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Purpose: Behçet's syndrome (BS) is a chronic inflammatory disease affecting the small and large vessels of the venous and arterial systems and is characterized by recurrent oral and genital ulcers. Uveitis represents the most typical ocular manifestation and completes the triple symptom complex originally described. Recognized treatments for Behçet's uveitis (BU) include systemic glucocorticoids and immunosuppressive agents. No study has reported on the use of upadacitinib for BS with panuveitis. Herein, we report the use of upadacitinib in two patients with BU suffering from macular edema and persistent inflammation, which was refractory to systemic glucocorticoids and immunosuppressive agents. Methods: We retrospectively followed-up two cases, including an adolescent girl and a man in his thirties, with a 2- and 10-year history of BS, respectively. Results: Upadacitinib successfully treated BU, leading to improved visual acuity, controlled intraocular inflammation, and the disappearance of macular edema in both patients. The patients in this study were either recalcitrant to or intolerant to conventional therapy and adalimumab. Only the female patient revealed a mildly abnormal blood picture and slight transaminitis after 6 months of upadacitinib administration. However, no serious adverse events were reported in either of the two patients during follow-up. Conclusion: Upadacitinib can be considered an important future option for managing recurrent and recalcitrant cases of BU, especially in those with chronic ocular inflammation and macular edema, which are refractory to conventional therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastasis, the hallmark of cancer, is accountable for about 90% of cancer-related deaths. Long noncoding RNA (lncRNA), a subset of the noncoding RNAs, has exhibited involvement in various processes, including immune evasion, cell proliferation, migration, and invasion, across multiple human diseases, notably cancer. The objective of our study was to identify a metastasis-associated lncRNA in lung cancer and elucidate the underlying mechanisms. Our findings indicate that Linc01703, which is notably downregulated in metastatic lung cancer cells, effectively suppresses lung cancer metastasis in vivo. Interestingly, Linc01703 does not directly impact the proliferation and invasion capabilities of lung cancer cells but rather inhibits cancer metastasis by promoting the secretion of CD81+ exosomes through the Rab27a/SYTL1/CD81 transport complexes. Consequently, our observations provide new insights into the potential clinical application of CD81+ exosome-based cancer therapy. Metastasis, a major cause of cancer-related mortality worldwide, frequently occurs early in the diagnosis of lung adenocarcinoma (LUAD). However, the precise molecular mechanisms governing the aggressive metastatic behavior of LUAD remain incompletely understood. In this study, we present compelling evidence indicating that the long noncoding RNA linc01703 is significantly downregulated in metastatic lung cancer cells. Intriguingly, in vivo experiments revealed that Linc01703 exerted a profound inhibitory effect on lung cancer metastasis without discernible impact on the in vitro proliferation or invasion capacities of LUAD cells. Mechanistically, Linc01703 enhanced the interaction between Rab27a, SYTL1, and CD81, consequently promoting the secretion of CD81+ exosomes. These exosomes, in turn, suppressed the infiltration of immune cells within the tumor microenvironment, thereby impeding LUAD metastasis. Importantly, our analysis of lung cancer tissues revealed a correlation between reduced CD81 expression and an unfavorable patient prognosis. Collectively, our findings suggest that Linc01703 functions as a metastasis suppressor by facilitating the secretion of CD81+ exosomes through the formation of the Rab27a/SYTL1/CD81 complex. [ABSTRACT FROM AUTHOR]

Uveitis is an inflammation of the iris, ciliary body, vitreous, retina, or choroid, which has been shown to be the first manifestation of numerous systemic diseases. Studies about the immunopathogenesis and treatment of uveitis are helpful to comprehend systemic autoimmune diseases, and delay the progression of systemic autoimmune diseases, respectively. Tumor necrosis factor-alpha (TNF-α), a pleiotropic cytokine, plays a pivotal role in intraocular inflammation based on experimental and clinical data. Evidence of the feasibility of using anti-TNF-α agents for uveitis management has increased. Although there are numerous studies on TNF-α in various autoimmune diseases, the pathological mechanism and research progress of TNF-α in uveitis have not been reviewed. Therefore, the objective of this review is to provide a background on the role of TNF-α in the immunopathogenesis of uveitis, as well as from bench to clinical research progress, to better guide TNF-α-based therapeutics for uveitis. [ABSTRACT FROM AUTHOR]