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Chinese Journal of Chemistry 2024年第2期42卷 157-163页

作者： Weicai Li Lu Tan Yijun Chen Rui Liu Zhongyu Qi Shixuan Yuan Zhanwen Huang Siping Wei Xi Du Dong Yi Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province School of PharmacySouthwest Medical UniversityLuzhouSichuan 646000China department of Chemistry School of Basic Medical ScienceSouthwest Medical UniversityLuzhouSichuan 646000China department of pharmacy Affiliated HospitalSouthwest Medical UniversityLuzhouSichuan 646000China

Tetralin-1-carboxamides are frequently incorporated in myriad medicinally important ***,their existing synthetic routes not only suffer from some drawbacks such as tedious procedures,harsh reaction conditions,narrow substrate scope,low yields,and environmental problems,but are also based upon the elaboration of uneasily available non-linear tetralin ***,we describe a metal-and additive-free visible light-induced[4+2]annulation of two simple linear starting materials,namely acrylamides and 2-benzyl-2-bromocarbonyls,through a cascade C(sp^(3))-Br/C(sp^(2))-H bond cleavage,double C-C bond formation,and aromatization *** developed protocol provides a convenient,efficient,and green approach to a variety of tetralin-1-carboxamide derivatives with good functional group ***,the resulting products could also undergo the Licl-mediated mono-decarboxylative cyclization process to further furnish the architecturally novel bridged polycyclic imides with excellentcis-diastereoselectivities.

关键词： Annulation Metal-free Photoredox catalysis Tetralin-1-carboxamide Cyclic imides Synthetic methods C-C coupling Radical reactions Reaction mechanisms

Saponin Ⅰ from Shuitianqi(Rhizoma Schizocapasae Plantagineae) inhibits metastasis by negatively regulating the transforming growth factor-β1/Smad7 network and epithelial-mesenchymal transition in the intrahepatic metastasis Bagg's Albino/c mouse model

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Journal of Traditional Chinese Medicine 2024年第4期44卷 642-651页

作者： LYU Meixian ZHOU Huan ZHI Limin ZHOU Jinling GAN Rizhi QIN Yanping HE Nengting ZUO Qiqi LI Hao DONG Min LIANG Gang Pharmaceutical College Guangxi Medical University department of pharmacy Affiliated Tumor Hospital of Guangxi Medical University Drug clinical trial Facility office the People's Hospital of Guangxi Zhuang Autonomous Region College of pharmacy Guangxi University of Chinese Medicine department of pharmacy the Second Affiliated Hospital of Guangxi Medical University department of pharmacy People's Hospital of Guangxi Hezhou department of pharmacy Guangzhou Women and Children's Medical Center Liuzhou Hospital department of pharmacy First Affiliated Hospital of Gannan Medical University

OBJECTIVE: To examine the influence of Saponin Ⅰ from Shuitianqi(Rhizoma Schizocapasae Plantagineae)(SSPH Ⅰ) on hepatocellular carcinoma(HCC) metastasis,and to elucidate the underlying ***: The intrahepatic metastasis Bagg's Albino/c(BALB/c) mouse model was established with human hepatocellular carcinomas(HepG2) cells, then treated with normal saline(once per day), cisplatin(2 mg/kg, once every 2 d), and SSPH Ⅰ(25, 50, and 75 mg/kg, once per day). Then, we assessed alterations in the hepatic pathology and target protein expressions in the intrahepatic metastasis BALB/c mouse model using a series of molecular biology ***: Based on our analysis, SSPH Ⅰ significantly alleviated hepatocyte necrosis and tumor cells ***, SSPH Ⅰ suppressed extracellular matrix(ECM) degradation and angiogenesis via a decrease in matrix etalloproteinase-2(MMP-2), MMP-9, CD31, CD34,and vascular endothelial growth factor(VEGF) ***, SSPH Ⅰ repressed invasion and metastasis by suppressing the transforming growth factor-β1(TGF-β 1)/Smad7 axis and epithelial-mesenchymal transition(EMT), as evidenced by the scarce TGF-β1, Ncadherin, and Vimentin expressions, and elevated Smad7 and E-cadherin ***: The SSPH Ⅰ-mediated negative regulation of the TGF-β 1/Smad7 axis and EMT are critical for the inhibition of HCC invasion and metastasis.

