PURPOSE:To explore the effect of Apabetalone on activating HIV-1 virus transcription and its molecular mechanism. METHODS:Peripheral blood mononuclear cells(PBMCs) latently infected with HIV-1 and J-Lat 10.6 cells were divided into two groups: a blank control group and an Apabetalone-treated group. After 48 h of culture with Apabetalone, bioinformatics and qRT-PCR were performed. Recombinant lentiviral vectors containing OSER1-AS1 and CDK9, along with empty vectors, were transfected into the cells for subsequent green fluorescent protein(GFP) fluorescence detection, cell cycle analysis, and apoptosis assays. RESULTS:Apabetalone efficiently activated HIV-1 viral transcription in J-Lat 10.6 and PBMC cells, increased the G0/G1 ratio of cells, and induced apoptosis. Apabetalone also downregulated the expression levels of MYC and p-Rb, and upregulated the expression levels of Tat and P21. Silencing OSER1-AS1 reduced apabetalone activation of HIV-1 transcription and inhibited apoptosis. CONCLUSION:Apabetalone enhances HIV-1 transcription by upregulating OSER1-AS1 expression, thereby promoting Tat-CDK9 binding.

Programmed cell death protein 1 (PD-1) is a key immune checkpoint involved in HIV-related immune escape, but its precise role and underlying mechanisms remain unclear. This study investigates the effects of PD-1 inhibition on HIV infection and T-cell function, focusing on the MAPK and NF-κB signaling pathways. Peripheral blood mononuclear cells (PBMCs) were isolated from HIV-infected individuals and healthy controls. T-cell subsets were analyzed for PD-1 expression via flow cytometry. The impact of antiretroviral therapy (ART) on T-cell numbers, apoptosis, and PD-1 expression was assessed. PD-1 blockade was performed using pembrolizumab, and its effects on T-cell survival and cytokine secretion were evaluated. MAPK/NF-κB signaling was analyzed using Western blot and co-immunoprecipitation, while latent HIV activation was assessed by measuring HIV-1 LTR transcriptional activity in J-Lat cells. Reverse-ChIP assays explored the interaction between HIV-1 Nef protein and the PD-1 promoter. PD-1 expression was higher in T cells from HIV-infected individuals compared to healthy controls, with no significant change following ART. PD-1 blockade with pembrolizumab reduced T-cell apoptosis and enhanced cytokine secretion (TNF-α, IFN-γ, IL-2). PD-1 inhibition also activated latent HIV in J-Lat cells. Western blotting revealed reduced phosphorylation of MAPK and NF-κB pathway components (p-MEK1/2, p-p38 MAPK, p-NF-κB p65), and co-immunoprecipitation confirmed a direct interaction between PD-1 and SHP-2, regulating these pathways. PD-1 mediates HIV immune evasion through the MAPK/NF-κB pathways. PD-1 blockade restores T-cell function and activates latent HIV, suggesting potential therapeutic strategies for HIV treatment.

OBJECTIVE:To investigate the molecular epidemiology of HIV-1 in Heilongjiang, China, and try to spot signs of new circulating recombinant form (CRF) in this region. DESIGN:A molecular epidemiological study was conducted in Heilongjiang, China during 2011-2020. METHODS:Plasma samples were collected from three HIV-1-positive patients (two MSM and one man lacking risk factor information). The near full-length genome sequences (NFLGs) of a novel CRF were then obtained and subjected to phylogenetic analysis using Mega 7.0.26. Recombination analysis was performed by the jumping profile Hidden Markov Model (jpHMM). Finally, the origin time of this novel CRF was inferred using the Bayesian phylogenetic analysis in Beast v1.10.4. RESULTS:The three NFLGs formed a distinct monophyletic cluster in the neighbor-joining (NJ) tree. Recombination analysis revealed that the recombinant genome was composed of five segments derived from CRF01_AE, subtypes B, and C, but further confirmed to be a second-generation recombinant form of CRF01_AE/CRF07_BC by a comparison of genome maps and subregion phylogenetic analysis and, therefore, designated as CRF136_0107. With Bayesian phylogenetic analysis, CRF136_0107 was estimated to originate around 2010-2011. CONCLUSION:A novel HIV-1 CRF01_AE/CRF07_BC second-generation CRF called CRF136_0107 was identified among MSM in Heilongjiang, a northeast province of China.

