scholarly journals Transkriptomik Veri Yaklaşımı ile Kutanöz Leyşmanyazisteki Moleküler Sinyal Yolakların ve Regülatör Moleküllerin Tanımlanması

2021 ◽  
Vol 55 (1) ◽  
pp. 67-80
Author(s):  
Özlem Ulusan Bağcı ◽  
Ayşe Caner
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Cutaneous Leishmaniasis ◽  
Ingenuity Pathway Analysis ◽  
Pathway Analysis ◽  
Leishmania Major ◽  
Parasite Species ◽  
Host Immune Response ◽  
Leishmania Braziliensis ◽  
Leishmania Spp

Leishmaniasis 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 braziliensis. 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< 0.05 and absolute log2FC> 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< 0.01, FDR q< 0.01, and absolute log2FC> 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-α, IFNy, IL-1 β, 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.

scholarly journals H-Ras gene takes part to the host immune response to COVID-19

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Salvatore Sciacchitano ◽  
Andrea Sacconi ◽  
Claudia De Vitis ◽  
Giovanni Blandino ◽  
Giulia Piaggio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Response ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Severe Disease ◽  
Host Immune Response ◽  
Severe Form ◽  
Ras Gene ◽  
Peripheral Blood Mononuclear ◽  
Ras Genes

AbstractRas gene family members play a relevant role in cancer, especially when they are mutated. However, they may play additional roles in other conditions beside cancer. We performed gene expression analysis using the NanoString PanCancer IO 360 panel in the peripheral blood mononuclear cell (PBMC) of six COVID-19 patients and we found that H-Ras gene was significantly upregulated, while both K-Ras and N-Ras genes were downregulated. In particular, H-Ras gene upregulation was more evident in COVID-19 patients with a more severe disease. We compared our results with those obtained by analyzing two different and independent datasets, including a total of 53 COVID-19 patients, in which the gene expression analysis was performed using the Immunology_V2 panel. Comparative analysis of the H-Ras gene expression in these patients confirmed our preliminary results. In both of them, in fact, we were able to confirm the upregulation of the expression of the H-Ras gene. The exact role of this specific upregulation of the H-Ras gene in response to SARS-CoV-2 infection and its possible role in cancer still remains to be elucidated. In conclusion, H-Ras gene participates to the host immune response to SARS-CoV-2 virus infection, especially in patients affected by the most severe form of the COVID-19.

scholarly journals Review on the Role of Host Immune Response in Protection and Immunopathogenesis during Cutaneous Leishmaniasis Infection

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Teshager Dubie ◽  
Yasin Mohammed
Keyword(s):  
Immune Response ◽  
Cutaneous Leishmaniasis ◽  
Proinflammatory Cytokines ◽  
Parasitic Infection ◽  
Host Immune Response ◽  
Immune Defense ◽  
Host Cells ◽  
Infected Host ◽  
Major Public Health Problem

Cutaneous leishmaniasis (CL) is a major public health problem worldwide and spreads to human via the bite of sand flies during blood meal. Following its inoculation, the promastigotes are immediately taken up by phagocytic cells and these leishmania-infected host cells produce proinflammatory cytokines that activate other immune cells and these infected host cells produce more cytokines and reactive nitrogen and oxygen species for efficient control of leishmania infection. Many experimental studies showed that resistance to infection with leishmania paraites is associated with the production of proinflammatory cytokines and activation of CD4+ Th1 response. On the other hand, vulnerability to this parasitic infection is correlated to production of T helper 2 cytokines that facilitate persistence of parasites and disease progression. In addition, some studies have also indicated that CD8+ T cells play a vital role in immune defense through cytokine production and their cytotoxic activity and excessive production of proinflammatory mediators promote amplified recruitment of cells. This could be correlated with excessive inflammatory reaction and ultimately resulted in tissue destruction and development of immunopathogenesis. Thus, there are contradictions regarding the role of immune responses in protection and immunopathogenesis of CL disease. Therefore, the aim of this paper was to review the role of host immune response in protection and its contribution to disease severity for CL infection. In order to obtain more meaningful data regarding the nature of immune response to leishmania, further in-depth studies focused on immune modulation should be conducted to develop better therapeutic strategies.

