Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 47
Filtrar
1.
Virol J ; 21(1): 48, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38395943

RESUMO

BACKGROUND: The antiviral properties of metal nanoparticles against various viruses, including those resistant to drugs, are currently a subject of intensive research. Recently, the green synthesis of nanoparticles and their anti-viral function have attracted a lot of attention. Previous studies have shown promising results in the use of Arabic gum for the green synthesis of nanoparticles with strong antiviral properties. In this study we aimed to investigate the antiviral effects of MnO2 nanoparticles (MnO2-NPs) synthesized using Arabic gum, particularly against the influenza virus. METHODS: Arabic gum was used as a natural polymer to extract and synthesize MnO2-NPs using a green chemistry approach. The synthesized MnO2-NPs were characterized using SEM and TEM. To evaluate virus titration, cytotoxicity, and antiviral activity, TCID50, MTT, and Hemagglutination assay (HA) were performed, respectively. Molecular docking studies were also performed to investigate the potential antiviral activity of the synthesized MnO2-NPs against the influenza virus. The molecular docking was carried out using AutoDock Vina software followed by an analysis with VMD software to investigate the interaction between Arabic gum and the hemagglutinin protein. RESULTS: Simultaneous combination treatment with the green-synthesized MnO2-NPs resulted in a 3.5 log HA decrement and 69.7% cellular protection, which demonstrated the most significant difference in cellular protection compared to the virus control group (p-value < 0.01). The docking results showed that binding affinities were between - 3.3 and - 5.8 kcal/mole relating with the interaction between target with MnO2 and beta-D-galactopyranuronic acid, respectively. CONCLUSION: The results of the study indicated that the MnO2-NPs synthesized with Arabic gum had significant antiviral effects against the influenza virus, highlighting their potential as a natural and effective treatment for inhibition of respiratory infections.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Nanopartículas Metálicas , Humanos , Influenza Humana/tratamento farmacológico , Simulação de Acoplamento Molecular , Compostos de Manganês/farmacologia , Óxidos/farmacologia , Nanopartículas Metálicas/química , Antivirais/farmacologia
2.
Gastroenterol Hepatol Bed Bench ; 16(3): 270-281, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37767323

RESUMO

Acute pancreatitis, a potentially fatal disease, with symptoms including nausea and/or vomiting, indigestion, and abdominal pain, is known to range from a mild self-limiting state up to a more severe and lethal form. This review aims to provide a clearer picture to improve understanding the role of viral agents in the development of acute pancreatitis. Common databases including PubMed, Google Scholar, and Scopus were used for the literature search. In this review search terms including virus, viral, infection, and specific descriptive terms for a virus were considered in different combinations. Various causative agents are recognized in the development of acute pancreatitis as one of the most frequent gastrointestinal diseases, such as gallstones, alcoholism, and hypertriglyceridemia. Microbial pathogens with about 10% of acute pancreatitis cases, mainly viruses, among other factors, are thought to play a role in this regard. Once the pancreatitis diagnosis has been made, depending on the causative agent, the management approach and specific interventions affect the final outcome. Virus-induced acute pancreatitis in patients should be considered. Advanced diagnostic tests such as PCR, in situ hybridization, and biopsy can help for a better understanding of the role of viruses in causing acute pancreatitis. Improvement in the tests will lead to timely diagnosis, treatment, and better management of pancreatitis.

3.
Front Immunol ; 14: 1226360, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37727791

RESUMO

Angiogenesis is a hallmark of cancer biology, and neoadjuvant therapies targeting either tumor vasculature or VEGF signaling have been developed to treat solid malignant tumors. However, these therapies induce complete vascular depletion leading to hypoxic niche, drug resistance, and tumor recurrence rate or leading to impaired delivery of chemo drugs and immune cell infiltration at the tumor site. Achieving a balance between oxygenation and tumor growth inhibition requires determining vascular normalization after treatment with a low dose of antiangiogenic agents. However, monotherapy within the approved antiangiogenic agents' benefits only some tumors and their efficacy improvement could be achieved using immunotherapy and emerging nanocarriers as a clinical tool to optimize subsequent therapeutic regimens and reduce the need for a high dosage of chemo agents. More importantly, combined immunotherapies and nano-based delivery systems can prolong the normalization window while providing the advantages to address the current treatment challenges within antiangiogenic agents. This review summarizes the approved therapies targeting tumor angiogenesis, highlights the challenges and limitations of current therapies, and discusses how vascular normalization, immunotherapies, and nanomedicine could introduce the theranostic potentials to improve tumor management in future clinical settings.


