FASTK family of genes linked to cancer.

Fas Activated Serine/Threonine Kinase (FASTK) family is a protein family encoded in the nuclear genome that spans the mitochondria and executes numerous functions, and consists of FASTK, the founding member along with 5 homologous proteins FASTKD1-5. Up regulation of FASTK family members have not only been implicated in tumour progression and invasion but also in increased resistance to chemotherapy proven by their knockdown leading to increased sensitivity to drugs. Thus, this review reports the implication of FASTK proteins in cancer and hence provides a scope to emphasise the role of these proteins in Oral Cancer.

Delineating the potential targets of thymoquinone in ESKAPE pathogens using a computational approach.

The present study was designed to identify and analyze the targets of thymoquinone on drug resistant pathogens employing in silico tools. The target identification was performed using STITCH tool, followed by the functional analysis of protein targets by VICMPred. Further, VirulentPred was used to determine the nature of virulence of target proteins. The putative epitopes present on the virulent proteins were identified using BepiPred tool. The subcellular location of the virulent proteins was assessed using PSORTb. The results showed multiple targets of the pathogens being targeted. The nitric-oxide synthase-like protein of Staphylococcus aureus and acetyltransferase family protein, histone acetyltransferase HPA2, GNAT family acetyltransferase of Acinetobacter baumannii was found to be the virulent proteins interacting with thymoquinone. Molinspiration assessments showed zero violations suggesting the druggability of TQ. The study unveils the molecular mechanisms underlying the antimicrobial effect of thymoquinone as demonstrated by in silico procedures.

Genetic alterations in Wnt family of genes and their putative association with head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the most frequent type of head and neck cancer that usually arises from the mucosal surfaces of several organs including nasal cavity, paranasal sinuses, oral cavity, tongue, pharynx, and larynx. The Wnt signaling pathway is a crucial mechanism for cellular maintenance and development. It regulates cell cycle progression, apoptosis, proliferation, migration, and differentiation. Dysregulation of this pathway correlates with oncogenesis in various tissues including breast, colon, pancreatic as well as head and neck cancers. The present study aims to assess the gene alterations in the Wnt family of genes so as to derive an association with HNSCC. Computational approaches have been utilized for the identification of gene alterations in the Wnt family of genes. Several databases such as cBioportal, STRING, and UALCAN were used for the purpose. The frequency of alteration was high in case of Wnt family member 11 (5%). Gene amplification, deep deletions, missense and truncating mutations were observed in HNSCC patients. There was a marked difference in the gene expression profile of WNT11 between grades as well as normal samples. The survival probability measured using the Kaplan-Meier curve also presented with a significant difference among male and female subjects experiencing a low/medium level expression. The female patients showed less survival probability when compared to the male subjects. This provides the prognostic significance of the WNT11 gene in HNSCC. Taken together, the present study provides clues on the possible association of WNT11 gene alterations with HNSCC, which has to be further validated using experimental approaches.

Decoding The Genetic Alterations In Cytochrome P450 Family 3 Genes And Its Association With HNSCC.

INTRODUCTION: Cytochrome P450 (CYPs) are enzymes belonging to the family of heme-containing proteins, most commonly found in the endoplasmic reticulum and mitochondria. These enzymes catalyze a variety of functions including metabolism of steroids, fatty acids, natural compounds, drugs and carcinogenic chemicals. The inherent association of CYPs with disease conditions have turned the focus into the genetic alterations or variations associated with phenotypes such as drug responsiveness, chemical toxicity and bioconversion of procarcinogens to active carcinogens. RESULTS: A total of 8 genes of the CYP3 family were analyzed, among which 4 genes were found to harbour gross abnormalities and variations. The genes CYP3A4, CYP3A5, CYP3A7, CYP3A43 showed a common pattern of gene amplification in a group of patients. Truncating and missense variants were also identified of which rs199908125 of CYP3A4 and rs768530577 of CYP3A5 were reported in different populations. MATERIALS AND METHODS: The present observation study utilizes several computational tools to identify and predict the possible outcomes of gene alterations in CYP3 family of genes with head and neck squamous cell carcinoma (HNSCC). cBioportal hosts an exhaustive collection of datasets of various cancers which was the primary source of analysis. Oncoprint data obtained was further analysed using tools such as PROVEAN, I-Mutant and gnomAD. DISCUSSION: The gnomAD analysis revealed a few polymorphic rare variants with minor allele frequency less than 0.01, which could have a putative association with HNSCC. Five out of eight variants identified were found to be deleterious exhibiting decreased protein stability. CONCLUSION: Further screening of the genetic abnormalities through experimental validation in different populations are warranted to derive an association between the gene identifiers and disease phenotype.

Aberrations in SMAD family of genes among HNSCC patients.

Head and neck cancer is a debilitating disease with several etiological factors. One of the main etiologies to be noticed is the alteration, which is either caused by genetic or environmental factors. Therefore, it is of interest to assess the effect of genetic alterations, especially the non-synonymous mutations of the SMAD gene family and its possible association with HNSCC. Data shows a significant novel mutation in the SMAD gene family in association with head and neck squamous cell carcinoma (HNSCC), which would aid in better diagnosis and treatment planning for cancer.

An in silico approach towards identification of virulence factors in red complex pathogens targeted by reserpine.

