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Cutaneous warts caused by human papillomavirus are benign proliferative lesions that occur at any ages in human lives. Updated, comprehensive and systematic evidence-based guidelines to guide clinical practice are urgently needed.We collaborated with multidisciplinary experts to formulate this guideline based on evidences of already published literature, focusing on 13 clinical questions elected by a panel of experts. We adopted Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to form classification of recommendations as well as the improved Delphi method to retain respective recommendations with a consensus degree of over 80%.Our guideline covered aspects of the diagnosis and treatment of cutaneous warts such as diagnostic gold standard, transmission routes, laboratory tests, treatment principle, clinical cure criterion, definitions, and treatments of common warts, flat warts, plantar warts, condyloma acuminatum, and epidermodysplasia verruciformis. Recommendations about special population such as children and pregnant women are also listed. In total, 49 recommendations have been obtained.It is a comprehensive and systematic evidence-based guideline and we hope this guideline could systematically and effectively guide the clinical practice of cutaneous warts and improve the overall levels of medical services.

Background and objectives Both artesunate and fractional CO2 laser have been proved effective in the treatment of hypertrophic scars, yet little data are available for the efficacy of artesunate combined with fractional CO2 laser. In order to assess the pre-clinical significance and the underlying mechanism of this combined treatment profile, we attempted to observe the effectiveness of this therapy in rabbit models through determining the expression of BMP-7 and Fas. Materials and methods Twenty-Four New Zealand white rabbits with established hypertrophic scar samples were randomly divided into control group and three treatment groups. Artesunate (20 μl/cm2) was injected into the rat’s scar of artesunate and combination groups, while fractional CO2 laser (Combo mode, deep energy:10 mJ, super energy: 50 mJ) was applied to rats in fractional CO2 laser and combination groups at week 4 after model establishment. All rabbits underwent a total of 3 sessions of treatment once every 2 weeks. Histological and immunohistochemistry study, Western blot assay, cell viability, ELISA and RT-QPCR were performed at week 10 to observe the aspects of hypertrophic scar sample changes and expression of BMP-7 and Fas in the scar tissues. Results Compared with control group, hypertrophic scars and the collagen fibers were significantly inhibited after treatment, and higher inhibition was seen in the samples in combination group compared to that in artesunate and fractional CO2 laser groups (P Conclusions Artesunate combined with fractional CO2 laser is effective in hypertrophic scarring in this rabbit model. Our findings can serve as a potential alternative strategy to treatment of hypertrophic scar in clinical practice.

595-nm pulsed dye laser and fractional CO2 laser have been demonstrated effective to treat hypertrophic scar. The underlying mechanism may involve transforming growth factor-beta1 (TGFβ1) and proliferating cell nuclear antigen (PCNA), but remains to be clarified. Our study was performed to investigate how 595-nm pulsed dye laser combined with fractional CO2 laser treats hypertrophic scars in a rabbit model through regulating the expression of TGFβ1 and PCNA. Twenty-four New Zealand white rabbits were randomly divided into control group, pulsed dye laser group, fractional CO2 laser group, and pulsed dye laser + fractional CO2 laser (combination) group. Surgical wounds were made and allowed to grow into hypertrophic scars at day 28. Next, 595-nm pulsed dye laser (fluence: 15 J/cm2; square: 7 mm; pulse duration: 10 ms) was used in pulsed dye laser and combination group, while fractional CO2 laser (combo mode, deep energy: 12.5 mJ; super energy: 90 mJ) in fractional CO2 laser and combination groups, once every 4 weeks for 3 times. The appearance and thickness of hypertrophic scar samples were measured with hematoxylin-eosin and Van Gieson’s straining. The expressions of TGFβ1 and PCNA were evaluated by immunohistochemical and western blot analysis. A significant improvement was noted in the thickness, size, hardness, and histopathology of hypertrophic scar samples after laser treatment, especially in combination group. Scar Elevation Index (SEI), fiber density (NA), and collagen fiber content (AA) decreased most significantly in combination group (2.10 ± 0.14; 2506 ± 383.00; 22.98 ± 2.80%) compared to 595-nm pulsed dye laser group (3.35 ± 0.28; 4857 ± 209.40; 42.83 ± 1.71%) and fractional CO2 laser group (2.60 ± 0.25; 3995 ± 224.20; 38.33 ± 3.01%) (P

