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1.
Arab J Chem ; 14(10): 103353, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34909059

RESUMO

The aim of this study was to investigate the mechanism of interaction between quercetin-3-O-sophoroside and different SARS-CoV-2's proteins which can bring some useful details about the control of different variants of coronavirus including the recent case, Delta. The chemical structure of the quercetin-3-O-sophoroside was first optimized. Docking studies were performed by CoV disease-2019 (COVID-19) Docking Server. Afterwards, the molecular dynamic study was done using High Throughput Molecular Dynamics (HTMD) tool. The results showed a remarkable stability of the quercetin-3-O-sophoroside based on the calculated parameters. Docking outcomes revealed that the highest affinity of quercetin-3-O-sophoroside was related to the RdRp with RNA. Molecular dynamic studies showed that the target E protein tends to be destabilized in the presence of quercetin-3-O-sophoroside. Based on these results, quercetin-3-O-sophoroside can show promising inhibitory effects on the binding site of the different receptors and may be considered as effective inhibitor of the entry and proliferation of the SARS-CoV-2 and its different variants. Finally, it should be noted, although this paper does not directly deal with the exploring the interaction of main proteins of SARS-CoV-2 Delta variant with quercetin-3-O-sophoroside, at the time of writing, no direct theoretical investigation was reported on the interaction of ligands with the main proteins of Delta variant. Therefore, the present data may provide useful information for designing some theoretical studies in the future for studying the control of SARS-CoV-2 variants due to possible structural similarity between proteins of different variants.

3.
Microb Pathog ; 160: 105184, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34508828

RESUMO

Hepatitis B virus (HBV) infection is limited through vaccination against HBsAg formulated in the Alum adjuvant. However, this alum-formulated vaccine fails to be preventive in some cases, also known as non-responders. Recent studies have shown the immunomodulatory effect of α-tocopherol in various models. Here, we developed a new formulation for HBsAg using α-tocopherol, followed by assessment of immune responses. Experimental BALB/c mice were immunized with a commercial alum-based vaccine or the one formulated in α-tocopherol at different doses. Mice were immunized subcutaneously with 5 µg of HBsAg with different formulations three times with 2-week intervals. Specific total IgG, IgG1, and IgG2a isotypes of antibodies were measured by ELISA. Immunologic cytokines, such as IFN-γ, IL-4, IL-2, and TNF-α, were also evaluated through commercial ELISA kits. Our results showed that the new α-tocopherol-formulated vaccine had the ability to reinforce specific total IgG responses. Moreover, α-tocopherol in the HBsAg vaccine increased IFN-γ, IL-2, and TNF-α cytokines at higher concentrations; however, the vaccine suppressed IL-4 cytokine release. At a lower concentration of α-tocopherol, the IL-4 cytokine response increased without a positive effect on IFN-γ and TNF-α cytokine response. It seems that α-tocopherol can change the immune responses against HBsAg; however, the type of response depends on the dose of α-tocopherol used in the vaccine formulation.


Assuntos
Citocinas , Vacinas contra Hepatite B , Interferon gama/imunologia , Adjuvantes Imunológicos , Animais , Citocinas/imunologia , Anticorpos Anti-Hepatite B , Vacinas contra Hepatite B/imunologia , Camundongos , Camundongos Endogâmicos BALB C
4.
Front Cell Infect Microbiol ; 11: 560622, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249771

RESUMO

AmpC ß-lactamases hydrolyze all ß-lactams except cefepime and carbapenems. The study of AmpC-producing E. coli has high priority for the infection control committee. This research is aimed to investigate the resistant urinary AmpC-generating E. coli isolates and identify their genetic variety. Some 230 E. coli isolates from patients suffering urinary tract infection symptoms were studied in 2017-2018 to assess their susceptibility toward antimicrobial agents. AmpC gene was evaluated by PCR and molecular typing using the 10-loci MLVA method. MLVA images were examined by BioNumerics 6.6 software through the use of the UPGMA algorithms. Thirty-eight AmpC-generating E. coli isolates were detected. The most abundant determinant was blaCIT and blaEBC , blaFOX , and blaDHA had the next ranks, respectively. Six major clusters and a singleton were identified by MLVA. AmpC beta-lactamases in urinary isolates of E. coli in the hospital under study and high rate of additional resistance to gentamicin, cotrimoxazole and ciprofloxacin. The most frequent gene determinant of AmpC beta-lactamase was blaCIT and vary depending on time and geographical location.


