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Davray, D.

Publications and source records attributed to Davray, D..

3 recordsLinked to original sources

Integrative Transcriptomics and Phytochemical Screening Reveal Pratenol B, Eriodictyol, Losbanine, and Isookanin, as Potential EGFR and HRAS Inhibitors in Indian Oral Squamous Cell Carcinoma Patients

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer, with India contributing nearly one-third of the global cases. Management of OSCC remains difficult due to increasing risk factors, limited therapeutic options, severe side effects, and rising drug resistance. Therefore, novel and safer treatment strategies are urgently needed. This study explores the potential of phytochemicals as targeted inhibitors of key dysregulated biomarkers in Indian OSCC patients. RNA sequencing and pathway analysis revealed significant alterations in the MAPK signaling pathway, highlighting EGFR and HRAS as crucial therapeutic targets. Given the limited clinical success of existing EGFR-targeted therapies and the scarcity of HRAS inhibitors, a natural product-based approach was adopted. Molecular docking of 17,000 phytochemicals identified Pratenol B, Eriodictyol, Losbanine, and Isookanin as promising inhibitors, with Pratenol B showing dual inhibition of EGFR and HRAS. These compounds exhibited strong binding affinities, favorable pharmacokinetic profiles, high bioavailability, and low toxicity. Molecular dynamics simulations confirmed the stability of Pratenol B with both target proteins, surpassing reference inhibitors. Utilizing vast medicinal plant diversity presents a cost-effective and low-toxicity avenue for OSCC therapy. Further in vitro, in vivo, and clinical studies are warranted to validate these phytochemicals as potential therapeutics.

cancer biology↗

Upregulation of a novel lncRNA KLHDC7B-DT in Head and Neck Cancers: Implications for Prognosis and Molecular Mechanisms

Head and neck cancer (HNC), the seventh most frequent malignancy globally, is a serious health concern. Despite advancements in treatment, the overall survival rate for HNC remains around 50%, with even poorer outcomes in metastatic cases. This highlights the urgent need to explore the molecular mechanisms underlying HNC for improved diagnostics and therapies. The importance of non-coding RNAs, especially long non-coding RNAs (lncRNAs), in a variety of malignancies, including HNC, has been highlighted in recent researches. Although lncRNAs and mRNA are very similar, lncRNAs do not encode proteins and they are longer than 200 nucleotides. While studies have implicated lncRNAs in several cancers, including HNC, their exact role in HNC remains unclear, and there are currently no clinically established lncRNA biomarkers for diagnosis or therapy. Thus, this study aims to identify novel lncRNAs and investigate their significance in HNC. For this, we looked over recent research and discovered a new lncRNA called KLHDC7B-DT. The KLHDC7B-DT is significantly upregulated in HNC patient samples, and this result is corroborated by TCGA HNC data and cell lines. Further investigation suggests that KLHDC7B-DT may be linked with cancer stage, grade, age, and worse patient survival. We identified potential miRNAs that interact with KLHDC7B-DT and presented mRNA targets of these miRNAs, along with their possible functions. We propose that KLHDC7B-DT may regulate IL-6 expression in HNC, either through miRNAs or alternative mechanisms. Additionally, we found a significant positive correlation between the neighboring protein-coding gene KLHDC7B and the KLHDC7B-DT in HNC, both of which are significantly upregulated in HNC. In conclusion, KLHDC7B-DT is upregulated in HNC and holds promise as a prognostic and therapeutic biomarker. This study marks the first report highlighting the significance of KLHDC7B-DT in HNC.

cancer biology↗

Plasmids encode niche-specific traits in Lactobacillaceae

The species of family Lactobacillaceae are found in highly diverse environments and play an important role in fermented foods and probiotic products. Many of these species have been individually reported to harbor plasmids that encode important genes. In this study, we performed comparative genomic analysis of the publically available data of 512 plasmids from 282 strains represented by 51 species of this family and correlated the genomic features of plasmids with the ecological niches in which these species are found. Two-third of the species had at least one plasmid-harboring strain. Plasmid abundance and GC content were significantly lower in the vertebrate-adapted species as compared to the nomadic and free-living species. Hierarchical clustering (HCL) highlighted the distinct nature of plasmids from the nomadic and free-living species than those from the vertebrate-adapted species. EggNOG assisted functional annotation revealed that genes associated with transposition, conjugation, DNA repair and recombination, exopolysaccharide production, metal ion transport, toxin-antitoxin system, and stress tolerance were significantly enriched on the plasmids of the nomadic and in some cases nomadic and free-living species. On the other hand, genes related to anaerobic metabolism, ABC transporters, and major facilitator superfamily were found to be overrepresented on the plasmids of the vertebrate-adapted species. These genomic signatures are correlated to the comparatively nutrient-depleted, stressful and dynamic environments of nomadic and free-living species and nutrient-rich and anaerobic environments of the vertebrate-adapted species. Thus, these results indicate the contribution of the plasmids in the adaptation of lactobacilli to the respective habitats. This study also underlines the potential application of these plasmids in improving the technological and probiotic properties of lactic acid bacteria. Impact statementThe bacteria of the family Lactobacillaceae are present in the wide range of habitats and play an important role in human health, fermented foods and chemical industries. A few studies have demonstrated the presence of plasmids in the individual strains of Lactobacillaceae species encoding various traits. Extensive data of genome sequences of the lactobacilli are becoming available; however, no comprehensive analysis of the plasmid-encoded genes and determining their biological relevance across lactobacilli has been undertaken at a larger scale. In this study, we explored the genomic content of 512 plasmids of Lactobacillaceae species and correlated it to the three types of these species according to their ecological niches - vertebrate-adapted, free-living and nomadic. Comparatively lower plasmid abundance and GC content in the vertebrate-adapted species could be correlated to the presence of these species in the nutrient-rich environment. The genomic content of the plasmids was consistent with the respective lifestyle adopted by lactobacilli suggesting that the plasmids might enhance the niche-specific fitness of the strains. The plethora of important genes present on the plasmids can also make them a highly useful tool in improving the probiotic, technological and food-related properties of lactobacilli. Data summaryNucleotide sequences of plasmids of Lactobacillus strains for which complete genome sequences were available were retrieved from the NCBI genome [https://www.ncbi.nlm.nih.gov/genome] and PATRIC 3.5.41 databases on 31st March 2019. The dataset includes 512 nucleotide sequences of plasmids of 282 strains belonging to genus Lactobacillus before its reclassification into several genera (1). Details of the plasmids have been given in Table S1.

genomics↗