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MicroRNA signature in patients with hepatocellular carcinoma associated with type 2 diabetes

World Journal of Gastroenterology 2019年第42期25卷 6322-6341页

作者： Moustafa Nouh Elemeery Marwa Anwar Mohamed Marwa Ahmed Madkour Mohammed Mohammed Shamseya Noha Mahmoud Issa Ahmed Noah Badr Doaa Ahmed Ghareeb Cheol-Ho Pan Département de Neurosciences CRCHUMUniversitéde MontréalMontréalQuebec H2X 3E4Canada Medical Biotechnology Laboratory Genetic Engineering and Biotechnology Research DivisionNational Research CentreCairo 12622Egypt Natural Product Informatics research Center KIST Gangneung Institute of Natural ProductsGangneung 25451South Korea Division of Bio-Medical Science and Technology KIST SchoolKorea University of Science and TechnologySeoul 02792South Korea Department of Chemical Pathology Medical Research InstituteAlexandria UniversityAlexandria 21511Egypt Experimental and clinical Internal Medicine Department Medical Research InstituteAlexandria UniversityAlexandria 21511Egypt Human Genetics Department Medical Research InstituteAlexandria UniversityAlexandria 21511Egypt Food Toxicology and Contaminates Department National Research CentreDokkiCairo 12622Egypt Bioscreening and preclinical trial lab Biochemistry DepartmentFaculty of ScienceAlexandria UniversityAlexandria 12522Egypt pharmaceutical and fermentation industries development center the city of scientific research and technological applicationsAlexandria 26411Egypt

BACKGROUND Nonalcoholic steatohepatitis-related cirrhosis is one of the liver complications in type 2 diabetes mellitus(T2DM)and reported to be a risk factor for developing hepatocellular carcinoma(HCC).A reliable screening biomarker of liver cirrhosis(LC)and HCC among T2DM patients is important to reduce the morbidity and mortality of this ***(miRNA)is considered a key player in HCC and T2DM,and it might be a hidden culprit in diabetes-associated HCC,making it a promising reliable prognostic *** To investigate the signature of serum miRNAs as early biomarkers for the screening of HCC among diabetic *** Expression profiles of miRNAs in serum samples of diabetic LC and diabetic HCC patients were assessed using Illumina sequencing;then,RT-qPCR was used to validate significantly altered miRNAs between the two *** miRNAs were tested in serum samples of 200 T2DM patients,270 LC patients,200 HCC patients,and 225 healthy control ***,receiver operating characteristic(ROC)analysis,with area under the curve(AUC),was performed to assess the diagnostic performance of the screened miRNAs for discriminating HCC from LC and nonmalignant patients(LC+T2DM).RESULTS Expression of the sequenced miRNAs in serum was different in HCC vs LCpositive T2DM *** miRNAs(miR-34a,miR-221)were significantly upregulated and five miRNAs(miR-16,miR-23-3p,miR-122-5p,miR-198,miR-199a-3p)were significantly down-regulated in HCC compared to LC *** of ROC curve demonstrated that the combination of these seven miRNAs can be used as a reliable biomarker for detection of HCC in diabetic patients,as it could identify HCC with high diagnostic accuracy in diabetic LC patients(AUC=0.993)and in diabetic nonmalignant patients(AUC=0.961).CONCLUSION This study validates a panel of serum miRNAs that can be used as a reliable noninvasive screening biomarker of HCC among T2DM cirrhotic and noncirrhotic *** study recommends furt

关键词： MicroRNA Hepatocellular carcinoma Type 2 diabetes Nonalcoholic fatty liver disease

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Efficacy of 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1) in treatment of iron-loaded hepatocyte cultures

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Advances in Bioscience and Biotechnology 2012年第7期3卷 1060-1067页

作者： Kanjana Pangjit Ratana Banjerdpongchai Chada Phisalaphong Suthat Fucharoen Somdet Srichairatanakool Department of Biochemistry Faculty of Medicine Chiang Mai University Chiang Mai Thailand Institute of research and Development Government Pharmaceutical Organization Ministry of Public Health Bangkok Thailand Thalassemia research Center Institute of Molecular Bioscience Mahidol University Salaya Campus Nakornpathom Thailand

