Astragalus polysaccharide suppresses excessive collagen accumulation in a murine model of bleomycin-induced scleroderma.

Systemic scleroderma is an autoimmune disease characterized by fibrotic changes in skin and other organs involving excessive collagen deposition. The transforming growth factor-ß (TGF-ß) signaling pathway plays a key role in the fibrotic process in systemic scleroderma (SSc). Astragalus polysaccharides (APS) isolated from one of the Chinese herbs, Astragalus mongholicus, are known to have a variety of immunomodulatory activities. The present study aimed to investigate the effect of APS on TGF-ß signaling and its potential mechanism using a murine model of bleomycin-induced scleroderma. Scleroderma was induced in C3H/He N mice by subcutaneous bleomycin injections daily for 21 days. Skin samples were obtained 7, 14, and 21 days and TGF-ß1, Smad2, Smad3 mRNA expression was observed by real time PCR. The hydroxyproline content which consistent with the collagen content in skin samples from the BLM-injected group was significantly higher than the PBS group, and corresponded with dermal thickening at the injection site. In contrast, mice treated with APS after initiating BLM injection showed obviously lesser collagen content. Increased TGF-ß1, Smad2, Smad3 mRNA expression were also observed in the BLM group. TGF-ß1, Smad2, Smad3 expression was significantly lesser for the APS group than for the BLM group. In contrast, TGF-ß1 mRNA expression was remarkably inhibited by APS. These results suggest that APS treatment may inhibit TGF-ß1 production, and thus could be a potential drug for managing fibrotic disorders such as SSc.

Activating transcription factor 3 interferes with p21 activation in histone deacetylase inhibitor-induced growth inhibition of epidermoid carcinoma cells.

Inhibition of histone deacetylase (HDAC) activity by HDAC inhibitors (HDACis) results in cancer cell growth inhibition, and HDACis have been revealed as potential anti-skin cancer agents. p21 is a cyclin-dependent kinase inhibitor and an essential regulator of growth inhibition. Recently, we reported that activating transcription factor 3 (ATF3) could significantly promote skin cancer cell growth. This study explored the relationship between ATF3 and HDACi-induced growth inhibition of epidermoid carcinoma cells. We found that trichostatin A (TSA) treatment inhibited cell growth in A431 epidermoid carcinoma cells in a dose-dependent manner. Simultaneously, p21 and ATF3 expression levels were upregulated and downregulated upon TSA stimulation, respectively. ATF3 overexpression promoted cell growth and downregulated p21 expression. In contrast, ATF3 depletion resulted in cell growth reduction and p21 transcriptional upregulation. More importantly, ATF3 overexpression partially antagonized TSA-induced growth inhibition and p21 activation. Collectively, these data demonstrate that ATF3 acts as an essential negative regulator of TSA-induced cell growth inhibition through interfering with TSA-induced p21 activation.

Environmental investigations and molecular typing of Aspergillus in a Chinese hospital.

Invasive fungal infections due to Aspergillus species have become a major cause of morbidity and mortality among immunocompromised patients. In order to determine the possible relationship between environmental contamination by Aspergillus and the occurrence of invasive aspergillosis, a 1-year prospective study was carried out in a tertiary hospital in China. Air, surface, and tap water sampling was performed twice monthly at the bone marrow transplant (BMT) department, intensive care unit (ICU), neurosurgery intensive care unit (NICU), and outdoors. Nose, pharynx, and sputum samples were collected from high-risk patients. Isolates of Aspergillus from the environment and patients were genotyped by random amplification of polymorphic DNA (RAPD) assay to investigate the origin of infection. Mean total Aspergillus count was 7.73, 8.94, 13.19, and 17.32 cfu/m(3) in the BMT department, ICU, NICU, and outdoors, respectively. RAPD analysis by R108 primer demonstrated that strains isolated from patients in NICU were identical to the environmental strain. Strains isolated from patients in ICU differed from the environmental strain. Aspergillus contamination was found in the BTM department, NICU, and ICU. Clinical and environmental strains from NICU had identical genotypes. These findings suggest that Aspergillus is found in the hospital environment including the air, surface, and tap water. The genotypes of Aspergillus were identical from patients and the environment, suggesting that clinical infection may originate from the hospital environment.

ATF3 activates Stat3 phosphorylation through inhibition of p53 expression in skin cancer cells.

