Publications

Fatal COVID-19 and Non-COVID-19 Acute Respiratory Distress Syndrome is associated with Incomplete Alveolar Type 1 Epithelial Cell Differentiation from the Transitional State Without Fibrosis

ARDS due to COVID-19 and other etiologies results from injury to the alveolar epithelial cell (AEC) barrier resulting in noncardiogenic pulmonary edema, which causes acute respiratory failure; clinical recovery requires epithelial regeneration. During physiologic regeneration in mice, AEC2s proliferate, exit the cell cycle, and transiently assume a transitional state before differentiating into AEC1s; persistence of the transitional state is associated with pulmonary fibrosis in humans.

Placozoan fiber cells: mediators of innate immunity and participants in wound healing

Placozoa is a phylum of non-bilaterian marine animals. These small, flat organisms adhere to the substrate via their densely ciliated ventral epithelium, which mediates mucociliary locomotion and nutrient uptake. They have only six morphological cell types, including one, fiber cells, for which functional data is lacking. Fiber cells are non-epithelial cells with multiple processes. We used electron and light microscopic approaches to unravel the roles of fiber cells in Trichoplax adhaerens, a representative member of the phylum.

Post-translational modifications by SIRT3 de-2-hydroxyisobutyrylase activity regulate glycolysis and enable nephrogenesis

Abnormal kidney development leads to lower nephron number, predisposing to renal diseases in adulthood. In embryonic kidneys, nephron endowment is dictated by the availability of nephron progenitors, whose self-renewal and differentiation require a relatively repressed chromatin state. More recently, NAD+-dependent deacetylase sirtuins (SIRTs) have emerged as possible regulators that link epigenetic processes to the metabolism. Here, we discovered a novel role for the NAD+-dependent deacylase SIRT3 in kidney development.

CD105+CD90+CD13+ identifies a clonogenic subset of adventitial lung fibroblasts

Mesenchymal cells are important components of specified niches in the lung, and can mediate a wide range of processes including tissue regeneration and repair. Dysregulation of these processes can lead to improper remodeling of tissue as observed in several lung diseases. The mesenchymal cells responsible remain poorly described, partially due to the heterogenic nature of the mesenchymal compartment and the absence of appropriate markers.

Molecular analysis of AAV5-hFVIII-SQ vector genome-processing kinetics in transduced mouse and nonhuman primate livers

Valoctocogene roxaparvovec (AAV5-hFVIII-SQ) is an adeno-associated virus serotype 5 (AAV5)-based gene therapy vector containing a B-domain-deleted human coagulation Factor VIII (hFVIII) gene controlled by a liver-selective promoter. AAV5-hFVIII-SQ is currently under clinical investigation as treatment for severe hemophilia A. The full-length AAV5-hFVIII-SQ is >4.9 kb, which is over the optimal packaging limit of AAV5.

P.0552 The early therapeutic efficacy of lurasidone in a rodent model of depression: a behavioural and biomolecular study

Background: Stress represents a major contributor for the development of mental illness. Accordingly, exposure of adult rats to chronic stress represents a valuable experimental tool to investigate the ability of pharmacological intervention to counteract the adverse effects produced by stress exposure. The aim of this study was to perform a time course analyses of the changes produced by the antipsychotic drug lurasidone in the Chronic Mild Stress (CMS) model, in order to identify early mechanisms that may contribute to its therapeutic activity.

Clinical impact of Fn-induced high expression of KIR2DL1 in CD8 T lymphocytes in oesophageal squamous cell carcinoma

To analyze the correlation between the inducing effect of Fusobacterium nucleatum (Fn) on the surface expression of the inhibitory receptor KIR2DL1 on CD8+ T cells in oesophageal squamous cell carcinoma (ESCC) and the clinicopathological features and survival prognosis and to explore its clinical significance.The inducing effect of Fn on CD8+ T cell surface inhibitory receptor KIR2DL1 expression was analyzed in a coculture system of human CD8+ T cells and ESCC cells infected with Fn.

Topical application of cannabinoid-ligands ameliorates experimental dry-eye disease

Dry eye disease (DED) is a multifactorial disease, with limitations regarding efficacy and tolerability of applied substances. Among several candidates, the endocannabinoid system with its receptors (CB1R and CB2R) were reported to modulate inflammation, wound healing and pain, which are also core DED pathomechanisms.

Prolyl-4-hydroxylases 2 and 3 control erythropoietin production in renin-expressing cells of mouse kidneys

Activation of the hypoxia-signalling pathway induced by deletion of the ubiquitin-ligase von Hippel-Lindau protein causes an endocrine shift of renin-producing cells to erythropoietin (EPO)-expressing cells. However, the underlying mechanisms have not yet been investigated. Since oxygen-regulated stability of hypoxia-inducible transcription factors relevant for EPO expression is dependent on the activity of prolyl-4-hydroxylases (PHD) 2 and 3, this study aimed to determine the relevance of different PHD isoforms for the EPO expression in renin-producing cells in vivo.

Vitamin D treatment induces in vitro and ex vivo transcriptomic changes indicating anti-tumor effects

Vitamin D deficiency is associated with risk of several common cancers, including colorectal cancer (CRC). Here we have utilized patient derived epithelial organoids (ex vivo) and CRC cell lines (in vitro) to show that calcitriol (1,25OHD) increased the expression of the CRC tumor suppressor gene, CDH1, at both the transcript and protein level. Whole genome expression analysis demonstrated significant differential expression of a further six genes after 1,25OHD treatment, including genes with established links to carcinogenesis GADD45, EFTUD1 and KIAA1199.

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