Multi-epitope vaccine against SARS-CoV-2 targeting the spike RBD: an immunoinformatics approach.

Aim: We designed a SARS-CoV-2 epitope vaccine based on the receptor-binding domain (RBD) in virus spike protein. Methods: RT-PCR performed on nasopharyngeal swab COVID-19 patients. After registering RBD region in the GenBank, physicochemical parameters, secondary structure, homology modeling, 3D structure of RBD region and antigenicity were determined using ProtParam ExPASy, PSIPRED, MolProbity, IEDB and Vaxijen online tools, respectively. Results: B and T cell epitopes were predicted in terms of non-allergenicity and antigenicity. MolProbity analysis provided a qualitative model for RBD. The homology model showed that most of the residues are in optimal district of energy. Conclusion: High immunogenicity score of epitopes indicates promising candidates for the development of multi-epitope vaccines. It may help to develop an effective vaccine.

In order to identify the sequence of RBD region of S protein in SARS-CoV-2, RT-PCR test was performed on nasopharyngeal swab samples of four COVID-19 patients referred to Imam Khomeini Hospital in Ardabil. After registering the sequence of the RBD region in the GenBank database, the physicochemical parameters, secondary structure, homology modeling, 3D structure of the RBD region and antigenicity were determined using ProtParam ExPASy, PSIPRED, MolProbity, IEDB and Vaxijen online tools, respectively.

Current and Novel Emerging Medical Therapies for Peripheral Artery Disease: A Literature Review.

Despite the improvements in endovascular techniques during the last decades, there is still an increase in the prevalence of peripheral artery disease (PAD) with limited practical treatment, which timeline impact of any intervention for critical limb ischemia (CLI) is poor. Most common treatments are not suitable for many patients due to their underlying diseases, including aging and diabetes. On the one hand, there are limitations for current therapies due to the contraindications of some individuals, and on the other hand, there are many side effects caused by common medications, for instance, anticoagulants. Therefore, novel treatment strategies like regenerative medicine, cell-based therapies, Nano-therapy, gene therapy, and targeted therapy, besides other traditional drugs combination therapy for PAD, are newly considered promising therapy. Genetic material encoding for specific proteins concludes with a potential future for developed treatments. Novel approaches for therapeutic angiogenesis directly used the angiogenetic factors originating from key biomolecules such as genes, proteins, or cell-based therapy to induce blood vessel formation in adult tissues to initiate the recovery process in the ischemic limb. As PAD is associated with high mortality and morbidity of patients causing disability, considering the limited treatment choices for these patients, developing new treatment strategies to prevent PAD progression and extending life expectancy, and preventing threatening complications is urgently needed. This review aims to introduce the current and the novel strategies for PAD treatment that lead to new challenges for relief the patient's suffered from the disorder.

Highly sensitive photoelectrochemical immunosensor for detecting cancer marker CA19-9 based on a new SnSe quantum dot.

A sandwich-type photoelectrochemical (PEC) immunosensor was constructed on a screen-printed electrode (SPE) using gold-coated tin selenide quantum dots (Au-SnSe QDs) to determine the carbohydrate antigen 19 9 (CA19-9). Water-soluble Au-SnSe QDs were prepared by coating low-cost SnSe QDs, prepared by reacting tin(II) 2-ethyl hexanoate with selenium ions (HNaSe) without needing to add an external capping agent (SnSe QDs). SnSe-based QDs were characterized using high-resolution transmission electron microscopy (HR-TEM) and dynamic light scattering (DLS). DSP (dithio-bis (succinimidyl propionate)) as a linker was attached on Au@SnSe QDs and conjugated with CA19-9 monoclonal antibodies (Ab2-DSP-Au@SnSE QD). For capture probe assembling, an Au nano-layer was electrochemically deposited on a SPE by HAuCl4 reduction using 12 cycles of cyclic voltammetry (0 to - 1.4 V) at the scan rate of 50 mV s-1, then covered by self-assembly of DSP and covalent conjugation of CA19-9 Ab1. Our developed PEC immunosensor showed a significant photoelectrochemical response, recorded using chronoamperometry (0.3 V), for the presence of CA19-9 antigen in serum samples under light irradiation, with a detection limit (LOD) of 0.0011 U mL-1 and a dynamic range of 0.005-100 U mL-1. The recovery of CA19-9 determination from serum samples was 101 to 113%.

COVID -19: From the Molecular Mechanisms to Treatment.