Background Trichosporon asahii is considered the most prominent species associated with invasive trichosporonosis, but little is known about the pathogenesis of T. asahii infection in the host. MicroRNAs (miRNAs) are a class of noncoding endogenous small RNAs that play vital roles by manipulating immune responses against pathogenic microorganisms. Nevertheless, the exact functions of miRNAs in T. asahii infection are still unknown. Objective To investigate the interactions involved in the miRNA immune response in THP-1 macrophages following in vitro exposure to T. asahii. Methods We utilized next-generation sequencing to detect differentially expressed (DE) miRNAs and mRNAs in THP-1 cells after 24 h of in vitro exposure to T. asahii. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to verify the sequencing results. The miRNA-mRNA regulatory network was constructed with the DE miRNAs and DE mRNAs. We performed Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis of the predicted targeting mRNAs in the miRNA-mRNA network. A dual-luciferase reporter assay and enzyme-linked immunosorbent assay (ELISA) were utilized to demonstrate the reliability of the miR-342-3p/Dectin-1 pair. Results A total of 120 DE miRNAs and 588 DE mRNAs were identified after 24 h of in vitro exposure to T. asahii. The miRNA-mRNA regulatory network was constructed with 39 DE miRNAs and 228 DE mRNAs. KEGG pathway analysis revealed that the up-regulated DE mRNAs in the complex interaction network were mainly involved in immune-related pathways. In addition, we verified the target relationship between miR-342-3p and Dectin-1 and found that miR-342-3p could promote the expression of TNF-α and IL-6 by negatively regulating Dectin-1. Conclusions This study evaluated the expression profiles of miRNA/mRNA and revealed the immunological consequences of THP-1 macrophages in response to T. asahii exposure. Moreover, our data suggest that miR-342-3p can indirectly promote inflammatory responses and may be a potential therapeutic target against trichosporonosis.

Small Extracellular Vesicles The simultaneous high expression of LAG‐3 and PD‐1 on T cells in cardiac transplantation mouse models and clinical renal transplantation patients provides the possibility to establish immune tolerance by giving their ligand molecules. In article number 2102634 by Bo Jia, Fang Cheng, Hongbo Chen, and co‐workers, small extracellular vesicles derived from bioengineered PD‐L1/FGL1‐expressed mesenchymal stem cells encapsulated with low‐dose FK506 exerted a powerful synergistic inhibitory effect on T cell activation and, therefore, prolonged grafts survival. [Image: see text]

There is an urgent need for developing new immunosuppressive agents due to the toxicity of long‐term use of broad immunosuppressive agents after organ transplantation. Comprehensive sample analysis revealed dysregulation of FGL1/LAG‐3 and PD‐L1/PD‐1 immune checkpoints in allogeneic heart transplantation mice and clinical kidney transplant patients. In order to enhance these two immunosuppressive signal axes, a bioengineering strategy is developed to simultaneously display FGL1/PD‐L1 (FP) on the surface of small extracellular vesicles (sEVs). Among various cell sources, FP sEVs derived from mesenchymal stem cells (MSCs) not only enriches FGL1/PD‐L1 expression but also maintain the immunomodulatory properties of unmodified MSC sEVs. Next, it is confirmed that FGL1 and PD‐L1 on sEVs are specifically bound to their receptors, LAG‐3 and PD‐1 on target cells. Importantly, FP sEVs significantly inhibite T cell activation and proliferation in vitro and a heart allograft model. Furthermore, FP sEVs encapsulated with low‐dose FK506 (FP sEVs@FK506) exert stronger effects on inhibiting T cell proliferation, reducing CD8+ T cell density and cytokine production in the spleens and heart grafts, inducing regulatory T cells in lymph nodes, and extending graft survival. Taken together, dual‐targeting sEVs have the potential to boost the immune inhibitory signalings in synergy and slow down transplant rejection., MSC‐derived FGL1/PD‐L1 sEVs encapsulated in FK506 exhibited a strong ability to inhibit T cell activation and proliferation, and also induced Tregs in organ recipient mice. An experimental basis for a novel intervention strategy is provided that leverages the function of target delivery sEVs to synergistically enhance two immunosuppression axes and reestablish immune tolerance, ultimately promoting organ acceptance.