Assuntos
Infecções por Escherichia coli , Infecções Urinárias , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Escherichia coli/genética , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Testes de Sensibilidade Microbiana , beta-Lactamases/genética
5.
Iran J Basic Med Sci ; 24(4): 437-443, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34094024

RESUMO

Objectives: Strain subtyping is an important epidemiological tool to trace contamination, determine clonal relationships between different strains, and the cause of outbreaks. Current subtyping methods, however, yield less than optimal subtype discrimination. Pulsed-field gel electrophoresis is the gold standard method for Escherichia coli and Multiple-Locus Variable-number tandem repeat Analysis is a rapid PCR-based method. The purpose of this study was to evaluate MLVA and PFGE methods for subtyping ß -lactamase-producing E. coli strains isolated from urinary tract infections. Materials and Methods: Overall, 230 E. coli isolates from patients with urinary tract infections were examined for antimicrobial susceptibility testing. 10-loci and 7-loci MLVA and PFGE methods were used for molecular typing of ß -lactamase-producing E. coli isolates. Results: Out of 230 isolates, 130 (56.5%) ß -lactamase-producing E. coli isolates were found in this study. The diversity indices of the VNTR loci showed an average diversity of 0.48 and 0.54 for 7-loci and 10-loci MLVA, respectively. The discriminatory power of PFGE showed a value of 0.87. The discordance between the methods was high. Conclusion: Our study showed that PFGE is more discriminatory than MVLA. MLVA is a PCR- based method and can generate unmistakable data, in contrast to PFGE. Optimization of polymorphic VNTR is essential to improve the discriminatory power of MLVA based on geographical region.

6.
Microb Pathog ; 157: 104953, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34044042

RESUMO

Methicillin resistant Staphylococcus aureus is one of the most common causes of nosocomial infections. Current therapeutic approaches are not always effective in treatment of nosocomial infections, thus, there is a global demand for the development of novel therapeutic strategies. Staphylococcus aureus possesses various systems to uptake iron. One of the most important of them is iron regulated surface determinant (Isd) which can be an excellent candidate for immunization. Here, following the preparation of recombinant IsdE protein, 20 µg of r-IsdE prepared in various formulations were subcutaneously injected in different groups of mice. Two booster vaccinations were administered in two-week intervals, then, blood samples were collected two weeks after each injection. ELISA was used for the evaluation of total IgG and its isotypes (IgG1 and IgG2a) as well as quantity of IFN-γ, IL-4, IL-17, IL-2 and TNF-α cytokines on the serum samples. Meanwhile, the immunized mice were intraperitoneally inoculated with 5 × 108 CFU of bacteria then, their mortality rate and bacterial load were assessed. Our results showed that immunization with the r-IsdE in various formulations raised total IgG and isotypes (IgG1 and IgG2a) compared with the control groups. Moreover, r-IsdE formulation with MF59 and Freund adjuvants raised production of IFN-γ, IL-4, IL-17, IL-2 and TNF-α cytokines and provided an acceptable protection against Staphylococcus aureus infections. Results of present study suggest that r-IsdE which can easily be expressed by Escherichia coli BL21 system shows a great potential to develop a protective immunity against infections caused by Methicillin resistant Staphylococcus aureus.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Vacinas , Animais , Clonagem Molecular , Staphylococcus aureus Resistente à Meticilina/genética , Camundongos , Camundongos Endogâmicos BALB C , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/genética
8.
Talanta ; 223(Pt 1): 121704, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33303154

RESUMO

The rapid outbreak of coronavirus disease 2019 (COVID-19) around the world is a tragic and shocking event that demonstrates the unpreparedness of humans to develop quick diagnostic platforms for novel infectious diseases. In fact, statistical reports of diagnostic tools show that their accuracy, specificity and sensitivity in the detection of COVID hampered by some challenges that can be eliminated by using nanoparticles (NPs). In this study, we aimed to present an overview on the most important ways to diagnose different kinds of viruses followed by the introduction of nanobiosensors. Afterward, some methods of COVID-19 detection such as imaging, laboratory and kit-based diagnostic tests are surveyed. Furthermore, nucleic acids/protein- and immunoglobulin (Ig)-based nanobiosensors for the COVID-19 detection infection are reviewed. Finally, current challenges and future perspective for the development of diagnostic or monitoring technologies in the control of COVID-19 are discussed to persuade the scientists in advancing their technologies beyond imagination. In conclusion, it can be deduced that as rapid COVID-19 detection infection can play a vital role in disease control and treatment, this review may be of great help for controlling the COVID-19 outbreak by providing some necessary information for the development of portable, accurate, selectable and simple nanobiosensors.