Oral cavity hosts an exhaustive collection of microorganisms which are known to be associated with disease such as dental caries, periodontal and deep-seated infections. Elimination of these pathogens from the site of infection remains a perplexing task, which demands the use of antibiotics. The emergence of drug resistant forms has spurred interest into identifying novel therapeutic targets against these pathogens. In this context, the present study has been designed to analyse and identify potential drug targets of the phytocompound reserpine in red complex pathogens. Computational tools were used to identify the targets, assess its functional role and virulence property. Further, the peptide epitopes present in the virulence factors were identified using BepiPred tool. The subcellular location of the virulence proteins were also elucidated using PSORTb. Reserpine was found to target vital protein transporters such as ABC transporter and efflux pumps which are known to play a crucial role in the survival of bacterial cells. Hence the present in silico study provides substantial evidence on the anti-bacterial activity of reserpine against red complex pathogens. However, in vitro studies using the compound is warranted to further confirm the efficacy of the compound.

Anticancer effects and lysosomal acidification in A549 cells by Astaxanthin from Haematococcus lacustris.

Astaxanthin (AXN) is known to have health benefits by epidemiological studies. Therefore, it is of interest to assess the effect of AXN (derived from indigenous unicellular green alga Haematococcus lacustris) to modulate cell cycle arrest, lysosomal acidification and eventually apoptosis using in vitro in A549 lung cancer cells. Natural extracts of astaxanthin were obtained by standardized methods as reported earlier and characterized by standard HPLC and MS. Treatment of A549 cells with AXN (purified fraction) showed significant reduction in cell viability (about 50%) as compared to crude extract at 50µM concentration. Thus, we show the anticancer effects and lysosomal acidification in A549 cells by Astaxanthin from Haematococcus lacustris for further consideration. Together, our results demonstrated the anticancer potential of AXN from Haematococcus lacustris, which is found to be mediated via its ability to induce cell cycle arrest, lysosomal acidification and apoptotic induction.

In silico analysis of virulence genes in an emerging dental pathogen A. baumannii and related species.

OBJECTIVES: Acinetobacter baumannii is an opportunistic pathogen which has recently been categorized as a high risk pathogen by World Health Organisation (WHO). The microbe has stealthily entered the oral cavity and has established itself as a potential pathogen by acquiring drug resistance and expression of several virulence genes. Surveillance on the type of virulence factors harboured by the organism will enable us to comprehend the mechanism of pathogenesis. The study was performed to screen for the presence of crucial virulence factors associated with Acinetobacter spp. as reviewed from the literature by employing computational tools. DESIGN: Nineteen genome sequences of Acinetobacter spp. with the predominance of different strains of A. baumannii were classified phylogenetically into clusters using in silico restriction digestion and pulse field gel electrophoresis (PFGE). Further, the frequency of common virulence genes in the genome of various Acinetobacter spp. was recorded using in silico PCR analysis. RESULTS: Based on PFGE pattern and phylogenetic tree the genomes of A. baumannii were clustered into 4 genotypes (G1-G4). Two species were excluded from the list since they were negative for almost all the virulence genes tested. Frequency of virulence genes in each of the 17 genomes analysed, found ompA and smpA to be the major virulence factors in A. baumannii and related species. Acinetobacter spp. belonging to genotypes 2 and 3 were found to harbour 1-15 and 6-10 potential genes encoding virulence factors respectively. CONCLUSIONS: The present study showed numerous virulence genes in genomes analysed. In silico analysis of these virulence genes can be used as candidates to build novel therapeutic targets against the pathogen. An extensive study on the functional role of these genes could aid in stalling the propagation and dissemination of A. baumannii among susceptible individuals.

An insight into the emergence of Acinetobacter baumannii as an oro-dental pathogen and its drug resistance gene profile - An in silico approach.

BACKGROUND: Acinetobacter baumannii, a potential nosocomial pathogen has stealthily gained entry into the oral cavity. Their association with other pathogens like Pseudomonas aeruginosa in chronic and aggressive periodontitis cases is well documented. The magnitude of problem caused by A . baumannii could be attributed to resistance genes acquired by the organism. Since the microbiome of oral cavity is heterogeneous and complex, the transfer of genes from multidrug resistant A . baumannii may be a serious threat in infection control and management. In view of this fact, the present study aims to categorize and characterize drug resistant genes present in each of the 19 genomes of Acinetobacter Sp. selected for the study. METHODS: About 19 genome sequences of Acinetobacter spp. with the predominance of different strains of A . baumannii was genotyped using in silico restriction digestion and pulse field gel electrophoresis (PFGE). Further, the prevalence of common drug resistant genes in the genome of various Acinetobacter spp. was recorded using in silico PCR analysis. RESULTS: Based on the PFGE pattern, phylogenetic tree was constructed and the genomes were clustered into 6 genotypes. Genotype 4 (n = 8; 42.10%) and 5 (n = 6; 31.57%) were predominant, followed by genotypes 2 (n = 2; 10.52%), 1, 3 and 6 (n = 1; 5.26%). Three species were excluded from the list since they were negative for most of the drug resistant genes tested. Prevalence of drug resistant genes in each of the 16 genomes analysed found oxa-51, ISAba 1 and ADC 1 to be the major genes found in A . baumannii. Acinetobacter spp. belonging to genotypes 4 and 5 were found to harbour 6-10 and 2-8 potential drug resistant genes respectively. CONCLUSION: The present study showed cluster of multi-drug resistant genes in genomes analysed, thus, warranting the need for antibiotic surveillance, alternate therapeutic measures and development of novel antimicrobials. An extensive study on the genes conferring drug resistance in this pathogen will open new avenues for battling the entry and spread of this pathogen in vulnerable patient groups.