Journal of Environmental Pathology Toxicology and Oncology最新文献

{"title":"Recent Evidence and Possible Therapy against COVID-19-Mediated Hepatic Dysfunction.","authors":"Nemat Ali","doi":"10.1615/JEnvironPatholToxicolOncol.2021039357","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2021039357","url":null,"abstract":"<p><p>Over the years, a novel RNA coronavirus has emerged with mutational episodes. This virus was confirmed to cause severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus infectious disease-2019 (COVID-19). This particular emphasis has raised the risk signal at the global level. Hepatic injury has been known to be a major impairment with varying factors. In recent years, the mechanistic event of hepatic injury is now more controversial and has a lack of justifiable set. Nevertheless, it has been investigated for the prominence of inflammatory signals, viral load in hepatocytes, followed by an intensive care therapeutic defense, and/or drug toxicity. Limited reports are available on infection-mediated hepatic injury, and its associated mechanism is still poorly understood. In the context of COVID-19 infections, the initial episode is pulmonary disorder with a systemic infection in multiple organs, including the liver. The majority of the reported cases reveal hepatic damage or dysfunction among COVID-19-infected patients. Prevalence of altered biochemistry of liver enzymes was also observed in the COVID-19 infected population. Our review focuses on the probable mechanisms and therapeutic options of COVID-19 and its associated hepatic dysfunction. We also discuss the available prescribed medications against COVID-19 infections, such as remdesiver, oseltamivir, lopina-vir/ritonavir, ribavirin, anticoagulant, anti-inflammatory, and immune-based therapies.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"40 4","pages":"33-41"},"PeriodicalIF":2.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39747692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Organochlorine Pesticide Tissue Levels in Benign and Malignant Breast Disease: A Comparative Exploratory Study.","authors":"Pankaj Kumar Garg,&nbsp;Nilokali Chishi,&nbsp;Rahul Kumar,&nbsp;Thammineni Krishna Latha,&nbsp;Shreyash Rai,&nbsp;Basu Dev Banerjee,&nbsp;Sanjay Gupta","doi":"10.1615/JEnvironPatholToxicolOncol.2020035783","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2020035783","url":null,"abstract":"<p><p>Exposure to organochlorine pesticides (OCPs) may be a risk factor for breast cancer (BC). Their role may be more relevant in developing countries such as India, where an abundance of these products is used for agricultural purposes. The present study compares OCP tissue levels in patients who underwent BC surgery (group A) or patients who had surgery for excision of breast fibroadenoma (group B). We perform OCP level quantification using a PerkinElmer, Inc. (Waltham, MA) gas chromatograph (GC) that is equipped with a 63Ni selective electron-capture detector. Significantly higher breast tissue OCP levels are present in the study population, indicating significant exposure. We detect 18 different types of OPCs in study subjects, with six OPCs (γ-hexachlorocyclohexane [HCH], δ-HCH, endrin, endosulfan-II, p,p'-dichlorodiphenyldichloroenthane [DDD], and p,p'-dichlorodiphenyltrichloroenthane [DDT]) present in all subjects. Endosulfan-II, p,p'-DDT, and p,p'-DDD tissue levels are significantly higher in BC patients than in those with fibroadenoma. Higher tissue levels of OCPs (α-HCH) are significantly associated with the presence of extracapsular spread (1.42 vs. 0.91; p = 0.04) and higher disease stage (early BC vs. locally advanced BC; 18.90 vs. 11.90; p = 0.04). The present pilot study indicates higher OCP tissue levels in northern India BC patients compared to patients with fibroadenoma.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"40 1","pages":"43-50"},"PeriodicalIF":2.