Assuntos
Técnicas Biossensoriais , COVID-19/diagnóstico , Nanotecnologia , Humanos , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade
9.
J Biomol Struct Dyn ; 39(10): 3771-3779, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-32397906

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative representative of a severe respiratory illness resulted in widespread human infections and deaths in nearly all of the countries since late 2019. There is no therapeutic FDA-approved drug against SARS-CoV-2 infection, although a combination of anti-viral drugs is directly being practiced in some countries. A broad-spectrum of antiviral agents are being currently evaluated in clinical trials, and in this review, we specifically focus on the application of Remdesivir (RVD) as a potential anti-viral compound against Middle East respiratory syndrome (MERS) -CoV, SARS-CoV and SARS-CoV-2. First, we overview the general information about SARS-CoV-2, followed by application of RDV as a nucleotide analogue which can potentially inhibits RNA-dependent RNA polymerase of COVs. Afterwards, we discussed the kinetics of SARS- or MERS-CoV proliferation in animal models which is significantly different compared to that in humans. Finally, some ongoing challenges and future perspective on the application of RDV either alone or in combination with other anti-viral agents against CoVs infection were surveyed to determine the efficiency of RDV in preclinical trials. As a result, this paper provides crucial evidence of the potency of RDV to prevent SARS-CoV-2 infections.Communicated by Ramaswamy H. Sarma.


Assuntos
Antivirais , COVID-19 , RNA Polimerase Dependente de RNA , Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Animais , Antivirais/farmacologia , COVID-19/tratamento farmacológico , Reposicionamento de Medicamentos , Humanos , RNA Polimerase Dependente de RNA/antagonistas & inibidores , SARS-CoV-2/efeitos dos fármacos
10.
Biomed Pharmacother ; 130: 110559, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32768882

RESUMO

As the number of people infected with the newly identified 2019 novel coronavirus (SARS-CoV2) is continuously increasing every day, development of potential therapeutic platforms is vital. Based on the comparatively high similarity of receptor-binding domain (RBD) in SARS-CoV2 and SARS-CoV, it seems crucial to assay the cross-reactivity of anti-SARS-CoV monoclonal antibodies (mAbs) with SARS-CoV2 spike (S)-protein. Indeed, developing mAbs targeting SARS-CoV2 S-protein RBD could show novel applications for rapid and sensitive development of potential epitope-specific vaccines (ESV). Herein, we present an overview on the discovery of new CoV followed by some explanation on the SARS-CoV2 S-protein RBD site. Furthermore, we surveyed the novel therapeutic mAbs for targeting S-protein RBD such as S230, 80R, F26G18, F26G19, CR3014, CR3022, M396, and S230.15. Afterwards, the mechanism of interaction of RBD and different mAbs were explained and it was suggested that one of the SARS-CoV-specific human mAbs, namely CR3022, could show the highest binding affinity with SARS-CoV2 S-protein RBD. Finally, some ongoing challenges and future prospects for rapid and sensitive advancement of therapeutic mAbs targeting S-protein RBD were discussed. In conclusion, it may be proposed that this review may pave the way for recognition of RBD and different mAbs to develop potential therapeutic ESV.


