PARIN5, a Novel Thrombin Receptor Antagonist Modulates a Streptozotocin Mice Model for Diabetic Encephalopathy.

Diabetic encephalopathy (DE) is an inflammation-associated diabetes mellitus (DM) complication. Inflammation and coagulation are linked and are both potentially modulated by inhibiting the thrombin cellular protease-activated receptor 1 (PAR1). Our aim was to study whether coagulation pathway modulation affects DE.

LPS-Induced Coagulation and Neuronal Damage in a Mice Model Is Attenuated by Enoxaparin.

Background. Due to the interactions between neuroinflammation and coagulation, the neural effects of lipopolysaccharide (LPS)-induced inflammation (1 mg/kg, intraperitoneal (IP), n = 20) and treatment with the anti-thrombotic enoxaparin (1 mg/kg, IP, 15 min, and 12 h following LPS, n = 20) were studied in C57BL/6J mice. Methods.

Intrinsic Expression of Coagulation Factors and Protease Activated Receptor 1 (PAR1) in Photoreceptors and Inner Retinal Layers.

The aim of this study was to characterize the distribution of the thrombin receptor, protease activated receptor 1 (PAR1), in the neuroretina. Neuroretina samples of wild-type C57BL/6J and PAR1 mice were processed for indirect immunofluorescence and Western blot analysis. Reverse transcription quantitative real-time PCR (RT-qPCR) was used to determine mRNA expression of coagulation Factor X (FX), prothrombin (PT), and PAR1 in the isolated neuroretina.

Suprachoroidal delivery of bevacizumab in rabbit in vivo eyes: Rapid distribution throughout the posterior segment.

Purpose: To test the in-vivo bio-distribution and safety of bevacizumab delivery into the suprachoroidal space (SCS) using a novel injection system in a large eye model.

Methods: Bevacizumab (1.25 mg) was injected into the vitreous (IVT, 50 µL, n = 12) or the SCS, (150 µL, n = 37) of live rabbits.

Efficacy and safety of injecting increasing volumes into the extravascular spaces of the choroid using a blunt adjustable depth injector.

Purpose: To evaluate the efficacy and safety of injecting increasing volumes into the extravascular spaces of the choroid (EVSC) in rabbit eyes in vivo using a blunt adjustable depth injector.

Methods: Indocyanine green (ICG) was injected in the superior-temporal quadrant, 2 mm posterior to the limbus at increasing volumes (0.1-0.

Repetitive magnetic stimulation protects corneal epithelium in a rabbit model of short-term exposure keratopathy.

Purpose: To investigate the effect of repetitive magnetic stimulation (RMS) on corneal epithelial permeability in a rabbit model of exposure keratopathy.

Methods: 61 female New Zealand White (NZW) rabbits were treated on one eye with repetitive magnetic stimulation (RMS) at a frequency of 20 Hz for 15 min. The other eye was untreated.

The p53-Mdm2 loop: a critical juncture of stress response.

The presence of a functional p53 protein is a key factor for the proper suppression of cancer development. A loss of p53 activity, by mutations or inhibition, is often associated with human malignancies. The p53 protein integrates various stress signals into a growth restrictive cellular response.

T cell survival and function requires the c-Abl tyrosine kinase.

C-Abl (Abl) regulates multiple cellular processes, including proliferation, survival, shape determination and motility, and participates in cellular responses to genotoxic and oxidative stress stimuli. Mice lacking Abl exhibit retarded growth, osteoporosis and defects in the immune system resulting in lymphopoenia and susceptibility to infections, leading to early death. To define the role of Abl in the regulation of adult T cells we ablated Abl exclusively in T cells by generating mice with floxed abl alleles and expressing an Lck-Cre transgene (Abl-T(-/-)).

C-Abl as a modulator of p53.

P53 is renowned as a cellular tumor suppressor poised to instigate remedial responses to various stress insults that threaten DNA integrity. P53 levels and activities are kept under tight regulation involving a complex network of activators and inhibitors, which determine the type and extent of p53 growth inhibitory signaling. Within this complexity, the p53-Mdm2 negative auto-regulatory loop serves as a major route through which intra- and extra-cellular stress signals are channeled to appropriate p53 responses.

Treatment of chronic myeloid leukemia cells with imatinib (STI571) impairs p53 accumulation in response to DNA damage.

Chronic myelogenous leukaemia (CML) is induced by the Bcr-Abl fusion protein. Inhibition of Bcr-Abl by STI571 is widely used to treat CML patients. Unlike in most cancer types, the frequency of p53 mutations in CML is low.

Apoptosis - the p53 network.

Exposure to cellular stress can trigger the p53 tumor suppressor, a sequence-specific transcription factor, to induce cell growth arrest or apoptosis. The choice between these cellular responses is influenced by many factors, including the type of cell and stress, and the action of p53 co-activators. p53 stimulates a wide network of signals that act through two major apoptotic pathways.

Tyrosine phosphorylation of Mdm2 by c-Abl: implications for p53 regulation.

The p53 tumor suppressor is inhibited and destabilized by Mdm2. However, under stress conditions, this downregulation is relieved, allowing the accumulation of biologically active p53. Recently we showed that c-Abl is important for p53 activation under stress conditions.