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Since 1997, highly pathogenic avian influenza viruses, such as H5N1, have been recognized as a possible pandemic hazard to men and the poultry business. The rapid rate of mutation of H5N1 viruses makes the whole process of designing vaccines extremely challenging. Here, we used an in silico approach to design a multi-epitope vaccine against H5N1 influenza A virus using hemagglutinin (HA) and neuraminidase (NA) antigens. B-cell epitopes, Cytotoxic T lymphocyte (CTL) and Helper T lymphocyte (HTL) were predicted via IEDB, NetMHC-4 and NetMHCII-2.3 respectively. Two adjuvants consisting of Human ß-defensin-3 (HßD-3) along with pan HLA DR-binding epitope (PADRE) have been chosen to induce more immune response. Linkers including KK, AAY, HEYGAEALERAG, GPGPGPG and double EAAAK were utilized to link epitopes and adjuvants. This construct encodes a protein having 350 amino acids and 38.46 kDa molecular weight. Antigenicity of ~ 1, the allergenicity of non-allergen, toxicity of negative and solubility of appropriate were confirmed through Vaxigen, AllerTOP, ToxDL and DeepSoluE, respectively. The 3D structure of H5N1 was refined and validated with a Z-Score of - 0.87 and an overall Ramachandran of 99.7%. Docking analysis showed H5N1 could interact with TLR7 (docking score of - 374.08 and by 4 hydrogen bonds) and TLR8 (docking score of - 414.39 and by 3 hydrogen bonds). Molecular dynamics simulations results showed RMSD and RMSF of 0.25 nm and 0.2 for H5N1-TLR7 as well as RMSD and RMSF of 0.45 nm and 0.4 for H5N1-TLR8 complexes, respectively. Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) confirmed stability and continuity of interaction between H5N1-TLR7 with the total binding energy of - 29.97 kJ/mol and H5N1-TLR8 with the total binding energy of - 23.9 kJ/mol. Investigating immune response simulation predicted evidence of the ability to stimulate T and B cells of the immunity system that shows the merits of this H5N1 vaccine proposed candidate for clinical trials.
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Virus da Influenza A Subtipo H5N1 , Vacinas , Animais , Humanos , Virus da Influenza A Subtipo H5N1/genética , Epitopos de Linfócito T/genética , Receptor 7 Toll-Like , Receptor 8 Toll-Like , Epitopos de Linfócito B , Biologia Computacional/métodos , Simulação de Acoplamento Molecular , Vacinas de Subunidades Antigênicas/genéticaRESUMO
INTRODUCTION: MicroRNAs, or miRNAs, with regulatory performance in inflammatory responses and infection are the prevalent manifestations of severe coronavirus disease (COVID-19). This study aimed to evaluate whether PBMC miRNAs are diagnostic biomarkers to screen the ICU COVID-19 and diabetic COVID-19 subjects. METHODS: Candidate miRNAs were selected through previous studies, and then the PBMC levels of selected miRNAs (miR-28, miR-31, miR-34a, and miR-181a) were measured via quantitative reverse transcription PCR. The diagnostic value of miRNAs was determined by the receiver operating characteristic (ROC) curve. The bioinformatics analysis was utilized to predict the DEM genes and relevant bio-functions. RESULTS: The COVID-19 patients admitted to ICU had significantly greater levels of selected miRNAs compared to non-hospitalized COVID-19 and healthy people. Besides, the mean miR-28 and miR-34a expression levels in the diabetic COVID-19 group were significantly upregulated when compared with the non-diabetic COVID-19 group. ROC analyses demonstrated the role of miR-28, miR-34a, and miR-181a as new biomarkers to discriminate the non-hospitalized COVID-19 group from the COVID-19 patients admitted to ICU samples, and also miR-34a can probably act as a useful biomarker for screening diabetic COVID-19 patients. Using bioinformatics analyses, we found the performance of target transcripts in many bioprocesses and diverse metabolic routes such as the regulation of multiple inflammatory parameters. DISCUSSION: The difference in miRNA expression patterns between the studied groups suggested that miR-28, miR-34a, and miR-181a could be helpful as potent biomarkers for diagnosing and controlling COVID-19.
