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Analysis of large datasets for identifying molecular targets in intestinal polyps and metabolic disorders

BIOCELL 2024年第3期48卷 415-429页

作者： SHAN OU YUN XU QINGLAN LIU TIANWEN YANG WEI CHEN XIU YUAN XIN ZUO PENG SHI JIE YAO Department of Gastroenterology The First Affiliated Hospital of Chongqing Medical and Pharmaceutical CollegeChongqingChina

Background:The interrelation between intestinal polyps,metabolic syndrome(MetS),and colorectal cancer(CRC)is a critical area of *** research focuses on pinpointing potential molecular targets to understand the link between intestinal polyp formation,metabolic irregularities,and CRC ***:We examined clinical samples from patients with intestinal polyps coexisting with MetS and compared them with samples from patients with standard intestinal *** sequencing and public database analysis were employed to identify significant pathways and *** targets were then validated through immunohistochemistry(IHC).Following the RNA interference of key target expression,a series of experiments,including the cell counting kit-8 assay,colony formation,wound healing,and Transwell assays,were ***:Comparative analysis revealed 75 up-regulated and 61 down-regulated differentially expressed genes(DEGs)in the MetS polyp group *** *** encyclopedia of genes and genomes(KEGG)pathway enrichment suggested these DEGs were primarily associated with cell cycle and *** with comparative toxicogenomics database(CTD)and the cancer genome atlas(TCGA)databases highlighted 44 key CRC-related *** interaction networks indicated connections of purkinje cell protein 4(PCP4),olfactomedin 1(OLFM1),fibronectin 1(FN1),and transforming growth factor beta 3(TGF-β3)with the mitogen-activated protein kinase(MAPK)*** correlation studies suggested higher risk associations with FN1,PCP4,and TGF-β3,while OLFM1 was identified as a lower risk *** analysis revealed a decrease in OLFM1 in MetS-associated intestinal *** interference with OLFM1 in polyp epithelial cells,there was a significant enhancement in cell proliferation,colony formation,and cell migration and invasion ***:Our study highlights a significant decrease in OLFM1 expression in MetS-associated intestinal

关键词： Colorectal cancer Metabolic syndrome Intestinal polyp OLFM1 Exosome

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Oral delivery of ferroptosis inducers for effective treatment of hepatic fibrosis

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Nano Research 2024年第8期17卷 7621-7630页

作者： Yinglan Yu Shunlong Zhang Yongfeng Xu Hao Shao Lei Luo college of pharmaceutical Sciences Southwest UniversityChongqing 400715China

Liver fibrosis is characterized by the excessive accumulation of extracellular matrix(ECM),which is primarily produced by activated hepatic stellate cells(HSCs).However,effective therapies for hepatic fibrosis are currently *** is a promising anti-fibrotic drug candidate,but its clinical application is hindered by limited ***,we present a novel oral delivery platform that enhances the HSCs uptake of artesunate and induces potent *** platform is vitamin Adecorated nanoparticles encapsulated with *** multifunctional ligand vitamin A interacts with retinol-binding proteins that are highly expressed on the intestinal epithelium to promote transcytosis,highly expressed on the surface of HSCs but lowly expressed in normal *** oral administration,this oral delivery platform enhances transepithelial transport in the intestine,improves drug accumulation in the liver,and continuously increases HSCs uptake of *** drug release in HSCs,artesunate depletes glutathione peroxidase 4 and glutathione,effectively initiating *** vivo experiments demonstrate that this strategy induces pronounced ferroptosis,efficiently relieving liver *** work provides a proof-ofconcept demonstration that an oral delivery strategy for ferroptosis inducers may be beneficial for liver fibrosis treatment.

关键词： liver fibrosis hepatic stellate cells oral delivery intestinal epithelium ferroptosis

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Complications and comorbidities associated with antineoplastic chemotherapy:Rethinking drug design and delivery for anticancer therapy

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Acta Pharmaceutica Sinica B 2024年第7期14卷 2901-2926页

作者： Xiaoman Mao Shuang Wu Dandan Huang Chong Li college of pharmaceutical Sciences Southwest UniversityChongqing 400715China medical Research Institute Southwest UniversityChongqing 400715China School of pharmaceutical Sciences Southern Medical UniversityGuangzhou 510515China

Despite the considerable advancements in chemotherapy as a cornerstone modality in cancer treatment,the prevalence of complications and pre-existing diseases is on the rise among cancer patients along with prolonged survival and aging *** relationships between these disorders and cancer are intricate,bearing significant influence on the survival and quality of life of individuals with cancer and presenting challenges for the prognosis and outcomes of ***,we review the prevailing complications and comorbidities that often accompany chemotherapy and summarize the lessons to learn from inadequate research and management of this scenario,with an emphasis on possible strategies for reducing potential complications and alleviating comorbidities,as well as an overview of current preclinical cancer models and practical advice for establishing bio-faithful preclinical models in such complex context.

