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Monotropein Induced Apoptosis and Suppressed Cell Cycle Progression in Colorectal Cancer Cells

Chinese Journal of Integrative Medicine 2024年第1期30卷 25-33页

作者： GAO Quan LI Lin ZHANG Qi-man SHENG Qin-song ZHANG Ji-liang JIN Li-jun SHANG Rui-yan School of Pharmacy and Department of Medical Oncology the Affiliated Hospital of Hangzhou Normal UniversityHangzhou Normal UniversityHangzhou(311121)China Key Laboratory of Elemene class Anti-Cancer Chinese Medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhou(311121)China Department of Colorectal Surgery the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina Beijing Tong Ren Tang Chinese Medicine Co. Ltd.Beijing(100000)China Department of Traditional Chinese Medicine Hangzhou Shangcheng District People's HospitalHangzhou(310006)China Department of gynecology Hangzhou Women's HospitalHangzhou(310008)China

Objective: To determine whether monotropein has an anticancer effect and explore its potential mechanisms against colorectal cancer(CRC) through network pharmacology and molecular docking combined with experimental verification. Methods: Network pharmacology and molecular docking were used to predict potential targets of monotropein against CRC. Cell counting kit assay, plate monoclonal assay and microscopic observation were used to investigate the antiproliferative effects of monotropein on CRC cells HCT116, HT29 and LoVo. Flow cytometry and scratch assay were used to analyze apoptosis and cell cycle, as well as cell migration, respectively in HCT116, HT29, and LoVo cells. Western blotting was used to detect the expression of proteins related to apoptosis, cell cycle, and cell migration, and the expression of proteins key to the Akt pathway. Results: The Gene Ontology and Reactome enrichment analyses indicated that the anticancer potential of monotropein against CRC might be involved in multiple cancer-related signaling pathways. Among these pathways, RAC-beta serine/threonine-protein kinase(Akt1, Akt2), cyclin-dependent kinase 6(CDK6), matrix metalloproteinase-9(MMP9), epidermal growth factor receptor(EGFR), cell division control protein 42 homolog(CDC42) were shown as the potential anticancer targets of monotropein against CRC. Molecular docking suggested that monotropein may interact with the 6 targets(Akt1, Akt2, CDK6, MMP9, EGFR, CDC42). Subsequently, cell activity of HCT116, HT29 and LoVo cell lines were significantly suppressed by monotropein(P<0.05). Furthermore, our research revealed that monotropein induced cell apoptosis by inhibiting Bcl-2 and increasing Bax, induced G_1–S cycle arrest in colorectal cancer by decreasing the expressions of CyclinD1, CDK4 and CDK6, inhibited cell migration by suppressing the expressions of CDC42 and MMP9(P<0.05), and might play an anticancer role through Akt signaling pathway. Conclusions: Monotropein exerts its antitumor

关键词： monotropein Chinese medicine anticancer activity colorectal cancer cells network pharmacology

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MiR-142-3p Regulates ILC1s by Targeting HMGB1 via the NF-κB Pathway in a Mouse Model of Early Pregnancy Loss

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Current Medical Science 2024年第1期44卷 195-211页

作者： Xiang-li PANG Jie LI Jing WANG Si-si YAN Jing YANG Department of Obstetrics and gynecology Renmin Hospital of Wuhan UniversityWuhan 430060China Reproductive Medical Center Renmin Hospital of Wuhan UniversityWuhan 430060China Clinic Research Center for Assisted Reproductive Technology and Embryonic Development in Hubei Province Wuhan 430060China

Objective Innate lymphoid cells(ILCs)are a class of newly discovered *** 1 ILCs(ILC1s)are identified in the decidua of humans and *** mobility group box 1(HMGB1)is predicted to be one of the target genes of miR-142-3p,which is closely related to pregnancy-related ***,miR-142-3p and HMGB1 are involved in regulating the NF-κB signaling *** study aimed to examine the regulatory effect of miR-142-3p on ILC1s and the underlying mechanism involving HMGB1 and the NF-κB signaling *** Mouse models of normal pregnancy and abortion were constructed,and the alterations of ILC1s,miR-142-3p,ILC1 transcription factor(T-bet),and pro-inflammatory cytokines of ILC1s(TNF-α,IFN-γand IL-2)were detected in mice from different *** targeting regulation of HMGB1 by miR-142-3p in ILC1s,and the expression of HMGB1 in normal pregnant mice and abortive mice were *** addition,the regulatory effects of miR-142-3p and HMGB1 on ILC1s were detected in vitro by CCK-8,Annexin-V/PI,ELISA,and RT-PCR,***,changes of the NF-κB signaling pathway in ILC1s were examined in the different *** the in vivo studies,miR-142-3p-Agomir was injected in the uterus of abortive mice to evaluate the abortion rate and alterations of ILC1s at the maternal-fetal interface,and further detect the expression of HMGB1,pro-inflammatory cytokines,and the NF-κB signaling *** The number of ILC1s was significantly increased,the level of HMGB1 was significantly upregulated,and that of miR-142-3p was considerably downregulated in the abortive mice as compared with the normal pregnant mice(all P<0.05).In addition,miR-142-3p was found to drastically inhibit the activation of the NF-κB signaling pathway(P<0.05).The number of ILC1s and the levels of pro-inflammatory cytokines were significantly downregulated and the activation of the NF-κB signaling pathway was inhibited in the miR-142-3p Agomir group(all P<0.05).Conclusion