Assuntos
Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Pandemias , Pneumonia Viral/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Sequência de Aminoácidos , Anticorpos Monoclonais/química , Anticorpos Monoclonais/metabolismo , Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/metabolismo , Anticorpos Antivirais/química , Anticorpos Antivirais/metabolismo , Afinidade de Anticorpos , Reações Antígeno-Anticorpo , Antígenos Virais/metabolismo , Sítios de Ligação de Anticorpos , COVID-19 , Vacinas contra COVID-19 , Coronavirus/química , Coronavirus/imunologia , Infecções por Coronavirus/prevenção & controle , Epitopos/imunologia , Humanos , Modelos Moleculares , Filogenia , Ligação Proteica , Conformação Proteica , Domínios Proteicos , SARS-CoV-2 , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/metabolismo , Vacinas Virais/imunologia
11.
Int J Nanomedicine ; 15: 4607-4623, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636621

RESUMO

Aim: The interaction of NPs with biological systems may reveal useful details about their pharmacodynamic, anticancer and antibacterial effects. Methods: Herein, the interaction of as-synthesized Co3O4 NPs with HSA was explored by different kinds of fluorescence and CD spectroscopic methods, as well as molecular docking studies. Also, the anticancer effect of Co3O4 NPs against leukemia K562 cells was investigated by MTT, LDH, caspase, real-time PCR, ROS, cell cycle, and apoptosis assays. Afterwards, the antibacterial effects of Co3O4 NPs against three pathogenic bacteria were disclosed by antibacterial assays. Results: Different characterization methods such as TEM, DLS, zeta potential and XRD studies proved that fabricated Co3O4 NPs by sol-gel method have a diameter of around 50 nm, hydrodynamic radius of 177 nm with a charge distribution of -33.04 mV and a well-defined crystalline phase. Intrinsic, extrinsic, and synchronous fluorescence as well as CD studies, respectively, showed that the HSA undergoes some fluorescence quenching, minor conformational changes, microenvironmental changes as well as no structural changes in the secondary structure, after interaction with Co3O4 NPs. Molecular docking results also verified that the spherical clusters with a dimension of 1.5 nm exhibit the most binding energy with HSA molecules. Anticancer assays demonstrated that Co3O4 NPs can selectively lead to the reduction of K562 cell viability through the cell membrane damage, activation of caspase-9, -8 and -3, elevation of Bax/Bcl-2 mRNA ratio, ROS production, cell cycle arrest, and apoptosis. Finally, antibacterial assays disclosed that Co3O4 NPs can stimulate a promising antibacterial effect against pathogenic bacteria. Conclusion: In general, these observations can provide useful information for the early stages of nanomaterial applications in therapeutic platforms.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Cobalto/química , Cobalto/farmacologia , Nanopartículas Metálicas/química , Óxidos/química , Óxidos/farmacologia , Albumina Sérica Humana/metabolismo , Antibacterianos/química , Antibacterianos/metabolismo , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cobalto/metabolismo , Escherichia coli/efeitos dos fármacos , Humanos , Células K562 , Testes de Sensibilidade Microbiana , Simulação de Acoplamento Molecular , Óxidos/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Albumina Sérica Humana/química , Staphylococcus aureus/efeitos dos fármacos , Difração de Raios X
12.
Rev Soc Bras Med Trop ; 53: e20200026, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32578708

RESUMO

INTRODUCTION: The human T-lymphotropic virus type 1 (HTLV-1) has a single-stranded RNA genome and expresses specific proteins that have oncogenic potential. Approximately 15 to 20 million people worldwide have been infected by this virus. Changes in protein or gene expression are the effects of single nucleotide polymorphisms (SNPs) within the Toll-like receptor 3 (TLR3) gene. The function and efficacy of signal transduction also lead to modified immune responses. The present study aimed to investigate the association of SNPs within TLR3 (rs3775291 and rs3775296) with susceptibility to HTLV-1 infection in Iranian asymptomatic blood donors. METHODS: This study was performed on 100 HTLV-1-infected asymptomatic blood donors and 118 healthy blood donors. Genomic DNA from all participants was purified and then amplified using specific PCR primers. SNPs within TLR3 were evaluated using the restriction fragmentation length polymorphism technique, and the results were analyzed using SPSS software (version 22). RESULTS: The frequencies of the TLR3 (rs3775296) CC, CA, AA genotypes were 70%, 24%, and 6% in the patient group, and 50.8%, 44.9%, and 4.2% in the control group, respectively. There was a significant difference in the frequency distribution of TLR3 (rs3775296) genotypes and alleles, but not in the frequency distribution of TLR3 (rs3775291) genotypes between the patient and control groups. CONCLUSIONS: The TLR3 SNP rs3775296 was significantly associated with HTLV-1 infection and may be a protective factor against this viral infection.


