Liver cancer is the third most common cancer, with increasing morbidity and mortality rates worldwide. Despite the increasing occurrence of liver cancer, it has a poor prognosis and potential treatment options are still lacking. The current study aimed to explore the anticancer potential of arbutin against diethylnitrosamine (DEN)-triggered liver carcinogenesis in rats. Liver cancer was initiated in rats via the administration of DEN (200 mg/kg) and then treated with 30 mg/kg of arbutin. Albumin, globulin, and total protein were quantified using kits. Antioxidant, liver injury marker, and tumor biomarker contents were quantified using marker-specific assay kits. The inflammatory markers c-JNK, TRAIL, caspase-8, and p53 contents were also detected using kits. Reverse transcription PCR analysis was used to study the expression of chaperones GRP78, GRP94, and PDIA4 as well as ERDJ4, ATF4, and GADD34. Liver histology was studied microscopically. The arbutin treatment effectively improved body weight and reduced liver weight in animals with DEN-provoked liver cancer. The treatment also improved the albumin, globulin, and total protein contents and antioxidants. In addition, arbutin reduced liver injury marker enzyme function and improved c-JNK, TRAIL, caspase-8, and p53 contents. Arbutin supplementation also decreased the expression of GRP78, PDIA4, GRP94, ERDJ4, ATF4, and GADD34 in the liver tissues of DEN-provoked animals. Arbutin effectively ameliorated the DEN-provoked histological alterations. Altogether, our findings show that arbutin has anti-inflammatory, antioxidant, and anticarcinogenic activities against DEN-provoked liver cancer in rats.
{"title":"Anticancer Effect of Arbutin on Diethylnitrosamine-Induced Liver Carcinoma in Rats via the GRP and GADD Pathway.","authors":"Xiangting Zeng, Haipeng Liu, Zeping Huang, Peng Dong, Xiao Chen","doi":"10.1615/jenvironpatholtoxicoloncol.2021039772","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021039772","url":null,"abstract":"Liver cancer is the third most common cancer, with increasing morbidity and mortality rates worldwide. Despite the increasing occurrence of liver cancer, it has a poor prognosis and potential treatment options are still lacking. The current study aimed to explore the anticancer potential of arbutin against diethylnitrosamine (DEN)-triggered liver carcinogenesis in rats. Liver cancer was initiated in rats via the administration of DEN (200 mg/kg) and then treated with 30 mg/kg of arbutin. Albumin, globulin, and total protein were quantified using kits. Antioxidant, liver injury marker, and tumor biomarker contents were quantified using marker-specific assay kits. The inflammatory markers c-JNK, TRAIL, caspase-8, and p53 contents were also detected using kits. Reverse transcription PCR analysis was used to study the expression of chaperones GRP78, GRP94, and PDIA4 as well as ERDJ4, ATF4, and GADD34. Liver histology was studied microscopically. The arbutin treatment effectively improved body weight and reduced liver weight in animals with DEN-provoked liver cancer. The treatment also improved the albumin, globulin, and total protein contents and antioxidants. In addition, arbutin reduced liver injury marker enzyme function and improved c-JNK, TRAIL, caspase-8, and p53 contents. Arbutin supplementation also decreased the expression of GRP78, PDIA4, GRP94, ERDJ4, ATF4, and GADD34 in the liver tissues of DEN-provoked animals. Arbutin effectively ameliorated the DEN-provoked histological alterations. Altogether, our findings show that arbutin has anti-inflammatory, antioxidant, and anticarcinogenic activities against DEN-provoked liver cancer in rats.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"52 1","pages":"15-26"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90603323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1615/jenvironpatholtoxicoloncol.2021040536
Lina Nguyen, Ethan-Quan Nguyen, Cassandra Tran, K. Nguyen, Ananya Devarajan, K. Berg, H. Hirschberg
One approach to reducing post-operative tumor recurrence and alleviate debilitating side effects of systemic chemotherapy, is work centered on the development of drug activation by focused and targeted externally applied physical energy thus providing site and temporal specificity. One such technique, light mediated photochemical internalization (PCI), has been shown to be a method to obtain enhanced chemotherapy efficacy for a wide variety of anti-cancer agents. A related technology, sonochemical internaization (SCI), is an extension of the PCI concept developed to overcome the limitations of poor light penetration in tissue. SCI utilizes ultrasonic energy, to activate sonosensitizers, co-administered with anti cancer agents. The purpose of the study reported here was to evaluate the inhibitory effects of SCI of bleomycin (BLM), both in vitro and in vivo, on the adenocarcinoma breast tumor rat cell line Mat B III. In vitro, the two aspects of sonication, sonoporation (SP) and sonochemical internalization (SCI) of BLM were examined. In vivo, BLM-SCI significantly inhibited tumor development, following Mat B III implantation, in an orthotopic breast tumor animal model using Fisher rats.