Objective: the purpose of this study was to assess the impact of 14 treatments including a total of 10 dietary antioxidants on the risk of prostate cancer.Material and methods: we searched PubMed, Embase, the Cochrane Library, and the Web of Science for only randomized controlled trials (RCTs) to investigate the effect of these 10 antioxidants on the risk of getting prostate cancer. Using the Cochrane Risk of Bias Assessment Tool, the methodological quality of the included studies was evaluated.Data extraction: studies were appraised by two investigators and data were extracted. Using a surface under cumulative ranking (SUCRA) probability, a Bayesian network meta-analysis was undertaken to evaluate the relative ranking of agents.Results: from the earliest accessible date through August 2022, RCTs were gathered. A total of 14 randomized controlled trials were included with a total sample size of 73,365 males. The results of the network meta-analysis showed that green tea catechins (GTCs) significantly reduced the risk of prostate cancer (SUCRA, 88.6 %) followed by vitamin D (SUCRA, 55.1 %), vitamin B6 (54.1 %), and folic acid was the lowest (22.0 %).Conclusion: based on the Ranking Plot of the Network, we can state that GTCs might have an impact on the prevention of prostate cancer compared to other dietary antioxidants, but we still need quality literature to further prove it.

乳头腺瘤(nipple adenoma)是起源于乳腺输乳管或输乳窦的良性肿瘤，属于导管内乳头状瘤的一种亚型。其发病率不足乳腺良性肿瘤的1%[1]，临床表现常为乳头、乳晕区肿块，伴疼痛、血性或浆液性乳头溢液，并可出现类似于乳腺Paget病的皮肤改变[2]，如乳头、乳晕区皮肤破溃、结痂等。镜下病理形态多种多样，易与浸润性癌和导管内癌相混淆[3]。组织病理学检查是当前诊断的金标准[2]。哈尔滨医科大学附属肿瘤医院乳腺外科收治了1例18岁乳头腺瘤患者，现将治疗过程报告如下。

BackgroundHuman immunodeficiency virus type 1 (HIV-1) epidemic in China is featured by geographical diversity of epidemic patterns. Understanding the characteristics of regional HIV-1 epidemic allows carrying out targeted prevention and controlling measures. This seven-year cross-sectional study was conducted in Heilongjiang, one province of Northeast China, where newly diagnosed infection is fast increasing yearly, but temporal HIV-1 epidemic trend is largely unknown.MethodsInformation of 1,006 newly diagnosed HIV-1-infected participants were collected before antiretroviral therapy during 2010–2016 in Heilongjiang province. HIV-1 genotype was identified based on the viral gag and env gene sequences. Recent infection was determined by Limiting-Antigen Avidity assays. Comparison analyses on the median ages, CD4 counts, proportions of stratified age groups and CD4 count groups, and rates of recent HIV-1 infection among different population and sampling times were performed to understand temporal HIV-1 epidemic features.ResultsHomosexual contact among men who have sex with men (MSM) was the main transmission route and CRF01_AE was the most dominant HIV-1 genotype. During 2010–2016, the HIV-1 epidemic showed three new changes: the median age continued to decline, the cases with a CD4 count more than 500 cells/μl (CD4hi cases) disproportionally expanded, and the recent HIV-1 infection rate steadily increased. MSM cases determined the temporal trend of HIV-1 epidemic here. Increase of young MSM cases (aged <30 years) made the main contribution to the younger age trend of MSM cases. These young MSM exhibited a higher median CD4 count, a higher proportion of CD4hi cases, and a higher rate of recent HIV-1 infection than cases aged 30 years and more. MSM infected by CRF01_AE virus mostly affected HIV-1 epidemic patterns among MSM population.ConclusionYoung MSM have become a new hotspot and vulnerable group for HIV-1 transmission in Heilongjiang Province, Northeast China. The rapid increase in the number of young MSM cases, mainly those with CRF01_AE infection, changed temporal HIV-1 epidemic pattern here. Measures for prevention and control of HIV-1 infection among this population are urgently needed in the future.

