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RNA m^(6)A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression

Genes & Diseases 2024年第1期11卷 382-396页

作者： Zheng Zhang Keren Zhou Li Han Andrew Small Jianhuang Xue Huilin Huang Hengyou Weng Rui Su Brandon Tan Chao Shen Wei Li Zhicong Zhao ying Qing Xi Qin kitty Wang Keith leung Mark Boldin Chun-Wei Chen David Ann Zhijian Qian Xiaolan Deng Jianjun Chen Zhenhua Chen Department of Systems Biology Beckman Research Institute of City of HopeMonroviaCA 91016USA Irell and Manella Graduate School of Biological Sciences Beckman Research Institute of City of HopeDuarteCA 91010USA Gehr Family Center for Leukemia Research City of HopeDuarteCA 91010USA Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510060China Guangzhou Laboratory GuangzhouGuangdong 510005China Bioland Laboratory GuangzhouGuangdong 51005China Department of Liver Surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of Diabetes Complications and Metabolism Beckman Research Institute of City of HopeDuarteCA 91010USA Department of Biochemistry and Molecular Biology University of FloridaGainesvilleFL 32603USA Tongji Hospital Affiliated to Tongji University Frontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China School of Pharmacy China Medical UniversityShenyangLiaoning 110001China

As the most common internal modification of mRNA,Ne-methyladenosine(m^(6)A)and its regulators modulate gene expression and play critical roles in various biological and patholog-ical processes including *** was reported previously that m^(6)A methyltransferase(writer),methyltransferase-like 3(METTL3)adds m^(6)A in primary microRNAs(pri-miRNAs)and fa-cilitates its processing into precursor miRNAs(pre-miRNAs).However,it is unknown whether m^(6)A modification also plays a role in the maturation process of pre-miRNAs and(if so)whether such a function contributes to ***,we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia(AML)patients,especially in relapsed patients,and plays an onco-genic role in ***,YTHDF2 promotes expression of miR-126-3p(also known as miR-126,as it is the main product of precursor miR-126(pre-miR-126)),a miRNA that was reported as an oncomiRNA in AML,through facilitating the processing of pre-miR-126 into mature ***,YTHDF2 recognizes m^(6)A modification in pre-miR-126 and recruits AGO2,a regulator of pre-miRNA processing,to promote the maturation of ***2 posi-tively and negatively correlates with miR-126 and miR-126's downstream target genes,respec-tively,in AML patients,and forced expression of miR-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis,indi-cating that miR-126 is a functionally important target of YTHDF2 in ***,our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the ther-apeutic potential of targeting this axis for AML treatment,but also suggest that m^(6)A plays a role in pre-miRNA processing that contributes to tumorigenesis.

关键词： AML miR-126 N^(6)-methyladenosine Pre-miRNA maturation YTHDF2

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Effect of tubastatin A on NLRP3 inflammasome activation in macrophages under hypoxia/ reoxygenation conditions

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World Journal of Emergency Medicine 2024年第4期15卷 289-296页

作者： Hao Li Chang Liu ying Cui Panpan Chang Wei Chong Department of Emergency Medicine the First Hospital of China Medical UniversityShenyang 110001China Trauma Medicine Center Peking University People's HospitalBeijing 100871China Key Laboratory of Trauma and Neural Regeneration Peking UniversityBeijing 100871China National Center for Trauma Medicine of China Beijing 100871China