减少术后肿瘤复发和减轻全身化疗副作用的一种方法是通过集中和靶向的外部施加物理能量来开发药物激活，从而提供部位和时间特异性。其中一种技术，光介导的光化学内化(PCI)，已被证明是一种获得各种抗癌药物增强化疗效果的方法。一项相关技术，超声化学内在化(SCI)，是PCI概念的延伸，旨在克服组织中光线穿透力差的局限性。SCI利用超声波能量，激活声敏剂，与抗癌药物共同施用。本文报道的研究目的是评估博来霉素(BLM)的SCI在体外和体内对乳腺腺癌大鼠肿瘤细胞系Mat B III的抑制作用。在体外研究了BLM的超声作用，即sonoporation (SP)和sonochemical internalization (SCI)。在体内，在Fisher大鼠原位乳腺肿瘤动物模型中，Mat B III植入后，BLM-SCI显著抑制肿瘤的发展。
{"title":"Sonochemical Internalization of Bleomycin Inhibits Adenocarcinoma Breast Tumor Development in an Orthotopic Rat Model.","authors":"Lina Nguyen, Ethan-Quan Nguyen, Cassandra Tran, K. Nguyen, Ananya Devarajan, K. Berg, H. Hirschberg","doi":"10.1615/jenvironpatholtoxicoloncol.2021040536","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021040536","url":null,"abstract":"One approach to reducing post-operative tumor recurrence and alleviate debilitating side effects of systemic chemotherapy, is work centered on the development of drug activation by focused and targeted externally applied physical energy thus providing site and temporal specificity. One such technique, light mediated photochemical internalization (PCI), has been shown to be a method to obtain enhanced chemotherapy efficacy for a wide variety of anti-cancer agents. A related technology, sonochemical internaization (SCI), is an extension of the PCI concept developed to overcome the limitations of poor light penetration in tissue. SCI utilizes ultrasonic energy, to activate sonosensitizers, co-administered with anti cancer agents. The purpose of the study reported here was to evaluate the inhibitory effects of SCI of bleomycin (BLM), both in vitro and in vivo, on the adenocarcinoma breast tumor rat cell line Mat B III. In vitro, the two aspects of sonication, sonoporation (SP) and sonochemical internalization (SCI) of BLM were examined. In vivo, BLM-SCI significantly inhibited tumor development, following Mat B III implantation, in an orthotopic breast tumor animal model using Fisher rats.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"21 1","pages":"25-35"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75296721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Signal transducers and activators of transcription 1 (STAT1) is an important transcription factor that regulates the growth, survival, differentiation and apoptosis of various tumor cells. However, the biological roles of STAT1 and potential mechanisms in triple-negative breast cancer (TNBC) remain largely unknown. The expression levels of STAT1, CircIFI30, CDCA4, and epithelial-mesenchymal transition (EMT)-associated molecules (MM2, MMP9, E-cadherin, and N-cadherin) were evaluated using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Furthermore, cell-counting kit-8 assay, Transwell assay, flow cytometry, and immunofluorescence staining were performed to investigate the biological functions of STAT1 and CircIFI30 in TNBC cells. In addition, Dual luciferase activity assay and chromatin immunoprecipitation qPCR were used to predict the interaction between STAT1 and CircIFI30 promoter. The effects of CircIFI30 on the stability of CDCA4 mRNA were also confirmed in further function study. Up-regulation of STAT1 was detected in TNBC tissues and cells, which were positively correlated with tumor metastasis, advanced clinical stage and poor survival rate. Up-regulated STAT1 could promote the proliferation, invasion, migration, EMT and inhibit the apoptosis of TNBC cells. RNA-seq indicated has_circ_0005571 (CircIFI30) was significantly down-regulated in TNBC cells after knockdown of STAT1. Moreover, STAT1 could be novel transcription factor that binds to CircIFI30 promoter to enhance its transcription. Additionally, knockdown of CirclFl30 down regulated the expression of cell division cycleassociated protein 4 (CDCA4) through reducing the stability of its mRNA. Our data revealed the STAT1/CircIFI30/CDCA4 axis could regulate the proliferation, invasion, migration, EMT and apoptosis of TNBC cells. Therefore, STAT1 may be a putative therapeutic candidate for targeted treatment of TNBC.
