The Protective Effects of Syringic Acid on Bisphenol A-Induced Neurotoxicity Possibly Through AMPK/PGC-1α/Fndc5 and CREB/BDNF Signaling Pathways.

Bisphenol A (BPA), an endocrine disruptor, is commonly used to produce epoxy resins and polycarbonate plastics. Continuous exposure to BPA may contribute to the development of diseases in humans and seriously affect their health. Previous research suggests a significant relationship between the increased incidence of neurological diseases and the level of BPA in the living environment. Syringic acid (SA), a natural derivative of gallic acid, has recently considered much attention due to neuromodulator activity and its anti-oxidant, anti-apoptotic, and anti-inflammatory effects. Therefore, in this study, we aimed to investigate the effects of SA on oxidative stress, apoptosis, memory and locomotor disorders, and mitochondrial function, and to identify the mechanisms related to Alzheimer's disease (AD) in the brain of rats receiving high doses of BPA. For this purpose, male Wistar rats received BPA (50, 100, and 200 mg/kg) and SA (50 mg/kg) for 21 days. The results showed that BPA exposure significantly altered the rats' neurobehavioral responses. Additionally, BPA, by increasing the level of ROS, and MDA level, increased the level of oxidative stress while reducing the level of antioxidant enzymes, such as SOD, CAT, GPx, and mitochondrial GSH. The administration of BPA at 200 mg/kg significantly decreased the expression of ERRα, TFAM, irisin, PGC-1α, Bcl-2, and FNDC5, while it increased the expression of TrkB, cytochrome C, caspase 3, and Bax. Moreover, the Western blotting results showed that BPA increased the levels of P-AMPK, GSK3b, p-tau, and Aß, while it decreased the levels of PKA, P-PKA, Akt, BDNF, CREB, P-CREB, and PI3K. Meanwhile, SA at 50 mg/kg reversed the behavioral, biochemical, and molecular changes induced by high doses of BPA. Overall, BPA could lead to the development of AD by affecting the mitochondria-dependent apoptosis pathway, as well as AMPK/PGC-1α/FNDC5 and CREB/BDNF/TrkB signaling pathways, and finally, by increasing the expression of tau and Aß proteins. In conclusion, SA, as an antioxidant, significantly reduced the toxicity of BPA.

In vitro antifungal potency of the moronecidin-like peptide against Candida albicans, Candida glabrata, and Candida tropicalis.

Background and Objectives: The aim of this study was to investigate the in vitro antifungal potency of the moronecidin-like peptide against Candida albicans, Candida glabrata, and Candida tropicalis. Materials and Methods: To evaluate the antifungal effect of moronecidin-like peptide, the protocol presented in CLSI M27-A3 and CLSI M27-S4 was used and the minimum inhibitory concentration was determined. Results: The minimum inhibitory effect of moronecidin-like peptide composition was 8 µg/ml for Candida tropicalis and Candida albicans and 32 µg/ml for Candida glabrata. The MIC of nystatin was determined to be 1.25 µg/ml for Candida glabrata and Candida albicans and 0.625 µg/ml for Candida tropicalis strains. The MFC composition of the moronecidin-like peptide was determined for Candida tropicalis and Candida albicans strains 8 µg/ml and for Candida glabrata strain 64 µg/ml. The results of cytotoxicity and hemolysis of the moronecidin peptide test on macrophage showed that moronecidin peptide has no cytotoxicity and toxicity properties. Conclusion: According to the results of the present study, the moronecidin-like peptide could be a new strategy in the treatment of infections caused by Candida strains. The discovery of the exact mechanism of which requires extensive clinical studies in this field.

Antifungal Resistance of Clinical Candida albicans Isolates in Iran: A Systematic Review and Meta-Analysis.

Background: The present systematic review aimed to investigate the drug susceptibility patterns of Iranian clinical Candida albicans isolates to antifungal drugs (azoles, polyenes, and echinocandins). Methods: Six electronic databases including "PubMed," "Scopus," "Web of Science," "IranDoc", "SID", and "Magiran" were searched from May 2000 to June 2021. The susceptibility of 6322 C. albicans strains from 19967 patients against 14 antifungal drugs was evaluated according to CLSI method. Results: The pooled prevalence of antifungal resistance ranged from 0% to 26%. The lowest resistance levels among azoles were observed in luliconazole with a frequency of 0% and voriconazole of 3.94%. Conclusion: Due to the emergence of multi-drug resistant C. albicans, rational drug prescription based on the anti-fungal stewardship strategy and therapeutic drug monitoring is warranted.

Barriers and facilitators of adherence to treatment among women with vulvovaginal candidiasis: a qualitative study.

BACKGROUND: Non-adherence of patients with vulvovaginal candidiasis (VVC) to treatment recommendations leads to treatment failure and recurrence of infection. Therefore, this qualitative study was conducted to identify barriers and facilitators of observance of treatment among women afflicted with vulvovaginal candidiasis. METHODS: This qualitative study was conducted through 26 in-depth unstructured interviews with 24 patients and 2 gynecologists using purposeful sampling with maximum variation in Ahvaz, southwest Iran. Interviews were conducted in person at health centers and the gynecologist's offices. MAXQDA 10 software and conventional content analysis were used for data analysis. RESULTS: The findings showed barriers and facilitator factors of adherence to treatment in women with VVC. Some of these factors lead to an increase in adherence to treatment, and others play the role of hindering factors. These factors were classified into two main categories: patients' beliefs and patients' fears and concerns. CONCLUSION: The results of this study showed that many of the behaviors of patients from the acceptance of the diagnosis process to treatment are rooted in the patient's beliefs and fears. Therefore, it seems necessary to design and carry out interventions based on the findings of this study, which can be used in the development of appropriate solutions, treatment guidelines, and adopting a policy for treatment adherence.

