A novel coronavirus of zoonotic origin(SARSCoV-2)has recently been recognized in patients with acute respiratory disease.COVID-19 causative agent is structurally and genetically similar to SARS and bat SARS-like coron...A novel coronavirus of zoonotic origin(SARSCoV-2)has recently been recognized in patients with acute respiratory disease.COVID-19 causative agent is structurally and genetically similar to SARS and bat SARS-like coronaviruses.The drastic increase in the number of coronavirus and its genome sequence have given us an unprecedented opportunity to perform bioinformatics and genomics analysis on this class of viruses.Clinical tests like PCR and ELISA for rapid detection of this virus are urgently needed for early identification of infected patients.However,these techniques are expensive and not readily available for point-of-care(POC)applications.Currently,lack of any rapid,available,and reliable POC detection method gives rise to the progression of COVID-19 as a horrible global problem.To solve the negative features of clinical investigation,we provide a brief introduction of the general features of coronaviruses and describe various amplification assays,sensing,biosensing,immunosensing,and aptasensing for the determination of various groups of coronaviruses applied as a template for the detection of SARS-CoV-2.All sensing and biosensing techniques developed for the determination of various classes of coronaviruses are useful to recognize the newly immerged coronavirus,i.e.,SARS-CoV-2.Also,the introduction of sensing and biosensing methods sheds light on the way of designing a proper screening system to detect the virus at the early stage of infection to tranquilize the speed and vastity of spreading.Among other approaches investigated among molecular approaches and PCR or recognition of viral diseases,LAMP-based methods and LFAs are of great importance for their numerous benefits,which can be helpful to design a universal platform for detection of future emerging pathogenic viruses.展开更多
Infection with high-risk human papillomavirus(HPV),including HPV-16 and HPV-18,is the main cause of malignancies,such as cervical cancer.Viral oncoproteins encoded by HPV are expressed in HPV-positive cancers and asso...Infection with high-risk human papillomavirus(HPV),including HPV-16 and HPV-18,is the main cause of malignancies,such as cervical cancer.Viral oncoproteins encoded by HPV are expressed in HPV-positive cancers and associated with the early cancer stages and the transformation of normal cells.The signaling pathways involved in the transformation of normal cells to cancerous form and the subsequently expressed programmed cell death-ligand 1(PD-L1)on the surface of the transformed cells lead to a disruption in recognition of tumor cells by the immune cell system,including T lymphocytes and dendritic cells which lead to the development of cervical cancer malignancy.These cells also produce modest levels of cytokines during exhaustion,tumor-infiltrating T CD4+cells with high levels of PD-1 and CD39 release considerable quantities of cytokines.The Wnt/β-catenin signaling pathway,which controls the expression of genes involved in the tumor cells’markers,is demonstrated to be one of the most potent cancer stimulants.It leads to the evasion of the tumor cells from immune cell detection and ultimately avoids being recognized by dendritic cells or T-cells.PD-L1,as an inhibitory immune checkpoint,is essential for controlling immune system activity by inhibiting T-cells’inflammatory function.In the present review,we looked into how Wnt/β-catenin affects the expression of PD-L1 and related genes like c-MYC in cancer cells and its role in the development of HPV-induced malignancy.We hypothesized that blocking these pathways could be a potential immunotherapy and cancer prevention method.展开更多
