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Abstract This study aimed to investigate the molecular mechanism of sporotrichosis and identify possible novel therapeutic targets. Total RNA was extracted from skin lesion samples from sporotrichosis patients and used to construct a long-chain RNA transcriptome library and miRNA transcriptome library for whole transcriptome sequencing. The differentially expressed genes (DEGs) between the groups were identified, and then Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and Gene Set Enrichment Analysis enrichment analyses were performed based on the DEGs. An lncRNA-miRNA-mRNA ceRNA network was constructed. The expressions of JAK/STAT pathway-related proteins were detected in the patient and control tissues using RT-qPCR and Western blot analysis. Enrichment analysis showed that the DEGs were mainly enriched in various infectious diseases and immune response-related signaling pathways. Competing endogenous RNA network analysis was performed and identified the hub lncRNAs, miRNAs, and mRNAs. Compared with the control group, the mRNA expressions of SOCS3, IL-6, and JAK3 were significantly upregulated, while the expression of STAT3 did not change significantly. Also, the protein expressions of SOCS3, IL-6, JAK3, and STAT3, as well as phosphorylated JAK3 and STAT3, were significantly upregulated. We identified 671 lncRNA DEGs, 3281 mRNA DEGs, and 214 miRNA DEGs to be involved in Sporothrix globosa infection. The study findings suggest that the JAK/STAT pathway may be a therapeutic target for sporotrichosis.

Abstract. Background. Benvitimod cream, a novel synthetic small molecule, was effective in treating mild-to-moderate plaque psoriasis. We conducted a phase III clinical trial to assess the efficacy and safety of benvitimod cream in patients with mild-to-moderate plaque psoriasis. Methods. We randomly assigned 686 patients (2:1:1) to receive 1% benvitimod cream, 0.005% calcipotriol ointment or placebo twice a day for 12 weeks. The primary efficacy end points were the percentage of patients with a 75% or greater reduction from baseline in the psoriasis area and severity index (PASI 75) score and with a score of 0 or 1 in static physician's global assessment (sPGA) at week 12. Results. The results showed that 50.4% of patients in the benvitimod group achieved PASI 75, which was significantly higher than that in the calcipotriol (38.5%, P

Abstract Background More and more azole-resistant strains emerged through the development of acquired resistance and an epidemiological shift towards inherently less susceptible species. The mechanisms of azoles resistance of Candida albicans is very complicated. In this study, we aim to investigate the mechanism of azole-resistant C. albicans isolated from the oral cavity of a patient with chronic mucocutaneous candidiasis (CMC). Case presentation CMC diagnosis was given based on clinical manifestations, laboratory test findings and gene sequencing technique. Minimum inhibitory concentration (MIC) of the fungal isolate, obtained from oral cavity termed as CA-R, was obtained by in vitro anti-fungal drugs susceptibility test. To further investigate the resistant mechanisms, we verified the mutations of drug target genes (i.e. ERG11 and ERG3) by Sanger sequencing, and verified the over-expression of ERG11 and drug efflux genes (i.e. CDR1 and CDR2) by RT-PCR. A heterozygous mutation of c.1162A > G resulting in p.K388E was detected in STAT1 of the patient. The expression of CDR1 and CDR2 in CA-R was 4.28-fold and 5.25-fold higher than that of type strain SC5314, respectively. Conclusions Up-regulation of CDR1 and CDR2 was mainly responsible for the resistance of CA-R. For CMC or other immunodeficiency patients, drug resistance monitoring is necessary.

Majocchi’s granuloma (MG) is an unusual but not rare dermatophyte infection of dermal and subcutaneous tissues. Dermatophytes usually result in the infections of hair, epidermis, and nail, and are rarely involved in deep cutaneous and subcutaneous tissues. Now it is considered that MG includes two forms: one is a small perifollicular papular form and the other is a deep subcutaneous nodular form; the front one mainly occurs in healthy individuals and the latter one usually presents in immunocompromised hosts. The clinical manifestations of MG are many and varied, except the common presentations of erythema, papule and nodules, and Kaposi sarcoma-like and molluscum-like lesions have been reported in literatures (Kim et al. (2011), Bord et al. (2007), and Lillis et al. (2010)). This characteristic induces the difficulty of diagnosis, and thus it is so important and necessary to make direct microscopical and histological examinations. We describe a case of MG over the face in a patient who had been treated with topical corticosteroids over a long time.