Excessive iron is toxic to cells and organelles, where it can generate harmful reactive oxygen species (ROS) resulting in oxidative tissue damage. Liver is the major organ for iron storage and redox active iron in this tissue can cause fibrosis and cirrhosis in β-thalassemia patients. Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are clinically approved iron chelators used for the treatment of patients with iron overload, but none of these chelators are completely free of side effects. In this study we report the properties of a new iron chelator 1-(N-acetyl-6-aminohexyl)-3-hydroxypyridin-4-one (CM1). The labile iron pool (LIP) content was measured by using a calcein fluorescence technique and the lipidperoxidation products were quantified using the thiobarbituric acid reactive substances (TBARS) method. The cytotoxicity of CM1 was also examined with the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. CM1 was demonstrated to reduce iron-induced redox damage and to decrease the levels of the intracellular iron pool in hepatocytes. CM1 is a potentially useful iron-chelating agent which has potential to ameliorate liver iron overload and ROS-induced lipid peroxidation. CM1 is currently under investigation for oral efficacy.

关键词： Iron 3-Hydroxypyridin-4-One Labile Iron Pool Lipid Peroxidation Hepatocyte

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Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1159-1174页

作者： Heng Xu Hongfang Zhao Chunyong Ding Defang Jiang Zijie Zhao Yang Li Xiaoyu Ding Jing Gao Hu Zhou Cheng Luo Guoqiang Chen Ao Zhang Ying Xu Hao Zhang School of pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Chemical Biology research Center State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China CAS Key Laboratory of Tissue Microenvironment and Tumor Shanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Department of Pathophysiology Key Laboratory of Cell Differentiation and Apoptosis of the Chinese Ministry of EducationShanghai Jiao Tong University School of MedicineShanghai 200025China Pharm-X center College of Pharmaceutical SciencesShanghai Jiao Tong UniversityShanghai 200240China School of Chinese Materia Medica Nanjing University of Chinese Medicine138 Xianlin RoadQixiaNanjing 210023 JiangsuChina University of Chinese Academy of Sciences No.19A Yuquan RoadBeijing 100049China State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteRen-Ji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China

As a terpenoids natural product isolated from the plant Thunder God Vine,Celastrol is widely studied for its pharmacological activities,including anti-tumor *** clinical application of Celastrol is strictly limited due to its severe side effects,whereas previously revealed targets and mechanism of Celastrol seldom reduce its in vivo toxicity via structural *** identification has a far-reaching influence on the development of innovative drugs,and omics data has been widely used for unbiased target ***,it is difficult to enrich target of specific phenotype from thousands of genes or proteins,especially for natural products with broad promising ***,we developed a text-mining-based web-server tool to enrich targets from omics data of inquired *** peroxiredoxin 1(PRDX1)was identified as the ROS-manipulating target protein of Celastrol in colorectal *** solved high-resolution crystal structure revealed the unique covalent binding mode of Celastrol with *** derivative compound 19-048 with improved potency against PRDX1 and selectivity towards PRDX2~PRDX6 were synthesized based on crystal structure *** Celastrol and 19-048 effectively suppressed the proliferation of colorectal cancer *** anti-tumor efficacy of Celastrol and 19-048 was significantly diminished on xenograft nude mice bearing PRDX1 knock-down colorectal cancer *** downstream genes of p53 signaling pathway were dramatically up-regulated with Celastrol or 19-048 *** findings reveal that the side effects of Celastrol could be reduced via structural modification,and PRDX1 inhibition is promising for the treatment of colorectal cancer.

关键词： colorectal cancer nude

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CAR-T cells for cancer immunotherapy

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中国化学快报:英文版 2023年第9期34卷 55-64页

作者： Yangyang Xie Xiaotong Li Jingyi Wu Huiling Zeng Hamza Boucetta Binru Wang Pei Yang Wei He School of Pharmacy China Pharmaceutical UniversityNanjing 210000China School of Science China Pharmaceutical UniversityNanjing 210000China Shanghai Skin Disease Hospital Tongji University School of MedicineShanghai 200443China

Adoptive immunotherapy expressing synthetic chimeric antigen receptors(CAR)on T cells through in vitro modifications represents a new and innovative strategy in cancer *** new approach enables T cells to recognize and bind tumor antigens via a single-chain variable fragment recognition domain,circumventing the restriction of major histocompatibility *** review summarized the structure/design of CAR-T cells and the evolution process this technology went through,displaying the theoretical foundation for CAR-T therapy,the marketed products and the latest preclinical and clinical research ***,we provided perspectives on this technology’s development and potential future applications,especially for treating hematological malignant and solid tumors.