AIM: ATF3, a member of the ATF/CREB family of transcription factors, has been found to be selectively induced by calcineurin/NFAT inhibition and to enhance keratinocyte tumor formation, although the precise role of ATF3 in human skin cancer and possible mechanisms remain unknown. METHODS: In this study, clinical analysis of 30 skin cancer patients and 30 normal donors revealed that ATF3 was accumulated in skin cancer tissues. Functional assays demonstrated that ATF3 significantly promoted skin cancer cell proliferation. RESULTS: Mechanically, ATF3 activated Stat3 phosphorylation in skin cancer cell through regulation of p53 expression. Moreover, the promotion effect of ATF3 on skin cancer cell proliferation was dependent on the p53-Stat3 signaling cascade. CONCLUSION: Together, the results indicate that ATF3 might promote skin cancer cell proliferation and enhance skin keratinocyte tumor development through inhibiting p53 expression and then activating Stat3 phosphorylation.

Environment surveillance of filamentous fungi in two tertiary care hospitals in China.

BACKGROUND: Invasive fungal infections have constituted an increasingly important cause of morbidity and mortality in immunocompromised patients. In this study, a surveillance project was conducted in three different intensive care units of two large tertiary hospitals in China. METHODS: A one-year surveillance project was conducted in two tertiary hospitals which located in northern China and southwest China respectively. Air, surfaces and tap water were sampled twice a month in a central intensive care unit, a bone marrow transplant unit, a neurosurgery intensive care unit and a live transplant department. Environmental conditions such as humidity, temperature and events taking place, for example the present of the visitors, healthcare staff and cleaning crew were also recorded at the time of sampling. RESULTS: The air fungal load was 91.94 cfu/m(3) and 71.02 cfu/m(3) in the southwest China hospital and the northern China hospital respectively. The five most prevalent fungi collected from air and surfaces were Penicillium spp., Cladospcrium spp., Alternaria spp., Aspergillus spp. and Saccharomyces spp. in the southwest China hospital, meanwhile Penicillium spp., Fusarium spp., Aspergillus spp., Alternaria spp. and Cladospcrium spp. in the northern China hospital. The least contaminated department was intensive care units, and the heaviest contaminated department was neurosurgery intensive care unit. Seventy-three percent of all surfaces examined in the northern China hospital and eighty-six percent in the southwest China hospital yielded fungi. Fifty-four percent of water samples from the northern China hospital and forty-nine percent from the southwest China hospital yielded fungi. CONCLUSIONS: These findings suggested that the fungus exist in the environment of the hospital including air, surface and water. Air and surface fungal load fluctuated over the year. Air fungal load was lower in winter and higher in summer and autumn, but seldom exceeded acceptable level. The higher values were created during May to August in the northern China hospital and May to June and September to October in the southwest China hospital. A correlation between air fungal load and humidity, as well as personnel was observed.

Pathogenicity of Trichosporon asahii in a murine model of disseminated trichosporonosis.

BACKGROUND: In recent years, superficial and deep mycoses caused by trichosporon were occasionally reported. In 2001, we reported the first case of disseminated trichosporonosis caused by Trichosporon asahii (T. asahii) in China. In this study, the pathogenicity of T. asahii was investigated in a murine model of disseminated trichosporonosis. METHODS: Seventy-five mice were randomly divided into 7 groups. Each group was inoculated with T. asahii, through intradermal, gastrointestinal tract or intravenous injection. The mice in the experimental groups were given an intraperitoneal injection of cyclophosphamide (CY) to induce granulocytopenia. Mice in the therapeutic group were given both liposomal amphotericin B and fluconazole. The main viscera of the mice were examined by means of tissue culture and pathologic sections. RESULTS: In the two intravenous inoculation groups, T. asahii was isolated from at least one organ in 10 of the 12 granulocytopenic mice and 2 of the 14 immunocompetent mice. Two of the 7 mice in the granulocytopenia group presented with lesions in the inoculation position, but none of the 30 mice in the granulocytopenia and the control group which were inoculated intradermally or through the gastrointestinal tract had viscera infection. In the therapeutic group, the ratio of consequently dead mice, the number of involved viscera, and the incidence of systemic infection were significantly less than the untreated group. Acute purulent inflammation and granulomatous inflammation were the main pathological changes in the course of the infection. Arthrospores and filaments were found in the focus. CONCLUSIONS: T. asahii is an opportunistic pathogen that causes cutaneous and visceral infections in immunologically impaired hosts. An immunocompetent host was to be infected by the invading T. asahii. Several organs, namely the liver, lungs, kidneys, spleen and heart, were predisposed. The therapy of combining liposomal amphotericin B with fluconazole can prevent the host from an infection and inhibit the diffusion of the infection.