BACKGROUND:There are currently no effective drugs to mitigate the ischemia/reperfusion injury caused by fluid resuscitation after hemorrhagic shock(HS).The aim of this study was to explore the potential of the histone deacetylase 6(HDAC6)-specific inhibitor tubastatin A(TubA)to suppress nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome activation in macrophages under hypoxia/reoxygenation(H/R)***:The viability of RAW264.7 cells subjected to H/R after treatment with different concentrations of TubA was assessed using a cell-counting kit-8(CCK8)***,2.5μmol/L TubA was used with RAW264.7 cells under H/R ***264.7 cells were divided into three groups,namely the control,H/R,and TubA *** levels of reactive oxygen species(ROS)in the cells were detected using fluorescence *** protein expression of HDAC6,heat shock protein 90(Hsp90),inducible nitric oxide synthase(iNOS),NLRP3,gasdermin-D(GSDMD),Caspase-1,GSDMD-N,and Caspase-1 p20 was detected by western *** levels of interleukin-1β(IL-1β)and IL-18 in the supernatants were detected using enzyme-linked immunosorbent assay(ELISA).RESULTS:HDAC6,Hsp90,and iNOS expression levels were significantly higher(P<0.01)in the H/R group than in the control group,but lower in the TubA group than in the H/R group(P<0.05).When comparing the H/R group to the control group,ROS levels were significantly higher(P<0.01),but significantly reduced in the TubA group(P<0.05).The H/R group had higher NLRP3,GSDMD,Caspase-1,GSDMD-N,and Caspase-1 p20 expression levels than the control group(P<0.05),however,the TubA group had significantly lower expression levels than the H/R group(P<0.05).IL-1βand IL-18 levels in the supernatants were significantly higher in the H/R group compared to the control group(P<0.01),but significantly lower in the TubA group compared to the H/R group(P<0.01).CONCLUSION:TubA inhibited the expression of HDAC6,Hsp90,and iNOS in macrophages

关键词： Hemorrhagic shock Hypoxia/reoxygenation Macrophage NLRP3 Tubastatin A

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香港前肠外科现状

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中华普通外科杂志 2024年第6期39卷 418-422页

作者：黄宇匡罗英杰香港大学临床医学院外科学系中国

前肠是指胚胎时期的消化道上部,进一步发育成为食管、肺、胃、肝脏、胰腺及部分十二指肠等器官.在中国香港,针对治疗和研究前肠相关良性疾病的前肠外科已经拥有相对成熟的技术和先进仪器配合,包括采用一系列的辅助检查方法,率先开展新... 详细信息

前肠是指胚胎时期的消化道上部,进一步发育成为食管、肺、胃、肝脏、胰腺及部分十二指肠等器官.在中国香港,针对治疗和研究前肠相关良性疾病的前肠外科已经拥有相对成熟的技术和先进仪器配合,包括采用一系列的辅助检查方法,率先开展新颖的抗反流手术方式,如机器人辅助下食管裂孔疝修补、磁珠环括约肌增强术等.目前亚洲各地学者开始越来越重视前肠相关疾病,本文通过介绍中国香港前肠外科情况促进与国际进行学术交流合作,谋求与亚太地区进一步共同建设亚洲前肠相关协会,分享诊治经验和学术成果.

关键词：胃食管反流疝,食管裂孔肥胖症机器人贲门失驰缓症前肠外科

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The Essential Role of Zheng Qi in Promoting Health: From the Perspective of Chinese Medicine and Modern Medicine

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Chinese Medicine 2024年第2期15卷 27-33页

作者： Kam Ming Ko Hoi Yan leung Division of Life Science Hong Kong University of Science & Technology Hong Kong SAR China

The concept of Zheng Qi in traditional Chinese medicine (TCM) refers to the vital energy produced by the interaction of Yin and Yang forces in the body. Zheng Qi performs two main functions: Wei Qi (defensive Qi), which shields the body from external pathogens, and ying Qi (nutritive Qi), which sustains the internal organs and enhances their functionality. In TCM, Chinese tonifying herbs can help restore the balance of Yin/Yang and Qi/Blood function in visceral organs (i.e., optimal physiological functions), thereby fostering the efficient production of Zheng Qi and enhancing health. To ensure the quality of Chinese herbal products, functional assays to measure Yin/Yang, Qi/Blood functions, and Zheng Qi production should be implemented. The efficacy of Yang and Qi herbs can be evaluated by their ability to increase mitochondrial ATP in cultured mouse cardiomyocytes, while Yin and Blood herbs are tested through their immunostimulatory effects on antigen-induced T/B cell proliferation in mouse splenocytes and the production of erythropoietin/nitric oxide in hepatocytes/vascular endothelial cells, respectively. Additionally, Zheng Qi’s effect can be gauged by examining natural killer cell activity and antigen-induced T/B cell proliferation in mice ex vivo. These assays act as biomarkers for assessing the quality and effectiveness of herbal health products within TCM theory.