Cervical cancer is a growing global disease in developing countries.Persistent infection with human papillomaviruses(HPV)is an essential causative agent in this type of cancer.Several studies demonstrate HPV E5 oncopr...Cervical cancer is a growing global disease in developing countries.Persistent infection with human papillomaviruses(HPV)is an essential causative agent in this type of cancer.Several studies demonstrate HPV E5 oncoprotein can impress the normal life cycle of HPV-infected cells by targeting some pivotal cellular signaling pathways,such as the epidermal growth factor receptor(EGFR)signaling pathway.In this study,we used E5-siRNA to knockdown that essential oncogene and considered the effect of E5 silencing on proliferation,apoptosis,cell cycle,apoptosis-related gene expression,and the initiator of the EGFR signaling pathway in cervical cancer cells.The results demonstrate that E5 plays an essential role in the proliferation and inhibited apoptosis in cervical cancer.Furthermore,silencing E5 reduces proliferation,increases apoptosis,and elevates related-genes expression of these malignant cells.Overall,E5 suppression may be appropriate for ameliorating cervical cancer progression.展开更多
Effects of irradiated and non-irradiated Ergosan extract(alginic acid) on rainbow trout growth performance and skin mucosal immunity were compared. Ergosan was irradiated at 30 kGy in a cobalt-60 irradiator. A total o...Effects of irradiated and non-irradiated Ergosan extract(alginic acid) on rainbow trout growth performance and skin mucosal immunity were compared. Ergosan was irradiated at 30 kGy in a cobalt-60 irradiator. A total of 252 fish(128.03±9.4 g) were randomly divided into four equal groups,given the basal diet either unsupplemented with Ergosan(control group) or supplemented with crude Ergosan(5 g/kg),ethanol-extracted Ergosan(0.33 g/kg) or irradiated Ergosan(0.33 g/kg) according to this protocol: basal diet for 15 days,treatment diet for 15 days,basal diet for 10 days and treatment diet for 15 days. Highest growth performance was observed in fish fed irradiated Ergosan(P<0.05). Dietary administration of different Ergosan types did not cause any changes in mucus protein level,but improved alkaline phosphatase level and hemagglutination titer compared with the control(basal diet without Ergosan) on day 55 offeeding trial(P<0.05). Furthermore,the highest value of lysozyme activity was observed in gamma-irradiated Ergosan on day 55. In conclusion,gamma-irradiated Ergosan at 0.33 g/kg was found to improve growth performance and mucus biological components significantly in comparison with the control group(basal diet without Ergosan).展开更多
Objective:To identify the frequencies(F) of ferredoxin and nitroreductase mutations were identified on Iranian clinical isolates of Giardia lamblia in order to predict whether the nitazoxanide can be prescribed as sui...Objective:To identify the frequencies(F) of ferredoxin and nitroreductase mutations were identified on Iranian clinical isolates of Giardia lamblia in order to predict whether the nitazoxanide can be prescribed as suitable drug for symptomatic to metronidazoleresistant giardiasis.Methods:Forty Giardia lamblia isolates as of 38 symptomatic and two metronidazole-resistant patients were collected from Iran.DNAs were extracted and amplified by targeting ferredoxin and Gl NR genes.The amplicons were directly sequenced to determine gene mutations.Results:The various amino acid substitutions(F:20%,Haplotype diversity:0.891,Tajima's D:-0.44013) were identified by analyzing ferredoxin gene in four symptomatic and two resistant isolates.Only,two haplotypes(F:5%,HD:0.345; Tajima's D:0.77815) characterized in metronidazole-resistant isolates of Gl NR,however,no point mutations was found in symptomatic isolates.Conclusions:Non-synonymous mutations of ferredoxin oxidoreductase gene reduce translational regulatory protein's binding affinity which concludes reduction of ferredoxin expression and its activity.This leads to decrease in metronidazole drug delivery into the cells.Mutations in these isolates may lead to their resistance to metronidazole.No to low synonymous mutations of Gl NR demonstrates that nitazoxanide can be prescribed as promising alternative treatment for symptomatic to metronidazole-resistant giardiasis in Iranian clinical isolates.展开更多
