Biomedical Relevance of Novel Anticancer Peptides in the Sensitive Treatment of Cancer.

The global increase in cancer mortality and economic losses necessitates the cautious quest for therapeutic agents with compensatory advantages over conventional therapies. Anticancer peptides (ACPs) are a subset of host defense peptides, also known as antimicrobial peptides, which have emerged as therapeutic and diagnostic candidates due to several compensatory advantages over the non-specificity of the current treatment regimens. This review aimed to highlight the ravaging incidence of cancer, the use of ACPs in cancer treatment with their mechanisms, ACP discovery and delivery methods, and the limitations for their use. This would create awareness for identifying more ACPs with better specificity, accuracy and sensitivity towards the disease. It would also promote their efficacious utilization in biotechnology, medical sciences and molecular biology to ease the severity of the disease and enable the patients living with these conditions to develop an accommodating lifestyle.

The Relationship between Cadmium Toxicity and the Modulation of Epigenetic Traits in Plants.

Elevated concentrations of heavy metals such as cadmium (Cd) have a negative impact on staple crop production due to their ability to elicit cytotoxic and genotoxic effects on plants. In order to understand the relationship between Cd stress and plants in an effort to improve Cd tolerance, studies have identified genetic mechanisms which could be important for conferring stress tolerance. In recent years epigenetic studies have garnered much attention and hold great potential in both improving the understanding of Cd stress in plants as well as revealing candidate mechanisms for future work. This review describes some of the main epigenetic mechanisms involved in Cd stress responses. We summarize recent literature and data pertaining to chromatin remodeling, DNA methylation, histone acetylation and miRNAs in order to understand the role these epigenetic traits play in cadmium tolerance. The review aims to provide the framework for future studies where these epigenetic traits may be used in plant breeding and molecular studies in order to improve Cd tolerance.

Expression of cyclin-dependent kinases and their clinical significance with immune infiltrates could predict prognosis in colorectal cancer.

INTRODUCTION: Colorectal cancer (CRC) is one of the most cancer-related mortalities worldwide and remains a major public health issue. Despite several attempts to develop promising therapies for CRC, its survival rate decreases with metastasis. Cyclin-dependent kinases (CDKs) are a family of protein kinases with various regulatory activities including cell cycle, mRNA expression, transcription, and differentiation. Aside from their role in cell proliferation when mutated, abnormal expression of these genes has been reported in some human cancer subtypes. This study explored the roles and therapeutic potentials of CDK 1 and 4 as prognostic biomarkers in CRC. METHODS: Bioinformatics analyses were carried out to demonstrate the expression and prognostic values of CDK-1 and CDK-4 with immune infiltrate in CRC. DISCUSSION: CDK levels in CRC were remarkably higher than those in normal tissues (p < 0.05), and overexpression in CRC tissues was significantly related to nodal metastatic status (p < 0.05) and histological subtypes. Kaplan-Meier analyses showed that patients with CRC who exhibited CDK-1 overexpression had worse overall survival (OS) as against patients with CDK-4 overexpression. The alteration observed was a mutation while the mutation hotspots include E163* and R24A/C/H/L respectively for CDK-1 and CDK-4 on the Pkinase domain. Of the associated genes, AURKA and RB1 were predominantly altered. Furthermore, CDK-4 is positively correlated with tumor purity in both COAD and READ while CDK-1is only positively correlated in COAD. CDK-1 overexpression was significantly associated with poor prognosis as opposed to CDK-4. CONCLUSION: The expression and prognostic values of AURKA and RB1 may also be significant to CRC diagnosis. CDKs together with the co-expressed genes and their association with immune infiltrates may serve as target molecules for immunotherapy in CRC.

Structural and Molecular Docking Analytical Studies of the Predicted Ligand Binding Sites of Cadherin-1 in Cancer Prognostics.

INTRODUCTION: Several studies have explored the design of antimicrobial peptides (AMPs) for the development of therapeutic and diagnostic molecules for the treatment and identification of pathogenic diseases as well as cancer. Human cadherin-1 protein has been identified to be involved in adhesion-mediated signalling pathways in normal cells and its loss through genetic and epigenetic alterations can result in an enhanced invasion and metastasis of malignancy in tumours. Therefore, the identification of cadherin during treatment of cancer can be used as prognostic biomarker to establish the responsiveness of patients to treatment regimen. Antimicrobial peptides (AMPs) offer several compensatory advantages in biomedical applications and have been used for treatment of diseases, dietary supplements and diagnosis of diseases. The aim of this research work was to use in silico approaches to analyse retrieved human cadherin-1 as prognostic targets in cancer treatments using modelled putative anticancer AMPs. METHODS: The structures of the putative AMPs and cadherin-1 were modelled using I-TASSER server and the protein overall quality was validated using PROCHECK. Thereafter, the protein motifs were predicted and the molecular interaction between the putative anticancer AMPs and protein was carried out using PatchDock. RESULTS: The results revealed that all the AMPs were good prognostic molecules for cancer with BOO1 having the highest binding affinity of 15,874. CONCLUSION: This study revealed that all the generated AMPs have good prognostic value for monitoring the progress of cancer treatment using human cadherin-1 as receptor. This is the first report where AMPs were used in prognostics of cancer using human cadherin-1.