Assuntos
Doadores de Sangue/estatística & dados numéricos , Infecções por HTLV-I/genética , Vírus Linfotrópico T Tipo 1 Humano/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor 3 Toll-Like/genética , Adulto , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Genótipo , Infecções por HTLV-I/diagnóstico , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade
13.
Microb Pathog ; 140: 103945, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31874228

RESUMO

Staphylococcus aureus is an important cause of both hospital and community acquired infections worldwide. S.aureus can develop multidrug resistance; thus, immunotherapy can be a rational alternative. High level ß-lactam resistance of S. aureus has been attributed to the penicillin binding protein 2a (PBP2a). In this study, we assessed the immunogenicity and protectivity of PBP2a formulated in Montanide ISA266 and Alum adjuvants. Recombinant PBP2a with a molecular weight of approximately 13 kDa was expressed and purified by nickel-nitrilotriacetic acid (NI-NTA) affinity chromatography and characterized by SDS-PAGE and Western blot. To investigate the immunogenicity and protective effects of recombinant protein, 20 µg of r-PBP2a in various formulations were subcutaneously injected in different groups. Two booster vaccinations were carried out in two-week intervals and blood samples were collected two weeks after each injection. To determine the type of induced immune response, sera and splenocytes were analyzed by ELISA for total IgG and isotypes (IgG1 and IgG2a) and cytokine secretion (IFN-γ, IL-4, IL-17 and TNF-α), respectively. Three weeks following the last immunization, experimental mice were challenged with 5 × 108 CFU of bacteria intraperitoneally and mortality rate and bacterial load were assessed. Interestingly, analysis of humoral immune responses revealed that administration of r-PBP2a with Montanide ISA266 significantly increased specific IgG responses and also IgG1 isotype compared to alum-adjuvanted vaccine group. Also, r-PBP2a formulation with alum and MontanideISA266 adjuvants raised IFN-γ, IL-4, IL-17 cytokines secretion, and protectivity following experimental challenge. The results of the present study provide evidences for immunogenicity and protectivity of PBP2a protein as a vaccine candidate.


Assuntos
Adjuvantes Farmacêuticos/administração & dosagem , Proteínas de Bactérias/administração & dosagem , Staphylococcus aureus Resistente à Meticilina/imunologia , Proteínas de Ligação às Penicilinas/administração & dosagem , Infecções Estafilocócicas/imunologia , Adjuvantes Farmacêuticos/análise , Compostos de Alúmen/administração & dosagem , Compostos de Alúmen/análise , Animais , Anticorpos Antibacterianos/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Composição de Medicamentos , Feminino , Humanos , Imunidade Celular , Imunidade Humoral , Imunoglobulina G/imunologia , Interleucina-17/genética , Interleucina-17/imunologia , Interleucina-4/genética , Interleucina-4/imunologia , Manitol/administração & dosagem , Manitol/agonistas , Staphylococcus aureus Resistente à Meticilina/genética , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Ligação às Penicilinas/genética , Proteínas de Ligação às Penicilinas/imunologia , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/prevenção & controle
14.
Rev. Soc. Bras. Med. Trop ; 53: e20200026, 2020. tab
Artigo em Inglês | LILACS, Coleciona SUS, Sec. Est. Saúde SP | ID: biblio-1136800

RESUMO

Abstract INTRODUCTION: The human T-lymphotropic virus type 1 (HTLV-1) has a single-stranded RNA genome and expresses specific proteins that have oncogenic potential. Approximately 15 to 20 million people worldwide have been infected by this virus. Changes in protein or gene expression are the effects of single nucleotide polymorphisms (SNPs) within the Toll-like receptor 3 (TLR3) gene. The function and efficacy of signal transduction also lead to modified immune responses. The present study aimed to investigate the association of SNPs within TLR3 (rs3775291 and rs3775296) with susceptibility to HTLV-1 infection in Iranian asymptomatic blood donors. METHODS: This study was performed on 100 HTLV-1-infected asymptomatic blood donors and 118 healthy blood donors. Genomic DNA from all participants was purified and then amplified using specific PCR primers. SNPs within TLR3 were evaluated using the restriction fragmentation length polymorphism technique, and the results were analyzed using SPSS software (version 22). RESULTS: The frequencies of the TLR3 (rs3775296) CC, CA, AA genotypes were 70%, 24%, and 6% in the patient group, and 50.8%, 44.9%, and 4.2% in the control group, respectively. There was a significant difference in the frequency distribution of TLR3 (rs3775296) genotypes and alleles, but not in the frequency distribution of TLR3 (rs3775291) genotypes between the patient and control groups. CONCLUSIONS: The TLR3 SNP rs3775296 was significantly associated with HTLV-1 infection and may be a protective factor against this viral infection.


