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Early diagnostic evaluation of miR-122 and miR-224 as biomarkers for hepatocellular carcinoma

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Genes & Diseases 2017年第4期4卷 215-221页

作者： Khalda S.Amr Hanan Abd Elmawgoud Atia Rehab Abd Elazeem Elbnhawy Wafaa M.Ezzat Medical Molecular Genetics department National Research CentreCairoEgypt biochemistry department Faculty of Pharmacy(Girls)Al-Azhar UniversityCairoEgypt Urology and Nephrology Center Mansoura UniversityMansouraEgypt Internal Medicine department National Research CenterCairoEgypt

Hepatocellular carcinoma(HCC)is one of the common lethal types of tumor all over the *** lethality of HCC accounts for many *** of them,the lack of reliable diagnostic markers at the early stage,in this context,serum miRNAs became promising diagnostic ***,we aimed to identify the predictive value of two miRNAs(miR-122 and miR-224)in plasma of patients with HCC preceded by chronic HCV *** miRNA assays specific for hsa-miR-122 and hsa-miR-224 were used to assess the expression levels of the chosen miRNAs in plasma samples collected from three groups;40 patients with HCC related to HCV,40 with CHC patients and 20 healthy *** study revealed that the mean plasma values of miRNA-122 were significantly lower among HCC group when compared to CHC and control groups(P1.2(RQ)and(AUC Z 0.93,P<0.001),while the accuracy of AFP to diagnose HCC was(AUC:0.619;P Z 0.06).In conclusion,the expression plasma of miR-122 and miR-224 could be used as noninvasive biomarkers for the early prediction of developing HCC at the early stage.

关键词： Diagnosis Hepatocellular carcinoma miR-122 miR-224 Sensitivity

Breeding for pre-harvest sprouting resistance in bread wheat under rainfed conditions

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Frontiers of Agricultural Science and Engineering 2018年第2期5卷 253-261页

作者： Muhammad ZEESHAN Waheed ARSHAD Muhammad Imran KHAN Shiraz ALI Ali NAWAZ Amina BATOOL Muhammad TARIQ Muhammad Imran AKRAM Muhammad Amjad ALI Barani Agricultural research Station Barani Agricultural research Institute Soil and Water Conservation research Station department of Plant Pathology and centre of Agricultural biochemistry & Biotechnology University of AgricultureFaisalabad

Pre-harvest sprouting in wheat is the germination of seeds within the spikes when rains occur after or during grain ripening, which occurs commonly in the barani tract of Pakistan. Therefore, 10 cultivars and five advanced lines of spring bread wheat were evaluated for pre-harvest sprouting resistance. After natural rainfall,seeds were immediately collected from the wet spikes and tested for germinating ability. Three different germination tests were applied to hand-threshed seed:(1) spikes threshed on the day of sampling and germination tested immediately,(2) spikes threshed on the day of sampling and germination tested 1 week later, and(3) spikes threshed 1 week after sampling and germination test immediately after threshing. Seeds and spikes kept for 1 week were place on blotting paper at room *** BARS-09, 09 FJ17, Doukkala-12, NARC-09 and Ouassou-20 exhibited higher sprouting resistance while other genotypes were susceptible to pre-harvest sprouting in each of the three tests. A diallel crossing was conducted with six susceptible and two resistant genotypes to assess the genetic behavior of pre-harvest sprouting *** combining ability(CA) demonstrated a higher proportion of additive genetic effects for sprouting resistance, because of higher variance of general and specific CA for both parameters under study. Doukkala-12 and BARS-09 showed increased pre-harvest sprouting resistance in their F1 descendants.

关键词： bread wheat germination index general combining ability pre-harvest sprouting specific combining ability

Avian influenza virus surveillance in migratory birds in Egypt revealed a novel reassortant H6N2 subtype

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Avian research 2019年第4期10卷 507-516页

作者： Ali M.Zanaty Ahmed M.Erfan Wessam H.Mady Fatma Amer Ahmed A.Nour Neveen Rabie Mohamed Samy Abdullah A.Selim Wafaa M.M.Hassan Mahmoud M.Naguib National Laboratory for Veterinary Quality Control on Poultry Production Animal Health Research InstituteGiza 12618Egypt Zoonosis Science centre Department of Medical Biochemistry and MicrobiologyUppsala University75123 UppsalaSweden

Background:Avian influenza viruses(AIVs)have been identified from more than 100 different species of wild birds around the *** migratory birds can act as potential spreaders for AIVs to domestic birds between different *** is situated on important migratory flyways for wild birds between different *** much is known about circulation of zoonotic potential H5N1 and H9N2 AIVs in domestic poultry in Egypt,little is known about the pivotal role of migratory birds in the maintenance and transmission of the viruses in ***:Targeted AIV surveillance has been conducted in 2017 in different wetlands areas in Northern and Eastern ***:AIV of subtype H5 was detected in two bird *** addition,a novel reassortant strain of the H6N2 subtype was identified which reveals the continuous risk of new influenza virus(es)introduction into *** novel virus possesses a reassortant pattern originating from different AIV gene ***:Intervention control strategies should be performed to minimize the possible contact of domestic birds with wild birds to lower the risk of virus transmission at this *** addition,constant monitoring of AIVs in migratory birds is essential in the early detection of influenza virus introduction into Egypt.