关键词： Traditional Chinese Medicine Zheng Qi Immunity Biomarkers Functional Assays

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Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin:Creation of an unnatural analogue with improved anticancer properties

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Acta Pharmaceutica Sinica B 2024年第1期14卷 421-432页

作者： Dexiu Yan Jemma Arakelyan Teng Wan Ritvik Raina Tsz Ki Chan Dohyun Ahn Vladimir Kushnarev Tsz Kiu Cheung Ho Ching Chan Inseo Choi Pui Yi Ho Feijun Hu Yujeong Kim Hill Lam Lau ying Lo Law Chi Seng leung Chun Yin Tong Kai Kap Wong Wing Lam Yim Nikolay S.Karnaukhov Richard Y.C.Kong Maria V.Babak Yudai Matsuda Department of Chemistry City University of Hong KongHong Kong SARChina iGEM Team“VarieCure” City University of Hong KongHong Kong SARChina Department of Biomedical Engineering City University of Hong KongHong Kong SARChina Moscow Clinical Research Center Named After A.S.Loginov Moscow 111123Russian Federation

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC *** production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 ***,the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues(5-7).Analysis of the compounds’anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities,5 was associated with significantly reduced toxic side effects in cancer-bearing mice,indicating its potentially broader therapeutic *** study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

关键词： Animal studies Anticancer properties Biosynthesis Natural products Sesterterpenoids Synthetic biology Terpene synthases Variecolin

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Synergistic Effects of Glutamine Deprivation and Metformin in Acute Myeloid Leukemia

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Current Medical Science 2024年第4期44卷 799-808页

作者： Tong-yuan LIU Xing FU ying YANG Jia GU Min XIAO Deng-ju LI Department of Hematology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective The metabolic reprogramming of acute myeloid leukemia(AML)cells is a compensatory adaptation to meet energy requirements for rapid *** study aimed to examine the synergistic effects of glutamine deprivation and metformin exposure on AML *** SKM-1 cells(an AML cell line)were subjected to glutamine deprivation and/or treatment with metformin or bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide(BPTES,a glutaminase inhibitor)or *** viability was detected by Cell Counting kit-8(CCK-8)assay,and cell apoptosis and reactive oxygen species(ROS)by flow *** blotting was conducted to examine the levels of apoptotic proteins,including cleaved caspase-3 and poly(ADP-ribose)polymerase(PARP).Moreover,the human long noncoding RNA(lncRNA)microarray was used to analyze gene expression after glutamine deprivation,and results were confirmed with quantitative RT-PCR(qRT-PCR).The expression of metallothionein 2A(MT2A)was suppressed using *** growth and apoptosis were further detected by CCK-8 assay and flow cytometry,respectively,in cells with MT2A *** Glutamine deprivation or treatment with BPTES inhibited cell growth and induced apoptosis in SKM-1 *** lncRNA microarray result showed that the expression of MT family genes was significantly upregulated after glutamine ***2A knockdown increased apoptosis,while proliferation was not affected in SKM-1 *** addition,metformin inhibited cell growth and induced apoptosis in SKM-1 *** glutamine deprivation and metformin enhanced the sensitivity of SKM-1 cells to ***,the combination of glutamine deprivation with metformin exhibited synergistic antileukemia effects on SKM-1 *** Targeting glutamine metabolism in combination with metformin is a promising new therapeutic strategy for AML.