STAT1 (Signal transducers and activators of transcription 1)是调控多种肿瘤细胞生长、存活、分化和凋亡的重要转录因子。然而，STAT1在三阴性乳腺癌(TNBC)中的生物学作用和潜在机制在很大程度上仍然未知。采用定量逆转录聚合酶链式反应(RT-qPCR)评估STAT1、CircIFI30、CDCA4和上皮-间质转化(EMT)相关分子(MM2、MMP9、E-cadherin和N-cadherin)的表达水平。通过细胞计数试剂盒-8、Transwell、流式细胞术、免疫荧光染色等方法研究STAT1和CircIFI30在TNBC细胞中的生物学功能。此外，利用双荧光素酶活性测定和染色质免疫沉淀qPCR预测STAT1与CircIFI30启动子之间的相互作用。CircIFI30对CDCA4 mRNA稳定性的影响也在进一步的功能研究中得到证实。STAT1在TNBC组织细胞中表达上调，与肿瘤转移、临床分期和生存率呈正相关。STAT1上调可促进TNBC细胞增殖、侵袭、迁移、EMT，抑制TNBC细胞凋亡。RNA-seq显示，在敲低STAT1后，TNBC细胞中has_circ_0005571 (CircIFI30)显著下调。此外，STAT1可能是结合CircIFI30启动子增强其转录的新型转录因子。此外，敲低CirclFl30可通过降低细胞分裂周期相关蛋白4 (CDCA4) mRNA的稳定性来下调其表达。我们的数据显示STAT1/CircIFI30/CDCA4轴可以调节TNBC细胞的增殖、侵袭、迁移、EMT和凋亡。因此，STAT1可能是一种假定的靶向治疗TNBC的候选药物。
{"title":"STAT1 Mediates the Transcription of CircIFI30 and Promotes the Progression of Triple-Negative Breast Cancer by Up-Regulating CDCA4.","authors":"Jie Zhang, Shufeng Xia, Xiao-you Liu, Deguang Qi, Xiao-song He, Daqin Chen","doi":"10.1615/jenvironpatholtoxicoloncol.2021039794","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021039794","url":null,"abstract":"Signal transducers and activators of transcription 1 (STAT1) is an important transcription factor that regulates the growth, survival, differentiation and apoptosis of various tumor cells. However, the biological roles of STAT1 and potential mechanisms in triple-negative breast cancer (TNBC) remain largely unknown. The expression levels of STAT1, CircIFI30, CDCA4, and epithelial-mesenchymal transition (EMT)-associated molecules (MM2, MMP9, E-cadherin, and N-cadherin) were evaluated using quantitative reverse transcription polymerase chain reaction (RT-qPCR). Furthermore, cell-counting kit-8 assay, Transwell assay, flow cytometry, and immunofluorescence staining were performed to investigate the biological functions of STAT1 and CircIFI30 in TNBC cells. In addition, Dual luciferase activity assay and chromatin immunoprecipitation qPCR were used to predict the interaction between STAT1 and CircIFI30 promoter. The effects of CircIFI30 on the stability of CDCA4 mRNA were also confirmed in further function study. Up-regulation of STAT1 was detected in TNBC tissues and cells, which were positively correlated with tumor metastasis, advanced clinical stage and poor survival rate. Up-regulated STAT1 could promote the proliferation, invasion, migration, EMT and inhibit the apoptosis of TNBC cells. RNA-seq indicated has_circ_0005571 (CircIFI30) was significantly down-regulated in TNBC cells after knockdown of STAT1. Moreover, STAT1 could be novel transcription factor that binds to CircIFI30 promoter to enhance its transcription. Additionally, knockdown of CirclFl30 down regulated the expression of cell division cycleassociated protein 4 (CDCA4) through reducing the stability of its mRNA. Our data revealed the STAT1/CircIFI30/CDCA4 axis could regulate the proliferation, invasion, migration, EMT and apoptosis of TNBC cells. Therefore, STAT1 may be a putative therapeutic candidate for targeted treatment of TNBC.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"75 1","pages":"1-13"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83782094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1615/jenvironpatholtoxicoloncol.2021039641
Cong Li, Jing Ding, Jianmin Mei
BACKGROUND Early detection of hepatocellular carcinoma (HCC) is significantly effective in clinical management. This study aimed to identify potential HCC biomarkers. METHODS Analysis of expression profiles in HCC clinical samples downloaded from the cancer genome atlas (TCGA) and the gene expression omnibus (GEO) datasets was performed to identify differentially expressed genes (DEGs) using R packages. The epigenetic differentially expressed genes (epiDEGs) were obtained after intersections of genes between DEGs and epigenetic factors (EFs). The biological functions of epiDEGs were annotated by gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. Protein-protein interaction and expression correlation were performed to investigate the interactions among epiDEGs by the STRING online tool and R packages. The epiDEGs associated with overall survival (OS) were identified as patient prognosis using the Cox regression analysis. The levels of gene expression were validated by RT-qPCR and Western blot between HCC cell lines, (HepG2, and Huh-7) and normal cell lines (THLE-2). RESULTS Thirty-five epiDEGs were obtained, including 25 upregulated genes and 10 downregulated genes. Functional enrichment and PPI analysis indicated the development of HCC is a complicated process involving various genes and proteins. Survival analysis showed nine epiDEGs associated with the OS of patients and these might be the independent prognostic biomarkers for HCC. The expressions of most epiDEGs were significantly higher in HCC patients with stage II and III compared with stage I. Furthermore, the expression of these epiDEGs between HCC cell lines with normal cell lines was shown to be consistent with the TCGA and GEO datasets except PBK. CONCLUSIONS Eight hub epiDEGs, including EZH2, CDK1, CENPA, RAD54L, HELLS, HJURP, AURKA, and AURKB, were associated with the overall survival of HCC patients and could be potential biomarkers to predict prognosis.
