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Summary Introduction: The main protease (Mpro) and the papain-like protease (PLpro) are essential for the replication of SARS-CoV-2. Both proteases can be targets for drugs acting against SARS-CoV-2. Objective: This paper aims to investigate the in silico activity of nine xanthophylls as inhibitors of Mpro and PLpro. Methods: The structures of Mpro (PDB-ID: 6LU7) and PLpro (PDB-ID: 6W9C) were obtained from RCSB Protein Data Bank and developed with BIOVIA Discovery Studio. Active sites of proteins were performed using CASTp. For docking the PyRx was used. Pharmacokinetic parameters of ADMET were evaluated using SwissADME and pkCSM. Results: β-cryptoxanthin exhibited the highest binding energy: –7.4 kcal/mol in the active site of Mpro. In PLpro active site, the highest binding energy had canthaxanthin of –9.4 kcal/mol, astaxanthin –9.3 kcal/mol, flavoxanthin –9.2 kcal/mol and violaxanthin –9.2 kcal/mol. ADMET studies presented lower toxicity of xanthophylls in comparison to ritonavir and ivermectin. Conclusion: Our findings suggest that xanthophylls can be used as potential inhibitors against SARS-CoV-2 main protease and papain-like protease.

Abstract Transporter associated with antigen processing 1 (TAP1) is a transporter protein that represent tumor antigen in the MHC I or HLA complex. Any defect in the TAP1 gene resulting in inadequate tumor tracking. TAP1 influences multidrug resistance (MDR) in human cancer cell lines and hinders the treatment during chemotherapeutic. The association of TAP1 in cancer progression remains mostly unknown and further study of the gene in relation with cancer need to conduct. Thus, the study has designed to analyze the association between the TAP1 with cancer by computationally. The expression pattern of the gene has determined by using ONCOMINE, GENT2, and GEPIA2 online platforms. The protein level of TAP1 was examined by the help of Human Protein Atlas. Samples with different clinical outcomes were investigated to evaluate the expression and promoter methylation in cancer vs. normal tissues by using UALCAN server. The copy number alteration, mutation frequency, and expression level of the gene in different cancer were analyzed by using cBioPortal server. The PrognoScan and KM plotter platforms were used to perform the survival analysis and represented graphically. Additionally, pathway and gene ontology (GO) features correlated to the TAP1 gene were analyzed and presented by bar charts. After arranging the data in a single panel like correlating expression to prognosis, mutational and alterations characteristic, and pathways analysis, we observed some interesting insights that emphasized the importance of the gene in cancer progression. The study found the relationship between the TAP1 expression pattern and prognosis in different cancer tissues and shows how TAP1 affects the clinical characteristics. The analytical data presented in the study is vital to learn about the effect of TAP1 in tumor tissue, where previously studies showing contradicting expression of TAP1 in cancer tissue. The analyzed data can also be utilized further to evade the threats against chemotherapy. Overall, the study provided a new aspect to consider the role of TAP1 gene in cancer progression and survival status. Key messages • This study demonstrated, for the first time, a correlation between the TAP1 gene and tumor progression. • An upregulation of TAP1 mRNA was demonstrated in various cancer types. • This study reported a significant negative correlation for TAP1 gene expression and the survival rate in different cancer types.

Introduction: Tragia involucrata L. have been utilized as traditional medicine in Indian subcontinent for the treatment of numerous illnesses such as inflammation, pain and skin infection. In this current study we sought to assess the anxiolytic, sedative and analgesic activity of Tragia involucrata L. leaves extract. Materials and methods: We first performed a phytochemical screening test of the leaves extracts following standard phytochemical screening protocols. We next examined the anxiolytic and sedative activity of crude methanol (TIME), ethyl acetate (TIEAE) and n-Hexane (TIHE) extract of Tragia involucrata L. leaves using mouse behavioral models such as elevated plus-maze test and pentobarbital-induced sleeping time test, respectively. Likewise, we evaluated the analgesic activity using acetic acid induced writhing test and formalin induced paw licking test. Additionally, we performed a quantitative analysis of heavy metals content of Tragia involucrata L. leaves by overnight digestion in concentrated nitric acid (HNO3). Results: Phytochemical screening demonstrated that TIME, TIEAE and TIHE contain flavonoids, alkaloids, tannins, phenols, terpenoids and sterols. Administration of these extracts resulted in higher number of open arm entry, lower number of close arm entry and higher time spent in open arm compared to control treatment (p < 0.05). Moreover, these treatments decreased the onset of sleep time and increased the duration of sleep compared to control treated mice (all p < 0.05). Likewise, extracts treated mice exhibited decreased number of writhing as well as lower acute phase and late phase duration compared to control treatment (all p < 0.05). The average level of As and Fe in Tragia involucrata L. leaves was 5.16 ± 0.012 ppm and 2.76 ± 0.015 ppm, respectively. Conclusion: Results from this study support that Tragia involucrata L. leaves extracts exhibit an anxiolytic, sedative and analgesic activity in mice.

