Biology subjects

Khan, F. F.

Publications and source records attributed to Khan, F. F..

5 recordsLinked to original sources

bioRxiv2026

Epigallocatechin Gallate (EGCG) as a Protective Agent Against Enzymatic Stromal Degradation in Caprine and Ovine Corneas: Towards Novel Therapeutics for Keratoconus

PurposeKeratoconus (KC) is a progressive corneal ectatic disorder marked by stromal thinning, enzymatic degradation, and oxidative stress. Conventional corneal collagen cross-linking (CXL) therapy poses risks. Epigallocatechin gallate (EGCG), a catechin found in green tea, has been shown to cross-link collagen, inhibit proteases, and modulate inflammation, suggesting its potential as an alternative therapy for KC. This study aimed to (1) evaluate the protective effects of EGCG against collagenase-mediated stromal degradation in caprine and ovine corneas and (2) investigate the use of caprine and ovine cornea as viable ex vivo models for corneal ectasia research. MethodsGoat (n=4) and sheep (n=8) corneoscleral buttons were cultured in an air-liquid interface (ALI). Tissue viability was monitored by transparency grading and histology. The corneal ectasia environment was induced by collagenase type I digestion. An EGCG-rich extract was utilized for the treatments. ResultsGoat and sheep corneas remained intact for 7 days in MEM-based medium, though transparency decreased, with edema (whitening) by Day 7. Histology confirmed stromal loosening and reduced keratocyte cell density but preserved architecture sufficient for enzymatic digestion. EGCG pre-treatment and post-treatment exposure were associated with greater resistance to enzymatic digestion, with greater stromal preservation of quadrants in the EGCG pre-treated quadrant than in PBS pre-treated controls. ConclusionsThis study provides proof of concept that EGCG extract confers protection against enzymatic degradation in goat and sheep corneas, highlighting its potential as a protective agent for corneal ectatic disorders like Keratoconus. Additionally, goat and sheep corneas can represent practical and ethical ex vivo models for short-term ocular research. Future work should focus on cytotoxicity, biomechanical validation, optimized culture conditions, and in vivo studies.

pathology↗

bioRxiv2023

Comparative analysis of HPV-Human Protein Interaction Networks in Oropharyngeal and Oral Squamous cell carcinomas

Oral Squamous Cell Carcinoma (OSCC) accounts for more than 90% of reported head and neck cancers which is the sixth leading cancer worldwide. Oropharyngeal squamous cell carcinoma (OPSCC) cases, a closely located but a different sub-type of head and neck cancer, are also rising worldwide specifically among young individuals with risk factors including viral infection, smoking and alcohol. HPV infection specifically the subtype HPV16 is a significant risk factor in the initiation and progression of OPSCC, but has not been reported to play a role in OSCC. This study sets out to decipher mechanistic differences at the molecular level by comparing the viral-human protein-protein interaction (PPI) networks both in oropharyngeal squamous cell carcinoma (OPSCC) and oral squamous cell carcinoma (OSCC). We found that the unbiased HPV16-Human network consisted of 479 nodes, including 7 HPV16 proteins and 472 human proteins. Enrichment analysis revealed significant involvement of the identified human proteins in ubiquitination, protein degradation, and cancer-related pathways. A subset of 37 genes showed differential expression in HPV-positive OPSCC and OSCC, with TP53 over-expressed and ENDOD1 under-expressed in both cancers. Six genes (NUTM1, MYC, SCN9A, COL27A1, ITGB4, and GNB2) exhibited distinct changes in HPV-positive OPSCC compared to the other groups, where NUTM1 was the most over-expressed in OPSCC HPV+. The identified genes and pathways could serve as potential targets for precision medicine and therapeutic interventions in HPV-associated cancers. Further investigations are required to validate their clinical implication in in vitro and in vivo models.

cancer biology↗

bioRxiv2021

Salmonella Outer Membrane Vesicles contain tRNA Fragments (tRFs) that Inhibit Bacteriophage P22 infection