Objective: To evaluate the capability of recombinant Leishmania LPG3 and its fragments in the activation of B cells. Methods: In the present study, human B cells were purified from peripheral blood of 10 adult healthy...Objective: To evaluate the capability of recombinant Leishmania LPG3 and its fragments in the activation of B cells. Methods: In the present study, human B cells were purified from peripheral blood of 10 adult healthy subjects using magnetic-activated cell sorting technique. Subsequently, purified B cells were treated with recombinant LPG3, and its N-terminal and C-terminal fragments at different concentrations(2, 10 and 20 μg/m L). B cell activation was assessed through expression of CD69 molecule by flowcytometry and secretion of IL-6, TNF-α and IL-10 cytokines via enzyme-linked immunosorbent assay following treatment with recombinant antigens. Results: Our results showed that while the recombinant LPG-3 could significantly increase the production of IL-6 and TNF-α(P<0.05) in B cells, it had no effect on the secretion of IL-10 by B cells. Conclusions: Our study indicated that recombinant LPG-3 and especially its N-terminal fragment could stimulate B cell response as an important immune response component against leishmaniasis. Thus, it seems that it can be considered as an effective adjuvant in vaccine developments against leishmaniasis.展开更多
AIM:To investigate the effect of MEK/ERK1/2 pathway on peroxisome proliferator-activated receptors(PPARγ)agonist-induced alterations in Δ6-desaturase(Δ6D)and stearoyl-CoA desaturase 1(SCD1)in hepatocellular carcino...AIM:To investigate the effect of MEK/ERK1/2 pathway on peroxisome proliferator-activated receptors(PPARγ)agonist-induced alterations in Δ6-desaturase(Δ6D)and stearoyl-CoA desaturase 1(SCD1)in hepatocellular carcinoma cell line HepG2.METHODS:HepG2 cells cultured in RPMI-1640 were exposed to the commonly used ERK1/2 pathway inhibitor PD98059 and PPARγ agonist,pioglitazone.Total RNA was isolated and reverse transcribed from treated cells.Changes in gene expression and metabolites ratio,as activity index for Δ6D and SCD1,were then determined using reverse transcriptionpolymerase chain reaction and gas liquid chromatography,respectively.RESULTS:The expression of both Δ6D(P = 0.03)and SCD1(P = 0.01)increased following PD98059 treatment,with a higher impact on SCD1(24.5%vs 62.5%).Although pioglitazone increased the mRNA level(1.47 ± 0.10 vs 0.88 ± 0.02,P = 0.006)and activity index(1.40 ± 0.07 vs 0.79 ± 0.11,P < 0.001)of Δ6D,no such changes have been observed for SCD1 activity index in pioglitazone-treated cells.SCD1 gene expression(+26.4%,P = 0.041)and activity index(+52.8%,P = 0.035)were significantly increased by MEK inhibition in the presence of pioglitazone,as compared with pioglitazone alone and control cells.However,the response of Δ6D expression and activity index to pioglitazone was unaffected by incubation with PD98059.CONCLUSION:PPARγ and ERK1/2 signaling pathway affect differentially and may have inhibitory crosstalk effects on the genes expression of 6D and SCD1,and subsequently on their enzymatic activities.展开更多
Background:Glioblastoma remains a highly invasive primary brain malignancy with an undesirable prognosis.Growing evidence has shed light on the importance of microRNAs(miRs),as small non-coding RNAs,in tumor developme...Background:Glioblastoma remains a highly invasive primary brain malignancy with an undesirable prognosis.Growing evidence has shed light on the importance of microRNAs(miRs),as small non-coding RNAs,in tumor development and progression.The present study leverages the in-silico and in-vitro techniques to investigate the significance of hsa-miR-181a-5p and the underlying hsa-miR-181a-5p-meidated signaling pathway in glioblastoma development.Methods:Bioinformatic studies were performed on GSE158284,GSE108474(REMBRANDT study),TCGA-GTEx,CCLE,GeneMANIA,Reactome,WikiPathways,KEGG,miRDB,and microT-CDS to identify the significance of hsa-miR-181a-5p and its underlying target.Afterward,the U373 cell line was selected and transfected with hsa-miR-181a-5p mimics,and the cell viability,clonogenicity,migration,mRNA expression,apoptosis,and cell cycle were studied using the MTT assay,colony formation test,migration assay,qRT-PCR,andflow cytometry respectively.Results:hsa-miR-181a-5p expression is decreased in glioblastoma samples.The in-silico results have shown that hsa-miR-181a-5p could regulate the MAPK pathway by targeting AKT3.The experimental assays have shown that hsa-miR-181a-5p decreases the migration of glioblastoma cells,arrests the cell cycle,and increases the apoptosis rate.Besides downregulating MMP9 and upregulating BAX,hsa-miR-181a-5p downregulates MET,MAP2K1,MAPK1,MAPK3,and AKT3 expression in U373 cells.The in-vitro results were consistent with in-silico results regarding the regulatory effect of hsa-miR-181a-5p on the MAPK pathway,leading to tumor suppression in glioblastoma.Conclusions:hsa-miR-181a-5p inhibits glioblastoma development partially by regulating the signaling factors of the MAPK pathway.展开更多
