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1.
Sci Rep ; 13(1): 14944, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37696867

RESUMO

The influenza virus hemagglutinin is an important part of the virus attachment to the host cells. The hemagglutinin proteins are one of the genetic regions of the virus with a high potential for mutations. Due to the importance of predicting mutations in producing effective and low-cost vaccines, solutions that attempt to approach this problem have recently gained significant attention. A historical record of mutations has been used to train predictive models in such solutions. However, the imbalance between mutations and preserved proteins is a big challenge for the development of such models that need to be addressed. Here, we propose to tackle this challenge through anomaly detection (AD). AD is a well-established field in Machine Learning (ML) that tries to distinguish unseen anomalies from normal patterns using only normal training samples. By considering mutations as anomalous behavior, we could benefit existing rich solutions in this field that have emerged recently. Such methods also fit the problem setup of extreme imbalance between the number of unmutated vs. mutated training samples. Motivated by this formulation, our method tries to find a compact representation for unmutated samples while forcing anomalies to be separated from the normal ones. This helps the model to learn a shared unique representation between normal training samples as much as possible, which improves the discernibility and detectability of mutated samples from the unmutated ones at the test time. We conduct a large number of experiments on four publicly available datasets, consisting of three different hemagglutinin protein datasets, and one SARS-CoV-2 dataset, and show the effectiveness of our method through different standard criteria.


Assuntos
COVID-19 , Vacinas contra Influenza , Influenza Humana , Unionidae , Animais , Humanos , Hemaglutininas , SARS-CoV-2 , Mutação
2.
IJID Reg ; 7: 233-236, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37351152

RESUMO

Multiple sclerosis (MS) is an immune system-mediated neurodegenerative disease. Recent studies suggest that viral agents, especially the Epstein Barr virus (EBV), are etiological agents for MS. The roles of other viruses in MS have been investigated. Studies have shown an increase in the level of antibodies against bovine leukemia virus (BLV) in patients with MS. In this regard, our study aimed to examine the presence of BLV DNA in peripheral blood mononuclear cells (PBMCs) of MS patients in Iran. In this cross-sectional study, the presence of BLV in 109 Iranian MS patients and 60 healthy controls was evaluated. The isolated PBMCs were used for DNA extraction and PCR, using specific primers for two distinct genes. The mean age of the participants was 39 ± 9.5 years, and 27 (24.77%) of them were male. Clinical evaluation of these patients showed the most frequent MS type to be relapsing-remitting MS (RRMS) (71; 65.14%). BLV evaluation did not show any BLV DNA presence in the PBMCs of individuals in either the MS or healthy control groups. Therefore, our study showed no evidence of BLV infection in Iranian MS patients.

4.
Infect Agent Cancer ; 18(1): 19, 2023 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-36959610

RESUMO

BACKGROUND: HPV-31, -33, and -58, along with HPV-45 and -52, account for almost 11% of HPV-associated cancers. Our previous studies showed that after HPV-16 and -51, HPV-58 was common and HPV-31 was as frequent as HPV-18 among Iranian women with normal cytology. Hence, in this study, we aimed to investigate the intra-type variations in L1 genes of HPV-58, -31, and -33 to find the predominant lineages circulating in women with normal cytology. METHODS: Complete coding sequencing of the L1 gene was amplified and nucleotide and amino acid sequences were compared to those of the references. The selective pressure on L1 protein and whether the variations of the L1 genes embed in L1 loops, or N-glycosylated sites were also investigated. RESULTS: B1, A, and A1 (sub)lineages were common in the HPV-58, -33, and -31 samples, respectively. Ninety nucleotide mutations were observed. Twenty nine nucleotide changes corresponded to nonsynonymous substitutions in which seventeen mutations were located in L1 loops. Only one codon position in HPV-58 sequences was found as the positive selection. No difference was observed in N-glycosylation sites between reference and understudied amino acid sequences. CONCLUSION: In the current study, we reported, for the first time, the (sub) lineages, amino acid, and genetic diversity in the L1 gene of circulating HPV-58, -33, and -31, in women with normal cytology, in Iran. Such studies can not only have epidemiological values, but also aid to set vaccination programs.