Gene Expression Profiling within the Context of JAK Inhibitor Therapy for Myelofibrosis: Correlation with Treatment Effect and Anemia Response

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1751-1751
Author(s):  
Animesh Pardanani ◽  
Rebecca R. Laborde ◽  
Terra L Lasho ◽  
Christy Finke ◽  
Alexey A. Leontovich ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
Immune Response ◽  
Gene Expression Profiling ◽  
Pathway Analysis ◽  
Treatment Effect ◽  
Expression Profiling ◽  
Phase 1 ◽  
Hemoglobin Level ◽  
Jak Inhibitors

Abstract Abstract 1751 Background: JAK inhibitors have significant palliative benefit in myelofibrosis (MF), mainly in the form of improved constitutional symptoms and reduced splenomegaly. Preliminary data suggests that CYT387, a JAK-1/2 inhibitor, also has the ability to produce anemia responses (ASH Annual Meeting, 2011). In general, the mechanism(s) underlying treatment effects of JAK inhibitors remain unclear but likely represent a drug-specific balance between anti-clonal activity and modulation of immuno cellular-cytokine pathways. We conducted a gene expression profiling (GEP) study using primary cells from MF patients undergoing therapy with CYT387 followed by correlation with clinical data. Methods: Study subjects were enrolled in the Phase-1/2 study of CYT387 treatment in patients with primary (PMF), post-polycythemia vera (PPMF) or post-essential thrombocythemia (PTMF) myelofibrosis. Paired research samples were collected; the time points were pre-study and 12 weeks after commencing study treatment. PBMCs were purified from whole blood by Ficoll separation; RNA was isolated from this cell fraction for GEP analysis. Gene expression profiles were generated using Illumnia Human HT-12 v4 microarray. Pair wise analysis was conducted using the Wilcoxon signed-rank test with a p-value cutoff of 0.05 to generate lists of differentially expressed genes between assigned groups. Pathway analysis was conducted to identify relevant pathways enriched for differentially expressed genes. Comprehensive plasma cytokine profiling was performed using Multiplex Bead-Based Luminex technology (Invitrogen, Carlsbad, CA). Results: Seventeen patients were studied based on sample availability; 11 (65%) mere male with median age of 66 years (range 53–85). Twelve (71%) were JAK2V617F mutation positive and the DIPSS-plus risk categorization was 10 (59%) high and 7 (41%) intermediate-2. All patients were evaluable for anemia response; 14 (82%) were red cell transfusion dependent at study start. Nine (53%) patients achieved anemia response by IWG-MRT criteria; of these, 8 patients achieved transfusion independence (minimum non-transfused hemoglobin level of 8 g/dL maintained for at least 12 weeks) and 1 had a sustained >2 g/dL increase in hemoglobin level above baseline. The initial pair wise analysis to identify differential patterns of gene expression compared pre- and post-treatment groups (Figure 1A). This revealed a cluster of significantly (p <0.05) down-regulated genes (minimum 2-fold; median 17-fold) following treatment (displayed in green; upper left quadrant). Pathway enrichment analysis revealed significant associations of these genes with cytokine regulation of immune response, cell proliferation, chemotaxis and cytoskeleton remodeling. We then conducted a pair wise analysis of anemia responders versus non-responders; this revealed a predominance of over expressed gene targets (median 35-fold) in the anemia responder group (Figure 1B) (displayed in red; upper right quadrant). Similar pathway analysis identified enrichment for genes involved in immune system function in this cluster. Conclusions: The current preliminary analysis suggests that genes relevant to immune response-cytokine pathways are significantly over expressed in patients who achieve anemia response following CYT387 therapy. This further suggests a dominant immune component that underpins ineffective hematopoiesis in responding patients. On the basis of broad treatment-related changes in gene expression we suggest that an important component of CYT387's treatment effect is down regulation of these dysregulated pathways. Ongoing studies include validation of select gene targets which will be tested prospectively in future treatment protocols, as well as correlation of gene expression with circulating cytokine-chemokine levels. Disclosures: Pardanani: Bristol-Myers Squibb: Clinical trial support, Clinical trial support Other; YM BioSciences: Clinical trial support, Clinical trial support Other; Sanofi-Aventis: Clinical trial support Other. Off Label Use: Data from Phase −1/2 study of CYT387 use in myelofibrosis is mentioned.

