Antileishmanial effects and drugability characteristics of a heterocyclic copper complex: An in silico, in vitro and molecular study.

Leishmaniasis caused by the protozoan Leishmania presents a severe illness, principally in tropical and subtropical areas. Antileishmanial metal complexes, like Glucantime®ï¸ with proven activity, are routinely studied to probe their potency. We investigated the effects of a Cu (II) homoleptic complex coordinated by two dimethyl-bipyridine ligands against Leishmania major stages in silico and in vitro. The affinity of this heterocyclic Cu (II) complex (CuDMBP) towards a parasitic metacaspase was studied by molecular docking. Key pharmacokinetic and pharmacodynamic properties of the complex were predicted using three web-based tools. CuDMBP was tested for in vitro antileishmanial activities using MTT assay, model murine macrophages, flow cytometry, and quantitative real-time polymerase chain reaction (qPCR). Molecular docking confirmed the tendency between the target macromolecule and the complex. ADMET evaluations highlighted CuDMBP's key pharmacological features, including P-glycoprotein-associated GI absorption and lack of trans-BBB permeability. MTT showed significant inhibitory effects against promastigotes. CuDMBP significantly increased the level of cellular IL-12 expression (p < 0.05), while the upregulation observed in the expression of iNOS was considered not significant (p > 0.05). It decreased the expression of IL-10 significantly (p < 0.05). Findings demonstrated that CuDMBP deserves to be introduced as a leishmanicidal candidate provided further studies are carried out.

Anti-biofilm properties of eucalyptol in combination with antifungals against Candida albicans isolates in patients with hematological malignancy.

Oral candidiasis is a fungal infection caused mainly by Candida albicans and it is a major problem among hematologic malignancy patients. Biofilm formation is an attributable factor to both virulence and drug resistance of Candida species. The aim of the study was to evaluate the biofilm-producing ability of oral C. albicans isolates and to evaluate the inhibitory activity of eucalyptol on Candida biofilm, alone and in combination with antifungal agents. Samples were collected from the oral cavity of 106 patients with hematologic malignancy. The isolated yeasts were identified by PCR-sequencing. Then C. albicans isolates were analyzed for their biofilm-producing ability by crystal violet staining and MTT assay. The minimum biofilm inhibition concentrations (MBIC) of eucalyptol, amphotericin B, itraconazole, and nystatin and the in vitro interaction of eucalyptol with these drugs were tested according to CLSI-M-27-A3 protocol and checkerboard methods, respectively. From 106 patients, 50 (47.2%) were confirmed for oral candidiasis [mean ± SD age 39 ± 14 years; female 31 (62%) and male 19 (38%)]. C. albicans was isolated from 40 of 50 (80%) patients. From 40 C. albicans isolates, 24 (60%) and 16 (40%) were moderate and weak biofilm producer, respectively. The geometric mean MBIC of amphotericin B, itraconazole, nystatin and eucalyptol were 3.93 µg/mL, 12.55 µg/mL, 0.75 µg/mL and 798 µg/mL, respectively. Eucalyptol interacted synergistically with amphotericin B, itraconazole and nystatin against 12.5, 10, and 22.5% of isolates, respectively. Eucalyptol demonstrated promising activity against biofilm of C. albicans when tested alone or combined with antifungal drugs.

Clinical impact of Candida respiratory tract colonization and acute lung infections in critically ill patients with COVID-19 pneumonia.