5.
APMIS ; 131(4): 161-169, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36478304

RESUMO

Autophagy is one of the important mechanisms in cell maintenance, which is considered associated with different pathological conditions such as viral infections. In this current study, the expression level and polymorphisms in some of the most important genes in the autophagy flux in COVID-19 patients were evaluated. This cross-sectional study was conducted among 50 confirmed COVID-19 patients and 20 healthy controls. The COVID-19 patients were divided into a severe group and a mild group according to their clinical features. The expression levels of ATG5, ATG16L1, LC3, and BECN1 were evaluated by the 2-∆∆CT method and beta-actin as the internal control. The polymorphisms of the ATG5 (rs506027, rs510432) and ATG16L1 (rs2241880 or T300A) were evaluated by the Sanger sequencing following the conventional PCR. The mean age of the included patients was 58.3 ± 17.9 and 22 (44%) were female. The expression levels of the LC3 were downregulated, while BECN1 and ATG16L1 genes represent an upregulation in COVID-19 patients. The polymorphism analysis revealed the ATG16L1 rs2241880 and AGT5 rs506027 polymorphism frequencies are statistically significantly different between COVID-19 and Healthy controls. The autophagy alteration represents an association with COVID-19 pathogenesis and severity. The current study is consistent with the alteration of autophagy elements in COVID-19 patients by mRNA expression-level evaluation. Furthermore, ATG16L1 rs2241880 and AGT5 rs506027 polymorphisms seem to be important in COVID-19 and are highly suggested for further investigations.


Assuntos
COVID-19 , Predisposição Genética para Doença , Humanos , Feminino , Masculino , Estudos Transversais , Polimorfismo de Nucleotídeo Único , Proteínas Relacionadas à Autofagia/genética , COVID-19/genética , Autofagia/genética
6.
Recent Adv Antiinfect Drug Discov ; 18(3): 205-214, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36345239

RESUMO

BACKGROUND: Considering the role of calcium in the replication and morphogenesis of rotaviruses, it is hypothesized that decreased cytosolic calcium levels by using calcium channel blockers can subsequently interfere with rotavirus replication. OBJECTIVE: The present study investigated the effects of two calcium ion channel blockers, amlodipine and diltiazem, against human rotavirus infection. METHODS: Cytotoxic effects of the drugs on MA-104 cells were evaluated using the neutral red assay. The effects of amlodipine and diltiazem at non-toxic concentrations on human rotavirus were examined using cytopathic effect inhibition, TCID50, and real-time PCR assays. RESULTS: The highest inhibitory effect was obtained at concentrations of 0.5 µg/ml of amlodipine and 3 µg/ml of diltiazem, leading to 4.6 and 5.5 logarithmic reductions in infectious rotavirus titer and four- and a five-fold increase in the Ct values compared to the virus control, respectively (p-value < 0.001). Conversely, infectious rotavirus titers were significantly elevated compared to the virus control at concentrations above 0.9 µg/ml of amlodipine and above 25 µg/ml of diltiazem. CONCLUSION: Our study suggests that in addition to cardiovascular diseases, calcium channel blockers at their optimal doses may also be used to treat gastroenteritis caused by rotavirus infection.


