ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Evaluation of the drug ligand interactions between the C. cassia bio-compounds with the SAP-1 in C. albicans to explore the inhibitory medicinal potential of C. cassia bio-compounds by a computational approach is performed in the present investigation. Antimicrobial assay was done using agar well diffusion method with the crude aqueous and ethanolic extracts of the dried barks of C. cassia against C. albicans. 2D & 3D structures of the active bio-compounds of C. cassia were optimized and the 3D structure of SAP-1 was retrieved from the PDB data bank. In-silico inhibitory potential of the selected C. cassia biocompounds against SAP-1 was done by Auto Dock 2.0 and was visualized with Accelrys discovery studio visualizing tool with the assessment of the molecular properties of the ligands against SAP-1 by molinspiration calculations and further assessment for their drug likeliness. In-vitro analysis showed a promising anti-fungal activity of C. cassia extracts against C. albicans. Cinnamoyl E-acetate and Eugenyl acetate seem to possess promising inhibitory effect to target SAP-1 with a least binding energy of –5.33 and -5.21 Kcal/mol with four hydrogen bonds respectively. Molinspiration assessments showed zero violations for all the C. cassia compounds with the TPSA scores of <140 Å towards the best oral bioavailability. The findings of the study emphasize that cinnamaldehyde, cinnamoyal acetate and eugenol from C. cassia seem to possess a promising inhibitory effect against SAP-1 of C. albicans suggesting the medicinal value of the spice against SAP-1
ABSTRACT
Fluoroquinolones are administered as routine drugs of choice for treating complicated urinary tract infections caused by multidrug resistant Acinetobacter baumannii strains. It is now a world-wide issue that gyr and par induced quinolone resistance as one of the major drug resistance mechanisms. This investigation is thus aimed to assess the prevalence of quinolone resistance and to characterize the gyrA and parC producing strains of A. baumannii. Genomic DNA from 50 fluoroquinolone resistant A. baumannii were screened for gyrA and parC by PCR for the genetic relatedness with fluoroquinolone resistance, with sequencing of the representative strains. All the strains were positive for gyrA(100%) and 82% (n=41)for parC. Presence of parC was observed in 56.09% (n=23) ciprofloxacin resistant A. baumannii with 43.90% (n=18) in levofloxacin resistant A baumannii. The findings of the present study showed the prevalence of fluoroquinolone resistance among A. baumannii in urinary tract infections and the frequency of gyrA and parC in inducing the resistance
ABSTRACT
The objective of the study was to detect the presence of fimH geneamong the drug resistanst strains of Acinetobacter baumannii.fimH gene was found to be associated with a catch bond mechanism which led to better evolution of biofilm formation. Since there are not many studies done with this gene it would be a timely investigation and this study mainly aims in molecular characterizationof fimHgene among clinical isolates of A.baumannii. Semi quantitative bio adherent assay was done by the multidrug resistant strains of A.baumannii to find the formation of biofilm. The DNA was extracted with the help of kit and PCR was performed for amplification. Pearson correlation analysis was done to find the existing correlation between the fimHgene and MDR strains of A.baumanniiwith significant p-value of (<0.05). From the screened 73 genomes of MDR A.baumannii 6.8% showed positive amplicons for the fimH gene which were related to biofilm and porin formation (Fig. 1). Correlation of its existence was high in beta lactamase (100%), cephems (100%), folate (100%) resistant strains, followed by aminoglycosides (80%), carbapenems (60%) and fluoroquinolones (60%) and efflux pumps (20%). In Spite of various measures undertaken to prevent the disease, the prevalence of the pathogen is multiplying. The current study recorded the presence of fimHgene (6.8%) among the clinical isolates of A.baumannii. This gene can be used as a target to develop new drugs and vaccines to combat the menace of A.baumannii infection
ABSTRACT
