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Bone marrow niche-mediated survival of leukemia stem cells in acute myeloid leukemia: Yin and Yang

Cancer biology & Medicine 2016年第2期13卷 248-259页

作者： Hong-Sheng Zhou Bing Z.Carter Michael Andreeff Section of molecular Hematology and Therapy Department of Leukemia The University of Texas M.D.Anderson Cancer Center Department of Hematology Nanfang Hospital Southern Medical University

Acute myeloid leukemia （AML） is characterized by the accumulation of circulating immature blasts that exhibit uncontrolled growth, lack the ability to undergo normal differentiation, and have decreased sensitivity to apoptosis. Accumulating evidence shows the bone marrow （BM） niche is critical to the maintenance and retention of hematopoietic stem cells （HSC）, including leukemia stem cells （LSC）, and an increasing number of studies have demonstrated that crosstalk between LSC and the stromal cells associated with this niche greatly influences leukemia initiation, progression, and response to therapy. Undeniably, stromal cells in the BM niche provide a sanctuary in which LSC can acquire a drug-resistant phenotype and thereby evade chemotherapy- induced death. Yin and Yang, the ancient Chinese philosophical concept, vividly portrays the intricate and dynamic interactions between LSC and the BM niche. In fact, LSC-induced microenvironmental reprogramming contributes significantly to leukemogenesis. Thus, identifying the critical signaling pathways involved in these interactions will contribute to target optimization and combinatorial drug treatment strategies to overcome acquired drug resistance and prevent relapse following therapy. In this review, we describe some of the critical signaling pathways mediating BM niche-LSC interaction, including SDFI/CXCL12, Wnt/β-catenin, VCAM/VLA-4/NF-κB, CD44, and hypoxia as a newly-recognized physical determinant of resistance, and outline therapeutic strategies for overcoming these resistance factors.

关键词： Bone marrow niche leukemia stem cell acute myeloid leukemia Yin and Yang

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Anti-cancer liposomal chemophototherapy using bilayer-localized photosensitizer and cabazitaxel

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Nano research 2022年第5期15卷 4302-4309页

作者： Boyang Sun Sanjana Ghosh Xuedan He Wei-Chiao Huang Breandan Quinn Meiling Tian Dushyant Jahagirdar Moustafa T.Mabrouk Joaquin Ortega Yumiao Zhang Shuai Shao Jonathan F.Lovell Translational Medicine center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China Department of Biomedical Engineering University at BuffaloState University of New YorkBuffaloNY 14260USA Department of Anatomy and cell biology McGill UniversityMontrealQuebec H3A0C7Canada School of Chemical Engineering and Technology Tianjin UniversityTianjin 300000China

Photodynamic therapy(PDT)is a non-invasive tumor ablation modality that can be enhanced in combination with concurrent ***,we demonstrated that liposomes containing a bilayer-anchored photosensitizer(porphyrin-phospholipid;PoP)can be loaded with drugs in their aqueous core to improve drug delivery and tumor ablation upon target tissue irradiation with *** the present work,we demonstrate that this concept can be extended to drugs loaded within the hydrophobic bilayer of ***(CTX)is a potent second generation taxane anti-cancer drug that was loaded in the bilayer of liposomes also containing 0.1 molar%PoP,generating CTX-loaded PoP liposomes(CTX-PoP-Lip).CTX-PoP-Lip showed unilamellar vesicle morphology,and exhibited integrity in storage and serum,while maintaining drug stability under laser *** vitro cell killing evaluation showed that red-light laser irradiation induced cytotoxicity in cells incubated with CTX-PoP-Lip,compared to control *** vivo pharmacokinetic analysis revealed that following intravenous administration to mice,CTX and PoP exhibited somewhat altered circulation profiles,suggesting that the CTX may have exchanged with serum factors in ***,when a single treatment of CTX-PoP-Lip with laser irradiation was administered to mice bearing human MIA Paca-2 tumors,tumors were effectively ablated whereas the equivalent chemotherapy and PDT monotherapies were *** results demonstrate the versatility of liposome delivery systems for achieving tumor ablation with chemophototherapy.