Coronavirus disease 2019 (COVID-19), which is attributable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been causing a worldwide health issue. Airways colonization by Candida spp. is prevalent among patients on automatic ventilation in intensive care units (ICUs). This research aimed to ascertain the risk factors and roles of Candida spp. respiratory tract colonization, and Candida lung infection during the progression of COVID-19 pneumonia in critically ill patients. In total, Candida spp. were recovered in 69 from 100 immunosuppressed patients with COVID-19. Bronchoscopy was used to collect the Bronchoalveolar lavage (BAL) specimens. For the identification of Candida spp. PCR sequencing was done using the ITS1 and ITS4 primers. The amplification of the HWP1 gene was conducted to identify the Candida albicans complex. The antifungal activities of fluconazole, itraconazole, voriconazole, amphotericin B and caspofungin against Candida spp. were evaluated using the Clinical and Laboratory Standards Institute M60. In 63.77% of the patients, Candida respiratory colonization at D0 and D14 had no impact on the severity of COVID-19. In comparison to C. albicans strains, Candida respiratory disorder with C. glabrata had influenced the severity of COVID-19 for critically ill patients following adjustment for the risk factors of COVID-19 (P < 0.05). Amphotericin B and caspofungin showed superior activity against all Candida spp. All antifungal agents showed 100% sensitivity against the two C. africana strains. Our observation on patients who used automatic ventilation, respiratory colonization by Candida spp. was not seen to influence the infection or death caused by COVID-19. Amphotericin B and caspofungin showed superior activity against all Candida spp. and were recommended for the treatment regime of pulmonary candidiasis associated with COVID-19 infection. Although "Candida pneumonia" is rarely being reported in critically ill patients, Candida airway colonization mainly by Candida albicans is common especially among patients with diabetes, malignancies, and kidney disorders.

Allergic fungal rhinosinusitis caused by Neoscytalidium dimidiatum: A case report: Allergic fungal rhinosinusitis due to Neoscytalidium dimidiatum.

Neoscytalidium dimidiatum is a rare dematiaceous fungus that was first described in 1916 as Dothiorella mangiferae. From the standpoint of epidemiology and therapy, early detection of fungal rhinosinusitis (FRS), the causative agents, and their associated risk factors can improve the therapeutic outcome and decrease the mortality rates among patients. In this study, we report a 34-year-old Iranian female patient with allergic bronchopulmonary aspergillosis (ABPA), who presented to our facility with an 8-year history of chronic fungal sinusitis, drug-resistant asthma, pneumonia, bronchitis, post-nasal discharge, nasal obstruction, nasal polyposis, and anemia. The patient was subjected to diagnostic nasal endoscopy and computed tomography (CT) scan of paranasal sinuses, as well as routine, complementary mycological, and molecular methods, which confirmed the diagnosis of allergic fungal rhinosinusitis in patients with ABPA. Neoscytalidium dimidiatum was isolated from the sinus of the patient. Results of in vitro susceptibility tests indicated that the case isolate was susceptible to amphotericin B and itraconazole at concentrations which are commonly achieved in patients receiving recommended dosages for invasive mycoses (0.25 to 0.75 mg/kg of body weight daily for amphotericin B and 100 to 400 mg daily for itraconazole) and resistant in vitro to caspofungin, voriconazole, and posaconazole. The patient was successfully treated with amphotericin B / itraconazole + postoperative oral corticosteroids (OCS). Neoscytalidium dimidiatum infection should be considered as a possible additional factor in the etiology of AFRS, especially in immunocompromised patients.

Human Toxocariasis in individuals with blood disorders and cancer patients: the first seroepidemiological study in Iran.

Toxocara is one of the most prevalent nematodes in Iran, which infect humans as an intermediate host. Infection complications result from the larva migration. Human toxocariasis prevalence was various in Iran according to the area of study and population. This study was designed to evaluate the seropositivity of Toxocara IgG in patients with blood disorders and cancer patients in southwest Iran. Moreover, the study of the associated risk factors for this infection. A total of 1122 serum samples, from February 8, 2019 to August 21, 2019, including 600 healthy individuals and 522 individuals with cancer and blood disorders patients were collected. Serum samples were collected for detection of Toxocara IgG by using ELISA (Enzyme-Linked Immunosorbent Assay) kit. Sociodemographic data of all participants were collected and examined to determine their association with the infection. Out of 101 individuals with white blood cell disorders (5.94%), red blood cell disorders (7.48%) and cancer patients (11.06%) were seropositive for Toxocara IgG antibodies. The infection rate among all study population revealed that (10.76%) were positive for Toxocara IgG. This study showed the fundamental role of contact with pets and infection in groups with blood cell disorders (P-value ≤ 0.05%); while in cancer patients the association wasn't significant. Other factors such as age, location of residence, and sex showed that the association with this infection wasn't significant.

