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1.
Gene ; 913: 148376, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38490510

RESUMO

The human BK Polyomavirus (BKPyV) is a DNA virus that is prevalent in 80 % of the population. Infection with this virus may begin in childhood, followed by asymptomatic persistence in the urinary tract. However, in immunocompromised individuals, especially kidney transplant recipients (KTRs), heightened replication of BKPyV can lead to severe complications. The genome of this virus is divided into three parts; the early and late region, and the non-coding control region (NCCR). Mutations in the NCCR can change the archetype strain to the rearranged strain, and NCCR rearrangements play a significant in virus pathogenesis. Interestingly, diverse types of NCCR block rearrangement result in significant differences in conversion potential and host cell viability in the infected cells. A correlation has been detected between increased viral replication potential and pathogenesis in BKPyV-infected KTRs with specific NCCR rearrangements. The objective of this review study was to examine the disease-causing and clinical consequences of variations in the NCCR in BKPyV-infected KTRs such as virus-associated nephropathy (BKPyVAN).


Assuntos
Vírus BK , Nefropatias , Transplante de Rim , Infecções por Polyomavirus , Humanos , Vírus BK/genética , Transplante de Rim/efeitos adversos , DNA Viral/genética , Transplantados
2.
Heliyon ; 10(4): e26359, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38420400

RESUMO

T helper 9 (Th9) cells, a subset of CD4+ T helper cells, have emerged as a valuable target for immune cell therapy due to their potential to induce immunomodulation and tolerance. The Th9 cells mainly produce interleukin (IL)-9 and are known for their defensive effects against helminth infections, allergic and autoimmune responses, and tumor suppression. This paper explores the mechanisms involved in the generation and differentiation of Th9 cells, including the cytokines responsible for their polarization and stabilization, the transcription factors necessary for their differentiation, as well as the role of Th9 cells in inflammatory and autoimmune diseases, allergic reactions, and cancer immunotherapies. Recent research has shown that the differentiation of Th9 cells is coregulated by the transcription factors transforming growth factor ß (TGF-ß), IL-4, and PU.1, which are also known to secrete IL-10 and IL-21. Multiple cell types, such as T and B cells, mast cells, and airway epithelial cells, are influenced by IL-9 due to its pleiotropic effects.

3.
Iran J Allergy Asthma Immunol ; 22(4): 379-389, 2023 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-37767680

RESUMO

The reactivation of polyomavirus BK (BKPyV) contributes to increased morbidity and mortality rates of transplant patients, especially kidney transplant recipients (KTRs). CD4+ T cells are important immune cells active during BKPyV infection in KTRs. This research tried to examine the phenotype of CD4+ T cells in the stage of BKPyV activation in KTRs.The re cipients were separated into 2 groups of BKPyV-active and nonactive KTRs (10 patients in each group) and were compared with 10 healthy control subjects. The viral load was evaluated by Taq-man quantitative real-time PCR. The frequency of different CD4+ T cell subsets was determined by analyzing markers such as CD45RO, CCR7, CD27, CD107a, perforin, and granzyme B using flow cytometry. The gene expression levels of transcription factors, including TBX21, GATA3, STAT3, and STAT6, contributing to CD4+ T cell activation, were also assessed. A significantly higher proportion in CCR7+CD27+CD45RO-CD4+ T cell (naive Tcell) subsets was detected in BKPyV-active KTRs compared to nonactive ones. A significant increase was detected in the frequency of CD107a+, perforin+, and granzyme B+ CD4+ T cells in the BKPyV-active group compared to the nonactive group. In CD4+ T cells of KTRs, the mRNA expression of TBX21  and GATA3 was significantly increased in KTRs without BKPyV reactivation compared to BKPyV-active ones. This investigation focused on the CD4+ T cell as an immunodominant T cell type with potential cytotoxicity. Based on these results, BKPyV may have a direct influence on the repertoire of CD4+ T cell subsets. Particularly, cytotoxic CD4+ T cells need further investigation to be considered as a therapeutic approach for BKPyV infection.