Esophageal cancer has been reported as the ninth most common malignancy and ranks as the sixth most frequent cause of death worldwide. Esophageal cancer treatment involves surgery, chemotherapy, radiation therapy, or ...Esophageal cancer has been reported as the ninth most common malignancy and ranks as the sixth most frequent cause of death worldwide. Esophageal cancer treatment involves surgery, chemotherapy, radiation therapy, or combination therapy. Novel strategies are needed to boost the oncologic outcome. Recent advances in the molecular biology of esophageal cancer have documented the role of genetic alterations in tumorigenesis. Oncogenes serve a pivotal function in tumorigenesis. Targeted therapies are directed at the unique molecular signature of cancer cells for enhanced efficacy with low toxicity. RNA interference(RNAi) technology is a powerful tool for silencing endogenous or exogenous genes in mammalian cells. Related results have shown that targeting oncogenes with siRNAs, specifically the mRNA, effectively reduces tumor cell proliferation and induces apoptotic cell death. This article will briefly review studies on silencing tumor enhancer genes related to the induction of esophageal cancer.展开更多
Immunotherapy has been recently considered as a promising alternative for cancer treatment.Indeed,targeting of immune checkpoint(ICP)strategies have shown significant success in human malignancies.However,despite rema...Immunotherapy has been recently considered as a promising alternative for cancer treatment.Indeed,targeting of immune checkpoint(ICP)strategies have shown significant success in human malignancies.However,despite remarkable success of cancer immunotherapy in pancreatic cancer(PCa),many of the developed immunotherapy methods show poor therapeutic outcomes in PCa with no or few effective treatment options thus far.In this process,immunosuppression in the tumor microenvironment(TME)is found to be the main obstacle to the effectiveness of antitumor immune response induced by an immunotherapy method.In this paper,the latest findings on the ICPs,which mediate immunosuppression in the TME have been reviewed.In addition,different approaches for targeting ICPs in the TME of PCa have been discussed.This review has also synopsized the cutting-edge advances in the latest studies to clinical applications of ICP-targeted therapy in PCa.展开更多
Aim:Immune challenge during early and late neonatal periods can induce robust alterations in physiological and behavioral functions,resulting in greater risk for the development of neuropsychiatric disorders,such as a...Aim:Immune challenge during early and late neonatal periods can induce robust alterations in physiological and behavioral functions,resulting in greater risk for the development of neuropsychiatric disorders,such as anxiety and depression,later in life.In addition,previous studies concluded that increasing age correlates with increased depression behaviors in humans and rodents.This study aimed to investigate for the first time whether immune challenge with a viral mimic,synthetic double-stranded ribonucleic acid(Poly I:C)during different neonatal periods can differently affect depression-related behaviors in adolescent and adult mice.Methods:Male C57BL/6 mice were treated with either saline or Poly I:C(1 mg/kg and 4 mg/kg)on postnatal days(PND)3-5(early neonatal phase)or PND 14-16(late neonatal phase),and then subjected to behavioral tests,including tail suspension test and forced swimming test,during adolescence(PND 35 or 40)and adulthood(PND 85 or 90).Results:The results demonstrated that early neonatal immune activation increases depression-related behaviors in both adolescent and adult mice,but late neonatal immune activation only increases depression in adult mice.In other words,these findings indicated that the nature of the offspring’s neuropathology can depend on the severity of the insult,the pup’s age at the time of the insult,and offspring age at the time of behavioral testing.Conclusion:These findings suggest that dose and timing of neonatal insult and offspring age may be important factors for evaluating neuropsychiatric disorders in adults who experienced early life infection.展开更多
基金Nanjing Forestry University[Grant Nos.163020139,164020818,163020217 and 16302023]National Natural Science Foundation of China(5201101466).
