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The modulation of radiation-induced cell death by genistein in K562 cells:Activation of thymidine kinase 1

Cell research 2004年第4期14卷 295-302页

作者： Min Ho JEONG,Young Hee JIN,Eun Young KANG,Wol Soon JO,Hwan Tae PARK,Jae Dong LEE,Yeo Jin YOO,Soo Jin JEONG research Supporting Center for Medical Science (BK21 program) Dong-A University College of Medicine Busan Korea research Supporting Center for Medical Science (BK21 program) Dong-A University College of Medicine Busan Korea research Supporting Center for Medical Science (BK21 program) Dong-A University College of Medicine Busan Korea research Supporting Center for Medical Science (BK21 program) Dong-A University College of Medicine Busan Korea research Supporting Center for Medical Science (BK21 program) Dong-A University College of Medicine Busan Korea Department of Microbiology Pusan National University Busan Korea research Supporting Center for Medical Science (BK21 program) Dong-A University College of Medicine Busan Korea research Supporting Center for Medical Science (BK21 program) Dong-A University College of Medicine Busan Korea Virus Tumor Biology Section Laboratory of Cellular Oncology Center for Cancer research National Cancer Institutes National Institute of Health Bethesda MD 20892 USA

Ionizing radiation is one of the most effective tools in cancer therapy. In a previous study, we reported that protein tyrosine kinase (PTK) inhibitors modulate the radiation responses in the human chronic myelogenous leukemia (CML) cell line K562. The receptor tyrosine kinase inhibitor, genistein, delayed radiation-induced cell death, while non-recepter tyrosine kinase inhibitor, herbimycin A (HMA) enhances radiation-induced apoptosis. In this study, we focused on the modulation of radiation-induced cell death by genistein and performed PCR-select suppression subtractive hybridization (SSH) to understand its molecular mechanism. We identified human thymidine kinase 1 (TK1), which is cell cycle regulatory gene and confirmed expression of TK1 mRNA by Northern blot analysis. Expression of TKl mRNA and TK1 enzymatic activity were parallel in their increase and decrease. TK1 is involved in G1-S phase transition of cell cycle progression. In cell cycle analysis, we showed that radiation induced G2 arrest in K

关键词： K562 radiation cell death genistein thymidine kinase 1 cell cycle.

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CXC family of chemokines as prognostic or predictive biomarkers and possible drug targets in colorectal cancer

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World Journal of Gastroenterology 2018年第42期24卷 4738-4749页

作者： Sara Cabrero-de las Heras Eva Martínez-Balibrea program Against Cancer Therapeutic Resistance Catalan Institute of OncologyGermans Trias i Pujol health research institute program of Predictive and Personalized Cancer Medicine Germans Trias i Pujol health research institute

Colorectal cancer(CRC) is the third most common cancer in men and the second most common cancer in women,worldwide. In the early stages of the disease, biomarkers predicting early relapse would improve survival *** metastatic patients, the use of predictive biomarkers could potentially result in more personalized treatments and better outcomes. The CXC family of chemokines(CXCL1 to 17) are small(8 to 10 kDa) secreted proteins that attract neutrophils and lymphocytes. These chemokines signal through chemokine receptors(CXCR) 1 to *** studies have reported that these chemokines and receptors have a role in either the promotion or inhibition of cancer, depending on their capacity to suppress or stimulate the action of the immune system, *** general terms, activation of the CXCR1/CXCR2 pathway or the CXCR4/CXCR7 pathway is associated with tumor aggressiveness and poor prognosis; therefore,the specific inhibition of these receptors is a possible therapeutic strategy. On the other hand, the lesser known CXCR3 and CXCR5 axes are generally considered to be tumor suppressor signaling pathways, and their stimulation has been suggested as a way to fight *** pathways have been studied in tumor tissues(using immunohistochemistry or measuring mRNA levels)or serum [using enzyme-linked immuno sorbent assay(ELISA) or multiplexing techniques], among other sample types. Common variants in genes encoding for the CXC chemokines have also been investigated as possible biomarkers of the disease. This review summarizes themost recent findings on the role of CXC chemokines and their receptors in CRC and discusses their possible value as prognostic or predictive biomarkers as well as the possibility of targeting them as a therapeutic strategy.