Assuntos
Antineoplásicos , Transplante de Rim , Polyomavirus , Humanos , Linfócitos T Citotóxicos , Granzimas , Transplante de Rim/efeitos adversos , Perforina , Receptores CCR7 , Linfócitos T CD4-Positivos
4.
Transpl Immunol ; 80: 101884, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37422092

RESUMO

BACKGROUND: In kidney transplant recipients (KTRs) who are immunosuppressed, human BK polyomavirus (BKPyV) infection can be reactivated, resulting in BKPyV-associated nephropathy (BKPyVN). Considering that BKPyV inhibits CD4+ T cell differentiation, we investigated the effect of BKPyV large T antigen (LT-Ag) on the maturation of CD4+ T cell subsets during active BKPyV infection. METHODS: In this cross-sectional study, we examined the following groups: 1) five KTRs with active viral infection (BKPyV+ KTRs), 2) five KTRs without active viral infection (BKPyV-KTRs), and 3) five healthy controls. We measured the frequency of CD4+ T cells and their different subsets, such as naive T cells, central memory T cells (Tcm), and effector memory T cells (Tem). All these subsets were analyzed by flow cytometry in peripheral blood mononuclear cells (PBMCs) stimulated with the overlapping BKPyV LT-Ag peptide pool. In addition, CD4+ T cell subsets were analyzed by flow cytometry for the presence of CD4, CCR7, CD45RO, CD107a, and granzyme B (GB). In addition, mRNA expression of transcription factors (TFs) such as T-bet, GATA-3, STAT-3, and STAT-6 was examined. The probability of inflammation with perforin protein was examined by SYBR Green real-time PCR. RESULTS: After stimulation of PBMCs, naive T cells (CD4+CCR7+CD45RO-) (p = 0.9) and CD4+ T cells which release CD107a+ (CD4+CD107a+Geranzyme B-) (p = 0.9) T cells were more abundant in BKPyV+ KTRs than in BKPyV- KTRs. In contrast, central memory T cells (CD4+CCR7+CD45RO+) (p = 0.1) and effector memory T cells (CD4+CCR7-CD45RO+) (p = 0.1) were more abundant in BKPyV- KTRs than in BKPyV+ KTRs. The mRNA expression levels of T-bet, GATA-3, STAT-3, and STAT-6 were significantly higher (p < 0.05) in BKPyV- KTRs than in BKPyV+ KTRs which may be due to a higher differentiation level of CD4+ T cells. Due to inflammation, the mRNA expression level of perforin was higher in BKPyV+ KTRs, than in BKPyV- KTRs, but the difference was not significant (p = 0.175). CONCLUSIONS: The high number of naive T cells after PBMC stimulation with the LT-Ag peptide pool was observed in BKPyV+ KTRs due to the interaction of LT-Ag with T cells. This means that BKPyV by using its LT-Ag can inhibit the naive T cell differentiation to other T cell subsets like central and effector memory T cells. However, the frequency of CD4+ T cell subsets and the combination of the activities of these cells with the expression profile of the target genes in this study may be efficient in treating and diagnosing BKPyV infections in kidney recipients.

5.
Gene ; 878: 147567, 2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37330024

RESUMO

BACKGROUND: BK polyomavirus (BKPyV) infection in immunocompromised patients can led to polyomavirus-associated nephropathy (BKPyVAN) especially after kidney transplantation. The polyomavirus genome contains enhancer elements that are important transcription activators. In this study, the association between viral and host gene expression and NCCR variations was evaluated in kidney transplant recipients (KTRs) with BKPyV active, and BKPyV in-active infection. METHODS AND RESULTS: Blood samples were collected from selected KTRs who divided to patients with active and in-active BKPyV infection. Transcriptional control region (TCR) anatomy was compared to the genomic sequence of archetype BKPyV strain WW using nested PCR method and sequencing. The expression level of some transcription factor genes was evaluated using in-house Real-time PCR (SYBR Green) technique. Most changes were observed after TCR anatomy detection in the Q and P blocks. The expression level of VP1 and LT-Ag viral genes were significantly higher in patients with active infection compared with non-infected ones. Transcription factor genes SP1, NF1, SMAD, NFκB, P53, PEA3, ETS1, AP2, NFAT and AP1 were significantly higher in BKPyV active group in comparison in-active and control groups. The analyses revealed that viral load level and mutations frequency has significant correlation. CONCLUSIONS: Based on the results, increasing of NCCR variations were associated with higher viral load of BKPyV especially in Q block. Host transcriptional factors and viral genes all had higher express level in active BKPyV patients versus no in-active ones. Detection of the relation between NCCR variation and BKPyV severity in KTRs need to be confirmed in further complicated studies.


