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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused COVID-19 disease in China. So far, no vaccine has licensed to protect against infection with COVID-19, therefore an effective COVID-19 vaccine needed. The aim of this study was to predict antigenic peptides of SARS-CoV-2 for designing the COVID-19 vaccine using immunoinformatic analysis. In this study, T and B-cell epitopes of S protein were predicted and screened based on the antigenicity, toxicity, allergenicity, and cross-reactivity with human proteomes. The epitopes were joined by the appropriate linker. LT-IIc as an adjuvant was attached to the end of the structure. The secondary and 3D structure of the vaccine was predicted. The refinement process was performed to improve the quality of the 3D model structure; the validation process is performed using the Ramachandran plot and ProSA z-score. The proposed vaccine's binding affinity to the HLA-A11:01 and HLA-DRB1_01:01 molecule was evaluated by molecular docking. Using molecular dynamics, the stability of vaccine-HLA complexes was also evaluated. Finally, in silico gene cloning was performed in the pET30a (+) vector. The findings suggest that the current vaccine may be a promising vaccine to prevent SARS-CoV-2 infection.

Background: Bromelain enhances anticancer impacts to chemotherapeutic agents. The question as to whether bromelain does promote in-vitro cytotoxic and proapoptotic effects of cisplatin on human prostatic carcinoma PC3 cell line was investigated. Materials and Methods: PC3 (human prostatic carcinoma) cells were treated either single or in combination with bromelain and/or cisplatin. MTT, clonogenic assay, flow cytometry and real-time quantitative polymerase chain reaction were used to investigate cell viability, colony formation, proapoptotic potential and p53 gene expression, respectively. Results: Cisplatin (IC10) combined with bromelain (IC40) significantly affected PC3 cell viability, inhibited colony formation, as well increased p53 proapoptotic gene expression compared to cisplatin single treatment. Nevertheless, bromelain-cisplatin chemoherbal combination did not display any additive proapoptotic effect compared to single treatments. Conclusion: Bromelain-cisplatin chemoherbal combination demonstrated synergistic in-vitro anticancer effect on human prostatic carcinoma cell line, PC3, that drastically reduced required cisplatin dose. [GMJ.2020;9:e1749]

Background: Combination therapy has been one of the most pioneering and strategic approaches implemented for malignancy treatment, which can intentionally influence multiple signaling pathways involved in cancer growth and progression. In the present study, the effects of 5-fluorouracil (5FU) in combination with everolimus (EVE) or lithium chloride (LiCl) were evaluated in 4T1 metastatic breast cancer cells and compared to control and each other. Methods and results: The resazurin assay, CompuSyn, flow cytometry, and real-time PCR were used to investigate cell proliferation, drug synergism, apoptosis, and gene expression. In comparison to the ternary combination of the drugs, the findings showed that cytotoxicity (p-value < 0.0001) and apoptosis (p-value < 0.0001) of two-by-two combinations increased dramatically as a consequence of the extreme synergy between 5FU and EVE or LiCl. Moreover, the hypoxia­inducible transcription factor 1-alpha (HIF-1α) and the vascular endothelial growth factor (VEGF) downregulated considerably compared to control (p-value < 0.0001) by combination therapies of EVE-5FU and 5FU-LiCl; however, only VEGF displayed significant downregulation in comparison to single therapies. Conclusion: The findings showed that the combination of 5FU-LiCl increased cell cytotoxicity and apoptosis significantly more than EVE-5FU but suggests a clinical potential for both to treat metastatic breast cancer encouraging validation of these results in pre-clinical models.

Background: Hepatocellular carcinoma (HCC) is a major worldwide health concern and is the third leading cause of cancer death. Recent studies have focused on the association between long non-coding RNAs (lncRNAs) and cancer, lncRNAs showed to have an important role in the prognosis, diagnostic, and investigation of liver cancer. Therefore, this study focuses on the expression profiles of HOTAIR, MALAT1, and UCA1 lncRNAs considering the clinicopathological characteristics of patients with liver tumors. Methods and Results: The expression profiles of HOTAIR, MALAT1, and UCA1 lncRNAs were evaluated using qRT-PCR in the paired liver tumor and the adjacent non-tumor samples. After RNA extraction from tissue samples, cDNA synthesis and the RT-qPCR method were performed. Livak method (2-ΔΔCt) was used for calculating the expression level of lncRNAs. Principal-component analyses followed by receiver operating characteristic (ROC) curve analyses were performed to evaluate the diagnostic potential of the selected lncRNAs. Our results showed that HOTAIR, MALAT1, and UCA1 were overexpressed significantly in patients with liver cancer compared to the healthy groups (P < 0.001). Moreover, the expression of HOTAIR was enhanced significantly compared to the expression of MALAT1 and UCA1 in patients with liver cancer (P < 0.001). This study showed that there were no significant associations between lncRNAs expression and the clinical characteristics (P > 0.05). Significantly elevated circulating lncRNAs were found to be liver cancer-specific and showed differentiation of liver cancer samples from the controls. Kaplan-Meier analysis revealed no significant correlations between the lncRNAs expression and overall survival. Conclusion: Based on our findings, the studied lncRNAs were not correlated with clinicopathological characteristics of the liver cancer patients although the overexpression of these lncRNAs might provide novel molecular biomarkers in HCC cases.