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Schistosome flukes induce pathology due to trapped parasite eggs, producing a granulomatous-immune response delineated by fibrosis and the deposition of collagen in the liver. The authors present whole animal imaging for the quantitation of hepatic collagen deposition during the early stages of pathology.
Having previously demonstrated that p17 from HIV can influence both lymphoma tumor growth and angiogenesis, here the authors investigated the mechanism of these findings. They show that p17 activates the epidermal growth factor-receptor on brain endothelial cells stimulating down-stream signalling responsible for initiating angiogenesis.
Highly immunogenic tumors were implanted in mice deficient in either T cell skin homing molecules or T cell gut homing molecules. Rejection of tumors was deficient in skin or gut, respectively, but intact in unaffected tissues. The authors conclude that T cell trafficking plays an important and heretofore overlooked role in tumor immunity.
This study evaluated both innate and adaptive cell types of myeloid and lymphoid lineage from both genders of three major immunocompetent mouse strains used in pre-clinical research. Results of the study underscore that both innate and cell-mediated immune profile varies dramatically based on mouse strain and gender, which will significantly impact on interpretation of experimental outcome in a wide spectrum of studies, including cancer.
Bone morphogenetic protein (BMP) 9 is a potent inducer of osteogenic differentiation from mesenchymal stem cells, but the mediators of BMP9-induced osteogenesis remain elusive. Here, the authors show that inhibition of Notch1 signaling effectively diminishes BMP9-induced osteogenesis. Genetic disruption of Notch pathway severely impairs BMP9-induced bone formation. Thus, these results demonstrate that Notch signaling may play an essential role in coordinating osteogenic differentiation.
In this study, the authors show that overexpression of hypoxia-inducible factor(HIF)-1α by ERK1/2, Akt and NF-κB activation contributes to melphalan-resistance in multiple myeloma (MM) cells. Additionally, inhibition of HIF-1α resensitizes melphalan-resistant MM cells to melphalan. Therefore, HIF-1α inhibitors may be therapeutically useful as anti-multidrug resistance protein agents in MM.
The cytoskeletal GTPase SEPT6 is elevated during hepatic stellate cell (HSC) activation and in liver fibrosis. SEPT6 promotes HSC activation, proliferation, cell cycle progression, survival and migration through the TGF-β1/Smad, MAPK and PI3K/AKT signaling pathways. Adenovirus-mediated SEPT6 inhibition attenuates thioacetamide-induced liver fibrosis.
This paper describes mini-XPerT, a multiplexed screen to simultaneously measure cellular contraction, endothelial barrier function, and cytoskeletal and cell-cell junctional changes. It is the unique combination of these measurements that has enabled the authors to unveil the distinct biophysical mechanisms of barrier defense conferred by Y-27632 and Angpt-1. Mini-XPerT is likely to be applicable across the spectrum of basic and translational science - in mechanistic studies of the endothelium across numerous diseases, and for high-throughput drug discovery.
Mitochondrial pyruvate carrier1 (MPC1) is a key factor that controls pyruvate transportation in mitochondria. Renal cell carcinoma (RCC) patients with higher MPC1 expression in tumors exhibit longer overall survival rate than those with lower MPC1. This study shows that MPC1 is a novel prognostic biomarker to predict patient.
A poorly developed placental capillary network is associated with early onset fetal growth restriction (FGR) and pre-eclampsia (PE). First trimester placental endothelial cells from pregnancies at increased risk of developing early onset FGR/PE were more sensitive to apoptotic stimuli and this was functionally linked to the synthesis of NO. This may contribute to the poor placental vascular development seen in ongoing pregnancies.
Using a novel slingshot 1 phosphatase (SSH1) knock-out mouse model, the authors demonstrate that loss of the actin-binding protein potentiates angiotensin II-induced medial thickening and fibrosis due to altered TGFβ1 signaling, resulting in increased expression of fibronectin and osteopontin.
Defective thermogenic response to calorie overload contributes to obesity and, in foz/foz mice, to nonalcoholic steatohepatitis (NASH). Activation of brown adipose tissue function by b3AR-agonists together with moderate calorie restriction improves the obese phenotype and resolves NASH pathology. This identifies the brown adipose tissue as a target for adjuvant therapy for NASH.
The underlying immunopathogenic mechanisms of autoimmune hepatitis (AIH) have not been well elucidated. Kruppel-like factors 14 (KLF14) may regulate Treg differentiation, but the biological functions remain unclear. In this study, the authors reveal that KLF14 plays an as yet unrecognized role in immune- mediated hepatitis via induced Treg differentiation and inflammatory cytokine suppression. These findings indicate the possibility of KLF14 as a therapeutic target in AIH patients.
Bronchial epithelium is now believed to participate in the pathophysiology of bronchial asthma. In this report, the authors show that the ΔNp63 transcription factor, expressed in the basal layer of bronchus, modulates distinctive survival and immune-related bronchial epithelial responses. These results suggest functional significance of the epithelial shedding found in the pathology of bronchial asthma.