Assuntos
Vírus BK , Transplante de Rim , Infecções por Polyomavirus , Humanos , Vírus BK/genética , Transplante de Rim/efeitos adversos , DNA Viral/genética , Infecções por Polyomavirus/genética , Infecções por Polyomavirus/diagnóstico , Fatores de Transcrição/genética , Receptores de Antígenos de Linfócitos T , Transplantados
6.
Wiley Interdiscip Rev RNA ; 14(4): e1769, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36470265

RESUMO

Early detection of BK polyomavirus (BKPyV) infection in kidney transplant recipients (KTRs) would enhance their quality of life and save the allograft. Still, many patients lose their grafted kidneys because of this infection. BKPyV microRNAs (miRNAs) have been detected in KTRs during viral infection. BKPyV produces two mature miRNAs that are named BKV-miR-B1-5p and BKV-miR-B1-3p. Additionally, BKPyV associated nephropathy (BKVAN) in kidney transplanted patients cause changes in the expression level of host genes and miRNAs such as IFN-É£, BCLA2A1, has-miR-10, and has-miR-30a. BKVAN can alter viral genes and miRNAs expression level, too, like viral miRNAs and T-Ag. However, their potential value as viral infection markers and the regulatory network produced by their expression during viral-host interactions needs more consideration since there are no approved medications for treating BKPyV-related diseases in KTRs. Hence, it is vital to recognize complicated facts regarding the impact of BKPyV infection on the distribution of miRNAs and mRNAs within the host cell and the virus. This article is categorized under: Translation > Regulation RNA Processing > Processing of Small RNAs RNA in Disease and Development > RNA in Disease.


Assuntos
Vírus BK , Transplante de Rim , MicroRNAs , Infecções por Polyomavirus , Humanos , Transplante de Rim/efeitos adversos , RNA Viral/genética , Qualidade de Vida , MicroRNAs/genética , Infecções por Polyomavirus/diagnóstico , Infecções por Polyomavirus/etiologia , Vírus BK/genética
7.
Arch Ital Urol Androl ; 95(4): 11691, 2023 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-38193229

RESUMO

BACKGROUND: Renal transplantation stands as the sole remedy for individuals afflicted with end-stage renal diseases, and safeguarding them from transplant rejection represents a vital, life-preserving endeavor posttransplantation. In this context, the impact of cytokines, notably IL-27, assumes a critical role in managing immune responses aimed at countering rejection. Consequently, this investigation endeavors to explore the precise function of IL-27 and its associated cytokines in the context of kidney transplant rejection. METHODS: The study involved the acquisition of blood samples from a cohort of participants, consisting of 61 individuals who had undergone kidney transplantation (comprising 32 nonrejected patients and 29 rejected patients), and 33 healthy controls. The expression levels of specific genes were examined using SYBR Green Real-time PCR. Additionally, the evaluation encompassed the estimation of the ROC curve, the assessment of the relationship between certain blood factors, and the construction of protein-protein interaction networks for the genes under investigation. RESULTS: Significant statistical differences in gene expression levels were observed between the rejected group and healthy controls, encompassing all the genes examined, except for TLR3 and TLR4 genes. Moreover, the analysis of the Area Under the Curve (AUC) revealed that IL-27, IL-27R, TNF-α, and TLR4 exhibited greater significance in discriminating between the two patient groups. These findings highlight the potential importance of IL-27, IL-27R, TNF-α, and TLR4 as key factors for distinguishing between individuals in the rejected group and those in the healthy control group. CONCLUSIONS: In the context of kidney rejections occurring within the specific timeframe of 2 weeks to 2 months post-transplantation, it is crucial to emphasize the significance of cytokines mRNA level, including IL-27, IL-27R, TNF-α, and TLR4, in elucidating and discerning the diverse immune system responses. The comprehensive examination of these cytokines' mRNA level assumes considerable importance in understanding the intricate mechanisms underlying kidney rejection processes during this critical period.


