Down-regulation of miR-135b in colon adenocarcinoma induced by a TGF-β receptor I kinase inhibitor (SD-208).

OBJECTIVES Transforming growth factor-β (TGF-β) is involved in colorectal cancer (CRC). The SD-208 acts as an anti-cancer agent in different malignancies via TGF-β signaling. This work aims to show the effect of manipulation of TGF-β signaling on some miRNAs implicated in CRC. MATERIALS AND METHODS We investigated the effects of SD-208 on SW-48, a colon adenocarcinoma cell line. The cell line was treated with 0.5, 1 and 2 μM concentrations of SD-208. Then, the xenograft model of colon cancer was established by subcutaneous inoculation of SW-48 cell line into the nude mice. The animals were treated with SD-208 for three weeks. A quantitative real-time PCR was carried out for expression level analysis of selected oncogenic (miR-21, 31, 20a and 135b) and suppressor-miRNAs (let7-g, miR-133b, 145 and 200c). Data were analyzed using the 2-∆∆CT method through student's t-test via the GraphPad Prism software. RESULTS Our results revealed that SD-208 could significantly down-regulate the expression of one key onco-miRNA, miR-135b, in either SW-48 colon cells (P=0.006) or tumors orthotopically implanted in nude mice (P=0.018). Our in silico study also predicted that SD-208 could modulate the expression of potential downstream tumor suppressor targets of the miR135b. CONCLUSION Our data provide novel evidence that anticancer effects of SD-208 (and likely other TGF-β inhibitors) may be owing to their ability to regulate miRNAs expression

A new record of Scedosporium dehoogii isolated from paddy field soil in Iran: Phylogeny and antifungal susceptibility profiles

Background and Purpose: Scedosporium species are ubiquitous environmental fungi,which are considered emerging agents that trigger disease in humans and animals. Thepresent study aimed to determine Scedosporium dehoogii strain isolated from paddy field soil samples using semi-selective media and evaluate its antifungal susceptibility profile.Materials and Methods: Three paddy field soil samples were collected during aninvestigation for the isolation of Scedosporium species in Mazandaran province, Iran.Morphological and molecular analyses based on ITS-rDNA sequencing were performed. Furthermore, in vitro antifungal susceptibility testing for conventional drugs and novel imidazole (luliconazole) was performed based on Clinical and Laboratory Standards Institute M38-A3 guidelines.Results: In this study, S. dehoogii was isolated from the soil in paddy fields. Based onthe results, itraconazole and luliconazole showed the least and most antifungal activityagainst this isolate, respectively.Conclusion: Based on the findings, molecular identification was essential fordistinguishing the species of S. dehoogii. Remarkably, luliconazole showed potent activity against this strain

Caspian Sea Mycosands: The Variety and Abundance of Medically Important Fungi in Beach Sand and Water

Samples from a total of 67 stations, distributed amongst 32 cities along the Caspian Sea coastline, were collected during the summer of 2021 on sunny days. The samples were collected from each station, including both dry/wet sand and shoreline water. The grown samples were primarily analyzed for the macro/microscopic morphologic features of the fungi. Moreover, identification by PCR-RFLP was performed for yeasts, dermatophytes, and Aspergillus sp. strains. Antifungal susceptibility tests were performed for probable-isolated Aspergillus and Candida sp. A total of 268 samples were collected, from which 181 (67.54%) isolates were recovered. Yeast-like fungi and potential pathogenic black fungi were detected in 12 (6.6%) and 20 (11%) of the sand (dry/wet) samples. Potential pathogenic hyaline fungi were identified in 136 (75.1%) samples, in which Aspergillus sp. was the predominant genus and was detected in 76/136 (47.8%) samples as follows: A. section Flavi n = 44/76 (57.9%), A. section Nigri n = 19/76 (25%), A. section Nidulantes n = 9/76 (11.8%), and A. section Fumigati n = 4/76 (5.3%). The most effective azole antifungal agent was different per section: in A. section Fumigati, PSZ; in Aspergillus section Nigri, ITZ and ISZ; in A. section Flavi, EFZ; and in A. section Nidulantes, ISZ. Candida isolates were susceptible to the antifungals tested.Authors wish to thank Mazandaran University of Medical Sciences for the financial support.info:eu-repo/semantics/publishedVersio