Trichosporon asahii is the major pathogen causing invasive trichosporonosis. Conventional methods of its detection are time-consuming or costly and often require complex DNA extraction and purification steps, which hinders rapid clinical diagnosis. In this study, we evaluated colony PCR, which directly uses colonies or trace clinical samples as the template for amplification, for rapid detection of T. asahii infection. Four methods, namely, direct colony, freeze-thaw, glass beads, and enzymolysis, were compared to select the best DNA extraction strategy. We subsequently designed and screened species-specific primers targeting the intergenic spacer 1 (IGS1) of the ribosomal DNA of T. asahii and used them to detect mock infection clinical samples. The species-specific colony PCR based on glass beads proved advantageous, with short procedure time (154.8 ± 0.6 min), good sensitivity (detection limit, 102 CFU/mL), and specificity for T. asahii, indicating that this method can be used for the rapid and simple identification of clinical samples of T. asahii infection.

Background Invasive Trichosporon asahii (T. asahii) infection frequently occurs with a high mortality in immunodeficient hosts, but the pathogenesis of T. asahii infection remains elusive. Circular RNAs (circRNAs) are a type of endogenous noncoding RNA that participate in various disease processes. However, the mechanism of circRNAs in T. asahii infection remains completely unknown. Methods RNA sequencing (RNA-seq) was performed to analyze the expression profiles of circRNAs, microRNAs (miRNAs), and mRNAs in THP-1 cells infected with T. asahii or uninfected samples. Some of the RNA-seq results were verified by RT-qPCR. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were used to analyze the differentially expressed mRNAs. A circRNA-miRNA-mRNA network was constructed and verified by dual-luciferase reporter assay and overexpression experiments. Results A total of 46 circRNAs, 412 mRNAs and 47 miRNAs were differentially expressed at 12 h after T. asahii infection. GO and KEGG analyses showed that the differentially expressed mRNAs were primarily linked to the leukocyte migration involved in the inflammatory response, the Toll-like receptor signaling pathway, and the TNF signaling pathway. A competing endogenous RNA (ceRNA) network was constructed with 5 differentially expressed circRNAs, 5 differentially expressed miRNAs and 42 differentially expressed mRNAs. Among them, hsa_circ_0065336 was found to indirectly regulate PTPN11 expression by sponging miR-505-3p. Conclusions These data revealed a comprehensive circRNA-associated ceRNA network during T. asahii infection, thus providing new insights into the pathogenesis of the T. asahii-host interactions.

BACKGROUND AND OBJECTIVES Hypertrophic scar (HS), a common complication in wound healing, is characterized by the disarrangement of collagen, fibers, and extracellular matrix. Artesunate (ART) can inhibit the abnormal formation of fibroblasts and collagens. Fractional CO2 laser (FCO2 L) can facilitate tissue remodeling and the absorption of drugs into ablative microthermal columns in HS. So far, no research has investigated the efficacy of ART combined with an FCO2 L in treating HS. To investigate the theoretical basis and clinical significance of this combination, we established a rabbit model of HS to observe the change in the expression of transforming growth factor β1 (TGF-β1) and proliferating cell nuclear antigen (PCNA). STUDY DESIGN/MATERIALS AND METHODS Forty New Zealand white rabbits were randomly divided into four groups: control group, ART group, FCO2 L group, and ART + FCO2 L (combination) group. Four wounds were surgically established in the ear of each rabbit and allowed to develop into HS. ART (20 μL/cm2 ) was injected in ART and combination groups, and FCO2 L (combo mode, deep energy:10m J, super energy: 50 mJ) in FCO2 L and combination groups on the 28th day after HS occurred. Three rounds of treatment were applied (once every 14 days). HS samples were measured by hematoxylin and eosin staining, Van Gieson staining, immunohistochemistry, and Western blot analysis on the 70th day. RESULTS The morphological and histopathological changes in HS were significant. HSs were smoother and smaller and the collagen fibers were thinner and less disordered in the combination group than those in ART and FCO2 L groups. Meanwhile, the hypertrophic index (HI), fiber density (NA), and collagen fiber content (AA) were lower in the combination group (1.54 ± 0.15, 3.30 ± 0.22, 30.37 ± 1.41%) than in the ART group (2.51 ± 0.22, 4.69 ± 0.16, 44.68 ± 2.30%) and FCO2 L group (1.99 ± 0.14, 4.13 ± 0.12, 37.74 ± 1.38%) (P

