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Human diseases have been a critical threat from the beginning of human history. Knowing the origin, course of action and treatment of any disease state is essential. A microscopic approach to the molecular field is a more coherent and accurate way to explore the mechanism, progression, and therapy with the introduction and evolution of technology than a macroscopic approach. Non-coding RNAs (ncRNAs) play increasingly important roles in detecting, developing, and treating all abnormalities related to physiology, pathology, genetics, epigenetics, cancer, and developmental diseases. Noncoding RNAs are becoming increasingly crucial as powerful, multipurpose regulators of all biological processes. Parallel to this, a rising amount of scientific information has revealed links between abnormal noncoding RNA expression and human disorders. Numerous non-coding transcripts with unknown functions have been found in addition to advancements in RNA-sequencing methods. Non-coding linear RNAs come in a variety of forms, including circular RNAs with a continuous closed loop (circRNA), long non-coding RNAs (lncRNA), and microRNAs (miRNA). This comprises specific information on their biogenesis, mode of action, physiological function, and significance concerning disease (such as cancer or cardiovascular diseases and others). This study review focuses on non-coding RNA as specific biomarkers and novel therapeutic targets. [ABSTRACT FROM AUTHOR]

Some individuals with non-small-cell lung cancer (NSCLC) benefit from therapies targeting epidermal growth factor receptor (EGFR), and the characterization of a new mechanism of resistance to the EGFR-specific antibody gefitinib will provide valuable insight into how therapeutic strategies might be designed to overcome this particular resistance mechanism. The G719S and T790M mutations and their combination were involved in causing different conformational redistribution of EGFR. In the present computational study, we analyzed the impact and structural influence of G719S/T790M double mutation (DM) in EGFR with ligand (gefitinib) through molecular dynamic simulation (50 ns) and docking analysis. We observed the escalation in distance between the functional loop and activation loop with respect to T790M mutation compared to the G719S mutation. Furthermore, we confirmed that the G719S mutation causes the ligand to move closer to the hinge region, whereas T790M makes the ligand escape from the binding pocket. Obtained results provide with an explanation for the resistance induced by T790M and a vital clue for the design of drugs to combat gefitinib resistance. [ABSTRACT FROM AUTHOR]

Single nucleotide polymorphisms (SNPs) are the most common type of genetic variations in humans. Understanding the functions of SNPs can greatly help to understand the genetics of the human phenotype variation and especially the genetic basis of human complex diseases. The method to identify functional SNPs from a pool, containing both functional and neutral SNPs is challenging by experimental protocols. To explore possible relationships between genetic mutation and phenotypic variation, different computational algorithm tools like Sorting Intolerant from Tolerant, Polymorphism Phenotyping, UTRscan, FASTSNP, and PupaSuite were used for prioritization of high-risk SNPs in coding region (exonic nonsynonymous SNPs) and noncoding regions (intronic and exonic 5’ and 3’-untranslated region (UTR) SNPs). In this work, we have analyzed the SNPs that can alter the expression and function of transcriptional factor TP53 as a pipeline and for providing a guide to experimental work. We identified the possible mutations and proposed modeled structure for the mutant proteins and compared them with the native protein. These nsSNPs play a critical role in cancer association studies aiming to explain the disparity in cancer treatment responses as well as to improve the effectiveness of the cancer treatments. Our results endorse the study with in vivo experimental protocols. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis (MPS) IIIA, also known as Sanfilippo syndrome type A, is a severe, progressive disease that affects the central nervous system (CNS). MPS IIIA is inherited in an autosomal recessive manner and is caused by a deficiency in the lysosomal enzyme sulfamidase, which is required for the degradation of heparan sulfate. The sulfamidase is produced by the N-sulphoglucosamine sulphohydrolase (SGSH) gene. In MPS IIIA patients, the excess of lysosomal storage of heparan sulfate often leads to mental retardation, hyperactive behavior, and connective tissue impairments, which occur due to various known missense mutations in the SGSH, leading to protein dysfunction. In this study, we focused on three mutations (R74C, S66W, and R245H) based on in silico pathogenic, conservation, and stability prediction tool studies. The three mutations were further subjected to molecular dynamic simulation (MDS) analysis using GROMACS simulation software to observe the structural changes they induced, and all the mutants exhibited maximum deviation patterns compared with the native protein. Conformational changes were observed in the mutants based on various geometrical parameters, such as conformational stability, fluctuation, and compactness, followed by hydrogen bonding, physicochemical properties, principal component analysis (PCA), and salt bridge analyses, which further validated the underlying cause of the protein instability. Additionally, secondary structure and surrounding amino acid analyses further confirmed the above results indicating the loss of protein function in the mutants compared with the native protein. The present results reveal the effects of three mutations on the enzymatic activity of sulfamidase, providing a molecular explanation for the cause of the disease. Thus, this study allows for a better understanding of the effect of SGSH mutations through the use of various computational approaches in terms of both structure and functions and provides a platform for the development of therapeutic drugs and potential disease treatments. [ABSTRACT FROM AUTHOR]