Expression Patterns of ABC Transporter Genes in Fluconazole-Resistant Candida glabrata.

Clinical management of fungal diseases is compromised by the emergence of antifungal drug resistance in fungi, which leads to elimination of available drug classes as treatment options. An understanding of antifungal resistance at molecular level is, therefore, essential for the development of strategies to combat the resistance. This study presents the assessment of molecular mechanisms associated with fluconazole resistance in clinical Candida glabrata isolates originated from Iran. Taking seven distinct fluconazole-resistant C. glabrata isolates, real-time PCRs were performed to evaluate the alternations in the regulation of the genes involved in drug efflux including CgCDR1, CgCDR2, CgSNQ2, and CgERG11. Gain-of-function (GOF) mutations in CgPDR1 alleles were determined by DNA sequencing. Cross-resistance to fluconazole, itraconazole, and voriconazole was observed in 2.5 % of the isolates. In the present study, six amino acid substitutions were identified in CgPdr1, among which W297R, T588A, and F575L were previously reported, whereas D243N, H576Y, and P915R are novel. CgCDR1 overexpression was observed in 57.1 % of resistant isolates. However, CgCDR2 was not co-expressed with CgCDR1. CgSNQ2 was upregulated in 71.4 % of the cases. CgERG11 overexpression does not seem to be associated with azole resistance, except for isolates that exhibited azole cross-resistance. The pattern of efflux pump gene upregulation was associated with GOF mutations observed in CgPDR1. These results showed that drug efflux mediated by adenosine-5-triphosphate (ATP)-binding cassette transporters, especially CgSNQ2 and CgCDR1, is the predominant mechanism of fluconazole resistance in Iranian isolates of C. glabrata. Since some novel GOF mutations were found here, this study also calls for research aimed at investigating other new GOF mutations to reveal the comprehensive understanding about efflux-mediated resistance to azole antifungal agents.

In Vitro Activities of Six Antifungal Drugs Against Candida glabrata Isolates: An Emerging Pathogen.

BACKGROUND: Candida glabrata is a pathogenic yeast with several unique biological features and associated with an increased incidence rate of candidiasis. It exhibits a great degree of variation in its pathogenicity and antifungal susceptibility. OBJECTIVES: The aim of the present study was to evaluate the in vitro antifungal susceptibilities of the following six antifungal drugs against clinical C. glabrata strains: amphotericin B (AmB), ketoconazole (KTZ), fluconazole (FCZ), itraconazole (ITZ), voriconazole (VCZ), and caspofungin (CASP). MATERIALS AND METHODS: Forty clinical C. glabrata strains were investigated using DNA sequencing. The in vitro antifungal susceptibility was determined as described in clinical laboratory standard institute (CLSI) documents (M27-A3 and M27-S4). RESULTS: The sequence analysis of the isolate confirmed as C. glabrata and deposited on NCBI GenBank under the accession number no. KT763084-KT763123. The geometric mean MICs against all the tested strains were as follows, in increasing order: CASP (0.17 g/mL), VCZ (0.67 g/mL), AmB (1.1 g/mL), ITZ (1.82 g/mL), KTZ (1.85 g/mL), and FCZ (6.7 g/mL). The resistance rates of the isolates to CASP, FCZ, ITZ, VZ, KTZ, and AmB were 5%, 10%, 72.5%, 37.5%, 47.5%, and 27.5%, respectively. CONCLUSIONS: These findings confirm that CASP, compared to the other antifungals, is the potent agent for treating candidiasis caused by C. glabrata. However, the clinical efficacy of these novel antifungals remains to be determined.

Co-infection of invasive pulmonary aspergillosis and cutaneous Fusarium infection in a patient with pyoderma gangrenosum.

We report an unusual case of co-infection of invasive pulmonary aspergillosis (IPA) and fusarial skin infection in a patient with classic pyoderma gangrenosum with unknown causes, which were previously controlled with oral prednisolone, cyclosporine. The diagnosis was made on direct microscopy and culture of endobronchial washing, bronchoalveolar lavage and skin lesion biopsy. The treatment failed, and the patient expired 12 days following hospitalization. This report highlights the rarity of coexistence of IPA and a chronic fusarial skin infection and thereby reinforcing the physician's attention toward the possibility of invasive fungal infection in the immunosuppressed patients.

In vitro antifungal activities of Allium cepa, Allium sativum and ketoconazole against some pathogenic yeasts and dermatophytes.

By using an agar dilution assay, the antifungal activity of aqueous extracts prepared from Allium cepa (onion; AOE) and Allium sativum (garlic; AGE) were evaluated against Malassezia furfur (25 strains), Candida albicans (18 strains), other Candida sp. (12 strains) as well as 35 strains of various dermatophyte species and compared with the activity of a known antifungal drug, ketoconazole (KTZ). All the AOE, AGE and KTZ were found to be able to inhibit growth of all fungi tested in a dose-dependent manner with maximum of 100% at defined concentrations. The results indicate that onion and garlic might be promising in treatment of fungal-associated diseases from important pathogenic genera Candida, Malassezia and the dermatophytes.