{"title":"Comprehensive Analysis of Epigenetic Associated Genes on Differential Gene Expression and Prognosis in Hepatocellular Carcinoma.","authors":"Cong Li, Jing Ding, Jianmin Mei","doi":"10.1615/jenvironpatholtoxicoloncol.2021039641","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021039641","url":null,"abstract":"BACKGROUND Early detection of hepatocellular carcinoma (HCC) is significantly effective in clinical management. This study aimed to identify potential HCC biomarkers. METHODS Analysis of expression profiles in HCC clinical samples downloaded from the cancer genome atlas (TCGA) and the gene expression omnibus (GEO) datasets was performed to identify differentially expressed genes (DEGs) using R packages. The epigenetic differentially expressed genes (epiDEGs) were obtained after intersections of genes between DEGs and epigenetic factors (EFs). The biological functions of epiDEGs were annotated by gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis. Protein-protein interaction and expression correlation were performed to investigate the interactions among epiDEGs by the STRING online tool and R packages. The epiDEGs associated with overall survival (OS) were identified as patient prognosis using the Cox regression analysis. The levels of gene expression were validated by RT-qPCR and Western blot between HCC cell lines, (HepG2, and Huh-7) and normal cell lines (THLE-2). RESULTS Thirty-five epiDEGs were obtained, including 25 upregulated genes and 10 downregulated genes. Functional enrichment and PPI analysis indicated the development of HCC is a complicated process involving various genes and proteins. Survival analysis showed nine epiDEGs associated with the OS of patients and these might be the independent prognostic biomarkers for HCC. The expressions of most epiDEGs were significantly higher in HCC patients with stage II and III compared with stage I. Furthermore, the expression of these epiDEGs between HCC cell lines with normal cell lines was shown to be consistent with the TCGA and GEO datasets except PBK. CONCLUSIONS Eight hub epiDEGs, including EZH2, CDK1, CENPA, RAD54L, HELLS, HJURP, AURKA, and AURKB, were associated with the overall survival of HCC patients and could be potential biomarkers to predict prognosis.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"69 1","pages":"27-43"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83803226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1615/jenvironpatholtoxicoloncol.2021039718
Junxia Gong, Chunlin Wang, Fang Zhang, Weidong Lan
BACKGROUND Allocryptopine is an isoquinoline alkaloid extracted from Macleaya cordata. This study aimed to explore the effects of allocryptopine on the growth and metastasis of oral squamous cell carcinoma (OSCC) cells. METHODS The human OSCC cell line HSC-3 and SAS were selected in this study. MTT assay was performed to measure cell viability. Western blot was used to detect protein expressions. transwell assay was conducted to determine the migrated and invaded cells. M6A modification was confirmed by methylated RNA immunoprecipitation assay. RESULTS Compared with the NC group, the cell viability, migration and invasion ability of OSCC cells were suppressed after allocryptopine treatment in a dose dependent manner. Allocryptopine upregulated the E-cadherin expression and downregulated N-cadherin and Vimentin expressions in the OSCC cells. In addition, the protein expressions of patched receptor 1 (PTCH1), smoothened co-receptor (SMO) and Gli family (GLI1) were downregulated after allocryptopine treatment. Furthermore, allocryptopine treatment decreased the expression of Methyltransferase like 3 (METTL3) and inhibited N6-methyladenosine (m6A) modification of PTCH1. Moreover, overexpression of PTCH1 reversed the effects of allocryptopine and induced the aggressiveness of OSCC cells. CONCLUSION Allocryptopine suppressed the proliferation and epithelial-mesenchymal transition (EMT) of OSCC cells via m6A mediated Hedgehog signaling pathway, relieving the carcinogenic behaviors of OSCC.