关键词： Saponin I from Shuitianqi (Rhizoma Schizocapasae Plantagineae) Smad7 protein carcinoma, hepatocellular epithelial-mesenchymal transition transforming growth factor beta1

Epigenetic regulation of SARS-Cov-2 spike protein modulates cellular viability and nascent RNA transcription in neuronal cells

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Genes & Diseases 2024年第2期11卷 535-538页

作者： Xi Kong Peng Lu Jinyue Zhang Zheng Bao Chenghao Kuang Bingqing Xie Jianhua Peng Ning Ma Yong Jiang Shigang Yin Laboratory of Neurological Diseases and Brain Function The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan 646000China Institute of Epigenetics and Brain Science Southwest Medical UniversityLuzhouSichuan 646000China department of Neurosurgery The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan 646000China Inflammation and Allergic Diseases Research Unit The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan 646000China

SARS-CoV-2 has been demonstrated to be highly susceptible to neuron-and glial-like cells,1 but there is no consensus regarding how the virus affects neurons following *** is therefore unknown if and how SARS-CoV-2 maintains the homeostasis of neuronal ***,we revealed that the receptor-binding domain(RBD)of the SARS-CoV-2 spike protein acted as an extracellular remodeling component to undermine epigenetic regulation,perturbnascentRNA(nsRNA)transcription,promote mitochondrial biogenesis,and increase cellular viability in SH-SY5Y cells.

关键词： invasion homeostasis maintain

Effects of Helicobacter pylori and Moluodan on the Wnt/β-catenin signaling pathway in mice with precancerous gastric cancer lesions

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 979-990页

作者： Yi-Mei Wang Zheng-Wei Luo Yu-Lin Shu Xiu Zhou Lin-Qing Wang Chun-Hong Liang Chao-Qun Wu Chang-Ping Li department of Gastroenterology The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina

BACKGROUND Helicobacter pylori(***)is the primary risk factor for gastric cancer(GC),the Wnt/β-Catenin signaling pathway is closely linked to *** has a high mortality rate and treatment cost,and there are no drugs to prevent the progression of gastric precancerous lesions to ***,it is necessary to find a novel drug that is inexpensive and preventive to against *** To explore the effects of *** and Moluodan on the Wnt/β-Catenin signaling pathway and precancerous lesions of GC(PLGC).METHODS Mice were divided into the control,N-methyl-N-nitrosourea(MNU),***+MNU,and Moluodan *** first created an *** infection model in the ***+MNU and Moluodan groups.A PLGC model was created in the remaining three groups except for the control *** was fed to mice in the Moloudan group ad *** general condition of mice were observed during the whole experiment *** tissues of mice were grossly and microscopically *** quantitative real-time PCR(qRT-PCR)and Western blotting analysis,the expression of relevant genes were *** Mice in the ***+MNU group showed the worst performance in general condition,gastric tissue visual and microscopic observation,followed by the MNU group,Moluodan group and the control ***-PCR and Western blotting analysis were used to detect the expression of relevant genes,the results showed that the ***+MNU group had the highest expression,followed by the MNU group,Moluodan group and the control *** *** can activate the Wnt/β-catenin signaling pathway,thereby facilitating the development and progression of *** suppressed the activation of the Wnt/β-catenin signaling pathway,thereby decreasing the progression of PLGC.

关键词： Helicobacter pylori Gastric cancer Wnt/β-catenin signaling pathway Moluodan

Prognostic value of circulating tumor cells combined with neutrophil-lymphocyte ratio in patients with hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 372-385页

作者： Jia-Li Chen Lu Guo Zhen-Ying Wu Kun He Han Li Chi Yang Yun-Wei Han department of Oncology The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina department of Ophthalmology The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina Clinical Research Institute The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina department of Plastic Surgery Meguiar's Medical Beauty HospitalChengdu 610000Sichuan ProvinceChina