Assuntos
Inibidores da Angiogênese , Imunoterapia , Humanos , Inibidores da Angiogênese/uso terapêutico , Hipóxia , Nanomedicina , Sistemas de Liberação de Fármacos por Nanopartículas
4.
Iran J Microbiol ; 15(3): 462-467, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37448684

RESUMO

Background and Objectives: Human rhinovirus (HRV), a major cause of common cold, was associated to the hospitalization of children and adults. This cross-sectional study aimed to determine the prevalence, and genotype distribution of HRV in the patients with mild to severe respiratory infections who were negative for SARS-Cov-2. Materials and Methods: Nasopharyngeal swab specimens (n = 356) from the patients aged 29 days to 82 years, received for the respiratory virus detection from January to December 2021, were analyzed for human rhinovirus (HRV) by RT-PCR. As a final step, genotyping was performed on obtained sequences. Results: A total of 37 HRV infections were identified (37/356, 10%). The highest rates of positive HRV tests were observed in February (21.6%), and January (18.9%), compared with June and August (0%). HRV-positive cases mainly appeared in winter. Among the age groups, those 2-<5 years of age had the highest detection rate (21%), however, those >55 years of age had the lowest detection rate (3%). Among HRV-positive samples, 30 (81%) were identified as type HRV-A, 5 (13.5%) as HRV-B, and 2 (5.5%) as HRV-C. Conclusion: Our results suggested that HRV frequency gradually decreased with the age of patients which is more active in Iran, especially in the cold months.

5.
Heliyon ; 9(3): e13882, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36895399

RESUMO

This work investigates the feasibility of net shape manufacturing of parts using water-atomized (WA) low-alloy steel with comparable densities to conventional powder metallurgy parts via binder jetting additive manufacturing (BJAM) and supersolidus liquid phase sintering (SLPS). In this study, a modified water-atomized powder grade with similar composition as MPIF FL-4405 was printed and pressure-less sintered under a 95% N2-5% H2 atmosphere. Combinations of two different sintering schedules (direct-sintering and step-sintering) and three different heating rates (1, 3, and 5 °C/min) were applied to study the densification, shrinkage, and microstructural evolution of BJAM parts. This study demonstrated that, although the green density of the BJAM samples was ∼42% of the theoretical density, the sintered parts experienced large linear shrinkage up to ∼25% and reached ∼97% density without compromising shape fidelity. This was ascribed to a more homogeneous pore distribution throughout the part before ramping up to the SLPS region. The synergistic effects of carbon residue, the slow heating rate, and the additional isothermal holding stage at the solid-phase sintering region were determined to be the key factors for sintering BJAM WA low-alloy steel powders with resulting minimal entrapped porosity and good shape fidelity.

6.
J Med Virol ; 95(3): e28608, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36815506

RESUMO

Skin rash is one of the most common complications during childhood. Viral agents play an essential role in the development of such symptoms. Present study aims to determine the prevalence and genetic variability of Human Herpesvirus 6 and 7 (HHV-6 and HHV-7) infections and their subtypes in children under 5 years of age with skin rash and negative for rubella and measles. We used serum and throat swap samples from 196 children with skin rash and fever. ELISA and IFA tests were performed to detect antibodies against HHV6/7. Sequencing was performed using Sanger sequencing, and BioEdit and MEGA10 software were used for sequence analysis. According to the results, 66% and 40% of cases were positive for HHV-6 IgM and HHV-7 IgM, respectively. According to the molecular analysis, HHV-6 Nested-PCR was positive in 18% of cases, however, HHV-7 Nested-PCR was positive in 7.7% of cases. On the other hand, HHV-6 IgG and HHV-7 IgG were positive in 91% and 55% of study cases, respectively. For HHV-6, we found some genetic variabilities resulting in antigenic changes compared to reference strains. HHV-7 isolates showed no genetic differentiation and had a stable gene sequence. Based on the results, the detection of some cases of HHV6/7 primary infection and the presence of specific symptoms of roseola in the study population needs continuous evaluation of HHV6/7 frequency and distribution, also genetic variabilities of HHV6. This can pave the way for investigating HHV6 immune evasion and vaccine research and studying the relationship between viral genetic variations and other factors like disease severity. Furthermore, it is necessary to determine the relation between HHV6 genetic changes and latent infection to be considered in possible future vaccines and antiviral drug development.