Assuntos
Infecções por Rotavirus , Rotavirus , Humanos , Diltiazem/farmacologia , Bloqueadores dos Canais de Cálcio/farmacologia , Anlodipino/farmacologia , Infecções por Rotavirus/tratamento farmacológico
7.
Malawi Med J ; 35(2): 101-105, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38264170

RESUMO

Background: The Coronavirus disease 2019 (COVID-19) pandemic influences all around the world. The SARS-CoV-2 ORF8 accessory gene represents multiple functions in virus-host interaction. The current study aimed to compare the ORF8 substitutions and epitope features of these substitutions in the various SARS-CoV-2 outbreaks including delta, alpha, and wild type variants in Iran from 2020 to 2022. In addition, we evaluate B cell, HLA I and II epitopes, by in-silico approach to ORF8 binding site prediction. Methods: The samples were collected from patients diagnosed with SARS-CoV-2 infection via a real-time PCR assay. Then, a conventional PCR was carried out for ORF8 mutations analysis and further Sanger sequencing. Possible important alterations in epitope features of the ORF8 were evaluated by epitope mapping. B cell, HLA class I and II epitopes, evaluated by online databases ABCpred, NetMHCpan-4.1, and NetMHCIIpan-3.2, respectively. Results: The current study results could not represent novel variations in seven full-length ORF8 sequences or major ORF8 deletions in 80 evaluated samples. In addition, we could not find any ORF8 A382 during each outbreak of variants. Epitope mapping represents differences between the Alpha and other variants, especially in B cell potential epitopes and HLA I. Conclusion: The immunoinformatic evaluation of ORF8 suggested epitopes represent major differences for the Alpha variant in comparison with other variants. In addition, having mild pathogenesis of the Omicron variant does not seem to be associated with ORF8 alteration by phylogenetic evaluation. Future in-vitro studies for a clear conclusion about the epitope features of ORF8 are required.


Assuntos
COVID-19 , SARS-CoV-2 , Proteínas Virais , Humanos , Epitopos , Imunoinformática , Irã (Geográfico) , Pandemias , Filogenia , SARS-CoV-2/genética , Proteínas Virais/genética
8.
Heliyon ; 8(9): e10483, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36158108

RESUMO

Globally, it is estimated that 43 million people are living with human immunodeficiency virus type 1 (HIV-1), and there are more than 600,000 acquired immunodeficiency syndrome (AIDS)-related deaths in 2020. The only way to increase the life expectancy of these patients right now is to use combination antiretroviral therapy (cART) for the lifetime. Due to the integration of the HIV-1 DNA in lymphocytes, the replication of the virus can only be reduced by using antiretroviral drugs. If the drug is stopped, the virus will replicate and reduce the number of lymphocytes. In recent years, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated endonuclease Cas9-mediated genome editing system has been considered, preventing HIV-1 replication by causing DNA double-stranded breaks (DSBs) or disrupting the integrated virus replication by targeting the provirus. In this study, we utilized the CRISPR/Cas9 without the nuclear localization signal sequence (w/o NLS) system to inhibit the VSV-G-pseudotyped HIV-1 replication by targeting the HIV-1 DNA as a prophylactic method. To this end, we designed a multiplex gRNA (guide RNA) cassette to target the pol, env, and nef/long terminal repeat (nef/LTR) regions of the HIV-1 genome and then cloned it in plasmid expressing no-NLS-Cas9 protein as an all-in-one CRISPR/Cas9 vector. Using HIV-1 pseudovirus transduction into HEK-293T cell lines, our results showed that the CRISPR/Cas9-no NLS system disrupts the pseudotyped HIV-1 DNA and significantly (P-value < 0.0001) decreases the p24 antigen shedding and viral RNA load in cell culture supernatants harvested 48h after virus transduction. Although these results revealed the potential of the CRISPR/Cas9-no NLS nuclease system as a prophylactic strategy against HIV-1 infections, due to inefficient impairments of HIV-1 DNA, further studies are required to enhance its effectiveness and application in clinical practice.