BACKGROUND Circulating tumor cell(CTC)count and neutrophil-to-lymphocyte ratio(NLR)are both closely associated with the prognosis of hepatocellular carcinoma(HCC).AIM To investigate the prognostic value of combining these two indicators in *** Clinical data were collected from patients with advanced HCC who received im-mune therapy combined with targeted therapy at the department of Oncology,the affiliated hospital of southwest medical university,Sichuan,China,from 2021 to *** optimal cutoff values for CTC programmed death-ligand 1(PD-L1)(+)>1 or CTC PD-L1(+)≤1 and NLR>3.89 or NLR≤3.89 were evaluated using X-Tile *** were categorized into three groups based on CTC PD-L1(+)counts and NLR:CTC-NLR(0),CTC-NLR(1),and CTC-NLR(2).The relationship between CTC-NLR and clinical variables as well as survival rates was *** Patients with high CTC PD-L1(+)expression or NLR at baseline had shorter median progression-free survival(m-PFS)and median overall survival(mOS)than those with low levels of CTC PD-L1(+)or NLR(P<0.001).Mean-while,patients in the CTC-NLR(2)group showed a significant decrease in mPFS and *** regression analysis revealed that alpha-fetoprotein(AFP),CTC PD-L1(+),and CTC-NLR were independent predictors of *** time-dependent receiver operating characteristic curve showed that the area under the curve of CTC-NLR at 12 months(0.821)and 18 months(0.821)was superior to that of AFP and CTC PD-L1(+).CONCLUSION HCC patients with high CTC PD-L1(+)or NLR expression tend to exhibit poor prognosis,and a high baseline CTC-NLR score may indicate low ***-NLR may serve as an effective prognostic indicator for patients with advanced HCC receiving immunotherapy combined with targeted therapy.

关键词： Circulating tumor cells Neutrophil–lymphocyte ratio Hepatocellular carcinoma Prognosis Survival Marker

Effect of acacetin on inhibition of apoptosis in Helicobacter pyloriinfected gastric epithelial cell line

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3624-3634页

作者： Qi-Xi Yao Zi-Yu Li Hou-Le Kang Xin He Min Kang department of Gastroenterology The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina department of Orthopaedics The Affiliated Hospital of Southwest Medical UniversityLuzhou 646000Sichuan ProvinceChina department of Emergency Luzhou People’s HospitalLuzhou 646000Sichuan ProvinceChina

BACKGROUND Helicobacter pylori(***)infection can cause extensive apoptosis of gastric epithelial cells,serving as a critical catalyst in the progression from chronic gastritis,gastrointestinal metaplasia,and atypical gastric hyperplasia to gastric *** eradication of *** is paramount for ameliorating the pathophysiological conditions associated with chronic inflammation of the gastric mucosa and the primary prevention of gastric ***,which has multifaceted pharmacological activities such as anti-cancer,anti-inflammatory,and antioxidative properties,has been extensively investigated across various ***,the impact and underlying mechanisms of action of acacetin on ***-infected gastric mucosal epithelial cells remain *** To explore the defensive effects of acacetin on apoptosis in ***-infected GES-1 cells and to investigate the underlying *** GES-1 cells were treated with *** and acacetin in *** viability was assessed using the CCK-8 assay,cell mortality rate via lactate dehydrogenase assay,alterations in cell migration and healing capacities through the wound healing assay,rates of apoptosis via flow cytometry and TUNEL staining,and expression levels of apoptosis-associated proteins through western blot *** *** infection led to decreased GES-1 cell viability,increased cell mortality,suppressed cell migration,increased rate of apoptosis,increased expressions of Bax and cle-caspase3,and decreased Bcl-2 ***,acacetin treatment enhanced cell viability,mitigated apoptosis induced by *** infection,and modulated the expression of apoptosis-regulatory proteins by upregulating Bcl-2 and downregulating Bax and cleaved *** Acacetin significantly improved GES-1 cell viability and inhibited apoptosis in ***-infected GES-1 cells,thereby exerting a protective effect on gastric mucosal epithelial cells.

关键词： Gastric epithelial GES-1 cells Helicobacter pylori Infection Acacetin Antibiotic resistance Apoptosis

ZIF-8 coated gold nanospheres: A multi-responsive drug delivery system promoting the killing effect of photothermal therapy against osteosarcoma cells

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Nano Research 2024年第3期17卷 1772-1784页

