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Identification of fangchinoline as a broad-spectrum enterovirus inhibitor through reporter virus based high-content screening

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Virologica Sinica 2024年第2期39卷 301-308页

作者： Qiu-Yan Zhang Jia-Qi Li Qi Li Yang Zhang Zhe-Rui Zhang Xiao-Dan Li Hong-Qing Zhang Cheng-Lin Deng Feng-Xia Yang Yi Xu Bo Zhang The Joint Center of Translational Precision medicine Department of Infections and DiseasesGuangzhou Institute of PediatricsGuangzhou Women and Children's Medical CenterGuangzhou510623China Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan430071China University of Science and Technology of China Department of Life Sciences and MedicineHefei230026China Hunan Normal University School of MedicineChangsha410081China

Hand,foot,and mouth disease(HFMD)is a common pediatric illness mainly caused by enteroviruses,which are important human pathogens.Currently,there are no available antiviral agents for the therapy of enterovirus infection.In this study,an excellent high-content antiviral screening system utilizing the EV-A71-eGFP reporter virus was developed.Using this screening system,we screened a drug library containing 1042 natural compounds to identify potential EV-A71 inhibitors.Fangchinoline(FAN),a bis-benzylisoquinoline alkaloid,exhibits potential inhibitory effects against various enteroviruses that cause HFMD,such as EV-A71,CV-A10,CV-B3 and CV-A16.Further investigations revealed that FAN targets the early stage of the enterovirus life cycle.Through the selection of FAN-resistant EV-A71 viruses,we demonstrated that the VP1 protein could be a potential target of FAN,as two mutations in VP1(E145G and V258I)resulted in viral resistance to FAN.Our research suggests that FAN is an efficient inhibitor of EV-A71 and has the potential to be a broad-spectrum antiviral drug against human enteroviruses.

关键词： Hand,foot,and mouth disease(HFMD) Enterovirus EV-A71 High-content screening Fangchinoline(FAN)

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Combined Treatment with Bojungikgi-tang(Buzhong Yiqi Decoction) and Riluzole Attenuates Cell Death in TDP-43-Expressing Cells

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Chinese Journal of Integrative medicine 2024年第7期30卷 616-622页

作者： Eun Jin Yang Department of KM Science Research Korea Institute of Oriental Medicine

Objective: To examine the effect of combined treatment with Bojungikgi-tang(BJIGT, Buzhong Yiqi Decoction) and riluzole(RZ) in transactive response DNA-binding protein 43(TDP-43) stress granule(SG) cells, a amyotrophic lateral sclerosis(ALS) cell line using transcriptomic and molecular techniques. Methods: TDP-43 SG cells were pretreated with BJIGT(100 μg/mL), RZ(50 μmol/L), and combined BJIGT(100 μg/mL)/RZ(50 μmol/L) for 6 h before treatment with lipopolysaccharide(LPS, 200 μmol/L). Cell viability assay was performed to elucidate cell toxicity in TDP-43 SC cells using a cell-counting kit-8(CCK8) assay kit. The expression levels of cell death-related proteins, including Bax, caspase 1, cleaved caspase 3 and DJ1 in TDP-43 SG cells were examined by Western blot analysis. The autophagy-related proteins, including pmTOR/mTOR, LC3b, P62, ATG7 and Bcl-2-associated athanogene 3(Bag3) were investigated using immunofluorescence and immunoblotting assays. Results: Cell viability assay and Western blot analysis showed that combined treatment with BJIGT and RZ suppressed LPS-induced cell death and expression of cell death-related proteins, including Bax, caspase 1, and DJ1(P<0.05 or P<0.01). Immunofluorescence and immunoblotting assays showed that combined treatment with BJIGT and RZ reduced LPS-induced formation of TDP-43 aggregates and regulated autophagy-related protein levels, including p62, light chain 3b, Bag3, and ATG7, in TDP-43-expressing cells(P<0.05 or P<0.01). Conclusion: The combined treatment of BJIGT and RZ might reduce inflammation and regulate autophagy dysfunction in TDP-43-induced ALS.