关键词： Complications Comorbidities Chemotherapy Preclinical cancer models Drug design Drug delivery

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A Robust N-Terminal Pro-Brain Natriuretic Peptide Assay for Clinical Diagnosis of Heart Failure in Elderly Patients

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Journal of Analysis and Testing 2024年第1期8卷 74-82页

作者： Xue Gong Jiangling Wu Jiajia Zhang Zhongwei Jiang Yi Wang Pu Zhang Engineering Research Center for Biotechnology of Active Substances(Ministry of Education) Chongqing Key Laboratory of Green Synthesis and ApplicationsCollege of ChemistryChongqing Normal UniversityChongqing 401331China chongqing Research Center for pharmaceutical Engineering College of PharmacyChongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory University Town Hospital of Chongqing Medical UniversityChongqing 401331China

Heart failure(HF)is a clinical hallmark of cardiovascular syndrome leading to substantial morbidity,repeated hospitalization,and enormous healthcare *** elderly populations continue to increase,biomarker-guided diagnosis and treatment for age-related cardiac decline have become *** evidence demonstrates that N-terminal proBNP(NT-proBNP)can provide a unique window into the diagnosis and risk stratification with ***,a simple yet robust aptasensor is developed for on-site recognizing the NT-proBNP by its targeting aptamer,thus achieving the accurate diagnosis of *** aptasensing system is prepared by absorbing the fluorophore-labeled aptamer strand onto the graphene oxide(GO),leading to efficient quenching without possible off-site signal *** aptamer strand can specifically identify target NT-proBNP molecules via a versatile conformational transformation,resulting in the desorption of the aptamer-NTproBNP complexes from GO and re-generation fluorescence signal,thus allowing sensitive detection of NT-proBNP in 37 clinical blood *** advantage of the high specificity of aptamer-guaranteed recognitions of NT-proBNP,this aptasensor system readily achieves better diagnostic performance for HF than commercially adopted chemiluminescence immunoassay(Siemens,CLIA)in hospitals in terms of accuracy(89.2%vs 83.8%),specificity(89.5%vs 84.2%),and positive predictive value(88.9%vs 83.3%).This work provides a stable option for the diagnosis and treatment of elderly HF-related diseases inclinics.

关键词： NT-proBNP Graphene oxide Aptamer Heart failure Clinical diagnosis

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Effect of magnetic resonance imaging in liver metastases

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World Journal of Gastroenterology 2024年第1期30卷 112-114页

作者： Xing-Liang Huang Xiao-Dong Wang Zhao-Miao Gong Yan-Feng Zheng Jing-Xin Mao Department of Science and Education Dianjiang People's Hospital of ChongqingChongqing 408399China Department of Science and Industry Chongqing Medical and Pharmaceutical CollegeChongqing 400030China

This letter to the editor is a commentary on a study titled"Liver metastases:The role of magnetic resonance imaging."Exploring a noninvasive imaging evaluation system for the biological behavior of hepatocellular carcinoma(HCC)is the key to achieving precise diagnosis and treatment and improving *** review summarizes the role of magnetic resonance imaging in the detection and evaluation of liver metastases,describes its main imaging features,and focuses on the added value of the latest imaging tools(such as T1 weighted in phase imaging,T1 weighted out of phase imaging;diffusion-weighted imaging,T2 weighted imaging).In this study,I investigated the necessity and benefits of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid for HCC diagnostic testing and prognostic evaluation.

关键词： Liver metastases Magnetic resonance imaging Liver-specific contrast agents Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid Hepatocellular carcinoma Hepatobiliary contrast agents

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Research progress on natural products against hepatocellular carcinoma

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BIOCELL 2024年第6期48卷 905-922页

作者： LINGLI ZHANG YAN LI JINGXIN MAO chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System Chongqing Medical and Pharmaceutical CollegeChongqing400030China Provincial Key Laboratory of pharmaceutical Bioactive Substances School of Life Sciences and BiopharmaceuticalsGuangdong Pharmaceutical UniversityGuangzhou510006China

Hepatocellular carcinoma(HCC)remains a prevalent and challenging malignancy globally,characterized by its numerous causal factors and generally unfavorable *** the relentless pursuit of effective treatment modalities,natural products have emerged as a promising and relatively non-toxic alternative,garnering signiﬁcant *** integration of natural products with contemporary medical research has yielded encouraging therapeutic outcomes in the management of *** review offers a comprehensive overview of the causal factors underlying HCC,and the diverse treatment options available,and highlights the advancements made by natural products in anti-HCC ***,we provide an outline of the various types of natural products,their corresponding nomenclature,target molecules,and mechanisms of action that exhibit anti-HCC *** products are anticipated to play a pivotal role in future comprehensive treatment plans for liver cancer,potentially offering patients improved survival rates and an enhanced quality of life.

