Endothelial PERK-ATF4-JAG1 axis activated by T-ALL remodels bone marrow vascular niche.

The endoplasmic reticulum unfolded protein response (UPR) is a conserved adaptive signaling in ER homeostasis and has emerged as critical in highly proliferating cells and potential treatment target for acute T-cell lymphoblastic leukemia (T-ALL). in this study, we assessed the transcriptomic and phenotypic alterations in UPR response of the bone marrow endothelial cells (ECs) in mice engrafted with T-ALL and in bone marrow specimens from patients who have T-ALL. We used PERK inhibitor and generated endothelial specific PERK knockout mice to study the impact of PERK on leukemia progression and hematopoiesis.

Targeting CRABP-II overcomes pancreatic cancer drug resistance by reversing lipid raft cholesterol accumulation and AKT survival signaling.

Background: Resistance to standard therapy is a major reason for the poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Developing novel therapy to overcome PDAC drug-resistance is urgently needed. CRABP-II was highly expressed in all PDAC but not expressed in normal pancreatic tissues and chronic pancreatitis.

Vascular thrombosis and vasculitis in the gastrointestinal tract are associated with poor prognosis in patients with COVID-19.

Aim: To report pathologic findings in the gastrointestinal (GI) tract of coronavirus disease 2019 (COVID-19) patients.

Material And Methods: we evaluated clinical and GI tract histologic findings in six COVID-19 patients that presented with GI symptoms like diarrhea, and abdominal pain. This study includes surgical resection specimens from five patients and two sets of biopsy specimens from one patient.

Notch-Regulated Dendritic Cells Restrain Inflammation-Associated Colorectal Carcinogenesis.

Conventional dendritic cells (cDC) play a central role in T-cell antitumor responses. We studied the significance of Notch-regulated DC immune responses in a mouse model of colitis-associated colorectal cancer in which there is epithelial downregulation of Notch/Hes1 signaling. This defect phenocopies that caused by (GDP-mannose 4,6-dehydratase) mutation in human colorectal cancers.

MUPP1 complexes renal K+ channels to alter cell surface expression and whole cell currents.

We previously found that the Ca(2+)-sensing receptor (CaR) interacts with and inactivates the inwardly rectifying K(+) channel Kir4.2 that is expressed in the kidney cortex and that has a COOH-terminal PDZ domain. To identify potential scaffolding proteins that could organize a macromolecular signaling complex involving the CaR and Kir4.

Inhibition of Nox-4 activity by plumbagin, a plant-derived bioactive naphthoquinone.

NAD(P)H oxidase contributes to the pathogenesis of cancer and cardiovascular diseases such as hypertension, atherosclerosis, restenosis, cardiac hypertrophy and heart failure. Plumbagin, a plant-derived naphthoquinone, has been shown to exert anticarcinogenic and anti-atherosclerosis effects in animals. However, the molecular mechanisms underlying these effects remain unknown.

Cyclophilin A functions as an endogenous inhibitor for membrane-bound guanylate cyclase-A.

Cyclophilin A (CypA), a receptor for the immunosuppressive agent cyclosporin A, is a cis-trans-peptidyl-prolyl isomerase (PPIase). It accelerates the cis-trans isomerization of prolyl-peptide bonds. CypA binds and regulates the activity of a variety of proteins.

Cyclosporin A disrupts bradykinin signaling through superoxide.

Cyclosporin A (CsA) is used to reduce transplant rejection rates. Chronic use, however, has a destructive toxic effect on the kidney, resulting in hypertension. In this study, we investigated the effects of CsA treatment on the bradykinin/soluble guanylate cyclase signaling cascade and the involvement of superoxide in LLC-PK1 porcine kidney proximal tubule cells.

The bradykinin/soluble guanylate cyclase signaling pathway is impaired in androgen-independent prostate cancer cells.

The activation of soluble guanylate cyclase by bradykinin and sodium nitroprusside (SNP), a direct activator of soluble guanylate cyclase, was evaluated in androgen-sensitive LNCaP and androgen-independent PC3 and DU145 prostate cancer cells. Bradykinin and SNP activated soluble guanylate cyclase in LNCaP cells, but not in PC3 and DU145 cells. Western blot analysis revealed that the bradykinin B2 receptor, Gqalpha, phospholipase Cgamma and endothelial nitric oxide synthase were expressed in LNCaP, PC3 and DU145 cells.