Abbas Khan

TM4SF1, a small transmembrane glycoprotein, has been implicated in tumor progression across multiple cancers. However, its functional and regulatory roles in esophageal cancer, particularly esophageal squamous cell carcinoma (ESCC), remain unclear. This study aims to characterize TM4SF1 expression in an ESCC cell line, KYSE150, determine its biological role in tumor cell phenotypes, and profile miRNA changes after TM4SF1 knockdown and perform in silico target or pathway analyses. First, TM4SF1 gene expression was analyzed in the KYSE150 cell line by qRT-PCR. shRNA-mediated TM4SF1 knockdown was applied to the KYSE150 cells, followed by proliferation, migration, and apoptosis assays. MiRNA sequencing followed by bioinformatic analyses predicted microRNAs and potential genes targeting TM4SF1, which also included putative composite pathways and gene ontologies. TM4SF1 gene expression was significantly upregulated in the KYSE150 cells compared to EC109 ESCC and HET1A cells, a normal esophageal epithelial cell. Functional bioassays revealed that TM4SF1 knockdown significantly reduced cell proliferation (MTT and CCK-8 assays) by 46%, while reducing wound closure at 24 h by 30.5% with recovery by 48 h and increased 90% of caspase 3/7 activity. The exploratory sequencing of miRNAs revealed the ten most differentially expressed miRNAs (hsa-miR-6510-3p, hsa-miR-675-5p, hsa-miR-524-5p, hsa-miR-9902, hsa-miR-520f-3p, hsa-miR-3192-5p, hsa-miR-1973, hsa-miR-3614-5p, hsa-miR-501-3p, and hsa-miR-1298-5p), whereas bioinformatic analyses predicted 54 target gene predictions, including TP53, RB1, and ICAM3, and 13 composite pathways that encompassed processes such as apoptosis, cell adhesion, and metabolic regulation. This study provides preliminary and useful insights into the role of TM4SF1 within the KYSE150 ESCC cell-line model and provide a basis for future validation in additional ESCC models, alongside initial investigations into its molecular mechanisms, and underscores the necessity of further validation in diverse cells and models and possible therapeutic implications.

Bacteriophytochrome-derived near-infrared fluorescent proteins (NIR FPs) provide deep tissue penetration, low autofluorescence, and endogenous biliverdin compatibility, enabling non-invasive visualization of viral processes in living systems. Engineering advances (iRFPs, monomeric miRFPs, photoactivatable PAiRFPs) have improved brightness, stability, and genetic encodability for robust use in mammalian models. These reporters support real-time tracking of infection dynamics and host-virus interactions and power diagnostic platforms including reporter viruses, CRISPR-based assays, and nanotechnology-enhanced biosensors. Multimodal integration with photoacoustic tomography and PET further extends their translational utility. Remaining challenges include brightness/photostability limits and the need for broader translational validation, yet progress in structure-guided mutagenesis, computational/AI-assisted protein design, and hybrid imaging strategies promises to close these gaps. This mini-review synthesizes the design principles, viral imaging/detection use cases, and translational prospects of bacteriophytochrome-derived NIR FPs, highlighting their potential to advance viral surveillance, therapeutic evaluation, and precision diagnostics. Graphical Abstract Engineering of bacteriophytochrome-derived NIR FPs (iRFPs, miRFPs, PAiRFPs) as versatile tools for viral imaging, biosensing, and diagnostics.

Sestrin2 (SESN2) is a stress-inducible protein known for its cytoprotective functions, but its role in diabetic vascular complications remains unclear. This study investigated the impact of SESN2 on methylglyoxal (MGO)-induced endothelial–mesenchymal transition (EndMT). Human endothelial cells were transfected with SESN2 siRNA duplexes to silence SESN2 expression, followed by MGO treatment. SESN2 knockdown significantly exacerbated MGO-induced oxidative stress, as evidenced by the reduced expression of antioxidant markers. Furthermore, SESN2 silencing enhanced the inflammatory response to MGO, demonstrated by the increased levels of pro-inflammatory cytokines. Notably, SESN2 deficiency promoted EndMT, a key process in diabetes-induced cardiovascular complications, as shown by the increased expression of mesenchymal markers and the decreased expression of endothelial markers. These findings suggest that SESN2 plays a critical protective role in endothelial cells against MGO-induced damage. The study provides novel insights into the molecular mechanisms underlying diabetic cardiovascular complications and identifies SESN2 as a potential therapeutic target for preventing endothelial dysfunction in diabetes. Our results indicate that SESN2 downregulation may contribute to the pathogenesis of diabetic vascular complications by promoting EndMT, increased oxidative stress, and inflammation.