关键词： Bojungikgi-tang Buzhong Yiqi Decoction transactive response DNA-binding protein 43 autophagy oxidative stress amyotrophic lateral sclerosis

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Current status of Mycoplasma pneumoniae infection in China

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World Journal of pediatrics 2024年第1期20卷 1-4页

作者： Chao Yan Guan-Hua Xue Han-Qing Zhao Yan-Ling Feng Jing-Hua Cui Jing Yuan Department of Bacteriology Capital Institute of PediatricsNo.2Yabao RoadBeijing 100020People's Republicof China

Mycoplasma pneumoniae(M.pneumoniae)is one of the most important pathogens for community-acquired pneumonia worldwide,especially in children and adolescents[1,2].M.pneumoniae is easily transmitted through droplets or direct contact in densely populated,enclosed,or poorly ventilated environments.The incubation period is 1-3 weeks,and it is contagious from the incubation period to a few weeks after clinical symptom relief.M.pneumoniae infection can occur in any season,and there are differences in the epidemic seasons among regions in China[3].The most suitable culture temperature for M.pneumoniae is between 35℃C and 37 C,and therefore,hot weather may make it survive longer in the environment and spread further.Infection is more common in autumn and winter in northern China,while it is more prevalent in summer and autumn in southern China.

关键词： winter weather autumn

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Differences in vascular endothelial function and serum proteome between obese people with phlegm-dampness constitution and balanced constitution

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Journal of Traditional Chinese medicine 2024年第1期44卷 188-196页

作者： ZHU Linghui SUN Ziwei GUAN Yuanyuan LIU Meiyi ZHENG Yi YU Ruoxi WANG Qi LI Lingru School of Chinese medicine Beijing University of Chinese MedicineBeijing 102488China National institute of TCM Constitution and Preventive medicine Beijing University of Chinese MedicineBeijing 100029China

OBJECTIVE:To evaluate the extent of vascular endothelial dysfunction and preliminary identify serum protein biomarkers associated with obese individuals at risk for cardiovascular disease(CVD).METHODS:Fifteen obese volunteers with the phlegmdampness constitution or balanced constitution were recruited for this study respectively.The clinical baseline data was collected,and the vascular endothelial function was evaluated using the EndoPAT?.Blood samples were collected for the serum proteome analysis.The differences in the serum protein expression levels between the two groups were detected and the protein interaction network analysis,correlation analysis,receiver operating characteristic(ROC)curve analysis,and random forest model investigation were conducted.RESULTS:There were no statistical differences found in the baseline data.For vascular endothelial function,the reactive hyperemia index(RHI)of the phlegm-dampness constitution obese group was significantly lower than that of the balanced constitution obese group(1.46±0.30 vs 2.82±0.78,P<0.0001),indicating vascular endothelial dysfunction.There are 66 differentially expressed serum proteins between the two groups.apolipoprotein A2(Apo A2),angiotensin-converting enzyme 2(ACE-2),interleukin-33(IL-33),and forkhead box P3(FoxP3)showed significant differences and area under curve values of their ROC curves were greater than 0.7 and correlated significantly with RHI.CONCLUSION:Vascular endothelial dysfunction was present in the phlegm-dampness constitution obese group.Thus,alterations in the expression levels of key serum proteins,including Apo A2,ACE-2,IL-33,and Fox P3 could serve as potential biomarkers in the obese population at risk of CVD.

关键词： obesity phlegm-dampness constitution vascular endothelial function proteome reactive hyperemia index

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Prenatal and postnatal factors associated with sudden infant death syndrome:an umbrella review of meta-analyses

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World Journal of pediatrics 2024年第5期20卷 451-460页

作者： Tae Hyeon Kim Hyeri Lee Selin Woo Hayeon Lee Jaeyu Park Gullume Fond Laurent Boyer Jong Woo Hahn Jiseung Kang Dong Keon Yon Department of medicine Kyung Hee University College of MedicineSeoulSouth Korea Center for Digital Health Medical Science Research InstituteKyung Hee University College of MedicineSeoulSouth Korea Department of Regulatory Science Kyung Hee UniversitySeoulSouth Korea Department of Biomedical Engineering Kyung Hee UniversityYonginSouth Korea CEReSS-Health Service Research and Quality of Life Center Assistance Publique des Hôpitaux de MarseilleAix-Marseille UniversityMarseilleFrance Department of pediatrics Seoul National University College of MedicineSeoulSouth Korea Department of pediatrics Seoul National University Bundang HospitalSeongnamSouth Korea Department of Anesthesia Critical Care and Pain MedicineMassachusetts General Hospital14913th StreetRoom 4140CharlestownBostonMAUSA Division of Sleep medicine Harvard Medical SchoolBostonMAUSA Department of pediatrics Kyung Hee University Medical CenterKyung Hee University College of Medicine23 Kyungheedae-roDongdaemun-guSeoul02447South Korea Department of Precision medicine Kyung Hee University College of MedicineSeoulSouth Korea

