Purpose: Antifungal resistance associated with the extensive use of antifungals and biofilm formation presents major clinical challenges. Thus, new therapeutic strategies for fungal infections are urgently required. This study aimed to evaluate the in vitro antifungal effects of the natural bioactive alkaloid berberine against Candida spp. in planktonic and biofilm conditions. Methods: Using the CLSI M27-A3 reference method for broth dilution antifungal susceptibility testing of yeasts, the MICs for five standard strains comprised of Candida albicans (ATCC 10231, ATCC 90028), Candida krusei (ATCC 6258), Candida glabrata (ATCC 90030), Candida dubliniensis (MYA 646), and six clinical isolates (CLC1-CLC6) were tested. The 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay was used to evaluate the inhibitory effects of berberine against Candida biofilms. The optical density value at 490 nm was measured and illustrated using concentrationabsorbance curves. Finally, the effects were quantified by confocal laser scanning microscopy (CLSM), and 3-dimensional reconstruction was performed. The viability inhibition rates, biofilm formation, and thickness decrease rates were tested and analyzed using independentsamples t-test. The differences among the five Candida strains were analyzed using one way ANOVA. Results: The MICs for the five standard strains described above were 80, 160, 10, 20, and 40 μg/ mL, respectively, which was similar to that of the clinical isolates, suggesting the stable, broadspectrum antifungal activity of berberine. Berberine exerted concentration-dependent inhibitory effects against Candida biofilms, which were enhanced with the maturation of Candida biofilms. Berberine decreased the viability of Candida biofilms, with inhibition rates by CLSM ranging from 19.89 ± 0.57% to 96.93 ± 1.37%. Following 3-dimensional reconstruction, the biofilms of the berberine-treated group displayed a poorly developed architecture, and the biofilm thickness decrease rates ranged from 15.49 ± 8.45% to 30.30 ± 15.48%. Conclusion: Berberine exhibited significant antifungal activity in Candida spp. The results provide a useful reference for multiple Candida infections and biofilm infections associated with antifungal resistance. Therefore, berberine might have novel therapeutic potential as an antifungal agent or a major active component of antifungal drugs.

The aberrant expression of interleukin-17 (IL-17) has been reported in primary Sjögren's syndrome (pSS). Abnormalities in IL-17 can promote the production of pro-inflammatory cytokines and aggravate autoimmune disorders. The aim of this study was to investigate alterations of IL-17 in patients with pSS and explore the correlation between IL-17 and disease severity. Eight databases were searched for original studies reporting the expression of IL-17 in patients with pSS and controls. Eligible reports were included in the pooled analysis, and subgroup evaluations were performed according to different types of controls and IL-17 measurement methods. Newcastle-Ottawa Scale criteria were used to assess the risk of bias of the included studies. In total, 45 articles are included in the meta-analysis. The expression of IL-17 is significantly increased in patients with pSS compared to controls. Furthermore, patients with pSS without immunosuppressive treatment show markedly higher IL-17 levels. In addition, patients with pSS with positive rheumatoid factors tend to express a higher level of IL-17 than patients with negative rheumatoid factors. Negative correlations between IL-17 levels and ocular parameters are also found in patients with pSS. The results are similar after adjustment by "trim and fill" methods. In conclusion, the expression of IL-17 is obviously increased in patients with pSS, especially among those without immunosuppressive treatment. In addition, IL-17 level correlates with the disease severity of pSS. These findings demonstrate the significance of IL-17 overexpression in patients with pSS and may provide insights for the development of therapeutic interventions targeting IL-17 for pSS.

No abstract

Candida spp. cause various infections involving the skin, mucosa, deep tissues, and even life-threatening candidemia. They are regarded as an important pathogen of nosocomial bloodstream infection, with a high mortality rate. As a result of prolonged exposure to azoles, the therapeutic failure associated with azoles resistance has become a serious challenge in clinical situations. Therefore, novel, alternative antifungals are required urgently. In the present study, the CLSI M-27A broth microdilution method and the 2,3-Bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) reduction assay were used to evaluate the antifungal effects of magnolol against various standard Candida strains in planktonic mode and biofilm formation, respectively. The antifungal activity of magnolol was demonstrated in planktonic C. albicans and non-albicans Candida species, especially fluconazole-resistant Candida krusei, with the minimum inhibitory concentrations ranging from 10 to 40 μg/mL. The BMIC90 (minimum concentration with 90% Candida biofilm inhibited) values of magnolol ranged from 20 to 160 μg/mL, whereas the BMIC90 values of fluconazole were more than 128 μg/mL. As an alternative and broad-spectrum antifungal agent, magnolol might be of benefit to the treatment of refractory Candida infection.