关键词： maternal-fetal interface group 1 innate lymphoid cells(ILCis) high mobility group box 1(HMGB1) miR-142-3p abortion

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The effectiveness and safety of acupuncture for poor semen quality in infertile males： a systematic review and meta-analysis

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Asian Journal of Andrology 2014年第6期16卷 884-891页

作者： Ui Min Jerng Jun-Young Jo Seunghoon Lee Jin-Moo Lee Ohmin Kwon class of Oncology class of gynecology Department of Clinical Korean Medicine Kyung Hee University Graduate School Seoul Korea Conmaul Hospital Seoul Korea class of Acupuncture and Moxibustion Department of Clinical Korean Medicine Kyung Hee University Graduate School Seoul Korea Medical History and Literature Group Korea Institute of Oriental Medicine Daejeon Korea

The aim of this review is to evaluate the effectiveness and safety of acupuncture for poor semen quality in infertile men. We searched for relevant trials registered up to May 2013 in 14 databases. We selected randomized controlled trials （RCTs） that compared acupuncture, with or without additional treatment, against placebo, sham, no treatment, or the same additional treatment. Two reviewers independently performed the study selection, data extraction, risk of bias and reporting quality appraisal. Risk of bias and reporting quality were appraised by the Cochrane risk of bias tool, the consolidated standards of reporting trials and Standards for Reporting Interventions in Clinical Trials of Acupuncture. The outcomes were sperm motility, sperm concentration, pregnancy rate, and adverse events. Pregnancy was defined as a positive pregnancy test. Four RCTs met the eligibility criteria. Acupuncture increased the percentage of sperm with rapid progression （mean difference - 6.35, 95% confidence interval （CI）. 4.38-8.32, P〈 0.00001） and sperm concentration （mean difference - 6.42, 95% CI. 4.91-7.92, P〈 0.00001）, but these two outcomes were substantially heterogeneous among the studies （F = 72% and 58%, respectively）. No differences in pregnancy rate were found between acupuncture and control groups （odds ratio 1.60, 95% CI. 0.70-3.69, P= 0.27, F = 0%）. No participants experienced adverse events. The current evidence showing that acupuncture might improve poor semen quality is insufficient because of the small number of studies, inadequacy of procedures and/or insufficient information for semen analysis, high levels of heterogeneity, high risk of bias, and poor quality of reporting. Further large, well-designed RCTs are required.

关键词： acupuncture asthenozoospermia male infertility oligozoospermia sperm quality

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Designing Bioorthogonal Reactions for Biomedical Applications

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Research 2024年第3期2023卷 625-650页

作者： Qingfei Zhang Gaizhen Kuang Li Wang Ping Duan Weijian Sun Fangfu Ye Wenzhou Institute University of Chinese Academy of SciencesWenzhou 325001China Beijing National Laboratory for Condensed Matter Physics Institute of PhysicsChinese Academy of SciencesBeijing 100190China. Department of Obstetrics and gynecology The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325027China. Department of Gastrointestinal Surgery The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityWenzhou325027China.

Bioorthogonal reactions are a class of chemical reactions that can be carried out in living organisms without interfering with other reactions, possessing high yield, high selectivity, and high efficiency. Since the first proposal of the conception by Professor Carolyn Bertozzi in 2003, bioorthogonal chemistry has attracted great attention and has been quickly developed. As an important chemical biology tool, bioorthogonal reactions have been applied broadly in biomedicine, including bio-labeling, nucleic acid functionalization, drug discovery, drug activation, synthesis of antibody–drug conjugates, and proteolysis-targeting chimeras. Given this, we summarized the basic knowledge, development history, research status, and prospects of bioorthogonal reactions and their biomedical applications. The main purpose of this paper is to furnish an overview of the intriguing bioorthogonal reactions in a variety of biomedical applications and to provide guidance for the design of novel reactions to enrich bioorthogonal chemistry toolkits.