关键词： Hepatocellular carcinoma Natural products Targets Research progress Drug

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Silvestrol alleviates glioblastoma progression through ERK pathway modulation and MANBA and NRG-1 expression

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BIOCELL 2024年第7期48卷 1081-1093页

作者： LAN ZHOU QI ZHANG BO TIAN FENG YANG Neurosurgery Department The First Affiliated Hospital of Chongqing Medical and Pharmaceutical CollegeChongqingChina Neurosurgery Department Changdu People’s Hospital of TibetChangduChina

Background:Glioblastoma,a notably malignant tumor within the central nervous system,is distinguished by its aggressive ***,a robust inhibitor of the RNA helicase eukaryotic initiation factor 4A(eIF4A),has shown significant potential as an anticancer ***,the impact of silvestrol on glioblastoma,especially its molecular mechanisms,has not been fully ***:This investigation employed a variety of in vitro assays,such as cell counting kit-8(CCK-8),clonogenic,5-ethynyl-2′-deoxyuridine(EDU),wound healing,and flow cytometry,to evaluate cell cycle progression,apoptosis,cell viability,and *** blot analysis was also performed to study the apoptosis and extracellular regulated kinase(ERK)*** the ERK pathway was inhibited,differentially expressed genes(DEGs)in U87 cells were identified,followed by an analysis of target genes using the gene expression profiling interactive analysis(GEPIA)***:Silvestrol significantly suppressed the proliferation,migration,and colony formation of glioma *** caused cell cycle arrest and enhanced apoptosis in these ***,silvestrol stimulated the ERK pathway,with these effects being reversible by an ERK phosphorylation *** combined with GEPIA,GSCA,UALCAN,TIMER database screened 4 potential drug targets of silvestrol:chromosome 1 open reading frame 226(C1ORF226),mannosidase beta A(MANBA),IQ motif and Sec7 domain 2(IQSEC2),neuregulin 1(NRG-1).Among them,C1ORF226 was lower risk gene while MANBA,IQSEC2,and NRG-1 were high-risk ***,silvestrol notably reduced MANBA mRNA levels,which could be reversed by inhibiting ERK ***,silvestrol markedly decreased NRG-1 protein levels,with an additional reduction observed when the ERK pathway was ***:Silvestrol’s anti-glioma effects are primarily due to the suppression of MANBA expression via the ERK pathway and possibly by hindering the translation of N

关键词： Glioblastoma Silvestrol ERK pathway MANBA NRG-1

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Yemazhui(Herba Eupatorii Lindleyani)ameliorates lipopolysaccharide-induced acute lung injury via modulation of the toll-like receptor 4/nuclear factor kappa-B/nod-like receptor family pyrin domain-containing 3 protein signaling pathway and intestinal flor

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Journal of Traditional Chinese Medicine 2024年第2期44卷 303-314页

作者： REN Li HAI Yang YANG Xue LUO Xianqin chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases College of Traditional Chinese MedicineChongqing Medical UniversityChongqing 400016China college of Basic Medicine Chongqing Medical UniversityChongqing 400016China

OBJECTIVE:To investigate the impact of Yemazhui(Herba Eupatorii Lindleyani,HEL)against lipopolysaccharide(LPS)-induced acute lung injury(ALI)and explore its underlying mechanism in ***:The chemical constituents of HEL were analyzed by ultra-high performance liquid chromatographyquadrupole time-of-flight mass spectrometry ***,HEL was found to suppress LPS-induced ALI in ***-week-old male Sprague-Dawley rats were randomly divided into 6 groups:control,LPS,Dexamethasone(Dex),HEL low dose 6 g/kg(HEL-L),HEL medium dose 18 g/kg(HEL-M)and HEL high dose 54 g/kg(HEL-H)*** model rats were intratracheally injected with 3 mg/kg LPS to establish an ALI *** counts,lung wet/dry weight ratio,as well as myeloperoxidase(MPO)activity were determined followed by the detection with hematoxylin and eosin staining,enzyme linked immunosorbent assay,quantitative real time polymerase chain reaction,western blotting,immunohistochemistry,and ***,to explore the effect of HEL on ALI-mediated intestinal flora,we performed 16s rRNA sequencing analysis of intestinal ***:HEL attenuated LPS-induced inflammation in lung tissue and intestinal flora *** study indicated that HEL suppressed the lung coefficient and wet/dry weight ratio of LPS-induced ALI in rats,inhibited leukocytes exudation and MPO activity,and improved the pathological injury of lung *** addition,HEL reduced the expression of tumor necrosis factoralpha,interleukin-1beta(IL-1β)and interleukin-6(IL-6)in bronchoalveolar lavage fluid and serum,and inhibited nuclear displacement of nuclear factor kappa-B p65(NF-κBp65).And 18 g/kg HEL also reduced the expression levels of toll-like receptor 4(TLR4),myeloid differentiation factor 88,NF-κBp65,phosphorylated inhibitor kappa B alpha(phospho-IκBα),nod-like receptor family pyrin domain-containing 3 protein(NLRP3),IL-1β,and interleukin-18(IL-18)in lung tissue,and regulated intestinal flora disturban