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25410260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HDAC3-Mediated Repression of LncRNA-LET Regulates Gastric Cancer Cell Growth Proliferation, Invasion, Migration, and Apoptosis via MiR-548k.","authors":"Jie Zhang,&nbsp;Xiaoyu Liu,&nbsp;Jun Chen,&nbsp;Shufeng Xia","doi":"10.1615/JEnvironPatholToxicolOncol.2021039050","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2021039050","url":null,"abstract":"<p><p>Emerging studies have indicated the aberrant expression of histone deacetylases (HDACs) is closely associated with the development of tumors. However, the regulatory roles of HDACs-regulated long noncoding RNAs (lncRNA) in gastric cancer (GC) remain largely unknown. In this study, the effects of HDAC3 and HDAC3-mediated lncRNA-LET on the progression of GC were investigated. The expressions of HDAC3, lncRNA-LET, and miR-548k in GC cell lines were analyzed. The biological functions of HDAC3 and lncRNA-LET were measured by CCK-8 assay, Transwell assay, Western blot analysis, and cell apoptosis assays. Chromatin immunoprecipitation and luciferase reporter assay verified the regulatory relationship between HDAC3 and lncRNA-LET, and lncRNA-LET and miR-548 in GC cells. HDAC3 was significantly overexpressed in GC cell lines compared to GES-1. Knockdown of HDAC3 suppressed the proliferation, invasion, and migration of AGS and SGC-7901 cells, while cell apoptosis was promoted. Silenced HDAC3 promoted histone acetylation in the promoter region of lncRNA-LET, subsequently upregulating the expression of lncRNA-LET in AGS and SGC-7901 cells. In addition, overexpressed lncRNA-LET notably inhibited the proliferation, invasion, and migration of GC cells, whereas apoptosis was enhanced. LncRNA-LET could function as the sponge of miR-548k. HDAC3 was able to regulate the progression of GC cells via the lncRNA-LET/miR-548k signaling pathway. We confirmed that the HDAC3/lncRNA-LET/miR-548k signal axis mediated the occurrence and development of GC, and HDAC3 could be a novel therapeutic target for the treatments of GC.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"40 4","pages":"21-32"},"PeriodicalIF":2.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39747290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Calcitriol Attenuates HRV-Induced Respiratory Injury through the AMPK-mTOR-ER Stress Signaling Pathway.","authors":"Chunfang Han,&nbsp;Haiying Yu,&nbsp;Qingxia Zhou","doi":"10.1615/JEnvironPatholToxicolOncol.2021037112","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2021037112","url":null,"abstract":"<p><p>Human rhinovirus (HRV) infection is one of the main causes of respiratory injury. Recently, calcitriol has been reported to have protective effect against respiratory infections. In this paper, we aimed to explore the effects and mechanisms of calcitriol on HRV-induced respiratory infection. Participants including pediatric patients diagnosed with HRV-induced respiratory infection (n = 50) and paired healthy controls (n = 40) were recruited at the Weifang People's Hospital between May 2019 and May 2020. The serum 25(OH)D3 level was measured in participants using ELISA kit. The HRV-induced respiratory infection model in human nasal mucosal epithelial cells (hNECs) was adapted, in vitro. HRV infection was measured by real-time PCR analysis of HRV expression. After HRV infection and treatment with calcitriol, the changes of cell viability were detected by MTT assay, the expression of ER stress-induced apoptosis and AMPK-mTOR related proteins by western blot, and the cell apoptosis by flow cytometry assay. In order to confirm whether AMPK-mTOR signal pathway was involved in the ER stress-induced apoptosis of hNECs, cells were pretreated with compound C which was a AMPK inhibitor. The 25-(OH)D3 concentration in serum collected in HRV-infected children was lower than that in controls. In vitro experiments showed that HRV infection decreased cell viability, and this effect was reversed when treated with calcitriol. Additionally, HRV increased levels of apoptosis and ER stress markers (including cleaved-caspase3, Bax, CHOP, nATF6, and BiP), while calcitriol significantly reversed these effects. Furthermore, calcitriol played a protective role by increasing p-AMPK and decreasing p-mTOR level. However, the protective effects of calcitriol could be abolished by compound C. Calcitriol protected HRV-infected hNECs by inhibiting the ER stress-induced apoptosis through the AMPK-mTOR signaling pathway. These protective effects of calcitriol against HRV-induced respiratory infection may provide an experimental basis for the clinical application.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"40 2","pages":"35-43"},"PeriodicalIF":2.