The C3/C3aR pathway exacerbates acetaminophen-induced mouse liver injury via upregulating podoplanin on the macrophage.

Acute liver failure (ALF) is a life-threatening condition that occurs when the liver sustains severe damage and rapidly loses its function. The primary cause of ALF is the overdose of acetaminophen (APAP), and its treatment is relatively limited. The involvement of the complement system in the development of ALF has been implicated.

Platelet ITGA2B inhibits caspase-8 and Rip3/Mlkl-dependent platelet death though PTPN6 during sepsis.

Platelets play an important role in the pathogenesis of sepsis and platelet transfusion is a therapeutic option for sepsis patients, although the exact mechanisms have not been elucidated so far. ITGA2B encodes the αIIb protein in platelets, and its upregulation in sepsis is associated with increased mortality rate. Here, we generated a (Q887X) knockin mouse, which significantly reduced ITGA2B expression of platelet and megakaryocyte.

Single-cell RNA-seq of heart reveals intercellular communication drivers of myocardial fibrosis in diabetic cardiomyopathy.

Myocardial fibrosis is the characteristic pathology of diabetes-induced cardiomyopathy. Therefore, an in-depth study of cardiac heterogeneity and cell-to-cell interactions can help elucidate the pathogenesis of diabetic myocardial fibrosis and identify treatment targets for the treatment of this disease. In this study, we investigated intercellular communication drivers of myocardial fibrosis in mouse heart with high-fat-diet/streptozotocin-induced diabetes at single-cell resolution.

Astrocyte-Derived TNF-α-Activated Platelets Promote Cerebral Ischemia/Reperfusion Injury by Regulating the RIP1/RIP3/AKT Signaling Pathway.

Ischemic stroke is a clinical syndrome caused by the disruption of blood flow into cerebral tissues and is associated with high disability and mortality rates. Studies have established the pathological role of platelets in cerebral ischemia/reperfusion (I/R) injury, although the underlying mechanism of action remains largely unclear. In this study, we created an I/R mouse model via middle cerebral artery occlusion and reperfusion (MCAO/R) and analyzed the transcriptomic profiles of the ipsilateral and contralateral cortices using RNA-seq.

Glaucocalyxin a protect liver function via inhibiting platelet over-activation during sepsis.

Background: Rabdosia japonica (Burm. f.) var.

[Effects of the ITGA2B Nonsense Mutation (c.2659C > T, p.Q887X) on Platelet Function in a Mouse Model of Glanzmann's Thrombasthenia Generated with CRISPR/Cas9 Technology].

Objective: To construct a mouse model of Glanzmann's thrombasthenia (GT) with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation by CRISPR/Cas9 technology, and then further explore the expression and function of glycoprotein αIIbβ3 on the surface of platelet membrane.

CLEC-2-dependent platelet subendothelial accumulation by flow disturbance contributes to atherogenesis in mice.

Platelets play an essential role in atherosclerosis, but the underlying mechanisms remain to be addressed. This study is to investigate the role of platelets in d-flow induced vascular inflammation and the underlying mechanism. We established a disturbed blood flow (d-flow) model by partial carotid ligation (PCL) surgery using atherosclerosis-susceptible mice and wild-type mice to observe the d-flow induced platelet accumulation in the subendothelium or in the plaque by immunostaining or transmission electron microscopy.

Nonsense-mediated mRNA decay efficiency influences bleeding severity in ITGA2B c.2659C > T (p.Q887X) knock-in mice.

Glanzmann's thrombasthenia (GT) is a severe hemorrhagic disease. It is caused by mutations in ITGA2B or ITGB3, which are the respective genes encoding integrin αIIb and β3. Despite widespread mutational analysis, the mechanisms underlying the extensive variability in bleeding severity observed among affected individuals remains poorly understood.

Monocyte upregulation of podoplanin during early sepsis induces complement inhibitor release to protect liver function.

Multiple organ failure in sepsis is a progressive failure of several interdependent organ systems. Liver dysfunction occurs early during sepsis and is directly associated with patient death; however, the underlying mechanism of liver dysfunction is unclear. Platelet transfusion benefits patients with sepsis, and inhibition of complement activation protects liver function in septic animals.

An essential role of high-molecular-weight kininogen in endotoxemia.

In this study, we show that mice lacking high-molecular-weight kininogen (HK) were resistant to lipopolysaccharide (LPS)-induced mortality and had significantly reduced circulating LPS levels. Replenishment of HK-deficient mice with human HK recovered the LPS levels and rendered the mice susceptible to LPS-induced mortality. Binding of HK to LPS occurred through the O-polysaccharide/core oligosaccharide, consistent with the ability to bind LPS from , , , and different strains.

[Antagonistic effects of estrogen on iron-induced bone resorption and its mechanism].

Objective: To explore the antagonistic effect of estrogen on iron-induced bone resorption and the role of oxidative stress.

Methods: In vivo, 8-week-old female imprinting control region mice were randomly divided into 3 groups of ferritin (F), ovariectomy (OVX) and F+OVX. Intervention was made by ferric ammonium citrate (FAC) and OVX.

High molecular weight kininogen binds phosphatidylserine and opsonizes urokinase plasminogen activator receptor-mediated efferocytosis.

Phagocytosis of apoptotic cells (efferocytosis) is essential for regulation of immune responses and tissue homeostasis and is mediated by phagocytic receptors. In this study, we found that urokinase plasminogen activator receptor (uPAR) plays an important role in internalization of apoptotic cells and also characterized the underlying mechanisms. In a flow cytometry-based phagocytic assay, uPAR-deficient macrophages displayed significant defect in internalization but not tethering of apoptotic cells.

A role for bradykinin in the development of anti-collagen antibody-induced arthritis.

Objectives: Clinical and experimental observations have suggested that bradykinin, a major activation product of the plasma kallikrein-kinin system, is involved in the pathogenesis of arthritis, but the pathogenic role of bradykinin receptors remains inconclusive. In this study we examined whether bradykinin receptors are important in the pathogenesis of anti-collagen antibody-induced arthritis (CAIA) using double receptor-deficient (B1RB2R(-/-)) mice.

Methods: CAIA was induced in B1RB2R(+/+) and B1RB2R(-/-) mice by injection of an anti-collagen antibody cocktail on day 0 and lipopolysaccharide on day 3.