Predictions of Immunodominant Epitope Peptides From the AsaA Type VI Secretion System in Acinetobacter baumannii: A Computational Approach.

Introduction Acinetobacter baumannii, designated as a priority pathogen by the World Health Organization (WHO), is responsible for recalcitrant infections in immunocompromised patients. The type VI secretion system (T6SS) is a class of macromolecular secretion machines, contributing to its virulence. The aim of this study is thus to predict the immune-dominant epitope peptides from the Acinetobacter T6SS-associated protein of A. baumannii (AsaA). Methods AsaA protein retrieval from the bacteria was carried out using computational platforms and the evaluation of antigenicity and allergenicity was performed. The T-cell epitopes of major histocompatibility complex class II binders were identified followed by molecular docking of the immune-dominant epitopes with human leukocyte antigen alleles using the ClusterPro server (https://cluspro.org/help.php). Additionally, the B-cell epitopes were predicted. Results Immune-informatic analysis showed immune-dominant peptides in the most favored regions with promising interactions with HLA alleles DP, DQ, DR, and toll-like receptor showing high binding capacity. Conclusion In the present investigation, epitope 1 (LILFLIGNY) was found to be a promising candidate for the synthesis of vaccines. However, it requires further experimentation for its immunological memory and response.

Molecular Characterization of the glyA Gene From the Clinical Isolates of Tannerella forsythia.

BACKGROUND: The glyA gene in Tannerella forsythia is attributed for its virulence by producing the enzyme serine hydroxymethyltransferase (SHMT), which plays a vital role in bacterial cell metabolism. OBJECTIVES: The study is thus aimed to determine the frequency of the glyA gene from the clinical strains of T. forsythia isolated from periodontitis patients. MATERIALS AND METHODS: Forty-five patients with varying degrees of periodontitis were included in the study, and the plaque samples collected from them were anaerobically processed by inoculating onto sterile anaerobic blood agar plates using a gaspak system, with incubation at 37°C for 5-7 days. The DNA was extracted from the obtained isolated colony, and PCR was performed to confirm the presence of the glyA gene. RESULTS: In total, 46.6% (n = 7) of the cases in group III aggressive periodontitis (n = 15) and 6.66% (n = 1) in group II stage II periodontitis (n = 15) showed the presence of T. forsythia, and among them, 57.14% (n = 4) showed the presence of the glyA gene.  Conclusion: The findings of the study showed that the glyA gene may be associated with the pathogenesis of T. forsythia and could be thus a novel candidate for the future theragnostic approach to combat periodontitis.

Genetic Association of Toll-Like Receptor 4 (TLR4) Gene Polymorphism (rs4986790) With Oral Squamous Cell Carcinoma (OSCC): A Pilot Case-Control Study.

Introduction Oral squamous cell carcinoma (OSCC) is a highly prevalent and most common form of oral malignancy in the Indian population. Toll-like receptors belong to an important family of receptors that are involved in the process of pathogen recognition and mounting immune response. The expression of this receptor is dysregulated on the tumor cells as reported across several cancer types. The genetic variants in this gene could have a profound impact on the expression of the Toll-like receptor 4 (TLR4) gene.  Objective This study aimed to understand the association of TLR4 gene polymorphism (rs4986790) with OSCC. The objective of this study was to compare the allele and genotype frequencies between the two groups, viz., OSCC and normal healthy subjects, recruited in the study. Materials and methods The blood samples were collected from normal healthy subjects (N = 25) and OSCC patients (N = 25). Genomic DNA was isolated from all samples, and genotyping was performed for the TLR4 gene polymorphism (rs4986790) employing the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach. The frequency distribution of genotypes and alleles across the study groups was determined by the Chi-square test.  Results The allele frequency for TLR4 gene polymorphism (rs4986790) in the case group was found to be 60% (A allele) and 40% (G allele), respectively. The study population in both groups were found to agree with the Hardy-Weinberg equilibrium (HWE). The genotype frequency did not differ significantly among the two study groups which was evident from the p-value = 0.8285.  Conclusion The present study did not report any significant association of the TLR4 polymorphic marker rs4986790 with OSCC. Further investigations into the association of other polymorphic markers in the TLR4 gene, among the larger population of OSCC patients, could provide evidence of their association with OSCC.

Role of the Growth Hormone Receptor (GHR) Gene in Skeletal Class II Malocclusion and Its Significant Influence on the Skeletal Facial Profile in Both the Sagittal and Vertical Dimensions: A Systematic Review.