9.
J Parasit Dis ; 46(3): 764-770, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36091287

RESUMO

Trichomonas vaginalis is a protozoan parasite that causes trichomoniasis with worldwide distribution. This study evaluated actin genotypes of T. vaginalis isolates using PCR-RFLP and sequence analysis in Tehran, Iran. Overall, 850 vaginal samples were collected from women admitted to hospitals affiliated with the Iran University of Medical Sciences in Tehran from 2020-to 2021. The samples were examined by wet mount and cultured. The parasites were harvested, and PCR-RFLP was performed using three endonuclease enzymes of HindII, MseI, and RsaI on all T. vaginalis isolates. Digestion patterns were then compared, and the genotype of these isolates was defined. The PCR products were sequenced. Overall, 12 (1.4%) isolates of T. vaginalis were identified from 850 vaginal samples collected. The most common genotypes were genotype E, seven (58.3%) and genotype G, three (25%), followed by genotype I, two (%16.7), using PCR-RFLP patterns and sequencing. No pattern indicative of mixed infection was found. PCR-RFLP is a proper technique to detect different T. vaginalis isolates, and noticeable polymorphism was found between isolates. Genotype E was the most common genotype in the studied group. The phylogenetic analysis indicated the T. vaginalis genotype E isolates in a distinct group compared to the genotypes G and I that evolved from a common ancestor.

10.
J Clin Lab Anal ; 36(7): e24481, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35582746

RESUMO

BACKGROUND: Probiotics promote a healthy balance of gut bacteria and have many beneficial effects on human digestive physiology. Although, few side effects of probiotics have been reported. This study aimed to assess the safety of five probiotic candidate Lactobacillus strains isolated from healthy individuals by examining mutagenicity, genotoxicity, and oral toxic effects. METHODS: Five selected candidate probiotic (SCPs) strains were evaluated for genotoxicity (Ames test with Salmonella typhimurium), in vitro mammalian chromosome aberration test and an in vivo mouse micronucleus assay on peripheral blood of mice. To evaluate the oral dose toxicity, BALB/c mice models were treated repeatedly (2000, 1000, and 500 mg/kg body weight /day) for 28-days. RESULTS: The Ames test performed for two S. typhimurium strains TA 98 and TA100 (both in the absence and in the presence of S-9 metabolic activation system) did not show an increase in reverse mutation because of exposure to the SCPs in any of the doses (5.0, 2.5, 1.25, 0.625, and 0.3125 mg/plate). There was no genotoxicity in the SCPs treatment in the vitro chromosome aberration assay with Chinese hamster ovary cells (CHO-K1). In addition, none of the tested strains increased the frequency of micronucleated reticulocytes in reticulocytes, the SCPs with the studied doses caused no substantial variation in the experimental groups compared to the negative control group (p > 0.05). SCPs were not acutely toxic when administered to male and female BALB/c mice by single gavage at (2000, 1000, and 500 mg/kg b.w/day) with no mortality or clinical signs, change in body weight or macroscopic abnormalities were observed in this dose range. CONCLUSION: As a result, SCPs did not induce mutagenic potential in vitro with bacterial reverse mutation, clastogenicity, and in vivo tests in the ranges of concentrations evaluated in our study.


Assuntos
Mutagênicos , Probióticos , Animais , Peso Corporal , Células CHO , Aberrações Cromossômicas , Cricetinae , Cricetulus , Feminino , Humanos , Lactobacillus , Masculino , Camundongos , Testes de Mutagenicidade , Mutagênicos/toxicidade
11.
Curr HIV Res ; 20(1): 42-53, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34493187

