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Sm-like 5 knockdown inhibits proliferation and promotes apoptosis of colon cancer cells by upregulating p53,CDKN1A and TNFRSF10B

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2716-2726页

作者： Cai-Jing Mo xiao-Yuan Deng Ru-Lan Ma Kun Zhu Lei Shi Kang Li Department of Surgical Oncology The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Department of Infectious Diseases The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina

BACKGROUND The role of Sm-like 5(LSM5)in colon cancer has not been *** this study,we investigated the role of LSM5 in progression of colon cancer and the potential underlying mechanism *** To determine the role of LSM5 in the progression of colon cancer and the potential underlying mechanism *** The Gene Expression Profiling Interactive Analysis database and the Human Protein Atlas website were used for LSM5 expression analysis and prognosis ***-time quantitative polymerase chain reaction and Western blotting were utilized to detect the expression of mRNAs and proteins.A lentivirus targeting LSM5 was constructed and transfected into colon cancer cells to silence LSM5 *** and apoptosis assays were also conducted to evaluate the growth of the colon cancer *** GeneChip assay and bioinformatics analysis were performed to identify the potential underlying mechanism of LSM5 in colon *** LSM5 was highly expressed in tumor tissue and colon cancer cells.A high expression level of LSM5 was related to poor prognosis in patients with colon *** of LSM5 suppressed proliferation and promoted apoptosis in colon cancer *** of LSM5 also facilitates the expression of p53,cyclin-dependent kinase inhibitor 1A(CDKN1A)and tumor necrosis factor receptor superfamily 10B(TNFRSF10B).The inhibitory effect of LSM5 knockdown on the growth of colon cancer cells was associated with the upregulation of p53,CDKN1A and *** LSM5 knockdown inhibited the proliferation and facilitated the apoptosis of colon cancer cells by upregulating p53,CDKN1A and TNFRSF10B.

关键词： Sm-like 5 Colon cancer Proliferation Apoptosis Knockdown

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USP19 Stabilizes TAK1 to Regulate High Glucose/Free Fatty Acid-induced Dysfunction in HK-2 Cells

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Current Medical Science 2024年第4期44卷 707-717页

作者： xiao-hui YAN Yin-na ZHU Yan-ting ZHU Kidney Disease and Dialysis Center Shaanxi Provincial People's HospitalXi'an 710068China Department of Nephrology The Third Affiliated Hospital of Xi'an Medical UniversityXi'an 710000China Nephrology and Hemodialysis Center Shaanxi Provincial People's HospitalXi'an 710068China

Objective Obesity-induced kidney injury contributes to the development of diabetic nephropathy(DN).Here,we identified the functions of ubiquitin-specific peptidase 19(USP19)in HK-2 cells exposed to a combination of high glucose(HG)and free fatty acid(FFA)and determined its association with TGF-beta-activated kinase 1(TAK1).Methods HK-2 cells were exposed to a combination of HG and ***19 mRNA expression was detected by quantitative RT-PCR(qRT-PCR),and protein analysis was performed by immunoblotting(IB).Cell growth was assessed by Cell Counting Kit-8(CCK-8)viability and 5-ethynyl-2′-deoxyuridine(EdU)proliferation *** cycle distribution and apoptosis were detected by flow *** USP19/TAK1 interaction and ubiquitinated TAK1 levels were assayed by coimmunoprecipitation(Co-IP)assays and *** In HG+FFA-challenged HK-2 cells,USP19 was highly ***19 knockdown attenuated HG+FFA-triggered growth inhibition and apoptosis promotion in HK-2 ***,USP19 knockdown alleviated HG+FFA-mediated PTEN-induced putative kinase 1(PINK1)/Parkin pathway inactivation and increased mitochondrial reactive oxygen species(ROS)generation in HK-2 ***,USP19 stabilized the TAK1 protein through ***,increased TAK1 expression reversed the USP19 knockdown-mediated phenotypic changes and PINK1/Parkin pathway activation in HG+FFA-challenged HK-2 *** The findings revealed that USP19 plays a crucial role in promoting HK-2 cell dysfunction induced by combined stimulation with HG and FFAs by stabilizing TAK1,providing a potential therapeutic strategy for combating DN.