关键词： CAR-T cells Cancer Immunotherapy Therapeutic techniques Marketed drugs Universal CAR-T Cell Therapy

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New KAT6 inhibitors induce senescence and arrest cancer growth

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Synthetic and Systems Biotechnology 2018年第4期3卷 244-245页

作者： Fei Huang School of pharmaceutical Sciences Nanjing Tech UniversityNanjingChina

Lysine acetyltransferases(KATs)catalyze lysine acetylation,a reversible protein modification implicated in a wide variety of disease *** acetyltransferases(HATs)comprise a KAT sub-class that acetylate specific lysines in histones,hence playing an important role in the regulation of chromatin organization and *** are critical regulators of signaling in many diseases,including ***6A(also known as monocytic leukemia zinc finger protein,MOZ)and KAT6B(also known as MORF and QKF)belong to the MYST family of HATs,that comprise KAT5–*** are the targets of chromosomal translocations identified in acute myeloid leukaemia and various *** seems logical therefore that inhibition of KAT6A and KAT6B may provide a therapeutic benefit in *** et *** a new class of anti-cancer drug that can put cancer cells into a permanent sleep or senescence,using high-throughput screening followed by medicinal chemistry optimization,in-cell assays,biochemical assessment of target engagement,and tumour models in mice and *** research showed promise in arresting tumour growth in pre-clinical models of blood and liver cancers as well as delaying or stopping relapse without damaging the cells'DNA or some harmful side-effects caused by chemotherapy and radiotherapy.

关键词： hence permanent senescence

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Natural products as LSD1 inhibitors for cancer therapy

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Acta Pharmaceutica Sinica B 2021年第3期11卷 621-631页

作者： Yuan Fang Chao Yang Zhiqiang Yu Xiaochuan Li Qingchun Mu Guochao Liao Bin Yu Joint Laboratory for Translational Cancer research of Chinese Medicine of the Ministry of Education of the People’s Republic of China International Institute for Translational Chinese MedicineGuangzhou University of Chinese MedicineGuangzhou 510006China Institute of Innovation&Application Zhejiang Ocean UniversityZhoushcm 316022China School of pharmaceutical Sciences Southern Medical UniversityGuangzhou 510515China The People’s Hospital of Gaozhou Gaozhou 525200China School of pharmaceutical Sciences Zhengzhou UniversityZhengzhou 450001China State Key Laboratory of Natural Medicines China Pharmaceutical UniversityNanjing 210009China

Natural products generally fall into the biologically relevant chemical space and always possess novel biological activities, thus making them a rich source of lead compounds for new drug discovery. With the recent technological advances, natural product-based drug discovery is now reaching a new era. Natural products have also shown promise in epigenetic drug discovery, some of them have advanced into clinical trials or are presently being used in clinic. The histone lysine specific demethylase1(LSD1), an important class of histone demethylases, has fundamental roles in the development of various pathological conditions. Targeting LSD1 has been recognized as a promising therapeutic option for cancer treatment. Notably, some natural products with different chemotypes including protoberberine alkaloids, flavones, polyphenols, and cyclic peptides have shown effectiveness against LSD1. These natural products provide novel scaffolds for developing new LSD1 inhibitors. In this review, we mainly discuss the identification of natural LSD1 inhibitors, analysis of the co-crystal structures of LSD1/natural product complex, antitumor activity and their modes of action. We also briefly discuss the challenges faced in this field. We believe this review will provide a landscape of natural LSD1 inhibitors.

关键词： Epigenetic regulation Histone demethylase Natural products LSD1 inhibitors Drug discovery Cancer therapy

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Pharmacokinetics and its Correlation with Toxicity of Pegylated-liposomal Doxorubicin in Chinese Patients with Breast Tumors

Pharmacokinetics and its Correlation with Toxicity of Pegyla...

