalinity is incipient abiotic stress that impairs plant growth and development.Rice(Oryza sativa)is a major food crop greatly affected by soil salinity and alkalinity,requiring tolerant varieties in the saline-alkali prone areas.Understanding the molecular and physiological mechanisms of saline-alkali tolerance paves the base for improving saline-alkali tolerance in rice and leads to progress in breeding.This review illustrated the physiological consequences,and molecular mechanisms especially signaling and function of regulating genes for saline-alkali tolerance in rice plants.We also discussed QTLs regarding saline-alkali tolerance accordingly and ways of deployment for improvement.More efforts are needed to identify and utilize the identified QTLs for saline-alkali tolerance in rice.

关键词： saline-alkali tolerance physiological mechanism molecular mechanism marker-assisted backcrossing rice

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molecular mechanism of mulberry response to drought stress revealed by complementary transcriptomic and iTRAQ analyses

Molecular mechanism of mulberry response to drought stress r...

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中国蚕学会2021年学术年会

作者： Li Ruixue Su Xueqiang Zhang Yuping Wang Taichu Sericultural Research Institute Anhui Academy of Agricultural Sciences

With the continuous improvement of mulberry(Morus alba) resources development and utilization,people’s use of mulberry leaves has long been not limited to raising silkworms,and various mulberry leaf extension products have emerged one after another.The requirements of the mulberry industry for the quality and yield of mulberry leaves are gradually increasing.However,the fresh leaves of mulberry trees have a strong period of time for picking and are susceptible to adverse factors such as drought and high temperature.Among them,drought stress is the most harmful,drought stress will not only reduce the yield of mulberry leaves per unit area,but also cause premature aging,shrinkage,and insufficient nutrient supply of mulberry leaves,which greatly damages the quality of mulberry leaves.Therefore,exploring the molecular mechanism of mulberry trees resisting drought stress and clarifying the regulation network of mulberry drought response is the focus of current work.In this study,mulberry grafted seedlings were subjected to natural drought treatment,and 9 day drought treatment(DS9) materials were collected and the control samples were compared for transcriptome and proteome analysis(CK VS.DS9),aiming to clarify the molecular mechanism of mulberry drought stress response.Through transcriptome and proteome sequencing,we identified 23,358 DEGs and 1,893 DEPs,enriched them in the stress-responsive GO functional categories such as signal transducer activity,antioxidant activity,and transcription regulator activity.Kyoto Encyclopedia of Genes and Genomes(KEGG) differential enrichment analysis shows that a large number of DEGs and DEPs are enriched in flavonoid biosynthesis pathways,hormone signaling pathways(ABA,gibberellin,salicylic acid,etc.),lignin metabolism and other pathways on.Through subsequent cooperation analysis,we identified 818 co-differentially expressed genes in the CK VS.DS9 comparison group,including:Peroxidase(PRX),Superoxide dismutase(SOD),Aldehyde dehydrogenase(ALDHs),Glutathione S-transferase(GST) and ot

关键词： Mulberry Drought stress Transcriptomic iTRAQ molecular mechanism

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molecular mechanism of peritoneal dissemination in gastric cancer

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Journal of Cancer Metastasis and Treatment 2018年第1期4卷 451-458页

作者： Qing-Jiang Hu Shuhei Ito Kazuyoshi Yanagihara Koshi Mimori Department of Surgery Kyushu University Beppu HospitalBeppu 874-0838Japan Department of Surgery and Science Kyushu University HospitalFukuoka 812-8582Japan Division of Biomarker Discovery Exploratory Oncology Research&Clinical Trial CenterNational Cancer CenterKashiwa 277-8577Japan

Peritoneal dissemination(PD)is the most common cause of metastasis in gastric cancer(GC).Because there are no standard treatments for PD,it is associated with a poor prognosis.Although clinicians have performed intraperitoneal chemotherapy for GC with PD,the outcome remains unsatisfactory.Therefore,the development of novel treatments and diagnostic tools for PD is expected to improve the prognosis of GC patients with PD.Notably,it is essential to elucidate the molecular mechanisms involved in the development of PD in GC.In this review,the molecular mechanisms of PD(three steps:detachment from the primary tumor,adaptation to the microenvironment of the peritoneal cavity,and attachment to peritoneal mesothelial cells)and new topics in GC are highlighted.

