Effect of Coriolus versicolor polysaccharides on the hematological and biochemical parameters and protection against Aeromonas hydrophila in allogynogenetic crucian carp (Carassius auratus gibelio).

The effect of dietary intake of Coriolus versicolor Polysaccharides (CVP) on the hematological and biochemical indices of Allogynogenetic crucian carp (Carassius auratus gibelio) was investigated. Fish were fed CVP supplemented diets (0, 0.25, 0.5, 1.0, 2.0 or 4.0 g CVP kg(-1)) for 56 days. The RBC, WBC counts, hemoglobin content, ESR in blood and TP, ALT, AST, ALP, GLU, CHO, TG, and BUN in serum were measured on day 0, 14, 28, 42, and 56. After feeding of 56 days, fish were infected with Aeromonas hydrophila and mortalities were recorded. The results indicated that feeding crucian carp with suitable dose of CVP enhanced the RBC, WBC counts, hemoglobin and TP content, ALP activity, and decreased the ESR, ALT, AST, GLU, CHO, TG and BUN. There was no effect in fish at low dose (0.25 g kg(-1)). Unexpectedly, the higher CVP dose used here (2.0 and 4.0 g kg(-1)) has a negative effect in fish. The results of challenge experiment indicated that a moderate level of CVP in the diet (1.0 g kg(-1)) was the most effective to enhance the survival of fish after infected with A. hydrophila. In summary, the use of CVP, as dietary supplements, can improve the innate defense of crucian carp providing resistance to pathogens.

Bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration.

Diabetes mellitus (DM) aggravates periodontitis, resulting in accelerated periodontal bone resorption. Disordered glucose metabolism in DM causes reactive oxygen species (ROS) overproduction resulting in compromised bone healing, which makes diabetic periodontal bone regeneration a major challenge. Inspired by the natural bone healing cascade, a mesoporous silica nanoparticle (MSN)-incorporated PDLLA (poly(dl-lactide))-PEG-PDLLA (PPP) thermosensitive hydrogel with stepwise cargo release is designed to emulate the mesenchymal stem cell "recruitment-osteogenesis" cascade for diabetic periodontal bone regeneration. During therapy, SDF-1 quickly escapes from the hydrogel due to diffusion for early rat bone marrow stem cell (rBMSC) recruitment. Simultaneously, slow degradation of the hydrogel starts to gradually expose the MSNs for sustained release of metformin, which can scavenge the overproduced ROS under high glucose conditions to reverse the inhibited osteogenesis of rBMSCs by reactivating the AMPK/ß-catenin pathway, resulting in regulation of the diabetic microenvironment and facilitation of osteogenesis. In vitro experiments indicate that the hydrogel markedly restores the inhibited migration and osteogenic capacities of rBMSCs under high glucose conditions. In vivo results suggest that it can effectively recruit rBMSCs to the periodontal defect and significantly promote periodontal bone regeneration under type 2 DM. In conclusion, our work provides a novel therapeutic strategy of a bioinspired drug-delivery system emulating the natural bone healing cascade for diabetic periodontal bone regeneration.

Microbial Natural Product Alternariol 5-O-Methyl Ether Inhibits HIV-1 Integration by Blocking Nuclear Import of the Pre-Integration Complex.

While Highly Active Antiretroviral Therapy (HAART) has significantly decreased the mortality of human immunodeficiency virus (HIV)-infected patients, emerging drug resistance to approved HIV-1 integrase inhibitors highlights the need to develop new antivirals with novel mechanisms of action. In this study, we screened a library of microbial natural compounds from endophytic fungus Colletotrichum sp. and identified alternariol 5-O-methyl ether (AME) as a compound that inhibits HIV-1 pre-integration steps. Time-of addition analysis, quantitative real-time PCR, confocal microscopy, and WT viral replication assay were used to elucidate the mechanism. As opposed to the approved integrase inhibitor Raltegravir, AME reduced both the integrated viral DNA and the 2-long terminal repeat (2-LTR) circular DNA, which suggests that AME impairs the nuclear import of viral DNA. Further confocal microscopy studies showed that AME specifically blocks the nuclear import of HIV-1 integrase and pre-integration complex without any adverse effects on the importin α/ß and importin ß-mediated nuclear import pathway in general. Importantly, AME inhibited Raltegravir-resistant HIV-1 strains and exhibited a broad anti-HIV-1 activity in diverse cell lines. These data collectively demonstrate the potential of AME for further development into a new HIV inhibitor, and suggest the utility of viral DNA nuclear import as a target for anti-HIV drug discovery.