关键词： orthogonal summarized chemistry

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TLR9 Expression and Its Role in Chemosensitivity to DDP in Human Cervical Cancer Cells in vitro

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2011年第4期31卷 550-554页

作者：翁艳洁王永军石英周文娟王鸿雁王常玉 Department of Obstetrics and gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Minimally Invasive Center of gynecology Beijing Obstetrics and Gynecology HospitalCapital Medical University

Inflammation and infection play an important role in the pathogenesis of many ***-like receptors（TLRs） are a class of pattern recognition receptors that recognize conserved components of microbes and trigger the immune response against invading ***-like receptor 9（TLR9） recognizes non-methylated cytosine-phosphateguanosine（CpG） DNA sequences which are the surrogate for viral ***9 may react to tumor development and progression during chronic inflammation that involves the tumor *** order to study the role of TLR9 in cervical cancer,we analyzed the TLR9 expression in different types of HPV infection cervical cancer *** we detected if CpG sequences influenced the TLR9 expression and the sensitivity to cisplatin（DDP） of these cervical cancer cells in *** expression of TLR9 mRNA and protein in SiHa,Hela and C33A cells was detected by RT-PCR and Western ***-time PCR was used to examine the TLR9 expression changes induced by *** of the cervical cancer cells to cisplatin（DDP） was measured by *** was observed that the expression of TLR9 mRNA and protein was increased gradually in SiHa（HPV16＋）,Hela（HPV18＋） and C33A（HPV-） *** doses of CpG increased the TLR9 expression only in C33A（HPV-） cells,but not in SiHa（HPV16＋） and Hela（HPV18＋） ***,low dose of CpG significantly increased the sensitivity of C33A（HPV-） cells,but not that of SiHa（HPV16＋） and Hela（HPV18＋） *** results indicated that TLR9 may serve as a protective agent in HPV negative cervical cancer *** was concluded that TLR9 could improve the sensitivity to DDP in HPV negative cervical cancer cells and might represent a potential therapeutic option in clinical practice.

关键词： cervical cancer Toll-like receptor 9 cisplatin HPV infection

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Oridonin induces apoptosis via PI3K/Akt pathway in cervical carcinoma HeLa cell line

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Acta Pharmacologica Sinica 2007年第11期28卷 1819-1826页

作者： Hong-zhen HU~2,Yue-bo YANG~3,Xiang-dong XU~4,Hong-wei SHEN~5,Yi-min SHU~6,Zi REN~7,Xiao-mao LI~3,Hui-ming SHEN~3,Hai-tao ZENG~(3,8)~2 Department of gynecology and Obstetrics,Yijishan Hospital,Wannan Medical College,Wuhu 241001,China ~3 Department of gynecologyand Obstetrics,the Third Affiliated Hospital,Sun Yat-sen University,Guangzhou 510080,China ~4 Department of Surgery,the First AffiliatedHospital,Sun Yat-sen University,Guangzhou 510080,China ~2 Department of gynecology and Obstetrics,the First Affiliated Hospital,SunYat-sen University,Guangzhou 510080.China ~6 Department of Obstetrics and gynecology,IVF Program,Stanford University MedicalCenter,Palo Alto,CA 94304,USA ~7 Department of gynecology and Obstetrics,Guangdong Provincial People's Hospital,Guangzhou510080.China Department of gynecology and Obstetrics Yijishan Hospital Wannan Medical College Wuhu China Department of gynecology and Obstetrics the Third Affiliated Hospital Sun Yat-sen University Guangzhou China Department of Surgery the First Affiliated Hospital Sun Yat-sen University Guangzhou China Department of gynecology and Obstetrics the First Affiliated Hospital Sun Yat-sen University Guangzhou China Department of Obstetrics and gynecology IVF Program Stanford University Medical Center Palo Alto USA Department of gynecology and Obstetrics Guangdong Provincial People's Hospital Guangzhou China