作者： Miao Lei Weiye Cai Luetao Zou Bin Yu Lin Chen Yang Cao Shanlin Xiang Chao Song Jiandu Lei Wei Jiang Zhenming Hu department of Orthopedics Orthopedic Laboratory of Chongqing Medical UniversityThe First Affiliated Hospital of Chongqing Medical UniversityNo.1 Youyi RoadChongqing 400010China The affiliated Traditional Chinese Medicine hospital of southwest medical university Luzhou 646699China department of Orthopedics The Third Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China department of Radiology The First Affiliated Hospital of Chongqing Medical UniversityNo.1 Youyi RoadChongqing 400010China department of Orthopedics Chongqing University Three Gorges HospitalChongqing 404000China department of Geriatrics The Affiliated Hospital of Guizhou Medical UniversityGuiyang 550025China Beijing Key Laboratory of Lignocellulosic Chemistry College of Material Science and TechnologyBeijing Forestry UniversityBeijing 100083China

Photothermal therapy(PTT)has been widely used in the treatment of tumors,but its efficacy is greatly limited by the inability of precise drug delivery and the increase of heat shock proteins(HSPs)caused by high *** article describes a therapeutic strategy to enhance PTT with starvation therapy in conjunction with ferroptosis mechanism.A nanoparticle platform ZIF-8@GA was constructed by wrapping together glucose oxidase(GOX)and gold nanospheres(AuNPs)loaded with dihydroartemisinin(DHA)with zeolitic imidazolate framework-8(ZIF-8).This platform can take advantage of the micro-environment of osteosarcoma(OS)cells,featuring low pH and high reactive oxygen species(ROS),for precision drug *** can effectively catalyze glucose to produce gluconic acid and H_(2)O_(2),and DHA can also induce ROS production in OS *** produced by GOX and DHA can further generate lipid peroxidation(LPO)and lead to ferroptosis of OS *** the same time,ROS and LPO produced can inhibit the expression of HSPs,thereby increasing the therapeutic effect of *** vitro experiments show that the nanoparticles are pH and ROS responsive.1μg/mL GOX combined with 0.2μg/mL DHA promotes ferroptosis of OS cells,and increases the killing effect of near-infrared(NIR)on OS *** in vivo experiments showed that the nano drug-delivery platform combined with PTT can effectively inhibit the growth of OS ***,this study provides a new idea for the treatment of OS with biomaterials combined with various treatment methods.

关键词： zeolitic imidazolate framework-8(ZIF-8) gold nanospheres(AuNPs) photothermal therapy(PTT) starvation therapy ferroptosis

Metformin:A promising clinical therapeutical approach for BPH treatment via inhibiting dysregulated steroid hormones-induced prostatic epithelial cells proliferation

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Journal of Pharmaceutical Analysis 2024年第1期14卷 52-68页

作者： Tingting Yang Jiayu Yuan Yuting Peng Jiale Pang Zhen Qiu Shangxiu Chen Yuhan Huang Zhenzhou Jiang Yilin Fan Junjie Liu Tao Wang Xueyan Zhou Sitong Qian Jinfang Song Yi Xu Qian Lu Xiaoxing Yin Jiangsu Key Laboratory of New Drug Research and Clinical pharmacy Xuzhou Medical UniversityXuzhouJiangsu221004China department of pharmacy Affiliated Lianyungang Hospital of Xuzhou Medical UniversityLianyungangJiangsu222061China department of pharmacy The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China New Drug Screening Center Jiangsu Center for Pharmacodynamics Research and EvaluationChina Pharmaceutical UniversityNanjing210009China School of Life Sciences University of EssexEssex CO43SQUnited Kingdom department of Urology The Affiliated Hospital of Xuzhou Medical UniversityXuzhouJiangsu221006China department of pharmacy Affiliated Hospital of Jiangnan UniversityWuxiJiangsu214000China

The occurrence of benign prostate hyperplasia(BPH)was related to disrupted sex steroid hormones,and metformin(Met)had a clinical response to sex steroid hormone-related gynaecological ***,whether Met exerts an antiproliferative effect on BPH via sex steroid hormones remains ***,our clinical study showed that along with prostatic epithelial cell(PEC)proliferation,sex steroid hormones were dysregulated in the serum and prostate of BPH *** the major contributor to dysregulated sex steroid hormones,elevated dihydrotestosterone(DHT)had a significant positive relationship with the clinical characteristics of BPH *** of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)by Met restored dysregulated sex steroid hormone homeostasis and exerted antiproliferative effects against DHT-induced proliferation by inhibiting the formation of androgen receptor(AR)-mediated Yes-associated protein(YAP1)-TEA domain transcription factor(TEAD4)***’s anti-proliferative effects were blocked by AMPK inhibitor or YAP1 overexpression in DHT-cultured BPH-1 *** findings indicated that Met would be a promising clinical therapeutic approach for BPH by inhibiting dysregulated steroid hormone-induced PEC proliferation.

