Background The global spread of terbinafine‐resistant Trichophyton mentagrophytes with point mutations in the squalene epoxidase (SQLE) gene is a big concern. Aim The present study presents a series of unusual familial cases of generalized dermatophytosis caused by multidrug‐resistant T. mentagrophytes genotype VIII. Methods Initially, the skin samples of each patient were taken and then subjected to direct microscopy and culture in Mycosel Agar. The molecular identification of Trichophyton species (spp.) was performed for all family members. In addition, the immunologic tests were requested, and an antifungal susceptibility test was carried out using the broth microdilution protocol based on the Clinical and Laboratory Standards Institute M38, third edition. The SQLE gene for a terbinafine‐resistant T. mentagrophytes genotype VIII was sequenced and confirmed its nucleotide sequence to KU242352 as a susceptible strain. Results Based on the results of mycological examination and ITS rDNA sequencing, the etiologic agent was identified as T. mentagrophytes as a zoophilic dermatophyte. This species showed multiple drug resistance in vitro against terbinafine (minimum inhibitory concentration (MICs ≥8 µg/ml), itraconazole (MIC ≥4), and fluconazole (MIC ≥16). The SQLE gene of the isolate was subjected to sequencing for mutation, which showed a point mutation as TTC/TTA in the gene leading to Phe397Leu amino acid substitution in the enzyme. Only one of the family members responded to itraconazole and was cured after the long‐term use of itraconazole. Other family members were treated with oral voriconazole with no recurrence. Conclusion The transmission of this resistant T. mentagrophytes to other countries due to globalization is a serious issue to be considered.
Long noncoding RNAs (lncRNAs) have been demonstrated to regulate a variety of cell processes and involve in the development and progression of colorectal cancer (CRC).Recently, the circulating lncRNAs have emerged as minimally invasive biomarkers for cancer diagnosis and prognosis. We aimed to examine the plasma expression level of long noncoding RNAs lnc-ATB, lnc-CCAT1, and lnc-OCC-1 in CRC patients and evaluate the clinical values. A total of 74 pretreatment CRC and 74 healthy blood biopsies were subjected to differentially evaluate the expression levels of three lncRNAs (OCC-1, CCAT1, and ATB). Briefly, after plasma separation and total RNA extraction, RNAs were reversely transcribed to complementary DNA followed by amplification using a quantitative real-time polymerase chain reaction technique for lncRNA expression analysis. The results showed that the expression levels of lnc-ATB (p < 0.001) and CCAT1 (p = 0.024), but not OCC-1 (p = 0.24), were significantly upregulated in the CRC compared with the healthy group. The calculated AUC of ROC was 0.78 (95% confidence interval [CI]: 0.811-0.94) for lnc-ATB and 0.64 (95% CI: 0.811-0.94) for CCAT1, which were indicative of a high discriminatory power (p < 0.001). The highest accuracy for lncRNA-ATB was obtained at a cutoff point of 2.5, which corresponded to sensitivity and specificity of 82% and 75%, respectively.Our results suggested a significant accuracy of lncRNA-ATB and lncRNA-CCAT1 in distinguishing CRC patients from healthy individuals. K E Y W O R D SATB, CCAT1, colorectal cancer, long noncoding RNA, OCC-1, plasma
The Candida (C.) albicans complex includes C. albicans, C. dubliniensis, C. stellatoidea, and C. africana, with the last mentioned as an important emerging agent of vulvovaginal candidiasis (VVC). The aim of the study was to identify C. africana and C. dubliniensis and assess their drug susceptibility in vaginitis. One-hundred Candida isolates of the C. albicans complex from women diagnosed with vaginitis and from vaginal samples in the culture collection of a medical mycology laboratory were examined. Species of the C. albicans complex were identified with conventional and molecular methods using polymerase chain reaction (PCR) for amplification and sequencing of the internal transcribed spacer (ITS) region, PCR for partial amplification of hyphal wall protein 1 (HWP1) gene and duplex PCR. The effects of antifungal drugs were evaluated according to standard broth microdilution protocols.Ninety-seven C. albicans (97%) and three C. africana (3%) isolates were identified. Results of susceptibility testing revealed one isolate of C. africana to be resistant to both clotrimazole and fluconazole, and one showed reduced susceptibility to itraconazole.Identification of Candida species especially C. africana in vaginitis is crucial, there are varying levels of resistance to antifungal drugs.
L-Asparaginases hydrolyzing plasma L-asparagine and L-glutamine has attracted tremendous attention in recent years owing to remarkable anticancer properties. This enzyme is efficiently used for acute lymphoblastic leukemia (ALL) and lymphosarcoma and emerged against ALL in children, neoplasia, and some other malignancies. Cancer cells reduce the expression of L-asparaginase leading to their elimination. The L-asparaginase anticancerous application approach has made incredible breakthrough in the field of modern oncology through depletion of plasma L-asparagine to inhibit the cancer cells growth; particularly among children. High level of L-asparaginase enzyme production by Escherichia coli, Erwinia species, Streptomyces, and Bacillus subtilis species is highly desirable as bacterial alternative enzyme sources for anticancer therapy.Thermal or harsh conditions stability of those from the two latter bacterial species is considerable. Some enzymes from marine bacteria have conferred stability in adverse conditions being more advantageous in cancer therapy. Several side effects exerted by L-asparaginases such as hypersensitivity should be hindered or decreased through alternative therapies or use of immune-suppressor drugs. The L-asparaginase from Erwinia species has displayed remarkable traits in children with this regard. Noticeably, Erwinia chrysanthemi L-asparaginase exhibited negligible glutaminase activity representing a promising efficiency mitigating related side effects. Application of software such as RSM would optimize conditions for higher levels of enzyme production. Additionally, genetic recombination of the encoding gene would indisputably help improving enzyme traits. Furthermore, the possibility of anticancer combination therapy using two or more L-asparaginases from various sources is plausible in future studies to achieve better therapeutic outcomes with lower side effects. K E Y W O R D S bacterial L-asparaginase, cancer therapy, optimized production
Background:Voriconazole Resistance (VRC-R) in Aspergillus flavus isolates impacts the management of aspergillosis, since azoles are the first choice for prophylaxis and therapy. However, to the best of our knowledge, the mechanisms underlying voriconazole resistance are poorly understood.Objectives:The present study was designed to evaluate mRNA expression levels of cyp51A and mdr1 genes in voriconazole resistant A. flavus by a Real-Time Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) technique.Materials and Methods:Five A. flavus isolates with resistance to VRC were examined by a RT-PCR approach.Results:Four out of five isolates revealed cyp51A and mdr1 mRNA overexpression. Interestingly, the isolate, which was negative for cyp51A and mdr1 mRNA expression showed a high voriconazole Minimum Inhibitory Concentration (MIC). Furthermore, a computational-based analysis predicted that voriconazole resistance could be mediated through cooperation with a network protein interaction.Conclusions:Our experimental and in silico findings may provide new insight in the complex molecular pathways of drug resistance and also could assist design an efficient therapeutic strategy for aspergillosis treatment.
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