关键词： Biomarkers Treatment Chemotherapy Oxaliplatin Irinotecan Immunotherapy Colorectal cancer CXC chemokines Immune system Bevacizumab

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Dephosphorylation of cGAS by PPP6C impairs its substrate binding activity and innate antiviral response

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Protein & Cell 2020年第8期11卷 584-599页

作者： Mi Li Hong-Bing Shu Department of Infectious Diseases Frontier Science Center for Immunology and MetabolismMedical Research InstituteZhongnan Hospital of Wuhan UniversityCollege of Life SciencesWuhan UniversityWuhan 430071China

The cyclic GMP-AMP (cGAMP) synthase (cGAS) plays a critical role in host defense by sensing cytosollc DNA derived from microbial pathogens or mls-located cellular *** DNA binding,cGAS utilizes GTP and ATP as substrates to synthesize cGAMP,leading to MITA-mediated innate immune *** this study,we identified the phosphatase PPP6C as a negative regulator of cGASmediated innate immune ***6C is constitutively associated with cGAS in un-stimulated *** virus infection causes rapid disassociation of PPP6C from cGAS,resulting in phosphorylation of human cGAS S435 or mouse cGAS S420 in its catalytic *** of this eerine residue of cGAS impairs its ability to synthesize cGAMP upon DNA virus *** vitro experiments indicate that S420-phosphorylated mcGAS has higher affinity to GTP and enzymatic ***6Cdeficiency promotes innate immune response to DNA virus in various *** findings suggest that PPP6Cmediated dephosphorylation of a catalytic pocket serine residue of cGAS impairs its substrate binding activity and innate immune response,which provides a mechanism for keeping the DNA sensor cGAS inactive in the absence of infection to avoid autoimmune response.

关键词： DNA virus PPP6C cGAS innate immune response phosphorylation substrate binding

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A quantitative analytical method for valienone and its application in the evaluation of valienone production by a breakthrough microbial process

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Chinese Journal of Natural Medicines 2017年第10期15卷 794-800页

作者： CUI Li Karin Yanagi SHI Ting LIU Zhang-Min BAI Lin-Quan FENG Yan State Key Laboratory of Microbial metabolism School of Life Science & Biotechnology and Joint International Research Laboratory of Metabolic & Developmental Sciences Shanghai Jiao Tong University Shanghai 200240 China

Valienone is a significant natural carbasugar member of the C7-cyclitol family as a valuable precursor for glycosidase inhibitor *** is an intermediate of validamycin A biosynthesis pathway and exhibits minimal accumulation in the fermentation broth of the natural Streptomyces producer.A quantitative analytical method is crucial for the development of a breakthrough microbial process overcoming the consumption of the natural metabolic *** present study was designed to develop a pre-column derivatization high-performance liquid chromatography method for quantification of valienone and to help establish a straightforward fermentation process for valienone production by metabolically engineered Streptomyces hygroscopicus *** was derivatized by 2,4-dinitrophenylhydrazine(DNPH)in 10 mmol×L^(-1) H_3PO_4 at 37℃ for 45 min and the derivatives were separated on Eclipse XDB-C18(5 μm,4.6 mm×150 mm)column at 30 °C eluted with 50% acetonitrile for 18 *** derivatives were detected by diode array detector at 380 nm and the configurations of the derivatives were determined by computational *** method was shown to be effective,sensitive,and *** linearity was found in the range of 5–2 000 μg×mL^(-1).The intra-and inter-day precisions were 1.1%–2.7% and 1.7%–2.2%,*** absolute recovery of the spiked samples was 97.2%–102.6%.To date,this is the first reversed-phase high-performance liquid chromatography detection method for valienone in microbial culture *** method successfully helped evaluate the valienone production capability of the engineered Streptomyces hygroscopicus 5008 and could be promising for C7-cyclitol profiling of different engineered mutants combined with the metabonomics methods.

关键词： Valienone Carbasugar Microbial process Derivatization HPLC

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Regulation of cancer cell metabolism:oncogenic MYC in the driver’s seat

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Signal Transduction and Targeted Therapy 2020年第1期5卷 1419-1429页

作者： Yang Dong Rongfu Tu Hudan Liu Guoliang Qing Department of Urology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Frontier Science Center for Immunology&metabolism Medical Research InstituteWuhan UniversityWuhan 430071China

Cancer cells must rewire cellular metabolism to satisfy the demands of unbridled growth and *** such,most human cancers differ from normal counterpart tissues by a plethora of energetic and metabolic *** factors of the MYC family are deregulated in up to 70%of all human cancers through a variety of *** levels of MYC regulates almost every aspect of cellular metabolism,a recently revisited hallmark of cancer ***,unrestrained growth in response to oncogenic MYC expression creates dependency on MYC-driven metabolic pathways,which in principle provides novel targets for development of effective cancer *** the current review,we summarize the significant progress made toward understanding how MYC deregulation fuels metabolic rewiring in malignant transformation.