Assuntos
Rejeição de Enxerto , Interleucina-27 , Transplante de Rim , Humanos , Citocinas , Complicações Pós-Operatórias , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa
8.
Adv Pharmacol Pharm Sci ; 2022: 1850732, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341080

RESUMO

Objective: Phenolic acids are well-known phytochemicals that are detected in a wide variety of medicinal plants, and their antiproliferative effects on cancer cells are known, but their mechanisms are poorly revealed. In most of cancer cells, telomerase reverse transcriptase (hTERT) is a dominant factor of telomere length regulation. The hTERT expression promotes invasiveness in tumor cells and is a hallmark of cancer. Therefore, in this study, the probable inhibitory effects of caffeic (Caf), coumaric (Cum), and ferulic acids (Fer) are investigated on the hTERT expression pattern in HepG2 cells. Methods: The MTT, apoptosis assays, and real-time PCR analysis were applied to evaluate viability, cytotoxicity, and hTERT gene expression level, respectively. Results: All of the studied phenolic acids showed cytotoxic effects on HepG2 cells in a timely manner and presented a time-dependent inhibitory effect on the growth of HepG2 cells. They reduced percentage of viable cells and induced apoptosis. Also, these phenolic acids had significant inhibitory effects on hTERT gene expression. Conclusion: These findings suggest that cell viability along with hTERT gene expression in HepG2 cells could be reduced by Cum, Caf, and Fer. As different cancer cells are resistant to conventional chemotherapeutics, this type of results proposes the telomerase as a proper target of cancer therapy development by natural products.

9.
Transpl Immunol ; 74: 101655, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35777612

RESUMO

Human BK polyomavirus (BKPyV) can affect the machinery of the host cell to induce optimal viral replication or transform them into tumor cells. Reactivation of BKPyV happens due to immunosuppression therapies following renal transplantation which might result in BK polyomavirus nephropathy (BKPyVAN) and allograft loss. The first protein that expresses after entering into host cells and has an important role in pathogenicity is the Large T antigen (LT-Ag). In this review tries to study the molecular and cellular inter-regulatory counteractions especially between CD4 and CD8 T cells, and BKPyV LT-Ag may have role in nephropathy after renal transplantation.


Assuntos
Vírus BK , Transplante de Rim , Nefrite Intersticial , Infecções por Polyomavirus , Infecções Tumorais por Vírus , Antígenos Virais de Tumores/farmacologia , Vírus BK/fisiologia , Linfócitos T CD8-Positivos , Humanos , Transplantados
10.
BMC Nephrol ; 23(1): 20, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-34996392

RESUMO

BACKGROUND: BK virus associated nephropathy (BKVAN) is one of the common causes of graft loss among kidney transplanted recipients (KTRs). The current treatment for BKV nephropathy is decreasing the immunosuppressive regimen in KTRs. Interleukin-27 (IL-27) is a multifunctional cytokine that might be the front-runner of an important pathway in this regard. Therefore, in current study it is tried to evaluate the changes in the expression level of IL-27 and some related molecules, resulting from BKV reactivation in KTR patients. METHODS: EDTA-treated blood samples were collected from all participants. Patients were divided into two groups, 31 kidney transplant recipients with active and 32 inactive BKV infection, after being monitored by Real time PCR (Taq-Man) in plasma. Total of 30 normal individuals were considered as healthy control group. Real time PCR (SYBR Green) technique is used to determine the expression level of studied genes. RESULTS: The results of gene expression comparisons showed that the expression level of IL-27, IFN-γ, TNF-α, TNFR2 and IRF7 genes was significantly higher in inactive group in comparison to active group. The expression level of TLR4 was lower in both active and inactive groups in comparison to control group. ROC curve analysis showed that IL-27 and IRF7 are significantly different amongst other studied genes. Finally, the analyses revealed that the expression level of most of the studied genes (except for TNF-α and TLR4) have significant correlation with viral load. CONCLUSIONS: Our findings revealed that IL-27, IFN-γ, TNF-α, TNFR2 and IRF7 expression level is higher in inactive group and TLR4 expression level is lower in patients' groups in comparison to control group. Also, ROC curve analysis showed IL-27 and IRF7 can significantly differentiate studied groups (BKV active vs. inactive). Therefore, these results might help elucidating the pattern in charge of BKV reactivation in kidney transplanted patients.


Assuntos
Vírus BK/fisiologia , Citocinas/fisiologia , Nefropatias/virologia , Transplante de Rim , Infecções por Polyomavirus/imunologia , Complicações Pós-Operatórias/imunologia , Complicações Pós-Operatórias/virologia , Infecções Tumorais por Vírus/imunologia , Ativação Viral , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
11.
BMC Gastroenterol ; 21(1): 262, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118888