Assuntos
Humanos , Masculino , Feminino , Adulto , Doadores de Sangue/estatística & dados numéricos , Vírus Linfotrópico T Tipo 1 Humano/genética , Infecções por HTLV-I/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor 3 Toll-Like/genética , Infecções por HTLV-I/diagnóstico , Estudos de Casos e Controles , Predisposição Genética para Doença , Genótipo , Irã (Geográfico) , Pessoa de Meia-Idade
15.
Gastroenterol Hepatol Bed Bench ; 12(4): 292-300, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31749917

RESUMO

Aim: In the present study, a new formulation of HBsAg vaccine was developed and compared with a commercial peer. Background: Vaccination of hepatitis B infection has been an unavoidable affair since the 1980s, though it has numerous limitations such as inefficacy in the induction of cellular immune responses. To address these limitations, research on novel formulations is necessary to develop a superior formulation with the potency of induction of both cellular and humoral immune responses. Methods: HBsAg was formulated in oil-in-water adjuvant Montanide ISA-266 (5 µg/dose) using homogenizer. Balb/C mice were then immunized three times at days 0, 14, and 28 with HBsAg/Montanide ISA-266 or HBsAg/alum with proper control groups. Two weeks after the last immunization, immunological parameters including IL-2, IL-4, TNF-α, IFN-γ, total IgG and IgG1/IgG2a isotypes were assessed by ELISA. Results: The results demonstrated that the formulation of HBsAg with Montanide ISA-266 enhanced humoral immune responses versus the commercial vaccine and control groups. No significant difference in terms of Th1 pattern was found between HBsAg/Montanide ISA-266 and the commercial vaccine. Conclusion: Formulation of HBsAg with an oil-based adjuvant may be useful for the induction of a more potent humoral immune response compared to the commercially available HBV vaccine.

16.
Int J Nanomedicine ; 14: 243-256, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30643404

RESUMO

Background: Nanoparticles (NPs) have been emerging as potential players in modern medicine with clinical applications ranging from therapeutic purposes to antimicrobial agents. However, before applications in medical agents, some in vitro studies should be done to explore their biological responses. Aim: In this study, protein binding, anticancer and antibacterial activates of zero valent iron (ZVFe) were explored. Materials and methods: ZVFe nanoparticles were synthesized and fully characterized by X-ray diffraction, field-emission scanning electron microscope, and dynamic light scattering analyses. Afterward, the interaction of ZVFe NPs with human serum albumin (HSA) was examined using a range of techniques including intrinsic fluorescence, circular dichroism, and UV-visible spectroscopic methods. Molecular docking study was run to determine the kind of interaction between ZVFe NPs and HSA. The anticancer influence of ZVFe NPs on SH-SY5Y was examined by MTT and flow cytometry analysis, whereas human white blood cells were used as the control cell. Also, the antibacterial effect of ZVFe NPs was examined on Pseudomonas aeruginosa (ATCC 27853), Escherichia coli (ATCC 25922), and Staphylococcus aureus (ATCC 25923). Results: X-ray diffraction, transmission electron microscope, and dynamic light scattering analyses verified the synthesis of ZVFe NPs in a nanosized diameter. Fluorescence spectroscopy analysis showed that ZVFe NPs spontaneously formed a complex with HSA through hydrogen bonds and van der Waals interactions. Also, circular dichroism spectroscopy study revealed that ZVFe NPs did not change the secondary structure of HSA. Moreover, UV-visible data presented that melting temperature (Tm) of HSA in the absence and presence of ZVFe NPs was almost identical. Molecular dynamic study also showed that ZVFe NP came into contact with polar residues on the surface of HSA molecule. Cellular assays showed that ZVFe NPs can induce cell mortality in a dose-dependent manner against SH-SY5Y cells, whereas these NPs did not trigger significant cell mortality against normal white bloods in the concentration range studied (1-100 µg/mL). Antibacterial assays showed a noteworthy inhibition on both bacterial strains. Conclusion: In conclusion, it was revealed that ZVFe NPs did not induce a substantial influence on the structure of protein and cytotoxicity against normal cell, whereas they derived significant anticancer and antibacterial effects.