The opportunistic fungal pathogen Trichosporon asahii (T. asahii) is an important causal agent of mortality in immunocompromised patients and associated with frequent relapses, even with sufficient antifungal treatment. Investigating the proteomes of initial and recurrent isolates may help to identify within-host adaptive changes. In this study, using tandem mass tag (TMT)-labeling combined with liquid chromatography-mass spectrometry/mass spectrometry (LC–MS/MS) technology, we analyzed the proteomes of two T. asahii strains that were isolated 15 years apart from the same patient who suffered initial and recurrent episodes of systemic disseminated trichosporonosis. A total of 597 differentially expressed proteins were identified. Functional analysis showed that the increased proteins were primarily concentrated on peptide/protein/energy/drug metabolism and translation. Most of the results were determined to be consistent with the findings of phenotypic assays, such as tests for drug susceptibility, temperature growth, biofilm formation, melanization and paromomycin assays. Moreover, we performed multiple reaction monitoring (MRM) mass spectrometry to verify 27 candidate proteins, and the results of this experiment were also highly consistent with the results of the TMT analysis. Therefore, to the best of our knowledge, these data provide the first molecular evidence of how the T. asahii proteome changes related to host-specific adaptation during human infection. Significance Systemic infection with Trichosporon asahii (T. asahii) has recently been recognized as an important causal agent of mortality in immunocompromised patients. Although triazole treatment usually works efficiently in the early phase of infection, many patients relapse. Hence, comparative analyses of the proteomics of initial and recurrent isolates may reveal evidence of adaptive changes within the host. Our study demonstrates that the recurrent strain has undergone proteomic changes using tandem mass tag (TMT)-labeling combined with liquid chromatography-mass spectrometry/mass spectrometry (LC–MS/MS). Moreover, the results of phenotypic assays, including drug susceptibility, temperature growth, biofilm formation, melanization and paromomycin assays, were highly consistent with the proteomic changes, and multiple reaction monitoring (MRM) verification also showed similar trends to the TMT results. In summary, our study is the first to investigate the adaptation of T. asahii under pressure from antifungal chemotherapy and host immune responses.

Background and ObjectivesAlthough the treatment of hypertrophic scar (HS) remain challenging, fractional CO2 laser (FCO2L) and 595-nm pulsed-dye laser (PDL) have proved clinical efficacy. Meanwhile, BMP-7 and Fas proteins are demonstrated to promote wound healing and inhibit scar formation, yet few reports on the effect of the two proteins on hypertrophic scarring are available, and their molecular mechanisms remain unclear. In current study, we attempted to observe the effect of combined use of FCO2L with 595-nm PDL in HS animal models through determining the expression of BMP-7 and Fas in scar inhibition.Materials and MethodsTwenty New Zealand white rabbits were randomized to control group, FCO2L group, PDL group and combined treatment group. Four HS samples were developed at each ear of individual rabbit. FCO2L was respectively applied to simple FCO2L and combined treatment group, and simple 595-nm PDL and combined treatment group. Totally, 3 sessions of treatments were carried out once every 14 days. Then, the changes of fibroblasts and collagens in HSs and expression of BMP-7 and Fas proteins in the scar tissues were determined via histological and immunohistochemical studies, ELISA, CCK8 test, RT-PCR and Western blot assay.ResultsHSs were flattened and shrunk after treatment, especially in rabbits treated by FCO2L plus 595-nm PDL group, in which obviously decreased abnormal fibroblast and collagen were noted. The deference was significant compared to other groups(P 2L or 595-nm PDL therapy group (P 2L combined with 595-nm PDL can improve HSs in rabbit models by inhibiting excessive fibroblast growth and collagen deposition. This may be associated with increased BMP-7 and Fas expression in the scar tissues. And our findings may pioneer a new therapeutic strategy for alternative treatment of HSs.

Trichosporon asahii (T. asahii) is a clinically important opportunistic pathogenic fungus capable of causing systemic lethal infection in immunosuppressive and immunodeficient hosts. However, the mechanism of the host immune response upon T. asahii infection has not been elucidated. Recent evidence has shown that long noncoding RNAs (lncRNAs) play key roles in regulating the immune response to resist microbial infections. In this study, we analyzed the expression profiles of lncRNAs at 12 and 24 h post-infection (hpi) in THP-1 cells infected with T. asahii using RNA sequencing (RNA-Seq). A total of 64 and 160 lncRNAs displayed significant differentially expressed (DE) at 12 h and 24 hpi, respectively. Among these lncRNAs, 18 lncRNAs were continuous DE at two time points. The DE of eight candidate lncRNAs were verified by real time quantitative polymerase chain reaction (RT-qPCR). Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to analyze the cis-target genes of 18 DE lncRNAs. The results showed that they were enriched in signaling pathways related to the host immune response, indicating that these lncRNAs might play important roles in fungi–host interactions. Finally, we explored the function of lncRNA NEAT1 and found that the expression of TNF-α and IL-1β declined after NEAT1 knockdown in T. asahii-infected THP-1 cells. To our knowledge, this is the first report of a expression analysis of lncRNAs in macrophages infected with T. asahii. Our study helps to elucidate the role of lncRNAs in the host immune response to early infection by T. asahii.

