The secreted extracellular protein, transforming growth factor beta induced (TGFBI or βIGH3), has roles in regulating numerous biological functions, including cell adhesion and bone formation, both during embryonic development and during the pathogenesis of human disease. TGFBI has been most studied in the context of hereditary corneal dystrophies, where mutations in TGFBI result in accumulation of TGFBI in the cornea. In cancer, early studies focused on TGFBI as a tumor suppressor, in part by promoting chemotherapy sensitivity. However, in established tumors, TGFBI largely has a role in promoting tumor progression, with elevated levels correlating to poorer clinical outcomes. As an important regulator of cancer progression, TGFBI expression and function is tightly regulated by numerous mechanisms including epigenetic silencing through promoter methylation and microRNAs. Mechanisms to target TGFBI have potential clinical utility in treating advanced cancers, while assessing TGFBI levels could be a biomarker for chemotherapy resistance and tumor progression.Investigations have shown that infection from the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is responsible also for initiating severe inflammatory responses that can lead macrovascular and microvascular thrombosis. Several studies have already described acute limb ischemia and peripheral arterial disease in critically ill patients with Coronavirus disease 2019 (Covid-19), as well as coronary artery disease and ischemic stroke as a manifestation usually associated with respiratory distress. However, what still remains unclear is how long inflammation and thrombotic derangements can last after recovery from the symptoms of Covid-19. Hence, in this article we report 3 cases of arterial thrombotic sequalae after this viral infection. To the best of our knowledge, this is the first cases' series that had described different delayed vascular arterial complications, which occurred after the index infection, with a negative nasopharyngeal swab and Covid-19 systemic symptoms resumption. A better understanding of the coagulopathy in Covid-19 could have an essential role to guide prevention and treatment of arterial thromboembolic events, both during and after the viral infection. Further investigations are required to confirm these data and to estabilish the type, dose and duration of anticoagulant/antiplatelet therapy not just during but also after Covid-19 infection. The SARS-CoV-2 infection is associated with significant morbidity and mortality rates. The impact of thrombotic complications has been increasingly recognized as an important component of this disease. We describe four cases of spontaneous acute aortic thrombosis in patients with SARS-CoV-2 infection observed from March to December 2020 at Fondazione Policlinico Universitario Gemelli IRCCS in Rome, Italy.We describe four cases of spontaneous acute aortic thrombosis in patients with SARS-CoV-2 infection observed from March to December 2020 at Fondazione Policlinico Universitario Gemelli IRCCS in Rome, Italy.Regulatory T cells (Tregs) control immune responses in autoimmune disease, transplantation, and enable antigen-specific tolerance induction in protein-replacement therapies. Tregs can exert a broad array of suppressive functions through their T cell receptor (TCR) in a tissue-directed and antigen-specific manner. This capacity can now be harnessed for tolerance induction by "redirecting" polyclonal Tregs to overcome low inherent precursor frequencies and simultaneously augment suppressive functions. buy BMS303141 With the use of hemophilia A as a model, we sought to engineer antigen-specific Tregs to suppress antibody formation against the soluble therapeutic protein factor (F)VIII in a major histocompatibility complex (MHC)-independent fashion. Surprisingly, high-affinity chimeric antigen receptor (CAR)-Treg engagement induced a robust effector phenotype that was distinct from the activation signature observed for endogenous thymic Tregs, which resulted in the loss of suppressive activity. Targeted mutations in the CD3ζ or CD28 signaling motifs or interleukin (IL)-10 overexpression were not sufficient to restore tolerance. In contrast, complexing TCR-based signaling with single-chain variable fragment (scFv) recognition to generate TCR fusion construct (TRuC)-Tregs delivered controlled antigen-specific signaling via engagement of the entire TCR complex, thereby directing functional suppression of the FVIII-specific antibody response. These data suggest that cellular therapies employing engineered receptor Tregs will require regulation of activation thresholds to maintain optimal suppressive function.Phosphoglycerate kinase 1 (PGK1), a critical component of the glycolytic pathway, relates to the development of various cancers. However, the mechanisms of PGK1 inhibition and physiological significance of PGK1 inhibitors in cancer cells are unclear. Long non-coding RNAs (lncRNAs) play a vital role in tumor growth and progression. Here, we identify a lncRNA LINC00926 that negatively regulates PGK1 expression and predicts good clinical outcome of breast cancer. LINC00926 downregulates PGK1 expression through the enhancement of PGK1 ubiquitination mediated by E3 ligase STUB1. Moreover, hypoxia inhibits LINC00926 expression and activates PGK1 expression largely through FOXO3A. FOXO3A/LINC00926/PGK1 axis regulates breast cancer glycolysis, tumor growth, and lung metastasis both in vitro and in vivo. In breast cancer patients, LINC00926 expression is negatively correlated with PGK1 and positively correlated with FOXO3A expression. Our work established FOXO3A/LINC00926/PGK1 as a critical axis to regulate breast cancer growth and progression. Targeting PGK1 or supplement of LINC00926 or FOXO3A could be potential therapeutic strategies in breast cancer.A molecular hallmark in Parkinson's disease (PD) pathogenesis are α-synuclein aggregates. Cerebral dopamine neurotrophic factor (CDNF) is an atypical growth factor that is mostly resident in the endoplasmic reticulum but exerts its effects both intracellularly and extracellularly. One of the beneficial effects of CDNF can be protecting neurons from the toxic effects of α-synuclein. Here, we investigated the effects of CDNF on α-synuclein aggregation in vitro and in vivo. We found that CDNF directly interacts with α-synuclein with a KD = 23 ± 6 nM and reduces its auto-association. Using nuclear magnetic resonance (NMR) spectroscopy, we identified interaction sites on the CDNF protein. Remarkably, CDNF reduces the neuronal internalization of α-synuclein fibrils and induces the formation of insoluble phosphorylated α-synuclein inclusions. Intra-striatal CDNF administration alleviates motor deficits in rodents challenged with α-synuclein fibrils, though it did not reduce the number of phosphorylated α-synuclein inclusions in the substantia nigra.