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.

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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.