关键词： Gastric cancer peritoneal dissemination molecular mechanism

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Future therapeutic implications of new molecular mechanism of colorectal cancer

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World Journal of Gastroenterology 2023年第16期29卷 2359-2368页

作者： Sen Lu Cheng-You Jia Jian-She Yang Department of Surgical Anesthesiology First Affiliated Hospital of Anhui University of Science and TechnologyHuainan 232001Anhui ProvinceChina Department of Nuclear Medicine and Oncology Research Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200072China

High incidence(10.2%)and mortality(9.2%)rates led to the ranking of colorectal cancer(CRC)as the second most malignant tumor spectrum worldwide in 2020.Treatment strategies are becoming highly dependent on the molecular characteristics of CRC.The classical theories accept two models depicting the origin of CRC:The progression of adenoma to cancer and transformation from serrated polyps to cancer.However,the molecular mechanism of CRC development is very complex.For instance,CRCs originating from laterally spreading tumors(LST)do not adhere to any of these models and exhibit extremely serious progression and poor outcomes.In this article,we present another possible pathway involved in CRC development,particularly from LST,with important molecular characteristics,which would facilitate the design of a novel strategy for targeted therapy.

关键词： Colorectal cancer Laterally spreading tumors molecular mechanism Truncated adenomatous polyposis coli mutation Golgi fragmentation Cancerous mechanism

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Absorption characteristics,model,and molecular mechanism of hydrogen sulfide in morpholine acetate aqueous solution

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Chinese Journal of Chemical Engineering 2024年第2期66卷 125-135页

作者： Hongwei Jin Yun Teng Kangkang Li Zhou Feng Zhonghao Li Shiqi Qu Hongzhi Xia Huanong Cheng Yugang Li Xinshun Tan Shiqing Zheng College of Chemical Engineering Qingdao University of Science and TechnologyQingdao 266042China

The solubility of H_(2)S was measured in solutions of N-butyl-N-methylmorpholine acetate([Bmmorp][Ac])containing 20%-40%(mass)water at experimental temperatures ranged from 298.15 to 328.15 K and pressures up to 320 k Pa.The total solubility of H_(2)S increased with higher temperatures,lower pressures,and reduced water content.The reaction equilibrium thermodynamic model was used to correlate the solubility data.The results indicate that the chemical reaction equilibrium constant decrease with increasing water content and temperature,whereas Henry constant increase with increasing water content and temperature.Compared with other ionic liquids,H_(2)S exhibits a higher physical absorption enthalpy and a lower chemical absorption enthalpy in[Bmmorp][Ac]aqueous solution.This suggests that[Bmmorp][Ac]has a strong physical affinity for H_(2)S and low energy requirement for desorption.Quantum chemical methods were used to investigate the molecular mechanism of H_(2)S absorption in ionic liquids.The interaction energy analysis revealed that the binding of H_(2)S with the ionic liquid in a1:2 ratio is more stable.Detailed analyses by the methods of the interaction region indicator and the atoms in molecules were conducted to the interactions between H_(2)S and the ionic liquid.

关键词： Ionic liquid Hydrogen sulfide Model Solubility molecular mechanism

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mechanism studies of the activation of DNA methyltransferase DNMT1 triggered by histone H3 ubiquitination,revealed by multi-scale molecular dynamics simulations

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Science China(Life Sciences) 2023年第2期66卷 313-323页

作者： Jixue Sun Fei Liu Longxiao Yuan Ning-Ning Pang Bing Zhu Na Yang State Key Laboratory of Medicinal Chemical Biology College of Pharmacy and Key Laboratory of Medical Data Analysis and Statistical Research of TianjinNankai UniversityTianjin 300353China National Laboratory of Biomacromolecules CAS Center for Excellence in BiomacromoleculesInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China

