Spike Protein Mutations and the Effects on SARS-CoV-2 Pathogenesis

The severe acute respiratory syndrome coronavirus 2 spike (S) glycoprotein facilitates receptor binding to initiate cell entry that is the critical initial step in the infection cycle. Due to S glycoprotein's pivotal role, in this review, we pointed to show potential functional and structural consequences of S glycoprotein and its variants, which has been related with increased viral load in humans with SARS-CoV-2 infection

Nanocomposite scaffolds for accelerating chronic wound healing by enhancing angiogenesis

Skin is the body�s first barrier against external pathogens that maintains the homeostasis of the body. Any serious damage to the skin could have an impact on human health and quality of life. Tissue engineering aims to improve the quality of damaged tissue regeneration. One of the most effective treatments for skin tissue regeneration is to improve angiogenesis during the healing period. Over the last decade, there has been an impressive growth of new potential applications for nanobiomaterials in tissue engineering. Various approaches have been developed to improve the rate and quality of the healing process using angiogenic nanomaterials. In this review, we focused on molecular mechanisms and key factors in angiogenesis, the role of nanobiomaterials in angiogenesis, and scaffold-based tissue engineering approaches for accelerated wound healing based on improved angiogenesis.Figure not available: see fulltext

Nanocomposite scaffolds for accelerating chronic wound healing by enhancing angiogenesis

Skin is the body�s first barrier against external pathogens that maintains the homeostasis of the body. Any serious damage to the skin could have an impact on human health and quality of life. Tissue engineering aims to improve the quality of damaged tissue regeneration. One of the most effective treatments for skin tissue regeneration is to improve angiogenesis during the healing period. Over the last decade, there has been an impressive growth of new potential applications for nanobiomaterials in tissue engineering. Various approaches have been developed to improve the rate and quality of the healing process using angiogenic nanomaterials. In this review, we focused on molecular mechanisms and key factors in angiogenesis, the role of nanobiomaterials in angiogenesis, and scaffold-based tissue engineering approaches for accelerated wound healing based on improved angiogenesis.Figure not available: see fulltext

Serum levels of IL-37 and correlation with inflammatory cytokines and clinical outcomes in patients with coronary artery disease

Coronary artery disease (CAD) due to atherosclerosis is one of the important reasons for death worldwide. Recent evidence has suggested the essential role of inflammation in the progression of atherosclerosis. Interleukin (IL)-37 is a critical anti-inflammatory member of the IL-1 family which regulates the inflammatory processes. The aim of this study was to compare the serum levels of IL-37 in patients with CAD compared with the control group and its correlation with oxidative stress, cholesterol homeostasis, and inflammation in patients with CAD. A total of 42 patients with CAD and 42 sex-matched and age- matched controls who underwent coronary angiography were included in this study. The serum levels of IL-37 were evaluated via ELISA. Serum levels of biochemical risk factors were determined by enzymatic methods. Serum levels of IL-37 in the CAD group subjects were significantly lower than in the control group and IL-37 was significantly increased in men with CAD than in women with CAD. IL-37 significantly had an inverse correlation with IL-6, tumor necrosis factor-alpha, IL-32, high-sensitivity C reactive protein, oxidized low-density lipoprotein, and malondialdehyde. Also, IL-37 had a significantly positive correlation with ferric-reducing antioxidant power (FRAP) assay. In addition, IL-37 has positively correlated with ATP-binding cassette transporter A1 and G1 gene expression in peripheral blood mononuclear cells and serum levels of the FRAP. A receiver operating characteristic test displayed that IL-37 level ratios were a relatively significant CAD predictor. Our results indicated that decreased serum levels of IL-37 in patients with CAD and its relationship with inflammatory cytokines and reverse cholesterol transport genes are more likely to be associated in the inflammatory process with disease pathology