scholarly journals Comparative and systems analyses of Leishmania spp. non-coding RNAs through developmental stages

2021 ◽  
Author(s):  
J. Eduardo Martinez-Hernandez ◽  
Victor Aliaga-Tobar ◽  
Carolina Gonzalez ◽  
Rubens Monte-Neto ◽  
Alberto J. M. Martin ◽  
...  
Keyword(s):  
Leishmania Major ◽  
Developmental Stages ◽  
Genomic Structure ◽  
Neglected Diseases ◽  
Leishmania Braziliensis ◽  
Functional Relationships ◽  
Host Interaction ◽  
Leishmania Spp ◽  
Non Coding Rnas ◽  
And Function

Leishmania spp. is the causal agent of several diseases called leishmaniases, neglected diseases that seek to be eradicated in the coming years. We aimed to study the genomic structure and function of non-coding RNAs (ncRNAs) from Leishmania spp. and to get insights into its RNAome. We studied 26 strains corresponding to 16 different species of Leishmania genus. RNAome analysis revealed the presence of several ncRNAs that are shared through different species, allowing us to differentiate between subgenus and as well as species that are canonically related to visceral leishmaniasis. We found coexpression relationships within coding genes and ncRNAs, thus suggesting possible functional relationships between different coding genes-ncRNAs. Expression analysis in the metacyclic developmental stage comparison for Leishmania braziliensis and Leishmania major reveals the presence of shared coexpressed ncRNAs to several other coding genes in both species involved in chromatin structure and host interaction. This work constitutes the first effort to characterize the Leishmania RNAome, supporting further approaches to better understand the role of ncRNAs in the gene regulation, infective process and host-parasite interaction.

scholarly journals Molecular Analysis of Aquaglyceroporin 1 Gene in Non-Healing Clinical Iso¬lates Obtained from Patients with Cutaneous Leishmaniasis from Central of Iran

2019 ◽  
Author(s):  
Yasaman Alijani ◽  
Saeedeh Sadat Hosseini ◽  
Salman Ahmadian ◽  
Sonia Boughattas ◽  
Gilda Eslami ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cutaneous Leishmaniasis ◽  
Molecular Characterization ◽  
Significance Level ◽  
Detection And Identification ◽  
Pcr Rflp ◽  
Leishmania Spp ◽  
Sensitive Isolate ◽  
The One

Background: Regarding the antimonial-resistant of Leishmania spp., understanding of related mechanism is neces­sary. One of the most important involved molecules is aquaglyceropin1 (AQP1). The aim of this study was molecu­lar analysis of AQP1 gene from antimonial-resistant clinical isolates and its expression. Methods: Overall, 150 patients with cutaneous leishmaniasis referring to the reference laboratories of Yazd and Varzaneh,, located 105km southeast of Isfahan and 240km away from Yazd, were assessed from Jun 2015 to Dec 2017. After sampling, staining was done and evaluated for Leishman by microscope. Samples were collected in RNAlater solution for gene expression analysis in non-healing isolates. DNA extraction was performed from each slide with Leishman body. All patients with L. major isolates detected by ITS1-PCR-RFLP were followed for find­ing the resistant isolates, consequence of molecular characterization of AQP1 using PCR-RFLP. Gene expression of AQP1 from all resistant isolates was assessed in comparison with the one in a sensitive isolate. Statistical analysis was done using SPSS. The significance level was considered ≤0.05. Results: Five isolates were detected as antimonial resistant. Molecular detection and identification were appeared that all were L. major. The molecular characterization of AQP1 showed G562A mutation. Gene expression of AQP1 in resistant isolates showed 1.67 fold higher than the sensitive isolate. Conclusion: We reported a new point mutation of G562A in AQP1 gene involved in molecular mechanism in re­sistant isolates.

