Platelet Glycoprotein Ibα Cytoplasmic Tail Exacerbates Thrombosis During Bacterial Sepsis.

Septic patients, coupling severe disseminated intravascular coagulation (DIC) and thrombocytopenia, have poor prognoses and higher mortality. The platelet glycoprotein Ibα (GPIbα) is involved in thrombosis, hemostasis, and inflammation response. However, it remains unclear whether the GPIbα cytoplasmic tail regulates sepsis-mediated platelet activation and inflammation, especially in Staphylococcus aureus () and Escherichia coli () infections.

The role of PKC in X-ray-induced megakaryocyte apoptosis and thrombocytopenia.

Thrombocytopenia is a critical complication after radiation therapy and exposure. Dysfunction of megakaryocyte development and platelet production are key pathophysiological stages in ionizing radiation (IR)-induced thrombocytopenia. Protein kinase C (PKC) plays an important role in regulating megakaryocyte development and platelet production.

X-rays Stimulate Granular Secretions and Activate Protein Kinase C Signaling in Human Platelets.

X-rays can induce morphological as well as functional changes in cells. Platelets are anuclear cellular fragments originating from megakaryocytes and are the major regulators in hemostasis and thrombosis. Platelet products are irradiated to avoid medical complications associated with platelet transfusion.

Actin polymerization regulates glycoprotein Ibα shedding.

Glycoprotein (GP) Ibα shedding mediated by ADAM17 (a disintegrin and metalloproteinase 17) plays an important role in negatively regulating platelet function and thrombus formation. However, the mechanism of GPIbα shedding remains elusive. Here, we show that jasplakinolide (an actin-polymerizing peptide)-induced actin polymerization results in GPIbα shedding and impairs platelet function.

[Effect of Protein Kinase A Activation on Aggregation Function of Platelets].

Objective: To investigate the effect of protein kinase A (PKA) activation on aggregation funetion of platelets in vitro.

Methods: The peripheral blood of healthy adults were collected, and the washed platelets were gained from collected peripheral blood. The washed platelets were treated with PKA activator Forskolin, then the platelet aggregation was induced by using Ristocetin, Thrombin, Collagen and ADP respectively, the platelet aggregation level was detected by the platelet aggregator.

Akt-mediated platelet apoptosis and its therapeutic implications in immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet count which can cause fatal hemorrhage. ITP patients with antiplatelet glycoprotein (GP) Ib-IX autoantibodies appear refractory to conventional treatments, and the mechanism remains elusive. Here we show that the platelets undergo apoptosis in ITP patients with anti-GPIbα autoantibodies.

Decreased Serum Lipid Levels and Ratios Correlate with Low Prevalence of Coronary Heart Disease in Patients with Parkinson's Disease.

Background: Patients with Parkinson's disease (PD) are at a lower risk of suffering cardiovascular events, but the underlying factors for this decreased risk remain unclear. Serum triglycerides (TG) and total cholesterol (TC), and their expression relative to high-density lipoprotein cholesterol (TG/HDL-C and TC/HDL-C), are independent predictors of cardiovascular events. This study aimed to determine if PD patients have decreased lipid levels and lipid ratios, which may underlie the decreased risk of coronary heart disease (CHD).

Protein kinase A determines platelet life span and survival by regulating apoptosis.

Apoptosis delimits platelet life span in the circulation and leads to storage lesion, which severely limits the shelf life of stored platelets. Moreover, accumulating evidence indicates that platelet apoptosis provoked by various pathological stimuli results in thrombocytopenia in many common diseases. However, little is known about how platelet apoptosis is initiated or regulated.

Receptor-interacting protein kinase 3 promotes platelet activation and thrombosis.

Previous studies have shown that receptor-interacting protein kinase 3 (RIP3) is involved in many important biological processes, including necroptosis, apoptosis, and inflammation. Here we show that RIP3 plays a critical role in regulating platelet functions and in vivo thrombosis and hemostasis. Tail bleeding times were significantly longer in -knockout (RIP3) mice compared with their wild-type (WT) littermates.

Ethanol Induces Platelet Apoptosis.

Background: Alcohol abuse incurs severe medical conditions, such as thrombocytopenia and hemorrhage, but the pathogenesis is not totally understood. Alcohol has been reported to induce apoptosis in eukaryotic cells, such as hepatocyte, nerve cell, corneal fibroblasts. However, it is still unclear whether alcohol induces platelet apoptosis.

Lovastatin induces platelet apoptosis.

Statins are widely used in the prevention of atherosclerosis and treatment of coronary artery disease because of pleiotropic effects on thrombosis. Thrombocytopenia and hemorrhage occurred in some statin-treated patients, but the reason remains unclear. In the current study, we show that lovastatin dose-dependently induces depolarization of mitochondrial inner transmembrane potential, leading to up-regulation of Bak, down-regulation of Bcl-XL, and activation of caspase-3/8/9.

Mechanism of TiO2 nanoparticle-induced neurotoxicity in zebrafish (Danio rerio).

Zebrafish (Danio rerio) has been used historically for evaluating the toxicity of environmental and aqueous toxicants, and there is an emerging literature reporting toxic effects of manufactured nanoparticles (NPs) in zebrafish embryos. Few researches, however, are focused on the neurotoxicity on adult zebrafish after subchronic exposure to TiO2 NPs. This study was designed to evaluate the morphological changes, alterations of neurochemical contents, and expressions of memory behavior-related genes in zebrafish brains caused by exposures to 5, 10, 20, and 40 μg/L TiO2 NPs for 45 consecutive days.