Background: Human immunodeficiency virus type 1 (HIV-1) epidemic in China is featured by geographical diversity of epidemic patterns. Understanding the characteristics of regional HIV epidemic allows carrying out targeted prevention and control measures. However, in some regions of Northeast China, current HIV-1 epidemic feature is largely unknown. Methods: Information of 1006 newly diagnosed HIV-1 infected participants were collected before antiretroviral therapy during 2010-2016 in Harbin city of Northeast China. HIV-1 genotype was identified based on the viral gag and env genes. Comparison analyses were made among different participant groups and sampling time periods to understand HIV-1 epidemic trend. Multivariable logistic regression was used to evaluate the factors associated with immune status of participants. Results: Homosexual contact among men who have sex with men (MSM) was the main transmission route and CRF01_AE was the most dominant HIV-1 genotype. Newly diagnosed cases were getting younger, which was mainly due to the continuous increase in the proportion of young cases (aged < 30 years) among CRF01_AE-infected individuals, especially the CRF01_AE-infected MSM. The proportion of cases with good immune status (CD4 count > 500 cells/μl) continued to increase, and younger in age, HIV-1 infection via homosexual contact among MSM and infection by non-CRF01_AE genotype were positive factors for the good immune outcome. Conclusions: Young MSM have become a new vulnerable group for HIV-1 transmission in Northeast China. This group is changing local HIV-1 epidemic pattern. Measures for preventing and controlling HIV-1 infection among this population are urgently needed in the future.

抗逆转录病毒治疗(antiretroviral therapy,ART)方案的推陈出新,进～步提升了人类免疫缺陷病毒(HIV)感染者/艾滋病(AIDS)患者的服药依从性并降低了疾病相关并发症出现的概率,从而延长了患者的寿命.但在ART方案广泛应用的同时,肝脏疾病已成为引起HIV感染者/AIDS患者的非AIDS相关死亡中最常见的一种疾病.由于传播途径相同,HBV、HCV与HIV合并感染最为常见.已有多项研究表明,HBV、HCV与HIV合并感染可促进肝脏炎症、坏死及纤维化改变,增加HBV DNA、HCV RNA的复制及CD4+T淋巴细胞的破坏,并可增加ART相关药物的肝脏毒性风险,最终加速患者发展至终末期肝病的进程.为更全面地了解HIV与HBV、HCV之间的相互作用,本文针对其合并感染的流行病学、临床结局及治疗进展做以下综述,旨为临床工作提供理论依据和指导.

获得性免疫缺陷综合征和慢性乙型肝炎是世界范围内广泛关注的两大传染性疾病,至今尚无有效的治愈方法.由于两者存在相同的传播途径,人类免疫缺陷病毒/乙型肝炎病毒(HIV/HBV)共感染患者在临床上较为常见.近年来,有效抗反转录病毒疗法的普及显著降低了HIV感染者的发病率和病死率,延长了HIV感染者的寿命.但HIV/HBV共感染者肝脏相关疾病的病死率仍显著高于单纯HIV感染患者.HIV可影响HBV感染的自然史,与单纯HBV感染相比,HIV/HBV共感染引起HBV-DNA水平升高、肝脏疾病进展加快及肝脏相关疾病病死率增高得到广泛认同.

近几年我国艾滋病病毒1型(HIV-1)的流行情况复杂,性接触传播逐渐成为感染HIV-1的最主要途径.CRF01_AE毒株在中国部分地区所占比例呈现逐年上升趋势,且与性传播密切相关,尤其在男男同性性行为者中广泛流行.本文对46篇针对CRF01_AE亚型研究的文献进行了综述,总结了我国HIV-1流行情况,并对我国黑龙江、河北、江苏、浙江、广西、广东、上海地区的HIV-1 CRF01_AE流行情况进行汇总,获得2004-2015年CRF01_AE亚型在HIV-1感染者基因亚型中所占比例变化规律,并分析了此毒株流行情况变化的原因.CRF01_AE毒株的快速传播和广泛分布为我国HIV-1感染的防控带来了挑战,在今后的防控工作中应密切关注该亚型毒株的变化情况.

