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Chinese Journal of Integrative Medicine 2024年第3期30卷 213-221页

作者： ZHANG Yue XIAO Yan-wei MA Jing-xin WANG Ao-xue Department of Dermatology the Second Hospital of Dalian Medical UniversityDalianLiaoning Province116021China Department of Cell Biology Dalian Medical UniversityDalianLiaoning Province116044China

Objective:To investigate the effect and possible mechanism of hydroxysafflor yellow A(HSYA) on human immortalized keratinocyte cell proliferation and ***:HaCaT cells were treated with *** proliferation was detected by the cell counting kit-8 assay,and cell migration was measured using wound healing assay and Transwell migration *** mRNA and protein expression levels of heparin-binding epidermal growth factor(EGF)-like growth factor(HBEGF),EGF receptor(EGFR),phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT),mammalian target of rapamycin(mTOR),and hypoxia-inducible factor-1α(HIF-1α) were detected by quantitative real-time polymerase chain reaction(qRT-PCR) and Western blot,***_0084443-overexpressing HaCaT cells and empty plasmid HaCaT cells were constructed using the lentiviral stable transfection and treated with *** expression of circ_0084443 was detected by ***:HSYA(800 μmol/L) significantly promoted HaCaT cell proliferation and migration(P0.05).Conclusion:HSYA played an accelerative role in HaCaT cell proliferation and migration,which may be attributable to activating HBEGF/EGFR and PI3K/AKT signaling pathways,and had a particular inhibitory effect on the keratinocyte negative

关键词： hydroxysafflor yellow A circ_0084443 heparin-binding epidermal growth factor-like growth factor/epidermal growth factor receptor phosphatidylinositol 3-kinase/protein kinase B

Washed microbiota transplantation for Crohn’s disease:A metagenomic,metatranscriptomic,and metabolomic-based study

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World Journal of Gastroenterology 2024年第11期30卷 1572-1587页

作者： Shi-Ju Chen Da-Ya Zhang Xia Wu Fa-Ming Zhang Bo-Ta Cui Yi-Hao Huang Zu-Lun Zhang Rui Wang Fei-Hu Bai Graduate School Hainan Medical UniversityHaikou 571199Hainan ProvinceChina Department of Microbiota Medicine&medical Center for Digestive Diseases The Second Affiliated Hospital of Nanjing Medical UniversityNanjing 210011Jiangsu ProvinceChina Department of Gastroenterology The Second Affiliated Hospital of Hainan Medical UniversityHaikou 570216Hainan ProvinceChina

BACKGROUND Fecal microbiota transplantation(FMT)is a promising therapeutic approach for treating Crohn’s disease(CD).The new method of FMT,based on the automatic washing process,was named as washed microbiota transplantation(WMT).Most existing studies have focused on observing the clinical ***,the mechanism of action of FMT for the effective management of CD-particularly in-depth multi-omics analysis involving the metagenome,metatranscriptome,and metabolome-has not yet been *** To assess the efficacy of WMT for CD and explore alterations in the microbiome and metabolome in response to *** We conducted a prospective,open-label,single-center clinical *** CD patients underwent *** clinical responses(defined as a decrease in their CD Activity Index score of>100 points)and their microbiome(metagenome,metatranscriptome)and metabolome profiles were evaluated three months after the *** Seven of the 11 patients(63.6%)showed an optimal clinical response three months *** microbiome diversity significantly increased after WMT,consistent with improved clinical *** of the metagenome and metatranscriptome analyses revealed consistent alterations in certain strains,such as Faecalibac-terium prausnitzii,Roseburia intestinalis,and Escherichia *** addition,metabolomics analyses demonstrated that CD patients had elevated levels of various amino acids before treatment compared to the ***,levels of vital amino acids that may be associated with disease progression(e.g.,L-glutamic acid,gamma-glutamyl-leucine,and prolyl-glutamine)were reduced after *** WMT demonstrated therapeutic efficacy in CD treatment,likely due to the effective reconstruction of the patient’s ***-omics techniques can effectively help decipher the potential mechanisms of WMT in treating CD.