Assuntos
Antibacterianos/administração & dosagem , Antineoplásicos/administração & dosagem , Bactérias/efeitos dos fármacos , Bactérias/metabolismo , Ferro/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Albumina Sérica Humana/metabolismo , Antibacterianos/química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/metabolismo , Humanos , Ferro/química , Nanopartículas Metálicas/química , Simulação de Acoplamento Molecular , Neuroblastoma/tratamento farmacológico , Neuroblastoma/patologia , Conformação Proteica , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismo , Albumina Sérica Humana/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/metabolismo , Células Tumorais Cultivadas
17.
J Biomol Struct Dyn ; 37(11): 3007-3017, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30044173

RESUMO

This study is focused on the fabrication and characterization of titanium oxide (TiO2) NPs. Afterwards; the interaction of TiO2 NPs with human hemoglobin (Hb) was investigated by FTIR spectroscopy, fluorescence spectroscopy, and molecular docking studies. Also, the cytotoxic effect of fabricated TiO2 NPs against human white blood cells (WBCs) was considered by MTT assay. The antibacterial effect of synthesized NPs was examined on Pseudomonas aeruginosa (ATCC 27853); Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 25923). TEM and DLS investigations showed that the synthesized TiO2 NPs have a narrow nano-sized distribution. XRD pattern of the fabricated NPs exhibited that the TiO2 NPs contain anatase phase. Similarity in amide I and II signal intensities showed that secondary structure of the adsorbed Hb is preserved. The intrinsic fluorescence study revealed that the fluorescence quenching of Hb was done by complex formation between Hb and TiO2 NPs trough the hydrogen bond and van der Waals interactions. Synchronous fluorescence spectroscopy determined that interaction of TiO2 NPs with Hb did not unfold the Hb structure in the vicinity of the Tyr and Trp residues. Molecular docking study depicted that Glu-95, Thr-134 and Tyr-140 are involved in the formation of hydrophilic bonds. MTT data and antibacterial assays indicated that TiO2 NPs endow distinguished antibacterial activities against Gram-negative and Gram positive strains at safe concentrations. This study may reveal that fabricated TiO2 NP can be used as a safe and potent antibacterial agent. Communicated by Ramaswamy H. Sarma.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Hemoglobinas/metabolismo , Leucócitos/patologia , Nanopartículas Metálicas/química , Titânio/farmacologia , Antibacterianos/química , Humanos , Leucócitos/efeitos dos fármacos , Nanopartículas Metálicas/administração & dosagem , Simulação de Acoplamento Molecular , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Prata/química , Espectrometria de Fluorescência , Titânio/química
18.
Immunol Lett ; 212: 125-131, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30496765

RESUMO

Staphylococcus aureus is a leading infectious cause of life-threatening diseases in human beings, with no effective vaccine available to date against this bacterium. Treatment of methicillin-resistant S. aureus (MRSA) infections has become increasingly difficult because of the emergence of multidrug-resistant isolates. Immunotherapy represents a potential approach to prevent S. aureus-related infections. Autolysin is one of the virulence factors, which controls the growth, cell lysis, daughter-cell separation, and biofilm formation. Our study focused on passive immunization against MRSA infection. Herein, rabbit polyclonal IgG was produced following the preparation of r-autolysin. Specificity of IgG against r-autolysin was investigated by ELISA and western blotting assays. IgG fraction was prepared using sulfate ammonium precipitation, and the ability of antiserum to promote phagocytosis of bacteria was assessed by opsonophagocytosis assay. Then, passive immunization of mice was carried out with polyclonal IgG fraction and, mice were sacrificed three days after challenge and their kidneys, liver, and spleen were collected. Results exhibited that the passive immunization with rabbit polyclonal anti-IgG fraction tremendously improved survival rates of mice challenged by S. aureus as well as vancomycin treatment compared with the negative control groups. In addition, a remarkable decrease in bacterial numbers was observed in mice treated with rabbit polyclonal anti-IgG. Importantly, our findings demonstrated that passive immunotherapy and antibiotic therapy lead to decreased histopathological damage in mice infected by S. aureus as compared with control groups. Our results suggested that the passive immunization may result in the introduction of excellent strategies to control infections caused by MRSA, like antibiotic therapy.


