Proteomic Perspective of Azole Resistance in Aspergillus fumigatus Biofilm Extracellular Matrix in Response to Itraconazole.

Azole-resistant Aspergillus fumigatus makes a major challenge to the chemotherapy for invasive aspergillosis, whereas cyp51A gene mutation is the most dominant mechanism for azole resistance. Moreover, biofilm contributes to drug resistance for A. fumigatus, and extracellular matrix (ECM) is essential to protect live cells from antifungal drugs.

Repression of the Antioxidant Pyrroloquinoline Quinone in Skin Aging Induced by Bmi-1 Deficiency.

It is uncertain whether Bmi-1 deficiency could lead to skin aging by redox imbalance and DNA damage. In this study, we first confirmed that Bmi-1 had a relatively high expression level in the skin and Bmi-1 expression levels gradually decreased with age. Then, we studied the role of Bmi-1 in the skin using a Bmi-1 mouse model.

Effects of Itraconazole and Micafungin on Aspergillus fumigatus Biofilms.

Aspergillus fumigatus (A. fumigatus) is the most common airborne opportunistic fungal pathogen. Biofilm formation is one of the main pathogenic mechanisms of A.

Uncovering New Mutations Conferring Azole Resistance in the Gene.

The opportunistic pathogen has developed worldwide resistance to azoles largely through mutations in cytochromeP450 enzyme Cyp51. In this study, we indicated that azole situation results in emergence of azole-resistant mutations. There are previously identified azole-resistant mutations (M220K, M220I, M220R, G54E and G54W mutations) and we successfully identified in this study two new mutations (N248K/V436A, Y433N substitution) conferring azole resistance among 18 independent stable azole-resistant isolates.

Triazoles bind the C-terminal domain of SMO: Illustration by docking and molecular dynamics simulations the binding between SMO and triazoles.

Itraconazole is an antagonist of the component Smoothened of Hedgehog pathway, which can inhibit the growth of medulloblastoma, basal cell carcinoma, and melanoma, etc. To research the binding mechanism of the Smoothened and triazoles, we used docking and molecular dynamics simulations on the Smoothened crystal structure and six triazoles. Unlike vismodegib, itraconazole can effectively bind into the pocket in the C-terminal domain of the Smoothened crystal structure instead of the N-terminal domain.

Itraconazole exerts its anti-melanoma effect by suppressing Hedgehog, Wnt, and PI3K/mTOR signaling pathways.

Malignant melanoma is the deadliest form of all skin cancers. Itraconazole, a commonly used systemic antifungal drug, has been tested for its anti-tumor effects on basal cell carcinoma, prostate cancer, and non-small cell lung cancer. Whether itraconazole has any specific anti-tumor effect on melanoma remains unknown.

cyp51A-based mechanism of azole resistance in Aspergillus fumigatus: Illustration by a new 3D Structural Model of Aspergillus fumigatus CYP51A protein.

Mutations of CYP51A protein (Cytochrome P450 14-α Sterol demethylase) play a central role in the azole resistance of Aspergillus fumigatus The available structural models of CYP51A protein ofA. fumigatus are built based on that of Homo sapiens and that of Mycobacterium tuberculosis, of which the amino acid homology is only 38% and 29% compared with CYP51A protein ofA. fumigatus, respectively.

Multiple cyp51A-based mechanisms identified in azole-resistant isolates of Aspergillus fumigatus from China.

Seventy-two A. fumigatus clinical isolates from China were investigated for azole resistance based on mutations of cyp51A. We identified four azole-resistant strains, among which we found three strains highly resistant to itraconazole, two of which exhibit the TR34/L98H/S297T/F495I mutation, while one carries only the TR34/L98H mutation.

Causes of death among active leprosy patients in China.

We analyzed the causes of death among active leprosy patients in China, to better understand the disease and improve the quality of services, by performing a retrospective study involving 24 provinces of China. Information about patients with active leprosy who were not clinically cured and died between January 1, 2000, and December 31, 2005, was collected by professionals at county levels. A total of 524 deaths were analyzed.

Occurrence and management of leprosy reaction in China in 2005.

Background: Leprosy reactions are a major cause of disability before, during and after anti-bacterial treatment. Prompt diagnosis and correct management of reaction is a crucial matter for improving the quality of leprosy health services.

Objectives: To describe the pattern of leprosy reaction and its management in China during 2005.

Current situation of leprosy colonies/leprosaria and their future in P.R. China.

Objective: To identify the current situation of leprosy colonies/leprosaria and make some recommendations for improving the quality of life of people affected by leprosy in China.

Methods: A national survey using designed forms was carried out in 2004. The forms were filled in by local heads responsible for the management of leprosy colonies/leprosaria and sent to Provincial and National Centres for analysis.

Risk of syphilis in STI clinic patients: a cross-sectional study of 11,500 cases in Guangxi, China.

Objective: To measure prevalence of syphilis among the STI clinic population in Guangxi, China, and to assess the socioeconomic and behavioural characteristics associated with the infection.

Methods: We undertook a cross-sectional survey and syphilis and HIV serologic testing among 11 473 patients attending 14 community and hospital-based dermatovenereal clinics across eight cities in Guangxi between December 2004 and February 2006.

Results: 1297 (11.

Relapse in MB leprosy patients treated with 24 months of MDT in south west China: a short report.

This study investigates the relapse rate among multibacillary leprosy patients treated with 24 months of MDT in south west China. A retrospective relapse survey was conducted in the southwest of China. A detailed questionnaire was designed to collect the data on relapse among MB patients who completed 2 years of the WHO/MB regimen, from 1989 to 2000.