关键词： Crohn’s disease Clinical trials Fecal microbiota transplant Metagenome Metatranscriptome Metabolome

DNA hypermethylation of COL4A1 in ultraviolet-Binduced age-related cataract models in vitro and in vivo

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International Journal of Ophthalmology(English edition) 2024年第10期17卷 1791-1799页

作者： Li Wang Dan Zhu Yang Yang Yuan He Jing Sun Yi-Ming Li Zi-Jing Wang Peng Li Department of Optometry Xi’an Medical UniversityXi’an 710021Shaanxi ProvinceChina Department of Ophthalmology the Second Affiliated Hospital of Xi’an Medical UniversityXi’an 710038Shaanxi ProvinceChina Department of Ophthalmology Xijing 986 HospitalFourth Military Medical UniversityXi’an 710054Shaanxi ProvinceChina

AIM:To explore the DNA methylation of COL4A1 in ultraviolet-B(UVB)-induced age-related cataract(ARC)models in vitro and in ***:Human lens epithelium B3(HLEB3)cells and Sprague Dawley rats were exposure to UVB *** MTT assay was utilized to evaluate cell *** cytometry was employed for analysis of cell apoptosis and cell ***4A1 expression in HLEB3 cells and anterior lens capsules were assessed using Western blot and reverse transcription-polymerase chain reaction(RTPCR).The localization of COL4A1 in HLEB3 cells was determined by *** methylation status of CpG islands located in COL4A1 promoter was verified using bisulfite-sequencing PCR(BSP).DNMTs and TETs mRNA levels was examined by ***:UVB exposure decreased HLEB3 cells proliferation,while increased the apoptosis rate and cells were arrested in G0/G1 ***4A1 expression was markedly inhibited in UVB treated cells compared to the *** status was detected in the CpG islands within COL4A1 promoter in HLEB3 cells subjected to UVB *** of DNMTs including DNMT1/2/3 were elevated in UVB treated HLEB3 cells compared to that in the controls,while expressions of TETs including TET1/2/3 showed the opposite *** from the UVB treated rat model further confirmed the decreased expression of COL4A1,hypermethylation status of the CpG islands at promoter of COL4A1 and abnormal expression of DNMT1/2/3 and TET1/2/in UVB exposure ***:DNA hypermethylation of COL4A1 promoter CpG islands is correlated with decreased COL4A1 expression in UVB induced HLEB3 cells and anterior lens capsules of rats.

关键词： human lens epithelium cells age-related cataract COL4A1 hypermethylation ultraviolet-B rat

Sorafenib sensitization in tumor therapy by iron overload and AMPK activation

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Nano Research 2024年第7期17卷 6386-6399页

作者： Jun Zhu Shoujie Zhao Yejing Zhu Shouzheng Ma Tenghui Han Fenghua Xu Huichen Li Bo Wang Zhixiong Guo Da Chen Yongquan Qu Zhimin Tian Junlong Zhao Lei Liu State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers National Clinical Research Center for Digestive DiseasesXijing HospitalFourth Military Medical UniversityXi’an 710032China Department of General Surgery The Southern Theater Air Force HospitalGuangzhou 510602China Department of General Surgery Tangdu HospitalFourth Military Medical UniversityXi’an 710038China Department of Thoracic Surgery Tangdu HospitalFourth Military Medical UniversityXi’an 710038China Department of Neurology Airborne Army HospitalWuhan 430012China Key Laboratory of Modern Teaching Technology(Ministry of Education) Shaanxi Normal UniversityXi’an 710062China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Department of Biochemistry and Molecular BiologySchool of Basic MedicineFourth Military Medical UniversityXi’an 710032China Key Laboratory of Special Functional and Smart Polymer Materials of Ministry of Industry and Information Technology School of Chemistry and Chemical EngineeringNorthwestern Polytechnical UniversityXi’an 710072China State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Department of Medical Genetics and Developmental BiologyFourth Military Medical UniversityXi’an 710032China Department of Pediatrics Tangdu HospitalFourth Military Medical UniversityXi’an 710000China