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25564154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-451 Promotes Cell Apoptosis and Inhibits Autophagy in Pediatric Acute Myeloid Leukemia by Targeting HMGB1.","authors":"Yingchun Zhang,&nbsp;Xiaojuan Chu,&nbsp;Qingjie Wei","doi":"10.1615/JEnvironPatholToxicolOncol.2021037139","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2021037139","url":null,"abstract":"<p><p>MiR-451 plays a tumor suppressive role in a variety of cancers. However, the function of miR-451 in acute myeloid leukemia (AML) has not been fully understood. Herein, we focused on the effect of miR-451 in pediatric AML and its regulatory mechanism. MiR-451 and high mobility group box 1 (HMGB1) levels were tested in bone marrow of pediatric AML patients and healthy controls, and in AML cells and HS-5 cells by qRT-PCR and Western blot analysis. HL-60 and THP-1 cells were treated with miR-451 mimics, pcDNA-HMGB1, and corresponding controls. The changes in apoptosis and autophagy were evaluated in miR-451 overexpressed AML cells with MTT and flow cytometry. The interaction between miR-451 and HMGB1 was determined by dual-luciferase reporter assay, qRT-PCR, and Western blot. After cells were co-transfected with pcDNA-HMGB1 and pc-DNA-ctrl, we investigated apoptosis and autophagy in miR-451 overexpressed cells perturbed by exogenous HMGB1 through MTT, flow cytometry, and Western blot. miR-451's role in drug sensitivity was further measured. Pediatric AML bone marrow and cell lines presented low expression of miR-451 coupled with high expression of HMGB1. HMGB1 was determined to be a functional target of miR-451. MiR-451 overexpression remarkably enhanced apoptosis and reduced autophagy in both AML cell lines, which was reversed by pcDNA-HMGB1 transfection. Additionally, exogenous miR-451 significantly enhanced the sensitivity of HL-60 cells to the chemotherapy drug As2O3. MiR-451 exerted a tumor suppressive effect in enhancing cell death and reducing autophagy of AML cells by targeting HMGB1. MiR-451 might be considered a candidate target for treating pediatric AML.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"40 2","pages":"45-53"},"PeriodicalIF":2.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25564155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Neuregulin 1 (NRG1): A Novel Biomarker for Non-Small-Cell Lung Cancer.","authors":"Chun Fang,&nbsp;Baoguo Kang,&nbsp;Pan Zhao,&nbsp;Jing Ran,&nbsp;Lifang Wang,&nbsp;Lingqiong Zhao,&nbsp;Hangyu Luo,&nbsp;Ling Tao","doi":"10.1615/JEnvironPatholToxicolOncol.2021039839","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2021039839","url":null,"abstract":"<p><p>The aim of this study was to identify the roles of neuregulin 1 (NRG1) during the tumor progression in non-small-cell lung cancer (NSCLC). NSCLC patients with lung squamous cell carcinoma and lung adenocarci-noma were enrolled in this study. The expression of NRG1, vascular endothelial growth factor (VEGF) and surviving in clinical specimens was examined using immunohistochemistry analysis. The cytokine production in plasma was evaluated by ELISA. The levels of NRG1-associated molecules were determined using western blotting. The proliferation and apoptosis of cells with NRG1 knockdown were accessed by CCK-8 assay and flow cytometry. Upregulation of NRG1 as well as tumor-associated angiogenesis markers VEGF and survivin was detected in tissue and serum samples of NSCLC patients compared with the control. Furthermore, positive correlation with NSCLC levels and VEGF/survivin was also found in NSCLC specimens. In addition, upregulation of NRG1, VEGF and survivin was associated with poor overall survival in NSCLC patients. Moreover, enhanced production of NRG1 was detected in serum samples from NSCLC patients compared with healthy donors, and ROC analysis revealed the importance of NRG1 levels on distinguishing NSCLC samples and the controls. These findings suggested the novel diagnostic value of NRG1 in NSCLC. Additionally, upregulated protein levels of NRG1 and its target genes were also found in tissues samples of NSCLC patients compared with normal controls. These data indicated that NRG1 was a promising marker NSCLC, and it could be involved in tumor progression by targeting its downstream target including ErbB-Akt axis. Furthermore, the growth of lung cancer cells was suppressed by the knockdown of NRG1. Our findings could provide guidance for more accurate diagnosis for NSCLC, and future therapeutic approaches might be developed by better understanding of NRG-1-modulated molecular mechanisms during the tumor development in NSCLC.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"40 4","pages":"61-72"},"PeriodicalIF":2.