Salmonella Outer Membrane Vesicles (OMVs) were recently shown to inhibit P22 bacteriophage infection. Furthermore, despite there being several published reports now independently describing (1) the marked prevalence of tRFs within secreted vesicle transcriptomes and (2) roles for specific tRFs in facilitating/inhibiting viral replication, there have been no examinations of the effects of vesicle-secreted tRFs on viral infection reported to date. Notably, while specific tRFs have been reported in a number of bacteria, the tRFs expressed by salmonellae have not been previously characterized. As such, we recently screened small RNA-seq datasets for the presence of recurrent, specifically excised tRFs and identified 31 recurrent, relatively abundant tRFs expressed by Salmonella enterica serovar Typhimurium (SL1344). Whats more, we find S. Typhimurium OMVs contain significant levels of tRFs highly complementary to known Salmonella enterica-infecting bacteriophage with 17 of 31 tRFs bearing marked complementarity to at least one known Salmonella enterica-infecting phage (averaging 97.4% complementarity over 22.9 nt). Most notably, tRNA-Thr-CGT-1-1, 44-73, bears 100% sequence complementary over its entire 30 nt length to 29 distinct, annotated Salmonella enterica-infecting bacteriophage including P22. Importantly, we find inhibiting this tRF in secreted OMVs improves P22 infectivity in a dose dependent manner whereas raising OMV tRF levels conversely inhibits P22 infectivity. Furthermore, we find P22 phage pre-incubation with OMVs isolated from naive, control SL1344 S. Typhimurium, successfully rescues the ability of S. Typhimurium transformed with a specific tRNA-Thr-CGT-1-1, 44-73 tRF inhibitor to defend against P22. Collectively, these experiments confirm tRFs secreted in S. Typhimurium OMVs are directly involved with and required for the ability of OMVs to defend against bacteriophage predation. As we find the majority of OMV tRFs are highly complementary to an array of known Salmonella enterica-infecting bacteriophage, we suggest OMV tRFs may primarily function as a broadly acting, previously uncharacterized innate antiviral defense.

microbiology↗

bioRxiv2021

Identification of antineoplastic agents for oral squamous cell carcinoma: an integrated bioinformatics approach using differential gene expression and network biology

Oral squamous cell carcinoma (OSCC) is the most common malignant epithelial neoplasm and anatomical subtype of head and neck squamous cell carcinoma (HNSCC) with an average 5-year survival rate of less than 50%. To improve the survival rate of OSCC, the discovery of novel anti-cancer drugs is urgently needed. In the present study, we performed metanalysis of 5 gene expression datasets (GSE23558, GSE25099, GSE30784, GSE37991 and TCGA-OSCC) that resulted in 1851 statistically significant DEGs in OSCC. The DEGs were involved in key biological pathways that drive the progression of OSCC. A comprehensive protein-protein interaction (PPI) network was constructed from the DEGs and the top protein clusters (modules) were extracted in Cytoscape. The DEGs from the top modules were searched for antineoplastic agents using L1000CDS2 server. The search resulted in a total of 37 perturbing agents from which 12 well-characterized antineoplastic agents were selected. The selected 12 antineoplastic agents namely Teniposide, Palbociclib, Etoposide, Fedratinib, Tivozanib, Afatinib, Vemurafenib, Mitoxantrone, Idamycin, Canertinib, Dovitinib and Selumetinib. These drugs showed interactions with the over expressed hub genes that regulate cellular proliferation and growth in OSCC progression. These identified antineoplastic agents are candidates for their potential role in treating OSCC.

bioinformatics↗

bioRxiv2021

From Decellurization to Imaging to 3-D Printing: low-cost plant-derived 3D-printed tissue scaffolds for tissue engineering

Natures most abundant carbohydrate, cellulose, has incredible structural properties that can be leveraged as scaffolds for tissue engineering. With plants being an inexpensive and easily accessible source, it is more feasible to experiment with these techniques and progress in the field of regenerative tissue engineering. In this study, we set out to optimize a low-cost method to obtain cellulose scaffolds that could potentially mimic a blood vessels after recellularization with endothelial cells. We chose a readily available plant specimen, i.e. cauliflower stalk, which offers anatomical similarity to blood vessels, vascular architecture and interconnected porosity. We went on to capture the cellulose scaffold digitally and created a 3-D model using a computer-aided design (CAD) software which was then used for 3-D printing the scaffold in two different sizes. We believe the decellularize-image-print cycle allows for skipping decellularization processes of new scaffolds every time a scaffold is required and therefore cutting cost and time needed, enables instant dissemination between individual researchers and communities and allows scalable printing at any size and level of detail. We hope this will catalyze even faster innovation in the space of tissue engineering and regenerative medicine.

bioengineering↗