Ocular surface inflammation associated with Sjögren’s syndrome is characterized by a loss of secretory function and alteration in numbers of mucin secreting goblet cells. Such changes are a prominent feature of ocular surface inflammatory diseases and are attributed to inflammation; however, the exact effect of the inflammatory cytokines on conjunctival goblet cell function remains largely unknown. In this study, we developed a primary culture of mouse goblet cells from conjunctival tissue and evaluated the effects on their function by inflammatory cytokines detected in the conjunctiva of mouse model of Sjögren’s syndrome (Thrombospondin-1 deficient mice). We found that apoptosis of goblet cells was primarily induced by TNF-αand IFN-γ. These two cytokines also inhibited mucin secretion by goblet cells in response to cholinergic stimulation, whereas IL-6 enhanced such secretion. No changes in secretory response were detected in the presence of IL-13 or IL-17. Goblet cells proliferated to varying degrees in response to all the tested cytokines with the greatest response to IL-13 followed by IL-6. Our results therefore reveal that inflammatory cytokines expressed in the conjunctiva during an ocular surface disease directly disrupt conjunctival goblet cell functions, compromising the protective function of tears, thereby contributing to ocular surface damage.

Background: Human Lung Carcinoma (LC) is among the most diagnosed cancers across the world among those non-small cell lung cancer (NSCLC) comprises about 85%. Next Generation Sequencing based detection of mutations are now well established in molecular oncology. With the advent of modern diagnostic methods, it is now well known that there are several mutations and gene rearrangements which are associated with the development of LC. Among those mutations, TP53 is the most prevalent with the concomitant EGFR mutation. Methods: In this retrospective study, a total number of 414 patients have been incorporated who have attended RGCIRC in the period between November 2015 to March 2024. Clinical stage has been determined as per NCCN Guideline version 2.2024. Nucleic Acid (DNA and RNA) from FFPE samples were extracted and detection of mutation was performed by Next generation sequencing (NGS) method. Results: All 414 patients opted for the customised NGS panel for lung cancer among those 203 patients were TP53 mutation and 87 patients were EGFR mutation positive. 62 patients were TP53-EGFR double mutation positive. The results of this study have shown that TP53 mutated patients show poor prognosis with conventional therapy. However, TP53-EGFR co-mutated patient’s recovery rates are comparatively promising due to the availability of the targeted therapy of EGFR. Conclusion: Studies have shown that TP53 mutation is unlikely to derive clinical benefit in LC patients and shows poorer prognosis when compared to TP53 wild type and EGFR mutated patients show improved recovery due to availability of the Kinase Inhibitor (KI) treatment. In this study we have observed and concluded that TP53-EGFR co-mutated group also shows promising prognosis for the application of KI treatment. A further large cohort study will establish this clinical observation and enlighten more therapeutically relevant information.

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Mitochondrial dysfunction is not merely a byproduct of transformation but a driver of tumorigenesis, metastasis, and therapeutic resistance. Recent advancements in intercellular communication have identified Extracellular Vesicles (EVs) or exosomes as critical mediators that bridge the gap between the tumor and its microenvironment (TME). These EVs contain a complex repertoire of bioactive cargo, including proteins, lipids, and RNAs. Among the class of RNAs, small non-coding RNAs, microRNAs (miRNAs), are the most abundantly expressed bioactive compounds that are selectively packaged and delivered to recipient cells. EV-delivered miRNAs can target nuclear-encoded mitochondrial genes and have also been reported to localize to mitochondria (mitomiRs), where they function as post-transcriptional regulators of bioenergetic and mitochondrial dynamic adaptations that support tumor progression. This review explores the “EV-miRNA-Mitochondria Axis”, delineating the molecular mechanisms by which EV-carried miRNAs reprogram the “Mitochondrial Information Processing System” (MIPS) - a signaling network where mitochondria integrate metabolic cues (e.g., ROS, calcium flux) to dictate critical biological outcomes, such as immune regulation and cell survival. We summarized specific sorting machineries (e.g., hnRNPA2B1, Lupus La) that package oncogenic miRNAs into EVs and how these cargoes hijack mitochondrial function upon delivery. Specifically, we discussed how EV-miRNAs induce metabolic shifts, manipulate mitochondrial dynamics (fission/fusion), and inhibit the intrinsic apoptosis to drive cancer progression. Finally, we highlighted the dual utility of these EV-miRNAs as drivers of pathogenesis and promising non-invasive biomarkers for early diagnosis, prognostic and therapeutic monitoring.