595-nm pulsed dye laser and fractional CO

Trichosporon is a yeast-like basidiomycete, a conditional pathogenic fungus that is rare in the clinic but often causes fatal infections in immunocompromised individuals. Trichosporon asahii is the most common pathogenic fungus in this genus and the occurrence of infections has dramatically increased in recent years. Here, we report a systematic literature review detailing 140 cases of T. asahii infection reported during the past 23 years. Statistical analysis shows that T. asahii infections were most frequently reported within immunodeficient or immunocompromised patients commonly with blood diseases. Antibiotic use, invasive medical equipment and chemotherapy were the leading risk factors for acquiring infection. In vitro susceptibility, clinical information and prognosis analysis showed that voriconazole is the primary drug of choice in the treatment of T. asahii infection. Combination treatment with voriconazole and amphotericin B did not show superiority over either drug alone. Finally, we found that the types of infections prevalent in China are significantly different from those in other countries. These results provide detailed information and relevant clinical treatment strategies for the diagnosis and treatment of T. asahii infection.

Background: Trichosporon asahii (T. asahii) invasive infection frequently occurs in immunodeficient hosts with high mortality, but the pathogenesis of T. asahii infection remains elusive. Circular RNAs (circRNAs) are a type of endogenous noncoding RNAs that participant various disease processes. However, the mechanism of circRNAs in T. asahii infection are still completely unknown.Methods: RNA sequencing (RNA-seq) was performed to analyse the expression profiles of circRNA, microRNA (miRNA), and mRNA in THP-1 cells infected with T. asahii or uninfected samples. Part of the RNA-seq results were verified by RT-qPCR. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to analyse the differentially expressed (DE) mRNA. The circRNA-miRNA-mRNA network was constructed and verified with dual-luciferase reporter assay and overexpression experiment.Results: A total of 46 circRNAs , 412 mRNAs and 47 miRNAs were DE after T. asahii infection at 12 h. GO and KEGG analysis showed that the DE mRNAs were primary linked to the leukocyte migration involved in inflammatory response, Toll-like receptor signaling pathway, and TNF signaling pathway. A competing endogenous RNA (ceRNA) network was constructed with five DE circRNAs, five DE miRNAs and 42 DE mRNAs. Among them, we verified that hsa_circ_0065336 indirectly regulate PTPN11 expression by sponging miR-505-3p.Conclusions: These data revealed a comprehensive circRNA-associated ceRNA network during T. asahii infection, thus providing new insights to clarify the pathogenesis between T. asahii-host interation.

Trichosporon is a yeast-like basidiomycete, a conditional pathogenic fungus that is rare in the clinic but often causes fatal infections in immunocompromised individuals.Trichosporon asahiiis the most common pathogenic fungus in this genus and the occurrence of infections has dramatically increased in recent years. Here, we report a systematic literature review detailing 140 cases ofT. asahiiinfection reported during the past 23 years. Statistical analysis shows thatT. asahiiinfections were most frequently reported within immunodeficient or immunocompromised patients commonly with blood diseases. Antibiotic use, invasive medical equipment and chemotherapy were the leading risk factors for acquiring infection.In vitrosusceptibility, clinical information and prognosis analysis showed that voriconazole is the primary drug of choice in the treatment ofT. asahiiinfection. Combination treatment with voriconazole and amphotericin B did not show superiority over either drug alone. Finally, we found that the types of infections prevalent in China are significantly different from those in other countries. These results provide detailed information and relevant clinical treatment strategies for the diagnosis and treatment ofT. asahiiinfection.