关键词： metabolism cancer Cancer

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Gravitational effects on global hemodynamics in different postures:A closed-loop multiscale mathematical analysis

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Acta Mechanica Sinica 2017年第3期33卷 595-618页

作者： Xiancheng Zhang Shigeho Noda Ryutaro Himeno Hao Liu Graduate School of Engineering Chiba University Computational Science research program RIKEN Shanghai Jiao Tong University and Chiba University International Cooperative Research Center (SJTU-CU ICRC)

We present a novel methodology and strategy to predict pressures and flow rates in the global cardiovascular network in different postures varying from supine to upright. A closed-loop, multiscale mathematical model of the entire cardiovascular system (CVS) is developed through an integration of one-dimensional (1D) modeling of the large systemic arteries and veins, and zero-dimensional (0D) lumped-parameter modeling of the heart, the cardiac-pulmonary circulation, the cardiac and venous valves, as well as the microcirculation. A versatile junction model is proposed and incorporated into the 1D model to cope with splitting and/or merging flows across a multibranched junction, which is validated to be capable of estimating both subcritical and supercritical flows while ensuring the mass conservation and total pressure continuity. To model gravitational effects on global hemodynamics during postural change, a robust venous valve model is further established for the 1D venous flows and distributed throughout the entire venous network with consideration of its anatomically realistic numbers and locations. The present integrated model is proven to enable reasonable prediction of pressure and flow rate waveforms associated with cardiopulmonary circulation, systemic circulation in arteries and veins, as well as microcirculation within normal physiological ranges, particularly in mean venous pressures, which well match the in vivo measurements. Applications of the cardiovascular model at different postures demonstrate that gravity exerts remarkable influence on arterial and venous pressures, venous returns and cardiac outputs whereas venous pressures below the heart level show a specific correlation between central venous and hydrostatic pressures in right atrium and veins.

关键词： Gravitational effects Cardiovascular system (CVS) Postural change Multiscale cardiovascular model Multibranched junction model Venous valve

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VRK2 is involved in the innate antiviral response by promoting mitostress-induced mtDNA release

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Cellular & Molecular Immunology 2021年第5期18卷 1186-1196页

作者： Wen-Rui He Li-Bo Cao Yu-Lin Yang Duo Hua Ming-Ming Hu Hong-Bing Shu Department of Infectious Diseases Frontier Science Center for Immunology and MetabolismMedical Research InstituteZhongnan Hospital of Wuhan UniversityWuhan UniversityWuhanChina research Unit of Innate Immune and Inflammatory Diseases Chinese Academy of Medical SciencesWuhanChina

Mitochondrial stress (mitostress) triggered by viral infection or mitochondrial dysfunction causes the release of mitochondrial DNA (mtDNA) into the cytosol and activates the cGAS-mediated innate immune response. The regulation of mtDNA release upon mitostress remains uncharacterized. Here, we identified mitochondria-associated vaccinia virus-related kinase 2 (VRK2) as a key regulator of this process. VRK2 deficiency inhibited the induction of antiviral genes and caused earlier and higher mortality in mice after viral infection. Upon viral infection, VRK2 associated with voltage-dependent anion channel 1 (VDAC1) and promoted VDAC1 oligomerization and mtDNA release, leading to the cGAS-mediated innate immune response. VRK2 was also required for mtDNA release and cGAS-mediated innate immunity triggered by nonviral factors that cause Ca^(2+) overload but was not required for the cytosolic nucleic acid-triggered innate immune response. Thus, VRK2 plays a crucial role in the mtDNA-triggered innate immune response and may be a potential therapeutic target for infectious and autoimmune diseases associated with mtDNA release.