文摘A novel coronavirus of zoonotic origin(SARSCoV-2)has recently been recognized in patients with acute respiratory disease.COVID-19 causative agent is structurally and genetically similar to SARS and bat SARS-like coronaviruses.The drastic increase in the number of coronavirus and its genome sequence have given us an unprecedented opportunity to perform bioinformatics and genomics analysis on this class of viruses.Clinical tests like PCR and ELISA for rapid detection of this virus are urgently needed for early identification of infected patients.However,these techniques are expensive and not readily available for point-of-care(POC)applications.Currently,lack of any rapid,available,and reliable POC detection method gives rise to the progression of COVID-19 as a horrible global problem.To solve the negative features of clinical investigation,we provide a brief introduction of the general features of coronaviruses and describe various amplification assays,sensing,biosensing,immunosensing,and aptasensing for the determination of various groups of coronaviruses applied as a template for the detection of SARS-CoV-2.All sensing and biosensing techniques developed for the determination of various classes of coronaviruses are useful to recognize the newly immerged coronavirus,i.e.,SARS-CoV-2.Also,the introduction of sensing and biosensing methods sheds light on the way of designing a proper screening system to detect the virus at the early stage of infection to tranquilize the speed and vastity of spreading.Among other approaches investigated among molecular approaches and PCR or recognition of viral diseases,LAMP-based methods and LFAs are of great importance for their numerous benefits,which can be helpful to design a universal platform for detection of future emerging pathogenic viruses.
基金supported by the Immunology Research Center,Tabriz University of Medical Sciences,Tabriz,Iran.
文摘Infection with high-risk human papillomavirus(HPV),including HPV-16 and HPV-18,is the main cause of malignancies,such as cervical cancer.Viral oncoproteins encoded by HPV are expressed in HPV-positive cancers and associated with the early cancer stages and the transformation of normal cells.The signaling pathways involved in the transformation of normal cells to cancerous form and the subsequently expressed programmed cell death-ligand 1(PD-L1)on the surface of the transformed cells lead to a disruption in recognition of tumor cells by the immune cell system,including T lymphocytes and dendritic cells which lead to the development of cervical cancer malignancy.These cells also produce modest levels of cytokines during exhaustion,tumor-infiltrating T CD4+cells with high levels of PD-1 and CD39 release considerable quantities of cytokines.The Wnt/β-catenin signaling pathway,which controls the expression of genes involved in the tumor cells’markers,is demonstrated to be one of the most potent cancer stimulants.It leads to the evasion of the tumor cells from immune cell detection and ultimately avoids being recognized by dendritic cells or T-cells.PD-L1,as an inhibitory immune checkpoint,is essential for controlling immune system activity by inhibiting T-cells’inflammatory function.In the present review,we looked into how Wnt/β-catenin affects the expression of PD-L1 and related genes like c-MYC in cancer cells and its role in the development of HPV-induced malignancy.We hypothesized that blocking these pathways could be a potential immunotherapy and cancer prevention method.
