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Signal Transduction and Targeted Therapy 2024年第3期9卷 1174-1185页

作者： Sumit Bhattacharyya Joanne K.Tobacman Jesse Brown va medical center and University of Illinois at chicago ChicagoIL 60612USA

Immunostaining in lungs of patients who died with CovID-19 infection showed increased intensity and distribution of chondroitin sulfate and decline in N-acetylgalactostamine-4-sulfatase(Arylsulfatase B;ARSB).To explain these findings,human small airway epithelial cells were exposed to the SARS-CoV-2 spike protein receptor binding domain(SPRBD)and transcriptional mechanisms were ***-p38 MAPK and phospho-SMAD3 increased following exposure to the SPRBD,and their inhibition suppressed the promoter activation of the carbohydrate sulfotransferases CHST15 and CHST11,which contributed to chondroitin sulfate *** in ARSB was mediated by phospho-38 MAPK-induced N-terminal Rb phosphorylation and an associated increase in Rb-E2F1 binding and decline in E2F1 binding to the ARSB *** increases in chondroitin sulfotransferases were inhibited when treated with phospho-p38-MAPK inhibitors,SMAD3(SIS3)inhibitors,as well as antihistamine desloratadine and antibiotic *** the mouse model of carrageenan-induced systemic inflammation,increases in phosphop38 MAPK and expression of CHST15 and CHST11 and declines in DNA-E2F binding and ARSB expression occurred in the lung,similar to theobserved effects in this SPRBD model of COVID-19 *** accumulation of chondroitin sulfates is associated with fibrotic lung conditions and diffuse alveolar damage,increased attention to p38-MAPK inhibition may be beneficial in amelioratingCovid-19infections.

关键词： ACE2 lung inhibited

Metabolites and micronutrition in modulating amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第6期19卷 1183-1184页

作者： Katerina Claud Jun Sun Department of Medicine University of Illinois ChicagoChicagoILUSA Jesse Brown va medical center chicago ChicagoILUSA

Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative *** majority of ALS cases are sporadic with only about 20%of familial *** in families with genetic predisposition,there is significant phenotypic va... 详细信息

关键词： sclerosis amyotrophic cases

Pretreating and normalizing metabolomics data for statistical analysis

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Genes & Diseases 2024年第3期11卷 188-205页

作者： Jun Sun Yinglin Xia Division of Gastroenterology and Hepatology Department of MedicineDepartment of Microbiology/ImmunologyUIC Cancer CenterUniversity of Illinois ChicagoJesse Brown VA Medical Center Chicago(537)ChicagoIL 60612USA Division of Gastroenterology and Hepatology Department of MedicineUniversity of Illinois ChicagoChicagoIL 60612USA

Metabolomics as a research field and a set of techniques is to study the entire small molecules in biological *** is emerging as a powerful tool generally for pre-cision ***,integration of microbiome and metabolome has revealed the mechanism and functionality of microbiome in human health and ***,metabo-lomics data are very ***/pretreating and normalizing procedures on metabolomics data are usually required before statistical *** this review article,we comprehensively review various methods that are used to preprocess and pretreat metabolo-mics data,including MS-based data and NMR-based data preprocessing,dealing with zero and/or missing values and detecting outliers,data normalization,data centering and scaling,data *** discuss the advantages and limitations of each *** choice for a suitable preprocessing method is determined by the biological hypothesis,the characteristics of the data set,and the selected statistical data analysis *** then provide the perspective of their applications in the microbiome and metabolome research.