RESUMO

BACKGROUND: Long-term non-progressors (LTNPs) are small subsets of HIV-infected subjects that can control HIV-1 replication for several years without receiving ART. The exact mechanism of HIV-1 suppression has not yet been completely elucidated. Although the modulatory role of microRNAs (miRNAs) in HIV-1 replication has been reported, their importance in LTNPs is unclear. OBJECTIVE: The aim of this cross-sectional study was to assess the expression pattern of miR-27b, -29, -150, and -221, as well as their relationship with CD4+ T-cell count, HIV-1 viral load, and nef gene expression in peripheral blood mononuclear cells (PBMCs) of untreated viremic patients and in LTNPs. METHODS: MiRNAs expression levels were evaluated with real-time PCR assay using RNA isolated from PBMCs of LTNPs, HIV-1 infected naive patients, and healthy people. Moreover, CD4 T-cell count, HIV viral load, and nef gene expression were assessed. RESULTS: The expression level of all miRNAs significantly decreased in the HIV-1 patient group compared to the control group, while the expression pattern of miRNAs in the LNTPs group was similar to that in the healthy subject group. In addition, there were significant correlations between some miRNA expression with viral load, CD4+ T-cell count, and nef gene expression. CONCLUSION: The significant similarity and difference of the miRNA expression pattern between LNTPs and healthy individuals as well as between elite controllers and HIV-infected patients, respectively, showed that these miRNAs could be used as diagnostic biomarkers. Further, positive and negative correlations between miRNAs expression and viral/cellular factors could justify the role of these miRNAs in HIV-1 disease monitoring.


Assuntos
Infecções por HIV , HIV-1 , MicroRNAs , Contagem de Linfócito CD4 , Estudos Transversais , HIV-1/genética , Humanos , Leucócitos Mononucleares , MicroRNAs/genética , MicroRNAs/metabolismo , Carga Viral
12.
J Clin Lab Anal ; 35(10): e23981, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34462972

RESUMO

BACKGROUND: Retinoblastoma is the most common primary intraocular malignancy in children less than 4 years. Retinoblastoma (RB) contains about 3%-5% of all childhood cancers. Recent studies demonstrated that interacting between RB tumor suppressor and oncoproteins of DNA tumor viruses such as human papillomavirus (HPV). The objective of the current systematic review study was to present conducted studies in the field of HPV infection and its possible role in retinoblastoma. METHODS: For this systematic review, all relevant original research studies were assessed by searching in electronic databases include PubMed, Embase, Scopus, Google Scholar, and Web of Science by using relevant keywords. The study was designed based on the PRISMA criteria. All publications with English literature and original researches are considered for screening. RESULTS: Conducted search results lead to 4070 studies. The title and abstract screening lead to 11 studies. Data extraction was performed on 8 included studies. The prevalence of the HPV was ranged from 0 to 69%, and HPV genotype 16 and 18 were the most detected types. The most used method for the detection of the viruses was PCR, and the most assessed sample was formalin-fixed, paraffin-embedded tissue blocks. CONCLUSION: The association between HPV and retinoblastoma is still inconsistent. The prevalence of the HPV in RB was ranged from 0 to 69%, which indicates a wide range and highlights the importance of further investigation for more accurate statistical of HPV prevalence in RB. Thus, further worldwide studies of larger sample sizes of cohorts should be investigated to clarify this uncertainty.


Assuntos
Infecções por Papillomavirus , Neoplasias da Retina , Retinoblastoma , Papillomavirus Humano 16 , Papillomavirus Humano 18 , Humanos , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Prevalência , Neoplasias da Retina/complicações , Neoplasias da Retina/epidemiologia , Retinoblastoma/epidemiologia , Retinoblastoma/virologia
13.
BMC Cancer ; 21(1): 926, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34399719