基金supported by a grant from Tabriz University of Medical Sciences(Tbzmed)(376 and 1397).
文摘Cervical cancer is a growing global disease in developing countries.Persistent infection with human papillomaviruses(HPV)is an essential causative agent in this type of cancer.Several studies demonstrate HPV E5 oncoprotein can impress the normal life cycle of HPV-infected cells by targeting some pivotal cellular signaling pathways,such as the epidermal growth factor receptor(EGFR)signaling pathway.In this study,we used E5-siRNA to knockdown that essential oncogene and considered the effect of E5 silencing on proliferation,apoptosis,cell cycle,apoptosis-related gene expression,and the initiator of the EGFR signaling pathway in cervical cancer cells.The results demonstrate that E5 plays an essential role in the proliferation and inhibited apoptosis in cervical cancer.Furthermore,silencing E5 reduces proliferation,increases apoptosis,and elevates related-genes expression of these malignant cells.Overall,E5 suppression may be appropriate for ameliorating cervical cancer progression.
基金Supported by the Research Affairs of University of Tabriz,Iran and Nuclear Science and Technology Institute,Karaj,Iran
文摘Effects of irradiated and non-irradiated Ergosan extract(alginic acid) on rainbow trout growth performance and skin mucosal immunity were compared. Ergosan was irradiated at 30 kGy in a cobalt-60 irradiator. A total of 252 fish(128.03±9.4 g) were randomly divided into four equal groups,given the basal diet either unsupplemented with Ergosan(control group) or supplemented with crude Ergosan(5 g/kg),ethanol-extracted Ergosan(0.33 g/kg) or irradiated Ergosan(0.33 g/kg) according to this protocol: basal diet for 15 days,treatment diet for 15 days,basal diet for 10 days and treatment diet for 15 days. Highest growth performance was observed in fish fed irradiated Ergosan(P<0.05). Dietary administration of different Ergosan types did not cause any changes in mucus protein level,but improved alkaline phosphatase level and hemagglutination titer compared with the control(basal diet without Ergosan) on day 55 offeeding trial(P<0.05). Furthermore,the highest value of lysozyme activity was observed in gamma-irradiated Ergosan on day 55. In conclusion,gamma-irradiated Ergosan at 0.33 g/kg was found to improve growth performance and mucus biological components significantly in comparison with the control group(basal diet without Ergosan).
基金financially supported by Immunology Research Center,Tabriz University of Medical Sciences,Tabriz,Iranthe master’s thesis of the first author(Thesis No.93/2-4/12)
文摘Objective:To identify the frequencies(F) of ferredoxin and nitroreductase mutations were identified on Iranian clinical isolates of Giardia lamblia in order to predict whether the nitazoxanide can be prescribed as suitable drug for symptomatic to metronidazoleresistant giardiasis.Methods:Forty Giardia lamblia isolates as of 38 symptomatic and two metronidazole-resistant patients were collected from Iran.DNAs were extracted and amplified by targeting ferredoxin and Gl NR genes.The amplicons were directly sequenced to determine gene mutations.Results:The various amino acid substitutions(F:20%,Haplotype diversity:0.891,Tajima's D:-0.44013) were identified by analyzing ferredoxin gene in four symptomatic and two resistant isolates.Only,two haplotypes(F:5%,HD:0.345; Tajima's D:0.77815) characterized in metronidazole-resistant isolates of Gl NR,however,no point mutations was found in symptomatic isolates.Conclusions:Non-synonymous mutations of ferredoxin oxidoreductase gene reduce translational regulatory protein's binding affinity which concludes reduction of ferredoxin expression and its activity.This leads to decrease in metronidazole drug delivery into the cells.Mutations in these isolates may lead to their resistance to metronidazole.No to low synonymous mutations of Gl NR demonstrates that nitazoxanide can be prescribed as promising alternative treatment for symptomatic to metronidazole-resistant giardiasis in Iranian clinical isolates.