DNMT1 is a DNA methyltransferase that catalyzes and maintains methylation in CpG dinucleotides.It blocks the entrance of DNA into the catalytic pocket via the replication foci targeting sequence(RFTS)domain.Recent studies have shown that an H3-tail-conjugated two-mono-ubiquitin mark(H3Ub2)activates DNMT1 by binding to the RFTS domain.However,the activation mechanism of DNMT1 remains unclear.In this work,we combine various sampling methods of extensive simulations,including conventional molecular dynamics,Gaussian-accelerated molecular dynamics,and coarse-grained molecular dynamics,to elucidate the activation mechanism of DNMT1.Geometric and energy analyses show that binding of H3Ub2 to the RFTS domain of DNMT1 results in the bending of theα4-helix in the RFTS domain at approximately 30°–35°,and the RFTS domain rotates~20°anti-clockwise and moves~3?away from the target recognition domain(TRD).The hydrogen-bonding network at the RFTSTRD interface is significantly disrupted,implying that the RFTS domain is dissociated from the catalytic core,which contributes to activating the auto-inhibited conformation of DNMT1.These results provide structural and dynamic evidence for the role of H3Ub2 in regulating the catalytic activity of DNMT1.

关键词： DNA methyltransferase conformational change molecular dynamics simulation activation molecular mechanism

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molecular mechanism of KDM5B Development in Hepatocellular Carcinoma

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Journal of Cancer Therapy 2024年第1期15卷 1-12页

作者： Shijian Fu Min Guo Dean’s Office The Fourth People’s Hospital of Haikou Haikou China

Objective: To investigate the mechanism of cell cyclin-dependent kinase (KDM5B), a key enzyme driving all cell cycle transitions, promoting HCC progression and metastasis. Methods: The expression of KDM5B in normal liver, HCC and its adjacent tissues was analyzed by RT-PCR and IHC. Lentivirus transfection method was used to construct stable cell lines with KDM5B overexpression and down-regulation, and the role of KDM5B in HCC migration and invasion was detected at cell level and animal level. Western blotting and Transwell experiments were performed to verify the effect of KDM5B and/or CCR2 inhibitors on HCC progression and metastasis by using liver orthotopic transplantation tumor model and immunofluorescence methods. Results: RT-PCR showed that the expression level of KDM5B in HCC was significantly higher than that in adjacent tissues, and the increase of KDM5B was relatively significant. Upregulation of KDM5B in nude mouse liver orthotopic transplantation tumor model can promote the incidence of lung metastasis and shorten the survival time of nude mice, whereas upregulation of KDM5B can reduce the incidence of lung metastasis and prolong the survival time of nude mice. Conclusion: This study clarified the expression of KDM5B in HCC and its function in promoting HCC migration, invasion and metastasis. The molecular mechanism of KDM5B promoting HCC metastasis was revealed, providing a potential therapeutic target for HCC.

关键词： Liver Cancer Cyclin-Dependent Kinase (KDM5B) Pathology molecular mechanism

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Advances in molecular mechanism of myocardial ischemia/reperfusion injury

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Journal of Hainan Medical University 2022年第16期28卷 67-72页

作者： WEI Cheng-lu FENG Qing-min CHEN Song-cheng ZHUO Huai-mi LI Ji-ke Hainan Medical University Haikou 571199China

Myocardial ischemia/reperfusion(I/R)injury is a pathological change that occurs during the restoration of blood supply to ischemic or occluded coronary arteries after coronary heart disease,stroke,cardiac arrest and resuscitation,organ transplantation,shock and other events.Myocardial I/R injury is often accompanied by cardiovascular adverse events,which seriously affect the prognosis of myocardial ischemia.The potential mechanism of myocardial I/R injury is complex,involving many pathological processes,such as oxygen free radical injury,calcium overload,inflammation,apoptosis,activation,immune imbalance,endoplasmic reticulum stress,autophagy,myocardial energy metabolism disorder,myocardial microvascular endothelial cell injury and so on.Ischemic preconditioning is an effective preventive and therapeutic measure to reduce ischemia-reperfusion(I/R)injury.At present,there are many experimental studies on the pathogenesis and prevention and treatment measures,but the clinical application is still limited,so the prevention and treatment of I/R injury is still a major challenge.The pathogenesis of myocardial I/R injury is not completely clear,and the treatment methods and drugs are limited,so this paper summarizes the molecular mechanism and related signal pathways involved in its injury,as well as the emerging targeted therapy,to provide strategy and theoretical basis for clinical prevention and treatment of myocardial I/R injury.

关键词： Ischemia/reperfusion injury Myocardial molecular mechanism Signal transduction pathway

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