In silico design of a multi-epitope vaccine against HPV16/18

Background Cervical cancer is the fourth most common cancer affecting women and is caused by human Papillomavirus (HPV) infections that are sexually transmitted. There are currently commercially available prophylactic vaccines that have been shown to protect vaccinated individuals against HPV infections, however, these vaccines have no therapeutic effects for those who are previously infected with the virus. The current study's aim was to use immunoinformatics to develop a multi-epitope vaccine with therapeutic potential against cervical cancer. Results In this study, T-cell epitopes from E5 and E7 proteins of HPV16/18 were predicted. These epitopes were evaluated and chosen based on their antigenicity, allergenicity, toxicity, and induction of IFN-gamma production (only in helper T lymphocytes). Then, the selected epitopes were sequentially linked by appropriate linkers. In addition, a C-terminal fragment of Mycobacterium tuberculosis heat shock protein 70 (HSP70) was used as an adjuvant for the vaccine construct. The physicochemical parameters of the vaccine construct were acceptable. Furthermore, the vaccine was soluble, highly antigenic, and non-allergenic. The vaccine's 3D model was predicted, and the structural improvement after refinement was confirmed using the Ramachandran plot and ProSA-web. The vaccine's B-cell epitopes were predicted. Molecular docking analysis showed that the vaccine's refined 3D model had a strong interaction with the Toll-like receptor 4. The structural stability of the vaccine construct was confirmed by molecular dynamics simulation. Codon adaptation was performed in order to achieve efficient vaccine expression in Escherichia coli strain K12 (E. coli). Subsequently, in silico cloning of the multi-epitope vaccine was conducted into pET-28a ( +) expression vector. Conclusions According to the results of bioinformatics analyses, the multi-epitope vaccine is structurally stable, as well as a non-allergic and non-toxic antigen. However, in vitro and in vivo studies are needed to validate the vaccine's efficacy and safety. If satisfactory results are obtained from in vitro and in vivo studies, the vaccine designed in this study may be effective as a therapeutic vaccine against cervical cancer

Exploring SARS-COV-2 structural proteins to design a multi-epitope vaccine using immunoinformatics approach: An in silico study

In December 2019, a new virus called SARS-CoV-2 was reported in China and quickly spread to other parts of the world. The development of SARS-COV-2 vaccines has recently received much attention from numerous researchers. The present study aims to design an effective multi-epitope vaccine against SARS-COV-2 using the reverse vaccinology method. In this regard, structural proteins from SARS-COV-2, including the spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins, were selected as target antigens for epitope prediction. A total of five helper T lymphocytes (HTL) and five cytotoxic T lymphocytes (CTL) epitopes were selected after screening the predicted epitopes for antigenicity, allergenicity, and toxicity. Subsequently, the selected HTL and CTL epitopes were fused via flexible linkers. Next, the cholera toxin B-subunit (CTxB) as an adjuvant was linked to the N-terminal of the chimeric structure. The proposed vaccine was analyzed for the properties of physicochemical, antigenicity, and allergenicity. The 3D model of the vaccine construct was predicted and docked with the Toll-like receptor 4 (TLR4). The molecular dynamics (MD) simulation was performed to evaluate the stable interactions between the vaccine construct and TLR4. The immune simulation was also conducted to explore the immune responses induced by the vaccine. Finally, in silico cloning of the vaccine construct into the pET-28 (+) vector was conducted. The results obtained from all bioinformatics analysis stages were satisfactory; however, in vitro and in vivo tests are essential to validate these results

Designing a novel multi‑epitope vaccine against Ebola virus using reverse vaccinology approach

Ebola virus (EBOV) is a dangerous zoonotic infectious disease. To date, more than 25 EBOV outbreaks have been documented, the majority of which have occurred in Central Africa. The rVSVG-ZEBOV-GP vaccine (ERVEBO), a live attenuated vaccine, has been approved by the US Food and Drug Administration (FDA) to combat EBOV. Because of the several drawbacks of live attenuated vaccines, multi-epitope vaccines probably appear to be safer than live attenuated vaccines. In this work, we employed immunoinformatics tools to design a multi-epitope vaccine against EBOV. We collected sequences of VP35, VP24, VP30, VP40, GP, and NP proteins from the NCBI database. T-cell and linear B-cell epitopes from target proteins were identified and tested for antigenicity, toxicity, allergenicity, and conservancy. The selected epitopes were then linked together in the vaccine's primary structure using appropriate linkers, and the 50S ribosomal L7/L12 (Locus RL7 MYCTU) sequence was added as an adjuvant to the vaccine construct's N-terminal. The physicochemical, antigenicity, and allergenicity parameters of the vaccine were all found to be satisfactory. The 3D model of the vaccine was predicted, refined, and validated. The vaccine construct had a stable and strong interaction with toll-like receptor 4 (TLR4) based on molecular docking and molecular dynamic simulation (MD) analysis. The results of codon optimization and in silico cloning revealed that the proposed vaccine was highly expressed in Escherichia coli (E. coli). The findings of this study are promising; however, experimental validations should be carried out to confirm these findings