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第十二届全国数学药理学术大会

作者：许羚王鲲盛玉成郑青山 Laboratory of Pharmacometrics Center for Drug Clinical ResearchShanghai University of Chinese Medicine Shanghai Fudan-zhangjiang Bio-pharmaceutical Co. Ltd

Aims:Pegylated liposomal doxorubicin(PLD) is a formulation of doxorubicin encapsulated polyethylene-glycol coated liposomes with prolonged circulation time and unique toxicity *** study deals with the pharmacokinetics and its correlation with toxicity in Chinese patients with breast ***:Twenty-two Chinese female patients with breast tumors were received two PLD products in single dose of 50 mg/m per 4 weeks with a randomized,two-period,and cross-over design. Blood was sampled immediately before and at 15 minutes,30 minutes,60 minutes,1.17 hours,2 hours,5 hours,13 hours,25 hours,49 hours,73 hours,97 hours,121 hours,145 hours and 241 hours after the PLD *** plasma level of doxorubicin was determined with ***:The pharmacokinetics of PLD was best described by a one-compartment linear structural model with a long T(64 hours),a slow clearance(0.025 L/hour/m),and a small volume of distribution(2.310 L/m).The main toxicities were neutropenia(22/44),nausea(22/44),vomiting(8/44),and pigmentation(4/44).The nausea and neutropenia were positively correlated with AUC and negatively correlated with CL(P<0.05).Conclusion:The toxicity of PLD is well correlated with AUC and CL of pharmacokinetic parameters which may be a useful tool for the agent dosing.

关键词： liposomes anthracyclines breast tumor pharmacokinetics toxicity population pharmacokinetics

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Cryptococcus neoformans,a global threat to human health

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Infectious Diseases of Poverty 2023年第2期12卷 1-18页

作者： Youbao Zhao Leixin Ye Fujie Zhao Lanyue Zhang Zhenguo Lu Tianxin Chu Siyu Wang Zhanxiang Liu Yukai Sun Min Chen Guojian Liao Chen Ding Yingchun Xu Wanqing Liao Linqi Wang College of Veterinary Medicine Henan Agricultural UniversityZhengzhou 450046HenanChina State Key Laboratory of Mycology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100039China Department of Dermatology Shanghai Key Laboratory of Molecular Medical MycologyChangzheng HospitalShanghai 200003China The Medical research Institute College of Pharmaceutical SciencesSouthwest UniversityChongqing 400715China College of Life and Health Sciences Northeastern UniversityShenyang 110819LiaoningChina Department of Laboratory Medicine and Beijing Key Laboratory for Mechanisms Research and Precision Diagnosis of Invasive Fungal DiseasesPeking Union Medical College HospitalChinese Academy of Medical SciencesBeijing 100730China

Background Emerging fungal pathogens pose important threats to global public health. The World Health organization has responded to the rising threat of traditionally neglected fungal infections by developing a Fungal Priority Pathogens List (FPPL). Taking the highest-ranked fungal pathogen in the FPPL,Cryptococcus neoformans, as a paradigm, we review progress made over the past two decades on its global burden, its clinical manifestation and management of cryptococcal infection, and its antifungal resistance. The purpose of this review is to drive research efforts to improve future diagnoses, therapies, and interventions associated with fungal *** We first reviewed trends in the global burden of HIV-associated cryptococcal infection, mainly based on a series of systematic studies. We next conducted scoping reviews in accordance with the guidelines described in the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews using PubMed and ScienceDirect with the keywordCryptococcus neoformans to identify case reports of cryptococcal infections published since 2000. We then reviewed recent updates on the diagnosis and antifungal treatment of cryptococcal infections. Finally, we summarized knowledge regarding the resistance and tolerance ofC. neoformans to approved antifungal *** There has been a general reduction in the estimated global burden of HIV-associated cryptococcal meningitis since 2009, probably due to improvements in highly active antiretroviral therapies. However, cryptococcal meningitis still accounts for 19% of AIDS-related deaths annually. The incidences of CM in Europe and North America and the Latin America region have increased by approximately two-fold since 2009, while other regions showed either reduced or stable numbers of cases. Unfortunately, diagnostic and treatment options for cryptococcal infections are limited, and emerging antifungal resistance exacerbates the public health bu