Assuntos
Exantema , Infecções por Herpesviridae , Herpesvirus Humano 6 , Herpesvirus Humano 7 , Infecções por Roseolovirus , Criança , Humanos , Pré-Escolar , Herpesvirus Humano 7/genética , Exantema/epidemiologia , Infecções por Roseolovirus/epidemiologia , Anticorpos Antivirais , Imunoglobulina M , Febre , Imunoglobulina G
7.
Cancer Lett ; 554: 216007, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36396102

RESUMO

Intra-tumoral immune cells promote the stemness of cancer stem cells (CSCs) in the tumor microenvironment (TME). CSCs promote tumor progression, relapse, and resistance to immunotherapy. Cancer stemness induces the expression of neoantigens and neo-properties in CSCs, creating an opportunity for targeted immunotherapies. Isolation of stem-like T cells or retaining stemness in T clonotypes strategies produces exhaustion-resistance T cells with superior re-expansion capacity and long-lasting responses after adoptive cell therapies. Stem cells-derived NK cells may be the next generation of NK cell products for immunotherapy. Here, we have reviewed mechanisms by which stemness factors modulated the immunoediting of the TME and summarized the potentials of CSCs in the development of immunotherapy regimens, including CAR-T cells, CAR-NK cells, cancer vaccines, and monoclonal antibodies. We have discussed the natural or genetically engineered stem-like T cells and stem cell-derived NK cells with increased cytotoxicity to tumor cells. Finally, we have provided a perspective on approaches that may improve the therapeutic efficacy of these novel adoptive cell-based products in targeting immunosuppressive TME.


Assuntos
Neoplasias , Humanos , Neoplasias/patologia , Imunoterapia , Células Matadoras Naturais , Linfócitos T/patologia , Imunoterapia Adotiva , Microambiente Tumoral
8.
Virol J ; 19(1): 106, 2022 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-35752792

RESUMO

BACKGROUND: MDA-7/IL-24 cytokine has shown potent antitumor properties in various types of cancer without exerting any significant toxicity on healthy cells. It has also been proved to encompass pro-immune Th1 cytokine-like behavior. Several E7 DNA vaccines have developed against human papillomavirus (HPV)-related cervical cancer. However, the restricted immunogenicity has limited their clinical applications individually. To address this deficiency, we investigated whether combining the E7 DNA vaccine with MDA-7/IL-24 as an adjuvant would elicit efficient antitumor responses in tumor-bearing mouse models. Next, we evaluated how suppression of immunosuppressive IL-10 cytokine would enhance the outcome of our candidate adjuvant vaccine. METHODS: For this purpose, tumor-bearing mice received either E7 DNA vaccine, MDA-7/IL-24 cytokine or combination of E7 vaccine with MDA-7/IL-24 adjuvant one week after tumor challenge and boosted two times with one-week interval. IL-10 blockade was performed by injection of anti-IL-10 mAb before each immunization. One week after the last immunization, mice were sacrificed and the treatment efficacy was evaluated through immunological and immunohistochemical analysis. Moreover, the condition of tumors was monitored every two days for six weeks intervals from week 2 on, and the tumor volume was measured and compared within different groups. RESULTS: A highly significant synergistic relationship was observed between the E7 DNA vaccine and the MDA-7/IL-24 cytokine against HPV-16+ cervical cancer models. An increase in proliferation of lymphocytes, cytotoxicity of CD8+ T cells, the level of Th1 cytokines (IFN-γ, TNF-α) and IL-4, the level of apoptotic markers (TRAIL and caspase-9), and a decrease in the level of immunosuppressive IL-10 cytokine, together with the control of tumor growth and the induction of tumor regression, all prove the efficacy of adjuvant E7&IL-24 vaccine when compared to their individual administration. Surprisingly, vaccination with the DNA E7&IL-24 significantly reduced the population of Regulatory T cells (Treg) in the spleen of immunized mice compared to sole administration and control groups. Moreover, IL-10 blockade enhanced the effect of the co-administration by eliciting higher levels of IFN-γ and caspase-9, reducing Il-10 secretion and provoking the regression of tumor size. CONCLUSION: The synergy between the E7 DNA vaccine and MDA-7/IL-24 suggests that DNA vaccines' low immunogenicity can be effectively addressed by coupling them with an immunoregulatory agent. Moreover, IL-10 blockade can be considered a complementary treatment to improve the outcome of conventional or novel cancer therapies.