Superoxide dismutase (SOD) and catalase are considered the most important antioxidant enzymes which protect fungus from the oxidant damage of reactive oxygen species. In this study, we collected 44 strains of Trichosporon asahii (T. asahii) from different sources and investigated their SOD and catalase activities. The results showed that the SOD and catalase activities of Clinical group were significantly higher than those of Environment group (p < 0.01). The SOD and catalase activities of T. asahii in Internal passage group went up gradually after passage in mice, and were significantly higher in 5th generation of Internal passage group (p < 0.05). The SOD and catalase activities of Fluconazole-resistant group strains also increased after resistant induction, and the SOD and catalase activities were significantly higher in the 10th generation of Fluconazole-resistant group (p < 0.05). This implied that T. asahii has stronger antioxidant ability. The strains of T. asahii from different sources have different antioxidant abilities, which mainly manifest in the difference of antioxidant enzymatic activities. Clinical group strains have the strongest antioxidant capacity; Internal passage group strains and Fluconazole resistant group strains better; Environmental group strains the lowest. These results also suggested that the antioxidant defensive response of T. asahii might be relevant to its infection mechanism and drug resistance mechanism.

BACKGROUND Our study aimed to explore the association between β1-adrenoceptor (ADRB1) rs1801253 polymorphism and analgesic effect of fentanyl after cancer surgeries in Chinese Han populations. MATERIAL AND METHODS Postoperative fentanyl consumption of 120 patients for analgesia was recorded. Genotype distributions were detected by allele specific amplification-polymerase chain reaction (ASA-PCR) method. Postoperative pain was measured by visual analogue scale (VAS) method. Differences in postoperative VAS score and postoperative fentanyl consumption for analgesia in different genotype groups were compared by analysis of variance (ANOVA). Preoperative cold pressor-induced pain test was also performed to test the analgesic effect of fentanyl. RESULTS Frequencies of Gly/Gly, Gly/Arg, Arg/Arg genotypes were 45.0%, 38.3%, and 16.7%, respectively, and passed the Hardy-Weinberg Equilibrium (HWE) test. The mean arterial pressure (MAP) and the heart rate (HR) had no significant differences at different times. After surgery, the VAS score and fentanyl consumption in Arg/Arg group were significantly higher than in other groups at the postoperative 2nd hour, but the differences were not obvious at the 4th hour, 24th hour, and the 48th hour. The results suggest that the Arg/Arg homozygote increased susceptibility to postoperative pain. The preoperative cold pressor-induced pain test suggested that individuals with Arg/Arg genotype showed worse analgesic effect of fentanyl compared to other genotypes. CONCLUSIONS In Chinese Han populations, ADRB1 rs1801253 polymorphism might be associated with the analgesic effect of fentanyl after cancer surgery.

Genome-wide association studies (GWASs) have reproducibly associated ∼40 susceptibility loci with psoriasis. However, the missing heritability is evident and the contributions of coding variants have not yet been systematically evaluated. Here, we present a large-scale whole-exome array analysis for psoriasis consisting of 42,760 individuals. We discover 16 SNPs within 15 new genes/loci associated with psoriasis, including C1orf141, ZNF683, TMC6, AIM2, IL1RL1, CASR, SON, ZFYVE16, MTHFR, CCDC129, ZNF143, AP5B1, SYNE2, IFNGR2 and 3q26.2-q27 (P, Psoriasis is a chronic inflammatory disease affecting up to 3% of the population. Here, Zuo et al. perform exome array analysis, identify single-nucleotide polymorphisms at 15 new loci, implicating several biological pathways in psoriasis risk and disease heritability.

Trichosporon asahii (T. asahii) has emerged as a dangerous pathogen that causes rare but life-threatening infections. Its resistance to certain antifungal agents makes it difficult to treat, especially for patients undergoing long-term antibiotic therapy. In this study, we performed a series of fluconazole (FLC) perturbation experiments for two T. asahii strains, a clinical isolate stain CBS 2479 (T2) and an environmental isolate strain CBS 8904 (T8), to uncover potential genes and pathways involved in FLC resistance. We achieved 10 transcriptomes of T2 and T8 that were based on dose and time series of FLC perturbations. Systematic comparisons of the transcriptomes revealed 32 T2 genes and 25 T8 genes that are highly sensitive to different FLC perturbations. In both T2 and T8 strains with the phenotype of FLC resistance, the processes of oxidation-reduction and transmembrane transport were detected to be significantly changed. The antifungal susceptibility testing of FLC and penicillin revealed their resistance pathways are merged. Accumulated mutations were found in 564 T2 and 225 T8 genes, including four highly mutated genes that are functionally related to the target of rapamycin complex (TOR). Our study provides abundant data towards genome-wide understanding of the molecular basis of FLC resistance in T. asahii.