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COVID-19 , Diabetes Mellitus , MicroRNAs , Humanos , Leucócitos Mononucleares , COVID-19/diagnóstico , MicroRNAs/genética , Biomarcadores , Unidades de Terapia IntensivaRESUMO
INTRODUCTION: This research aimed to evaluate the specific microRNA (miRNA) including miR-17-5p, miRN-140-3p miR-191-5p, miR-200c-3p, and miR-N367 and cellular factors (p21, SDF-1, XCL1, CCL-2, and IL-2) in controlling replication of human immunodeficiency virus (HIV) in ECs. METHODS: The expression of miRNAs was assessed between healthy control groups and patient groups including ART-naïve HIV, HIV ART, ECs, and coinfection (HIV-HBV and HIV-HCV) via real-time PCR technique. Besides, the expression level of the nef gene and cellular factors were assessed by the ELISA method. The differences in the level of cellular factors and selected miRNAs between study groups were analyzed using the Kruskal-Wallis H or one-way ANOVA test. In addition, the potential of selected miRNAs as biomarkers for discriminating study groups was assessed by the receiver-operator characteristic (ROC) curve analysis. RESULTS: Some miRNAs in ECs, HIV ART, and healthy controls have similar expression patterns, whereas a miRNA expression profile of patient groups significantly differed compared to EC and control groups. According to ROC curve analyses, the miR-17-5p, miR-140-3p miR-191-5p, miR-200c-3p, and miR-N367 can be served as biomarkers for discriminating ECs from ART-naïve HIV-infected groups. There was a significant correlation between some miRNAs and cellular factors/the viral load as well. CONCLUSION: This report demonstrated a differentiation in the expression of selected immunological factors and cellular/viral miRNAs in ECs compared to other patient groups. Some miRNAs and cellular factors are involved in the viral replication control, immune response/modulation and can be used as biomarkers for diagnosis of ECs and differentiation with other groups. Differential expression of these miRNAs and cellular factors in different stages of HIV infection can help in finding novel ways for infection control.
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Coinfecção , Infecções por HIV , Hepatite C , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Vírus da Hepatite B/genética , Hepacivirus/genética , Infecções por HIV/complicações , HIV , Perfilação da Expressão Gênica/métodos , Biomarcadores , Hepatite C/complicaçõesRESUMO
MicroRNAs (miRNAs) are fundamental post-transcriptional modulators of several critical cellular processes, a number of which are involved in host defense mechanisms. In particular, miRNA let-7 functions as an essential regulator of the function and differentiation of both innate and adaptive immune cells. Let-7 is involved in several human diseases, including cancer and viral infections. Several viral infections have found ways to dysregulate the expression of miRNAs. Extracellular vesicles (EV) are membrane-bound lipid structures released from many types of human cells that can transport proteins, lipids, mRNAs, and miRNAs, including let-7. After their release, EVs are taken up by the recipient cells and their contents released into the cytoplasm. Let-7-loaded EVs have been suggested to affect cellular pathways and biological targets in the recipient cells, and can modulate viral replication, the host antiviral response, and the action of cancer-related viruses. In the present review, we summarize the available knowledge concerning the expression of let-7 family members, functions, target genes, and mechanistic involvement in viral pathogenesis and host defense. This may provide insight into the development of new therapeutic strategies to manage viral infections.