Assuntos
Vacinas Anticâncer , Interleucinas/imunologia , Vacinas contra Papillomavirus , Neoplasias do Colo do Útero , Vacinas de DNA , Adjuvantes Imunológicos , Animais , Linfócitos T CD8-Positivos , Vacinas Anticâncer/genética , Caspase 9 , Citocinas/metabolismo , Feminino , Humanos , Inibidores de Checkpoint Imunológico , Interleucina-10/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteínas E7 de Papillomavirus/genética
9.
Int Immunopharmacol ; 108: 108882, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35623296

RESUMO

Oncolytic viruses (OVs) harness the hallmarks of tumor cells and cancer-related immune responses for the lysis of malignant cells, modulation of the tumor microenvironment, and exertion of vaccine-like activities. However, efficient clinical exploitation of these potent therapeutic modules requires their systematic administration, especially against metastatic and solid tumors. Therefore, developing methods for shielding a virus from the neutralizing environment of the bloodstream while departing toward tumor sites is a must. This paper reports the latest advancements in the employment of chemical and biological compounds aimed at safe and efficient delivery of OVs to target tissues or tumor deposits within the host.


Assuntos
Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Morte Celular , Humanos , Imunidade , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos/fisiologia , Microambiente Tumoral
11.
Mol Biol Rep ; 49(5): 4013-4024, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35067816

RESUMO

Accumulating molecular evidence suggests that insulin resistance, rather than SARS-CoV-2- provoked beta-cell impairment, plays a major role in the observed rapid metabolic deterioration in diabetes, or new-onset hyperglycemia, during the COVID-19 clinical course. In order to clarify the underlying complexity of COVID-19 and diabetes mellitus interactions, we propose the imaginary diabetes-COVID-19 molecular tetrahedron with four lateral faces consisting of SARS-CoV-2 entry via ACE2 (lateral face 1), the viral hijacking and replication (lateral face 2), acute inflammatory responses (lateral face 3), and the resulting insulin resistance (lateral face 4). The entrance of SARS-CoV-2 using ACE2 receptor triggers an array of multiple molecular signaling beyond that of the angiotensin II/ACE2-Ang-(1-7) axis, such as down-regulation of PGC-1 α/irisin, increased SREBP-1c activity, upregulation of CD36 and Sirt1 inhibition leading to insulin resistance. In another arm of the molecular cascade, the SARS-CoV-2 hijacking and replication induces a series of molecular events in the host cell metabolic machinery, including upregulation of SREBP-2, decrement in Sirt1 expression, dysregulation in PPAR-É£, and LPI resulting in insulin resistance. The COVID-19-diabetes molecular tetrahedron may suggest novel targets for therapeutic interventions to overcome insulin resistance that underlies the pathophysiology of worsening metabolic control in patients with diabetes mellitus or the new-onset of hyperglycemia in COVID-19.


Assuntos
COVID-19 , Diabetes Mellitus , Hiperglicemia , Resistência à Insulina , Enzima de Conversão de Angiotensina 2 , Diabetes Mellitus/metabolismo , Humanos , SARS-CoV-2 , Sirtuína 1/genética
12.
Iran J Microbiol ; 14(4): 568-573, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36721508

RESUMO

Background and Objectives: Parvovirus B19 (B19V) is usually transmitted through respiratory tract, but can also be received through blood transfusion. This study evaluated the seroprevalence, DNA existence, and circulating genotypes of B19V in hemophilia patients. Materials and Methods: Serum samples of cases and controls were analyzed for B19V using ELISA and real-time PCR. Finally, obtained sequences were used for genotyping. Results: Among cases, 3% were anti-B19V IgM positive and 47% were anti-B19V IgG positive and B19V DNA was detected in 16% of them. However, among controls, 38% were anti-B19V IgG positive (P>0.05) and 5% were B19V DNA positive (P= 0.019). Also ∼13% of cases were positive and all of controls were negative for IgG avidity test (P= 0.029). Viral load in case group was higher than control group (P = 0.037). Conclusion: Since hemophilia patients receive large amounts of blood factors, prevalence of B19V in these patients might be higher than normal subjects.

