ABSTRACT
BACKGROUND: Given the significant occurrence of skin cancer in the Middle East and the existing research gap concerning its incidence and trends, this research aimed to study the epidemiology and trend changes of skin cancer in the Golestan province, Northeastern Iran. METHODS: The Golestan Population-based Cancer Registry's (GPCR's) data bank was utilized to gather information on confirmed skin cancer cases in the province during 2005-2018. We used Poisson regression analysis for comparing incidence rates between groups. P values less than 0.05 were considered statistically significant. RESULTS: Of 1690 patients (mean age: 62.05±15.83 years), most were male (60.1%) and resided in urban areas (61.5%). The age-standardized rate (ASR) of non-melanoma and melanoma skin cancer was 8.49 and 0.56 per 100000 persons-year, respectively. A notably higher ASR for non-melanoma skin cancer (NMSC) was observed in men (ASR: 10.60; 95% CI: 9.91-11.29) (P<0.01) and urban residents (ASR: 10.19; 95% CI: 9.52-10.82) (P<0.01). There was no significant difference in the ASR of melanoma skin cancer based on gender (P=0.24) and place of residence (P=0.48). The incidence trend of melanoma (estimated annual percent change [EAPC]: -3.28; 95% CI: -18.54 to 14.83) and NMSC (EAPC: 0.39; 95% CI: -3.99 to 4.97) did not differ significantly. CONCLUSION: During the 14-year study period, the ASR of both types of skin cancer exhibited a consistent pattern, except for NMSC, which showed higher rates among men and urban residents. This should be taken into consideration when formulating preventive and control strategies in the study area.
Subject(s)
Melanoma , Registries , Skin Neoplasms , Humans , Iran/epidemiology , Male , Skin Neoplasms/epidemiology , Incidence , Female , Middle Aged , Aged , Adult , Melanoma/epidemiology , Aged, 80 and over , Sex Distribution , Age Distribution , Young Adult , Urban Population/statistics & numerical data , Adolescent , Carcinoma, Basal Cell/epidemiologyABSTRACT
OBJECTIVES: HIV infection still remains a leading cause of morbidity and mortality worldwide. The inability of highly-active antiretroviral therapy in HIV-1 eradication led to development of therapeutic vaccines. Exploiting effective immunogenic constructs and potent delivery systems are important to generate effective therapeutic vaccines, and overcome their poor membrane permeability. Among HIV-1 proteins, the Nef and Vpr proteins can be considered as antigen candidates in vaccine design. METHODS: In this study, the immunogenicity of Nef-Vpr antigen candidate in different regimens along with antimicrobial peptide LL-37 (as a DNA carrier) and Montanide 720 (as an adjuvant) was studied in mice. Moreover, the secretion of cytokines was assessed in virion-exposed mice lymphocytes in vitro. RESULTS: Our data indicated that groups immunized with the homologous protein + Montanide regimen (group 1), and also the heterologous DNA + LL-37 prime/protein + Montanide boost regimen (group 2) could significantly generate strong immune responses as compared to groups immunized with the DNA constructs (groups 3 & 4). Moreover, immunization of mice with the homologous DNA + LL-37 regimen in low dose of DNA (5 µg) could induce higher immune responses than the homologous naked DNA regimen in high dose of DNA (50 µg) indicating the role of LL-37 as a cell penetrating peptide. Additionally, the heterologous DNA + LL-37 prime/protein + Montanide boost regimen (group 2) induced significantly IFN-gamma secretion from virion-exposed lymphocytes in vitro. CONCLUSION: Generally, the use of LL-37 for DNA delivery, Montanide 720 as an adjuvant, and heterologous DNA prime/protein boost strategy could significantly increase IgG2a, IFN-gamma, and Granzyme B, and maintain cytokine secretion after exposure to virions. Indeed, the heterologous DNA + LL-37 prime/protein + Montanide boost regimen can be considered as a potent strategy for development of therapeutic HIV vaccines.
Subject(s)
HIV Infections , HIV-1 , Vaccines, DNA , Animals , Mice , Adjuvants, Immunologic , Antigens, Viral , DNA , HIV Infections/prevention & control , HIV-1/genetics , Human Immunodeficiency Virus Proteins , Immunity , Mice, Inbred BALB C , Vaccination , Virion , Immunoglobulin GABSTRACT
Multiepitope vaccines could induce multiantigenic immunity against large complex pathogens with different strain variants. Herein, the in silico, in vitro and in vivo studies were used to design and develop a novel candidate antigenic multiepitope vaccine against SARS-CoV-2 pathogen. The designed multiepitope construct targets the spike glycoprotein (S), membrane protein (M), and nucleocapsid phosphoprotein (N) of SARS-CoV-2 (i.e., the S-N-M construct). This construct contains the cytotoxic T lymphocyte (CTL)-, helper T lymphocyte (HTL)-, and linear B lymphocyte (LBL)-inducing epitopes. The multiepitope s-n-m fusion gene was subcloned in prokaryotic (pET24a) and eukaryotic (pcDNA3.1) expression vectors. Its expression was evaluated in mammalian cell line using LL37 cell penetrating peptide. Moreover, the recombinant multiepitope S-N-M peptide was produced in E. coli strain. Finally, mice were immunized using homologous and heterologous regimens for evaluation of immune responses. Our data indicated that the multiepitope S-N-M peptide construct combined with Montanide 720 in homologous regimen significantly stimulated total IgG, IgG2a, IFN-γ, TNF-α, IL-15, IL-21 and IL-6, and Granzyme B secretion as compared to other groups. Moreover, the pcDNA-s-n-m/ LL37 nanoparticles significantly induced higher immune responses than the naked DNA in both homologous and heterologous regimens. In general, our designed multiepitope vaccine construct can be considered as a vaccine candidate in SARS-CoV-2 infection model.