关键词： Avian in fluenza virus H6N2 Egypt Reassortment Wild birds

Protecting future antimalarials from the trap of resistance:Lessons from artemisinin-based combination therapy (ACT) failures

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Journal of Pharmaceutical Analysis 2021年第5期11卷 541-554页

作者： Nekpen Erhunse Dinkar Sahal Malaria Drug Discovery research Group International Centre for Genetic Engineering and BiotechnologyNew Delhi110067India department of biochemistry Faculty of Life SciencesUniversity of BeninBenin CityEdo-StateNigeria

Having faced increased clinical treatment failures with dihydroartemisinin-piperaquine(DHA-PPQ),Cambodia swapped the first line artemisinin-based combination therapy(ACT)from DHA-PPQ to artesunate-mefloquine given that parasites resistant to piperaquine are susceptible to ***,triple mutants have now emerged,suggesting that drug rotations may not be adequate to keep resistance at *** is,therefore,an urgent need for alternative treatment strategies to tackle resistance and prevent its spread.A proper understanding of all contributors to artemisinin resistance may help us identify novel strategies to keep artemisinins effective until new drugs become available for their *** review highlights the role of the key players in artemisinin resistance,the current strategies to deal with it and suggests ways of protecting future antimalarial drugs from bowing to resistance as their predecessors did.

关键词： Artemisinin resistance Quiescence K13 mutations Non-K13 mutations Artemisinin-based combination therapy (ACT)failure Drugs in development Malaria eradication

When Kinases Meet PROTACs

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Chinese Journal of Chemistry 2018年第10期36卷 971-977页

作者： Li Tan Nathanael S. Gray Interdisciplinary research Center on Biology and Chemistry Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 26 Qiuyue Rd Pudong Shanghai 201210 China department of cancer Biology Dana-Father Cancer Institute Boston MA 02215 USA department of biochemistry and Molecular Pharmacology Harvard Med- ical School Boston MA 02115 USA

Small molecule drugs targeting kinases have revolutionized treatment options for millions of patients worldwide, especially in oncology. These targeted treatments have less side effects because they inhibit a specific dysfunctional kinase usually with relatively narrow selectivity. However, kinase inhibitors do have well-established liabilities, most prominently the emergence of drug resistance. Moreover, the majority of kinases are multi- domain and multifunctional proteins that in addition to their enzymatic activity have scaffolding and other roles, and inhibitors seldom address these alternative functions. Recently, small molecule mediated targeted protein degradation emerged as a new pharmacological strategy. The majority of small molecule degraders are bispecific molecules called proteolysis targeting chimeras （PROTACs）, and their mechanism of action is based on simultaneous recruitment of the target of interest and an E3 ligase, resulting in target polyubiquitination and eventual destruction by the proteasome. Over the last couple of years, PROTAC strategy has been developed and validated for a range of targets, including kinases. Here, we introduce the targeted protein degradation strategy, provide an overview of representative kinase PROTACs, and describe design rationales, efficacy and specificity. We also discuss their potential advantages, as well as comment on some of the limitations of this emerging pharmacological modality.

关键词： kinase inhibitors PROTACs drug discovery ligases kinase degradation drug design

Structure and sequence analysis of influenza A virus nucleoprotein

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Science China(Life Sciences) 2009年第5期52卷 439-449页

作者： NG Andy Ka-Leung SHAW Pang-Chui Molecular Biotechnology Programme Department of Biochemistry and Centre for Protein Science and Crystallography The Chi-nese University of Hong Kong

Influenza A virus nucleoprotein (NP) forms homo-oligomers and multiple copies of NP wrap around genomic RNA, along with a trimeric polymerase making up ribonucleoprotein (RNP) complex. Sequence comparison of more than 2500 influenza A NP showed that this protein contains 30.1 % of polymorphic residues. NP is composed of a head and a body domain and a tail loop/ linker region. The head domain is more conserved than the body domain, as revealed from the structure-based sequence alignment. NP oligomerization is mediated by the insertion of the non-polymorphic and structurally conserved tail loop of one NP molecule to a groove of another NP. The different form of NP oligomers is due to the flexibility of the polymorphic linkers that join the tail loop to the rest of the protein. The RNA binding property of NP is known to involve the protruding element and the flexible basic loop between the head and body domains, both having high degree of primary sequence conservation. To bind RNA, NP may first capture the RNA by the flexible basic loop and then the RNA is clamped by the protruding element.