13.
Gene Rep ; 25: 101417, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34778602

RESUMO

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) directly interacts with host's epithelial and immune cells, leading to inflammatory response induction, which is considered the hallmark of infection. The host immune system is programmed to facilitate the clearance of viral infection by establishing a modulated response. However, SARS-CoV-2 takes the initiative and its various structural and non-structural proteins directly or indirectly stimulate the uncontrolled activation of injurious inflammatory pathways through interaction with innate immune system mediators. Upregulation of cell-signaling pathways such as mitogen-activate protein kinase (MAPK) in response to recognition of SARS-CoV-2 antigens by innate immune system receptors mediates unbridled production of proinflammatory cytokines and cells causing cytokine storm, tissue damage, increased pulmonary edema, acute respiratory distress syndrome (ARDS), and mortality. Moreover, this acute inflammatory state hinders the immunomodulatory effect of T helper cells and timely response of CD4+ and CD8+ T cells against infection. Furthermore, inflammation-induced overproduction of Th17 cells can downregulate the antiviral response of Th1 and Th2 cells. In fact, the improperly severe response of the innate immune system is the key to conversion from a non-severe to severe disease state and needs to be investigated more deeply. The virus can also modulate the protective immune responses by developing immune evasion mechanisms, and thereby provide a more stable niche. Overall, combination of detrimental immunostimulatory and immunomodulatory properties of both the SARS-CoV-2 and immune cells does complicate the immune interplay. Thorough understanding of immunopathogenic basis of immune responses against SARS-CoV-2 has led to developing several advanced vaccines and immune-based therapeutics and should be expanded more rapidly. In this review, we tried to delineate the immunopathogenesis of SARS-CoV-2 in humans and to provide insight into more effective therapeutic and prophylactic strategies.

14.
Front Chem ; 9: 722633, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34712648

RESUMO

Although SARS-CoV-2 entry to cells strictly depends on angiotensin-converting enzyme 2 (ACE2), the virus also needs transmembrane serine protease 2 (TMPRSS2) for its spike protein priming. It has been shown that the entrance of SARS-CoV-2 through ACE2 can be blocked by cellular TMPRSS2 blockers. The main aim of this study was to find potential inhibitor(s) of TMPRSS2 through virtual screening against a homology model of TMPRSS2 using the library of marine natural products (MNPs). The homology modeling technique for generating a three-dimensional structure of TMPRSS2 was applied. Molecular docking, MM-GBSA and absorption, distribution, metabolism, excretion (ADME) evaluations were performed to investigate the inhibitory activity of marine natural products (MNPs) against TMPRSS2 and their pharmacokinetic properties. Camostat and nafamostat mesylate were used as the standard inhibitory molecules. Seven MNPs were able to inhibit TMPRSS2 better than the standard compounds. MNP 10 with CAS number 107503-09-3, called Watasenia ß-D- Preluciferyl glucopyrasoiuronic acid, was found to be the best inhibitor of TMPRSS2 with acceptable pharmacokinetic properties. Herein, for the first time, a new marine natural product was introduced with potent inhibitory effects against TMPRSS2. MNP 10 exhibited favorable drug-like pharmacokinetic properties and it promises a novel TMPRSS2 blocker to combat SARS-CoV-2.