关键词： Metformin Benign prostatic hyperplasia Sex steroid hormones homeostasis Proliferation DHT YAP1-TEAD4 heterodimer

SENP3 Promotes Mantle Cell Lymphoma Development through Regulating Wnt10a Expression

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Current medical Science 2024年第1期44卷 134-143页

作者： Yan-ni MA Yun-ding ZOU Zhi-long LIU Gui-xian WU Yuan-ze ZHOU Cheng-xin LUO Xiang-tao HUANG Ming-ling XIE Shuang-nian XU Xi LI department of Hematology Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China department of Hematology the Third Affiliated Hospital(Daping Hospital)Third Military Medical University(Army Medical University)Chongqing 400042China

Objective SUMO-specific protease 3(SENP3),a member of the SUMO-specific protease family,reverses the SUMOylation of SUMO-2/3 *** of SENP3 has been proven to be involved in the development of various ***,its role in mantle cell lymphoma(MCL),a highly aggressive lymphoma,remains *** study was aimed to elucidate the effect of SENP3 in *** The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR,Western blotting or *** cells with stable SENP3 knockdown were constructed using short hairpin *** proliferation was assessed by CCK-8 assay,and cell apoptosis was determined by flow *** sequencing(mRNA-seq)was used to investigate the underlying mechanism of SENP3 knockdown on MCL development.A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in *** SENP3 was upregulated in MCL patient samples and *** of SENP3 in MCL cells inhibited cell proliferation and promoted cell ***,the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 ***,the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse *** SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.

关键词： mantle cell lymphoma SENP3 cell proliferation apoptosis

Neferine inhibits the progression of diabetic nephropathy by modulating the miR-17-5p/nuclear factor E2-related factor 2 axis

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Journal of Traditional Chinese Medicine 2024年第1期44卷 44-53页

作者： HUANG Hongmei YANG Maojun LI Ting WANG Dandan LI Ying TANG Xiaochi YUAN Lu GU Shi XU Yong department of Endocrinology Chengdu Shuangliu District First People's Hospital(West China Airport of Sichuan University)Chengdu 610200China department of Endocrinology Affiliated Hospital of Southwest Medical UniversityLuzhou 646000China

OBJECTIVE:To investigate the effect of Neferine(Nef)on diabetic nephropathy(DN)and to explore the mechanism of Nef in DN based on miRNA regulation ***:A DN mouse model was constructed and treated with *** creatinine(Crea),blood urea(UREA)and urinary albumin were measured in mice by kits,and renal histopathological changes and fibrosis were observed by hematoxylin-eosin staining and Masson *** tissue superoxide dismutase(SOD),malondialdehyde(MDA)and glutathione peroxidase(GSH-Px)activities were measured by enzyme-linked immunosorbent assay(ELISA).Western blotting was used to detect the expression of nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)signaling pathway-related proteins in kidney *** reverse transcription-polymerase chain reaction(q RT-PCR)was used to detect the expression of miR-17-5p in kidney ***,a DN in vitro model was constructed by high glucose culture of human mesangial cells(HMCs),cells were transfected with miR-17-5p mimic and/or treated with Nef,and we used q RTPCR to detect cellular miR-17 expression,flow cytometry to detect apoptosis,ELISAs to detect cellular SOD,MDA,and GSH-Px activities,Western blots to detect Nrf2/HO-1 signaling pathway-related protein expression,and dual luciferase reporter gene assays to verify the targeting relationship between Nrf2 and ***:Administration of Nef significantly reduced the levels of blood glucose,Crea,and UREA and the expression of miR-17-5p,improved renal histopathology and fibrosis,significantly reduced MDA levels,elevated SOD and GSH-Px activities,and activated Nrf2 expression in kidney tissues from mice with ***2 is a post-transcriptional target of *** HMCs transfected with miR-17-5p mimics,the m RNA and protein levels of Nrf2 were significantly ***,miR-17-5p overexpression and Nef intervention resulted in a significant increase in high glucose-induced apoptosis and MDA levels in HMC

关键词： diabetic nephropathies neferine miR-17-5p NF-E2-related factor 2 oxidative stress