To investigate the inhibitory effect of imatinib on the migration of normal human epidermal melanocytes (NHEM), the growth and differentiation of NHEM were measured by MTT assay. Transwell Cell Migration Assay was performed to determine the migration of NHEM following imatinib treatment. The phosphorylation of c-kit in NHEM after imatinib treatment was measured by western blot assay. Imatinib at 0.1 ?M, 1.0 ?M and 5.0 ?M could inhibit the SCF (50 ng/mL) induced NHEM migration and suppress the phosphorylation of c-kit in NHEM. The result concluded that imatinib can inhibit SCF induced NHEM migration and suppress the c-kit phosphorylation in NHEM. This provide theoretical basis for the prevention of post-treatment recurrence of nevus spilus.

In this paper, an experimental program was reported to investigate the effects of polyester fibers on the mechanical properties of cement treated clay soil. Five different fiber contents and same number cement content were randomly inserted into the soil. Thirty samples were prepared and stored in the curing box for seven, twenty-eight, and ninety days, respectively, and then subjected to unconfined compressive tests and indirect tensile tests. It was found that the values of tests increased as the fiber content and curing time increased. Fiber inclusion improved the ductile failure characteristic of soil. From results of the test, there was a certain linear relationship between two kinds of strengths. The micro structures were obtained from scanning electron microscopy (SEM) analysis. It was found that a strong cohesive force obstructed the relative sliding between fiber and cement-soil mixture. [ABSTRACT FROM AUTHOR]

Abstract: Since the histidine-containing dipeptide carnosine (β-alanyl-l-histidine) is believed to have many physiological functions in the brain, we investigated the neuroprotective effects of carnosine and its mechanisms of action in an in vitro model of neurotoxicity induced by N-methyl-d-aspartate (NMDA) in differentiated PC12 cells. Pretreatment with carnosine increased the viability and decreased the number of apoptotic and necrotic cells measured by MTT and Hoechst 33342 and propidium iodide (PI) double staining assays. Carnosine also can inhibite the glutamate release and increase HDC activity and the intracellular and extracellular contents of carnosine, histidine and histamine detected by high-performance liquid chromatography (HPLC). The protection by carnosine was reversed by α- fluoromethylhistidine, a selective and irreversible inhibitor of histidine decarboxylase (HDC). Pyrilamine and thioperamide, selective central histamine H1 and H3 antagonists also significantly reversed the protection of carnosine. Further, the inhibition of glutamate release by carnosine was reversed by thioperamide. Therefore, the protective mechanism of carnosine may not only involve the carnosine-histidine-histamine pathway, but also H1/H3 receptors and the effective inhibition of glutamate release. This study indicates that carnosine may be an endogenous protective factor and calls for its further study as a new antiexcitotoxic agent. [Copyright &y& Elsevier]

Objective: To investigate the effects of histamine on the neurotoxicity induced by beta-amyloid(1-42)(Abeta42) in rat phaeochromocytoma (PC12) cells., Methods: The in vitro model of Alzheimer's disease was constructed with A beta42-treated PC12 cells. Cell morphology and MTT assay were used to evaluate the cell toxicity and histamine effects. The different histamine antagonists were applied to investigate the involvement of receptor subtypes., Result: The neurotoxicity was induced by A beta42 in a concentration-dependent manner, which was reversed by histamine at concentration of 10(-7), 10(-6) mol/L. The effect was reversed by H(2) antagonist zolantidine and H(3)antagonist clobenpropit, but not by H(1) antagonist diphenhydramine., Conclusion: Histamine reduces neurotoxicity induced by beta-amyloid(1-42), which may be mediated by H(2) and H(3)receptors.