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Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1271-1287页

作者： Cancan Zheng Xiaomei Yu Yiyao Liang Yidong Zhu Yan He Long Liao Dingkang Wang Yanming Yang Xingfeng Yin Ang Li Qingyu He Bin Li MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes Institute of Life and Health EngineeringJinan UniversityGuangzhou 510632China Guangdong Key Laboratory of Non-human Primate Research Guangdong-Hong Kong-Macao Institute of CNS RegenerationKey Laboratory of CNS RegenerationMinistry of EducationJinan UniversityGuangzhou 510632China MOE Key Laboratory of Tumor Molecular Biology and Guangdong provincial Key Laboratory of Bioengineering Medicine National Engineering Research Center of Genetic MedicineInstitute of BiomedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China

As one of the hallmarks of cancer,metabolic reprogramming leads to cancer progression,and targeting glycolytic enzymes could be useful strategies for cancer *** screening a small molecule library consisting of 1320 FDA-approved drugs,we found that penfluridol,an antipsychotic drug used to treat schizophrenia,could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma(ESCC).Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of *** using drug affinity responsive target stability(DARTS)technology and proteomics,we identified phosphofructokinase,liver type(PFKL),a key enzyme in glycolysis,as a direct target of *** could not exhibit its anticancer property in PFKL-deficient cancer cells,illustrating that PFKL is essential for the bioactivity of *** PFKL expression is correlated with advanced stages and poor survival of ESCC patients,and silencing of PFKL significantly suppressed tumor ***,direct binding of penfluridol and PFKL inhibits glucose consumption,lactate and ATP production,leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent *** together,PFKL is a potential prognostic biomarker and therapeutic target in ESCC,and penfluridol may be a new therapeutic option for management of this lethal disease.

关键词： Drug repurposing Metabolic reprogramming Glycolysis PFKL DARTS technology Esophageal cancer Penfluridol

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Pakl mediates the stimulatory effect of insulin and curcumin on hepatic ChREBP expression

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Journal of Molecular Cell Biology 2017年第5期9卷 384-394页

作者： Kejing Zeng Lili Tian Adam Sirek Weijuan Shao Ling Liu Yu-Ting Chiang Jonathan Chernoff Dominic S. Ng Jianping Weng Tianru Jin Department of Endocrinology and Metabolism the Third Affiliated Hospital of Sun Yat-Sen University and Guangdong Provincial Key Laboratory of Diabetology Guangzhou 510630 china Toronto General Research Institutes University Health Network Toronto M56 1L7 Canada Department of Physiology Faculty of Medicine University of Toronto Toronto MSS 1A8 Canada Cancer Biology Program Fox Chase Cancer Center PhiLadelphia PA 19111-2497 USA Keenan Research Centre Li Ka Shing Knowledge Institute Department of Medicine St. Michael's Hospital Toronto MSB lW8 Canada

Insulin can stimulate hepatic expression of carbohydrate-responsive element-binding protein （ChREBP）. As recent studies revealed potential metabolic beneficial effects of ChREBP, we asked whether its expression can also be regulated by the dietary polyphenoi curcumin. We also aimed to determine mechanisms underlying ChREBP stimulation by insulin and curcumin. The effect of insulin on ChREBP expression was assessed in mouse hepatocytes, while the effect of curcumin was assessed in mouse hepatocytes and with curcumin garage in mice. Chemical inhibitors for insulin signaling molecules were utilized to identify involved signaling molecules, and the involvement of p21-activated protein kinase 1 （Pakl） was determined with its chemical inhibitor and Pokl-/- hepatocytes. We found that both insulin and curcumin-stimulated ChREBP expression in Akt-independent but MEK/ERK-dependent manner, involving the inactivation of the transcriptional repressor Oct-1. Aged Pokl-/- mice showed reduced body fat volume. Pakl inhibition or its genetic deletion attenuated the stimulatory effect of insulin or curcumin on ChREBP expression. Our study hence suggests the existence of a novel signaling cascade Pakl/MEK/ERK/Oct-1 for both insulin and curcumin in exerting their glucose-lowering effect via promoting hepatic ChREBP production, supports the recognition of beneficial functions of ChREBP, and brings us a new overview on dietary polyphenols.