Subject(s)
COVID-19 , SARS-CoV-2 , Animals , COVID-19/prevention & control , COVID-19 Vaccines , Epitopes, B-Lymphocyte , Epitopes, T-Lymphocyte/genetics , Escherichia coli , Humans , Mammals , Mice , Mineral Oil , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/genetics , Vaccines, SubunitABSTRACT
BACKGROUND AND OBJECTIVES: DNA-based therapeutic vaccines have been proposed as a promising strategy for the treatment of established HIV infections. However, these vaccines are often associated with certain shortcomings, such as poor immunogenicity and low transfection efficiency. In this study, we investigated the ability of LL-37 to deliver a potential immunogenic fusion construct comprising HIV-1 nef and vpr genes into a mammalian cell line. METHODS: First, the pEGFP-N1 eukaryotic expression vector harboring the HIV-1 nef-vpr fusion was produced free of endotoxin on a large scale. Then, DNA/LL-37 complexes were prepared by coincubation of pEGFP-nef-vpr with LL-37 for 45 minutes at different nitrogen to phosphate (N/P) ratios. The formation of DNA/peptide complexes was investigated by gel retardation assay. Next, the stability and morphological characteristics of the nanoparticles were evaluated. The toxicity of LL-37 and the nanoparticles in HEK-293T cells were assessed by MTT assay. The transfection efficiency of the DNA/LL-37 complexes was studied by fluorescence microscopy, flow cytometry, and western blot analysis. RESULTS: LL-37 formed stable complexes with pEGFP-nef-vpr (diameter of 150-200 nm) while providing good protection against nucleolytic and proteolytic degradation. The peptide significantly affected cell viability even at low concentrations. However, the LL-37/DNA complexes had no significant cytotoxic effect. Treatment of cells with pEGFP-N1/LL-37 and pEGFP-nef-vpr/LL-37 resulted in transfection of 36.32% ± 1.13 and 25.55% ± 2.07 of cells, respectively. CONCLUSION: Given these findings and the important immunomodulatory and antiviral activities of LL- 37, the use of this peptide can be further exploited in the development of novel gene delivery strategies and vaccine design.
Subject(s)
HIV Infections , HIV-1 , Antimicrobial Cationic Peptides , Antimicrobial Peptides , DNA , Genes, vpr , HEK293 Cells , HIV Infections/genetics , HIV-1/genetics , Humans , nef Gene Products, Human Immunodeficiency Virus/genetics , nef Gene Products, Human Immunodeficiency Virus/metabolism , vpr Gene Products, Human Immunodeficiency Virus , CathelicidinsABSTRACT
UNLABELLED: Background : Congenital heart disease (CHD) is the most common congenital anomaly in newborns. This study was performed to determine the live birth incidence of CHD by ethnicity and sex in Gorgan, Northern Iran. METHODS: In this longitudinal, hospital-based study, 18162 live births in Dezyani Hospital in Gorgan, North of Iran, were screened for CHD, from 2007 through 2009. Clinical examination, echocardiography, color Doppler, and cardio catheterization were used as diagnostic tools. Sex, ethnicity, and type of CHD for each case were recorded in a pre-designed questionnaire. Results : The incidence rates of CHD in the native Fars, Sistani, and Turkmen subjects were 5.73 (95%CI: 4.53-7.15), 12.27 (95%CI: 8.74-16.73), and 15.93 (95%CI: 10.00-24.02) per 1000 live births, respectively. The Turkmen to native Fars and Sistani to native Fars relative risk for congenital CHD malformations was 2.77 (95%CI: 1.73-4.44; p value < 0.001) and 1.29 (95%CI: 0.77-2.18; p value < 0.323), respectively. While atrial septal defect was the most common lesion in the native Fars subjects (2.14 per 1000 [95%CI: 1.42-3.06]) and in the Sistani subjects (2.84 per 1000 [95%CI: 1.29-5.36]), in the Turkmen subjects, ventricular septal defect (4.36 per 1000 [95%CI: 1.59-9.43]), followed by atrial septal defect, was the most frequent lesion. Conclusion : This study showed that the incidence and pattern of CHD among live births in Gorgan, North of Iran, varied according to ethnicity. The risk of CHD was higher in the Turkmen and Sistani groups than in the Fars population.