RESUMO

BACKGROUND: This study aimed to evaluate the possible role of human papillomavirus (HPV) and Epstein-Barr virus (EBV) coinfection as an etiological factor for prostate cancer (PCa) development. METHODS: This case-control study was conducted on 67 patients with PCa and 40 control subjects. The expression levels of cellular and viral factors involved in inflammation, tumor progression, and metastasis were quantified, using the enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR) assay. RESULTS: The EBV/HPV coinfection was reported in 14.9% of patients in the case group and 7.5% of the control subjects. The high-risk types of HPV, that is, HPV 16 and HPV 18, were responsible for 50 and 30% of HPV/EBV-coinfected PCa cases (n = 10), respectively. No significant relationship was observed between PCa and HPV/EBV coinfection (OR = 2.9, 95% CI: 0.18-45.2, P = 0.31). However, the highest percentage of HPV genome integration was found in the HPV/EBV-coinfected PCa group (8/10; 80%). Also, the mean expression levels of inflammatory factors (IL-17, IL-6, TNF-α, NF-κB, VEGF, ROS, and RNS), anti-apoptotic mediators (Bcl-2 and survivin), and anti-anoikis factors (Twist and N-cadherin) were significantly higher in the HPV/EBV-coinfected PCa group, compared to the non-coinfected PCa cases. Nevertheless, the tumor-suppressor proteins (p53 and pRb) and E-cadherin (inhibitor of anoikis resistance) showed significant downregulations in the HPV/EBV-coinfected PCa group, compared to the non-coinfected PCa cases. CONCLUSION: The HPV/EBV coinfection may be an etiological factor for PCa through modulation of cellular behaviors.


Assuntos
Alphapapillomavirus/isolamento & purificação , Anoikis , Coinfecção/complicações , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/isolamento & purificação , Infecções por Papillomavirus/complicações , Neoplasias da Próstata/patologia , Estudos de Casos e Controles , Infecções por Vírus Epstein-Barr/virologia , Seguimentos , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Prognóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/virologia
15.
Microb Pathog ; 158: 104998, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34044041

RESUMO

AIMS AND BACKGROUND: Lactobacillus spp. are an important element in breast milk. This component has a beneficial effect on the composition of the intestinal microflora and the intestinal immune system. The aim of this study was to isolate and identify Lactobacillus strains in breast milk and evaluate some of their probiotic properties, such as presence of bacteriocin genes, adhesion to HT-29 cell line, competition with enteropathogens in cell culture, and effect on serum level of lipids and digestive enzymes, and mice model of inflammatory bowel disease (IBD). MATERIALS AND METHODS: A total of 323 lactic acid bacteria (LAB) were isolated from breast milk samples of healthy mothers with the age ranges from 21 to 45 years old. These isolates were subjected to phenotypic and molecular experiments. The frequency of bacteriocin genes was determined by polymerase chain reaction (PCR). Adhesion of Lactobacillus isolates to HT-29 cells was measured based on the number of attached bacterial cells in 20 fields of the light microscopy. Competition test was done by colony count and real-time PCR procedures. Five strongly adhesive Lactobacillus strains were selected and administered orally to the treatment groups. After 8 days, the serum level of digestive enzymes and improvement in induced IBD, and after 14 days, the serum level of lipids (triglycerides, total cholesterol, HDL, and LDL) in treated mice were surveyed compared to the control groups. RESULTS: Based on the phenotypic and molecular experiments, L. casei, L. plantarum, L. rhamnosus, and L. acidophilus strains were isolated and identified in the breast milk samples. The highest frequency of bacteriocin genes belonged to Plantaricin B (100%), followed by Plantaricin D (84.7%), Plantaricin G (84.7%), and Plantaricin EF (54.3%). Also, 71.8% of the isolates were strongly adhesive, 21.8% were non-adhesive, and 6.4% were adhesive. Lactobacillus strains had a significant effect on the displacement of enteropathogens. The in vitro cholesterol-removing ability of L. casei (L1), L. casei (L2), L. casei (L3), L. plantarum (L4), and L. rhamnosus (L5) was 3.5, 31.5, 21.3, 18.7, and 27.3%, respectively. The serum level of total cholesterol in the L. plantarum (L4) group as well as LDL in the L. casei (L3) (p = .0108) and L. rhamnosus (L5) (p = .0206) groups decreased significantly compared to the control group. The serum level of lipase increased in all the treatment groups compared to the control group, which was significant in the L. plantarum (L4) group (p = .0390). Disease activity index (DAI) scores were improved significantly in L. casei (L3) group compared to the IBD control group (p < .0001). CONCLUSION: It could be concluded that lactobacilli strains isolated from the breast milk samples had good probiotic properties, such as presence of bacteriocin genes, attaching to enterocyte-like HT-29 cells, competing with intestinal pathogens, lowering cholesterol, and improving IBD. Thus, after further studies, they could be considered as probiotic strains.