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Vesículas Extracelulares , MicroRNAs , Viroses , Vesículas Extracelulares/metabolismo , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Viroses/genética , Viroses/metabolismo , Replicação ViralRESUMO
Autophagy is known as a conserved self-eating mechanism that contributes to cells to degrade different intracellular components (i.e., macromolecular complexes, aggregated proteins, soluble proteins, organelles, and foreign bodies). Autophagy needs formation of a double-membrane structure, which is composed of the sequestered cytoplasmic contents, called autophagosome. There are a variety of internal and external factors involved in initiation and progression of autophagy process. Viruses as external factors are one of the particles that could be associated with different stages of this process. Viruses exert their functions via activation and/or inhibition of a wide range of cellular and molecular targets, which are involved in autophagy process. Besides viruses, a variety of cellular and molecular pathways that are activated and inhibited by several factors (e.g., genetics, epigenetics, and environment factors) are related to beginning and developing of autophagy mechanism. Exosomes and microRNAs have been emerged as novel and effective players anticipated in various stages of autophagy. More knowledge in these pathways and identification of accurate roles of them could help to provide better therapeutic approaches in several diseases such as cancer. We highlighted the roles of viruses, exosomes, and microRNAs in the autophagy processes.
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Exossomos , MicroRNAs , Vírus , Exossomos/metabolismo , MicroRNAs/metabolismo , Autofagia/fisiologia , Autofagossomos/metabolismoRESUMO
Chemoresistance is often referred to as a major leading reason for cancer therapy failure, causing cancer relapse and further metastasis. As a result, an urgent need has been raised to reach a full comprehension of chemoresistance-associated molecular pathways, thereby designing new therapy methods. Many of metastatic tumor masses are found to be related with a viral cause. Although combined therapy is perceived as the model role therapy in such cases, chemoresistant features, which is more common in viral carcinogenesis, often get into way of this kind of therapy, minimizing the chance of survival. Some investigations indicate that the infecting virus dominates other leading factors, i.e., genetic alternations and tumor microenvironment, in development of cancer cell chemoresistance. Herein, we have gathered the available evidence on the mechanisms under which oncogenic viruses cause drug-resistance in chemotherapy.
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Antineoplásicos/uso terapêutico , Transformação Celular Viral , Farmacorresistência Viral , Neoplasias/tratamento farmacológico , Vírus Oncogênicos/patogenicidade , Animais , Antineoplásicos/efeitos adversos , Regulação Neoplásica da Expressão Gênica , Interações Hospedeiro-Patógeno , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/virologia , Transdução de Sinais , Microambiente TumoralRESUMO
Cervical cancer (CC) is the fourth most common cause of cancer death in women. The most important risk factor for the development of CC is cervical infection with human papilloma virus (HPV). Inflammation is a protective strategy that is triggered by the host against pathogens such as viral infections that acts rapidly to activate the innate immune response. Inflammation is beneficial if it is brief and well controlled; however, if the inflammation is excessive or it becomes of chronic duration, it can produce detrimental effects. HPV proteins are involved, both directly and indirectly, in the development of chronic inflammation, which is a causal factor in the development of CC. However, other factors may also have a potential role in stimulating chronic inflammation. MicroRNAs (miRNAs) (a class of noncoding RNAs) are strong regulators of gene expression. They have emerged as key players in several biological processes, including inflammatory pathways. Abnormal expression of miRNAs may be linked to the induction of inflammation that occurs in CC. Exosomes are a subset of extracellular vesicles shed by almost all types of cells, which can function as cargo transfer vehicles. Exosomes contain proteins and genetic material (including miRNAs) derived from their parent cells and can potentially affect recipient cells. Exosomes have recently been recognized to be involved in inflammatory processes and can also affect the immune response. In this review, we discuss the role of HPV proteins, miRNAs and exosomes in the inflammation associated with CC.
