Oral and uterine leiomyomas exhibit high immunoexpression of Cripto-1 compared to normal myometrium.

Leiomyomas are the most common benign tumors in women. Many of them are associated with significant morbidity. The present study aimed to analyze histomorphological and histochemical characteristics and immunoexpression of Cripto-1 in oral leiomyomas (OL), uterine leiomyomas (UL), and normal myometrium (NM). Sample was composed of ten OL, 11 UL and 11 NM. Histomorphological characteristics were analyzed at 100 and 400x magnifications with HE staining. The immunoexpression of Cripto-1 was analyzed in five high-power fields. Statistical analysis considered a significant difference when p<0.05. Six OL disclosed moderate/intense inflammatory infiltrate, while ten UL exhibited mild infiltrate (p=0.024). When analyzing all leiomyomas together, 20 exhibited hyalinization, whereas no NM exhibited this alteration (p<0.001). There was no statistical difference in the distribution of mast cells among the lesions. The median Cripto-1 was higher in UL (9.0), followed by OL and NM (4.0). Associations of the Cripto-1 expression between leiomyomas (separately and together) and NM were statistically significant (p<0.001). These results indicate that OL and UL exhibit similar histomorphological and histochemical characteristics, as well as differences to NM. The higher immunoexpression of Cripto-1 in leiomyomas compared to NM suggests that this protein may influence cell proliferation and tissue architecture of oral and uterine leiomyomas.

Effect of the Ethyl Acetate Fraction of Eugenia uniflora on Proteins Global Expression during Morphogenesis in Candida albicans.

Candida albicans is able to switch from yeast to hyphal growth and this is an essential step for tissue invasion and establishment of infection. Due to the limited drug arsenal used to treat fungal infections and the constant emergence of resistant strains, it is important to search for new therapeutic candidates. Therefore, this study aimed to investigate by proteomic analysis the role of a natural product (Eugenia uniflora) in impairing hypha formation in C. albicans. We also tested the potential action of E. uniflora to prevent and treat oral candidiasis induced in a murine model of oral infection and the ability of polymorphonuclear neutrophils to phagocytize C. albicans cells treated with the ethyl acetate fraction of the extract. We found that this fraction greatly reduced hypha formation after morphogenesis induction in the presence of serum. Besides, several proteins were differentially expressed in cells treated with the fraction. Surprisingly, the ethyl acetate fraction significantly reduced phagocytosis in C. albicans (Mean 120.36 ± 36.71 yeasts/100 PMNs vs. 44.68 ± 19.84 yeasts/100 PMNs). Oral candidiasis was attenuated when C. albicans cells were either pre-incubated in the presence of E. uniflora or when the fraction was applied to the surface of the oral cavity after infection. These results were consistent with the reduction in CFU counts (2.36 vs. 1.85 Log10 CFU/ml) and attenuation of tissue damage observed with histopathological analysis of animals belonging to treated group. We also observed shorter true hyphae by direct examination and histopathological analysis, when cells were treated with the referred natural product. The E. uniflora ethyl acetate fraction was non-toxic to human cells. E. uniflora may act on essential proteins mainly related to cellular structure, reducing the capacity of filamentation and attenuating infection in a murine model, without causing any toxic effect on human cells, suggesting that it may be a future therapeutic alternative for the treatment of Candida infections.

The role of myofibroblasts and interstitial fibrosis in the progression of membranous nephropathy.

Renal interstitial fibrosis has been observed in a large number of nephropathies and contributes to the progressive deterioration of renal function. Myofibroblasts have been implicated in the reparative process of tissue injury, including renal scarring secondary to glomerular diseases. We performed a retrospective study on 28 patients with biopsy-proven primary membranous nephropathy, to determine whether interstitial myofibroblasts and tubulointerstitial lesions correlated with renal function at follow-up. Tubulointerstitial pathology was evaluated by morphometric and semiquantitative methods. Interstitial myofibroblasts were counted; 24-hour urinary protein and serum creatinine at the time of diagnosis and at the end of follow-up were available for all the patients. There were 20 males and 8 females, age 2-67 years (mean 42.3+/-15.3), most of them with nephrotic syndrome (78.6%). The final renal function had deteriorated in 16 patients (57.1%) and in 5 patients (17.8%) reached end-stage. The renal outcome was correlated with histological changes. We found a positive correlation between the severity of tubulointerstitial damage and the deterioration of the final serum creatinine (r2=0.185; p=0.016). Myofibroblasts did not predict impaired renal function at the final follow-up. The current data do not support previous suggestions that myofibroblasts are a useful a predictor of end-stage renal disease.