关键词： HK-2 cells high glucose free fatty acid dysfunction USP19 deubiquitination

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Mesenchymal stem cells-extracellular vesicles alleviate pulmonary fibrosis by regulating immunomodulators

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World Journal of Stem Cells 2024年第6期16卷 670-689页

作者： Ying Gao Mei-Fang Liu Yang Li xi Liu Yu-Jie Cao Qian-Fa Long Jun Yu Jian-Ying Li Department of Respiratory and Critical Care Medicine Shaanxi Provincial Rehabilitation HospitalXi’an 710000Shaanxi ProvinceChina Department of Respiratory and Critical Care Medicine Second Affiliated Hospital of Ningxia Medical University(The First People’s Hospital of Yinchuan)Yinchuan 750001Ningxia Hui Autonomous RegionChina School of Clinical Medicine Xi’an Medical UniversityXi’an 710021Shaanxi ProvinceChina Department of Respiratory and Critical Care Medicine Xi’an Central HospitalXi’an 710000Shaanxi ProvinceChina Department of Neurosurgery Xi’an Central HospitalXi’an 710000Shaanxi ProvinceChina Department of Emergency Xi’an Central HospitalXi’an 710000Shaanxi ProvinceChina

BACKGROUND Pulmonary fibrosis(PF)is a chronic interstitial lung disease characterized by fibroblast proliferation and extracellular matrix formation,causing structural damage and lung *** cell therapy and mesenchymal stem cells-extracellular vesicles(MSC-EVs)offer new hope for PF *** To investigate the therapeutic potential of MSC-EVs in alleviating fibrosis,oxidative stress,and immune inflammation in A549 cells and bleomycin(BLM)-induced mouse *** The effect of MSC-EVs on A549 cells was assessed by fibrosis markers[collagen I andα-smooth muscle actin(α-SMA),oxidative stress regulators[nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1),and inflammatory regu-lators[nuclear factor-kappaB(NF-κB)p65,interleukin(IL)-1β,and IL-2].Similarly,they were assessed in the lungs of mice where PF was induced by BLM after MSC-EV ***-EVs ion PF mice were detected by pathological staining and western ***-cell RNA sequencing was performed to investigate the effects of the MSC-EVs on gene expression profiles of macrophages after modeling in *** Transforming growth factor(TGF)-β1 enhanced fibrosis in A549 cells,significantly increasing collagen I andα-SMA ***,treatment with MSC-EVs demonstrated a remarkable alleviation of these ***,the expression of oxidative stress regulators,such as Nrf2 and HO-1,along with inflammatory regulators,including NF-κB p65 and IL-1β,were mitigated by MSC-EV ***,in a parallel manner,MSC-EVs exhibited a downregulatory impact on collagen deposition,oxidative stress injuries,and inflammatory-related cytokines in the lungs of mice with ***,the mRNA sequencing results suggested that BLM may induce PF in mice by upregulating pulmonary collagen fiber deposition and triggering an immune inflammatory *** findings collectively highlight the potential therapeutic efficacy of MSC-EVs in ameliorating fibrotic processes,oxidative stres

关键词： Mesenchymal stem cells Extracellular vesicles Pulmonary fibrosis Oxidative stress response Epithelial-mesenchymal transition

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The roles of macrophage migration inhibitory factor in retinal diseases

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Neural Regeneration Research 2024年第2期19卷 309-315页

作者： Hongbing Zhang xianjiao Zhang Hongsong Li Bing Wang Pei Chen Jiamin Meng Shaanxi Institute of Ophthalmology Xi’anShaanxi ProvinceChina Department of Ophthalmology First Affiliated Hospital of Northwest UniversityXi’anShaanxi ProvinceChina Department of Pathology First Affiliated Hospital of Northwest UniversityXi’anShaanxi ProvinceChina

Macrophage migration inhibitory factor(MIF),a multifunctional cytokine,is secreted by various cells and participates in inflammatory reactions,including innate and adaptive *** are some evidences that MIF is involved in many vitreoretinal *** example,MIF can exacerbate many types of uveitis;measurements of MIF levels can be used to monitor the effectiveness of uveitis *** also alleviates trauma-induced and glaucoma-induced optic nerve ***,MIF is critical for retinal/choroidal neovascularization,especially complex *** exacerbates retinal degeneration;thus,anti-MIF therapy may help to mitigate retinal *** protects uveal melanoma from attacks by natural killer *** mechanism underlying the effects of MIF in these diseases has been demonstrated:it binds to cluster of differentiation 74,inhibits the c-Jun N-terminal kinase pathway,and triggers mitogen-activated protein kinases,extracellular signal-regulated kinase-1/2,and the phosphoinositide-3-kinase/Akt *** also upregulates Toll-like receptor 4 and activates the nuclear factor kappa-B signaling *** review focuses on the structure and function of MIF and its receptors,including the effects of MIF on uveal inflammation,retinal degeneration,optic neuropathy,retinal/choroidal neovascularization,and uveal melanoma.