First report of chronic invasive fungal rhinosinusitis in a patient with ovarian cancer caused by Didymella pedeiae and successful treatment with voriconazole: A case report.

BACKGROUND AND PURPOSE: Didymella pedeiae is a dematiaceous fungus that belongs to the Coelomycetes class. While species within this class are known to cause human infection,  D. pedeiae had previously only been known as phytopathogens and had never been isolated from a human sample. CASE REPORT: A 51-year-old Iranian female patient with ovarian cancer was admitted with unilateral lesions in paranasal sinuses and a five-month history of nasal obstruction, headache, postnasal drainage, swelling on the left side of the face, and orbital pain. Paranasal sinus computerized tomography scan revealed a soft tissue mass that filled the left nasal cavity, ethmoid, sphenoid, and frontal sinuses with more involvement in the maxillary and ethmoid sinuses. Antifungal treatment was simultaneously initiated with itraconazole+prednisolone 15 mg/day, and levofloxacin. Due to poor clinical response, IV voriconazole and amphotericin B were added to the treatment as well. The patient recovered completely after 10 weeks of therapy. CONCLUSION: Here, we report the first case of human D. pedeiae infection in a patient with ovarian cancer.

Acute invasive fungal rhinosinusitis: Molecular identification and update in management of frozen section biopsy.

The clinical diagnosis of Acute Invasive Fungal Rhinosinusitis (AIFRS) is technically difficult because it presents with non-exclusive and nonspecific clinical symptoms. Laboratory confirmation (usually via histopathologic techniques such as formalin-fixed paraffin-embedded (FFPE)) is necessary but it is time-consuming, despite the urgent need for timely diagnosis of AIFRS for effective management. This study aimed to investigate the sensitivity and specificity of the GMS frozen-section biopsy in the diagnosis of AIFRS and compare the same with that of different tissue staining methods to provide valid decision-grounds that may guide clinicians in prompt diagnosis of acute fungal invasive rhinosinusitis. A cross-sectional study was conducted in the Medical Mycology Laboratory, Faculty of Medicine, Iran University of Medical Sciences between 2018 and 2020 on 200 patients with suspected AIFRS referred to Baqiyatallah and Imam Khomeini Hospital, Tehran. All patients were subjected to diagnostic nasal endoscopy and computed tomography (CT) scan of paranasal sinuses. Magnetic resonance imaging (MRI) was done in cases of suspected intracranial extension. After screening by routine mycological examination, the diagnosis was confirmed using complementary molecular methods. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the frozen-section biopsy were also compared with FFPE. Of the 200 suspect patients, 47 cases (23.5%) met the criteria for AIFRS. Species of the genus Aspergillus were the predominant 27 (57.4%) followed by Mucorales species 10 (21.3%), and Fusarium spp 3 (6.4%). Also, 3 cases (6.4%) of co-infection due to Aspergillus/Rhizopus were reported. The accuracy, sensitivity, specificity, PPV, and NPV of frozen section assessments were 99.5%, 97.9%, 100%, 100% and 99.3%, respectively. For GMS frozen-section alone, sensitivity, specificity, NPV, and PPV was 100%. Overall, the calculated accuracy of FFPE was 98.5%, sensitivity was 94%, specificity was 100%, PPV was 100%, and NPV was 98.1%. Examination of the frozen-section biopsy is a highly predictive tool for a rapid and effective diagnosis of patients with suspected AIFRS. We observed that GMS frozen-section is a fast and reliable exam to confirm the diagnosis of fungal invasion, with good accuracy, sensitivity, and specificity compared to the gold-standard FFPE biopsy.

Parasite-derived microRNAs as a diagnostic biomarker: potential roles, characteristics, and limitations.