Background Comprehensive quantitative evidence on the risk and protective factors for sudden infant death syndrome(SIDS)effects is lacking.We investigated the risk and protective factors related to SIDS.Methods We conducted an umbrella review of meta-analyses of observational and interventional studies assessing SIDS-related factors.PubMed/MEDLINE,Embase,EBSCO,and Google Scholar were searched from inception until January 18,2023.Data extraction,quality assessment,and certainty of evidence were assessed by using A Measurement Tool Assessment Systematic Reviews 2 following PRISMA guidelines.According to observational evidence,credibility was graded and classified by class and quality of evidence(CE;convincing,highly suggestive,suggestive,weak,or not significant).Our study protocol was registered with PROSPERO(CRD42023458696).The risk and protective factors related to SIDS are presented as equivalent odds ratios(eORs).Results We identified eight original meta-analyses,including 152 original articles,covering 12 unique risk and protective factors for SIDS across 21 countries/regions and five continents.Several risk factors,including prenatal drug exposure[eOR=7.84(95%CI=4.81–12.79),CE=highly suggestive],prenatal opioid exposure[9.55(95%CI=4.87–18.72),CE=suggestive],prenatal methadone exposure[9.52(95%CI=3.34–27.10),CE=weak],prenatal cocaine exposure[4.38(95%CI=1.95–9.86),CE=weak],prenatal maternal smoking[2.25(95%CI=1.95–2.60),CE=highly suggestive],postnatal maternal smoking[1.97(95%CI=1.75–2.22),CE=weak],bed sharing[2.89(95%CI=1.81–4.60),CE=weak],and infants found with heads covered by bedclothes after last sleep[11.01(95%CI=5.40–22.45),CE=suggestive],were identified.On the other hand,three protective factors,namely,breastfeeding[0.57(95%CI=0.39–0.83),CE=non-significant],supine sleeping position[0.48(95%CI=0.37–0.63),CE=suggestive],and pacifier use[0.44(95%CI=0.30–0.65),CE=weak],were also identified.Conclusions Based on the evidence,we propose several risk and protective factors for SIDS.This study suggests the need

关键词： Infant Protective factor Risk factor Sudden infant death syndrome Umbrella review

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Childhood sleep:physical,cognitive,and behavioral consequences and implications

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World Journal of pediatrics 2024年第2期20卷 122-132页

作者： Jianghong Liu Xiaopeng Ji Susannah Pitt Guanghai Wang Elizabeth Rovit Terri Lipman Fan Jiang School of Nursing University of Pennsylvania418 Curie Blvd.Room 424Claire M.Fagin HallPhiladelphiaPA 19104USA College of Health Sciences University of DelawareNewarkDE 19716USA Geisinger Commonwealth School of medicine ScrantonPA 18510USA Pediatric Translational medicine institute Department of Developmental and Behavioral PediatricsSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background Sleep problems in children have been increasingly recognized as a major public health issue.Previous research has extensively studied and presented many risk factors and potential mechanisms for children’s sleep problems.In this paper,we aimed to identify and summarize the consequences and implications of child sleep problems.Data sources A comprehensive search for relevant English language full-text,peer-reviewed publications was performed focusing on pediatric sleep studies from prenatal to childhood and adolescence in a variety of indexes in PubMed,SCOPUS,and Psych Info published in the past two decades.Both relevant data-based articles and systematic reviews are included.Results Many adverse consequences are associated with child sleep deficiency and other sleep problems,including physical outcomes(e.g.,obesity),neurocognitive outcomes(e.g.,memory and attention,intelligence,academic performance),and emotional and behavioral outcomes(e.g.,internalizing/externalizing behaviors,behavioral disorders).Current prevention and intervention approaches to address childhood sleep problems include nutrition,exercise,cognitive–behavioral therapy for insomnia,aromatherapy,acupressure,and mindfulness.These interventions may be particularly important in the context of coronavirus disease 2019.Specific research and policy strategies can target the risk factors of child sleep as well as the efficacy and accessibility of treatments.Conclusions Given the increasing prevalence of child sleep problems,which have been shown to affect children’s physical and neurobehavioral wellbeing,understanding the multi-aspect consequences and intervention programs for childhood sleep is important to inform future research direction as well as a public health practice for sleep screening and intervention,thus improving sleep-related child development and health.