关键词： Data centering and scaling Data normalization Data transformation Missing values MS-Baseddata preprocessing NMRData preprocessing Outliers Preprocessing/pretreatment

Microbiome and intestinal pathophysiology in post-acute sequelae of COVID-19

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Genes & Diseases 2024年第3期11卷 220-231页

作者： Jilei Zhang Yongguo Zhang Yinglin Xia Jun Sun Division of Gastroenterology and Hepatology Department of MedicineUniversity of Ilinois ChicagoIL60612USA Uic Cancer center Department of Microbiology and ImmunologyUniversity of Ilinois ChicagoChicagoIL60612USA Jesse Brown va medical center ChicagoIL60612USA

Long CoVID,also known for post-acute sequelae of CovID-19,describes the people who have the signs and symptoms that continue or develop after the acute coviD-19 *** CovID patients suffer from an inflammation or host responses towards the virus approx-imately 4 weeks after initial infection with the SARS CoV-2 virus and continue for an unchar-acterized *** infected with CovID-19 before could experience long-CcovID conditions,including the patients who were infected with SARS CoV-2 virus confirmed by tests and those who never knew they had an infection *** with long CoviD may experience health problems from different types and combinations of symptoms over time,such as fa-tigue,dyspnea,cognitive impairments,and gastrointestinal(Gl)symptoms(e.g.,nausea,vom-iting,diarrhea,decreased or loss of appetite,abdominal pain,and dysgeusia).The critical role of the microbiome in these Gl symptoms and long CovID were reported in clinical patients and experimental ***,we provide an overall view of the critical role of the Gl tract and microbiome in the development of long COVID,including the clinical Gl symptoms in patients,dysbiosis,viral-microbiome interactions,barrier function,and inflammatory bowel disease patients with long *** highlight the potential mechanisms and possible treatment based on Gl health and ***,we discuss challenges and future direction in the long CoVID clinic and research.

关键词： Gastrointestinal symptoms Gl tract Gut microbiome Inflammatorybowel diseases Intestinal barrier Long CoVID Metabolites Tight junctions

Emergency department management of acute agitation in the reproductive age female and pregnancy

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World Journal of Emergency Medicine 2024年第2期15卷 83-90页

作者： Ariella Gartenberg Kayla Levine Alexander Petrie Department of Emergency Medicine Jacobi Medical Center and Montefiore Medical CenterNY 10461USA Department of Psychiatry and Behavioral Sciences Albert Einstein College of Medicine and Montefiore Medical CenterNY 10461USA Department of Emergency Medicine Jacobi Medical Center and North Central Bronx HospitalNY 10461USA

BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and *** safety of psychotropic medications in the reproductive age female has not been well *** review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during ***:A literature review was conducted to explore the pathophysiology of acute agitation and devise a preferred treatment plan for ED management of acute agitation in the reproductive age or pregnant ***:While nonpharmacological management is preferred,ED visits for agitation often require medical *** should be selected based on the etiology of agitation and the clinical setting to avoid major adverse *** effects are common in pregnant *** mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse *** moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on *** has become the most frequently utilized psychotropic for agitation during *** generation psychotropics are often utilized as second-line therapy,including *** and ketamine have demonstrated adverse fetal ***:While randomized control studies cannot be ethically conducted on pregnant patients requiring sedation,animal models and epidemiologic studies have demonstrated the effects of psychotropic medication exposure in *** the fetal risk associated with multiple doses of psychotropic medications remains unknown,weighing the risks and benefits of each agent,while utilizing the lowest effective dose remains critical in the treatment of acute agitation within the EDs.

关键词： Agitation Pregnancy Haloperidol Ketamine Benzodiazepines

Current research status of transarterial therapies for hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第9期16卷 3752-3760页

作者： Mao-Ting Zhou Peng Zhang Qi Mao Xiao-Qin Wei Lin Yang Xiao-Ming Zhang Department of Radiology Interventional Medical CenterScience and Technology Innovation CenterThe Affiliated Hospital of North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina School of medical Imaging North Sichuan Medical CollegeNanchong 637000Sichuan ProvinceChina

With continuous advancements in interventional radiology,considerable progress has been made in transarterial therapies for hepatocellular carcinoma(HCC)in recent years,and an increasing number of research papers on transarterial therapies for HCC have been *** this editorial,we comment on the article by Ma et al published in the recent issue of the World Journal of Gastrointestinal Oncology:“Efficacy and predictive factors of transarterial chemoembolization combined with lenvatinib plus programmed cell death protein-1 inhibition for unresectable HCC”.We focus specifically on the current research status and future directions of transarterial *** the future,more studies are needed to determine the optimal transarterial local treatment for *** the emergence of checkpoint immunotherapy modalities,it is expected that the results of trials of transarterial local therapy combined with systemic therapy will bring new hope to HCC patients.

