Defining the Molecular Signal Pathways and Upstream Regulators in Cutaneous Leishmaniasis with Transcriptomic Data Approach

WOS:000613932200006PubMed: 33590982Leishmaniasis is a disease caused by the genus Leishmania spp., which are intracellular parasites. Depending on parasite species and host immune response, there are three basic clinical forms of the disease: cutaneous, mucocutaneous, and visceral leishmaniasis. Cutaneous leishmaniasis is a chronic disease and characterized by the presence of ulcerated skin lesions. The type of skin pathology seen during disease is determined in part by the infecting Leishmania spp., but also by a combination of inflammatory and antiinflammatory host immune response factors resulting in diverse clinical outcomes. in this study, it was aimed to determine the genes, molecular signaling mechanisms and biological functions of the molecules that play a role in the pathogenesis of the disease and immune response and determine host-parasite interactions in mice that are naturally resistant and susceptible to Leishmania major and Leishmania brazifiensis. For this, transcriptomic series GSE56029 was downloaded from "Gene Expression Omnibus" (GEO) data base, including expression profiling of twenty-four tissue samples that were recovered from both naive mice and mice (BALB/c, C57BL/6) infected with L.major and L.braziliensis. Then, "Differentially Expressed Genes" (DEGs) were identified by limma package in R script. FDR q 2 as threshold values were accepted in the analysis. Subsequently, functional and pathway enrichment analyses were performed for the DEGs by "Ingenuity Pathway Analysis" (IPA). For each of DEGs, p 1 were used and analyzed with the software program IPA 8.0. Ingenuity Pathway Analysis revealed the most enrichment pathways to be the inflammation, dendritic cell maturation and "Triggering Receptor Expressed on Myeloid Cells 1" (TREM-1) signal mechanisms and that the DEGs related to the regulation of immune system process were closely associated with the progress of cutaneous leishmaniasis. The upstream regulator analysis predicted that TNF-alpha, IFN gamma, IL-1 beta, IL-10RA and "Signal Transducer and Activator of Transcription-1" (STAT-1) are the regulators that explained gene expression changes causing biological activities in the tissues. Chemical compounds that may have anti-leishmanial effects were also identified in the study. in this study, the mechanisms belonging to the parasite species and host that determine the resistance/susceptibility phenotype were attempted to elucidate. Assessment of gene expression patterns, cytokine/chemokines, and signaling pathways in BALB/c and C57BL/6 mice infected with L.major and L.braziliensis will provide a better understanding of the potential mechanisms underlying infection from a genetic perspective. These results may guide for the future studies in terms of developing potential biomarkers for the diagnosis and prognosis prediction of cutaneous leishmaniasis and providing information about new treatment targets

The Spectrum of Infections in Patients with Lung Cancer

Although diagnostic and therapeutic advances in lung cancer (LC) have increased the survival of patients, infection and its complications are still among the most important causes of mortality. The disruption of tissue caused by tumor mass, management of cancer therapy and alteration in the humoral/cellular immune systems due to both cancer itself and therapy considerably increase susceptibility to infection in cancer patients. Particularly, opportunistic microorganisms should be considered, then applying rapid and sensitive diagnostic methods for them. Thus, cancer patients who are already exposed to difficult, long-term and expensive treatments can be prevented from dying from complications related to infections.TUBITAK; [120N924]This work is supported by TUBITAK with Project No: 120N924

Changes in the Prevalence of Coccidian Protozoa in Immunocompromised Patients Over the Last Decade

Introduction: Coccidian protozoal infection is one of the most important causes of diarrhea, which could prove to be fatal in immunosuppressed patients. The present study aimed to determine changes in the incidences and prevalence of coccidian protozoa in immunocompromised patients in two different time frames, and thus draw attention toward these neglected microorganisms. Materials and Methods: The present study involved retrospective analysis of 311 stool samples obtained from 311 immunocompromised patients, collected over two time frames (2009 and 2016-2019). Results: The study included 40.5% female and 37.6% pediatric immunocompromised patients (aged 0-18 years). In 2009, the incidences of Cryptosporidium spp. were 51.4% and this decreased to 41.6% in 2016-2019. Cyclospora spp. incidences decreased from 24.6% in 2009 to 9.8% in 2016-2019. Coccidian infection in pediatric patients was found to decrease over the stipulated time, where Cryptosporidium spp. incidences decreased from 63.9% to 34.6% and Cyclospora spp. detection rate decreased from 30.6% to 4.9%. In adults, detection rate for Cryptosporidium spp. changed from 47% to 47.8%, while Cyclospora spp. incidences changed from 22.5% to 14.1%, over the period of 10 years. Conclusion: The study demonstrated no significant changes in coccidian parasitic detection rates in immunocompromised adults over the period of 10 years, which remained high. However, a significant decrease in the detection rates of both Cryptosporidium and Cyclospora spp. was reported in pediatric patients over the years. A comparison with previously reported data revealed higher detection rates of coccidian parasite in immunocompromised patients as compared to the general patient population. These results also highlighted the importance of detailed patient information, especially clinical diagnosis and drug usage, to ensure application of appropriate diagnostic methods for laboratory evaluation of the stool samples obtained from immunocompromised patients. This will further aid in early diagnosis and management of such infections

Pathological and immunohistochemical findings of lungs, heart, liver, and kidneys, and unexpected findings of fungi and parasites in lungs of deceased COVID-19 patients: A case series

Objective: To define histopathologic and immunohistochemical features of the lungs, heart, liver, and kidneys in patients who died from coronavirus disease 2019 (COVID-19), and to determine the presence of SARS-CoV-2 in all tissues, as well as the presence of fungi and parasites in lung tissues.Methods: This retrospective case study was conducted in the intensive care units of Dokuz Eyl & uuml;l University Hospital, and patients (>= 18 years) who died due to COVID-19 between October 2020 and April 2021 were included. The biopsy samples of the patient's lung, heart, liver, and kidney tissues were studied.Results: In the study, we enrolled 12 patients (mean age: 70 years; 50% male). Alveolar epithelial cell damage and diffuse alveolar damage were predominant in lung tissues. Lobular lymphocyte infiltration, centrilobular sinusoidal dilatation, and microvesicular steatosis in the liver, together with pigmented cast, non-isometric vacuolar degeneration, and capillary plugging in the kidneys, were commonly found among the patients. SARS-CoV-2 nucleocapsid protein antibodies were detected in three lung and two kidney tissues, and so did angiotensin-converting enzyme 2 receptor positivity in one lung and more than half of the kidney tissues. The RT-PCR tests were positive in three lungs and one kidney tissue. After DNA isolation from lung tissues, Pneumocystis jirovecii was detected in nine patients, Aspergillus fumigatus in two, Microsporidia in three, and Cryptosporidium in two.Conclusions: SARS-CoV-2 is a multisystemic disease. Fungi and parasites should be investigated in critically ill COVID-19 patients prescribed corticosteroids