Trichosporon asahii (T. asahii) can cause invasive infections, particularly catheter-related bloodstream infections (CR-BSIs). T. asahii biofilm, which is resistant to the most common clinical antifungal agents, may play an important role in these life-threatening infections. This study focused on the effects of ethanol on the different phases of T. asahii biofilm formation. At the concentrations clinically used, ethanol killed T. asahii planktonic cells (MIC90 = 15% and m-MIC90 = 15%) and biofilm (SMIC90 = 50%), and exposure to 25% ethanol for 12 h or to 50% ethanol for 8 h completely inhibited biofilm development and eradicated mature T. asahii biofilm. Thus, our results showed that ethanol effectively inhibited the main phases of T. asahii biofilm formation. This study reveals a new potential strategy to prevent and treat T. asahii biofilm-related CR-BSIs.

SummaryBackground 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.

Optimization of Radix Rehmanniae polysaccharides (RRPs) was done using response surface methodology (RSM). Optimum extraction conditions for maximizing the determination of Radix Rehmanniae polysaccharides were: extraction temperature 100 °C, extraction time 2h and ratio of liquid to solid 6. The model had a satisfactory coefficient of R(2) (=0.9815) and was verified experimentally. The results suggested that the conditions were mild and useful for extraction yield of Radix Rehmanniae polysaccharides. Pharmacological experiment showed that Radix Rehmanniae polysaccharides could enhance serum interleukin-2 (IL-2), interleukin-4 (IL-4) and interleukin-10 (IL-10) levels, skin glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, and decrease skin malondialdehyde (MDA) level in ultraviolet B (UVB) ray treated mice, this study suggests that Radix Rehmanniae polysaccharides extract may prove to be a useful therapeutic option in the reversal of skin diseases.

Trichosporon asahii (T. asahii) is the major pathogen of invasive trichosporonosis which occurred mostly in immunocompromised patients. The biofilms formation ability of T. asahii may account for resistance to antifungal drugs and results a high mortality rate. Sertraline, a commonly prescribed antidepressant, has been demonstrated to show in vitro and in vivo antifungal activities against many kinds of pathogenic fungi, especially Cryptococcus species. In the present study, the in vitro activities of sertraline alone or combined with fluconazole, voriconazole, itraconazole, caspofungin and amphotericin B against planktonic forms and biofilms of 21 clinical T. asahii isolates were evaluated using broth microdilution checkerboard method and XTT reduction assay, respectively. The fractional inhibitory concentration index (FICI) was used to interpret drug interactions. Sertraline alone exhibited antifungal activities against both T. asahii planktonic cells (MICs, 4–8 μg/ml) and T. asahii biofilms (SMICs, 16–32 μg/ml). Furthermore, SRT exhibited synergistic effects against T. asahii planktonic cells in combination with amphotericin B, caspofungin or fluconazole (FICI≤0.5) and exhibited synergistic effects against T. asahii biofilms in combination with amphotericin B (FICI≤0.5). SRT exhibited mostly indifferent interactions against T. asahii biofilms in combination with three azoles in this study. Sertraline-amphotericin B combination showed the highest percentage of synergistic effects against both T. asahii planktonic cells (90.5%) and T. asahii biofilms (81.0%). No antagonistic interaction was observed. Our study suggests the therapeutic potential of sertraline against invasive T. asahii infection, especially catheter-related T. asahii infection. Further in vivo studies are needed to validate our findings.

Superoxide dismutase (SOD) and catalase are considered the most important antioxidant enzymes which protect fungus from the oxidant damage of reactive oxygen species. In this study, we collected 44 strains of Trichosporon asahii (T. asahii) from different sources and investigated their SOD and catalase activities. The results showed that the SOD and catalase activities of Clinical group were significantly higher than those of Environment group (p

Epidermal stem cells are of major importance for skin regeneration and tissue engineering, but differentiated epidermal cells lost their proliferative capacity and are no longer able to regenerate a skin equivalent. Here, we investigated the role of β-catenin in regulating regenerative functions of differentiated epidermal cells. Lithium chloride and a highly specific glycogen synthase kinase (GSK)-3β inhibitor were applied to induce the expression of β-catenin in differentiated epidermal cells. After a 6-day induction, the large flat-shaped cells with a small nuclear-cytoplasmic ratio had changed into small round-shaped cells with a large nuclear-cytoplasmic ratio. Phenotypic assays showed a remarkably higher expression of CK19, β1-integrin, Oct4 and Nanog in induced cells than in the control group (p < 0.01). In addition, the results of growth and functional investigations demonstrated that the induced epidermal cells exhibited a high colony-forming ability, a long-term proliferative potential and the ability to regenerate a skin equivalent, which were regarded as the most important features of epidermal stem cells. These results suggest that the activation of β-catenin favors the reversion or dedifferentiation of differentiated epidermal cells to an immature or a less differentiated state. This study may also offer a new approach to yield enough epidermal stem cells for skin regeneration and tissue engineering.

