In silico study of polyphenols as potential inhibitors of MALT1 protein in non-Hodgkin lymphoma.

Non-Hodgkin lymphoma (NHL) is one of the most common cancer types. Deregulated signaling pathways can trigger certain NHL subtypes, including Diffuse Large B-cell lymphoma. NF-ĸB signaling pathway, which is responsible for the proliferation, growth, and survival of cells, has an essential role in lymphoma development. Although different signals control NF-ĸB activation in various lymphoid malignancies, the characteristic one is the CARD11-BCL10-MALT1 (CBM) complex. The CBM complex is responsible for the initiation of adaptive immune response. Our study is focused on the molecular docking of ten polyphenols as potential CARD11-BCL10-MALT1 complex inhibitors, essentially through MALT1 inhibition. Molecular docking was performed by Auto Dock Tools and AutoDock Vina tool, while SwissADME was used for drug-likeness and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of the ligands. Out of 66 ligands that were used in this study, we selected and visualized five. Selection criteria were based on the binding energy score and position of the ligands on the used protein. 2D and 3D visualizations showed interactions of ligands with the protein. Five ligands are considered potential inhibitors of MALT1, thus affecting NF-ĸB signaling pathway. However, additional in vivo and in vitro studies are required to confirm their mechanism of inhibition.

Investigation of miRNAs that are effective in the pathogenesis of asthma.

OBJECTIVES: Asthma is a complex disease characterized by inflammation of the airways, involving epigenetic changes, in which genetic and environmental factors act together. MicroRNAs as candidate biomarkers stand out as target molecules in the diagnosis and treatment of immunological and inflammatory diseases. Our aim of this study is to identify miRNAs that are thought to be effective in the pathogenesis of allergic asthma and to reveal candidate biomarkers associated with the disease. METHODS: Fifty patients, aged between 18-80 years, who were diagnosed with allergic asthma and 18 healthy volunteers were included in the study. After the collection 2 mL of total blood from volunteers, RNA isolation and cDNA synthesis were performed. For miRNA profile screening, expression analysis was performed by real-time PCR method using miScript miRNA PCR Array. GeneGlobe Data Analysis Center was used to evaluate dysregulated miRNAs. RESULTS: In the allergic asthma group, 9 (18%) of the patients were male and 41 (82%) of them were female. In the control group, 7 (38.89%) were male and 11 (61.1%) were female (P:0.073). As a result of the research, the expression levels of miR-142-5p, miR-376c-3p and miR-22-3p were down-regulated, while miR-27b-3p, miR-26b-5p, miR-15b-5p and miR-29c-3p detected as up-regulated. DISCUSSION: The results of our study suggest that miR142-5p, miR376c-3p and miR22-3p promote Ubiquitin-mediated proteolysis by inhibiting TGF-ß expression through a mechanism involving the p53 signaling pathway. The deregulated miRNAs may be used as a diagnostic and prognostic biomarker in asthma.

Structural and functional characterization of SARS-CoV-2 nucleocapsid protein mutations identified in Turkey by using in silico approaches.

Missense mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus may cause changes in the structure of proteins. The nucleocapsid (N) protein is an important target for drugs and vaccines. The main purpose of this study is to detect missense mutations in the SARS-CoV-2 N protein and to reveal the effects of these mutations on protein structure by using in silico approaches. 161 missense mutations of the N protein were determined in 2286 SARS-CoV-2 genomes derived from the GISAID EpiCoV database in the Turkish population. Identified 161 missense mutations were analyzed by using sequence and structure-based methods to predict effects of mutation on function and structure of SARS-CoV-2 N protein. These analyzes revealed that some mutations showed deleterious effects and change of stability and flexibility of nucleocapsid protein. D3L, S194L, S235F, and P13L (Omicron variant) mutations were further analyzed in our study due to their importance in the literature and in our results. Even though, our findings are essential for research of SARS-CoV-2 virus, in vitro and in vivo validations are necessary. Keywords: nucleocapsid protein; SARS-CoV-2; missense mutations; protein stability; protein flexibility.

A comprehensive in silico analysis of multiple sclerosis related non-synonymous SNPs and their potential effects on protein structure and function.

BACKGROUND: Multiple Sclerosis (MS) is an autoimmune and central nervous system disease characterized by an inflammatory demyelinating process in the brain. Although the exact cause of MS is still unclear, environmental, and genetic factors are known to play a role in the development of disease. New molecular markers must be identified to understand the mechanism of disease formation and progression. We investigated the effects of MS-related non-synonymous single-nucleotide polymorphisms (nsSNPs) on the structure and function of identified proteins in this study. METHODS: Missense variations associated with MS were extracted from the NHGRI-EBI GWAS database. Functional and structural analysis of nsSNPs on mapped genes was performed using g:Profiler, Wikipathway, KEGG, Reactome and Gene ontology programs (p < 0.05 was accepted statistically significant). Amino acid sequence-based analysis was performed to identify deleterious variants by using PROVEAN and PredictSNP tools. Finally, protein structure analyzes were performed on deleterious protein variants by DynaMut, Mutabind2 and Missense3D servers to identify changes in protein stability and flexibility. RESULTS: 10 target nsSNPs were identified. Among these rs34536443, rs10936599, rs2293152, rs11808092, rs1129183 were found deleterious according to amino acid sequence-based analysis. Furthermore, structure-based analyses show that TYK2 (P1104A), MYNN (H6Q), EVI5 (Q612H), and LZTFL1 (D246N) substitutions increase protein stability and decrease structure flexibility, whereas STAT3 (R426G) substitution decreases protein stability and increases structure flexibility. CONCLUSION: We revealed that identified nsSNPs have potential effects on stability and flexibility of the target proteins. The prominent target genes are thought to have significant impacts on the pathogenesis of MS. Further in vitro and in vivo studies are required to validate our in silico results.

Perceptions of students in health and molecular life sciences regarding pharmacogenomics and personalized medicine.

BACKGROUND: Increasing evidence is demonstrating that a patient's unique genetic profile can be used to detect the disease's onset, prevent its progression, and optimize its treatment. This led to the increased global efforts to implement personalized medicine (PM) and pharmacogenomics (PG) in clinical practice. Here we investigated the perceptions of students from different universities in Bosnia and Herzegovina (BH) towards PG/PM as well as related ethical, legal, and social implications (ELSI). This descriptive, cross-sectional study is based on the survey of 559 students from the Faculties of Medicine, Pharmacy, Health Studies, Genetics, and Bioengineering and other study programs. RESULTS: Our results showed that 50% of students heard about personal genome testing companies and 69% consider having a genetic test done. A majority of students (57%) agreed that PM represents a promising healthcare model, and 40% of students agreed that their study program is well designed for understanding PG/PM. This latter opinion seems to be particularly influenced by the field of study (7.23, CI 1.99-26.2, p = 0.003). Students with this opinion are also more willing to continue their postgraduate education in the PM (OR = 4.68, CI 2.59-8.47, p < 0.001). Furthermore, 45% of students are aware of different ethical aspects of genetic testing, with most of them (46%) being concerned about the patient's privacy. CONCLUSIONS: Our results indicate a positive attitude of biomedical students in Bosnia and Herzegovina towards genetic testing and personalized medicine. Importantly, our results emphasize the key importance of pharmacogenomic education for more efficient translation of precision medicine into clinical practice.