关键词： diabetic retinopathy glaucoma macrophage migration inhibitory factor migration inhibitory factor receptor optic neuropathy retinal degeneration retinal neovascular uveal melanoma uveitis

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Retinitis pigmentosa and stem cell therapy

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1363-1369页

作者： xin-Ya Qi Chen-Hui Mi De-Rui Cao xie-Qun Chen Peng Zhang School of Medicine Department of Life Sciences and MedicineNorthwest UniversityXi’an 710069Shaanxi ProvinceChina The Third hospital of xi’an Affiliated Hospital of Northwest UniversityXi’an 710021Shaanxi ProvinceChina

Retinitis pigmentosa(RP)is a group of genetic disorders characterized by progressive degeneration of photoreceptors and retinal pigment epithelium(RPE)*** main clinical manifestations include night blindness and progressive loss of peripheral vision,making it a prevalent debilitating eye disease that significantly impacts patients’quality of *** exhibits significant phenotypic and genetic *** instance,numerous abnormal genes are implicated in RP,resulting in varying clinical presentations,disease progression rates,and pathological characteristics among different ***,gene therapy for RP poses challenges due to these ***,stem cells have garnered considerable attention in the field of RPE therapy since both RPE cells and photoreceptors can be derived from stem *** recent years,a large number of animal experiments and clinical trials based on stem cell transplantation attempts,especially cord blood mesenchymal stem cell(MSC)transplantation and bone marrow-derived MSC transplantation,have confirmed that stem cell therapy can effectively and safely improve the outer retinal function of the RP-affected ***,stem cell therapy also has certain limitations,such as the fact that RP patients may involve multiple types of retinal cytopathia,which brings great challenges to stem cell transplantation therapy,and further research is needed to solve various problems faced by this approach in the *** comprehensive analysis of the etiology and histopathological changes associated with RP,this study substantiates the efficacy and safety of stem cell therapy based on rigorous animal experimentation and clinical trials,while also highlighting the existing limitations that warrant further investigation.

关键词： retinitis pigmentosa photoreceptor stem cell therapy

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UPLC-Q-TOF/MS-Based Serum Metabolomics Reveals Potential Anti-tumor Mechanism of Banxia xiexin Decoction in Colorectal Cancer Mice

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Chinese Journal of Integrative Medicine 2024年第7期30卷 623-632页

作者： YUE Yin-zi LI Ming-xuan WANG xiao-hui QIN Yuan-yuan WANG Ya-hui TAN Jin-hua SU Lian-lin YAN Shuai Department of General Surgery Suzhou TCM Hospital Affiliated to Nanjing University of Chinese MedicineSuzhou215009China School of Pharmacy Nanjing University of Chinese MedicineNanjing210023China Department of General Surgery Bayinguoleng Mongolian Autonomous Prefecture People’s HospitalXinjiang Uygur Autonomous RegionKorla841000China Department of Pharmacy Suzhou TCM Hospital Affiliated to Nanjing University of Chinese MedicineSuzhou215009China Department of Anorectal Surgery Suzhou TCM Hospital Affiliated to Nanjing University of Chinese MedicineSuzhou215009China

Objective To clarify the potential mechanism of Banxia xiexin Decoction(BXD)on colorectal cancer(CRC)from the perspective of *** Forty male C57BL/6 mice were randomly divided into normal control(NC),azoxymethane/dextran sulfate sodium(AOM/DSS)model,low-dose BXD(L-BXD),high-dose BXD(H-BXD)and mesalamine(MS)groups according to a random number table,8 mice in each *** cancer model was induced by AOM/*** was administered daily at doses of 3.915(L-BXD)and 15.66 g/kg(H-BXD)by gavage for consecutive 21 days,and 100 mg/kg MS was used as positive *** the entire modeling cycle,colon length of mice was measured and quantity of colorectal tumors were *** spleen and thymus index were determined by calculating the spleen/thymus weight to body *** cytokine and changes of serum metabolites were analyzed by enzyme-linked immunosorbent assay kits and ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry(UPLC-Q/TOF-MS),*** Notably,BXD supplementation protected against weight loss,mitigated tumor formation,and diminished histologic damage in mice treated with AOM/DSS(P<0.05 or P<0.01).Moreover,BXD suppressed expression of serum inflammatory enzymes,and improved the spleen and thymus index(P<0.05).Compared with the normal group,102 kinds of differential metabolites were screened in the AOM/DSS group,including 48 potential biomarkers,involving 18 main metabolic *** 18 potential biomarkers related to CRC were identified,and the anti-CRC mechanism of BXD was closely related to D-glutamine and D-glutamate metabolism,phenylalanine,tyrosine and tryptophan biosynthesis,arginine biosynthesis,nitrogen metabolism and so *** BXD exerts partial protective effects on AOM/DSS-induced CRC by reducing inflammation,protecting organism immunity ability,and regulating amino acid metabolism.