关键词： Akt ChREBP curcumin dietary polypheno[ intervention insulin Oct-l Pakl

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Analysis of genetic alterations identifies the frequent mutation of GNAS in colorectal laterally spreading tumors

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Cancer Communications 2020年第11期40卷 636-640页

作者： Lei Pan Junsheng Chen Chaojun Zhu Lu Han Aimin Li Side Liu Guangdong provincial Key Laboratory of Gastroenterology Department of GastroenterologyNanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515P.R.China

Dear Editor,Colorectal cancer(CRC)is among the most commonly diagnosed cancer and the leading cause of cancer-related death worldwide[1].Most CRCs develop from *** spreading tumors(LSTs)are non-polypoid superficial colorectal neoplasms(CRNs)that are larger than 1 cm and typically extend laterally along the luminal *** on surface morphology,it can be classified into a granular or nongranular *** pathological morphology of LST manifests only as adenoma or with *** studies have characterized 45-79%of LSTs as high-grade intraepithelial neoplasia(HGIN)or submucosal invasion;and the risk of submucosal invasion increases with lesion size[2].Hence,LST is considered a precancerous CRC *** with LSTs are usually asymptomatic and diagnosis typically occurs during physical examinations or screening colonoscopy.

关键词： invasion colorectal alterations

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Introduction of graphene oxide-supported multilayer-quantum dots nanofilm into multiplex lateral flow immunoassay:A rapid and ultrasensitive point-of-care testing technique for multiple respiratory viruses

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Nano Research 2023年第2期16卷 3063-3073页

作者： Wenqi Wang Xingsheng Yang Zhen Rong Zhijie Tu Xiaochang Zhang Bing Gu Chongwen Wang Shengqi Wang Beijing Institute of Microbiology and Epidemiology Beijing 100850China College of Life Sciences Anhui Agricultural UniversityHefei 230036China Laboratory Medicine Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510000China

A lateral flow immunoassay(LFA)biosensor that allows the sensitive and accurate identification of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)and other common respiratory viruses remains highly desired in the face of the coronavirus disease 2019 ***,we propose a multiplex LFA method for the on-site,rapid,and highly sensitive screening of multiple respiratory viruses,using a multilayered film-likeﬂuorescent tag as the performance enhancement and signal amplification *** film-like three-dimensional(3D)tag was prepared through the layer-by-layer assembly of highly photostable CdSe@ZnS-COOH quantum dots(QDs)onto the surfaces of monolayer graphene oxide nanosheets,which can provide larger reaction interfaces and specific active surface areas,higher QD loads,and better luminescence and dispersibility than traditional spherical fluorescent microspheres for LFA *** constructedﬂuorescent LFA biosensor can simultaneously and sensitively quantify SARS-CoV-2,influenza A virus,and human adenovirus with low detection limits(8 pg/mL,488 copies/mL,and 471 copies/mL),short assay time(15 min),good reproducibility,and high ***,our proposed assay has great potential for the early diagnosis of respiratory virus infections given its robustness when validated in real saliva samples.

关键词： lateral flow immunoassay multilayered film-like quantum dots(QDs) simultaneous detection respiratory viruses severe

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Anthrahydroquinone-2,6-disulfonate alleviates paraquat-induced kidney injury via the apelin-APJ pathway in rats

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Asian Pacific Journal of Tropical Biomedicine 2022年第8期12卷 333-342页

作者： Qi Li Bo Wang Kai-Wen Lin Tang Deng Qi-Feng Huang Shuang-Qin Xu Hang-Fei Wang Xin-Xin Wu Nan Li Yang Yi Ji-Chao Peng Yue Huang Jin Qian Xiao-Ran Liu College of Emergency and Trauma Hainan Medical UniversityKey Laboratory of Emergency and Trauma of Ministry of EducationThe First Affiliated Hospital of Hainan Medical UniversityHaikou 571199China Jiangdong health center Meilan DistrictHaikou 571126China Hainan Women and Children's Medical center Haikou 570312China

Objective:To explore the protective effects of anthrahydroquinone-2,6-disulfonate(AH_(2)QDS)on the kidneys of paraquat(PQ)poisoned rats via the apelin-APJ ***:Male Sprague Dawley rats were divided into four experimental groups:control,PQ,PQ+sivelestat,and PQ+AH_(2)*** PQ+sivelestat group served as the positive control *** model of poisoning was established via intragastric treatment with a 20%PQ pesticide solution at 200 mg/*** hours after poisoning,the PQ+sivelestat group was treated with sivelestat,while the PQ+AH_(2)QDS group was given AH_(2)*** rats were selected from each group on the first,third,and seventh days after poisoning and dissected after *** PQ content of the kidneys was measured using the sodium disulfite ***-eosin staining of renal tissues was performed to detect pathological *** expression in the renal tissues was detected using *** blotting was used to detect the expression levels of the following proteins in the kidney tissues:IL-6,TNF-α,apelin-APJ(the apelin-angiotensin receptor),NF-κB p65,caspase-1,caspase-8,glucose-regulated protein 78(GRP78),and the C/EBP homologous protein(CHOP).In in vitro study,a PQ toxicity model was established using human tubular epithelial cells treated with standard ***-four hours after poisoning,sivelestat and AH_(2)QDS were *** levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence ***:The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH_(2)QDS ***-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ *** degeneration of the renal tubule epithelial cells,deposition of crescent-like red staining material in renal follicles,infiltration by a few inflammatory cells,and a small number of cast formation were also ***,these pat