关键词： Influenza H5N1 nucleoprotein oligomerization RNA binding

Recent advances in the targeted fluorescent probes for the detection of metastatic bone cancer

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Science China Chemistry 2021年第8期64卷 1283-1296页

作者： Peng Wu Daniel J.Siegwart Hu Xiong research Center for Analytical Sciences Tianjin Key Laboratory of Biosensing and Molecular RecognitionCollege of ChemistryNankai UniversityTianjin300071China department of biochemistry Simmons Comprehensive Cancer CenterThe University of Texas Southwestern Medical CenterDallasTexas75390USA

Tumors of the breast,prostate,and lung are most likely to metastasize to the bone and typically indicates a poor cure and survival rate in cancer *** of metastatic bone cancer in early stage would save many lives and greatly improve patients’quality of ***,bone scintigraphy is often utilized to visualize bone metastases due to its relatively low cost and high ***,a growth number of analytical researches aimed at developing targeted fluorescent probes to noninvasively image bone metastases with improved spatial resolution and specificity has been *** this review,we will summarize and discuss the recent published fluorescent probes on the accurate detection of metastatic bone ***,the design principles of various targeted probes for imaging bone metastases will be presented,highlighting the signal moieties,targeting ligands,and physicochemical properties of the bone-specific ***,the up-to-date bone-targeting fluorescent probes will be summarized and ***,future perspectives and challenges confronting the researchers in this field will be *** believe this review will encourage novel ideas to develop smart targeted molecular probes for bone metastasis imaging,image-guided surgery,and therapeutic imaging materials.

关键词： bone metastasis targeted probes fluorescence imaging smart design bone-targeting moieties

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Thiolated arsenicals in arsenic metabolism: Occurrence,formation, and biological implications

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Journal of Environmental Sciences 2016年第11期28卷 59-73页

作者： Yuzhen Sun Guangliang Liu Yong Cai Institute of Environment and Health Jianghan University department of Chemistry and biochemistry&Southeast Environmental research Center Florida International University

Arsenic（As） is a notoriously toxic pollutant of health concern worldwide with potential risk of cancer induction, but meanwhile it is used as medicines for the treatment of different conditions including hematological cancers. Arsenic can undergo extensive metabolism in biological systems, and both toxicological and therapeutic effects of arsenic compounds are closely related to their metabolism. Recent studies have identified methylated thioarsenicals as a new class of arsenic metabolites in biological systems after exposure of inorganic and organic arsenicals, including arsenite, dimethylarsinic acid（DMAV）, dimethylarsinous glutathione（DMAIIIGS）, and arsenosugars. The increasing detection of thiolated arsenicals,including monomethylmonothioarsonic acid（MMMTAV）, dimethylmonothioarsinic acid（DMMTAV） and its glutathione conjugate（DMMTAVGS）, and dimethyldithioarsinic acid（DMDTAV） suggests that thioarsenicals may be important metabolites and play important roles in arsenic toxicity and therapeutic effects. Here we summarized the reported occurrence of thioarsenicals in biological systems, the possible formation pathways of thioarsenicals, and their toxicity, and discussed the biological implications of thioarsenicals on arsenic metabolism, toxicity, and therapeutic effects.

关键词： Arsenic Thioarsenicals Occurrence Formation pathways Toxicity

Selected Secondary Plant Metabolites for cancer Therapy

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World Journal of Traditional Chinese Medicine 2015年第1期1卷 24-28页

作者： Simone Fulda Thomas Efferth Institute of Experimental cancer research in Pediatry Goethe-Universitat Frankfurt department of Pharmaceutical Biology Institute of Pharmacy and BiochemistryJohannes Gutenberg-Universitat Mainz

Secondary plant metabolites reveal numerous biological activities making them attractive as resource for drug development of human *** the majority of cancer drugs clinically established during the past half century is derived from nature, cancer researchers worldwide try to identify novel natural products as lead compounds for cancer therapy. Natural products are considered as promising cancer therapeutics,either as single agents or in combination protocols, to enhance the antitumor activity of additional therapeutic modalities. Most natural compounds exert pleotrophic effects and modulate various signal transduction pathways. A better understanding of the complex mechanisms of action of natural products is expected to open new perspectives in coming years for their use alone or in combination therapies in *** major strategies to identify novel drug candidates from nature are the bioactivity-guided fractionation of medicinal plant extracts to isolate cytotoxic chemicals and the identification of small molecules inhibiting specific targets in cancer cells. In the present review, we report on our own efforts to unravel the molecular modes of action of phytochemicals in cancer cells and focus on resveratrol, betulinic acid,artesunate, dicentrine and camptothecin derivatives.

关键词： Apoptosis Bioactivity-guided fractionation Drug development Drug resistance Epidermal growth factor receptor Phytochemicals Targeted tumor therapy