Objective To analyze the epidemiological features of newly diagnosed HIV-1-infected individuals in Jiamusi city of Heilongjiang province. Methods Newly infected individuals were identified among 57 HIV-1-infected individuals who were diagnosed as HIV-1 positive during the years 2016 to 2017 by Lag Avidity EIA.Genomic DNAs were extracted from peripheral blood mononuclear cells (PBMCs) of all patients; viral gag and env gene fragments were amplified and subjected to sequencing.Phylogenetic trees were constructed to analyze gag and env gene features using Mega software, and the genotypes of viruses with intragenic or intergenic recombination were confirmed by the online jpHMM software in HIV database. Results Among the 57 newly diagnosed individuals, 38 (66.7％) were identified as newly infected cases.Homosexual contact among men who have sex with men (MSM) was the major route, accounted for 93.0％ (53/57) of HIV-1 cases, followed by heterosexual contact, responsible for 7.0％ (4/57) of the cases.Viral gag and env genes from these 57 newly diagnosed individuals were distributed into four genotypes: 33 (57.9％) of CRF01_AE, 11 (19.3％) of CRF07_BC, 6 (10.5％) of subtype B and 2 (3.5％) of subtype A1.Another 5 (8.8％) individuals were confirmed as infected by unique recombinant forms (URFs) viruses, including two variants containing intragenic recombination of CRF01_AE and subtype B gaggenes, two variants containing intergenic recombination of CRF07_BC gag and CRF01_AE env genes and one variants containing intergenic recombination of CRF07_BC gagand subtype Benvgenes.All the five URFs were derived from the MSM population. Conclusions Homosexual contact among MSM was the major transmission route of newly diagnosed HIV-1 infections in Jiamusi city of China.CRF01_AE was the dominant genotype.MSM population has become the critical source for generation of complicated recombinant viruses in this city.Timely survey of newly diagnosed HIV-1 infections among Jiamusi MSM population and development of effective prevention and control measures are urgently required.

OBJECTIVE:The current study aimed to understand epidemiological feature and critical factors associated with pathogenesis of circulating recombinant form (CRF) 01_AE strains in Northeast China.DESIGN:Compared analysis was made between CRF01_AE and non-CRF01_AE samples to understand the pathogenicity features of CRF01_AE. Further analyses between CRF01_AE samples with high or low CD4 cell counts and between samples with different coreceptor usages were done to explore the possible factors correlating to the pathogenesis of CRF01_AE viruses.METHODS:The genotypes of newly identified strains were determined by phylogenetic analyses using Mega 6.06. Coreceptor usage was predicted by Geno2Pheno algorithm. Potential N-linked glycosylation site (PNGS) number was calculated using the online N-glycosite software. The properties of amino acid sequences were analyzed by the online ProtParam tool.RESULTS:CRF01_AE become the main HIV-1 genotype since 2010. Compared with non-CRF01_AE group, the CRF01_AE group showed a higher proportion of samples with CD4 cell count less than 200 cells/μl. Shorter amino acid length, fewer PNGSs and the presence of a basic motif R/KNXT or NR/KT in V4 correlated to a lower CD4 cell count, and existence or coexistence of Thr12, Arg13, Val21 and Lys33, presence of more than 4 of net charges and lack of the PNGS within V3 favored to the X4/R5X4 coreceptor usage of CRF01_AE viruses.CONCLUSION:CRF01_AE has dominated HIV-1 genotype in Northeast China. Infection with CRF01_AE exhibited a fast disease progression, which may be associated with specific amino acid residues and PNGSs in V3 and V4 regions as well as amino acid length of V4 region.

The current HIV-1 epidemic in China is featured by diverse subtypes and continual emergence of new recombinant viruses. This study identified a novel unique recombinant form (URF), JL16013, among men who have sex with men (MSM) in Jilin, China. The JL16013 virus was different from all known subtypes and set up a distinct branch on the phylogenetic tree. This virus had a CRF01_AE backbone with two subtype B' fragments and one CRF65_cpx fragment inserted into gag, pol, env, and nef regions, suggesting that this novel URF might have originated from the CRF01_AE, subtype B', and CRF65_cpx viruses that were cocirculating in Jilin province. This was the first report of the CRF01_AE/B'/CRF65_cpx recombinant in China. Identification of this URF indicated the severity and complexity of the HIV-1 epidemic among MSM in Jilin province. Timely surveillance of new HIV-1 infections and new recombinants among the MSM population is urgently required.