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Exossomos/imunologia , Inflamação/imunologia , MicroRNAs/metabolismo , Infecções por Papillomavirus/imunologia , Neoplasias do Colo do Útero/imunologia , Feminino , Regulação da Expressão Gênica/imunologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Inflamação/patologia , Inflamação/virologia , Papillomaviridae/imunologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Fatores de Risco , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Proteínas Virais/imunologia , Proteínas Virais/metabolismoRESUMO
The alarming rise of morbidity and mortality caused by influenza pandemics and epidemics has drawn attention worldwide since the last few decades. This life-threatening problem necessitates the development of a safe and effective vaccine to protect against incoming pandemics. The currently available flu vaccines rely on inactivated viral particles, M2e-based vaccine, live attenuated influenza vaccine (LAIV) and virus like particle (VLP). While inactivated vaccines can only induce systemic humoral responses, LAIV and VLP vaccines stimulate both humoral and cellular immune responses. Yet, these vaccines have limited protection against newly emerging viral strains. These strains, however, can be targeted by universal vaccines consisting of conserved viral proteins such as M2e and capable of inducing cross-reactive immune response. The lack of viral genome in VLP and M2e-based vaccines addresses safety concern associated with existing attenuated vaccines. With the emergence of new recombinant viral strains each year, additional effort towards developing improved universal vaccine is warranted. Besides various types of vaccines, microRNA and exosome-based vaccines have been emerged as new types of influenza vaccines which are associated with new and effective properties. Hence, development of a new generation of vaccines could contribute to better treatment of influenza.
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Pesquisa Biomédica/tendências , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/isolamento & purificação , Tecnologia Farmacêutica/tendências , Animais , Proteção Cruzada , Transmissão de Doença Infecciosa/prevenção & controle , Humanos , Imunidade Heteróloga , Influenza Humana/prevenção & controle , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/isolamento & purificação , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/isolamento & purificação , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/isolamento & purificaçãoRESUMO
BACKGROUND: Thyroid cancer is a common endocrine malignancy whose incidence has increased in recent years. Several internal and external risk factors are involved in the development of this cancer, such as infectious agents. Evidence supporting the role of viral infection as an etiology for the invasiveness of thyroid cancer is increasing. The aim of this study was to determine the presence of the Epstein-Barr virus (EBV) and the association between viral gene products and thyroid tumor development. METHODS: Fifty-seven thyroid cancer specimens were collected from the same number of patients as well as 18 samples from healthy controls. The presence of the EBV genome and the genotyping was examined by polymerase chain reaction (PCR). Also, an enzyme-linked immunosorbent assay and real-time PCR were used to measure the expression levels of viral and cellular genes. RESULTS: The EBV DNA was detected in 71.9% of the samples, and it was also found that the presence of the EBV was associated with increasing development of thyroid tumor. CONCLUSION: Our results demonstrated that EBV infection may play a role in the development of thyroid tumor.
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Transformação Celular Viral , DNA Viral/genética , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , Neoplasias da Glândula Tireoide/virologia , Proteínas Virais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , DNA Viral/metabolismo , Feminino , Regulação Viral da Expressão Gênica , Herpesvirus Humano 4/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Proteínas Virais/metabolismoRESUMO
Hepatocellular carcinoma (HCC) is known as one of the major health problems worldwide. Pathological analysis indicated that a variety of risk factors including genetical (i.e., alteration of tumor suppressors and oncogenes) and environmental factors (i.e., viruses) are involved in beginning and development of HCC. The understanding of these risk factors could guide scientists and clinicians to design effective therapeutic options in HCC treatment. Various viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) via targeting several cellular and molecular pathways involved in HCC pathogenesis. Among various cellular and molecular targets, microRNAs (miRNAs) have appeared as key players in HCC progression. miRNAs are short noncoding RNAs which could play important roles as oncogenes or tumor suppressors in several malignancies such as HCC. Deregulation of many miRNAs (i.e., miR-222, miR-25, miR-92a, miR-1, let-7f, and miR-21) could be associated with different stages of HCC. Besides miRNAs, exosomes are other particles which are involved in HCC pathogenesis via targeting different cargos, such as DNAs, RNAs, miRNAs, and proteins. In this review, we summarize the current knowledge of the role of miRNAs and exosomes as important players in HCC pathogenesis. Moreover, we highlighted HCV- and HBV-related miRNAs which led to HCC progression.