Breast cancer (BC) is the most common type of invasive cancer diagnosed in women. It is the second leading cause of death from cancer and the utmost important medical concern women face today. Growth differentiation factor 10 (GDF10) is a member of the transforming growth factor β (TGF-β) superfamily and has been found to play a central role during the growth and differentiation of developing tissues. Recent studies have demonstrated the linkage between GDF10 and different types of cancer. But the relation of GDF10 expression in developing BC has not been established with concrete evidence. Therefore, we performed a multi-omics analysis to evaluate the potentiality of GDF10 as a therapeutic biomarker for human BC. We analyzed the mRNA expression patterns of GDF10 in BC subtypes using Oncomine, GEPIA2, immunohistochemistry, and UALCAN databases. Resultant data obtained from the analysis has provided clear evidence to the downregulation of GDF10 expression in BC subtypes. Additionally, three subsequent missense mutations were identified with a frequency of 0.62%–2.95% copy number alterations in the GDF10 protein sequence by analyzing 16 BCE studies from the cBioPortal database. Furthermore, the Kaplan-Meier plots revealed a positive correlation between the downregulation of GDF10 and the lower survival rate of the BC patients. The co-expressed genes profile of GDF10 was also associated with BC development. ABCA8 has been identified as the most positively co-expressed gene, which was confirmed by correlation analysis using bc-GenExMiner and UCSC Xena server. We also determined different cancer progression pathways mediated by GDF10 and its co-expressed genes by utilizing the Enrichr database. Cumulatively, the outcome data conclude that the down expression of GDF10 is associated with BC progression and patient's survival, which may serve as a therapeutic biomarker for treating BC.

Breast cancer ranked second among most frequent cancer in the world playing a significant role in mortality rate. Having prior knowledge on differentially expressed genes in breast cell carcinoma elucidated important indications to understand the molecular mechanism underneath breast carcinogenesis. In this study we have investigated the distinguished CSN1S1 expression in human breast cancer. We have analyzed CSN1S1 mRNA expression between cancer and normal tissues using TCGA datasets. Moreover, analysis including promoter methylation, mutations, prognosis, co-expression, gene ontology, and pathways of CSN1S1 were performed by the TCGA Wanderer, UCSC Xena, cBioPortal, PrognoScan, UALCAN, and Enricher server. We have observed low mRNA expression and high promoter methylation of CSN1S1 in cancer tissues compared to normal tissues. Furthermore, we have also identified low mRNA expression in clinicopathological patients, as well as 9 deleterious mutations with highly co-expressed protein MRC1, and significantly related signaling pathways. We have found a positive correlation between the lower expression of CSN1S1 and patients surviving with breast cancer. Here we have concluded that CSN1S1 acts as a biomarker for the surveillance and prognosis of breast cancer, and also works as a novel therapeutic target at the molecular and pathway levels., Highlights • Low transcriptional expression and low survival rate of CSN1S1 in breast cancer. • The investigation of clinical profiles and mutational positions of CSN1S1 in breast cancer. • The investigation of gene ontology and signaling pathway of CSN1S1 and their co-expressed genes. • We identified CSN1S1 and also their co-expressed proteins are the potential biomarkers in breast cancer.

Minichromosome maintenance protein 2 (MCM2) is a highly conserved protein from the MCM protein family that plays an important role in eukaryotic DNA replication as well as in cell cycle progression. In addition, it maintains the ploidy level consistency in eukaryotic cells, hence, mutations or alteration of this protein could result in the disintegration of the fine-tuned molecular machinery that can lead to uncontrolled cell proliferation. Moreover, MCM2 has been found to be an important marker for progression and prognosis in different cancers. Therefore, we aimed to analyze the MCM2 expression and the associated outcome in breast cancer (BC) patients based on the publicly available online databases. In this study, server-based gene expression analyses indicate the upregulation of MCM2 (p < 10−6; fold change>2.0) in various BC subtypes as compared to the respective normal tissues. Besides, the evaluation of histological sections from healthy and cancer tissues showed strong staining signals indicating higher expression of MCM2 protein. The overexpression of MCM2 was significantly correlated to promoter methylation and was related to patients' clinical features. Further, mutation analysis suggested missense as the predominant type of mutation (71.4%) with 18 copy-number alterations and 0.2% mutation frequency in the MCM2 gene. This study revealed a significant correlation (Cox p ≤ 0.05) between the higher MCM2 expression and lower patient survival. Finally, we identified the co-expressed genes with gene ontological features and signaling pathways associated in BC development. We believe that this study will provide a basis for MCM2 to be a significant biomarker for human BC prognosis., Data analysis; Information retrieval; Computational chemistry; Computational biology; Bioinformatics; Biocomputational method; Gene expression; Gene mutation; Gene regulation; Microarray; Cancer research; MCM2; Breast cancer; Mutation analysis; Prognostic biomarker; Transcriptional expressions