关键词： Behavior Child sleep Consequences Implications Neurocognitive Physical Prevention/intervention

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Whole-genome sequencing in medicinal plants:current progress and prospect

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Science China(Life Sciences) 2024年第2期67卷 258-273页

作者： Yifei Pei Liang Leng Wei Sun Baocai Liu Xue Feng Xiwen Li Shilin Chen institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China institute of Herbgenomics Chengdu University of Traditional Chinese MedicineChengdu 611137China Innovative institute of Chinese medicine and Pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137China institute of Agricultural Bioresource Fujian Academy of Agricultural SciencesFuzhou 350003China

Advancements in genomics have dramatically accelerated the research on medicinal plants,and the development of herbgenomics has promoted the“Project of 1K Medicinal Plant Genome”to decipher their genetic code.However,it is difficult to obtain their high-quality whole genomes because of the prevalence of polyploidy and/or high genomic heterozygosity.Whole genomes of 123 medicinal plants were published until September 2022.These published genome sequences were investigated in this review,covering their classification,research teams,ploidy,medicinal functions,and sequencing strategies.More than 1,000 institutes or universities around the world and 50 countries are conducting research on medicinal plant genomes.Diploid species account for a majority of sequenced medicinal plants.The whole genomes of plants in the Poaceae family are the most studied.Almost 40%of the published papers studied species with tonifying,replenishing,and heat-cleaning medicinal effects.Medicinal plants are still in the process of domestication as compared with crops,thereby resulting in unclear genetic backgrounds and the lack of pure lines,thus making their genomes more difficult to complete.In addition,there is still no clear routine framework for a medicinal plant to obtain a high-quality whole genome.Herein,a clear and complete strategy has been originally proposed for creating a high-quality whole genome of medicinal plants.Moreover,whole genome-based biological studies of medicinal plants,including breeding and biosynthesis,were reviewed.We also advocate that a research platform of model medicinal plants should be established to promote the genomics research of medicinal plants.

关键词： herbgenomics whole genome high throughput sequencing research strategy model species application

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Tryptophan-specific peptide modification through metal-free photoinduced N-H alkylation employing N-aryl glycines

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Chinese Chemical Letters 2024年第6期35卷 316-319页

作者： Jianhui Yin Wenjing Huang Changyong Guo Chao Liu Fei Gao Honggang Hu School of medicine or institute of Translation medicine Shanghai UniversityShanghai 200444China

Tryptophan(Trp)carries a unique heteroaromatic indole side chain and plays a critical role in peptide or protein modification.Herein,we have reported a metal-free photoinduced N-H alkylation strategy using N-aryl glycines for specific modification of tryptophan-containing peptides.The robustness of our approach is demonstrated by its wide substrate scope,excellent isolated yields,as well as almost unobservable side effects.Using this highly efficiently metal-free condition,alkylated Trp-containing peptides can be smoothly assembled.This study provides a reliable and practical tool for the chemo-selective modification of various tryptophan containing oligopeptides.

关键词： Tryptophan Peptide Modification Glycine Photoinduced

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Pien Tze Huang Inhibits Proliferation of Colorectal Cancer Cells through Suppressing PNO1 Expression and Activating p53/p21 Signaling Pathway

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Chinese Journal of Integrative medicine 2024年第6期30卷 515-524页

作者： CAO Liu-jing LIU Li-ya CHEN You-qin HAN Yu-ying WEI Li-hui YAO Meng-ying FANG Yi WU Mei-zhu CHENG Ying Thomas J.Sferra LIU Hui-xin LI Li PENG Jun SHEN A-ling Clinical Research institute the Second Affiliated Hospital&Academy of Integrative MedicineFujian University of Traditional Chinese MedicineFuzhou350122China Fujian Key Laboratory of Integrative medicine in Geriatrics Fujian University of Traditional Chinese MedicineFuzhou350122China Department of pediatrics Case Western Reserve University School of MedicineUH Rainbow Babies and Children’s HospitalClevelandOH44106USA Innovation and Transformation Center Fujian University of Traditional Chinese MedicineFuzhou350122China Department of Health Management Fujian Provincial HospitalShengli Clinical College of Fujian Medical UniversityFuzhou000000China