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) can lead to liver failure which renders to liver transplant. miRNAs might be detected as biomarkers in subclinical stage of several hepatobiliary disorders like HCC. Therefore, in the present study, alterations in miRNAs as biomarkers were detected in LT patients with HCC. METHODS: Fourteen tissue samples composed of 5 rejected and 9 non-rejected ones were used for studying the miRNAs expression pattern using LNA-array probe assay and the result was evaluated by in house SYBR Green Real-time PCR protocols on 30 other tissue samples composed of 10 rejected and 20 non-rejected ones for the selected miRNAs. All samples were collected from liver transplanted patients with HCC. RESULTS: The study results revealed that in rejected patients compared to non-rejected ones, hsa-miR-3158-5p, -4449, -4511, and -4633-5p were up-regulated and hsa-miR-122-3p, -194-5p, 548as-3p, and -4284 were down-regulated. ROC curve analysis also confirmed that miR194-5p and -548as-3p in up-regulated and also, miR-3158-5p, -4449 in down-regulated microRNAs are significantly important molecules in rejection. CONCLUSION: Finally, the tissue levels of specific miRNAs (especially hsa-miR-3158-5p, -4449, -194-5p and -548as-3p) significantly correlated with the development of HCC, which can be present as biomarkers after further completing studies.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , MicroRNAs , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/cirurgia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgia , MicroRNAs/genética , Transcriptoma
12.
Infect Genet Evol ; 88: 104669, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33301988

RESUMO

Members of Coronaviridae family have been the source of respiratory illnesses. The outbreak of SARS-CoV-2 that produced a severe lung disease in afflicted patients in China and other countries was the reason for the incredible attention paid toward this viral infection. It is known that SARS-CoV-2 is dependent on TMPRSS2 activity for entrance and subsequent infection of the host cells and TMPRSS2 is a host cell molecule that is important for the spread of viruses such as coronaviruses. Different factors can increase the risk of prostate cancer, including older age, a family history of the disease. Androgen receptor (AR) initiates a transcriptional cascade which plays a serious role in both normal and malignant prostate tissues. TMPRSS2 protein is highly expressed in prostate secretory epithelial cells, and its expression is dependent on androgen signals. One of the molecular signs of prostate cancer is TMPRSS2-ERG gene fusion. In TMPRSS2-ERG-positive prostate cancers different patterns of changed gene expression can be detected. The possible molecular relation between fusion positive prostate cancer patients and the increased risk of lethal respiratory viral infections especially SARS-CoV-2 can candidate TMPRSS2 as an attractive drug target. The studies show that some molecules such as nicotinamide, PARP1, ETS and IL-1R can be studied deeper in order to control SARS-CoV-2 infection especially in prostate cancer patients. This review attempts to investigate the possible relation between the gene expression pattern that is produced through TMPRSS2-ERG fusion positive prostate cancer and the possible influence of these fluctuations on the pathogenesis and development of viral infections such as SARS-CoV-2.


Assuntos
Enzima de Conversão de Angiotensina 2/genética , COVID-19/genética , Proteínas de Fusão Oncogênica/genética , Neoplasias da Próstata/genética , Serina Endopeptidases/genética , Glicoproteína da Espícula de Coronavírus/genética , Idoso , Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/complicações , COVID-19/patologia , COVID-19/virologia , Di-Hidrotestosterona/metabolismo , Regulação da Expressão Gênica , Interações Hospedeiro-Patógeno/genética , Humanos , Masculino , Proteínas de Fusão Oncogênica/metabolismo , Neoplasias da Próstata/complicações , Neoplasias da Próstata/patologia , Neoplasias da Próstata/virologia , Receptores Androgênicos/genética , Receptores Androgênicos/metabolismo , SARS-CoV-2/genética , SARS-CoV-2/metabolismo , SARS-CoV-2/patogenicidade , Serina Endopeptidases/metabolismo , Transdução de Sinais , Glicoproteína da Espícula de Coronavírus/metabolismo , Transcrição Gênica , Internalização do Vírus
13.
Stem Cell Res Ther ; 11(1): 54, 2020 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-32033595

RESUMO

Due to the prominent role of the liver in the body and detoxification, its functionality can be affected in an irreversible manner by diseases. This phenomenon renders the liver to stop working, leading to morbidity and mortality. Therefore, liver transplantation is the only way to tackle this issue.In order to compensate for the lack of adequate healthy liver tissue for transplantation, therapeutic approaches such as hepatocyte transplantation have been proposed as an alternative. Recognizing the fact that mesenchymal stem cells are adult stem cells with the capacity to differentiate into several cell types, different methods have been invented to produce hepatocyte-like cells from mesenchymal stem cells. They can be divided into three main categories, such as addition of cytokines and growth factors, genetic modifications, and adjustment of microenvironment as well as physical parameters.In this review, we attempted to introduce diverse efficient methods for differentiating mesenchymal stem cells and their capability for transformation into hepatocyte-like cells.