关键词： photodynamic therapy cabazitaxel liposome chemotherapy porphyrin-phospholipid

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molecular cloning,characterization and expression profile of the sucrose synthase gene family in Litchi chinensis

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Horticultural Plant Journal 2021年第6期7卷 520-528页

作者： Dan Wang Jietang Zhao Yaqi Qin Yonghua Qin Guibing Hu State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources/Key Laboratory of biology and Genetic Improvement of Horticultural Crops(South China) Ministry of Agriculture and Rural Affairs/Guangdong Litchi Engineering Research CenterCollege of HorticultureSouth China Agricultural UniversityGuangzhou 510642China

Sucrose synthase(SUS,EC 2.***.1.13)is widely considered as a key enzyme involved in plant sucrose metabolism,and the gene family encoding different SUS isozymes has been identified and characterized in several plant ***,to date scant information about the SUS genes is available in Litchi chinensis ***,we identified five SUS genes in *** Lc SUSs shared high levels of similarity in both nucleotide and amino acid *** gene structure,phylogenetic relationships,and expression profiles were *** structure analysis indicated that the Lc SUSs have similar exon-intron *** analysis revealed that the five members could be classified into three groups(LcSUS1 and LcSUS2 in SUSⅡ,LcSUS4 and LcSUS5 in SUSⅢ,and LcSUS3 in SUSⅠ),demonstrating evolutionary conservation in the SUS family across litchi and other plant *** expression levels of Lc SUSs were investigated via real-time PCR in various tissues and different developmental stages of *** tissues and organs,Lc SUSs exhibited distinct but partially redundant expression profiles in litchi,being predominantly expressed in young leaves(sink).During aril development,the expression pattern of LcSUS1 was consistent with the trend of sugar accumulation,indicating it may play important roles in determination of sink strength in ***,transcript levels of LcSUS2,LcSUS4,and LcSUS5 varied between cultivars with different hexose/sucrose ratios,which may regulate the sugar composition in *** results provide insights into physiological functions of SUS genes in litchi,especially roles in regulating sugar accumulation in aril.

关键词： Litchi chinensis Sucrose synthase Gene expression Aril Sugar accumulation

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Annual advances of integrative pharmacology in 2020

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Traditional Medicine research 2021年第4期6卷 1-12页

作者： Ke-Wu Zeng Ming-Yao Gu State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China Department of cell biology and Medical Genetics School of Basic Medical SciencesShenzhen University Health Science CenterShenzhen 518061China

Major studies on the pharmacology of traditional herbs as well as active compounds have been introduced in this review over the previous 12 *** annual integrative pharmacology review includes the reports published in 2020 on bioactive herbal extracts and novel compounds in traditional *** reports on traditional herbs as well as their active compounds for anticancer,inflammation,and metabolic diseases occupy dominant *** medicines are still widely reported as a crucial treatment to exhibit anticancer efficacy in numerous human cancer ***,the focus on the discovery of bioactive compounds from traditional medicines against mental disorders and neurodegenerative diseases seems to *** reports on bone loss and organ fibrosis treatments have notably gradually ***,studies of traditional herbs on cardiovascular and cerebrovascular diseases show a declining *** pharmacological reports in 2020 collectively show several crucial therapeutic targets and promising candidate compounds from traditional medicines for human diseases.