{"title":"Effects of Allocryptopine on the Proliferation and Epithelial-Mesenchymal Transition of Oral Squamous Cell Carcinoma through m6A Mediated Hedgehog Signaling Pathway.","authors":"Junxia Gong, Chunlin Wang, Fang Zhang, Weidong Lan","doi":"10.1615/jenvironpatholtoxicoloncol.2021039718","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021039718","url":null,"abstract":"BACKGROUND Allocryptopine is an isoquinoline alkaloid extracted from Macleaya cordata. This study aimed to explore the effects of allocryptopine on the growth and metastasis of oral squamous cell carcinoma (OSCC) cells. METHODS The human OSCC cell line HSC-3 and SAS were selected in this study. MTT assay was performed to measure cell viability. Western blot was used to detect protein expressions. transwell assay was conducted to determine the migrated and invaded cells. M6A modification was confirmed by methylated RNA immunoprecipitation assay. RESULTS Compared with the NC group, the cell viability, migration and invasion ability of OSCC cells were suppressed after allocryptopine treatment in a dose dependent manner. Allocryptopine upregulated the E-cadherin expression and downregulated N-cadherin and Vimentin expressions in the OSCC cells. In addition, the protein expressions of patched receptor 1 (PTCH1), smoothened co-receptor (SMO) and Gli family (GLI1) were downregulated after allocryptopine treatment. Furthermore, allocryptopine treatment decreased the expression of Methyltransferase like 3 (METTL3) and inhibited N6-methyladenosine (m6A) modification of PTCH1. Moreover, overexpression of PTCH1 reversed the effects of allocryptopine and induced the aggressiveness of OSCC cells. CONCLUSION Allocryptopine suppressed the proliferation and epithelial-mesenchymal transition (EMT) of OSCC cells via m6A mediated Hedgehog signaling pathway, relieving the carcinogenic behaviors of OSCC.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"67 2 1","pages":"15-24"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78315361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1615/jenvironpatholtoxicoloncol.2021040128
Sobia Nida, Hemalatha Srinivisan, A. Pandurangan, M. Waseem
Recently, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been critically recognized and spread rapidly on this planet. Considerable recognition of SARS-CoV-2 has been known with a range of viruses that are more capable to cause diseases in avian and mammals including humans. The virus was found as a main culprit for major defects in respiratory system and thereby caused severe acute respiratory syndrome disease. This has led to depict the mortality in human population. Nevertheless, compromised reports on SARS-CoV-2 has also shown neurological complications in both central nervous system (CNS) and peripheral nervous system (PNS). This virus has notified with neurological defects as stroke, encephalopathy, cerebral edema, erythema, seizures, meningitis, ischemic, ageusia, loss of smell, myalgia and Guillain Barre Syndrome. In this review, we focused on COVID-19 mediated neurodegeneration and its mechanistic episodes on affected patients. We also discuss the possible available therapeutic interventions with clinically investigated drugs against COVID-19 mediated neurological impairment in patients and experimental in vitro and in vivo research models required for the development of drugs and/or vaccines against COVID-19 mediated neurological complications.