关键词： cGAS Mita/Sting mitostress innate immune response mitochondrial DNA

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Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion

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Neural Regeneration research 2025年第10期20卷 2838-2854页

作者： Lu Guan Mengting Qiu Na Li Zhengxiang Zhou Ru Ye Liyan Zhong Yashuang Xu Junhui Ren Yi Liang Xiaomei Shao Jianqiao Fang Junfan Fang Junying Du Department of Neurobiology and Acupuncture research Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Key Laboratory for research of Acupuncture Treatment and Transformation of Emotional Diseases Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Fuchun Community Health Service Center of Fuyang District HangzhouZhejiang ProvinceChina

Pain is often comorbid with emotional disorders such as anxiety and *** of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid *** review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain *** understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these ***,the mechanisms that regulate gamma-aminobutyric acidergic systems remain *** is also unclear as to whether the mechanisms are presynaptic or *** exploration of the complexities of this system may reveal new pathways for research and drug development.

关键词： anterior cingulate cortex anxiety chronic pain circuit communication comorbidity depression gamma-aminobutyric acidergic neurons parvalbumin neurons synaptic transmission

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Planting position and shade enhance native seedling performance in forest restoration for an endangered malagasy plant

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Plant Diversity 2019年第2期41卷 118-123页

作者： Cyprien Miandrimanana J.Leighton Reid Tahiry Rivoharison Chris Birkinshaw Missouri Botanical Garden Madagascar Research and Conservation Program Center for Conservation and Sustainable Development Missouri Botanical Garden

The critically endangered tree Schizolaena tampoketsana is confined to a few diminished and degraded forest fragments on the Malagasy highlands. This habitat is vulnerable to loss due to frequent fires in the surrounding grassland that threaten to spread into the forest. One of these fragments is the focus a conservation project and here the managers aim to conserve S. tampoketsana by restoring its forest habitat to its former extent as evidenced by remnant woody plants. To inform this activity the survival and early-stage growth of seedlings of four locally native tree species were compared under contrasting conditions of proximity to the remaining forest and shade. After 12 months, seedlings of three species(Baronia taratana, Eugenia pluricymosa, Uapaca densifolia) survived better and experienced improved growth in height in grassland close to the existing forest rather than distant from it, and two survived better with shade rather than unshaded. A number of mechanisms could explain these results including reduced exposure to desiccating sunlight and winds and better soil and greater water availability close to the forest. The seedlings of one species(Nuxia capitata) survived well under all conditions. This study suggests that reforestation in these dry highlands is most feasible adjacent to remnant forest fragments and in microhabitats that minimize water loss, though young plants of some tree species may be capable of surviving in harsher conditions.

关键词： Grassland Fire Forest restoration Local environment Schizolaena tampoketsana

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3D tomographic analysis of equatorial plasma bubble using GNSS-TEC data from Indonesian GNSS Network

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Earth and Planetary Physics 2025年第1期9卷 127-136页

作者： Ihsan Naufal Muafiry Prayitno Abadi Teguh N.Pratama Dyah R.Martiningrum Sri Ekawati Yuandhika GWismaya Febrylian FChabibi Gatot HPramono research Center for Climate and Atmosphere Indonesian National Research and Innovation Agency(BRIN)BandungIndonesia Indonesian Geospatial Information Agency(BIG) JakartaIndonesia Dept.of Physics Faculty of ScienceUniversiti Teknologi MalaysiaJohor BahruMalaysia Dept.Earth Planet Sci. Hokkaido UniversitySapporoJapan School of Electrical Engineering Telkom UniversityBandungIndonesia

Equatorial Plasma Bubbles(EPBs)are ionospheric irregularities that take place near the magnetic *** most commonly occur after sunset during the equinox months,although they can also be observed during other *** phenomenon significantly disrupts radio wave signals essential to communication and navigation *** national network of Global Navigation Satellite System(GNSS)receivers in Indonesia(>30°longitudinal range)provides an opportunity for detailed EPB *** explore this,we conducted preliminary 3D tomography of total electron content(TEC)data captured by GNSS receivers following a geomagnetic storm on December 3,2023,when at least four EPB clusters occurred in the Southeast Asian *** and extracted TEC depletion with a 120-minute running average were then used as inputs for a 3D tomography *** 2D spatial distribution consistently captured the four EPB clusters over *** tomography results were validated through a classical checkerboard test and comparisons with other ionospheric data sources,such as the Global Ionospheric Map(GIM)and International Reference Ionosphere(IRI)*** of the results demonstrates the capability of the Indonesian GNSS network to measure peak ionospheric *** findings highlight the potential for future three-dimensional research of plasma bubbles in low-latitude regions using existing GNSS networks,with extensive longitudinal coverage.

关键词： EPB Indonesian GNSS Network 3D tomography

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