ObjectiveTo explore the regulatory effect of Pien Tze Huang (PZH) on targeting partner of NOB1 (PNO1) and it’s down-stream mediators in colorectal cancer (CRC) cells.MethodsQuantitative polymerase chain reaction was performed to determine mRNA levels of PNO1, TP53, and CDKN1A. Western blotting was performed to determine protein levels of PNO1, p53, and p21. HCT-8 cells were transduced with a lentivirus over-expressing PNO1. Colony formation assay was used to detect cell survival in PNO1 overexpression of HCT-8 cells after PZH treatment. Cell-cycle distribution, cell viability and cell apoptosis were performed to identify the effect of PNO1 overexpression on cell proliferation and apoptosis of HCT-8 cells after PZH treatment. Xenograft BALB/c nude mice bearing HCT116 cells transduced with sh-PNO1 or sh-Ctrl lentivirus were evaluated. Western blot assay was performed to detect PNO1, p53, p21 and PCNA expression in tumor sections. Terminal deoxynucleotidyl transferase dUTP nick end labling (TUNEL) assay was used to determine the apoptotic cells in tissues.ResultsPZH treatment decreased cell viability, down-regulated PNO1 expression, and up-regulated p53 and p21 expressions in HCT-8 cells (P<0.05). PNO1 overexpression attenuated the effects of PZH treatment, including the expression of p53 and p21, cell growth, cell viability, cell cycle arrest and cell apoptosis in vitro (P<0.05). PNO1 knockdown eliminated the effects of PZH treatment on tumor growth, inhibiting cell proliferation inhibition and apoptosis induction in vivo (P<0.05). Similarly, PNO1 knockdown attenuated the effects of PZH treatment on the down-regulation of PNO1 and up-regulation of p53 and p21 in vivo (P<0.05).ConclusionThe mechanism by which PZH induces its CRC anti-proliferative effect is at least in part by regulating the expression of PNO1 and its downstream targets p53 and p21.

关键词： colorectal cancer Pien Tze Huang Chinese medicine partner of NOB1 proliferation p53/p21 pathway

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Cardiac regeneration: Pre-existing cardiomyocyte as the hub of novel signaling pathway

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Genes & Diseases 2024年第2期11卷 747-759页

作者： Tao Wang Xinzhe Chen Kai Wang Jie Ju Xue Yu Wanpeng Yu Cuiyun Liu Yin Wang institute for Translational medicine The Affiliated Hospital of Qingdao UniversityCollege of MedicineQingdao UniversityQingdaoShandong 266023China College of medicine Qingdao UniversityQingdaoShandong 266023China

In the mammalian heart,cardiomyocytes are forced to withdraw from the cell cycle shortly after birth,limiting the ability of the heart to regenerate and repair.The development of multimodal regulation of cardiac proliferation has verified that pre-existing cardiomyocyte proliferation is an essential driver of cardiac renewal.With the continuous development of genetic lineage tracking technology,it has been revealed that cell cycle activity produces polyploid cardiomyocytes during the embryonic,juvenile,and adult stages of cardiogenesis,but newly formed mononucleated diploid cardiomyocytes also elevated sporadically during myocardial infarction.It implied that adult cardiomyocytes have a weak regenerative capacity under the condition of ischemia injury,which offers hope for the clinical treatment of myocardial infarction.However,the regeneration frequency and source of cardiomyocytes are still low,and the mechanism of regulating cardiomyocyte proliferation remains further explained.It is noteworthy to explore what force triggers endogenous cardiomyocyte proliferation and heart regeneration.Here,we focused on summarizing the recent research progress of emerging endogenous key modulators and crosstalk with other signaling pathways and furnished valuable insights into the internal mechanism of heart regeneration.In addition,myocardial transcription factors,non-coding RNAs,cyclins,and cell cycle-dependent kinases are involved in the multimodal regulation of pre-existing cardiomyocyte proliferation.Ultimately,awakening the myocardial proliferation endogenous modulator and regeneration pathways may be the final battlefield for the regenerative therapy of cardiovascular diseases.

关键词： Cardiac regeneration Cell cycle re-enter Myocardial infarction Pre-existing cardiomyocyte proliferation Regenerative therapy of cardiovascular diseases

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