{"title":"Mechanistic Episodes on SARS-CoV-2-Mediated Neurological Manifestations and Their Possible Therapeutic Interventions.","authors":"Sobia Nida, Hemalatha Srinivisan, A. Pandurangan, M. Waseem","doi":"10.1615/jenvironpatholtoxicoloncol.2021040128","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021040128","url":null,"abstract":"Recently, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been critically recognized and spread rapidly on this planet. Considerable recognition of SARS-CoV-2 has been known with a range of viruses that are more capable to cause diseases in avian and mammals including humans. The virus was found as a main culprit for major defects in respiratory system and thereby caused severe acute respiratory syndrome disease. This has led to depict the mortality in human population. Nevertheless, compromised reports on SARS-CoV-2 has also shown neurological complications in both central nervous system (CNS) and peripheral nervous system (PNS). This virus has notified with neurological defects as stroke, encephalopathy, cerebral edema, erythema, seizures, meningitis, ischemic, ageusia, loss of smell, myalgia and Guillain Barre Syndrome. In this review, we focused on COVID-19 mediated neurodegeneration and its mechanistic episodes on affected patients. We also discuss the possible available therapeutic interventions with clinically investigated drugs against COVID-19 mediated neurological impairment in patients and experimental in vitro and in vivo research models required for the development of drugs and/or vaccines against COVID-19 mediated neurological complications.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"60 1","pages":"85-98"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89170416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1615/jenvironpatholtoxicoloncol.2022040132
S. Bhattacharya
Lead (Pb) is the most common toxic heavy metal that is physiologically non-essential and imposes health complications in animals and humans. Chelation therapy is considered as the definite therapy for acute lead toxicity; clinical uses of chelating agents are not recommended in long-term lead toxicity and in children. Research reveals that essential trace metals can counteract empirical Pb toxicity. This article collates the prototypical evidence of the preventive action of essential trace metals towards Pb toxicity in animals. Zinc, selenium, and their combinations are effective here. The key mechanisms of homeostasis of essential metals and cytoprotection are: modulation of signal transduction pathways of apoptosis, inflammation and immune functions (for selenium), attenuation of oxidative stress by augmenting non-enzymatic and enzymatic antioxidative systems and interference in lead accumulation in the body. By means of these mechanisms, these essential trace metals may counteract long-term lead toxicity for susceptible subjects. These mineral nutritional supplementation can easily be employed with no or less adverse effects compared to the typical chelation treatment.
{"title":"Essential Trace Metals as Countermeasure for Lead Toxicity.","authors":"S. Bhattacharya","doi":"10.1615/jenvironpatholtoxicoloncol.2022040132","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2022040132","url":null,"abstract":"Lead (Pb) is the most common toxic heavy metal that is physiologically non-essential and imposes health complications in animals and humans. Chelation therapy is considered as the definite therapy for acute lead toxicity; clinical uses of chelating agents are not recommended in long-term lead toxicity and in children. Research reveals that essential trace metals can counteract empirical Pb toxicity. This article collates the prototypical evidence of the preventive action of essential trace metals towards Pb toxicity in animals. Zinc, selenium, and their combinations are effective here. The key mechanisms of homeostasis of essential metals and cytoprotection are: modulation of signal transduction pathways of apoptosis, inflammation and immune functions (for selenium), attenuation of oxidative stress by augmenting non-enzymatic and enzymatic antioxidative systems and interference in lead accumulation in the body. By means of these mechanisms, these essential trace metals may counteract long-term lead toxicity for susceptible subjects. These mineral nutritional supplementation can easily be employed with no or less adverse effects compared to the typical chelation treatment.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"29 1","pages":"61-67"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78857662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01DOI: 10.1615/jenvironpatholtoxicoloncol.2021039719
Sinem Coskun, M. Gamsızkan, U. Yalçınkaya, M. Sungur
Malignant peripheral nerve sheath tumors (MPNSTs), glioblastomas (GBMs), and malignant melanomas (MMs) are neural crest-originating aggressive tumors with a poor prognosis. Signal transducer and transcription activator 3 (STAT3) plays a role in many biological processes, including cell life and proliferation, the acute phase response, chronic inflammation, autoimmunity, metabolism, and cancer progression, It is also known to be a prooncogenic transcription factor. Vascular endothelial growth factor (VEGF) is one of the most potent proangiogenic stimuli ever identified. It mediates tumor neovascularization, and is associated with angiogenesis and lymphangiogenesis. The prostate-specific membrane antigen (PSMA) folate hydrolase I, despite its name, has been found in tissues other than the prostate. It is overexpressed in prostate cancer cells and several other cancers, and has the potential to be a target for radioligand therapy. We investigated the value of STAT3, VEGF and PSMA immunohistochemical expression patterns and their effects on survival in MPNSTs, GBMs, and MMs. Their expression patterns were evaluated in 25 MPNSTs, 27 GBMs, and 25 MM cases. All GBM cases stained positively for STAT3 and VEGF. In the other groups, the staining patterns were heterogeneous. None of the cases showed positive staining with PSMA. There was no statistically significant difference in survival between cases with differing VEGF and STAT3 staining patterns in the MPSNT and MM groups, but there was an increase in mortality as the VEGF score increased in the GBM group. The suppression of VEGF and STAT3 may be a promising avenue for treatment of MPNSTs, GBMs, and MMs, although further research is needed.