Aim:To investigate the apoptosis-inducing effect of oridonin,a diterpenoid iso-lated from Rabdosia rubescens,in the human cervical carcinoma HeLa cell ***:A morphological analysis,nuclear condensation,and fragmentation ofchromatin were monitored using Hoechst 33342 *** viability was as-sessed using the 3-(4,5-dimethylthiazol-(2)-yl)-2,5-diphenyl tetrazolium bromide(MTT) *** apoptosis and the apoptosis-related activation in the HeLa cellline were evaluated by flow cytometry and Western ***:Oridoninsuppressed the proliferation of the HeLa cell line in a dose-and *** treatment downregulated the activation of protein kinase B(Akt),the expression of forkhead box class O (FOXO) transcription factor,andglycogen synthase kinase 3 (GSK3).Oridonin also induced the release of cyto-chrome c accompanied by the activation of caspase-3 and poly-adenosine diphos-phate-ribose polymerase *** addition,Z-D(OMe)-E(OMe)-V-D(OMe)-FMK (z-DEVD-fmk),an inhibitor of caspases,prevented caspase-3 activation andabrogated oridonin-induced cell ***,oridonin treatment of the HeLa cellline downregulated the expression of the inhibitor of the apoptosis ***:Our results showed that oridonin-induced apoptosis involved sev-eral molecular *** may suppress constitutively activated targetsof phosphatidylinositol 3-kinase (Akt,FOXO,and GSK3) in the HeLa cell line,inhibiting the proliferation and induction of caspase-dependent apoptosis.

关键词： cervical carcinoma oridonin apoptosis Akt

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Binding of Human SWI1 ARID Domain to DNA without Sequence Specificity: A Molecular Dynamics Study

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2015年第4期35卷 469-476页

作者：孙茜朱涛王常玉马丁 Department of Obstetrics and gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology

SWI 1 is a member of a new class of tumor DNA-binding proteins named as the AT-rich in- teraction domain family （ARID）, and considered to bind with AT base pairs specifically. Genomic and functional data support ARID1A as a tumor suppressor because AR1D1A/BAF250a （SWI1） subunit of the SWI/SNF chromatin-remodeling complex has emerged as recurrently mutated in a broad array of tumor types. But the crystal structure of SWI1 has not been solved as yet. Using docking and molecular dynamics, we predicted the DNA interaction pattern of human SWI1 ARID and made comparisons with the other two representative ARID family members, human Mrf-2 ARID and Drosophila Dri ARID. Dynamic results revealed that the N-terminal and loop L1 of SWI1 ARID bound with the DNA major groove, while the loop L2 and helix H6 bound with the minor groove. Moreover, it was found that SWI1 ARID bound with DNA apparently in a sequence-nonspecific manner. It was concluded that SWI1 ARID can form stable complex with sequence-nonspecific DNA segment comparing to Mrf-2 ARID/DNA and Dri ARID/DNA sequence-specific complexes.

关键词： AT-rich interaction domain family 1A (ARID) BAF250a Mrf-2 ARID Dri ARID pro- tein-DNA interaction ovarian cancer

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The role of AFAP1-AS1 in mitotic catastrophe and metastasis of triple-negative breast cancer cells by activating the PLK1 signaling pathway

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Oncology Research 2023年第3期31卷 375-388页

作者： SHUIZHONG CEN XIAOJIE PENG JIANWEN DENG HAIYUN JIN ZHINAN DENG XIAOHUA LIN DI ZHU MING JIN YANWEN ZHU PUSHENG ZHANG YUNFENG LUO HONGYAN HUANG Department of Spinal Surgery Orthopedic Medical CenterZhujiang HospitalSouthern Medical UniversityGuangzhou510280China Department of Critical Care Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou510515China Department of Breast Surgery Zhujiang HospitalSouthern Medical UniversityGuangzhou510280China Department of gynecology and Obstetrics Southern Hospital Taihe BranchSouthern Medical UniversityGuangzhou510540China Department of Clinical Medicine Nanshan ClassGuangzhou Medical UniversityGuangzhou511436China Department of Gastroenterology Shenzhen HospitalSouthern Medical UniversityShenzhen518110China