关键词： Hepatocellular carcinoma Transarterial therapies Transarterial chemoembolization Hepatic artery infusion chemotherapy Transarterial embolization Transarterial radioembolization

Canonical and noncanonical Wnt signaling: Multilayered mediators, signaling mechanisms and major signaling crosstalk

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Genes & Diseases 2024年第1期11卷 103-134页

作者： Kevin Qin Michael Yu Jiaming Fan Hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui Wang Annie Wang Zander Schwartz Jeffrey Hong Lily Song William Wagstaff Rex C.Haydon Hue H.Luu Sherwin H.Ho Jason Strelzow Russell R.Reid Tong-Chuan He Lewis L.Shi chicago medical School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School of Biomedical Engineering Vanderbilt UniversityNashvilleTN 37235USA Laboratory of Craniofacial Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signaling plays a major role in regulating cell proliferation and *** Wnt ligands are a family of 19 secreted glycoproteins that mediate their signaling effects via binding to Frizzled receptors and LRP5/6 coreceptors and transducing the signal either throughβ-catenin in the canonical pathway or through a series of other proteins in the nonca-nonical *** of the individual components of both canonical and noncanonical Wnt signaling have additional functions throughout the body,establishing the complex interplay between Wnt signaling and other signaling *** crosstalk between Wnt signaling and other pathways gives Wnt signaling a vital role in many cellular and organ ***-regulation of this system has been implicated in many diseases affecting a wide array of organ systems,including cancer and embryological defects,and can even cause embryonic *** complexity of this system and its interacting proteins have made Wnt signaling a target for many therapeutic ***,both stimulatory and inhibitory treatments come with potential risks that need to be *** review synthesized much of the current knowl-edge on the Wnt signaling pathway,beginning with the history of Wnt *** thoroughly described the different variants of Wnt signaling,including canonical,noncanonical Wnt/PCP,and the noncanonical Wnt/Ca2+*** description involved each of its components and their involvement in other cellular ***,this review explained the various other pathways and processes that crosstalk with Wnt signaling.

关键词： β-catenin Canonical Wnt Noncanonical Wnt Signal transduction Signaling crosstalk

肠上皮细胞Axin1缺失可调节肠道微生态预防结肠炎

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Engineering 2024年第4期35卷 241-256页

作者： Shari Garrett Yongguo Zhang Yinglin Xia Jun Sun Division of Gastroenterology and Hepatology Department of MedicineUniversity of Illinois ChicagoChicagoIL 60612USA Department of Microbiology and Immunology College of MedicineUniversity of Illinois ChicagoChicagoIL 60612USA Cancer center University of Illinois ChicagoChicagoIL 60612USA Jesse Brown va medical center ChicagoIL 60612USA

Intestinal homeostasis is maintained by specialized host cells and the gut ***/β-catenin signaling is essential for gastrointestinal development and homeostasis,and its dysregulation has been implicated in inflammation and colorectal ***1 negatively regulates activated Wnt/β-catenin signaling,but little is known regarding its role in regulating host–microbial interactions in health and ***,we aim to demonstrate that intestinal Axin1 determines gut homeostasis and host response to ***1 expression was analyzed in human inflammatory bowel disease *** explore the effects and mechanism of intestinal Axin1 in regulating intestinal homeostasis and colitis,we generated new mouse models with Axin1 conditional knockout in intestinal epithelial cell(IEC;Axin1^(ΔIEC))and Paneth cell(PC;Axin1^(ΔPC))to compare with control(Axin1^(LoxP);LoxP:locus of X-over,P1)*** found increased Axin1 expression in the colonic epithelium of human inflammatory bowel disease(IBD).Axin1^(ΔIEC) mice exhibited altered goblet cell spatial distribution,PC morphology,reduced lysozyme expression,and enriched Akkermansia muciniphila(***).The absence of intestinal epithelial and PC Axin1 decreased susceptibility to dextran sulfate sodium(DSS)-induced colitis in ***1^(ΔIEC) and Axin1^(ΔPC)mice became more susceptible to DSS-colitis after cohousing with control *** with *** reduced DSS-colitis *** treatment did not change the IEC proliferation in the Axin1Loxp ***,the intestinal proliferative cells in Axin1^(ΔIEC)mice with antibiotic treatment were reduced compared with those in Axin1^(ΔIEC) mice without *** data suggest non-colitogenic effects driven by the gut *** conclusion,we found that the loss of intestinal Axin1 protects against colitis,likely driven by epithelial Axin1 and Axin1-associated *** study demonstrates a novel role of Axin1 in mediating intes