Assuntos
Hepatócitos/metabolismo , Fígado/metabolismo , Células-Tronco Mesenquimais/metabolismo , Diferenciação Celular , Células Cultivadas , Humanos
14.
Microb Pathog ; 129: 187-194, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30769026

RESUMO

Polyomavirus BK infection is a common complication and a major cause of morbidity after kidney transplantation. Surveillance of kidney transplant recipients was threatened by reactivation of polyomavirus BK infection can lead to polyomavirus BK-associated nephropathy (PVN). Antiviral immunoregulatory markers like Gamma interferon (IFN-γ) might also affect the polyomavirus BK pathogenesis for its role in antiviral host defense, graft rejection, and regulative of the adaptive immune responses. After screening polyomavirus BK infection, using Real time PCR (Taq-Man), the possible association between polyomavirus BK infection with IFN-γ gene expression was assessed. The mRNA levels of IFN-γ was examined in (n = 23) polyomavirus BK infected and (n = 23) non-infected kidney transplant patients in comparison with healthy controls (n = 23), using an in-house Real time PCR (SYBR Green) assay. The correlation of IFN-γ expression with viral load as well as other variables was also performed. The mRNA expression level of IFN-γ was significantly higher in polyomavirus BK infected patients (fold = 58.47) compared with non-infected ones (fold = 4.62), and healthy controls (p = 0.002). IFN-γ expression was higher in patients with higher viral load (p = 0.001). IFN-γ expression was correlated with viral load (r = 0.7, p < 0.0001). Accordingly, polyomavirus BK infection can induce IFN-γ gene over expression in kidney transplant infected patients. The results emphasized on the determinative role of IFN-γ in the pathogenesis of activated polyomavirus BK infection and also its importance in managing the clinical complications after kidney transplantation due to virus reactivation, requiring further investigation.


Assuntos
Vírus BK/isolamento & purificação , Expressão Gênica , Interferon gama/biossíntese , Transplante de Rim , Infecções por Polyomavirus/patologia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo Real , Transplantados , Carga Viral , Adulto Jovem
15.
Ann Lab Med ; 39(1): 58-66, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30215231

RESUMO

BACKGROUND: Single nucleotide polymorphisms (SNPs) can modulate various biological processes by influencing microRNA (miRNA) biogenesis and altering target selection. Common SNPs may alter the processing of miRNA and may be associated with hepatocellular carcinoma (HCC). We investigated the relationship between miR-499A>G, miR-149C>T, miR-196a2T>C, and miR-146aG>C and HCC susceptibility, examining the interaction of the miRNAs with hepatitis B virus (HBV). METHODS: We evaluated the associations of miR-499A>G (rs3746444), miR-149C>T (rs2292832), miR-196a2T>C (rs11614913), and miR-146aG>C (rs2910164) with HCC susceptibility in 100 HCC patients (70 males and 30 females) and 120 healthy controls (70 males and 50 females), using the PCR-restriction fragment length polymorphism method. RESULTS: For miR-499A>G, the frequencies of the AG genotype and G allele were higher in female HCC patients than in female controls (P=0.02 and 0.045, respectively). The frequency of the A allele was higher in HBV-positive HCC patients than in controls (P=0.019). For miR-149C>T, the frequency of the CC genotype was higher in female HCC patients than in female controls (P=0.009). For miR-196a2T>C, the frequencies of the CT and CC genotypes and the C allele were higher in HBV-positive HCC patients than in controls (P<0.001, P=0.009, and P<0.001, respectively). The frequencies of miR-146aG>C polymorphisms did not differ between HCC patients and controls. CONCLUSIONS: miR-499A>G, miR-149C>T, and miR-196a2T>C were associated with the development of HCC in women and/or that of HBV-related HCC. They can be considered genetic risk factors for the development of HCC among Iranians.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , MicroRNAs/metabolismo , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Hepatite B/complicações , Hepatite B/diagnóstico , Humanos , Irã (Geográfico) , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/genética , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Fatores de Risco
16.
Exp Clin Transplant ; 15(5): 554-560, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26925776