目的 分析哈尔滨市新确诊男男同性性接触者(men who have sex with men,MSM) HIV-1感染病例的毒株基因型特征.方法 收集2012-2015年新确诊且未经过抗病毒治疗的HIV-1感染者抗凝血,分离外周血单核细胞,从中提取基因组DNA,采用巢式PCR法扩增gag和env基因.采用MEGA7.0软件构建gag和env基因系统发育树,分析基因型特点.结果 共收集148例MSM HIV-1感染者样本,均获得gag和env基因序列.系统发育树显示,其中CRF01_AE亚型108例,占73.0％;B亚型19例,占12.8％;CRF07_BC12例,占8.1％;独特重组型9例,占6.1％.在不同年份、不同年龄群体的标本中,CRF01_AE均为优势基因型.在CRF01_AE毒株中,98.1％ (106/108)与我国MSM人群参考株成簇,1.9％ (2/108)与泰国及我国西南地区异性传播参考株成簇.77.8％ (7/9)的独特重组型毒株来自20～40岁群体.2012年开始出现gag和env基因间重组亚型,2014年发现gag基因内重组亚型,2015年出现基因内和基因间均发生重组的复杂亚型,尚未发现env基因内重组毒株.结论 哈尔滨市2012年至2015年新确诊男男同性性接触人群HIV-1感染病例中流行毒株基因型较复杂,CRF01_AE亚型毒株一直是本地区的优势毒株,同时,基因间和基因内重组毒株已出现.因此,加强MSM人群新发感染病例的实时监测,并制定有效的预防措施是非常必要的.

This study reported a new HIV-1 circulating recombinant form CRF65_cpx virus isolated from a man who have sex with men (MSM) in Jilin, China. The near full-length genome of this virus was composed of 14 mosaic gene fragments derived from CRF01_AE, subtype B' (Thai B) and subtype C, highly similar to the CRF65_cpx viruses recently identified in Yunnan and Anhui of China. Phylogenetic tree analysis suggested that this CRF65_cpx strain was not generated among MSM in Jilin, but originated in southern regions of China and spread to Jilin by MSM population. The emergence of CRF65_cpx in Jilin indicated HIV-1 epidemic in this area was more and more complicated and the MSM population has become the important source for generation of new recombinant viruses. Real-time surveillance of new HIV-1 infections among MSM population is quite required.

Increasing attention has been focused on the malignant tumor microenvironment, which plays important roles in tumor occurrence, progression and metastasis. Fibroblasts are recruited by platelet-derived growth factor (PDGFs) and invade the tumor microenvironment. In the PDGF family, PDGF-B has been reported to play an important role in the recruitment and invasion programs. However, whether PDGF-D plays a role in these programs remains unclear. We generated a recombinant plasmid expressing human PDGF-D and transfected the plasmid to dermal fibroblasts to examine the effects on cell invasive activities in 3D type I collagen gels. PDGF-D plasmid transfection enhanced fibroblast invasive activities both in invasive cell numbers and invasion depth in 3D collagen gels. These effects were blocked by Snail-specific siRNA transfection. PDGF-D transfection significantly induced Snail expression at both mRNA and protein levels. PDGF-D further upregulated MT1-MMP mRNA and protein expressions and this was inhibited when Snail was knocked down by siRNA. Both Snail and MT1-MMP expressions in fibroblasts and cellular invasive activities in 3D collagen induced by PDGF-D were inhibited by LY294002, SP600125, and U1026, the inhibitors of PI3K, JNK, and ERK1/2 signaling pathways, respectively. However, no effects were observed in response to the P38MAPK signaling pathway inhibitor SB203580. These effects of PDGF-D were confirmed by using the culture supernatants of the transfectants. Taken together, these data demonstrate that PDGF-D plays important roles in the recruitment and invasion programs of fibroblasts via the activation of PI3K, JNK and ERK1/2 signaling pathways, and upregulation of Snail and downstream effecter MT1-MMP. These findings indicate that PDGF-D is an important player in the tumor microenvironment for fibroblast recruitment.

Cardiac autoimmune reaction takes part in myocarditis, dilated cardiomyopathy and heart failure. Existing literature has confirmed that the occurrence of cardiomyopathy belongs to mitochondrial diseases and is related to the oxidative respiratory chain subunit. The special structure of iron-sulfur protein (ISP) is responsible for the oxidative stress in oxidative phosphorylation, which is also a target that is easily attacked by various damage factors. Using gene therapy technology to restore succinate dehydrogenase iron-sulfur protein (SDISP) function- and thus resume myocardial mitochondria function and myocardial function is hypothesized to alleviate the experimental autoimmunity myocarditis (EAM).