History of treated pulmonary tuberculosis will also be an underlying symptom of opportunistic aspergillosis by Aspergillus flavus: A case report

AbstractIntroductionAspergillus species as cosmopolitan fungi with remarkable virulence factors were found to be agents of pulmonary aspergillosis in patients with impaired immunity. The formed cavity of some previously treated lung diseases, such as tuberculosis, sarcoidosis and pneumoconiosis, is usually predisposed to the development of aspergillosis.Pulmonary aspergillosis (PA) is an uncommon disease which is characterized by hemoptysis, malaise, fever, cough, weight loss and nonspecific radiographic manifestations, including an oval or round mass with a radiolucent halo or crescent of air, a focal consolidation, and cavitary lesions.Case presentationThis study presents the case of a 54-year-old woman with dyspnea alongside a history of treated pulmonary tuberculosis (PTB) by ATT 2years ago. X-ray confirmed the presence of a rounded mass in a surrounding cavity in the lung. Tracheobronchial and chest CT images of the patient showed cavities with tuberculous nodules. Clinical symptoms of the patient were fever, malaise, anorexia, weight loss, chest pain, cough and dark mucus sputum. Aspergillus sp. was detected primarily as branching hyaline hyphae in direct examination of the sputum by calcofluor-white staining. The sample was positive with culture as well. Aspergillus flavus was identified in culture and confirmed by polymerase chain reaction (PCR) and sequencing of the ITS region of rDNA and β-tubulin of fungus. The patient signed an agreement for reporting her case as a medical document in journals or in conferences.ConclusionThe importance of tuberculosis (TB) in the development of aspergillosis, even after treatment, has been highlighted by multiple studies. Microbiological and molecular evaluation are needed to detect PA quickly and accurately. The WHO reported about 8.8million new cases of TB in 2010. Therefore, it is essential to focus more on monitoring of diagnosis and treatment of PA

Use of PCR-RFLP and PCR-HWP1 for Identification of Candia Species Isolated from Cystic Fibrosis Patients

Background: Due to the predisposing conditions in patients with cystic fibrosis (CF) caused by defective mucociliary clearance facilitating colonization and invasion with Candida species has dramatically increased. Traditional methods for identifying problems are imminent and time-consuming. Therefore, molecular techniques utilizing amplification of target DNA provide quick and precise methods for the diagnosis and identification of Candida species. Therefore, the aim of the current study was to identify the most medically common isolated Candida species from the air way of CF patients by PCR-RFLP and amplification of HWP1 gene. Materials and Methods: A total of 42 CF patients presenting symptoms who referred to pediatric respiratory diseases research center were screened for the presence of Candida spp. The isolates initially were phenotypically identified and confirmed by molecular approaches based on restriction fragment length polymorphism (PCR-RFLP) for the discrimination of C. albicans of non-albicans and the amplification of HWP1 gene for the discrimination of C. albicans from C. dubliniensis and C. africana was conducted. Results: The results show that C. albicans was the most frequently isolated species (83.8%) followed by non-albicans included C. parapsilosis (7.1%), C. glabrata (3.2%), and C. tropicalis (3.2%). The restriction patterns of each Candida species were perfectly specific. Since MspI could not discriminate between the three morphological related species, C. albicans, C. dubliniensis and C. africana, we used PCR amplification of HWP1 gene, which (7.1%) species from C. albicans identified as C. dubliniensis, however C. africana strains were not found. Discussion: The present study found that C. albicans as predominant species wereisolated from the CF patients. It could be concluded that molecular diagnostic methods are reliable and would be useful for the identification of medically important Candida species in clinical samples. Therefore, considerable attention has been paid to the prevention and treatment of microbial growth, which has resulted in the improvement of patient management

First report of tinea corporis caused by Trichophyton quinckeanum in Iran and its antifungal susceptibility profile