The 2019 novel coronavirus (SARS-CoV-2) causes severe pneumonia called COVID-19 and leads to severe acute respiratory syndrome with a high mortality rate. The SARS-CoV-2 virus in the human body leads to jumpstarting immune reactions and multi-organ inflammation, which has poorer outcomes in the presence of predisposing conditions, including hypertension, dyslipidemia, dysglycemia, abnormal adiposity, and even endothelial dysfunction via biomolecular mechanisms. In addition, leucopenia, hypoxemia, and high levels of both cytokines and chemokines in the acute phase of this disease, as well as some abnormalities in chest CT images, were reported in most patients. The spike protein in SARS-CoV-2, the primary cell surface protein, helps the virus anchor and enter the human host cells. Additionally, new mutations have mainly happened for spike protein, which has promoted the infection's transmissibility and severity, which may influence manufactured vaccines' efficacy. The exact mechanisms of the pathogenesis, besides molecular aspects of COVID-19 related to the disease stages, are not well known. The altered molecular functions in the case of immune responses, including T CD4+, CD8+, and NK cells, besides the overactivity in other components and outstanding factors in cytokines like interleukin-2, were involved in severe cases of SARS-CoV-2. Accordingly, it is highly needed to identify the SARSCoV-2 biomolecular characteristics to help identify the pathogenesis of COVID-19. This study aimed to investigate the biomolecular aspects of SARSCoV-2 infection, focusing on novel SARS-CoV-2 variants and their effects on vaccine efficacy.

Cigarette smoking and risk of palindromic rheumatism: A propensity score matching analysis.

Present study was conducted to investigate smoking status in palindromic rheumatism (PR) patients compared to healthy individuals as well as to assess the effect of smoking on clinical features and outcomes of PR. One hundred and forty-six patients with diagnosis of PR and 346 healthy controls were included in this study. Demographic, clinical, and laboratory characteristics and the smoking history of PR patients at the cohort entry were obtained from patients' records. Demographic and smoking history of the control group were obtained by direct interview. In order to reduce heterogeneity between the studied groups, propensity score matching (PSM) analyses was performed. Matching was achieved by considering age, gender, educational status, and marital status. After PSM, we carried out a multivariate analysis with PR as the main outcome variable, ever smoking as the main predictor variable and age, gender, educational status, and marital status as covariates. PSM resulted in 123 PR patients and 246 matched controls. Multivariate analysis did not show a significant increase in the risk of PR in ever smokers. Seventy-six patients were anti-citrullinated protein/peptide antibody positive (ACPA-positive). Multivariate logistic regression showed a significant increase in the risk of PR in ACPA-positive ever smokers. Except lower sustained remission rate in ever smokers, no significant differences were observed in clinical manifestations and outcomes of PR between ever and never smokers. In conclusion, smoking is a risk factor for ACPA-positive PR.

Baculoviral inhibitor of apoptosis family of proteins repeat-containing 5 gene methylation status in peripheral blood mononuclear cells and plasma survivin levels in patients with Behçet's disease.

OBJECTIVES: This study aims to evaluate the baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) gene methylation in the peripheral blood mononuclear cells (PBMCs) in patients with Behçet's disease (BD) compared to healthy controls and the association of survivin with BD activity. PATIENTS AND METHODS: A cross-sectional study was conducted on 43 BD patients (22 males, 21 females; mean age 36.6±10.1 years; range, 18 to 66 years) and 44 age- and sex-matched healthy controls (23 males, 21 females; mean age 35.4±7.5 years; range, 18 to 61 years) between August 2019 and December 2019. Sample size was calculated guided by taking into account the difference of 1.5 units between the mean expression of BIRC5 gene in the BD and control groups, as well as considering α=0.5 and power=80%. We assessed the methylation status of the BIRC5 gene in PBMCs of BD and control groups by methylation-specific polymerase chain reaction (MS-PCR). Plasma levels of survivin were measured by enzyme- linked immunosorbent assay. RESULTS: Oral aphthous ulcer, genital ulcer, and skin lesions were the most common clinical manifestations in BD group. MS-PCR showed that the deoxyribonucleic acid samples of BD and control groups were not different in methylated and unmethylated areas and alleles were heterozygote. No significant difference was observed in the plasma levels of survivin in BD (98.86±25.5 pg/mL) and control (118.16±37.4 pg/mL) groups. There was no significant correlation between survivin plasma levels and BD activity. CONCLUSION: Our study did not show any evidence of association between the alteration in the BIRC5 gene methylation, survivin production, and apoptosis dysregulation in BD.

Prominent roles of microRNA-142 in cancer.