关键词： Paraquat poisoning AH2QDS Apelin/APJ Acute kidney injury Oxidative stress Rat Human tubular epithelial cell

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Identification of STAT5B as a biomarker for an early diagnosis ofendometrial carcinoma

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BIOCELL 2023年第10期47卷 2283-2300页

作者： XUELIAN CHEN YUNZHENG ZHANG JUNJIAN HE YIBING LI Chunliu Maternity Hospital District of Dalian Women and Children Medical center Dalian116033China Department of Obstetrics and Gynecology The General Hospital of Northern Theater CommandShenyang110016China Department of Gynecology Shaanxi Provincial People’s HospitalXi’an710068China Department of Obstetrics and Gynecology The Second Hospital of Dalian Medical UniversityDalian116023China

Background: The late detection of endometrial carcinoma (EC) at an advanced stage often results in a poorpatient prognosis. It is hence important to identify reliable biomarkers to facilitate early detection of EC. Signaltransducer and activator of transcription (STAT) family members play an important role in several tumors, however,their impact on EC development and progression remains unclear. Methods: Machine learning methods were used toinvestigate the importance of STAT5B in EC. Results: Hence, we explored the UALCAN data mining platform andfound that while STAT1 and STAT2 were upregulated, STAT5A, STAT5B, and STAT6 were downregulated in *** high expression of STAT5B and STAT6 predicted favorable clinical outcomes, whereas the increased expressionof STAT1 and STAT2 predicted poor clinical outcomes. Subsequent pathway enrichment analysis revealed that theSTAT family was mainly involved in apoptosis pathway activation, cell cycle disruption, and epithelial–mesenchymaltransition. Drug sensitivity analysis demonstrated that STAT5A/5B expression was negatively correlated with drugresistance in EC. Further, the expression of STAT5B mRNA and protein was correlated with severalclinicopathological characteristics. Tumor Immune Estimation Resource (TIMER) analysis revealed that STAT5Bexpression was positively correlated with the abundance of infiltrating CD8+ T cells and neutrophils while its copynumber variation was associated with the overall immune cell infiltration. The data on the correlations betweenSTAT5B expression and related genes in uterine corpus endometrial carcinoma (UCEC) in cBio Cancer Portalshowed the closest correlation of STAT5B expression with that of KIAA0753 (also known as moonraker and OFIP),followed by COL27A1 in EC. Pathway enrichment analysis further showed that STAT5B-related genes were involvedin the mitogen-activated protein kinase (MAPK) and Ras signaling pathways. Conclusion: Collectively, our findingsprovided new insights into the role

关键词： STAT5B Endometrial Carcinoma Signal transducer and activator of transcription

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Green development of western cities from the perspective of informatization and greenization

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Ecological Economy 2016年第3期9卷 227-237页

作者： LIU Ying-xiao WANG Heng Institute of Gui-An New District Research center for Western Modernization Research Base of Humanities and Social Science at Universities of Guizhou Province Guizhou provincial Collaborative Innovation center For Poverty and Development of Poverty-Stricken area

The Fifth Plenary meeting of the 18 th Central Committee put forward the idea of creative green development, which become the guide which is important concept of economic and social development in our country in the future. The contradiction between resource environment and economic development is becoming more and more outstanding with the speeding up of urbanization process in western region. The coming of big data and information age, makes the wisdom of ecological city construction to be the mainstream direction of urban development, and green development also become the core of the ecological city wisdom. In ecological concept gradually deepening of the information age, the construction of smart ecological city becomes the mainstream direction, green development also becomes the core of the smart ecological city. The path and strategies of promoting green development of western cities based on the smart ecological cities were presented in this paper, through the analysis of the background of the smart ecological city construction, the calculation of the environment carrying capacity and the ecological footprint, as well as the target for the sustainable green development of the western cities.