Background and Purpose: Trichophyton quinckeanum, a known zoophilicdermatophyte responsible for favus form in rodents and camels, is occasionally reported to cause human infections.Case Report: This study aimed to report a case of tinea corporis caused by T. quinckeanum that experienced annular erythematous pruritic plaque with abundantpurulent secretions. In June 2021, a 15-year-old girl with an erythematous cup shape lesion on the right wrist bigger than 3 cm in diameter was examined for tinea corporis. Since March, 2016 her family has kept several camels at home. Direct examination of skin scraping and purulent exudates revealed branching septal hyaline hyphae and arthrospore. Morphological evaluation of the recovered isolate from the culture and sequencing of ITS1-5.8S rDNA-ITS2 region resulted in the identification of T. quinckeanum. Antifungal susceptibility testing showed that this isolate had low minimum inhibitory concentration (MIC) values for luliconazole,terbinafine, and tolnaftate, but high MICs to itraconazole, fluconazole, posaconazole, miconazole, isavuconazole, ketoconazole, clotrimazole, andgriseofulvin. However, the patient was successfully treated with oral terbinafine andtopical ketoconazole.Conclusion: It can be said that T. quinckeanum is often missed or misidentified due to its morphological similarity to T. mentagrophytes/T. interdigitale or other similar species. This dermatophyte species is first reported as the cause of tinea corporis in Iran. As expected, a few months after our study, T. quinckeanum was detected in other areas of Iran, in a few case

Evaluation of antitumor activity of a TGF-beta receptor I inhibitor (SD-208) on human colon adenocarcinoma.

BACKGROUND: Transforming growth factor-β (TGF-β) pathway is involved in primary tumor progression and in promoting metastasis in a considerable proportion of human cancers such as colorectal cancer (CRC). Therefore, blockage of TGF-β pathway signaling via an inhibitor could be a valuable tool in CRC treatment. METHODS: To evaluate the efficacy of systemic targeting of the TGF-β pathway for therapeutic effects on CRC, we investigated the effects of a TGβRI (TGF-β receptor 1) or TβRI kinase inhibitor, SD-208, on SW-48, colon adenocarcinoma cells. In this work, in vitro cell proliferation was studied by methyl thiazolyl tetrazolium (MTT) and bromo-2'-deoxyuridine (BrdU) assays. Also, the histopathological and immunohistochemical evaluations were conducted by hematoxylin and eosin, and Ki-67 and CD34 markers were stained, respectively. RESULTS: Our results showed no significant reduction in cell proliferation and vessel formation (170 ± 70 and 165 ± 70, P > 0.05) in treated SW-48 cells with SD-208 compared to controls. CONCLUSION: Our data suggested that SD-208 could not significantly reduce tumor growth and angiogenesis in human colorectal cancer model at least using SW-48 cells

Indoor environment assessment of special wards of educational hospitals for the detection of fungal contamination sources: A multi-center study (2019-2021)

Background and Purpose: The hospital environment was reported as a real habitat for different microorganisms, especially mold fungi. On the other hand, these opportunistic fungi were considered hospital-acquired mold infections in patients with weak immune status. Therefore, this multi-center study aimed to evaluate 23 hospitals in 18 provinces of Iran for fungal contamination sources.Materials and Methods: In total, 43 opened Petri plates and 213 surface samples were collected throughout different wards of 23 hospitals. All collected samples were inoculated into Sabouraud Dextrose Agar containing Chloramphenicol (SC), and the plates were then incubated at 27-30ºC for 7-14 days.Results: A total of 210 fungal colonies from equipment (162, 77.1%) and air (48,22.9%) were identified. The most predominant isolated genus was Aspergillus (47.5%),followed by Rhizopus (14.2%), Mucor (11.7%), and Cladosporium (9.2%). Aspergillus(39.5%), Cladosporium (16.6%), as well as Penicillium and Sterile hyphae (10.4% each), were the most isolates from the air samples. Moreover, intensive care units (38.5%) and operating rooms (21.9%) had the highest number of isolated fungal colonies. Out of 256 collected samples from equipment and air, 163 (63.7%) were positive for fungal growth.The rate of fungal contamination in instrument and air samples was 128/213 (60.1%) and 35/43 (81.2%), respectively. Among the isolated species of Aspergillus, A. flavus complex (38/96, 39.6%), A. niger complex (31/96, 32.3%), and A. fumigatus complex (15/96, 15.6%) were the commonest species.Conclusion: According to our findings, in addition to air, equipment and instrument should be considered among the significant sources of fungal contamination in the indoor environment of hospitals. Airborne fungi, Hospital, Indoor air, Equipment, Sources of fungal contamination in the indoor environment of hospitals