MicroRNAs (miRNAs) are single-stranded non-coding RNAs that regulate gene expression post-transcriptionally via mRNA degradation, or translational repression. They have important roles in normal development and homeostasis maintenance. Many studies have revealed that aberrant expression of miRNAs is associated with development of pathological conditions, including cancers. MiRNAs can either promote or suppress tumorigenesis based on the regulation of gene expression by targeting multiple molecules. In recent years, several miRNAs have been reported to be dysregulated in various cancers. Most recent findings have shown that miR-142 gene, located at chromosome 17q22, is involved in cellular migration, proliferation, and apoptosis in different human cancers. The present review discusses some molecular mechanisms and the expression status of miRNA-142 in the pathogenesis of various cancers.

Phosphorylation Modulates Survivin Function in Behcet's Disease.

Purpose: Survivin is critical for proliferation, maturation, homeostasis and differentiation of effector and memory lymphocytes. In this study the baculoviral inhibitors of apoptosis proteins (IAPs) repeat containing 5 (BIRC5) mRNA, survivin, and phosphorylated survivin expression were evaluated in peripheral blood mononuclear cells (PBMCs), and plasma of patients with Behcet's disease (BD). Methods: In this study, 26 Iranian Azari patients diagnosed with BD and 30 healthy controls were recruited. Total RNA was extracted from PBMCs. The expression level of survivin was measured by quantitative real-time polymerase chain reaction (PCR). Survivin plasma levels were measured using survivin Enzyme-linked immunosorbent assays. Also, western blotting analysis was performed to measure phosphorylated-survivin and survivin levels in PBMCs and plasma of patients with BD. Results: In a pilot study, we showed that BIRC5 gene expression increased in BD patients compared with healthy controls (P<0.05). Western blotting analysis indicated that there was an increase in phosphorylated survivin expression in PBMCs of BD patients. Our data from western blot analysis showed survivin level in plasma samples of BD patients was similar to healthy controls. No significant differences were observed between plasma survivin levels in the BD patients compared with control group (P>0.05). The expression of phosphorylated survivin at Thr34 in PBMCs of BD patients with active disease was increased. Plasma phosphorylated survivin levels in having BD patients were also downregulated compared to healthy individuals. Conclusion: Analysis of PBMCs indicated increasing expression level of phosphorylated survivin in PBMCs of BD patients. There was also a downregulation in phosphorylated survivin levels in plasma of BD patients.

Survivin modulatory role in autoimmune and autoinflammatory diseases.

Baculoviral IAP repeat containing 5 (BIRC5) gene encodes the important protein as survivin, a multifunctional protein, which is involved in cellular and molecular networks, progression of cell cycle, homeostasis, developmental morphogenesis, and apoptosis. The proximal BIRC5 promoter possesses specific binding sites for key transcription factors such as nuclear factor κB and signal transducer and activator of transcription 3. Upregulation of survivin exacerbates the autoimmune diseases (AIDs) including multiple sclerosis and myasthenia gravis by reducing the activity threshold of survivin-specific cytotoxic T cells. DNA damage along with upregulation or downregulation of survivin have been demonstrated in initiation and pathogenesis of cancers and AIDs. However, detailed mechanism of survivin function in pathogenesis of AIDs is not well understood. This review focuses on the structure, specificity, regulation, and function of survivin in physiologic conditions and pathogenesis of AIDs.

Antinociceptive Effect of Aqueous Extract of Origanum vulgare L. in Male Rats: Possible Involvement of the GABAergic System.

The objective of the present investigation was to assess the possible involvement of GABAergic mechanism in analgesic effect of aqueous extract of Origanum Vulgare (ORG) in a rat model of acute pain test. Sixty-three anaesthetized male Wistar rats (200-250 g) were cannulated into the left ventricle. Five to seven days after the recovery from surgery, ORG extract was intraventricularly injected at dose of 3 µg/rat i.c.v. Then, baclofen (10 mg/Kg, IP), CGP35348 (100 nmol/Kg, i.c.v), muscimol (1 mg/Kg IP) and bicuculline (5 mg/Kg IP) were separately injected 20 min before the injection of ORG. The experimental groups were compared with intact (control) group (n = 7). The response latency of rats to thermal stimulation was recorded using Tail-Flick test. Injection of ORG extract resulted in a significant and dose-dependent increase in the response latency. There was also a significant increase in the response latency after co-administration of ORG extract with baclofen when compared with control group. However, following co-administration of ORG extract/bicuculline, a significant decrease in the response latency was observed compared to control group. In conclusion, the results of the present study suggest that aqueous extract of Origanum vulgare L. ssp. viridis possesses antinociceptive activity in a dose-dependent manner and ORG-induced antinociception might be mediated, at least in part, by both GABA receptors.