{"title":"STAT3, VEGF, and PSMA Expression Patterns in Malignant Peripheral Nerve Sheath Tumors, Malignant Melanomas, and Glioblastomas: Does Staining Percentage and Intensity Have an Effect on Survival?","authors":"Sinem Coskun, M. Gamsızkan, U. Yalçınkaya, M. Sungur","doi":"10.1615/jenvironpatholtoxicoloncol.2021039719","DOIUrl":"https://doi.org/10.1615/jenvironpatholtoxicoloncol.2021039719","url":null,"abstract":"Malignant peripheral nerve sheath tumors (MPNSTs), glioblastomas (GBMs), and malignant melanomas (MMs) are neural crest-originating aggressive tumors with a poor prognosis. Signal transducer and transcription activator 3 (STAT3) plays a role in many biological processes, including cell life and proliferation, the acute phase response, chronic inflammation, autoimmunity, metabolism, and cancer progression, It is also known to be a prooncogenic transcription factor. Vascular endothelial growth factor (VEGF) is one of the most potent proangiogenic stimuli ever identified. It mediates tumor neovascularization, and is associated with angiogenesis and lymphangiogenesis. The prostate-specific membrane antigen (PSMA) folate hydrolase I, despite its name, has been found in tissues other than the prostate. It is overexpressed in prostate cancer cells and several other cancers, and has the potential to be a target for radioligand therapy. We investigated the value of STAT3, VEGF and PSMA immunohistochemical expression patterns and their effects on survival in MPNSTs, GBMs, and MMs. Their expression patterns were evaluated in 25 MPNSTs, 27 GBMs, and 25 MM cases. All GBM cases stained positively for STAT3 and VEGF. In the other groups, the staining patterns were heterogeneous. None of the cases showed positive staining with PSMA. There was no statistically significant difference in survival between cases with differing VEGF and STAT3 staining patterns in the MPSNT and MM groups, but there was an increase in mortality as the VEGF score increased in the GBM group. The suppression of VEGF and STAT3 may be a promising avenue for treatment of MPNSTs, GBMs, and MMs, although further research is needed.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"1 1","pages":"45-53"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89673827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2019030154
Xinjun Yang, G. Guo, Minyan Dang, Lei Yan, Xin Kang, Kunjin Jia, Hongrui Ren
Asthma has affected more than 300 million people worldwide and is considered one of the most debilitating global public health problems based on a recent statistical report from the Global Initiative for Asthma. Inflammation of the airways leads to the various interrelated mechanisms of innate and adaptive immunity acting mutually with the epithelium of the respiratory organ. Fucoxanthin is an orange or brown pigment which is naturally found in various seaweeds. To the best of our knowledge, there are no scientific claims or evidence of the curative effects of fucoxanthin against asthma. Hence, this present research was designed to investigate the curative activity of fucoxanthin against ovalbumin-induced asthma in a mouse model. Fucoxanthin (50 mg/kg) showed significant (P < 0.001) antiasthma activity. It effectively decreased intracellular secretion of reactive oxygen species and increased antioxidant enzyme activity. Fucoxanthin also decreased inflammatory cytokine markers in bronchoalveolar lavage fluid. Because fucoxanthin showed effective antiasthma activity against ovalbumin-induced asthma in experimental animals, further research on this natural antioxidant could lead to development of a novel drug for the treatment of asthma in humans.