关键词： western cities green development smart ecological city ecological footprint informatization and greenization

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Aloin ameliorates cecal ligation and puncture-induced sepsis in mice by attenuating inflammation and modulating gut microbiota

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Food Science and Human Wellness 2024年

作者： Jingqian Su Jianbin Xiao Siyuan Chen Heng Zhao Xiaoni Zhang Zhihua Feng Kunsen Chen Biyun Guan Wenzhi Chen Youqiang Chen Duo Chen Qi Chen Fujian Key Laboratory of Innate Immune Biology， Biomedical Research center of South China， College of Life Science， Fujian Normal University The Public Service Platform for Industrialization Development Technology of Marine Biological Medicine and Products of the State Oceanic Administration， Fujian Key Laboratory of Special Marine Bioresource Sustainable Utilization， Southern Institute of Oceanography， College of Life Science， Fujian Normal University

Most Aloe species are used as new food or functional food ingredient. Even though widely known for its health benefits， the anti-inflammatory effects and underlying mechanisms of Aloin (Alo)， an anthraquinone compound isolated from plant species of the genus Aloe， remain unidentified. Here， we investigated the protective effects of Alo against cecal ligation and puncture (CLP)-induced sepsis and microflora in mice. Alo significantly improved CLP-induced sepsis and the survival rate of septic mice， downregulated the expression of proinflammatory factors， and decreased the infiltration of inflammatory cells in tissues. Alo upregulated the proportion of peritoneal macrophages， reduced the number of peritoneal bacteria， decreased the content of short-chain fatty acids and bile acids in the abdominal cavity， and suppressed TLR-2/4/NF-κB/NLRP3/Caspase-1/3/8 signaling. Furthermore， Alo altered the composition of the microbiome and promoted the growth of Lactobacillus， which showed a stronger anti-inflammatory effect. Whole-genome analysis identified the genes Saa3， Il10， Fpr1， and Eif4a1 associated with the protective effects of Alo in mice with CLP-induced sepsis. Overall， our results provide novel insights into the therapeutic potential and mechanism of action of Alo in the treatment of sepsis.

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Reyanning Mixture on Asymptomatic or Mild SARS-CoV-2 Infection in Children and Adolescents:A Randomized Controlled Trial

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中国结合医学杂志:英文版 2023年第10期29卷 867-874页

作者： XU Xiang-ru ZHOU Shuang JIN Guo-qiang WU Hong-ze LI Jin-hua ZHOU Jing PENG Wei ZHANG Wen SUN Ding FANG Bang-jiang Department of Emergency Longhua Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai200032China Acupuncture and Massage College Shanghai University of Traditional Chinese MedicineShanghai201203China Department of health Management The First Affiliated Hospital of Nanchang UniversityNanchang330006China Jiangxi provincial Traditional Chinese Medicine Nephropathy Clinical Research center Jiujiang Hospital of Traditional Chinese MedicineJiujiangJiangxi Province332099China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Nanchang UniversityNanchang330006China Institute of Critical Care Shanghai University of Traditional Chinese MedicineShanghai200032China

Objective: To assess the effect and safety of Reyanning Mixture(RYN) in treating asymptomatic or mild severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) infection in children and adolescents. Methods: This is a prospective, open-label, randomized control ed trial. Patients aged 1–17 years and diagnosed with asymptomatic or mild coronavirus disease-2019(COVID-19) were assigned to an intervention group(RYN plus standard care) and a control group(standard care) according to a randomization list. The primary outcomes were SARS-Co V-2 negative conversion time. Secondary outcomes included negative conversion rate on days 3 and 7, hospital length of stay, symptom relief rate, new-onset symptoms of asymptomatic infected patients, and progressive disease rate. The cycle threshold(Ct) values of ORF1ab or N genes were also tested. Results: A total of 214 patients in the intervention group and 217 in the control group were analyzed. The SARS-CoV-2 negative conversion time was significantly shortened in the intervention group [5 days(interquartile range(IQR): 5–6) vs. 7 days(IQR: 6–7), P0.05). Symptoms of cough were significantly improved(82.2% vs. 70.0%, P=0.02) and wheezing was significantly reduced(0.7% vs. 12.9%, P<0.01) in the intervention group compared with the control group. During the trial, no disease progression or serious adverse events were reported. Conclusion: Add

关键词： coronavirus diseases-2019 severe acute respiratory syndrome coronavirus 2 Omicron children Reyanning Mixture randomized controlled trial Chinese medicine

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Direct DNA sequencing of FBN1 gene associated with marfan's syndrome in two Chinese families

Direct DNA sequencing of FBN1 gene associated with marfan's ...

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2016年浙江省眼科学学术年会

作者：吴梦晗鱼音慧姚克 Eye center Second Affiliated Hospital of Zhejiang University School of Medicine Zhejiang provincial Key Lab of Ophthalmology

Background:Aimed to identify the disease-causing mutation which is responsible for the presence of marfan’s syndrome in two Chinese ***:Blood samples were collected from all individuals for DNA *** DNA sequencing of ...

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