Sorafenib,as a first-line drug for advanced hepatocellular carcinoma(HCC),could trigger ferroptosis by inhibiting cystine/glutamate ***,low-level intracellular iron and insufficient activation of adenosine monophosphate(AMP)-activated protein kinase(AMPK)confer impaired response to *** this study,a unique sorafenib nanocomposite dexterously modified with Fe-Material of Institut Lavoisier(sora@Fe-MIL)was synthesized to escalate intracellular iron level and activate AMPK,further potentiating the ferroptotic effect of ***,this strategic deployment of sora@Fe-MIL triggered an extensive demise of cancer cells,while manifesting negligible deleterious impact on normal *** prominent ferroptosis biomarkers,glutathione peroxidase 4(GPX4)and solute carrier family 7 member 11(SLC7A11),underwent pronounced downregulation,underscoring the efficacy of this strategy in inducing ***,the bioactivity of AMPK was considerably elevated,and its downstream targets were conspicuously inhibited by the treatment with sora@*** orthotopic HCC animal models,we observed a substantial suppression of primary in situ tumor growth,and ribonucleic acid(RNA)sequencing elucidated an elevated degree of ferroptosis and AMPK activation with the treatment of sora@*** conclusion,we proposed that the meticulously designed strategy for secure and efficacious iron release and AMPK activation could significantly potentiate the ferroptotic impact of sorafenib,thus resuscitating its therapeutic response in HCC patients.

关键词： anti-tumor ferroptosis Fe-Material of Institut Lavoisier(Fe-MIL) sorafenib adenosine monophosphate(AMP)-activated protein kinase(AMPK)

GATA binding protein 2 mediated ankyrin repeat domain containing 26 high expression in myeloid-derived cell lines

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World Journal of Stem Cells 2024年第5期16卷 538-550页

作者： Yang-Zhou Jiang Lan-Yue Hu Mao-Shan Chen Xiao-Jie Wang Cheng-Ning Tan Pei-Pei Xue Teng Yu Xiao-Yan He Li-Xin Xiang Yan-Ni Xiao Xiao-Liang Li Qian Ran Zhong-Jun Li Li Chen Laboratory of Radiation Biology Department of Blood TransfusionLaboratory Medicine CenterThe Second Affiliated HospitalThird Military Medical UniversityChongqing 400037China Hematopoietic Acute Radiation Syndrome medical and Pharmaceutical Basic Research Innovation Center Ministry of Education of the People’s Republic of ChinaChongqing 400037China

BACKGROUND Thrombocytopenia 2,an autosomal dominant inherited disease characterized by moderate thrombocytopenia,predisposition to myeloid malignancies and normal platelet size and function,can be caused by 5’-untranslated region(UTR)point mutations in ankyrin repeat domain containing 26(ANKRD26).Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1)have been identified as negative regulators of ***,the positive regulators of ANKRD26 are still *** To prove the positive regulatory effect of GATA binding protein 2(GATA2)on ANKRD26 *** Human induced pluripotent stem cells derived from bone marrow(hiPSC-BM)INTRODUCTION Ankyrin repeat domain containing protein 26(ANKRD26)acts as a regulator of adipogenesis and is involved in the regulation of feeding behavior[1-3].The ANKRD26 gene is located on chromosome 10 and shares regions of homology with the primate-specific gene family *** to the Human Protein Atlas database,the ANKRD26 protein is localized to the Golgi apparatus and vesicles,and its expression can be detected in nearly all human tissues[4].Moreover,UniProt annotation revealed that ANKRD26 is localized in the centrosome and contains coiled-coil domains formed by spectrin helices and ankyrin repeats[5,6].The most common disease related to ANKRD26 is thrombocytopenia 2(THC2),which is a rare autosomal dominant inherited disease characterized by lifelong mild-to-moderate thrombocytopenia and mild bleeding[7-9].Caused by the variants in the 5’-untranslated region(UTR)of ANKRD26,THC2 is defined by a decrease in the number of platelets in circulating blood and results in increased bleeding and decreased clotting ability[8,10].Due to the point mutations that occur in the 5’-UTR of ANKRD26,its negative transcription factors(TFs),Runt related transcription factor 1(RUNX1)and friend leukemia integration 1(FLI1),lose their repression effect[11].The persistent expression of ANKRD26 increases the activi

关键词： Ankyrin repeat domain containing 26 GATA binding protein 2 Thrombocytopenia 2 Transcriptional regulation Myeloid-derived cell lines

New phenylbutenoids and terpene glycosides from Ginkgo biloba leaves

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Chinese Journal of Natural Medicines 2024年第02期 161-170页

作者： SUN Zeshi LIN Shan WU Zhi-Li DONG Hong-Yuan XU Xi-Ke LI Hui-Liang WANG Jinxin School of Pharmacy Second Military Medical University State Key Laboratory of New Drug and Pharmaceutical Process Shanghai Institute of Pharmaceutical Industry China State Institute of Pharmaceutical Industry

