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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.

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Here, we have investigated the therapeutic potency of EW-7197, a transforming growth factor-β type I receptor kinase inhibitor, against postsurgical adhesion band formation. Our results showed that this pharmacological inhibitor prevented the frequency and the stability of adhesion bands in mice model. We have also shown that downregulation of proinflammatory cytokines, reduce submucosal edema, attenuation of proinflammatory cell infiltration, inhibition of oxidative stress, decrease in excessive collagen deposition, and suppression of profibrotic genes at the site of surgery are some of the mechanisms by which EW-7197 elicits its protective responses against adhesion band formation. These results clearly suggest that EW-7197 has novel therapeutic properties against postsurgical adhesion band formation with clinically translational potential of inhibiting key pathological responses of inflammation and fibrosis in postsurgery patients. K E Y W O R D S EW-7197, fibrosis, inflammation, postsurgical adhesion band formation, TGF-β signaling *Atena Soleimani and Fereshteh Asgharzadeh contributed equally to this study.

: The MAPK/ERK signaling pathway regulates cancer cell proliferation, apoptosis, inflammation, angiogenesis, metastasis and drug resistance. Mutations and up-regulation of components of the MAPK/ERK signaling pathway, as well as over-activation of this critical signaling pathway, are frequently observed in colorectal carcinomas. Targeting the MAPK/ERK signaling pathway, using specific pharmacological inhibitors, elicits potent anti-tumor effects, supporting the therapeutic potential of these inhibitors in the treatment of CRC. Several drugs have recently been developed for the inhibition of the MEK/ERK pathway in preclinical and clinical settings, such as MEK162 and MK-2206. MEK1/2 inhibitors demonstrate promising efficacy and anticancer activity for the treatment of this malignancy. This review summarizes the current knowledge on the role of the MAPK/ERK signaling pathway in the pathogenesis of CRC and the potential clinical value of synthetic inhibitors of this pathway in preventing CRC progression for a better understanding, and hence, better management of colorectal cancer.

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Brain trauma is an important cause of mortality and disability among young people worldwide. One of the mechanisms of post-traumatic secondary brain damage is related to free radical release and oxidative stress (OS). OS is the consequence of an imbalance between pro-oxidants and antioxidants in favor of pro-oxidants. This imbalance may lead to macromolecule damage including lipid peroxidation, protein crosslinking, DNA damage and changes in growth and function of cells in brain. Free radical release and subsequent lipid peroxidation are early events following neural tissues injury and are associated with hypo-perfusion, edema, and disruption of axonal guidance. In this study, we determined the prooxidant-antioxidant balance (PAB) in patients with brain injury, and its correlation with number of demographic and clinical parameters. Sera from 98 patients with traumatic brain and 100 healthy subjects were collected. The serum PAB was measured. Age, sex, GCS (Glasgow coma scale), mechanism of injury, brain lesions found on CT scan and lesions in other parts of the body, caused by trauma, were determined. A significantly higher PAB value was observed in the patient group (138.97 ± 15.9 HK unit) compared to the controls (60.82 ± 12.6 HK) (P = 0.001). In the patient group, there was no significant correlation of PAB with GCS, brain lesion characteristic, mechanism of injury, other accompanying traumatic injury, age and gender. When patients were classified into three groups according to GCS: group 1 (GCS>13, n = 28, PAB serum value = 138.51 ± 62.66 HK), group 2 (GCS between 8 and 12, n = 29, PAB serum value = 162.7 ± 50.6 HK) and group 3 (GCS <8, n = 41, PAB serum value = 155.56 ± 58.21 HK); there was no significant difference between groups. The serum PAB values were higher in patients with traumatic brain injury, although this was not associated with the extent of injury.

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