15.
Biomed Pharmacother ; 144: 112346, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34678727

RESUMO

The expansion of myeloid-derived suppressor cells (MDSCs), known as heterogeneous population of immature myeloid cells, is enhanced during several pathological conditions such as inflammatory or viral respiratory infections. It seems that the way MDSCs behave in infection depends on the type and the virulence mechanisms of the invader pathogen, the disease stage, and the infection-related pathology. Increasing evidence showing that in correlation with the severity of the disease, MDSCs are accumulated in COVID-19 patients, in particular in those at severe stages of the disease or ICU patients, contributing to pathogenesis of SARS-CoV2 infection. Based on the involved subsets, MDSCs delay the clearance of the virus through inhibiting T-cell proliferation and responses by employing various mechanisms such as inducing the secretion of anti-inflammatory cytokines, inducible nitric oxide synthase (iNOS)-mediated hampering of IFN-γ production, or forcing arginine shortage. While the immunosuppressive characteristic of MDSCs may help to preserve the tissue homeostasis and prevent hyperinflammation at early stages of the infection, hampering of efficient immune responses proved to exert significant pathogenic effects on severe forms of COVID-19, suggesting the targeting of MDSCs as a potential intervention to reactivate T-cell immunity and thereby prevent the infection from developing into severe stages of the disease. This review tried to compile evidence on the roles of different subsets of MDSCs during viral respiratory infections, which is far from being totally understood, and introduce the promising potential of MDSCs for developing novel diagnostic and therapeutic approaches, especially against COVID-19 disease.


Assuntos
Antivirais/farmacologia , Tratamento Farmacológico da COVID-19 , COVID-19 , Células Supressoras Mieloides , COVID-19/imunologia , COVID-19/virologia , Descoberta de Drogas , Humanos , Tolerância Imunológica , Imunidade Inata , Células Supressoras Mieloides/efeitos dos fármacos , Células Supressoras Mieloides/fisiologia , SARS-CoV-2
16.
Biomolecules ; 11(9)2021 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-34572503

RESUMO

Gold nanoparticles (GNPs) have been recently applied for various diagnostic and therapeutic purposes. The unique properties of these nanoparticles (NPs), such as relative ease of synthesis in various sizes, shapes and charges, stability, high drug-loading capacity and relative availability for modification accompanied by non-cytotoxicity and biocompatibility, make them an ideal field of research in bio-nanotechnology. Moreover, their potential to alleviate various inflammatory factors, nitrite species, and reactive oxygen production and the capacity to deliver therapeutic agents has attracted attention for further studies in inflammatory and autoimmune disorders. Furthermore, the characteristics of GNPs and surface modification can modulate their toxicity, biodistribution, biocompatibility, and effects. This review discusses in vitro and in vivo effects of GNPs and their functionalized forms in managing various autoimmune disorders (Ads) such as rheumatoid arthritis, type 1 diabetes, and multiple sclerosis.


Assuntos
Doenças Autoimunes/terapia , Ouro/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , Animais , Citocinas/metabolismo , Humanos , Nanotecnologia
17.
Biomed Pharmacother ; 141: 111936, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34328094

RESUMO

Sea cucumber has antiviral activities against various viruses including herpes simplex virus type 1 (HSV-1). The purpose of the current study was to determine the chemical profile and inhibitory effects of tegument ethanolic extract of Holothuria parva on HSV-1 infection and to elucidate the mechanism of antiviral action of this marine invertebrate. Cytotoxic activity of the extract on Vero cell line was determined using the methyl thiazolyl tetrazolium (MTT) method. The different components in H. parva were determined by GC-MS analysis. To assess the antiviral activity of the extract, MTT and 50% tissue culture infective dose (TCID50) were applied. Finally, computational molecular docking was performed to screen the potential binding ability of extract contents with HSV-1 surface glycoproteins and host cell surface receptors. Using MTT assay, the non-cytotoxic concentration of the extract was measured 46.5 µg/mL. Octadecanoic acid 2-hydroxy-1-(hydroxymethyl) ethyl ester and 2',6'-acetoxylidide were two major constituents in the H. parva extract. Pre-treatment of HSV-1 with the ethanolic extract of H. parva led to a 2.1 log10 TCID50 reduction in virus titers when compared to the control group (P = 0.002). The log10 TCID50 reductions relative to the control group for co-penetration and post-penetration assays were 1.5 (P = 0.009) and 0.7 (P = 0.09), respectively. The tegument ethanolic extract of H. parva has significant antiviral properties against HSV-1. Docking analysis demonstrated that compounds of the extract [lidocaine and 2-hydroxy-1-(hydroxymethyl) ethyl ester octadecanoic acid] may cover similarly both virus and host cells binding domains leading to interference in virus attachment to cell receptors.