A systematic search was implemented using four literature databases (PubMed, Embase, Science Direct and Web of Science) to capture all the causative mutations of Glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDD) in the 22 Arab countries. Our search yielded 43 studies that captured 33 mutations (23 missense, one silent, two deletions, and seven intronic mutations), in 3,430 Arab patients with G6PDD. The 23 missense mutations were then subjected to phenotypic classification using in silico prediction tools, which were compared to the WHO pathogenicity scale as a reference. These in silico tools were tested for their predicting efficiency using rigorous statistical analyses. Of the 23 missense mutations, p.S188F, p.I48T, p.N126D, and p.V68M, were identified as the most common mutations among Arab populations, but were not unique to the Arab world, interestingly, our search strategy found four other mutations (p.N135T, p.S179N, p.R246L, and p.Q307P) that are unique to Arabs. These mutations were exposed to structural analysis and molecular dynamics simulation analysis (MDSA), which predicting these mutant forms as potentially affect the enzyme function. The combination of the MDSA, structural analysis, and in silico predictions and statistical tools we used will provide a platform for future prediction accuracy for the pathogenicity of genetic mutations. [ABSTRACT FROM AUTHOR]

In this work we have analyzed the genetic variation that can alter the expression and the function of the VHL gene using computational methods. Of 110 single nucleotide polymorphisms (SNPs), 33 were found to be nonsynonymous (nsSNPs) and 23 SNPs were found in untranslated regions. Of the 33 nsSNPs investigated, 36.3% were found to be deleterious by both SIFT and PolyPhen servers. An untranslated region (UTR) resource tool suggested that two SNPs in the 5′ UTR region and six SNPs in the 3′ UTR region might change the protein expression levels. It was found by both SIFT and PolyPhen servers that a mutation from histidine to arginine at position 115 of the native protein of the VHL gene was most deleterious. A structural analysis of this mutated protein and the native protein was performed and had a root mean square deviation (RMSD) of 2.78 Å. Based on this work, we propose that the nsSNP with a SNPid of rs5030812 is an important candidate for the cause of von Hippel–Lindau syndrome via the VHL gene. [ABSTRACT FROM AUTHOR]