Assuntos
Antibacterianos/uso terapêutico , Imunização Passiva/métodos , Imunoglobulina G/administração & dosagem , Staphylococcus aureus Resistente à Meticilina/imunologia , N-Acetil-Muramil-L-Alanina Amidase/imunologia , Infecções Estafilocócicas/terapia , Animais , Proteínas de Bactérias/imunologia , Modelos Animais de Doenças , Feminino , Humanos , Imunoglobulina G/imunologia , Staphylococcus aureus Resistente à Meticilina/genética , Camundongos , N-Acetil-Muramil-L-Alanina Amidase/genética , Coelhos , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Resultado do Tratamento , Fatores de Virulência/imunologia
19.
Adv Pharm Bull ; 8(3): 395-400, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30276135

RESUMO

Purpose: Wound healing is a natural biologic process, but the duration of it may take too long. Trying to shorten this process is one of the challenges for scientists. Many technologies were applied to achieve this goal as well as nanotechnology. In this study semi solid formulations containing curcumin and ampicillin solid lipid nanoparticles (SLNs) were prepared to evaluate as burn wound healing agent. Methods: Curcumin as an anti-inflammatory and anti-bacterial agent and ampicillin as an antibiotic were applied. In-vitro and in-vivo evaluations were carried out. Particle size, loading efficiency, release profile, morphology and anti-bacterial efficacy of desired nanoparticles were evaluated at first. Then the remaining of the antibacterial effect in semi solid preparations was studied. Animal studies for both toxicology using rabbits and skin burn model using rats were designed. Pathology studies after applying of formulations was done too. Results: Desired nanoparticles were spherical in shape and particle size in range of 112-121 nm, with low zeta potential. For increasing stability of particles they were freeze dried using cryoprotectant. Lyophilized particles show no significant size enlargement. Results showed that both ointment and gel preparations have reasonable anti-bacterial effects, both of them cause increasing in the rate of wound healing in comparison with placebos and control groups and none of the formulations showed acute toxicity. Conclusion: It seems that using nanotechnology could shorten wound healing process to reduce treatment costs and increase compliance of patients.

20.
Int Immunopharmacol ; 56: 186-192, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29414649

RESUMO

Methicillin resistant Staphylococcus aureus (MRSA) is a representative pathogen that is responsible for a nosocomial infection and considerable yearly mortality rate. Antibiotic resistance provides a great reason for immunotherapy as an alternative strategy to prevent and/or treat the infection. Herein, following the preparation of recombinant penicillin binding protein 2a (r-PBP2a), rabbit polyclonal IgG was purified. Specificity of IgG to r-PBP2a was evaluated by ELISA and western blotting. IgG fraction was prepared by sulfate ammonium precipitation. In addition opsonophagocytosis assay confirmed bioactivity of purified IgG. Experimental mice were challenged with lethal dose of MRSA (5 × 108) and mortality rate was recorded in the mice treated with IgG fraction for anti-rPBP2a, normal rabbit IgG, vancomycin therapy, and PBS control group. Bacterial quantity was evaluated by culture of liver, kidney and spleen homogenates. Results showed that passive immunization with anti r-PBP2a resulting in a significant improvement in survival rate as well as vancomycin treatment compared with control groups. Furthermore, anti r-PBP2a IgG enhanced considerably the phagocytosis of the S. aureus COL strain, reduced bacterial load, and inhibited the systemic spread of COL strain to the internal organs. These results confirmed that passive immunization by anti-r-PBP2a plays a considerable role in the control of infections caused by S. aureus similar to that of antibiotic therapy.


Assuntos
Proteínas de Bactérias/imunologia , Epitopos/imunologia , Imunoglobulina G/imunologia , Staphylococcus aureus Resistente à Meticilina/fisiologia , Proteínas de Ligação às Penicilinas/imunologia , Proteínas Recombinantes/imunologia , Sepse/imunologia , Infecções Estafilocócicas/imunologia , Animais , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Feminino , Imunização Passiva , Imunoglobulina G/metabolismo , Imunoterapia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas de Ligação às Penicilinas/genética , Coelhos , Proteínas Recombinantes/genética , Sepse/tratamento farmacológico
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