Our continued works on the chemical constituents of Ginkgo biloba(G. biloba) leaves has led to the isolation of two novel phenylbutenoids(1, 2), along with five previously unidentified terpene glycosides(3-7). Among them, compounds 1 and 2 represent unique(Z)-phenylbutenoids, 3-6 are megastigmane glycosides, and 7 is identified as a rare bilobanone glycoside(Fig. 1). This study marks the first reported isolation of phenylbutenoid and bilobanone glycoside from G. biloba. The chemical structures of these compounds were elucidated through extensive spectroscopic analysis, including HR-ESI-MS and various 1D and 2D NMR experiments. Furthermore, the absolute configurations of these molecules were determined using Mosher's method, ECD experiments, and Cu-Kα X-ray crystallographic analyses.

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Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1564-1577页

作者： Sai-Nan Li Shan Yang Hao-Qi Wang Tian-Li Hui Meng Cheng Xi Zhang Bao-Kun Li Gui-Ying Wang The First Department of Surgery The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina The second Department of Surgery The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina Department of General Surgery The Second Hospital of Hebei Medical UniversityShijiazhuang 050000Hebei ProvinceChina

BACKGROUND Colorectal cancer(CRC)is the third most common cancer and a significant cause of cancer-related mortality *** to chemotherapy,especially during CRC treatment,leads to reduced effectiveness of drugs and poor patient *** noncoding RNAs(lncRNAs)have been implicated in various pathophysiological processes of tumor cells,including chemotherapy resistance,yet the roles of many lncRNAs in CRC remain *** To identify and analyze the lncRNAs involved in oxaliplatin resistance in CRC and to understand the underlying molecular mechanisms influencing this *** Gene Expression Omnibus datasets GSE42387 and GSE30011 were reanalyzed to identify lncRNAs and mRNAs associated with oxaliplatin *** bioinformatics tools were employed to elucidate molecular *** expression levels of lncRNAs and mRNAs were assessed via quantitative reverse transcription-polymerase chain *** assays,including MTT,wound healing,and Transwell,were conducted to investigate the functional implications of lncRNA *** between lncRNAs and trans-cription factors were examined using RIP and luciferase reporter assays,while Western blotting was used to confirm downstream ***,a xenograft mouse model was utilized to study the in vivo effects of lncRNAs on chemotherapy *** LncRNA prion protein testis specific(PRNT)was found to be upregulated in oxaliplatin-resistant CRC cell lines and negatively correlated with homeodomain interacting protein kinase 2(HIPK2)*** was demonstrated to sponge transcription factor zinc finger protein 184(ZNF184),which in turn could regulate HIPK2 *** expression of PRNT influenced CRC cell sensitivity to oxaliplatin,with overexpression leading to decreased sensitivity and decreased expression reducing *** RIP and luciferase reporter assays indicated that ZNF184 and HIPK2 are targets of *** PRNT/ZNF184

关键词： Colorectal cancer Oxaliplatin resistance Prion protein testis specific Zinc finger protein 184 Homeodomain interacting protein kinase 2

Effect of Platelet-rich Plasma in Stimulating Macrophage Transformation into M2 Type under AMPK Signaling Pathway

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Chinese Journal of Biomedical Engineering 2024年第02期33卷 85-92页

作者： ZHONG Chang-rui FU Chun-hua Longyan First Affiliated Hospital of Fujian medical university The second Hospital of Longyan