MicroRNAs (miRNAs), a subclass of small regulatory RNAs that present from ancient unicellular protozoans to parasitic helminths and parasitic arthropods. MiRNAs' mode of action has attracted wide attention as a result of their unique functional importance. MiRNAs play a role in diverse physiological and pathological processes ranging from organ development, immune function to apoptosis and cancer at the post-transcription gene expression. Thus, miRNAs are known to be targets for clinical treatment and therapy. The discovery of the high stability of circulating miRNA in various types of host body fluids, such as whole blood, serum, plasma, saliva, and urine has increased great interest among researchers in the potential of circulating miRNA as a prognosis/diagnosis of infectious. Some circulating miRNAs biomarkers advanced to clinical applications related to human diseases. However, this idea starts to come only in the fields of infectious disease. The goal of this review is to enhance the current understanding of these molecules and their applicability in the field of medicine. A detailed review of the available literature consulting tools performed in online repositories such as NCBI, PubMed, Medline, ScienceDirect, and UpToDate. This review summarizes an overview of preclinical studies using circulating miRNAs biomarkers against infectious diseases affecting humans. The use of miRNA as a safe and potential tool is encouraging news, considering that until now, guidelines for the use of miRNA in clinical practice are still lacking.

Molecular Characterization and Phylogeny of Taenia hydatigena and Echinococcus granulosus from Iranian Sheep and Cattle Based on COX1 Gene.

Hydatid cyst, the larval stage of Echinococcus granulosus, and Cysticercus tenuicollis, the larval stage of Taenia hydatigena, are prevalent in domestic, livestock, and wild ruminants. The main goal of this research was to identify the isolates of E. granulosus and C. tenuicollis by partial sequencing with PCR amplification of the cytochrome C oxidase 1 (COX1) gene. During a routine veterinary inspection at a Chabahar city slaughterhouse, two samples of hydatid cysts from sheep's liver and cattle's lung and two samples of C. tenuicollis from sheep's liver were collected. After DNA extraction, the fragment of the COX1 gene was amplified by the PCR method. Sample sequences were modified and synchronized by Chromas and CLC genomic workbench 11 software. Sequence analysis was carried out by BLAST algorithms and GenBank databases. Phylogenetic trees were performed using MEGA 7 software and the neighbor-joining and maximum likelihood method for T. hydatigena and E. granulousus. The result indicated that the main genotype of parasites and the amplified fragment size were G1 and approximately 455 bp, respectively. The analysis of phylogenetic trees based on nucleic acid for four samples showed that there was a common ancestor. However, the shift in nucleotides in the two isolates in E. granulosus and the two isolates of T. hydatigena were non-synonymous type and synonymous type, respectively. The present study showed that the dominant genotype in all isolates was G1 and this report was similar to other studies in Iran and the world. Also, the partial COX1 gene sequence was matched with T. hydatigena.

Distribution of invasive fungal infections: Molecular epidemiology, etiology, clinical conditions, diagnosis and risk factors: A 3-year experience with 490 patients under intensive care.

Recently, the prevalence of invasive fungal infections (IFIs) is rising. The global mortality rate of IFIs is 10-49%. This study aimed to determine the prevalence, the causative agents, and the risk factors associated with the invasive fungal infections in a tertiary health center to provide valid decision-grounds for healthcare professionals to effectively prevent, control, and treat fungal infections. The current study was conducted on 1477 patients suspected to have systemic fungal infections from different units of the hospital. After screening using routine mycological examination, the patients were confirmed with complementary mycological and molecular methods. Patients were included based on the confirmed diagnosis of IFI and excluded based on lack of a microbiologically and histologically proven diagnosis of IFI. Of the 1477 patients recruited in this study, confirmed cases of fungal infection were 490 (169 proven; 321 cases probable). Among the fungi recovered, Candida species had the highest frequency 337 (68.8%) followed by Aspergillus species 108 (22.1%), Zygomycetes species 21 (4.3%), non-Candida yeast 9 (1.8%). Others were black fungi 5 (1%), mycetoma agents 5 (1%), Fusarium 4 (0.8%), and Trichoderma (0.2%). Hematologic malignancies and diabetes mellitus were the most common underlying diseases among IFI-confirmed patients. This study observed an increased frequency of invasive candidiasis with non-albicans Candida and other invasive saprophytic fungal infections. The increased rate of invasive candidiasis with non-albicans agents highlights a new perspective in the epidemiology and treatment of invasive fungal infections.