Pathogenicity of phospholipase B1 of Trichosporon asahii in immunosuppressed mice.

BACKGROUND: Trichosporon asahii is an opportunistic pathogenic yeast-like fungus. Phospholipase B1 (PLB1) is an important virulence factor of pathogenic fungi such as Candida albicans and Cryptococcus neoformans, and there are few studies on the role of PLB1 in the pathogenicity of T. asahii. OBJECTIVES: To investigate the role of PLB1 in the pathogenicity of T. asahii. METHODS: A strain with low secretion of PLB1 (4848) was screened, a PLB1 overexpression strain (PLB1OX ) was constructed, and the differences in histopathology, fungal load of organ, survival time of mice, the levels of IL-6, IL-10, TNF-α, and GM-GSF in the serum and organs caused by the two strains were compared. RESULTS: Histopathology showed that spores and hyphae were observed in both groups, and PLB1OX led to more fungal invasion. The fungal loads in the kidney, lung, spleen and liver in the PLB1OX group were significantly higher than those in the 4848 group, and the survival time of mice was significantly lower than that in the 4848 group. The levels of TNF-α in the serum, liver, spleen, lung and kidney of the PLB1OX group were lower than those of the 4848 group, while the level of IL-10 in the serum was higher than that of the 4848 group. CONCLUSIONS: These results suggest that PLB1 can enhance the invasive function of T. asahii and affect the secretion of TNF-α and IL-10 which may affect the host antifungal immune response, providing evidence that PLB1 plays a role in the pathogenic infection of T. asahii.

Chronic Psychological Stress Disrupts Iron Metabolism and Enhances Hepatic Mitochondrial Function in Mice.

To explore the changes in iron metabolism and mitochondrial function exposed to chronic psychological stress, seventy-five male mice aged 5 ~ 6 weeks were randomly sorted into 2 groups: control group and chronic psychological stress group. Mice were conducted by communication box to induce psychological stress for 21 consecutive days. The results showed that chronic psychological stress led to a significant reduction in average daily gain (P < 0.01) and the final weight (P < 0.05). Chronic psychological stress greatly increased plasma and duodenal iron level (P < 0.05), whereas markedly decreased hepatic iron content in mice (P < 0.05). Increasing expression of duodenal DCYTB and FPN (P < 0.05) was observed in mice exposed to chronic psychological stress. Moreover, chronic psychological stress greatly enhanced hepatic TFR1, FTL, and FPN protein expression (P < 0.05) in mice. Additionally, chronic psychological stress enhanced the levels of hepatic NADH, NAD + , ATP, mtDNA content, mtDNA-encoded genes, and the activity of mitochondrial complex I and II (P < 0.05). Taken together, chronic psychological stress impairs growth, disrupts iron metabolism, and enhances hepatic mitochondrial function in mice. These results will provide new insights for understanding the mechanisms of iron metabolism and mitochondrial function during chronic psychological stress.

Effectiveness of artesunate combined with fractional CO2 laser in a hypertrophic scar model with underlying mechanism.

BACKGROUND AND OBJECTIVES: Both artesunate and fractional CO2 laser have been proved effective in the treatment of hypertrophic scars, yet little data are available for the efficacy of artesunate combined with fractional CO2 laser. In order to assess the pre-clinical significance and the underlying mechanism of this combined treatment profile, we attempted to observe the effectiveness of this therapy in rabbit models through determining the expression of BMP-7 and Fas. MATERIALS AND METHODS: Twenty-Four New Zealand white rabbits with established hypertrophic scar samples were randomly divided into control group and three treatment groups. Artesunate (20 µl/cm2) was injected into the rat's scar of artesunate and combination groups, while fractional CO2 laser (Combo mode, deep energy:10 mJ, super energy: 50 mJ) was applied to rats in fractional CO2 laser and combination groups at week 4 after model establishment. All rabbits underwent a total of 3 sessions of treatment once every 2 weeks. Histological and immunohistochemistry study, Western blot assay, cell viability, ELISA and RT-QPCR were performed at week 10 to observe the aspects of hypertrophic scar sample changes and expression of BMP-7 and Fas in the scar tissues. RESULTS: Compared with control group, hypertrophic scars and the collagen fibers were significantly inhibited after treatment, and higher inhibition was seen in the samples in combination group compared to that in artesunate and fractional CO2 laser groups (P < 0.01). Meanwhile, BMP-7 and Fas expressions were both notably increased in all treatment groups, and upregulation of the two proteins was dominant in combination group (P < 0.01). CONCLUSIONS: Artesunate combined with fractional CO2 laser is effective in hypertrophic scarring in this rabbit model. Our findings can serve as a potential alternative strategy to treatment of hypertrophic scar in clinical practice.

595-nm pulsed dye laser combined with fractional CO2 laser reduces hypertrophic scar through down-regulating TGFß1 and PCNA.

595-nm pulsed dye laser and fractional CO2 laser have been demonstrated effective to treat hypertrophic scar. The underlying mechanism may involve transforming growth factor-beta1 (TGFß1) and proliferating cell nuclear antigen (PCNA), but remains to be clarified. Our study was performed to investigate how 595-nm pulsed dye laser combined with fractional CO2 laser treats hypertrophic scars in a rabbit model through regulating the expression of TGFß1 and PCNA. Twenty-four New Zealand white rabbits were randomly divided into control group, pulsed dye laser group, fractional CO2 laser group, and pulsed dye laser + fractional CO2 laser (combination) group. Surgical wounds were made and allowed to grow into hypertrophic scars at day 28. Next, 595-nm pulsed dye laser (fluence: 15 J/cm2; square: 7 mm; pulse duration: 10 ms) was used in pulsed dye laser and combination group, while fractional CO2 laser (combo mode, deep energy: 12.5 mJ; super energy: 90 mJ) in fractional CO2 laser and combination groups, once every 4 weeks for 3 times. The appearance and thickness of hypertrophic scar samples were measured with hematoxylin-eosin and Van Gieson's straining. The expressions of TGFß1 and PCNA were evaluated by immunohistochemical and western blot analysis. A significant improvement was noted in the thickness, size, hardness, and histopathology of hypertrophic scar samples after laser treatment, especially in combination group. Scar Elevation Index (SEI), fiber density (NA), and collagen fiber content (AA) decreased most significantly in combination group (2.10 ± 0.14; 2506 ± 383.00; 22.98 ± 2.80%) compared to 595-nm pulsed dye laser group (3.35 ± 0.28; 4857 ± 209.40; 42.83 ± 1.71%) and fractional CO2 laser group (2.60 ± 0.25; 3995 ± 224.20; 38.33 ± 3.01%) (P < 0.001). Furthermore, TGFß1 and PCNA expressions were more suppressed in combination group (8.78 ± 1.03; 7.81 ± 1.51) than in 595-nm pulsed dye laser (14.91 ± 1.68; 15.73 ± 2.53) and fractional CO2 laser alone group (15.96 ± 1.56; 16.13 ± 1.72) (P < 0.001). The combination of 595-nm pulsed dye laser with fractional CO2 laser can improve the morphology and histology of hypertrophic scars in a rabbit model through inhibiting the expression of TGFß1 and PCNA protein. Our findings can pave the way for new clinical treatment strategies for hypertrophic scars.