Assuntos
Antivirais/química , Produtos Biológicos/química , Simulação por Computador , Etanol/química , Herpesvirus Humano 1/efeitos dos fármacos , Holothuria , Animais , Antivirais/farmacologia , Produtos Biológicos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Chlorocebus aethiops , Etanol/farmacologia , Herpesvirus Humano 1/fisiologia , Estrutura Secundária de Proteína , Células Vero
18.
Microbes Infect ; 23(8): 104831, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33878459

RESUMO

This paper reviews epigenetic mechanisms by which influenza viruses affect cellular gene activity to control their life cycles, aiming to provide new insights into the complexity of functional interactions between viral and cellular factors, as well as to introduce novel targets for therapeutic intervention and vaccine development against influenza infections.


Assuntos
Vírus da Influenza A , Vacinas contra Influenza , Influenza Humana , Infecções por Orthomyxoviridae , Orthomyxoviridae , Epigênese Genética , Humanos , Vírus da Influenza A/genética , Vacinas contra Influenza/genética
19.
Cancer Cell Int ; 21(1): 100, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568147

RESUMO

BACKGROUND: The expansion and metastasis of colorectal cancers are closely associated with the dynamic growth of cancer stem cells (CSCs). This study aimed to explore the possible effect of LXR (a regulator of glycolysis and lipid hemostasis) in the tumorgenicity of human colorectal CD133 cells. METHODS: Human HT-29 CD133+ cells were enriched by MACS and incubated with LXR agonist (T0901317) and antagonist (SR9243) for 72 h. Cell survival was evaluated using MTT assay and flow cytometric analysis of Annexin-V. The proliferation rate was measured by monitoring Ki-67 positive cells using IF imaging. The modulation of LXR was studied by monitoring the activity of all factors related to ABC transporters using real-time PCR assay and western blotting. Protein levels of metabolic enzymes such as PFKFB3, GSK3ß, FASN, and SCD were also investigated upon treatment of CSCs with LXR modulators. The migration of CSCs was monitored after being exposed to LXR agonist using scratch and Transwell insert assays. The efflux capacity was measured using hypo-osmotic conditions. The intracellular content of reactive oxygen species was studied by DCFH-DA staining. RESULTS: Data showed incubation of CSCs with T0901317 and SR9243 reduced the viability of CD133 cells in a dose-dependent manner compared to the control group. The activation of LXR up-regulated the expression and protein levels of ABC transporters (ABCA1, ABCG5, and ABCG8) compared to the non-treated cells (p < 0.05). Despite these effects, LXR activation suppressed the proliferation, clonogenicity, and migration of CD133 cells, and increased hypo-osmotic fragility (p < 0.05). We also showed that SR9243 inhibited the proliferation and clonogenicity of CD133 cells through down-regulating metabolic enzymes PFKFB3, GSK3ß, FASN, and SCD as compared with the control cells (p < 0.05). Intracellular ROS levels were increased after the inhibition of LXR by SR9243 (p < 0.05). Calling attention, both T0901317 and SR9243 compounds induced apoptotic changes in cancer stem cells (p < 0.05). CONCLUSIONS: The regulation of LXR activity can be considered as a selective targeting of survival, metabolism, and migration in CSCs to control the tumorigenesis and metastasis in patients with advanced colorectal cancers.

20.
Eur J Clin Microbiol Infect Dis ; 40(3): 637-642, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33011904

RESUMO

This study aimed to evaluate the prevalence of human rhinoviruses (HRVs) and the emergence of enterovirus D68 (EV-D68) in children. A total of 322 nasopharyngeal swab samples were provided from children with an initial diagnosis of upper and lower respiratory tract infections. A total of 34 and 70 cases were positive for EV-D68 and HRV, respectively. The phylogenetic analysis revealed that the clades A and B are the prevalent genotypes for EV-D68 and the HRV-positive samples belong to three types including HRV-A, HRV-B, and HRV-C. The results showed that EV-D68 and HRV-C are circulating in Iran especially in the winter.


Assuntos
Infecções por Enterovirus/virologia , Enterovirus/isolamento & purificação , Infecções Respiratórias/virologia , Doença Aguda , Pré-Escolar , Enterovirus/classificação , Enterovirus/genética , Infecções por Enterovirus/epidemiologia , Feminino , Genótipo , Humanos , Lactente , Recém-Nascido , Irã (Geográfico)/epidemiologia , Masculino , Nasofaringe/virologia , Razão de Chances , Filogenia , Infecções Respiratórias/epidemiologia , Estações do Ano
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...