目的 对比紫绀型先心病(cyanotic congenital heart disease,C-CHD)和非紫绀型先心病(acyanotic congenital heart disease,A-CHD)患儿来源的骨髓间充质干细胞(human mesenchymal stem cells,hMSCs)在乏氧环境下的抗凋亡能力,并探讨其发生机制.方法 hMSCs取自C-CHD(C组)和A-CHD(A组)患儿(男女不限,0～5岁),于体外乏氧环境下(1％O2,5％ CO2,94％ N2)培养.以Annexin V/PI双染结合流式细胞技术对比两组细胞抵御缺血缺氧诱导细胞凋亡的能力;以Western blot法检测两组细胞中B细胞淋巴瘤-2基因(B-cell lymphoma-2,Bcl-2),Bcl-2相关X蛋白(Bax)以及半胱氨酸天冬氨酸蛋白酶-3(caspase-3)的含量.结果 Annexin V/PI双染结合流式细胞检测结果显示:在缺血缺氧环境下,C组细胞的早期凋亡率(P＜0.01)和总体凋亡率(P＜0.05)低于A组细胞.Western-blot检测结果显示:C组细胞的凋亡抑制基因Bcl-2的含量高于A组细胞(P＜0.05),抗凋亡抑制基因Bax (P＜0.05)以及caspase-3 (P＜0.05)的含量低于A组细胞.结论 C-CHD患者来源的hMSCs具有更好的抗缺血缺氧诱导的总凋亡及早期凋亡能力,这可能与其天然乏氧诱导的Bcl-2表达上调,Bax,caspase-3表达下调有关.

Epithelial-mesenchymal transition (EMT) is critical for carcinoma invasiveness and metastasis. To investigate the role of membrane-type-2 matrix metalloproteinase (MT2-MMP) in EMT, we generated lentiviral constructs of wild-type (WT) and an inactive Glu260Ala (E260A) mutant MT2-MMP and derived stably transfected HCT116 and A549 cell lines. WT-transfected cells appeared mesenchymal-like, whereas cells transfected with the E260A mutant were epithelial-like, as were cells treated with an MMP inhibitor (GM6001). Expression of E-cadherin, β-catenin, and zonula occludens-1 was lower in cells transfected with WT MT2-MMP compared to vector controls, cells treated with GM6001, or cells transfected with the E260A mutant. An 80-kD N-terminal fragment of E-cadherin was immunoprecipitated in conditioned medium from WT MT2-MMP cells, but not in the medium from vector controls, cells treated with GM6001, or E260A mutant cells. When endogenous expression of MT2-MMP in A2780 human ovarian cancer cells was inhibited using GM6001 or MT2-MMP-specific siRNA, levels of the 80-kD E-cadherin fragment in conditioned medium were decreased. Chick embryo chorioallantoic membrane invasion assays demonstrated that cells transfected with WT MT2-MMP were more invasive than cells transfected with control vector, treated with GM6001, or transfected with the E260A mutant. These results suggest that MT2-MMP degrades adherens and tight junction proteins and results in EMT, making it a potential mediator of EMT in carcinomas.

The molecular mechanisms of ovarian cancer cell invasion under hypoxia remain unclear. Here we employed a 3D collagen model and chick chorioallantoic membrane (CAM) invasion assay to explore the influence of hypoxia on ovarian cancer cell invasion. Hypoxia (both 1% O2 and CoCl2 150 and 250 µM) induced HO-8910PM ovarian cancer cell invasion in 3D collagen and collagenolysis determined by hydroxyproline. Pretreatment with a hypoxia inducible factor-1α inhibitor, YC-1, or MMP inhibitor, GM6001, significantly inhibited 3D collagen invasion and degradation and cell proliferation. Hypoxia stimulated both mRNA and protein expressions of membrane-type 1 matrix metalloproteinase (MT1-MMP) and promoted MT1-MMP translocation to the cell surface in an YC-1 sensitive manner. MT1-siRNA transfection inhibited hypoxia-induced invasion, proliferation, and collagen degradation of cells in 3D collagen. Hypoxia stimulated Snail mRNA and protein expression as well as translocation to nucleus in an YC-1 sensitive manner. Overexpression of Snail with a recombinant plasmid in HO-8910PM cells resulted in an enhanced invasion in 3D collagen. Transfection with Snail-specific siRNA significantly decreased MT1-MMP expression and 3D collagen invasion. Hypoxia-treated cells significantly broke the upper CAM surface of 11-day-old chick embryos and infiltrated interstitial tissue, completely blocked in the presence of YC-1 or GM6001, or after MT1-MMP siRNA or Snail siRNA transfection. Together, these data suggest that hypoxia promotes HO-8910PM ovarian cancer cell traffic through 3D matrix via Snail-mediated MT1-MMP upregulation, a possible molecular mechanism of ovarian cancer cell invasion under hypoxia.