关键词： Yemazhui(Herba Eupatorii Lindleyani) acute lung injury anti-inflammation toll-like receptor 4 nuclear factor kappa-B nod-like receptor family pyrin domain-containing 3 protein signal transduction gastrointestinal microbiome

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The emerging tumor microbe microenvironment: From delineation to multidisciplinary approach-based interventions

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1560-1591页

作者： Yu Fu Jia Li Wenyun Cai Yulan Huang Xinlong Liu Zhongyi Ma Zhongjie Tang Xufei Bian Ji Zheng Jiayun Jiang Chong Li medical Research Institute College of Pharmaceutical SciencesSouthwest UniversityChongqing 400715China Institute of Hepatobiliary Surgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Department of Urology Urologic Surgery CenterXinqiao HospitalThird Military Medical University(Army Medical University)Chongqing 400037China

Intratumoral microbiota has become research hotspots,and emerges as a non-negligent new component of tumor microenvironments(TME),due to its powerful infuence on tumor initiation,metas-tasis,immunosurveillance and prognosis despite in *** accumulations of microbes,and their related components and metabolites within tumor tissues,endow TME with additional pluralistic features which are distinct from the conventional ***,it's definitely necessary to comprehen-sively delineate the sophisticated landscapes of tumor microbe microenvironment,as well as their func-tions and related underlying ***,in this review,we focused on the fields of tumor microbe microenvironment,including the heterogeneity of intratumor microbiota in different types of tu-mors,the controversial roles of intratumoral microbiota,the basic features of tumor microbe microenvi-ronment(i.e.,pathogen-associated molecular patterns(PAMPs),typical microbial metabolites,autophagy,infammation,multi-faceted immunomodulation and chemoresistance),as well as the multi-disciplinary approach-based intervention of tumor microbiome for cancer therapy by applying wild-type or engineered live microbes,microbiota metabolites,antibiotics,synthetic biology and rationally de-signed *** hope our work will provide valuable insight to deeply understand the interplay of cancer-immune-microbial,and facilitate the development of microbes-based tumor-specific treatments.

关键词： Tumor microbe microenvironment Microbiota metabolites Immunomodulation Chemoresistance Multidisciplinary approach Genetically engineered microbiota Autophagy Outer membrane vesicles

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Cerebral furin deficiency causes hydrocephalus in mice

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Genes & Diseases 2024年第3期11卷 438-451页

作者： Shiqi Xie Xiaoyong Xie Jing Tang Biao Luo Jian Chen Qixin Wen Jianrong Zhou Guojun Chen Nursing college Chongqing Medical UniversityChongqing 400016China Department of Neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqing Key Laboratory of Major Neurological and Mental DisordersChongqing Key Laboratory of NeurologyChongqing 400016China

Furin is a pro-protein convertase that moves between the trans-Golgi network and cell surface in the secretory *** have previously reported that cerebral overexpres-sion of furin promotes cognitive functions in ***,by generating the brain-specific furin conditional knockout(ckO)mice,we investigated the role of furin in brain *** found that furin deficiency caused early death and growth *** resonance im-aging showed severe *** the brain of furin cko mice,impaired ciliogenesis and the derangement of microtubule structures appeared along with the down-regulated expres-sion of RAB28,a ciliary vesicle *** line with the widespread neuronal loss,ependymal cell layers were *** proteomics analysis revealed that cell adhesion molecules including astrocyte-enriched ITGB8 and BCAR1 were altered in furin cKO mice;and astrocyte overgrowth was accompanied by the reduced expression of sox9,indicating a disrupted differ-entiation into ependymal ***,whereas alteration of RAB28 expression correlated with the role of vesicle trafficking in ciliogenesis,dysfunctional astrocytes might be involved in ependymal damage contributing to hydrocephalus in furin ckO *** structural and mo-lecular alterations provided a clue for further studying the potential mechanisms of furin.

关键词： Astrocyte Ciliogenesis Conditionalknockout Ependymal Furin Hydrocephalus Proteomics

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