文摘Objective: To evaluate the capability of recombinant Leishmania LPG3 and its fragments in the activation of B cells. Methods: In the present study, human B cells were purified from peripheral blood of 10 adult healthy subjects using magnetic-activated cell sorting technique. Subsequently, purified B cells were treated with recombinant LPG3, and its N-terminal and C-terminal fragments at different concentrations(2, 10 and 20 μg/m L). B cell activation was assessed through expression of CD69 molecule by flowcytometry and secretion of IL-6, TNF-α and IL-10 cytokines via enzyme-linked immunosorbent assay following treatment with recombinant antigens. Results: Our results showed that while the recombinant LPG-3 could significantly increase the production of IL-6 and TNF-α(P<0.05) in B cells, it had no effect on the secretion of IL-10 by B cells. Conclusions: Our study indicated that recombinant LPG-3 and especially its N-terminal fragment could stimulate B cell response as an important immune response component against leishmaniasis. Thus, it seems that it can be considered as an effective adjuvant in vaccine developments against leishmaniasis.
基金Supported by A Grant from the Drug Applied Research Center of Tabriz University of Medical Sciences,to Darabi M,Research Projects numbers 89/102 and 90/73
文摘AIM:To investigate the effect of MEK/ERK1/2 pathway on peroxisome proliferator-activated receptors(PPARγ)agonist-induced alterations in Δ6-desaturase(Δ6D)and stearoyl-CoA desaturase 1(SCD1)in hepatocellular carcinoma cell line HepG2.METHODS:HepG2 cells cultured in RPMI-1640 were exposed to the commonly used ERK1/2 pathway inhibitor PD98059 and PPARγ agonist,pioglitazone.Total RNA was isolated and reverse transcribed from treated cells.Changes in gene expression and metabolites ratio,as activity index for Δ6D and SCD1,were then determined using reverse transcriptionpolymerase chain reaction and gas liquid chromatography,respectively.RESULTS:The expression of both Δ6D(P = 0.03)and SCD1(P = 0.01)increased following PD98059 treatment,with a higher impact on SCD1(24.5%vs 62.5%).Although pioglitazone increased the mRNA level(1.47 ± 0.10 vs 0.88 ± 0.02,P = 0.006)and activity index(1.40 ± 0.07 vs 0.79 ± 0.11,P < 0.001)of Δ6D,no such changes have been observed for SCD1 activity index in pioglitazone-treated cells.SCD1 gene expression(+26.4%,P = 0.041)and activity index(+52.8%,P = 0.035)were significantly increased by MEK inhibition in the presence of pioglitazone,as compared with pioglitazone alone and control cells.However,the response of Δ6D expression and activity index to pioglitazone was unaffected by incubation with PD98059.CONCLUSION:PPARγ and ERK1/2 signaling pathway affect differentially and may have inhibitory crosstalk effects on the genes expression of 6D and SCD1,and subsequently on their enzymatic activities.
文摘Background:Glioblastoma remains a highly invasive primary brain malignancy with an undesirable prognosis.Growing evidence has shed light on the importance of microRNAs(miRs),as small non-coding RNAs,in tumor development and progression.The present study leverages the in-silico and in-vitro techniques to investigate the significance of hsa-miR-181a-5p and the underlying hsa-miR-181a-5p-meidated signaling pathway in glioblastoma development.Methods:Bioinformatic studies were performed on GSE158284,GSE108474(REMBRANDT study),TCGA-GTEx,CCLE,GeneMANIA,Reactome,WikiPathways,KEGG,miRDB,and microT-CDS to identify the significance of hsa-miR-181a-5p and its underlying target.Afterward,the U373 cell line was selected and transfected with hsa-miR-181a-5p mimics,and the cell viability,clonogenicity,migration,mRNA expression,apoptosis,and cell cycle were studied using the MTT assay,colony formation test,migration assay,qRT-PCR,andflow cytometry respectively.Results:hsa-miR-181a-5p expression is decreased in glioblastoma samples.The in-silico results have shown that hsa-miR-181a-5p could regulate the MAPK pathway by targeting AKT3.The experimental assays have shown that hsa-miR-181a-5p decreases the migration of glioblastoma cells,arrests the cell cycle,and increases the apoptosis rate.Besides downregulating MMP9 and upregulating BAX,hsa-miR-181a-5p downregulates MET,MAP2K1,MAPK1,MAPK3,and AKT3 expression in U373 cells.The in-vitro results were consistent with in-silico results regarding the regulatory effect of hsa-miR-181a-5p on the MAPK pathway,leading to tumor suppression in glioblastoma.Conclusions:hsa-miR-181a-5p inhibits glioblastoma development partially by regulating the signaling factors of the MAPK pathway.
