Systematic analysis of protein expression in Candida albicans exposed to farnesol / 中华医学杂志(英文版)

BACKGROUND@#The phenotypic switching of Candida spp. plays an important role in the development of vulvovaginal candidiasis (VVC). Farnesol, as a quorum-sensing molecule in Candida albicans, has the ability to prevent yeast-to-hyphal conversion in vitro. However, the mechanism underlying this ability is unclear. This study aimed to investigate changes in protein levels to better understand how farnesol impacts processes contributing to VVC.@*METHODS@#The isobaric tag for relative and absolute quantitation technique was used to detect protein expression in C. albicans strain SC5314 (ATCC MYA-2876) with or without farnesol exposure. Proteins with a threshold fold change greater than 1.5 were screened and considered differentially expressed proteins. All the altered proteins were analyzed using Gene Ontology annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation, and metabolic pathway annotation.@*RESULTS@#Between the farnesol-exposed group and the farnesol-unexposd group, we detected 297 altered proteins among all 2047 tested proteins based on a threshold fold change of more than 1.5 (P < 0.05). Eighty-seven of the 297 altered proteins exhibited metabolic enzyme activity and participated in 85 metabolic pathways according to KEGG pathway analysis. Most of these metabolic pathways were associated with central carbon metabolism processes. In the sterol synthesis pathway, which involves the synthesis of farnesol, ERG25 (methylsterol monooxygenase) and ERG4 (delta 24(24(1))-sterol reductase) were both down-regulated in the farnesol-exposed group. All six altered proteases associated with the oxidative phosphorylation process were down-regulated in the farnesol-exposed group relative to the farnesol-unexposed group.@*CONCLUSIONS@#The mechanisms underlying farnesol-induced phenotype switching involves the adjustment of metabolic activities and epigenetic modification. Exogenous farnesol had an evident, but non-deterministic effect on the synthesis of ergosterol. The potential drug activity of farnesol warrants further investigation.

Systematic analysis of protein expression in Candida albicans exposed to farnesol / 中华医学杂志(英文版)

Background@#The phenotypic switching of Candida spp. plays an important role in the development of vulvovaginal candidiasis (VVC). Farnesol, as a quorum-sensing molecule in Candida albicans, has the ability to prevent yeast-to-hyphal conversion in vitro. However, the mechanism underlying this ability is unclear. This study aimed to investigate changes in protein levels to better understand how farnesol impacts processes contributing to VVC.@*Methods@#The isobaric tag for relative and absolute quantitation technique was used to detect protein expression in C. albicans strain SC5314 (ATCC MYA-2876) with or without farnesol exposure. Proteins with a threshold fold change greater than 1.5 were screened and considered differentially expressed proteins. All the altered proteins were analyzed using Gene Ontology annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation, and metabolic pathway annotation.@*Results@#Between the farnesol-exposed group and the farnesol-unexposd group, we detected 297 altered proteins among all 2047 tested proteins based on a threshold fold change of more than 1.5 (P < 0.05). Eighty-seven of the 297 altered proteins exhibited metabolic enzyme activity and participated in 85 metabolic pathways according to KEGG pathway analysis. Most of these metabolic pathways were associated with central carbon metabolism processes. In the sterol synthesis pathway, which involves the synthesis of farnesol, ERG25 (methylsterol monooxygenase) and ERG4 (delta 24(24(1))-sterol reductase) were both down-regulated in the farnesol-exposed group. All six altered proteases associated with the oxidative phosphorylation process were down-regulated in the farnesol-exposed group relative to the farnesol-unexposed group.@*Conclusions@#The mechanisms underlying farnesol-induced phenotype switching involves the adjustment of metabolic activities and epigenetic modification. Exogenous farnesol had an evident, but non-deterministic effect on the synthesis of ergosterol. The potential drug activity of farnesol warrants further investigation.