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Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/virologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , MicroRNAs/genética , Animais , Carcinoma Hepatocelular/etiologia , Hepacivirus/patogenicidade , Hepatite B/complicações , Hepatite B/virologia , Vírus da Hepatite B/patogenicidade , Hepatite C/complicações , Humanos , Neoplasias Hepáticas/etiologiaRESUMO
Astrocytic gliomas are the most common and lethal form of intracranial tumors. These tumors are characterized by a significant heterogeneity in terms of cytopathological, transcriptional, and (epi)genomic features. This heterogeneity has made these cancers one of the most challenging types of cancers to study and treat. To uncover these complexities and to have better understanding of the disease initiation and progression, identification, and characterization of underlying cellular and molecular pathways related to (epi)genetics of astrocytic gliomas is crucial. Here, we discuss and summarize molecular and (epi)genetic mechanisms that provide clues as to the pathogenesis of astrocytic gliomas.
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Astrocitoma/genética , Astrocitoma/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Epigênese Genética , Animais , HumanosRESUMO
Background: Human parvovirus B19 (B19V) can cause anemia in some patients, including those with compromised immunity system. There are a few studies on molecular epidemiology of B19V and its association with anemia in Iran. Therefore, the aim of this study was to determine the B19V DNA, IgM, IgG, genotyping, and viral load in HIV patients in different groups of pregnant women, general population, injection drug users (IDU), and Elite controllers. Also, the possible association of B19V with anemia was studied. Methods: In this case-control study, B19V DNA, anti-B19V IgM, anti-B19V IgG, viral load, and hemoglobin level were assessed in 113 HIV positive patients and 72 healthy controls. Also, CD4+ T cell counts and HIV load were measured in the patients' group. All statistical analyses were done using STATA 14.2 software (Stata Corporation, College Station, Texas, USA). P value < 0.05 was considered statistically significant. Results: Among HIV patients, 19 (16.8%) cases had B19V DNA, 3 (2.7%) had B19V IgM, and 7 (6.2%) had B19V IgG. In control group, the prevalence of B19V DNA, IgM, and IgG was 6 (8.33%), 7(9.7%), and 19 (26.4%), respectively. In subpopulations based on transmission routes, general population had the highest B19V IgG and DNA positivity prevalence and viral load level. There was no significant association between B19V antibodies and DNA with anemia. Conclusion: The results demonstrated that B19V infection cannot be considered as a high-risk factor for anemia in adult HIV patients. However, further studies are needed to determine the exact role of B19V infection in HIV patients.
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Cell therapy is an emerging fields in the treatment of various diseases such as cardiovascular, pulmonary, hepatic, and neoplastic diseases. Stem cells are an integral tool for cell therapy. Multipotent stem cells are an important class of stem cells which have the ability to self-renew through dividing and developing into multiple specific cell types in a specific tissue or organ. These cells are capable to activate or inhibit a sequence of cellular and molecular pathways leading to anti-inflammatory and anti-apoptotic effects which might contribute to the treatment of various diseases. It has been showed that multipotent stem cells exert their therapeutic effects via inhibition/activation of a sequence of cellular and molecular pathways. Although the advantages of multipotent stem cells are numerous, further investigation is still necessary to clarify the biology and safety of these cells before they could be considered as a potential treatment for different types of diseases. This review summarizes different features of multipotent stem cells including isolation, differentiation, and therapeutic applications.