Understanding the epidemiology, pathophysiology, diagnosis and management of SARS-CoV-2.

The emergence of coronavirus disease 2019 (COVID-19) in December 2019 has resulted in over 20 million cases and 741,808 deaths globally, affecting more than 200 countries. COVID-19 was declared a pandemic on 11 March 2020 by the World Health Organization. The disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). There is limited information on COVID-19, and treatment has so far focused on supportive care and use of repurposed drugs. COVID-19 can be transmitted via person-to-person contact through droplet spread. Some of the recommended precautionary measures to reduce the rate of disease spread include social distancing, good hygiene practices, and avoidance of crowded areas. These measures are effective because the droplets are heavy and can only travel approximately 1 meter in the air, settling quickly on fixed surfaces. Promising strategies to combat SARS-CoV-2 include discovery of therapeutic targets/drugs and vaccines. In this review, we summarize the epidemiology, pathophysiology, and diagnosis of COVID-19. We also address the mechanisms of action of approved repurposed drugs for therapeutic management of the disease.

Genomic profiling of microRNA target genes in colorectal cancer.

Colorectal cancer is the second and third most common cancer in men and women, respectively, worldwide. Alterations such as genetic and epigenetic are common in colorectal cancer and are the basis of tumor formation. The exploration of the molecular basis of colorectal cancer can drive a better understanding of the disease as well as guide the prognosis, therapeutics, and disease management. This study is aimed at investigating the genetic mutation profile of five candidate microRNAs (hsa-miR-513b-3p, hsa-miR-500b-3p, hsa-miR-500a-3p, hsa-miR-450b-3p, hsa-miR-193a-5p) targeted by seven genes (APC, KRAS, TCF7L2, EGFR, IGF1R, CASP8, and GNAS)) using in silico approaches. Two datasets (dataset 1 from our previous study and dataset two (The Cancer Genome Atlas, Nature 2012) were considered for this study. Protein-protein interaction, expression analysis, and genetic profiling were carried out using STRING, FireBrowse, and cBioPortal, respectively. Protein-protein interaction network showed that epidermal growth factor receptor has the highest connection among the target genes and this can be considered as the hub gene. Relative to other solid tumors, in colorectal cancer, six of the target genes were downregulated and only CASP8 was upregulated. Genes with protein tyrosine kinases domain were frequently altered in colorectal cancer and the most common alteration in these genes/domain are missense mutation. These results could serve as a lead in the identification of driver genes responsible for colorectal cancer initiation and progression. However, the intense mechanism of these results remains unclear and further experimental validation and molecular approaches are the focal points in the nearest future.

Gene Expression Alterations and Molecular Analysis of CHEK1 in Solid Tumors.

Alterations in the Checkpoint kinase (CHEK1) gene, its regulation, and the possible clinical outcomes in human solid tumors have not been previously examined. Therefore, the present study was carried out to evaluate the expression of CHEK1 in solid tumors as well as the mechanism by which it can be regulated through non-coding RNAs. The expression of CHEK1 was investigated using Oncomine analysis. cBioPortal, Kaplan-Meier Plotter, and PrognoScan were performed to identify the prognostic roles of this gene in solid tumors. The copy number alteration, mutation, interactive analysis, and visualization of the altered networks were performed by cBioPortal. The molecular binding analysis was carried out by Schrodinger suite, PATCHDOCK, and discovery studio visualizer. The study demonstrated that the CHEK1 gene was differentially expressed in four different cancers, and that reduced CHEK1 mRNA expression is an unfavorable prognostic factor for patients with gastric and colorectal cancer. The molecular docking results showed that the CHEK1 gene can be regulated by microRNAs (miR-195-5p) due to the number of stable hydrogen atoms observed within the distance of 2.0 Å and the favorable amino acids (Ala221, Ile353, Ile365, Ile756, Val797, Val70, Val154, Ile159, Val347, Tyr804, Phe811, Tyr815, and Phe156) identified in the binding pocket of the argonaute protein. Due to the possibility of CHEK1's involvement in solid tumors, it may potentially be a target for therapeutic intervention in cancer. Further studies into the interaction between CHEK1 and other co-expressed genes may give further insight into other modes of regulation of this gene in cancer patients.