关键词： colorectal cancer metabolomics ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry azoxymethane dextran sulfate sodium Banxia xiexin Decoction Chinese medicine

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Depletion of anti-CD47mAb in plasma by genetically modified cells for pre-transfusion testing

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Genes & Diseases 2024年第5期11卷 102-104页

作者： Fei Wang Wenting Wang xiaoshuang Wu Zhixin Liu Yafen Wang Rong Zhang Shunli Gu Qunxing An Yaozhen Chen xingbin Hu Department of Transfusion Medicine Xijing HospitalFourth Military Medical UniversityXi’anShaanxi 710032China xi’an Medical University Xi’anShaanxi 710021China

Allogeneic red blood cell(RBC)transfusion is commonly performed in medical practice because of its efficacy and low-risk ***,pre-transfusion tests are susceptible to monoclonal antibody(mAb)interference.1 Currently,mAb therapies are being developed to treat many diseases,such as ***,certain mAbs,such as anti-CD38mAb and anti-CD47mAb,can bind to RBC membranes;this binding interferes with pre-transfusion tests.2 CD47 has gained considerable attention in recent years because of its potential as a therapeutic target for hematologic malignancies and solid tumors.3 The binding of anti-CD47mAb to RBCs may lead to false-positive results in pan-agglutination tests and cause delays and risks in establishing compatible RBCs for transfusion.

关键词： CD47 transfusion diseases

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Optimization of tracheoesophageal fistula model established with Tshaped magnet system based on magnetic compression technique

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World Journal of Gastroenterology 2024年第16期30卷 2272-2280页

作者： Miao-Miao Zhang Jian-Qi Mao Lin-xin Shen Ai-Hua Shi xin Lyu Jia Ma Yi Lyu xiao-Peng Yan Department of Hepatobiliary Surgery The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Shaanxi Provincial Key Laboratory of Magnetic Medicine The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Zonglian College Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina National Local Joint Engineering Research Center for Precision Surgery&Regenerative Medicine The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Department of Pulmonary and Critical Care Medicine The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004Shaanxi ProvinceChina Department of Surgical Oncology Shaanxi Provincial People’s HospitalXi’an 710068Shaanxi ProvinceChina

BACKGROUND The magnetic compression technique has been used to establish an animal model of tracheoesophageal fistula(TEF),but the commonly shaped magnets present limitations of poor homogeneity of TEF and poor model *** designed a Tshaped magnet system to overcome these problems and verified its effectiveness via animal *** To investigate the effectiveness of a T-shaped magnet system for establishing a TEF model in beagle *** Twelve beagles were randomly assigned to groups in which magnets of the Tshaped scheme(study group,n=6)or normal magnets(control group,n=6)were implanted into the trachea and esophagus separately under *** time,operation success rate,and accidental injury were *** operation,the presence and timing of cough and the time of magnet shedding were *** in the control group were euthanized after X-ray and gastroscopy to confirm establishment of TEFs after coughing,and gross specimens of TEFs were *** in the study group were euthanized after X-ray and gastroscopy 2 wk after surgery,and gross specimens were *** size was measured in all animals,and then harvested fistula specimens were examined by hematoxylin and eosin(HE)and Masson trichrome *** The operation success rate was 100%for both *** time did not differ between the study group(5.25 min±1.29 min)and the control group(4.75 min±1.70 min;P=0.331).No bleeding,perforation,or unplanned magnet attraction occurred in any animal during the *** the early postoperative period,all dogs ate freely and were generally in good *** in the control group had severe cough after drinking water at 6-9 d after surgery.X-ray indicated that the magnets had entered the stomach,and gastroscopy showed TEF *** specimens of TEFs from the control group showed the formation of fistulas with a diameter of 4.94 mm±1.29 mm(range,3.52-6.56 mm).HE and Masson trichrome staining showed s

关键词： Magnetic surgery Magnetic compression technique Tracheoesophageal fistula Magnet Animal model Beagles

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Bone morphogenetic protein-6 suppresses TGF-β_(2)-induced epithelial-mesenchymal transition in retinal pigment epithelium

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International Journal of Ophthalmology(English edition) 2024年第4期17卷 646-652页

