In vitro antifungal activity of aqueous-ethanolic extract of Allium jesdianum against fluconazole-susceptible and -resistant human vaginal Candida glabrata isolates

Introduction: About 50 of women are diagnosed with an episode of vulvovaginal candidiasis (VVC) during first 25 years of their lives. Candida glabrata is considered the second most prevalent non-C. albicans species associated with VVC. In this study, we examined the antifungal effect of a medicinal plant, Allium jesdianum, as a natural therapeutic agent against fluconazole-susceptible and -resistant human vaginal C. glabrata isolates, collected from two groups of volunteers; healthy women and women with VVC.Methods: An aqueous-ethanolic extract of A. jesdianum was prepared by maceration method. Vaginal specimens were collected from 28 women diagnosed with VVC and eight healthy subjects. The specimens were cultured using fungal-specific media in optimum conditions. The antifungal susceptibility of clinical isolates of C. glabrata to the plant extract and fluconazole was evaluated according to the standard protocols.Results: Candida glabrata was found to be the major cause of vaginal infection among 15.2 of women with VVC. We could identify the Candida spp. yeasts that colonized the vagina of 35 of healthy women while 19 of the isolated yeasts strains were detected as C. glabrata. Moreover, 7.1 of isolates obtained from VVC-patients were fluconazole resistant. The results showed the antifungal effect of A. jesdianum against all fluconazole resistant and susceptible C. glabrata vaginal isolates. The MIC90 of aqueous-ethanol (A-EtOH) extract of A. jesdianum against C. glabrata isolates from both VVC-patients and healthy women was 3 mg/mL.Conclusion: Our results showed the promising antifungal efficacy of aqueous-ethanolic extract of A. jesdianum. A. jesdianum extract might be used as an alternative choice to treat the VVC infections caused by fluconazole resistant Candida spp

Fungicidal effect of Origanum vulgare essential oil against Candida glabrata and its cytotoxicity against macrophages

Introduction: Candida glabrata is a yeast fungus regularly isolated from patients with impaired immunity who receive a routine antifungal therapy. Drug-resistant strains of C. glabrata have been emerged in recent years. The aim of this study was to examine the therapeutic efficacy Origanum vulgare essential oil (OVEO) against drug-resistant strains of C. glabrata and its cytotoxic effect on macrophages.Methods: Specimens were collected from mucosal surfaces of the oral cavity of medically approved oropharyngeal candidiasis (OPC) in HIV-positive patients and volunteered healthy individuals using sterile swabs or mouthwashes. In vitro antifungal susceptibility testing was done using microdilution and disc diffusion methods. Chemical composition of OVEO was determined using gas chromatography mass spectrometry. The cytotoxic effect of essential oil on macrophages was examined using tetrazolium dye (MTT).Results: Minimum inhibitory concentration (MIC) range of OVEO in healthy individuals and OPC patients was 150-200 and 150-250 &mu;g/mL, respectively. OVEO efficiently inhibited growth of resistant isolates. In isolates obtained from HIV patients, both MIC50 and MIC90 of OVEO were 200 &mu;g/mL while in healthy individuals were 150 and 200 &mu;g/mL, respectively. Moreover, OVEO induced significant reduction in proliferation of murine RAW264.7 and peritoneal macrophages in concentrations higher than 100 and 300 &mu;g/mL, respectively. Main constituents of OVEO were thymol (27.3), &gamma;-terpinene (20.7) and carvacrol (16.1).Conclusion: OVEO could be used as a fungicidal agent against fungal infections caused by azole-resistant C. glabrata. A combination therapy along with standard antifungals is suggested to avoid its cytotoxic effects.</p

Mesenchymal Stromal/Stem Cells: A New Era in the Cell-Based Targeted Gene Therapy of Cancer

In recent years, in light of the promising potentials of mesenchymal stromal/stem cells (MSCs) for carrying therapeutic anticancer genes, a complete revisitation on old chemotherapy-based paradigms has been established. This review attempted to bring forward and introduce the novel therapeutic opportunities of using genetically engineered MSCs. The simplicities and advantages of MSCs for medical applications make them a unique and promising option in the case of cancer therapy. Some of the superiorities of using MSCs as therapeutic gene micro-carriers are the easy cell-extraction procedures and their abundant proliferation capacity in vitro without losing their main biological properties. Targeted therapy by using MSCs as the delivery vehicles of therapeutic genes is a new approach in the treatment of various types of cancers. Some of the distinct properties of MSCs, such as tumor-tropism, non-immunogenicity, stimulatory effect on the anti-inflammatory molecules, inhibitory effect on inflammatory responses, non-toxicity against the normal tissues, and easy processes for the clinical use, have formed the basis of attention to MSCs. They can be easily used for the treatment of damaged or injured tissues, regenerative medicine, and immune disorders. This review focused on the drugability of MSCs and their potential for the delivery of candidate anticancer genes. It also briefly reviewed the vectors and methods used for MSC-mediated gene therapy of malignancies. Also, the challenges, limitations, and considerations in using MSCs for gene therapy of cancer and the new methods developed for resolution of these problems are reviewed

Zymosan attenuates melanoma growth progression, increases splenocyte proliferation and induces TLR-2/4 and TNF-α expression in mice

Background: Melanoma is one of the most common types of skin malignancies. Since current therapies are suboptimal, considerable interest has focused on novel natural-based treatments. Toll-like receptors (TLRs) play an important role in evoking innate immunity against cancer cells. Zymosan, a known TLR-2 agonist, is a glucan derived from yeast cell walls with promising immunomodulatory effects. The aim of this study was to evaluate whether Saccharomyces cerevisiae-derived zymosan-modulated skin melanoma progression by regulation of TLR-2 and TLR-4 expression in peritoneal macrophages and serum TNF-α level. Methods: Male C57BL/6 mice were divided into four groups: i) zymosan-treated (Z), ii) Melanoma-bearing mice (M), iii) Melanoma-bearing mice treated with zymosan (ZM) and iv) a healthy control group (negative control). 15 days after melanoma induction, mice were injected i.p. with zymosan (10 μg) daily for 4 consecutive days. Mice were CO2-euthanized and serum TNF-α level, TLR-2 and TLR-4 expression in peritoneal macrophages and tumor growth measured. Splenocytes were treated ex-vivo with zymosan to determine viability and proliferation. Results: Tumor weight significantly decreased following therapeutic dosing with zymosan (P < 0.05). This was associated with zymosan-induced upregulation of TLR-2, TLR-4 and TNF-α mRNA in peritoneal macrophages and enhanced serum TNF-α levels (P < 0.05). Splenocyte number and viability were increased in a concentration-dependent manner by zymosan. Conclusions: Our study suggests that zymosan-induced upregulation of TLR-2, TLR-4 and TNF-α gene expression and of TNF-α release; together with increased level of lymphocyte proliferation may play a role in the inhibition of melanoma progression