文摘Esophageal cancer has been reported as the ninth most common malignancy and ranks as the sixth most frequent cause of death worldwide. Esophageal cancer treatment involves surgery, chemotherapy, radiation therapy, or combination therapy. Novel strategies are needed to boost the oncologic outcome. Recent advances in the molecular biology of esophageal cancer have documented the role of genetic alterations in tumorigenesis. Oncogenes serve a pivotal function in tumorigenesis. Targeted therapies are directed at the unique molecular signature of cancer cells for enhanced efficacy with low toxicity. RNA interference(RNAi) technology is a powerful tool for silencing endogenous or exogenous genes in mammalian cells. Related results have shown that targeting oncogenes with siRNAs, specifically the mRNA, effectively reduces tumor cell proliferation and induces apoptotic cell death. This article will briefly review studies on silencing tumor enhancer genes related to the induction of esophageal cancer.
文摘Immunotherapy has been recently considered as a promising alternative for cancer treatment.Indeed,targeting of immune checkpoint(ICP)strategies have shown significant success in human malignancies.However,despite remarkable success of cancer immunotherapy in pancreatic cancer(PCa),many of the developed immunotherapy methods show poor therapeutic outcomes in PCa with no or few effective treatment options thus far.In this process,immunosuppression in the tumor microenvironment(TME)is found to be the main obstacle to the effectiveness of antitumor immune response induced by an immunotherapy method.In this paper,the latest findings on the ICPs,which mediate immunosuppression in the TME have been reviewed.In addition,different approaches for targeting ICPs in the TME of PCa have been discussed.This review has also synopsized the cutting-edge advances in the latest studies to clinical applications of ICP-targeted therapy in PCa.
文摘Aim:Immune challenge during early and late neonatal periods can induce robust alterations in physiological and behavioral functions,resulting in greater risk for the development of neuropsychiatric disorders,such as anxiety and depression,later in life.In addition,previous studies concluded that increasing age correlates with increased depression behaviors in humans and rodents.This study aimed to investigate for the first time whether immune challenge with a viral mimic,synthetic double-stranded ribonucleic acid(Poly I:C)during different neonatal periods can differently affect depression-related behaviors in adolescent and adult mice.Methods:Male C57BL/6 mice were treated with either saline or Poly I:C(1 mg/kg and 4 mg/kg)on postnatal days(PND)3-5(early neonatal phase)or PND 14-16(late neonatal phase),and then subjected to behavioral tests,including tail suspension test and forced swimming test,during adolescence(PND 35 or 40)and adulthood(PND 85 or 90).Results:The results demonstrated that early neonatal immune activation increases depression-related behaviors in both adolescent and adult mice,but late neonatal immune activation only increases depression in adult mice.In other words,these findings indicated that the nature of the offspring’s neuropathology can depend on the severity of the insult,the pup’s age at the time of the insult,and offspring age at the time of behavioral testing.Conclusion:These findings suggest that dose and timing of neonatal insult and offspring age may be important factors for evaluating neuropsychiatric disorders in adults who experienced early life infection.