关键词： glutamine metformin acute myeloid leukemia metallothionein

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Electroacupuncture inhibits hippocampal oxidative stress and autophagy in sleep-deprived rats through the protein kinase B and mechanistic target of rapamycin signaling pathway

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Journal of Traditional Chinese Medicine 2024年第5期44卷 974-980页

作者： ZHENG Peng MENG ying LIU Meijun YU Di LIU Huiying WANG Fuchun XU Xiaohong Department of Neurology The Third Affiliated Clinical Hospital of Changchun University of Chinese Medicine Rehabilitation Medicine Academy Changchun University of Chinese Medicine

OBJECTIVE: To investigate the effects of acupuncture on learning and memory impairment, oxidative stress and autophagy induced by sleep depriv ation in rats, and to analyze the related ***: Thirty Wistar rats were randomly divided into a normal group, sleep deprivation group and acupuncture group. The rat model of sleep deprivation was established by a modified multiplatform sleep deprivation *** Baihui(GV20), Shenmen(HT7) and Sanyinjiao(SP6)acupoints of rats were located to give electroacupuncture(density wave, frequency 20 Hz, intensity 1 mA) to maintain the needle feeling, and to keep the needle for 15min and continuous acupuncture for 7 d. The spatial learning and memory abilities of the rats were detected by the water maze test. The content of malondialdehyde(MDA) and the activities of superoxide dismutase(SOD)and glutathione peroxidase(GPX) in the brain were detected by an assay kit, and the autophagy related proteins light chain 3 alpha(LC3A), light chain 3 beta(LC3B) and Beclin 1 and the activation of the protein kinase B(PKB/AKT) and mechanistic target of rapamycin(mTOR) signaling pathway in the rat's brain were detected by Western ***: Compared with the normal group, the time spent in the target quadrant(P < 0.05) and the number of times entering the target quadrant(P < 0.05) in the rats of sleep deprivation group were significantly reduced, and the content of MDA was significantly increased(P < 0.01),while the activities of SOD and GPX(P < 0.01) in the brain were significantly decreased, and LC3A Ⅱ/Ⅰ, LC3B Ⅱ/Ⅰand Beclin 1 increased significantly(P < 0.01), while pAKT(ser473)/AKT, p-mTOR(ser2448)/mTOR and pp70s6K(thr389)/p70S6 decreased significantly(P < 0.01).Compared with the sleep deprivation group, the time spent in the target quadrant and the times of entering the target quadrant(P < 0.05) in the rats of acupuncture group after 7 d of treatment were significantly increased,Additionally, the content of MDA was signific

关键词： acupuncture autophagySupporting information memory and learning tests oxidative stress sleep deprivation

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Trimethylamine N-oxide aggravates vascular permeability and endothelial cell dysfunction under diabetic condition:in vitro and in vivo study

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 25-33页

作者： Jia-Yi Jiang Wei-Ming Liu Qiu-Ping Zhang Hang Ren Qing-ying Yao Gao-Qin Liu Pei-Rong Lu Department of Ophthalmology the First Affiliated Hospital of Soochow UniversitySuzhou 215006Jiangsu ProvinceChina Suzhou Center for Disease Prevention and Control Suzhou 215004Jiangsu ProvinceChina

AIM:To provide the direct evidence for the crucial role of trimethylamine N-oxide(TMAO)in vascular permeability and endothelial cell dysfunction under diabetic ***:The role of TMAO on the in vitro biological effect of human retinal microvascular endothelial cells(HRMEC)under high glucose conditions was tested by a cell counting kit,wound healing,a transwell and a tube formation *** inflammation-related gene expression affected by TMAO was tested by real-time polymerase chain reaction(RT-PCR).The expression of the cell junction was measured by Western blotting(WB)and immunofluorescence *** addition,two groups of rat models,diabetic and non-diabetic,were fed with normal or 0.1%TMAO for 16wk,and their plasma levels of TMAO,vascular endothelial growth factor(VEGF),interleukin(IL)-6 and tumor necrosis factor(TNF)-αwere *** vascular permeability of rat retinas was measured using FITC-Dextran,and the expression of zonula occludens(ZO)-1 and claudin-5 in rat retinas was detected by WB or immunofluorescence ***:TMAO administration significantly increased the cell proliferation,migration,and tube formation of primary HRMEC either in normal or high-glucose ***-PCR showed elevated inflammation-related gene expression of HRMEC under TMAO stimulation,while WB or immunofluorescence staining indicated decreased cell junction ZO-1 and occludin expression after high-glucose and TMAO *** rats showed higher plasma levels of TMAO as well as retinal vascular leakage,which were even higher in TMAO-feeding diabetic ***,TMAO administration increased the rat plasma levels of VEGF,IL-6 and TNF-αwhile decreasing the retinal expression levels of ZO-1 and ***:TMAO enhances the proliferation,migration,and tube formation of HRMEC,as well as destroys their vascular integrity and tight *** also regulates the expression of VEGF,IL-6,and TNF-α.