Assuntos
Bacteriocinas , Doenças Inflamatórias Intestinais , Lactobacillus , Leite Humano/microbiologia , Probióticos , Adulto , Animais , Bacteriocinas/genética , Feminino , Humanos , Doenças Inflamatórias Intestinais/terapia , Camundongos , Pessoa de Meia-Idade , Mães , Adulto Jovem
16.
Cancer Treat Res Commun ; 27: 100323, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33530025

RESUMO

Human telomerase reverse transcriptase (hTERT) is an enzyme that is critically involved in elongating and maintaining telomeres length to control cell life span and replicative potential. Telomerase activity is continuously expressed in human germ-line cells and most cancer cells, whereas it is suppressed in most somatic cells. In normal cells, by reducing telomerase activity and progressively shortening the telomeres, the cells progress to the senescence or apoptosis process. However, in cancer cells, telomere lengths remain constant due to telomerase's reactivation, and cells continue to proliferate and inhibit apoptosis, and ultimately lead to cancer development and human death due to metastasis. Studies demonstrated that several DNA and RNA oncoviruses could interact with telomerase by integrating their genome sequence within the host cell telomeres specifically. Through the activation of the hTERT promoter and lengthening the telomere, these cells contributes to cancer development. Since oncoviruses can activate telomerase and increase hTERT expression, there are several therapeutic strategies based on targeting the telomerase of cancer cells like telomerase-targeted peptide vaccines, hTERT-targeting dendritic cells (DCs), hTERT-targeting gene therapy, and hTERT-targeting CRISPR/Cas9 system that can overcome tumor-mediated toleration mechanisms and specifically apoptosis in cancer cells. This study reviews available data on the molecular structure of telomerase and the role of oncoviruses and telomerase interaction in cancer development and telomerase-dependent therapeutic approaches to conquest the cancer cells.


Assuntos
Neoplasias/genética , Proteínas Oncogênicas Virais/metabolismo , Retroviridae/patogenicidade , Telomerase/metabolismo , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/genética , Senescência Celular/genética , Modelos Animais de Doenças , Terapia Genética/métodos , Interações entre Hospedeiro e Microrganismos/genética , Humanos , Camundongos , Neoplasias/terapia , Neoplasias/virologia , Proteínas Oncogênicas Virais/genética , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/genética , Vírus Oncolíticos/imunologia , Regiões Promotoras Genéticas , Retroviridae/genética , Telomerase/antagonistas & inibidores , Telômero/metabolismo , Homeostase do Telômero
17.
Asian Pac J Cancer Prev ; 22(1): 257-266, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33507707

RESUMO

INTRODUCTION: Central nervous system tumors are a diverse group of tumors that account for 2% of all adult cancers and 17% of childhood malignancies. Several internal and external risk factors are involved in the development of this cancer such as viral infections. The aim of this study was to the determination of the EBV infection frequency and the expression level of miR-122 and miR-BART in CNS tumors samples. METHODS: One hundred and thirty-eight  fresh tissue sample (106 case and 32 control) was collected from CNS specimens. The presence of Epstein-Barr virus (EBV) DNA was examined by PCR assay and the expression level of miR-122 and miR-BART were evaluated by using real-time PCR assay in CNS tissue samples. RESULTS: EBV DNA was detected in 17% (18 of 106) of tumors tissue samples and 6.4% (2 of 32) of control samples. according to results, there was a significant relationship between the presence of EBV-DNA with CNS tumors. Additionally, the expression level of miR-122 was significantly downregulated in the EBV-positive sample compared to that of the EBV-negative sample. Also, the level of EBV-BART1-3p expression was significantly higher in EBV-positive tumors samples than EBV-positive normal samples. CONCLUSION: The results of this study suggest that the EBV could change the condition of cancer cells by altering the expression of miR-122 and EBV-BART1-3p and maybe contribute to the development of cancer cells. However, the role of viral infections in CNS cancer requires further studies. 
.