Species Distribution and In Vitro Antifungal Susceptibility of Vulvovaginal Candida Isolates in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Vulvovaginal candidiasis (VVC) was a common infection associated with lifelong harassment of woman's social and sexual life. The purpose of this study was to describe the species distribution and in vitroCandidaCandida spp.) isolated from patients with VVC over 8 years.</p><p><b>METHODS</b>Species which isolated from patients with VVC in Peking University First Hospital were identified using chromogenic culture media. Susceptibility to common antifungal agents was determined using agar diffusion method based on CLSI M44-A2 document. SPSS software (version 14.0, Inc., Chicago, IL, USA) was used for statistical analysis, involving statistical description and Chi-square test.</p><p><b>RESULTS</b>The most common strains were Candida (C.) albicans, 80.5% (n = 1775) followed by C. glabrata, 18.1% (n = 400). Nystatin exhibited excellent activity against all species (<4% resistant [R]). Resistance to azole drugs varied among different species. C. albicans: clotrimazole (3.1% R) < fluconazole (16.6% R) < itraconazole (51.5% R) < miconazole (54.0% R); C. glabrata: miconazole (25.6% R) < clotrimazole (50.5% R) < itraconazole (61.9% R) < fluconazole (73.3% R); Candida krusei: clotrimazole (0 R) < fluconazole (57.7% R) < miconazole (73.1% R) < itraconazole (83.3% R). The susceptibility of fluconazole was noticeably decreasing among all species in the study period.</p><p><b>CONCLUSIONS</b>Nystatin was the optimal choice for the treatment of VVC at present. The species distribution and in vitroCandida spp. isolated from patients with VVC had changed over time.</p>

Morinda officialis how extract improves microwave-induced reproductive impairment in male rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of different concentrations of Morinda Officialis How (MOH) extracts on microwave radiation-induced injury to the spermatogenic function of male rats.</p><p><b>METHODS</b>Forty SD male rats were equally divided into four groups: control, microwave injury model, aqueous extract of MOH treatment, and alcohol extract of MOH treatment. Models of microwave-induced injury were made by exposing the rats to microwave radiation from a microwave signal generator (900 MHz 1.0 W) at 218 microm/cm2, 12 h/d, for 2 weeks. The model rats of the two treatment groups were intragastrically given aqueous extract and alcohol extract of MOH, respectively, both at 20 g per kg per day for 2 weeks. Then we observed the growth, capture incubation period (CIP), capture times (CT), changes in testicular and epididymal weight and morphology, sperm concentration and malformation, and levels of serum testosterone.</p><p><b>RESULTS</b>Compared with the controls, the rats of the model group showed a slightly reduced body weight, markedly prolonged CIP and decreased CT (P < 0.05), significantly reduced sperm concentration (P < 0.05) and remarkably in- creased sperm malformation (P < 0.05), but no statistically significant differences in the testosterone level. The two treatment groups exhibited obviously decreased body weight, CIP and sperm malformation compared with the control group (P < 0.05) but markedly increased CT, sperm concentration and testosterone level as compared with the models (P < 0.05). The microwave radiation-induced testis injury was repaired perfectly in the two treatment groups, the epididymal ducts filled with sperm and cast-off cells.</p><p><b>CONCLUSION</b>Both aqueous and alcohol extracts of MOH can promote spermatogenesis and repair of reproductive injury induced by microwave radiation.</p>

Influence of clinical and pathomorphological parameters on prognosis in colon carcinoma and rectal carcinoma / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the effects of clinical and pathomorphological parameters on the prognosis of colon carcinoma and rectal carcinoma.</p><p><b>METHODS</b>Univariate and multivariate COX proportional hazard models were used to study the effects of the clinical and pathomorphological factors on the prognosis in 101 cases of colon carcinoma, 219 of rectal carcinoma and 137 of rectal carcinoma under curative resections.</p><p><b>RESULT</b>By using univariate analysis, we identified that lymph node metastasis and distant metastasis were the common prognostic factors for both colon carcinoma and rectal carcinoma. Smoking, deep infiltration, chemotherapy and serum albumin concentration were the uncertain prognostic factors for colon carcinoma. Signet-ring cell carcinoma, larger tumor size (>6 cm), deep infiltration, lack of radical surgery, and advanced TNM stage were the exclusive adverse prognostic factors for rectal carcinoma. Further studies showed that the adverse prognostic factors for the rectal carcinoma under curative resection included deep infiltration, lymph node metastasis, vessel invasion, less of peritumoral lymphocyte infiltration, lack of Crohn's like reactivity, high level of tumor budding, advanced TNM stage and positive urine glucose. By using multivariate analysis based on a COX proportional hazard model, it was identified that smoking, lymph node metastasis and serum albumin concentration were independent prognostic factors for colon carcinoma; advanced TNM stage, distant metastasis and palliative surgery for rectal carcinoma; and vessel invasion, lymph node metastasis and urine glucose for rectal carcinoma under curative resections.</p><p><b>CONCLUSION</b>The various clinical and pathomorphological parameters show different prognostic value for colon carcinoma, rectal carcinoma and rectal carcinoma under curative resections.</p>