Invalid freeze-dried platelet gel promotes wound healing.

Wound healing is the curative process of tissue injury, composed of three phases: the inflammatory phase, proliferative phase, followed by the maturation cum remodeling phase. Various treatment options were previously depicted for wound healing, however a treatment that accelerates these phases would be highly valuable. Platelet aggregation at the bleeding vessels and release of various growth factors are the most promising factors that stimulates the wound healing progress. In the present study, we hypothesized that the freeze-dried platelet which were normally discarded from the blood banks due to invalidity, might be promising to accelerate the phases of wound healing. The invalid freeze-dried platelets were prepared to a gel form called invalid freeze-dried platelet gel (IF-PG), which was tested for its efficacy in a cutaneous punch wound model in rats. Mupirocin antibiotic gel was used as a bio-equivalent formulation. The wound healing phases and changes in the wound sites were determined by assessing the wound sizes, histopathological analysis, immunohistochemical staining. The re-epithelialization at the wound sites at different time intervals till the wound closure was also determined. Our results suggest the beneficial effects of IF-PG; in reducing the wound area and accelerating wound closure in the cutaneous punch wound in rats. Histopathology and immunostaining results support the improvements in the wound when treated with IF-PG, which were similar to that of mupirocin antibiotic gel. Our preliminary findings also warrant the competency of IF-PG in modulating the different phases of wound healing process. In conclusion, IF-PG might be a resourceful alternative for the wound care management, however further studies are required to validate its impact on various growth factors before proceeding to clinical studies.

SB203580 Modulates p38 MAPK Signaling and Dengue Virus-Induced Liver Injury by Reducing MAPKAPK2, HSP27, and ATF2 Phosphorylation.

Dengue virus (DENV) infection causes organ injuries, and the liver is one of the most important sites of DENV infection, where viral replication generates a high viral load. The molecular mechanism of DENV-induced liver injury is still under investigation. The mitogen activated protein kinases (MAPKs), including p38 MAPK, have roles in the hepatic cell apoptosis induced by DENV. However, the in vivo role of p38 MAPK in DENV-induced liver injury is not fully understood. In this study, we investigated the role of SB203580, a p38 MAPK inhibitor, in a mouse model of DENV infection. Both the hematological parameters, leucopenia and thrombocytopenia, were improved by SB203580 treatment and liver transaminases and histopathology were also improved. We used a real-time PCR microarray to profile the expression of apoptosis-related genes. Tumor necrosis factor α, caspase 9, caspase 8, and caspase 3 proteins were significantly lower in the SB203580-treated DENV-infected mice than that in the infected control mice. Increased expressions of cytokines including TNF-α, IL-6 and IL-10, and chemokines including RANTES and IP-10 in DENV infection were reduced by SB203580 treatment. DENV infection induced the phosphorylation of p38MAPK, and its downstream signals including MAPKAPK2, HSP27 and ATF-2. SB203580 treatment did not decrease the phosphorylation of p38 MAPK, but it significantly reduced the phosphorylation of MAPKAPK2, HSP27, and ATF2. Therefore, SB203580 modulates the downstream signals to p38 MAPK and reduces DENV-induced liver injury.

Effects of Phikud Navakot Extract on Myocardial Ischemia/Reperfusion Injury in Rats.

BACKGROUND: Phikud Navakot (PN) is a set of nine medicinal plants and the main ingredient of "Yahom Navakot", a traditional Thai herbal formula for treatment of cardiovascular symptoms. OBJECTIVE: To investigate the cardioprotective effects of PN on myocardial ischemia/reperfusion (IR) in male Sprague Dawley rats. MATERIAL AND METHOD: Rats were randomly divided into 7 groups: sham, IR, and IR orally pretreated with PN (10, 50, 100, 200, and 400 mg/kg B W)for 7 days. After treatment, IR induction was performed by left coronary artery (LCA) ligation for 30 min, followed by reperfusion for 24 h. At the end of the experiment, blood was collected for hematological and biochemical parameters, and hearts were immediately removed for histopathological examination and Western blot analysis. RESULTS: IR induction caused ST elevation in the electrocardiogram and an increase in serum troponin I (TnI), confirming myocardial damage. In addition, histopathological changes of ischemic myocardium showed inflammation, infiltration, and edema. Oral administration of PN (10, 50, 100, 200, and 400 mg/kg BW) for 7 days prior to IR simulation showed no change on serum TnI and histopathology ofcardiac tissues, when compared to IR group. However Western blot analysis showed that IR rats pretreated with PN (10 mg/kg BW) significantly increased (p < 0.05) pERK/ERK ratio, meanwhile pretreated with PN (50-200 mg/kg BW) up-regulated (p < 0.05) the protein expression of HO-1, when compared with IR group. CONCLUSION: The present study implied that 7-day pretreatment of PN failed to protect cardiac tissues against IR injury induced by LCA ligation. Investigation at molecular level found however that PN up-regulated the expression of protective proteins pERK/ERK ratio and HO-1 in cardiac tissues, suggesting molecular mechanism of PN in cardioprotection against IR injury.

Role of ERK1/2 signaling in dengue virus-induced liver injury.

The liver is considered to be an important organ of dengue virus (DENV) replication and pathogenesis. However, molecular mechanisms of hepatic injury are still poorly understood. Modulation of Mitogen Activated Protein Kinases (MAPKs) was previously shown to affect DENV-induced apoptosis of hepatocytes in vitro. However, the in vivo role of ERK1/2, a member of the MAPK family, and the question whether its activation can facilitate cell survival or cell death, has not been thoroughly investigated. Therefore, the role of ERK1/2 in a mouse model of DENV infection was examined. Our results show that DENV induces phosphorylation of ERK1/2 and increases apoptosis. Inhibition of phosphorylated ERK1/2 by the selective ERK1/2 inhibitor, FR180204, limits hepatocyte apoptosis and reduces DENV-induced liver injury. Clinical parameters, including leucopenia, thrombocytopenia, transaminases and histology, show improvements after FR180204 treatment. The expression of cell death genes was further identified using real-time PCR array and Western blot analysis. Caspase-3 was significantly decreased in FR180204 treated DENV-infected mice compared to the levels of untreated DENV-infected mice suggesting the role of ERK1/2 signaling in immune-mediated liver injury during DENV infection.

Effects on high cholesterol-fed to liver, retina, hippocampus, and Harderian gland in Goto-Kakizaki rat.

To understand the relationship among cholesterolemia, hyperglycemic stage in non obese type 2 diabetes mellitus, and histological perturbations on liver, retina, hippocampus, and Harderian gland, we maintained rat on a diet high in cholesterol for fourteen weeks, then analyzed blood lipid profiles, blood glucose, hepatic enzymes, and microscopic lesion of those tissues. We observed that high cholesterol-treated rat elevated in cholesterol and low density lipoprotein with not correlated to hyperglycemia. Histopathological changing in Goto-Kakizaki rat on liver (microvesicular steatosis) and Harderain gland (tubular lesions) were related to hyperglycemic effect rather than cholesterolemic effect. These may be related to hypoinsulinemic characteristic of this diabetic model. However increasing pyknotic nuclei on hippocampus and reducing of retinal ganglionic cell were related to the high level of cholesterol loaded with synergized effect due to diabetic stage.