This systematic review aims to determine the role of the growth hormone receptor (GHR) gene in skeletal malocclusion and its significant influence on the growth of the maxilla and the mandible in both sagittal and vertical dimensions. A search of the electronic databases of PubMed, Google Scholar, and Cochrane up to and including the year 2023 was made. In addition to this, a hand search of orthodontic and dentofacial orthopaedic journals was carried out. This search included randomized control trials. The Mesh terms used were "skeletal class II malocclusion", "mandibular retrognathism", "sagittal malocclusion", "genetic expression", "genetic factors", "genetic study", "genetic polymorphism", and "single nucleotide polymorphism". The inclusion criteria included studies such as clinical trials and orthopaedic appliances in the presurgical phase. The exclusion criteria for the study were studies not in the English language, case reports, case series, and studies with irrelevant data. It has been cited in various literature that polymorphic variations of the GHR gene could cause variations in mandibular morphogenesis affecting both the mandibular body length and ramal height. However, its effects are quite variable and are based on different population groups. Polymorphism of the GHR gene can be considered a reliable indicator predicting variations in affecting the growth of the mandible with greater significance in affecting the vertical ramal height compared to the body length of the mandible. Its effects on the maxillary skeletal base are rather limited comparatively.

Identification of Pathogenic Missense Mutations in the CHRNA5 Gene: A Computational Approach.

Aim The CHRNA5/A3/B4 gene locus is closely related to nicotine dependence and other smoking-related disorders. Coupling genetic and clinical studies of nicotine dependence and smoking behaviors may open new avenues for medication development. The aim of this study is to investigate the functional missense mutations in the CHRNA5 gene. Methodology The Ensembl database was used to gather data on missense mutations of the human CHRNA5 gene. Computational tools viz. SIFT (Sorting Intolerant From Tolerant), PolyPhen (Polymorphism Phenotyping), PROVEAN (Protein Variation Effect Analyzer), I-Mutant, and MutPred were used to uncover the pathogenic mutations in the gene under investigation.  Results Among 161 missense variants reported inthe CHRNA5 gene, 94 variants were found to be highly pathogenic. Moreover, 20 were pathogenic and 4 were not pathogenic. Conclusion The computational analysis disclosed harmful mutations in the CHRNA5 gene which could be potentially associated with smoking-related traits.

Molecular Detection of Secreted Aspartyl Proteinases (Saps) From Dental Isolates of Candida albicans and Targeting With Psidium guajava Biocompounds: An In Vitro and In Silico Analysis.

Introduction Candida albicans (C. albicans) is an opportunistic yeast-like fungus and is considered a functional biome of the oral and gut microbiomes. The sap gene and its types play a vital role in the pathogenesis of C. albicans. The emergence of resistance traits is a major problem, and targeting the same with alternative medicines has sparked renewed interest in recent years. Objectives This study is thus aimed at detecting the frequency of sap gene types in the clinical isolates of C. albicans and evaluating the antifungal effect of the crude methanolic extract of Psidium guajava (P. guajava). Further in silico assessments will assess the inhibitory effect of six compounds of P. guajava against the Sap protein. Materials and methods C. albicans was characterized phenotypically in 20 patients with root caries, and the sap gene was detected by PCR. The crude methanolic extract was prepared, and its antifungal efficacy was evaluated by the agar well diffusion method. Auto-docking was performed to assess the best compound based on the docking and overall interactions. Results Six isolates were identified as C. albicans and sap gene types 1-3 were detected in the four strains. P. guajava methanolic extracts showed a promising antifungal effect at varying concentrations. In silico analysis showed myricetin possessing the maximum number of hydrogen bonds and high docking energy with one violation. Conclusion The study concludes that P. guajava has a promising inhibitory effect against C. albicans with myricetin as the best compound to target the sap gene of C. albicans. However, further experimental studies are to be considered for its effectiveness in treating the infections caused by C. albicans.

Exploring the Expression of BCAS3 in Head and Neck Squamous Cell Carcinoma and Its Association With Prognosis.

Background Head and neck squamous cell carcinoma (HNSCC) is a prominent global cancer that manifests across diverse sites such as the oral cavity, oropharynx, and larynx. Human papillomavirus (HPV) infection and genetic alterations contribute to HNSCC development. Objective To investigate the complex role of breast carcinoma amplified sequence (BCAS3) in HNSCC pathogenesis. Methods We used multiple databases to analyze BCAS3 expression in HNSCC using The Cancer Genome Atlas-Head-Neck Squamous Cell Carcinoma (TCGA-HNSC) dataset and validated it in oral squamous cell carcinoma (OSCC) using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The BCAS3 gene and protein networks were analyzed to identify their functional pathways. Results The results revealed significant overexpression of BCAS3 was observed in HNSCC and OSCC tumors. Our study explores BCAS3's correlation with clinicopathological features and patient prognosis, suggesting its involvement in tumor aggressiveness. Notably, BCAS3 expression in HPV-positive and HPV-negative HNSCC samples emphasizes the intricate viral interactions. Kaplan-Meier plots demonstrate BCAS3's impact on patient survival. Furthermore, BCAS3's association between tumor immune infiltration and autophagy was uncovered. Conclusion Our study contributes to the understanding of BCAS3's role in HNSCC and suggests its potential as a therapeutic target and diagnostic marker for these malignancies.