RESUMO

OBJECTIVES: Hepatitis B viral infection is among the most common causes of cirrhosis and hepatocellular carcinoma and a frequent viral indication for liver transplant. Cytokine-mediated immunity plays a critical role in introducing and promoting hepatitis B virus outcomes and in graft microenvironment. Interleukin 27 is a heterodimeric cytokine and a member of interleukin-6/interleukin-12 family. Interleukin-27 shows a broad range of pro- and antiinflammatory properties and plays a determining role during immune responses in combating hepatitis B virus. Therefore, in this study, the possible association between expressions of interleukin-27 gene with hepatitis B virus infection was evaluated in liver transplant patients. MATERIALS AND METHODS: In a cross-sectional study from liver transplant patients with the risk of hepatitis B virus infection who admitted to Namazi Hospital affiliated to Shiraz University of Medical Sciences, 50 patients were selected and subgrouped to 25 hepatitis B virus-infected and 25 noninfected ones between years 2011 and 2013. The 25 healthy controls also were enrolled in this study. The presence of hepatitis B virus infection was assessed using polymerase chain reaction and enzyme-linked immunosorbent assay protocols in liver transplant patients. In addition, the interleukin-27 gene expression level was analyzed using an in-house-SYBER Green real time polymerase chain reaction method. The rate of interleukin-27 gene expression level was statistically analyzed in studied patient groups and controls using the Livak (2-▵▵CT) method. RESULTS: The expression level of interleukin-27 gene was increased 10.27- and 2.36-fold in hepatitis B virus-infected and uninfected liver transplanted patients compared with healthy controls. CONCLUSION: Hepatitis B virus infection can lead to overexpression of interleukin-27 gene in liver transplant patients compared with uninfected ones and controls. However, further studies are needed to characterize the effective antihepatitis B virus effects of interleukin-27 in liver transplant patients.


Assuntos
Doença Hepática Terminal/genética , Vírus da Hepatite B/imunologia , Hepatite B/genética , Interleucinas/genética , Transplante de Fígado , Adulto , Estudos de Casos e Controles , Estudos Transversais , Doença Hepática Terminal/imunologia , Doença Hepática Terminal/cirurgia , Doença Hepática Terminal/virologia , Feminino , Hepatite B/imunologia , Hepatite B/cirurgia , Hepatite B/virologia , Hospitais Universitários , Interações Hospedeiro-Patógeno , Humanos , Interleucinas/imunologia , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Regulação para Cima
17.
Immunol Invest ; 44(5): 427-37, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26107743

RESUMO

Mesenchymal stem cells (MSCs) can modulate dendritic cells (DCs) activation and induce tolerogenic characteristics in DCs. All mechanisms involved in MSCs-induced tolerogenic DCs are not fully understood. MicroRNAs (miRs) play important role in maturation and function of DCs. In this study, we investigated the effects of MSCs culture supernatant (C.S.) on expression of miR-155 and miR-23b in mice DCs. BALB/c mice spleens were used for DCs isolation. MSCs were isolated from the mice bone marrow and cultured in DMEM media. When MSCs expanded to sixth passage, C.S. was collected after 12, 24 and 48 h. Quantitative polymerase chain reaction (QPCR) was used to determine the expression of miR-155 and miR-23b in DCs treated with C.S. after 6 and 12 h. Secretion of IL-23 and TGF- ß were detected in DCs treated with C.S. by ELISA after 24 h. miR-23b expression was significantly increased in DCs treated with 12 h C.S. for 12 h compared to negative controls. miR-155 expression did not change in DCs treated with C.S. after 6 and 12 h. miR-23b expression was significantly increased in DCs treated with 12 h C.S. for 12 h, compared to those treated with C.S. for 6 h. Similarly, miR-23b expression was increased in DCs treated with 24 h C.S. for 12 h when compared to those treated for 6 h. Production of TGF-ß and IL-23 were not influenced by C.S. In conclusion, miR-23b is considered to be one of the mechanisms involved in tolerogenic DCs induction by C.S. in a time-dependent manner.


Assuntos
Meios de Cultivo Condicionados/farmacologia , Células Dendríticas/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/biossíntese , Adipogenia , Animais , Diferenciação Celular , Células Cultivadas , Citocinas/metabolismo , Células Dendríticas/metabolismo , Fatores Imunológicos/isolamento & purificação , Fatores Imunológicos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Osteogênese , Organismos Livres de Patógenos Específicos , Baço/citologia , Fatores de Tempo
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