关键词： Fungal infections Cryptococcus neoformans Cryptococcal meningitis Antifungal resistance Antifungal tolerance

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Determination of a novel ACE inhibitor in the presence of alkaline and oxidative degradation products using smart spectrophotometric and chemometric methods

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Journal of pharmaceutical Analysis 2014年第2期4卷 132-143页

作者： Maha Abdel-Monem Hegazy Maya Shaaban Eissa Osama Ibrahim Abd El-Sattar Mohamed Mohamed Abd El-Kawy Analytical Chemistry Department Faculty of PharmacyCairo UniversityCairoEgypt Analytical Chemistry Department Faculty of PharmacyEgyptian Russian UniversityCairoEgypt National organization of Drug Control and research GizaEgypt

Simple, accurate, sensitive and validated UV spectrophotometric and chemometric methods were developed for the determination of imidapril hydrochloride （IMD） in the presence of both its alkaline （AKN） and oxidative （OXI） degradation products and in its pharmaceutical formulation. Method A is the fourth derivative spectra （D4） which allows the determination of IMD in the presence of both AKN and OXD, in pure form and in tablets by measuring the peak amplitude at 243.0 nm. Methods B, C and D, manipulating ratio spectra, were also developed. Method B is the double divisor-ratio difference spectrophotometric one （DD-RD） by computing the difference between the amplitudes of IMD ratio spectra at 232 and 256.3 nm. Method C is the double divisor-first derivative of ratio spectra method （DD-DR1） at 243.2 nm, while method D is the mean centering of ratio spectra （MCR） at 288.0 nm. Methods A, B, C and D could successfully determine IMD in a concentration range of 4.0-32.0 mg/mL. Methods E and F are principal component regression （PCR） and partial least-squares （PLS）, respectively, for the simultaneous determination of IMD in the presence of both AKN and OXI, in pure form and in its tablets. The developed methods have the advantage of simultaneous determination of the cited components without any pre-treatment. The accuracy, precision and linearity ranges of the developed methods were determined. The results obtained were statistically compared with those of a reported HPLC method, and there was no significant difference between the proposed methods and the reported method regarding both accuracy and precision.

关键词： Double divisor-ratio difference Double divisor-ratio derivative Mean centering of ratio spectra Chemometry Imidapril hydrochloride

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Advances on marine-derived natural radioprotection compounds:historic development and future perspective

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Marine Life Science & Technology 2021年第4期3卷 474-487页

作者： Reinu E.Abraham Mousa Alghazwi Qi Liang Wei Zhang Centre for Marine Bioproducts Development College of Medicine and Public HealthFlinders UniversityBedford ParkSA 5042Australia Department of pharmaceutical Sciences College of Clinical PharmacyKing Faisal UniversityAI-AhsaKingdom of Saudi Arabia Shanxi University of Traditional Chinese Medicine Taiyuan 030619China

Natural extracts and compounds from marine resources have gained intensive scientific and industry attention for radio-protective activities in the past ten ***,the marine-derived radioprotectants have been studied against UV-rays,gamma(y)-rays and X-rays for more than 30 *** review aims to identify key marine-derived extracts/compounds and their modes of action studied for radioprotective activities from 1986 to 2019.A comprehensive survey was conducted to establish the trend in terms of the publications each year and the countries of origin.A total of 40 extracts and 34 natural compounds showing radioprotective activities against UV-rays,gamma(y)-rays and X-rays were identified from a range of marine plants and *** extracts and compounds are broadly categorized into polysaccharides,phlorotannins,carotenoids and mycosporine-like amino acids(MAAs).Macroalgae and microalgae were found to be the dominant sources of polysaccharides,phlorotannins and *** were mainly identified in algae,sponges,sea cucumber and corals that showed significant UV-absorbing activities.A number of radioprotective mechanisms were shown by these compounds,predominantly free radicals scavenging,inhibition of apoptosis,UV-ray absorption and DNA damage-repair signaling *** these bio-discoveries warrant further investigation and development of radioprotective therapeutics,however,the lack of clinical studies is a major obstacle to be tackled in the future.

关键词： Radio-protective Therapeutics Natural compounds Macro/microalgae Marine organisms Mechanism

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