Objective: To explore the effect of platelet-rich plasma(RPR) in stimulating the transformation of pro-inflammatory(M1) macrophages into antiinflammatory(M2) under the adenosine-monophosphate-dependent protein kinase(AMPK) signaling pathway. Methods: Rat peritoneal macrophages(RAW264.7) were cultured and randomly divided into 8 groups: blank control group, LPS group, RPR group A, RPR group B, LPS+RPR(12 h) group, LPS+RPR(24 h) group A, LPS+RPR(24 h)group B, LPS+RPR(24 h) group C. RPR was prepared based on blood donors. The expressions of AMPK signaling pathway-related proteins(AMPK, ULK1, m TOR) and macrophage markers(i NOS, Arg-1) in the blank control group, LPS group, LPS+RPR(12 h)group and LPS+RPR(24 h) group were observed and compared. The expressions of macrophage markers in LPS+RPR(24 h) B and C groups were compared, and the expressions of AMPK and TGF-β in RPR A and B groups were compared. Results: The gray values of AMPK and ULK1 in LPS cells decreased significantly, while those in LPS+RPR(12 h) and LPS+RPR(24 h) A cells increased significantly. The gray values of AMPK and ULK1 in LPS+RPR(24 h) A cells were higher than those in LPS+RPR(12 h)cells(P<0.05). The m TOR gray value of LPS cells was significantly higher than that of LPS+RPR(24 h) A cells, and the m TOR gray value of LPS+RPR(24 h) A cells was significantly lower than that of LPS+RPR(12 h) cells(P<0.05). The expression of i NOS in LPS cells was significantly decreased, the expression of i NOS in LPS+RPR(12 h) and LPS+RPR(24 h) cells was significantly increased, and the expression of i NOS in LPS+RPR(24 h) cells was higher than that in LPS+RPR(12 h) cells(P<0.05). The expression of Arg-1 in LPS cells was significantly decreased, the expression of Arg-1 in LPS+RPR(12 h) and LPS+RPR(24 h) A cells was significantly increased, and the expression of Arg-1 in LPS+RPR(24 h) A cells was higher than that in LPS+RPR(12 h)cells(P<0.05). The i NOS expression level of LPS+PRP(24 h) C cells was significantly higher

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SETDB1-mediated CD147-K71 di-methylation promotes cell apoptosis in non-small cell lung cancer

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Genes & Diseases 2024年第2期11卷 978-992页

作者： Ming-Yan Shi Yarong Wang Ying Shi Ruofei Tian Xiaohong Chen Hai Zhang Ke Wang Zhinan Chen Ruo Chen National Translational Science Center for Molecular Medicine & Department of Cell Biology Fourth Military Medical UniversityXi'anShaanxi 710032China

Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor ***147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism ***,the relationship between the PTMs of CD147 and apoptosis has not been *** our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immunizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent ***1 was identified as the methyltransferase catalyzing CD147 to generate ***-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)***,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell *** vivo experiments showed that CD147-K71me2 significantly inhibited tumor progression by promoting cell *** together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.

关键词： CD147 di-methylation Cell apoptosis FOSB Non-small cell lung cancer SETDB1

Construction of millimeter-scale vascularized engineered myocardial tissue using a mixed gel

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Regenerative Biomaterials 2024年第3期3卷 56-67页

作者： Ming Ke Wenhui Xu Yansha Hao Feiyang Zheng Guanyuan Yang Yonghong Fan Fangfang Wang Zhiqiang Nie Chuhong Zhu Department of Anatomy Third Military Medical UniversityChongqing 400038China State Key Laboratory of Trauma Burn and Combined InjuryChongqing 400038China Department of Plastic and Aesthetic Surgery Southwest HospitalThird Military Medical UniversityChongqing 400038China Engineering Research Center of Tissue and Organ Regeneration and Manufacturing Ministry of EducationChongqing 400038China

Engineering myocardium has shown great clinal potential for repairing permanent myocardial ***,the lack of perfusing blood vessels and difficulties in preparing a thick-engineered myocardium result in its limited clinical *** prepared a mixed gel containing fibrin(5 mg/ml)and collagen I(0.2 mg/ml)and verified that human umbilical vein endothelial cells(HUVECs)and human-induced pluripotent stem cell-derived cardiomyocytes(hiPSC-CMs)could fom microvascular lumens and myocardial cell clusters by harnessing the low-hardness and hyperelastic characteristics of ***-CMs and HUVECs in the mixed gel formed self-organized cell clusters,which were then cultured in different media using a three-phase *** successfully constructed vascularized engineered myocardial tissue had a spherical structure and final diameter of *** tissue exhibited autonomous beats that occured at a frequency similar to a normal human heart *** internal microvascular lumen could be maintained for 6 weeks and showed good results during preliminary surface re-vascularization in vitro and vascular remodeling in *** summary,we propose a simple method for constructing vascularized engineered myocardial tissue,through phased cultivation that does not rely on high-end manufacturing equipment and cutting-edge preparation *** constructed tissue has potential value for clinical use after preliminary evaluation.

关键词： engineered myocardium vascularized hiPSC-CM HUVEC fibrin