Nano-sized titanium dioxide-induced splenic toxicity: a biological pathway explored using microarray technology.

Titanium dioxide nanoparticles (TiO2 NPs) have been widely used in various areas, and its potential toxicity has gained wide attention. However, the molecular mechanisms of multiple genes working together in the TiO2 NP-induced splenic injury are not well understood. In the present study, 2.

Gene-expression changes in cerium chloride-induced injury of mouse hippocampus.

Cerium is widely used in many aspects of modern society, including agriculture, industry and medicine. It has been demonstrated to enter the ecological environment, is then transferred to humans through food chains, and causes toxic actions in several organs including the brain of animals. However, the neurotoxic molecular mechanisms are not clearly understood.

Nanosized TiO2-induced reproductive system dysfunction and its mechanism in female mice.

Recent studies have demonstrated nanosized titanium dioxide (nano-TiO2)-induced fertility reduction and ovary injury in animals. To better understand how nano-TiO2 act in mice, female mice were exposed to 2.5, 5, and 10 mg/kg nano-TiO2 by intragastric administration for 90 consecutive days; the ovary injuries, fertility, hormone levels, and inflammation-related or follicular atresia-related cytokine expression were investigated.

Cardiac oxidative damage in mice following exposure to nanoparticulate titanium dioxide.

Nanoparticulate titanium dioxide (nano-TiO2 ) is a widely used powerful nanoparticulate material with high stability, anticorrosion, and photocatalytic property. However, it is possible that during nano-TiO2 exposure, there may be negative effects on cardiovascular system in intoxicated mice. The present study was therefore undertaken to determine nano-TiO2 -induced oxidative stress and to determine whether nano-TiO2 intoxication alters the antioxidant system in the mouse heart exposed to 2.

Neurotoxicity and gene-expressed profile in brain-injured mice caused by exposure to titanium dioxide nanoparticles.

Titanium dioxide nanoparticles (TiO2 NPs) are widely used in toothpastes, sunscreens, and products for cosmetic purpose that the human use daily. Although the neurotoxicity induced by TiO2 NPs has been demonstrated, very little is known about the molecular mechanisms underlying the brain cognition and behavioral injury. In this study, mice were exposed to 2.

Molecular mechanism of titanium dioxide nanoparticles-induced oxidative injury in the brain of mice.

Numerous studies have demonstrated that the brain is one of the target organs in acute or chronic titanium dioxide (TiO2) nanoparticles (NPs) toxicity, and oxidative stress plays an important role in this process. However, whether brain oxidative injury responds to TiO2 NPs by activating the P38-nuclear factor-E2-related factor-2 (Nrf-2) pathway is not fully understood. The present study aimed to examine activation of the P38-Nrf-2 signaling pathway associated with oxidative stress in the mouse brain induced by intranasal administration of TiO2 NPs for 90 consecutive days.

Intragastric exposure to titanium dioxide nanoparticles induced nephrotoxicity in mice, assessed by physiological and gene expression modifications.

Background: Numerous studies have demonstrated that titanium dioxide nanoparticles (TiO2 NPs) induced nephrotoxicity in animals. However, the nephrotoxic multiple molecular mechanisms are not clearly understood.

Methods: Mice were exposed to 2.

Gene expression profile in chronic mouse liver injury caused by long-term exposure to CeCl3.

Numerous studies have demonstrated lanthanide (Ln) accumulation in the liver, and the corresponding damage; however, very little work has been done to evaluate the relationship between Ln-induced liver injury and its gene expression profile in mice. In this study, liver injury and gene-expressed profiles in male mice induced by oral administration of CeCl3 (2 mg/kg) via gavage for 90 consecutive days were investigated. The results showed that cerium accumulation, liver inflammation, and hepatocyte necrosis were observed.

Pulmotoxicological effects caused by long-term titanium dioxide nanoparticles exposure in mice.

Exposure to titanium dioxide nanoparticles (TiO(2) NPs) has been demonstrated to result in pulmonary inflammation in animals; however, very little is known about the molecular mechanisms of pulmonary injury due to TiO(2) NPs exposure. The aim of this study was to evaluate the oxidative stress and molecular mechanism associated with pulmonary inflammation in chronic lung toxicity caused by the intratracheal instillation of TiO(2) NPs for 90 consecutive days in mice. Our findings suggest that TiO(2) NPs are significantly accumulated in the lung, leading to an obvious increase in lung indices, inflammation and bleeding in the lung.

Gene expression in liver injury caused by long-term exposure to titanium dioxide nanoparticles in mice.

Although liver toxicity induced by titanium dioxide nanoparticles (TiO(2) NPs) has been demonstrated, very little is known about the molecular mechanisms of multiple genes working together underlying this type of liver injury in mice. In this study, we used the whole-genome microarray analysis technique to determine the gene expression profile in the livers of mice exposed to 10 mg/kg body weight TiO(2) NPs for 90 days. The findings showed that long-term exposure to TiO(2) NPs resulted in obvious titanium accumulation in the liver and TiO(2) NP aggregation in hepatocyte nuclei, an inflammatory response, hepatocyte apoptosis, and liver dysfunction.

Oxidative damage of lung and its protective mechanism in mice caused by long-term exposure to titanium dioxide nanoparticles.

Exposure to titanium dioxide nanoparticles (TiO(2) NPs) elicits an adverse response such as oxidative damage. The molecular targets of TiO(2) NPs remain largely unidentified. In the present study, the function and signal pathway of nuclear factor erythroid 2 related factor 2 (Nrf2) in protection against TiO(2) NPs-induced oxidative stress in the mouse lung were investigated.