The rise of pollution due to the dye industries and textile wastes are evolving rapidly every day. The dyes are used in different trade names by the textile industries. The actual chemistry of dye is vague and difficult to understand even today though we are equipped technically. The toxic effects of the dyes and the reasons behind the acute toxicity are also an undiscovered mystery; therefore, no effective measures can be employed to degrade dyes. Deploying physical or chemical methods to pre-treat the azo dyes are expensive, extremely energy-consuming, and are not environment friendly. Hence, the use of microbes for textile dye degradation will be eco-friendly and is probably a cost-effective alternative to physicochemical methods. The present study was conducted to investigate the degradation of azo dyes isolated from textile effluent contaminated soil by employing the bacterial strains for degradation. The bacterial strains could degrade the optimum concentration of mixed azo dyes (200 mg/L) with an incubation up to 5 days. The decolourization of the dyes was expressed in terms of percentage of decolourization, and was found that about 87.35% of degradation by Bacillus subtilis strain. The enzyme responsible was analyzed as intracellular azoreductase involved in the degradation of mixed azo dyes. The enzymatic pathway and 1-phenyl-2–4(4-methyl phenyl)-diazene 1-oxide was observed as the major metabolite by GC–MS analysis. The in silico study determined the binding of mixed azo dye with azoreductase and hypothesized that their linking could be the main reason for the degradation of mixed azo dye. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) are pivotal for cancer cell migration and metastasis which are generally over-expressed in such cell types. Many drugs targeting MMPs do so by binding to the conserved catalytic domains and thus exhibit poor selectivity due to domain-similarities with other proteases. We report herein the binding of a novel compound [3-(E-3,4-dihydroxycinnamaoyloxyl)-2-hydroxypropyl 9Z, 12Z-octadeca-9, 12-dienoate; Mol. wt: 516.67 Da], (C1), isolated from a seagrass, Cymodocea serrulata to the unconserved hemopexin-like (PEX) domain of MMP2 (− 9.258 kcal/mol). MD simulations for 25 ns, suggest stable ligand-target binding. In addition, C1 killed an ovarian cancer cell line, PA1 at IC50: 5.8 μM (lesser than Doxorubicin: 8.6 µM) and formed micronuclei, apoptotic bodies and nucleoplasmic bridges whilst causing DNA laddering, S and G2/M phase dual arrests and MMP disturbance, suggesting intrinsic apoptosis. The molecule increased mRNA transcripts of BAX and BAD and down-regulated cell survival genes, Bcl-xL, Bcl-2, MMP2 and MMP9. The chemical and structural details of C1 were deduced through FT-IR, GC–MS, ESI–MS, 1H and 13C NMR [both 1D and 2D] spectra. [ABSTRACT FROM AUTHOR]

The effect of salt stress on pigment synthesis and antioxidant enzyme activity as well as in the genes involved in the biosynthetic pathway of bixin was studied. The 14-day germinated seedlings of Bixa orellana were induced into the various NaCl concentration (0, 25, 50, 75, 100 mM). After 45 days, leaves were taken for pigment analysis, antioxidant assays, and gene expression analysis to study the response of salt stress. The pigment content such as chlorophyll level was increased upon salt stress with a reduction in total carotenoid clearly indicating the adaptability of plants towards the stressed state. The level of β-carotene was increased in the highest concentration of salt stress treatment. The secondary metabolites such as bixin and abscisic acid (ABA) content were also high in elevated concentration of salt-treated seedling than control. The antioxidant enzyme activity was increased with the highest dose of salt stress suggesting the antioxidant enzymes to protect the plant from the deleterious effects. The mRNA transcript gene of the carotenoid biosynthetic pathway such as phytoene synthase (PSY), 1-deoxyxylulose-5-phosphate synthase (DXS), phytoene desaturase (PDS), beta-lycopene cyclase (LCY-β), epsilon lycopene cyclase (LCY-ε), carboxyl methyl transferase (CMT), aldehyde dehydrogenase (ADH), lycopene cleavage dioxygenase (LCD), and carotenoid cleavage dioxygenase (CCD) showed differential expression pattern under salt stress. In addendum, we studied the co-expression network analysis of gene to assess the co-related genes associated in the biosynthesis pathway of carotenoid. From the co-expression analysis result showed, the LCY, PDS, and PSY genes were closely correlated with other genes. These finding may provide insight to the plants to exist in the stress condition and to improve the industrially important pigment production. [ABSTRACT FROM AUTHOR]