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39747695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phyllanthin Averts Oxidative Stress and Neuroinflammation in Cerebral Ischemic-Reperfusion Injury through Modulation of the NF-κB and AMPK/Nrf2 Pathways.","authors":"Haitao Yuan,&nbsp;Qin Yang,&nbsp;Bo Yang,&nbsp;Hong Xu,&nbsp;Omaima Nasif,&nbsp;Sankareswaran Muruganantham,&nbsp;Jing Chen","doi":"10.1615/JEnvironPatholToxicolOncol.2020036307","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2020036307","url":null,"abstract":"<p><p>Cerebral ischemia-reperfusion (CIR) is a common feature of ischemic stroke and is a major cause of disability and death among stroke patients worldwide. Phyllanthin, a lignin polyphenol, is known for its varied biological properties, although its protective effects against CIR have not been reported. We evaluated the neuroprotective property of phyllanthin against CIR as well as the involvement of the AMP-activated protein kinase/nuclear factor erythroid 2-related factor 2 (AMPK/Nrf2) and nuclear factor kappa B (NF-κB) signaling pathways. Experimental animals were divided into five groups: controls (sham-operated), CIR-induced by middle cerebral artery occlusion (MCAO), and CIR-induced and administered phyllanthin at 2.5, 5, and 10 mg/kg, respectively. We investigated neurological functions, various signaling genes, and inflammatory clues. The results of in vitro assays demonstrated that phyllanthin assertively improved cellular functions through abrogation of the Nrf2 pathway. In vivo, CIR rats demonstrated neurological function deficits, while ischemic severity was evidenced by the activation of neuroinflammatory cytokines and tissue oxidative stress. Moreover, the expression of apoptosis markers such as Bax, B-cell lymphoma (Bcl-2), caspase-3, COX-2, PGE2, and LOX-1 abruptly increased. Phyllanthin prevented brain dysfunction and cerebral edema, and protected brain integrity. Conversely, it improved antioxidative enzyme activity, abrogated inflammatory cytokines, and increased IL-10 in chemokines. Also, phyllanthin significantly reduced Nrf2 and AMPK levels, with reduced expression of NF-κB indicating that cross-talk between the NF-kB and Nrf2 pathways is activated in CIR. Phyllanthin rescues the ischemic brain by regulating cellular signaling, which supports its use for complications like CIR and associated injury.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"40 1","pages":"85-97"},"PeriodicalIF":2.4,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25410264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginkgo biloba Extract Mechanism Inhibits Hepatocellular Carcinoma through the Nuclear Factor-κB/p53 Signaling Pathway.","authors":"Ruike Wang,&nbsp;Xiaomei Shao,&nbsp;Jiping Yang,&nbsp;Zhenzhen Liu,&nbsp;Lisah Chew,&nbsp;Ying Shao","doi":"10.1615/JEnvironPatholToxicolOncol.2020034510","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2020034510","url":null,"abstract":"<p><p>Ginkgo biloba extract EGb761 conveys an anticancer effect, but little is known regarding its role in hepatocellular carcinoma (HCC). Our study aims to determine the anticancer effect of EGb761 on HCC cell lines and clarify the underlying molecular mechanism. We explore biological functions of EGb761 in HCC using morphological observation, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cytotoxic analysis. We investigate the effects of EGb761 on proliferation and apoptosis of HCC cells using plate clone formation, proliferating cell nuclear antigen, and terminal deoxynucleotidyl transferase d-untranslated protein nick end labeling assays. Protein expressions of the NF-κB/p53 signal pathway were detected and identified using immunohistochemistry. The effect of EGb761 on the p53 signaling pathway was further confirmed by adding pifithrin (PFT)-α, an inhibitor of p53. We determine that EGb761 inhibits cell growth, reduces cell viability, and promotes apoptosis of HCC cells. In addition, EGb761 reduces proliferation and increases apoptosis of human hepatocellular carcinomas (HepG2) cells in a dose-dependent manner. We also find that EGb761 exerts an anticancer effect on HepG2 cells by activating p53 and inhibiting nuclear factor (NF)-κB signaling pathways. This study confirms that EGb761 inhibits proliferation and triggers apoptosis of HCC cells through the NF-κB/p53 signaling pathway.