{"title":"Assessment of the Therapeutic Effects of Fucoxanthin by Attenuating Inflammation in Ovalbumin-Induced Asthma in an Experimental Animal Model.","authors":"Xinjun Yang, G. Guo, Minyan Dang, Lei Yan, Xin Kang, Kunjin Jia, Hongrui Ren","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2019030154","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2019030154","url":null,"abstract":"Asthma has affected more than 300 million people worldwide and is considered one of the most debilitating global public health problems based on a recent statistical report from the Global Initiative for Asthma. Inflammation of the airways leads to the various interrelated mechanisms of innate and adaptive immunity acting mutually with the epithelium of the respiratory organ. Fucoxanthin is an orange or brown pigment which is naturally found in various seaweeds. To the best of our knowledge, there are no scientific claims or evidence of the curative effects of fucoxanthin against asthma. Hence, this present research was designed to investigate the curative activity of fucoxanthin against ovalbumin-induced asthma in a mouse model. Fucoxanthin (50 mg/kg) showed significant (P < 0.001) antiasthma activity. It effectively decreased intracellular secretion of reactive oxygen species and increased antioxidant enzyme activity. Fucoxanthin also decreased inflammatory cytokine markers in bronchoalveolar lavage fluid. Because fucoxanthin showed effective antiasthma activity against ovalbumin-induced asthma in experimental animals, further research on this natural antioxidant could lead to development of a novel drug for the treatment of asthma in humans.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"16 1","pages":"229-238"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82396313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-01-01DOI: 10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029549
Zhenjiang Zhao, A. Malhotra, Wu Yuan Seng
UNCI 19 expression has been reported to be significantly higher in hepatic cancer cells (HCC). However, the clinical significance of modulating UNC119 expression in HCC is not well understood. The study described here aimed to explore the potential of curcumin in modulation of UNC119 expression in HCC by assessment with quantitative real-time PCR, western blot, and immune-histochemical analyses in HCC cell lines and tissues. The biological functions of UNC119 in the proliferation, growth, and cycle of tumor cells were analyzed both in vitro and in vivo. UNC119 expression was upregulated in HCC cell lines and tissues as indicated by comparison with normal liver cells and tissues. Cellular function assays showed that higher levels of UNC119 not only promoted proliferation but also enhanced HCC cell migration and invasion. UNC119 promoted progression of the cell cycle and significantly promoted HCC cell growth through the Wnt/β-catenin signal pathway, and enhanced tumor migration and invasion by the TGF-β/EMT pathway. Curcumin efficiently inhibited HCC cell proliferation by blocking the Wnt/β-catenin pathway and inhabited migration and invasion by blocking the TGF-p/EMT signal pathway. Curcumin not only was beneficial for tumor remission but also contributed to the long-term survival of HCC-bearing mice. UNC119 was significantly upregulated and promoted cell growth in hepatic cancer cells and tissues by the Wnt/β-catenin signal pathway and migration by TGF-β/EMT signal pathway. Curcumin treatment inhibited cell proliferation, growth, migration, and invasion by inhibition of those pathways.
{"title":"Curcumin Modulates Hepatocellular Carcinoma by Reducing UNC119 Expression.","authors":"Zhenjiang Zhao, A. Malhotra, Wu Yuan Seng","doi":"10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029549","DOIUrl":"https://doi.org/10.1615/JENVIRONPATHOLTOXICOLONCOL.2019029549","url":null,"abstract":"UNCI 19 expression has been reported to be significantly higher in hepatic cancer cells (HCC). However, the clinical significance of modulating UNC119 expression in HCC is not well understood. The study described here aimed to explore the potential of curcumin in modulation of UNC119 expression in HCC by assessment with quantitative real-time PCR, western blot, and immune-histochemical analyses in HCC cell lines and tissues. The biological functions of UNC119 in the proliferation, growth, and cycle of tumor cells were analyzed both in vitro and in vivo. UNC119 expression was upregulated in HCC cell lines and tissues as indicated by comparison with normal liver cells and tissues. Cellular function assays showed that higher levels of UNC119 not only promoted proliferation but also enhanced HCC cell migration and invasion. UNC119 promoted progression of the cell cycle and significantly promoted HCC cell growth through the Wnt/β-catenin signal pathway, and enhanced tumor migration and invasion by the TGF-β/EMT pathway. Curcumin efficiently inhibited HCC cell proliferation by blocking the Wnt/β-catenin pathway and inhabited migration and invasion by blocking the TGF-p/EMT signal pathway. Curcumin not only was beneficial for tumor remission but also contributed to the long-term survival of HCC-bearing mice. UNC119 was significantly upregulated and promoted cell growth in hepatic cancer cells and tissues by the Wnt/β-catenin signal pathway and migration by TGF-β/EMT signal pathway. Curcumin treatment inhibited cell proliferation, growth, migration, and invasion by inhibition of those pathways.","PeriodicalId":94332,"journal":{"name":"Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer","volume":"2 1","pages":"195-203"},"PeriodicalIF":0.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88760049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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