Assuntos
Neoplasias Encefálicas/patologia , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4/isolamento & purificação , MicroRNAs/genética , RNA Viral/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/virologia , Estudos de Casos e Controles , DNA Viral/análise , DNA Viral/genética , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/virologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
18.
Iran J Microbiol ; 13(6): 878-886, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35222867

RESUMO

BACKGROUND AND OBJECTIVES: Human immunodeficiency virus (HIV) has various transmission routes. Instant antiretroviral therapy (ART) is the recommended treatment for HIV infection. Highly active antiretroviral therapy (HAART) significantly decreases the acquired immunodeficiency syndrome (AIDS) and AIDS-related co-morbidities. Notwithstanding the suitability of HAART, the antiretrovirals (ARVs) have adverse effects and antiretroviral drug resistance mutations are reported among those who receive ARVs. In this survey, the abundance of HIV-1 infection in Iranians with high-risk behaviors, and detection of the surveillance drug-resistant mutations (SDRMs) were evaluated. MATERIALS AND METHODS: This cross-sectional study was conducted on 250 individuals with high-risk behaviors from September 2014 to February 2020. HIV-1 Ag/Ab in plasma samples was detected using enzyme immunoassay (EIA) kits. The conserved region of HIV-1 was detected in the plasma samples by real-time polymerase chain reaction (PCR) assay. Furthermore, in individuals with positive HIV-1 RNA, HIV-1 viral load testing was performed. After amplification and sequencing of the HIV-1 protease, reverse transcriptase, and integrase genes, surveillance drug resistance mutation (SDRM) and phylogenetic analysis were determined. RESULTS: Out of the 250 participants with high-risk behaviors, six (2.4%) were infected with HIV-1. According to the phylogenetic analysis, the CRF35_AD (83.3% or 5/6) was the dominant subtype, followed by CRF01_AE (16.7% or 1/6). In this research, in none of the HIV-1 infected patients, SDRM for protease inhibitors (PIs), nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and integrase inhibitors (INs) were observed. Nevertheless, in one of the patients, V179L mutation was detected which is a rare non-polymorphic mutation and is listed as a rilpivirine (RPV) -associated resistance mutation. CONCLUSION: The results of the current survey revealed that 2.4% of people with high-risk behaviors are infected with HIV and the level of drug resistance mutations (DRMs) in these people is very low.

19.
Vet Med Sci ; 7(2): 559-571, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33210477

RESUMO

Since emerging coronaviruses have always become a human health concern globally especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV) and Middle East respiratory syndrome coronavirus and a novel coronavirus was introduced in Wuhan, China, in December 2019 (called SARS-CoV-2), many researchers focused on its epidemics, virological and clinical features. SARS-CoV-2 is classified as Betacoronaviruses genus and Sarbecovirus subgenus (lineage B). The virus shows a great similarity with SARS-CoV and bat SARS-like coronaviruses. In this study, we evaluate SARS-CoV-2 virus phylogeny and evolution by using current virus and related sequences.


Assuntos
Evolução Biológica , COVID-19/virologia , Filogenia , SARS-CoV-2/classificação , Zoonoses Virais/virologia , Animais , COVID-19/epidemiologia , Genoma Viral , Humanos , Fases de Leitura Aberta , SARS-CoV-2/genética , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Zoonoses Virais/epidemiologia
20.
PLoS One ; 15(11): e0242387, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33211751

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0232930.].

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