关键词： diabetic model trimethylamine N-oxide inflammation endothelial dysfunction rats retinal microvascular endothelial cells

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Investigation on the Consumption Values of Hong Kong People on Tie Products

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Journal of Donghua University(English Edition) 2004年第2期21卷 52-59页

作者： Sarah Mei-yi leung Alice Wai-ching Chu kit-lun Yick Institute of Textiles & Clothing The Hong Kong Polytechnic University Hung Hom Kowloon Hong KongDrInstitute of Textiles & Clothing The Hong Kong Polytechnic University Hung Hom Kowloon Hong KongInstitute of Textiles & Clothing The Hong Kong Polytechnic University Hung Hom Kowloon Hong Kong

This study aims at investigating the consumption values of Hong Kong people on necktie. Based on the Sheth-Newman-Gross Model of consumption values on consumers’ choice decision as conceptual framework, results from the focus group interview, a questionnaire was designed and adopted for conducting the survey. Data collected from 245 respondents were analysed using the Factor Analysis to review the important elements of consumers’ decision of purchasing tie products. Implications on the results on the Functional value were reviewed and discussed in details. Interesting elements such as fabric hand-feel were also identified as influential associated in Hong Kong consumers’ selection of necktie. Since, both fibre content and fabric handle were also found as major selection criteria for fabric materials, the study was focused on the analysis of functional value of the product and further extended to study the handle preference for Hong Kong customers, in which a subjective handle assessment of a wide range of tie fabrics being newly developed and introduced in the market was conducted and objective fabric physical and mechanical properties were measured. Important fabric handle attributes that influence the consumers’ preference on tie fabrics were identified and their objective translation by fabric physical and mechanical properties were also obtained. The investigation provides decision support to necktie manufacturers and retailers through scientific and quantitative recommendations for product development of tie products and material selection.

关键词： Necktie Hand-feel Consumption Values and Consumer Behaviour

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Polysaccharide of Alocasia cucullata Exerts Antitumor Effect by Regulating Bcl-2, Caspase-3 and ERK1/2 Expressions during Long-Time Administration

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Chinese Journal of Integrative Medicine 2024年第1期30卷 52-61页

作者： ZHOU Qi-chun XIAO Shi-lin LIN Ru-kun LI Chan CHEN Zhi-jie CHEN Yi-fei LUO Chao-hua MO Zhi-xian LIN ying-bo School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou(510515)China Clinical and Basic Research Team of TCM Prevention and Treatment of Non-Small Cell Lung Cancer the Second Clinical College of Guangzhou University of Chinese MedicineGuangzhou(510120)China Department of Chinese Medicine Zhujiang Hospital Affiliated to Southern Medical UniversityGuangzhou(510282)China Department of Pharmacy Jiangmen Central HospitalJiangmen(529000)China

Objective: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata(PAC) and the underlying mechanism. Methods: B16F10 and 4T1 cells were cultured with PAC of 40 μg/m L, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction(qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with normal saline, positive control group(LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The cell apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. Results: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein(P <0.05), up-regulation of Caspase-3 protein(P<0.05) and ERK1 mRNA(P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. Conclusions: Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.

关键词： polysaccharide of Alocasia cucullata tumor cells Bcl-2 Caspase-3 ERK1/2 Chinese medicine

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