BACKGROUND MicroRNAs (miRNA) dysregulation has been considered to be significantly related to the occurrence and development of cancers. Several studies had proved that DNA methylation is an important cause of the abnormal expression of miRNAs. The purpose of this study was to investigate the methylation status of miR-148a and its effects on the metastasis and prognosis of skin cancer, as well as the interaction with TGIF2 gene. MATERIAL AND METHODS According to the qRT-PCR analysis, the expression of miR-148a was down-regulated in tumor tissues compared with the adjacent tissues and healthy controls (P

The transforming growth factor-β (TGF-β) signaling pathway plays a key role in the fibrotic process in systemic scleroderma (SSc). Curcumin, a Turmeric root extract, has been demonstrated to exert antifibrotic activity. In the present study, we carefully investigated the effect of curcumin on TGF-β signaling and its potential mechanism in SSc fibroblasts. We demonstrated a potent inhibitory effect of curcumin on TGF-β signaling. Curcumin counteracted TGF-β-induced phosphorylation of Smad2 but not Smad3. Further study revealed curcumin induced upregulation of TGF-β-induced factor (TGIF), a negative regulator of TGF-β signaling. The TGIF silencing results evidenced the essential role of TGIF in curcumin-mediated TGF-β/Smad2 suppression. Moreover, our data indicated that the upregulation of TGIF by curcumin might result from decreased ubiquitination of TGIF, which blocks its proteasome-mediated degradation. Collectively, our data provide a novel mechanism of curcumin-mediated suppression of fibrotic process in scleroderma.

A polysaccharide was isolated from the Herba Cistanches. This polysaccharides contained glucose, galactose, rhamnose, arabinose and fructose. The native polysaccharide could be fractionated by size exclusion chromatography into one major fraction. The apparent average molecular weight of the purified polysaccharide was estimated to be approximately 385 kDa by size-exclusion HPLC. Furthermore, this polysaccharides still exhibited strong antioxidant activities in aged rats’ skin. Namely, Herba Cistanches polysaccharides inhibited the oxidative modification of lipids, thus protecting cells from injury by the oxidized molecules in aged rats’ skin. The present results were in accordance with previous studies on the mode of the protective effect of the plant extract which showed positively that the protection may possibly be attributed to the combination of more than one biological activities and that the use of antioxidants might be an useful approach in the treatment of some skin aging diseases.

We first reviewed the English-language literature for reported cases of Trichosporon fungemia over the past four decades, and did comprehensive analysis in order to guide our understanding of epidemiology and outcome-related aspects, especially the antifungal treatment and CVC management., Background. Trichosporon species have emerged as an important non-Candida spp yeast pathogen in immunocompromised patients in recent decades; however, the systemic analysis of Trichosporon epidemiology has seldom been reported. Methods. We reviewed 185 reported cases of Trichosporon fungemia from 1975 to 2014 in the English-language literature, and the epidemiology and prognostic factors of the included cases are described. Results. The number of cases reported has increased with time, especially over the past decade. During the 3 decades from 1975 to 2004, the most commonly used antifungal compounds were amphotericin B/liposomal amphotericin B; however, in recent decades (2005–2014), triazoles (especially voriconazole) have become the most widely used agents, significantly improving outcome in the reported cases. Correlation analysis revealed that negative outcome is associated with several prognostic factors, including a history of antimicrobial use, bacterial bloodstream coinfection, prophylactic/empirical antifungal therapy, Trichosporon beigelii infection, and receiving the antifungal regimen of amphotericin B/liposomal amphotericin B. In addition, a significantly greater proportion of patients with a positive outcome had fungemia without invasive tissue infection and received a voriconazole regimen or an AmB-triazole combined regimen. Significant positive outcome was also associated with patients who had recovered from neutropenia or after central venous catheter removal. Conclusions. Voriconazole can be recommended as a first-line antifungal compound to treat Trichosporon fungemia; the immune status of the host plays a crucial role in the outcome of this infection, and the removal of vascular catheters should be considered if feasible.