作者： Xuan Liu Ming Liu Meng Ji Bo Ma Yu-Cen Hou xin-Yue Yao Qiao-Chu Cheng Li Chen Department of Ophthalmology the First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Department of Ophthalmology Xi’an No.1 HospitalXi’an 710000Shaanxi ProvinceChina Shaanxi Institute of Ophthalmology Xi’an 710000Shaanxi ProvinceChina Department of Ophthalmology Ankang Hospital of Traditional Chinese MedicineAnkang 725000Shaanxi ProvinceChina

AIM:To evaluate the effect of bone morphogenetic protein-6(BMP-6)on transforming growth factor(TGF)-β_(2)-induced epithelial-mesenchymal transition(EMT)in retinal pigment epithelium(RPE).METHODS:Adult retinal pigment epithelial cell line(ARPE-19)were randomly divided into control,TGF-β_(2)(5μg/L),and BMP-6 small interfering RNA(siRNA)*** cell morphology was observed by microscopy,and the cell migration ability were detected by Transwell *** EMT-related indexes and BMP-6 protein levels were detected by Western ***,a BMP-6 overexpression plasmid was constructed and RPE cells were divided into the control group,TGF-β_(2)+empty plasmid group,BMP-6 overexpression group,and TGF-β_(2)+BMP-6 overexpression *** EMT-related indexes and extracellular regulated protein kinases(ERK)protein levels were ***:Compared with the control group,the migration of RPE cells in the TGF-β_(2) group was significantly ***-β_(2) increased the protein expression levels ofα-smooth muscle actin(α-SMA),fibronectin and vimentin but significantly decreased the protein levels of E-cadherin and BMP-6(P<0.05)in ***,the migration of RPE cells in the BMP-6 siRNA group was also significantly ***-6 siRNA increased the protein expression levels ofα-SMA,fibronectin and vimentin but significantly decreased the protein expression levels of E-cadherin(P<0.05).Overexpression of BMP-6 inhibited the migration of RPE cells induced by TGF-β_(2) and prevented TGF-β_(2) from affecting EMT-related biomarkers(P<0.05).CONCLUSION:BMP-6 prevents the EMT in RPE cells induced by TGF-β_(2),which may provide a theoretical basis for the prevention and treatment of proliferative vitreoretinopathy.

关键词： bone morphogenetic protein-6 epithelialmesenchymal transition transforming growth factor-β_(2) retinal pigment epithelial cells cell migration

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Ghrelin inhibits autophagy mediated by AKT/mTOR pathway to ameliorate retinal angiogenesis induced by high glucose stress

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 785-793页

作者： Jiang-Li Fan Rong Li Min Zhang Chao Chen Guo-Min Yao Ling-xiao Zhou Department of Ophthalmology Gongshu District People’s Hospital of Integrated Traditional Chinese and Western MedicineHangzhou 310004Zhejiang ProvinceChina Department of Ophthalmology the First Affiliated Hospital of Xi’an Medical UniversityXi’an 710077Shaanxi ProvinceChina Department of Endocrinology the First Affiliated Hospital of Xi’an Medical UniversityXi’an 710077Shaanxi ProvinceChina Department of General Surgery the First Affiliated Hospital of Xi’an Medical UniversityXi’an 710077Shaanxi ProvinceChina

AIM:To observe the effect of ghrelin,a growth hormonereleasing peptide,on retinal angiogenesis in vitro under high glucose(HG)stress and to explore the possible mechanism of ***:Human retinal microvascular endothelial cells(HRMECs)were treated with high concentration of glucose alone or in combination with *** cell migration,tube formation and the expression of the autophagy-related proteins LC3-II/I,Beclin-1,p62,phosphorylated AKT(p-AKT)/AKT and phosphorylated mammalian target of rapamycin(p-mTOR)/mTOR were ***,to clarify the correlation between ghrelin effect and autophagy,AKT inhibitor VIII was adopted to treat HRMECs,and cell migration,tube formation as well as the protein expressions of LC3-II/I,Beclin-1 and p62 were ***:Under HG stress,ghrelin inhibited migration and tube formation of *** inhibited the increases in the protein levels of LC3-II/I,Beclin-1 and the decreases in the protein levels of p62,p-AKT/AKT and p-mTOR/mTOR induced by HG ***,under the action of AKT/mTOR pathway inhibitors,the effects of ghrelin on migration and tube formation were both *** addition,the expression of LC3-II/I and Beclin-1 were significantly up-regulated and the expression of p62 was ***:Retinal angiogenesis under in vitro HG stress can be inhibited by ghrelin through activating AKT/mTOR pathway to inhibit autophagy.

关键词： ghrelin retinal endothelial cell angiogenesis autophagy stress

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