关键词： Traditional medicine Natural product Pharmacology Cancer Inflammation Infectious diseases

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Annual advances of integrative pharmacology in 2019

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Traditional Medicine research 2020年第2期5卷 74-82页

Representative studies concerning the pharmacology of traditional medicine and active herbal products have been summarized over the past 12 *** annual integrative pharmacology review encompasses research articles published during 2019 on the bioactive compounds and extracts used in traditional *** highlighting the pharmacology progress of traditional medicine were specifically introduced,including artemisinin for cancer cell sensibility and induction to ferroptosis,rutin for neuroinflammation suppression,Ginseng Radix et Rhizoma for gut microbiota regulation against obesity,green tea and Pu-erh tea for metabolic syndrome,and marine-derived oligosaccharide(GV-971)from brown algae for ***,novel TCM molecular targets and pharmacological mechanisms were trialed against different human diseases,including cancers,cardiovascular,cerebrovascular diseases,diabetes,and metabolic ***,herb-derived bioactive products have become important treatment alternatives for cancer research in *** and cerebrovascular diseases,together with diabetes and metabolic diseases,are ongoing research areas for traditional ***,inflammation and infectious disease are also attracting more attention by researchers,which might have been influenced by seasonal influenza or HIV/Ebola viral *** traditional medicine investigations are required in neurodegenerative diseases,depression,and mental *** together,the findings of the integrative pharmacology review in 2019 provide a vast number of novel lead compounds or drug candidates for future clinical agent development and also details a novel series of attractive therapeutic targets and molecular mechanisms for human diseases.

关键词： Traditional medicine Natural product Pharmacology Cancer Inflammation Infectious diseases

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Extracellular vesicles:General features and usefulness in diagnosis and therapeutic management of colorectal cancer

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World Journal of Gastrointestinal Oncology 2021年第11期13卷 1561-1598页

作者： Aurelien Mammes Jennifer Pasquier Olivier Mammes Marc Conti Richard Douard Sylvain Loric INSERM UMR-938 Cancer Biology and Therapeutics UnitSaint-Antoine Research CenterSaint Antoine University HospitalParis 75012France UCBM Necker University HospitalParis 75015France Metabolism research Unit Integracell SASLongjumeau 91160France Gastrointestinal Surgery Department Clinique BizetParis 75016France

In the world,among all type of cancers,colorectal cancer(CRC)is the third most commonly diagnosed in males and the second in *** most of cases,(RP1)patients’prognosis limitation with malignant tumors can be attributed to delayed diagnosis of the *** of patients with early-stage disease leads to more effective therapeutic ***,new screening methods and further innovative treatment approaches are mandatory as they may lead to an increase in progression-free and overall survival *** the last decade,the interest in extracellular vesicles(EVs)research has exponentially increased as EVs generation appears to be a universal feature of every cell that is strongly involved in many mechanisms of cell-cell communication either in physiological or pathological *** can cargo biomolecules,such as lipids,proteins,nucleic acids and generate transmission signal through the intercellular transfer of their *** this mechanism,tumor cells can recruit and modify the adjacent and systemic microenvironment to support further invasion and *** review intends to cover the most recent literature on the role of EVs production in colorectal normal and cancer *** attention is paid to the use of EVs for early CRC diagnosis,follow-up,and prognosis as EVs have come into the spotlight of research as a high potential source of‘liquid biopsies’.The use of EVs as new targets or nanovectors as drug delivery systems for CRC therapy is also summarized.

关键词： Extracellular vesicles Colorectal cancer Diagnostic Prognosis Vector Therapy

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Tumor-and osteoclast-derived NRP2 in prostate cancer bone metastases

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Bone research 2021年第2期9卷 233-247页