关键词： Axin1 Bacteria Microbiome inflammation Inflammatory bowel disease Immunity Microbiome Paneth cells Akkermansia muciniphila Wnt

The evolving roles of Wnt signaling in stem cell proliferation and differentiation, the development of human diseases, and therapeutic opportunities

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Genes & Diseases 2024年第3期11卷 155-187页

作者： Michael Yu Kevin Qin Jiaming Fan Guozhi Zhao Piao Zhao Wei Zeng Connie Chen Annie Wang Yonghui Wang jiamin Zhong Yi Zhu William Wagstaff Rex C.Haydon Hue H.Luu Sherwin Ho Michael J.Lee Jason Strelzow Russell R.Reid Tong-Chuan He School of Medicine Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Molecular Oncology Laboratory Department of Orthopedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key Laboratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Department of Orthopedic Surgery The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China Department of Orthopaedic Surgery Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China Laboratory of Craniofacial Suture Biology and Development Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA Department of Neurology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China

The evolutionarily conserved Wnt signaling pathway plays a central role in develop-ment and adult tissue homeostasis across *** proteins are secreted,lipid-modified signaling molecules that activate the canonical(β-catenin dependent)and non-canonical(β-catenin independent)Wnt signaling *** behaviors such as proliferation,differ-entiation,maturation,and proper body-axis specification are carried out by the canonical pathway,which is the best characterized of the known Wnt signaling *** signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various *** includes but is not limited to embryonic,hematopoietic,mesenchymal,gut,neural,and epidermal stem *** signaling has also been implicated in tumor cells that exhibit stem cell-like *** signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone *** surprisingly,aberrant Wnt signaling is also associated with a wide variety of diseases,including *** of Wnt pathway members in cancer can lead to unchecked cell proliferation,epithelial-mesenchymal transition,and ***,advances in the understand-ing of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt *** with a brief overview of the mechanisms of canonical and non-canonical Wnt,this review aims to summarize the cur-rent knowledge of Wnt signaling in stem cells,aberrations to the Wnt pathway associated with diseases,and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

关键词： β-Catenin Cancer Canonical Wnt Disease Non-canonical Wnt Stem cells Targeted therapy Wnt signaling

Syrosingopine,an anti-hypertensive drug and lactate transporter(MCT1/4)inhibitor,activates hepatic stellate cells and exacerbates liver fibrosis in a mouse model

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Genes & Diseases 2024年第4期11卷 28-30页

作者： Meichun Guo Yannian Gou Xiangyu Dong Jiamin Zhong Aohua Li Ailing Hao Tongchuan He Jiaming Fan Ministry of Education Key Laboratory of Diagnostic Medicine and the School of Laboratory Diagnostic MedicineChongqing Medical UniversityChongqing 400016China Molecular Oncology Laboratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA

Syrosingopine is an anti-hypertensive drug and can cause high intracellular lactate levels and end-product inhibition of lactate dehydrogenase by inhibiting the lactate transporters MCT1 and *** studies have shown that syrosingopine plays an essential role in the process of glycolytic blockade,ATP depletion,and cell death in cancer due to high intracellular levels of lactate.

关键词： hypertensive MCT1 drug