Expression of mitochondrial transcription factor A in granulosa cells: implications for oocyte maturation and in vitro fertilization outcomes.

OBJECTIVE: In vitro fertilization-embryo transfer (IVF-ET) is a widely used treatment for infertility, with oocyte maturation and quality having a significant impact on oocyte fertilization, embryo development, and fetal growth. Mitochondrial transcription factor A (TFAM) is essential for maintaining the mitochondrial oxidative respiratory chain and supplying energy for oocyte development, fertilization, and embryonic development. In this study, we aimed to examine TFAM expression in women undergoing IVF-ET and assess its impact on the IVF outcomes. METHODS: We recruited 85 women who underwent IVF-ET treatment for infertility. On the date of egg collection, granulosa cells were extracted from the clear follicular fluid of the first mature egg using ultrasound-guided needle aspiration. The collected granulosa cells served three purposes: (1) detecting TFAM gene expression in granulosa cells via immunocytochemistry, (2) determining TFAM mRNA expression using reverse transcription-PCR (RT-PCR), and (3) measuring TFAM protein expression through western blotting. RESULT: Based on the results, we found that TFAM was localized and expressed in the cytoplasm of granulosa cells, whereas no expression was detected in the nucleus. Granulosa cells exhibited a linear correlation between TFAM mRNA and TFAM protein expression. The study participants were divided into three groups using the ternary method based on relative TFAM mRNA expression thresholds of 33% and 76%: the low-expression group (n = 30), the moderate-expression group (n = 27), and the high-expression group (n = 28). When compared to the other two groups, the moderate expression group exhibited a significantly higher egg utilization rate, 2 pronucleus rate, fertilization rate, and clinical pregnancy rate (P < 0.05). CONCLUSION: TFAM was detected in the cytoplasm of human ovarian granulosa cells. Women with moderate TFAM expression demonstrate enhanced outcomes in IVF.

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.

Synthesis, characterization and luminescent properties of lanthanide complexes with a novel multipodal ligand.

Solid complexes of lanthanide nitrates with an novel multipodal ligand, 1,2,4,5-tetramethyl-3,6-bis{N,N-bis[((2'-furfurylaminoformyl)phenoxyl)ethyl]-aminomethyl}-benzene (L) have been synthesized and characterized by elemental analysis, infrared spectra and molar conductivity measurements. At the same time, the luminescent properties of the Sm(III), Eu(III), Tb(III) and Dy(III) nitrate complexes in solid state were investigated. Under the excitation of UV light, these complexes exhibited characteristic emission of central metal ions. The lowest triplet state energy level of the ligand indicates that the triplet state energy level (T1) of the ligand matches better the resonance level of Tb(III) than other lanthanide ions.

Randomized trial of three phototherapy methods for the treatment of acne vulgaris in Chinese patients.

BACKGROUND AND AIMS: Acne vulgaris is common in Asian populations. We compared three methods of phototherapy for the treatment of moderate to severe facial acne vulgaris in Chinese patients. METHODS: Patients were randomly assigned to receive photodynamic therapy (PDT), intense pulsed light (IPL) or blue-red light-emitting diode (LED) phototherapy to the right side of the face until the inflammatory lesion count reduced by ≥ 90%. Patients were examined at 1 and 3 months after the final treatment. RESULTS: We enrolled 150 patients (92 males; mean age, 28 years). At 1 month, ≥90% clearance or moderate improvement occurred in 46/50 (92%), 29/50 (58%) and 22/50 (44%) patients in the PDT, IPL and LED groups, respectively (mean number of sessions required, PDT: 3 ± 1.52; IPL: 6 ± 2.15; LED: 9 ± 3.34). Forty-six (92%) patients experienced mild to moderate pain, erythema and edema after PDT, which resolved within 5-7 days. Slight erythema and stinging were reported immediately after IPL and LED, resolving within 2 h. After 3 months, minimal papules and pustules were observed in 4 patients in the PDT group, 7 in the IPL group and 12 in the LED group, but no nodular pustules recurred. CONCLUSIONS: Phototherapy is efficacious for moderate to severe facial acne vulgaris.

Acitretin exhibits inhibitory effects towards UDP-glucuronosyltransferase (UGT)1A9-mediated 4-methylumbelliferone (4-MU) and propofol glucuronidation reaction.

The present study aimed to evaluate the potential risk of drug-drug interactions associated with acitretin which is a drug for therapy of psoriasis approved by the Food and Drug Administration (FDA). The initial screening of acitretin's inhibition towards 4-methylumbelliferone (4-MU) glucuronidation catalyzed by important UDP-glucuronosyltransferase (UGT) isoforms in the liver showed that UGT1A9 activity was strongly inhibited by acitretin with other UGT isoforms negligibly influenced. The inhibition type is best fit to competitive inhibition, and the inhibition kinetic parameter (K(i)) was determined to be 3.5 microM. The inhibition behaviour of acitretin towards UGT1A9 activity did not exhibit probe substrate-dependent behaviour when selecting human liver microsomes (HLMs)-catalyzed propofol-O-glucuronidation as probe reaction of UGT1A9. The same inhibition type and similar inhibition parameters (K(i) = 3.2 microM) were obtained. Using the maximum plasma exposure dose of acitretin (C(max)), the C(max)/K(i) values were calculated to be 0.23 and 0.25 when selecting 4-MU and propofol as probe substrates, respectively. All these results indicate a potential clinical drug-drug interaction between acitretin and 4-MU or propofol.

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.

[Significance of IGS1, ITS and D1/D2 regions in molecular identification of Trichosporon species and genotype of T. asahii in China].

OBJECTIVE: To compare the sensitivity and specificity in molecular identification in different DNA regions of Trichosporon species and to study the genotype of T. asahii isolated from clinical specimens in China. METHODS: DNA was extracted from the cells of all experimental strains by using a method of glass bead method. The D1/D2, ITS and IGS1 regions were amplified by PCR with specific primers, the PCR products were cloned and sequenced. The sequences were referred to GenBank and compared with the other sequences of the Trichosporon species from GenBank by the software CLUSTAL X 1.83. Phylogenetic trees were constructed and genotypes were determined. RESULTS: The D1/D2 regions in T. asahii (CBS2479), T. dermatis, and T. laibachii were 640, 639, and 637 bp in length respectively, the ITS regions were 541, 528, and 531 bp respectively in length, and the IGS1 regions were 643, 515, and 411 bp respectively. The sequence similarity of the D1/D2 region was 89% - 99%, that of ITS and IGS1 regions were 85% - 99% and 11% - 95% respectively. The clinically isolated strains BZP07001, BZP07002, BZP07004, and BZP07005 belonged to genotype I, and the strain BZP07003 to genotype IV. CONCLUSION: The sensitivity and specificity of the IGS1 region was higher than those of the D1/D2 and ITS regions in identification of phylogenetically closely related Trichosporon species. T. asahii isolated from clinical specimens in China belongs to either genotype I or genotype IV.