作者： Navatha Shree Polavaram Samikshan Dutta Ridwan Islam Arup K.Bag Sohini Roy David Poitz Jeffrey Karnes Lorenz C.Hofbauer Manish Kohli Brian A.Costello Raffael Jimenez Surinder K.Batra Benjamin A.Teply Michael H.Muders Kaustubh Datta Department of Microbiology and Pathology University of Nebraska Medical CenterOmahaNEUSA Department of Biochemistry and molecular biology University of Nebraska Medical CenterOmahaNEUSA Institute for Clinical Chemistry University Hospital DresdenDresdenGermany Department of Urology Mayo ClinicRochesterMNUSA center for Healthy Aging and Bone Lab Dresden Department of Medicine IIITechnische Universität DresdenDresdenGermany School of Medicine Division of OncologyHuntsman Cancer InstituteSalt Lake CityUTUSA Division of Anatomic Pathology Department of Pathology and Laboratory MedicineMayo ClinicRochesterMNUSA Internal Medicine Division of Oncology&HematologyUniversity of Nebraska Medical CenterOmahaNEUSA Rudolf-Becker Laboratory for Prostate Cancer research Institute of PathologyUniversity of Bonn Medical CenterBonnGermany

Understanding the role of neuropilin 2(NRP2)in prostate cancer cells as well as in the bone microenvironment is pivotal in the development of an effective targeted therapy for the treatment of prostate cancer bone *** observed a significant upregulation of NRP2 in prostate cancer cells metastasized to ***,we report that targeting NRP2 in cancer cells can enhance taxane-based chemotherapy with a better therapeutic outcome in bone metastasis,implicating NRP2 as a promising therapeutic ***,osteoclasts present in the tumor microenvironment express NRP2,we have investigated the potential effect of targeting NRP2 in *** results revealed NRP2 negatively regulates osteoclast differentiation and function in the presence of prostate cancer cells that promotes mixed bone *** study further delineated the molecular mechanisms by which NRP2 regulates osteoclast ***,depletion of NRP2 in osteoclasts in vivo showed a decrease in the overall prostate tumor burden in the *** results therefore indicate that targeting NRP2 in prostate cancer cells as well as in the osteoclastic compartment can be beneficial in the treatment of prostate cancer bone metastasis.

关键词： metastasis chemotherapy treatment

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Primary root and root hair development regulation by OsAUX4 and its participation in the phosphate starvation response

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Journal of Integrative Plant biology 2021年第8期63卷 1555-1567页

作者： Rigui Ye Yunrong Wu Zhenyu Gao Hao Chen Lixia Jia Dongming Li Xugang Li Qian Qian Yanhua Qi State Key Laboratory of Plant Physiology and Biochemistry College of Life SciencesZhejiang UniversityHangzhou310058 China Key Laboratory of Herbage&Endemic Crop biology of Ministry of Education Inner Mongolia Key Laboratory of Herbage&Endemic Crop BiotechnologySchool of Life SciencesInner Mongolia UniversityHohhot010000 China State Key Laboratory of Rice biology China National Rice Research InstituteChinese Academy of Agricultural SciencesHangzhou310006 China State Key Laboratory of Crop biology College of Life SciencesShandongAgricultural UniversityTai'an271018 China Sino-German Joint research center on Agricultural biology College of Life SciencesShandong Agricultural UniversityTai'an271018 China

Among the five members of AUX1/LAX genes coding for auxin carriers in rice,only OsAUX1 and OsAUX3 have been *** understand the function of the other AUX1/LAX genes,two independent alleles of osaux4 mutants,osaux4-1 and osaux4-2,were constructed using the CRISPR/Cas9 editing *** osaux4-1 or osaux4-2 exhibited shorter primary root(PR)and longer root hair(RH)compared to the wild-type Dongjin(WT/DJ),and lost response to indoleacetic acid(IAA)***4 is intensively expressed in roots and localized on the plasma membrane,suggesting that OsAUX4 might function in the regulation of root *** decreased meristem cell division activity and the downregulated expression of cell cycle genes in root apices of osaux4 mutants supported the hypothesis that OsAUX4 positively regulates PR ***4 is expressed in RH,and osaux4 mutants showing longer RH compared to WT/DJ implies that OsAUX4 negatively regulates RH ***,osaux4 mutants are insensitive to Pi starvation(-Pi)and OsAUX4 effects on the-Pi response is associated with altered expression levels of Pi starvation-regulated genes,and auxin distribution/*** study revealed that OsAUX4 not only regulates PR and RH development but also plays a regulatory role in crosstalk between auxin and-Pi signaling.