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"39 2","pages":"179-189"},"PeriodicalIF":2.4,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38227028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of Betulin on Inflammatory Biomarkers and Oxidative Status of Ova-Induced Murine Asthma.","authors":"Lei Wang,&nbsp;Diansheng Zhong","doi":"10.1615/JEnvironPatholToxicolOncol.2020031970","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2020031970","url":null,"abstract":"<p><p>Asthma is a chronic, serious allergic inflammatory disease in the airway. The inflammation in the airway is induced by the allergic T-helper 2 cells (Th2 cells), which leads to unfettered production of inflammatory cytokines. The accretion of inflammatory cells in the airway also speeds up the secretion of reactive oxygen species (ROS) and suppresses antioxidative processes. Hence, the present work aimed to study the antiasthmatic efficacy of betulin and its effect in suppressing the inflammatory markers of ovalbumin (OVA) challenged asthmatic mice. The observed results revealed that the levels of inflammatory cells including neutrophils, eosinophils, lymphocytes, and macrophages were effectively decreased by betulin treatment; furthermore, the inflammatory markers IL-4, IL-5, IL-13, and TNF-α levels were notably suppressed by betulin administration in OVA-challenged asthmatic mice. Similarly, the oral administration of betulin showed a reduction in IgE level and elevation in the IFN-γ level in bronchoalveolar lavage fluid (BALF). The elevated levels of antioxidant enzymes like catalase (CAT), glutathione (GSH), and superoxide dismutase (SOD) were observed in betulin treated mice. Furthermore, reduced levels of reactive oxygen species like NO2, NO3, and MDA were noted in the betulin treated group. Consistently, airway hyperreactivity (AHR) was depleted in the betulin administered group compared with the OVA-challenged asthmatic group. Betulin treatment was revealed to have noteworthy antiasthmatic effects mediated by the suppression of production of inflammatory cells and the expression of other inflammatory markers. Furthermore, the elevation in the level of antioxidant markers helped to disclose the original regulatory mode of betulin on asthma treatment.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"39 3","pages":"213-224"},"PeriodicalIF":2.4,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38327724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nobiletin Inhibits Helicobacterium pylori Infection-Induced Gastric Carcinogenic Signaling by Blocking Inflammation, Apoptosis, and Mitogen-Activated Protein Kinase Events in Gastric Epithelial-1 Cells.","authors":"Yiming Ouyang,&nbsp;Linhai Li,&nbsp;Ping Ling","doi":"10.1615/JEnvironPatholToxicolOncol.2020031272","DOIUrl":"https://doi.org/10.1615/JEnvironPatholToxicolOncol.2020031272","url":null,"abstract":"<p><p>Helicobacter pylori causes a Gram-negative bacterial infection that can increase the risk of gastric cancer. Consequently, meticulous prevention of an H. pylori infection is significant for averting gastric cancer in humans. Nobiletin, an important dietary polymethoxylated flavonoid in citrus fruits, possesses multidimensional pharmaceutical properties, including its ability to act as an anticancer, anti-inflammatory, antioxidative, cardiovascularly defensive, neuroprotective, and antimetabolic agent. Our study evaluates the role of nobiletin in inflammation-mediated gastric carcinogenic signaling of H. pylori-arbitrated coculture in the human gastric epithelial (GES)-1 cell line. Our results show that the culture system of H. pylori-tainted GES-1 cells demonstrates maximum fabrication of reactive oxygen species (ROS), mediating DNA injury and augmenting nuclear fragmentations. Treatment with nobiletin reduces ROS levels and apoptotic morphological changes by dual staining and decreases levels of lipid peroxides and glutathione content in H. pylori-infected GES-1 cells. Phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT)/phosphatase and tensin homolog signaling have been implicated to affect cell endurance, inflammation, proliferation, and carcinogenic activity in gastric GES-1 cells. We find that nobiletin strongly impedes tumor necrosis factor-α, interleukin-6, cyclooxygenase-2, PI3K, AKT, and mitogen-activated protein kinase molecules, including p38, extracellular receptor kinase 1, and c-Jun amino-terminal expression in H. pylori-infected GES-1 cells. We conclude that nobiletin potentially impedes H. pylori infection and its related activation, likely preventing H. pylori infection-mediated gastric cancer.</p>","PeriodicalId":50201,"journal":{"name":"Journal of Environmental Pathology Toxicology and Oncology","volume":"39 1","pages":"77-88"},"PeriodicalIF":2.4,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37993787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}