Increased Expression of LIPC Is Associated With the Clinicopathological Features and Development of Head and Neck Squamous Cell Carcinoma.

Introduction Lipase C hepatic type (LIPC) is a member of the lipase family and plays a role in tumor development. However, its specific role in head and neck squamous cell carcinoma (HNSCC) is not well understood. Objective This study aims to investigate LIPC gene expression in HNSCC and elucidate its potential role in the context of the disease. Methods LIPC expression was analyzed using the Cancer Genome Atlas-HNSCC (TCGA-HNSCC) dataset. Real-time polymerase chain reaction (qPCR) was used to validate LIPC expression in oral squamous cell carcinoma (OSCC) tissue samples, which is the most common type of HNSCC. The LIPC was assessed to find out if there is a link with HNSCC clinicopathological features, prognosis, and tumor infiltration. Functional pathways associated with the LIPC network were also examined. Results LIPC expression was found to be elevated in both HNSCC and OSCC tissues. The heightened expression of LIPC correlated with various clinicopathological features and influenced the prognosis of HNSCC patients. The LIPC gene demonstrated connections with several oncogenic genes and proteins, participating in lipid catabolic processes and other pathways. These findings suggest that LIPC expression may play a role in the pathogenesis of HNSCC. Conclusion Our study affirms that LIPC expression is linked to the development of HNSCC, suggesting its potential utility as a biomarker or therapeutic target for the disease. However, further functional studies are imperative to validate and expand upon these findings.

Establishing the Role of Neurogenic Inflammation in the Pathogenesis of Periodontitis: A Systematic Review.

The role of neurogenic inflammation in various systemic diseases has been well established, but there is a dearth of studies and evidence regarding its role in periodontitis. This study aimed to systematically review the evidence in establishing the role of neurogenic inflammation in chronic periodontitis. Databases such as PubMed, Scopus, and Google Scholar were reviewed. We analyzed studies of any design that compared and evaluated the presence of neuropeptides such as substance P, calcitonin gene-related peptide, neurokinin A, neuropeptide Y, and vasoactive intestinal polypeptide in systemically healthy patients with and without periodontitis. We screened 2,495 articles and abstracts electronically and manually, which yielded 191 articles relevant to our study. Full-text examination of these 191 articles led to the final inclusion of 14 publications. Most studies here confirmed an association between various neuropeptides and periodontitis, but there is a high heterogeneity between the studies, making it necessary to clarify the mechanism between these two. Although most studies included in this review found a positive association between neurogenic inflammation and periodontitis, the evidence is of moderate to low quality.

Detection of csgA gene in carbapenem-resistant Acinetobacter baumannii strains and targeting with Ocimum sanctum biocompounds.

OBJECTIVES: Carbapenem-resistant Acinetobacter baumannii (CRAB) is considered highly virulent due to csgA gene-mediated biofilm formation. The present study aimed to target the same gene, employing the antibiofilm effect of Ocimum sanctum (O. sanctum) essential oil compounds among CRAB strains. MATERIALS AND METHODS: A semi-quantitative adherent bioassay was performed to detect the biofilm formation in 73 CRAB strains. This was followed by molecular characterization, Polymerase Chain Reaction (PCR) amplification, and csgA gene sequencing. An antibiofilm assay under in vitro conditions, with essential oils of O. sanctum was performed. This was followed with further docking analysis of csgA protein with the selected compounds from the O. sanctum essential oils. A Molinspiration assessment was also done to elicit the drug likeliness of the biocompounds. RESULTS: The biofilm assay showed 58.9% as high-grade and 31.5% as low-grade biofilm formers, while 9.58% were non-biofilm formers. Molecular characterization of the csgA gene showed 20.54% (15/73) positivity. The strains that were imipenem resistant also showed the csgA gene to be present (100%; 15/15), with 60% (9/15) and 20% (3/15) for meropenem and doripenem resistance respectively. A crystal violet assay for determining cell viability was done in vitro, which gave Minimum biofilm inhibition concentrations of 50% (MBEC50) at 25 µl and 90% (MBEC90) at 50 µl. The docking analysis done in silico showed benzofuran to possess the lowest binding energy and highest hydrogen bond interactions. CONCLUSION: The results indicate benzofuran, from the O. sanctum essential oils, to be effective in targeting the csgA gene among CRAB strains. Additionally, validation of these findings through in vivo studies is required.