A review on insights and lessons from COVID-19 to the prevent of monkeypox pandemic

Re-emerging of monkeypox virus (MPXV), a neglected viral zoonotic disease, is a potential global threat. In the current COVID-19 pandemic status, the increasing reporting of positive cases of human MPXV in most countries of the world is a major reason for concern. This paper aims to describe the insights and lessons from COVID-19 pandemic in preventing the impending danger MPXV. In order to prevent further outbreak of disease, identify and control of MPXV transmission routes is necessary. Public health authorities should be vigilant and applied of effective strategies to mitigate the potential spread of MPXV. To address research gaps related to MPX outbreaks, national, regional, and international collaborations are required in time. Finally, the lessons and insights put forward point to the fact that, like the COVID-19 pandemic, people's health by and large depends on the decisions of government officials and people must continue to adhere to health principles. Hence, governments and policymakers must take appropriate precautionary measures to prevent similar crises like COVID-19 in the world

Biopolymer-based scaffolds for corneal stromal regeneration: A review

The stroma is one of the 5 layers of the cornea that comprises more than 90% of the corneal thickness, and is the most important layer for the transparency of cornea and refractive function critical for vision. Any significant damage to this layer may lead to corneal blindness. Corneal blindness refers to loss of vision or blindness caused by corneal diseases or damage, which is the 4th most common cause of blindness worldwide. Different approaches are used to treat these patients. Severe corneal damage is traditionally treated by transplantation of a donor cornea or implantation of an artificial cornea. Other alternative approaches, such as cell/stem cell therapy, drug/gene delivery and tissue engineering, are currently promising in the regeneration of damaged cornea. The aim of tissue engineering is to functionally repair and regenerate damaged cornea using scaffolds with or without cells and growth factors. Among the different types of scaffolds, polymer-based scaffolds have shown great potential for corneal stromal regeneration. In this paper, the most recent findings of corneal stromal tissue engineering are reviewed

Stem cell-based therapeutic strategies for corneal epithelium regeneration

Any significant loss of vision or blindness caused by corneal damages is referred to as corneal blindness. Corneal blindness is the fourth most common cause of blindness worldwide, representing more than 5 of the total blind population. Currently, corneal transplantation is used to treat many corneal diseases. In some cases, implantation of artificial cornea (keratoprosthesis) is suggested after a patient has had a donor corneal transplant failure. The shortage of donors and the side effects of keratoprosthesis are limiting these approaches. Recently, researchers have been actively pursuing new approaches for corneal regeneration because of these limitations. Nowadays, tissue engineering of different corneal layers (epithelium, stroma, endothelium, or full thickness tissue) is a promising approach that has attracted a great deal of interest from researchers and focuses on regenerative strategies using different cell sources and biomaterials. Various sources of corneal and non-corneal stem cells have shown significant advantages for corneal epithelium regeneration applications. Pluripotent stem cells (embryonic stem cells and iPS cells), epithelial stem cells (derived from oral mucus, amniotic membrane, epidermis and hair follicle), mesenchymal stem cells (bone marrow, adipose-derived, amniotic membrane, placenta, umbilical cord), and neural crest origin stem cells (dental pulp stem cells) are the most promising sources in this regard. These cells could also be used in combination with natural or synthetic scaffolds to improve the efficacy of the therapeutic approach. As the ocular surface is exposed to external damage, the number of studies on regeneration of the corneal epithelium is rising. In this paper, we reviewed the stem cell-based strategies for corneal epithelium regeneration