Glycyrrhizin is a phytocompound which is derived from Glycyrrhiza glabra. It is used in treating the upper respiratory tract disease like cough, bronchitis, laryngitis, sore throat, etc. It has various medicinal uses in rheumatism, peptic ulcers, asthma, allergies, and inflammation. Glycyrrhizin has been reported to possess antibacterial, antiviral, antioxidant, anti inflammatory properties. In view of the above facts, the present in silicostudy was designed to demonstrate the molecular mechanism underlying the antimicrobial activity of glycyrrhizin against common dental pathogens such as Streptococcus mutans, Porphyromonas gingivalis, Treponema denticola, Enterococcus faecalisandTannerella forsythia.The STITCH tool was used to identify the drug-protein interaction. The functional class of the protein was deduced using VICMPred, followed by the identification of epitopes on the virulence factors using BepiPred. Further, the subcellular location of the virulence factors were also studied using PSORTb software. The computational analysis performed identified several virulence factors viz., short chain dehydrogenase/reductase family oxidoreductase of Treponema denticola and D-mannonate oxidoreductase of Tannerella forsythiawhich were found to interact with glycyrrhizin. Interestingly, phosphopyruvate hydratase was found to be the protein present in all the five genera was shown to interact with glycyrrhizin. Thus the present study reveals the target proteins on the dental pathogens which were shown to interact with glycyrrhizin. Furthermore,experimental validation of the resultsare warranted to provide substantial details on the anti-microbial activity of glycyrrhizin against common dental pathogens
ABSTRACT
Head and neck squamous cell carcinoma (HNSCC) includes carcinomas in the oral cavity, pharynx and larynx. It is considered as the sixth most common form of cancer in the world. Severalstudies have confirmed that smoking and alcohol consumption are the major risk factors for HNSCC. DNA damage response genes play an important role in the maintenance of the genome. Defects in cell cycle checkpoint and DNA repair mechanisms, such asmutation or abnormalities, may lead to the wide spectrum of human diseases. The present study employs databases and computational tools to identify the genetic abnormalities associated with DNA damage related genes which might have a direct or indirect association with HNSCC. The demographic details of HNSCC patients was obtained from The Cancer Gene Atlas (TCGA, Firehose Legacy) dataset hosted by the cBioportal database. The oncoprint data analysis revealed the highest frequency of gene alteration in the ATR gene (15%), followed by ATM, BRCA2and CHEK2(5%). Other genes showed less than 5% alteration. The gene expression profile of ATRgene revealed its differential expression pattern in different grades of tumor relative to normal samples. The survival curve analysis using Kaplan-Meier method revealed that a high level expression of the ATR gene leads to poor survival rate in the female HNSCC patients when compared to males. Thus the present study has identified gross and single nucleotide variants in the ATRgene which could have a putative role in the development of tumor. Further experimental research is required to confirm this association
ABSTRACT
The cell suicide pathway of apoptosis is a necessary event in the life of multicellular organisms. It is involved in many biological processes ranging from development to the immune response. Over expression of interleukin-1β-converting enzyme (later renamed caspase-1) was shown to be sufficient to induce apoptosis in mammalian cells. The present study aims to assess the gene alterations in the Caspase family of cytochromes so as to derive an association with HNSCC. Earlier eleven genes were found in the human genome to encode 11 human caspases, caspase-1 to caspase-10 and caspase-14, which is now populated to 13, whereas 10 genes were found in the mouse genome to encode 10 murine caspases including caspase-1, 2, 3, 6, 7, 8, 9, 11, 12 and 14 Caspases share a number of features distinguishable from other proteases. The analysis follows an observational study design, employing several computational tools to identify and predict the possible outcomes of gene alterations identified in HNSCC patients. cBioportal server was used to identify the gene alterations which was further analyzed using tools such as PROVEAN, I-Mutant and gnomAD. Several reported polymorphic variants were also identified. The pathogenicity and protein stability of gene alterations documented in the present study were identified at standard biological conditions. Further experimental studies would provide concrete evidence on the association of the observed genetic abnormalities with HNSCC especially in individuals exposed to habitual carcinogens