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Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/transplante , Transplante de Células-Tronco , Animais , Separação Celular , Ensaios Clínicos como Assunto , Humanos , Neoplasias/terapiaRESUMO
Curcumin is known as a natural dietary polyphenol which is extracted from Curcuma longa L. It has been shown that curcumin has a variety of pharmacological effects such as antioxidant, anti-cancer, anti-inflammatory, and anti-microbial activities. Anti-cancer effects of curcumin are due to targeting of a wide range of cellular and molecular pathways involved in cancer pathogenesis including NF-kB, MAPK, PTEN, P53, and microRNAs (miRNA) network. Multiple lines of evidence have indicated that curcumin exerts its therapeutic effects via regulating miRNA expression (e.g., miR-1, miR-7, miR-9, miR-34a, miR-181, miR-21, and miR-19) which could lead to the regulation of underlying cellular and molecular pathways involved in cancer pathogenesis. Exosomes are one of the important classes of biological vehicles which could be released from various types of cells such as cancer cells and stem cells and could change the behavior of recipient cells. It has been shown that treatment of cancer cells with different dose of curcumin leads to the release of exosomes containing curcumin. These exosomes could induce anti-cancer properties in recipient cells and reduce tumor growth. Hence, exosomes containing curcumin could be applied as powerful tools for cancer treatment. Here, we highlighted various miRNAs which could be affected by curcumin in various types of cancer. Moreover, we highlight exosomes containing curcumin as suitable therapeutic tools in cancer therapy.
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Curcumina/uso terapêutico , MicroRNAs/metabolismo , Terapia de Alvo Molecular , Neoplasias/tratamento farmacológico , Neoplasias/genética , Ensaios Clínicos como Assunto , Humanos , Transdução de SinaisRESUMO
Elite controllers (ECs) defined as a small subclass of subjects with HIV capable of controlling human immunodeficiency virus (HIV) replication in the lack of antiretroviral treatment. One class of RNA molecules that serve as vital components in the network of HIV-related transcriptional regulation, are long noncoding RNAs (lncRNAs). The critical part that they take is in transcriptional regulation of HIV through monitoring various cellular signaling pathways. Reportedly, AKT and MAPK signaling pathways serve a crucial role in modulation of HIV infection. In the current investigation, we utilized bioinformatics tools to predict the lncRNAs that have the ability to interact with MAPK3, AKT, and FOXO1. Then, PBMC expression levels of lncRNAs and their target genes (AKT, FOXO1 and MAPK3) measured in the ECs (n = 15), HIV-positive (n = 40) patients and healthy control subjects (n = 40). We found a significant increase and decrease in the level of AKT and FOXO1 expression within the ECs group, respectively than in the HIV + group (P-value <0.0001 and 0.04, respectively). In the ECs group, the level of TINCR and RP11-156E8.1 was overexpressed compared to the HIV + group (P-value: 0.004 and 0.001, respectively). While RP11-573D15.8 level in ECs exhibited a significant suppression in contrast to HIV + group (P-value: 0.02). According to the receiver-operating characteristic (ROC) curve results, AKT and TINCR could serve as useful biomarkers for screening ECs groups from HIV + patients and healthy control groups. Overall, different expression patterns of selected factors and ROC curve results showed these factors could critically contribute to HIV controlling and be considered as diagnostic markers for ECs from HIV + samples.
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Background and aims: MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are well-known types of noncoding RNAs (ncRNAs), which have been known as the key regulators of gene expression. They can play critical roles in viral infection by regulating the host immune response and interacting with genes in the viral genome. In this regard, ncRNAs can be employed as biomarkers for viral diseases. The current study aimed to evaluate peripheral blood mononuclear cell (PBMC) ncRNAs (lncRNAs-homeobox C antisense intergenic RNA [HOTAIR], -H19, X-inactive-specific transcript [XIST], plasmacytoma variant translocation 1 [PVT-1], and miR-34a) as diagnostic biomarkers to differentiate severe COVID-19 cases from mild ones. Methods: Candidate ncRNAs were selected according to previous studies and assessed by real-time polymerase chain reaction in the PBMC samples of patients with severe coronavirus disease 2019 (COVID-19) (n = 40), healthy subjects (n = 40), and mild COVID-19 cases (n = 40). Furthermore, the diagnostic value of the selected ncRNAs was assessed by analyzing the receiver-operating characteristic (ROC). Results: The results demonstrated that the expression pattern of the selected ncRNAs was significantly different between the studied groups. The levels of HOTAIR, XIST, and miR-34a were remarkably overexpressed in the severe COVID-19 group in comparison with the mild COVID-19 group, and in return, the PVT-1 levels were lower than in the mild COVID-19 group. Interestingly, the XIST expression level in men with severe COVID-19 was higher compared to women with mild COVID-19. ROC results suggested that HOTAIR and PVT-1 could serve as useful biomarkers for screening mild COVID-19 from severe COVID-19. Conclusions: Overall, different expression patterns of the selected ncRNAs and ROC curve results revealed that these factors can contribute to COVID-19 pathogenicity and can be considered diagnostic markers of COVID-19 severe outcomes.