关键词： OsAUX4 phosphate starvation primary root root hair development rice

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Potato Virus Y mRNA Expression Knockdown Mediated by siRNAs in Cultured Mammalian cell Line

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Virologica Sinica 2011年第2期26卷 105-113页

作者： Bushra Tabassum Idrees Ahmad Nasir Tayyab Husnain National Centre of Excellence in molecular biology(CEMB) University of the Punjab

RNA interference(RNAi) is a powerful tool for functional gene analysis which has been successfully used to downregulate the expression levels of target *** goal of this research was to provide a highly robust and concise methodology for in-vitro screening of efficient siRNAs from a bulk to be used as a tool to protect potato plants against PVY *** our study,a 480bp fragment of the capsid protein gene of potato virus Y(CP-PVY) was used as a target to downregulate PVY mRNA expression in-vitro,as the CP gene interferes with viral uncoating,translation and replication.A total of six siRNAs were designed and screened through transient transfection assay and knockdown in expression of CP-PVY mRNA was calculated in CHO-k ***-PVY mRNA knockdown efficiency was analyzed by RT-PCR and real-time PCR of CHO-k cells co-transfected with a CP gene construct and *** biological replicates were performed in this *** our findings,one CP gene specific siRNA out of a total of six was found to be the most effective for knockdown of CP-PVY mRNA in transfected CHO-k cells by up to 80%-90%.

关键词： RNAi Potato virus Y siRNA in-vitro Expression knockdown Transfection

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Small G Protein as a Novel Component of the Rice Bmssinosteroid Signal Transduction

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molecular Plant 2016年第9期9卷 1260-1271页

作者： Ge Zhang Xiaoguang Song Hongyan Guo Yao Wu Xiaoying Chen Rongxiang Fang State Key Laboratory of Plant Genomics Institute of Microbiology Chinese Academy of Sciences Beijing 100101 China National center for Plant Gene research (Beijing) Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China These authors contributed equally to this article. Present address: State Key Laboratory of Plant Genomics and NationaT center for Plant Gene research (Beijing) Institute of Genetics and Developmental BiologyChinese Academy of Sciences Beijing 100101 China

Brassinosteroids （BRs） are a class of steroid hormones that are essential for plant growth and development. The BR signal transduction pathway in the dicot model plantArabidopsis is well established, but the components connecting the BR signaling steps in rice have not been fully explored. For example, how the BR signaling is fine-tuned in rice, especially at the BR receptor level, is largely unknown. Here we show that OsPRA2, a rice small G protein, plays a repressive role in the BR signaling pathway. Lamina inclination, coleoptile elongation, and root inhibition assays indicated that rice plants with suppressed expression of OsPRA2 were more sensitive to exogenously applied brassinolide than the wild-type plants. Conversety, rice overexpressing OsPRA2 was less sensitive to exogenous brassinolide. Further study uncovered that OsPRA2 inhibited the dephosphorylation of, and thus inactivated the transcription factor BRASSINAZOLE- RESISTANT 1 （OsBZR1）. More importantly, OsPRA2 was found to co-localize with and directly bind to rice BR receptor BRASSlNOSTEROID-INSENSITIVE 1 （OsBRI1） at the plasma membrane. Additionally, the in vitro assays showed that OsPRA2 inhibits its autophosphorylation. This OsPRA2-OsBRI1 interaction led to the dissociation of OsBRI1 from its co-receptor OsBAK1, and abolished OsBRIl-mediated phosphorylation of OsBAK1. Together, these results reveal a possible working mechanism of OsPRA2 as a novel negative regu- lator on OsBRI1 and OsBZR1 and extend the knowledge about the regulatory mechanism of rice BR signaling.

关键词： brassinosteroid small G protein plant hormone signal transduction

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