Triple-negative breast cancer(TNBC)is characterized by fast growth,high metastasis,high invasion,and a lack of therapeutic *** and metastasis of TNBC cells are two important biological behaviors in TNBC malignant *** is well known that the long noncoding RNA AFAP1-AS1 plays a crucial role in various tumors,but whether AFAP1-AS1 is involved in the mitosis of TNBC cells remains *** this study,we investigated the functional mechanism of AFAP1-AS1 in targeting Polo-like Kinase 1(PLK1)activation and participating in mitosis of TNBC *** detected the expression of AFAP1-AS1 in the TNBC patient cohort and primary cells by in situ hybridization(ISH),northern blot,fluorescent in situ hybridization(FISH)and cell nucleus/cytoplasm RNA fraction *** AFAP1-AS1 expression was negatively correlated with overall survival(OS),disease-free survival(DFS),metastasis-free survival(MFS)and recurrence-free survival(RFS)in TNBC *** explored the function of AFAP1-AS1 by transwell,apoptosis,immunofluorescence(IF)and patient-derived xenograft(PDX)models in vitro and in *** found that AFAP1-AS1 promoted TNBC primary cell survival by inhibiting mitotic catastrophe and increased TNBC primary cell growth,migration and ***,AFAP1-AS1 activated phosphorylation of the mitosis-associated kinase PLK1 *** levels of AFAP1-AS1 in TNBC primary cells increased PLK1 pathway downstream gene expression,such as CDC25C,CDK1,BUB1 and *** importantly,AFAP1-AS1 increased lung metastases in a mouse metastasis *** together,AFAP1-AS1 functions as an oncogene that activates the PLK1 signaling ***1-AS1 could be used as a potential prognostic marker and therapeutic target for TNBC.

关键词： TNBC AFAP1-AS1 Mitotic catastrophe Metastasis PLK1

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Is There Any Role for Calcium Ionophore in ICSI Cycles for Cases of Non Obstructive Azoospermia?

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Open Journal of Obstetrics and gynecology 2021年第8期11卷 1037-1049页

作者： Mohamed Elmahdy Yasser Oreif Soad Musleh Emadeldin Khalifa Obstetrics and gynecology Alexandria University Alexandria Egypt

Objectives: Evaluate the effect of artificial oocyte activation (AOA) using calcium ionophore (A23187) on the rate of fertilization and cleavage of embryos in surgically retrieved sperm of patients with non-obstructive azoospermia undergoing intracytoplasmic sperm injection (ICSI). Study design: This study was conducted on 60 infertile couples undergoing ICSI cycles as a randomized controlled parallel group’s experimental study in a private IVF center in Egypt from January 2018 to July 2019. ICSI cycles were divided into two groups: Group A: includes 30 ICSI patients with surgically retrieved sperms of non-obstructive azoospermia treated with calcium ionophore (A23187). Group C/Control: includes 30 ICSI patients with surgically retrieved sperms of non-obstructive azoospermia non-treated with calcium ionophore (A23187). Results: There was no statistical difference between both groups regarding the fertilization rate (p = 0.853). There was no statistical difference between them regarding implantation rate (p = 0.237). The percentage of Class A embryos in the ca ionophore group was 81.7%, while it was 82.8% in the control group. There was insignificant difference between them (

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Molecular subtypes identified by gene expression profiling in early stage endometrioid endometrial adenocarcinoma

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Chinese Medical Journal 2013年第19期126卷 3680-3684页

作者： GAO Bao-rong CHEN Yong-hua YAO Yuan-yang LI Xiao-ping WANG jian-liu WEI Li-hui Department of Obstetrics and gynecology Peking UniversityPeople's Hospital Beijing 100044 China

Background Early stage （FIGO stage Ⅰ-Ⅱ） endometrioid endometrial adenocarcinoma （EEA） is very common in clinical ***,patients with the early stage EEA show various clinical behaviors due to biological ***,we aimed to discover distinct classes of tumors based on gene expression profiling,and analyze whether the molecular classification correlated with the histopathological stages or other clinical *** Hierarchical clustering was performed for class discovery in 28 eady stage EEA samples using a special cDNA microarray chip containing 492 genes designed for endometrial *** between clinicopathologic parameters and our classification were *** the significance analysis of microarrays （SAM） array was used to identify the signature genes according to the tumor grade and myometrial *** Three tumor subtypes （subtypes Ⅰ,Ⅱ and Ⅲ） were identified by hierarchical clustering,each subtype had different clinicopathological factors,such as tumor grade,myometrial invasion status,and FIGO ***,SAM analysis showed 34 up-regulated genes in high grade tumors,and 38 up-regulated genes and 1 down-regulated in deep myometrial invasive *** overlap genes between these two high-risk factors were markedly up-regulated in subtype Ⅰ,but down-regulated in subtype Ⅲ.Conclusion We have identified novel molecular subtypes in early stage *** gene signatures characterize each tumor subtype,which could be used for recognizing the tumor risk and providing a basis for further treatment stratification.

关键词： endometrioid adenocarcinoma molecular classification gene expression profiling risk factor

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