Objective: THROMBIN is a proinflammatory and pro-coagulant agent which is upregulated in several human diseases. THROMBIN has a critical role in promoting cell proliferation and microvascular leakage in malignant cells, resulting in cancer growth and progression. Here, we explored the potential therapeutic value of curcumin on permeability induced by THROMBIN in mice. Materials and Methods: To assess the activity of curcumin on THROMBIN-induced vascular permeability mice model, C57BL / 6 mice were randomly divided into four groups: (1) control (2) THROMBIN (3) THROMBIN + Curcumin and (4) THROMBIN + Metformin. Thirty minutes after treatment, Evans blue was injected intravenously through the tail vein to mice. Then, animals were sacrificed and the dye was extracted from the skin tissue by incubation with formamide. Heatmap and correlation map were generated and protein-protein interaction network of the hub genes was drawn by Cytoscape software. Results: Hub DEG expression rate showed that Heat shock protein a1 (Hspa1) family (comprised of HSPa1a, b, and HSPa5), caspase 3, and minichromosome maintenance complex component 2 were overexpressed after treatment with curcumin. Functional modules of curcumin enriched through Enrich gene biological process and revealed positive association of gene expression of apoptosis process with the therapy. Curcumin was also found to reduce leucocyte migration in murine tissues. Additionally, treatment with curcumin resulted in downregulation of heat shock proteins and proinflammatory cytokines such as monocyte chemotactic protein 1, interleukin-6 and chemokine (C-X-C motif) ligand 3. Conclusion: Curcumin inhibited the proinflammatory cytokines and inflammatory HSPs in endothelial cells and reduced THROMBINinduced barrier destabilization in vivo.

Lungs possess dynamic and complex coagulation-thrombolytic and inflammatory sets of innate reactive responses, which generate changes that cause a dramatic alteration in its parenchyma. Clinically, since its steps are reciprocally inter-connected, the pulmonary embolic injury is very complex to describe as one exclusive progression. For example, each step in a coagulation-fibrinolytic-inflammation-integrated pathway produces more side-steps, which later plays an important role in a specific lung damage description. In this clinical review, the enzyme THROMBIN, an ontogenetically very old and key blood coagulation serine protease is centrally placed as a mediator, activator and up-regulator of postpulmonary embolic damage to reveal its enormous flexibility in post-pulmonary embolism damage and its reparative processes. Additionally, some beneficial aspects of its control throughout its inhibition are discussed. ABBREVIATIONS: ADP adenosine 5 diphosphate; APC activated protein C; APTT activated partial thromboplastin time; ASA Acetylsalicylic acid; AT III antiTHROMBIN; C-1INH C-1Inhibitor; EC endothelial cells; eNOS endothelial nitric oxide synthase; EPCR endothelial protein C receptor; FDP’s fibrin degradation products; fibrin stabilization factor FSF; FM Fibrin monomer; GAG Glycosaminoglycans; GP glycoprotein; HC II Heparin cofactor II; HIT heparin induced thrombocytopenia; HMWK High Molecular Weight Kininogen; LDUH low dose unfractionated heparin; LMWH low molecular weight heparin (s); LV left ventricle; MAP mean arterial pressure; MLCK myosin light chain kinase; NO nitric oxide; PA pulmonary artery; PARs Proteinase (or protease)-activated receptors; PC protein C; PAI-1 plasminogen activator inhibitor; PE pulmonary embolism; PF 4 platelet factor 4; PLA-2 phospholipase A 2; PN-1 Protease Nexin; PT proTHROMBIN time; RBC red blood cell; RV right ventricle; SMC’S’ s vascular smooth muscle cells; t-Pa tissue plasminogen activator; TAFI THROMBIN activatable fibrinolysis inhibitor; TF tissue factor (factor III); TFPI Tissue factor pathway inhibitor; TM Thrombomodulin; TNF tumor necrosis factor; TXA 2 thromboxane A2; VEGF vascular endothelial growth factor; vWf von Willebrand factor.

PRESENTATION: A 23-year-old man was presented with slowly progressive bilateral decreasing vision over the past 3 years. He had no remarkable medical, surgical or family history of ocular or systemic disease. Best-corrected visual acuity (BCVA) was 20/200 in both eyes with -1-0.75×90 and -1.50-0.50×90 correction in the right and left eyes, respectively. Anterior segment examination revealed diffuse neovascularization of iris (NVI) in both eyes [Figure 1]. Diffuse capillary non-perfused areas associated with occluded retinal vessels in both eyes, and fibrovascular membrane with traction on the macula in the left eye were present in dilated fundus examination [Figures 2 and 3].