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Thrombocytopenia, characterized by a decrease in platelet count, is a multifaceted clinical manifestation that can arise from various underlying causes. This review delves into the intriguing nexus between viruses and thrombocytopenia, shedding light on intricate pathophysiological mechanisms and highlighting the pivotal role of platelets in viral infections. The review further navigates the landscape of thrombocytopenia in relation to specific viruses, and sheds light on the diverse mechanisms through which hepatitis C virus (HCV), measles virus, parvovirus B19, and other viral agents contribute to platelet depletion. As we gain deeper insights into these interactions, we move closer to elucidating potential therapeutic avenues and preventive strategies for managing thrombocytopenia in the context of viral infections.
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Mesoporous silica nanoparticles (MSNPs) have been reported as an effective system to co-deliver a variety of different agents to enhance efficiency and improve biocompatibility. This study was aimed at the preparation, physicochemical characterization, antimicrobial effects, biocompatibility, and cytotoxicity of vancomycin and meropenem co-loaded in the mesoporous silica nanoparticles (Van/Mrp-MSNPs). The prepared nanoparticles were explored for their physicochemical features, antibacterial and antibiofilm effects, biocompatibility, and cytotoxicity. The minimum inhibitory concentrations (MICs) of the Van/Mrp-MSNPs (0.12-1 µg/mL) against Staphylococcus aureus isolates were observed to be lower than those of the same concentrations of vancomycin and meropenem. The minimum biofilm inhibitory concentration (MBIC) range of the Van/Mrp-MSNPs was 8-64 µg/mL, which was lower than the meropenem and vancomycin MBICs. The bacterial adherence was not significantly decreased upon exposure to levels lower than the MICs of the MSNPs and Van/Mrp-MSNPs. The viability of NIH/3T3 cells treated with serial concentrations of the MSNPs and Van/Mrp-MSNPs were 73-88% and 74-90%, respectively. The Van/Mrp-MSNPs displayed considerable inhibitory effects against MRSA, favorable biocompatibility, and low cytotoxicity. The Van/Mrp-MSNPs could be a potential system for the treatment of infections.
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Despite the need for novel, effective therapeutics for the COVID-19 pandemic, no curative regimen is yet available, therefore patients are forced to rely on supportive and nonspecific therapies. Some SARS-CoV-2 proteins, like the 3 C-like protease (3CLpro) or the major protease (Mpro), have been identified as promising targets for antiviral drugs. The Mpro has major a role in protein processing as well as pathogenesis of the virus, and could be a useful therapeutic target. The antiviral drug nirmatrelvir can keep SARS-CoV-2 from replicating through inhibiting Mpro. Nirmatrelvir was combined with another HIV protease inhibitor, ritonavir, to create Paxlovid (Nirmatrelvir/Ritonavir). The metabolizing enzyme cytochrome P450 3 A is inhibited by ritonavir to lengthen the half-life of nirmatrelvir, so rintonavir acts as a pharmacological enhancer. Nirmatrelvir exhibits potent antiviral activity against current coronavirus variants, despite significant alterations in the SARS-CoV-2 viral genome. Nevertheless, there are still several unanswered questions. This review summarizes the current literature on nirmatrelvir and ritonavir efficacy in treating SARS-CoV-2 infection, and also their safety and possible side effects.