scholarly journals Molecular Detection of Leishmania major in Hemiechinus auritus, A Potential Reservoir of Zoonotic Cutaneous Leishmaniasis in Damghan, Iran

2019 ◽  
Author(s):  
Behrad Pourmohammadi ◽  
Sadegh Mohammadi-Azni
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Natural Infection ◽  
Leishmania Infection ◽  
Northern Iran ◽  
Zoonotic Cutaneous Leishmaniasis ◽  
Potential Reservoir ◽  
Leishmania Spp ◽  
First Time ◽  
Leishmania Parasites

Background: Zoonotic cutaneous leishmaniasis caused by Leishmania major is endemic in 17 of 31 Iranian provinces. Various species of rodents have been introduced as the main reservoirs of the disease. This study was conducted to de­termine the natural infection of hedgehogs with Leishmania spp. in an endemic area of the disease, northern Iran. Methods: Fifteen long-eared hedgehogs were captured alive during 18 months study period, from Apr 2015 to Sep 2016, in Damghan City, Semnan Province, Iran. The animals were identified using apparent characteristics and to de­termine the Leishmania infection, impression smears were prepared from their ear lobes, hind feet, livers, and spleens. Micro­scopic examination and semi-nested PCR were applied to determine the infection and to identify the parasites species respectively. Results: All examined animals were identified as Hemiechinus auritus (Family: Erinaceidae). In microscopic examina­tion, 8 (53.3%) samples were shown to be infected with Leishmania parasites. The higher and lower rate of the infection was observed in the ears as well as the feet and in the liver specimens, 53.3%, and 33.3% respectively. Forty percent (6/ 15) of the samples were molecularly positive and all were identified as L. major parasites. All the examined animals in au­tumn and 50% of them in summer were shown to be infected with Leishmania parasites. Conclusion: This study demonstrated the natural infection of H. auritus with L. major for the first time in Damghan City and introduced these mammals as new potential reservoirs of ZCL in the study area.

scholarly journals Analysis of the Immune Responses of Mice to Infection with Leishmania braziliensis

1998 ◽  
Vol 66 (2) ◽  
pp. 827-829 ◽  
Author(s):  
Gregory K. DeKrey ◽  
Hermenio C. Lima ◽  
Richard G. Titus
Keyword(s):  
Immune Responses ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
Leishmania Braziliensis ◽  
Dependent Mechanism

ABSTRACT Leishmania major and Leishmania braziliensis both cause cutaneous leishmaniasis, but the former kills BALB/c mice while the latter is killed by the mice. This killing of L. braziliensis occurred by a gamma interferon-dependent mechanism, potentially made possible by the observed lack of high interleukin-4 production.

scholarly journals Pre-Exposure to Defibrotide Prevents Endothelial Cell Activation by Lipopolysaccharide: An Ingenuity Pathway Analysis

2020 ◽  
Vol 11 ◽  
Author(s):  
Nicoletta Orlando ◽  
Gabriele Babini ◽  
Patrizia Chiusolo ◽  
Caterina Giovanna Valentini ◽  
Valerio De Stefano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
Inflammatory Response ◽  
Ingenuity Pathway Analysis ◽  
Pathway Analysis ◽  
Endothelial Protein C Receptor ◽  
Collagen Xviii ◽  
Wide Range ◽  
Regulated Gene Expression

Defibrotide (DFB) effects on different endothelial cell pathways have been investigated focusing on a limited number of genes or molecules. This study explored the modulation of the gene expression profile of steady-state or lipopolysaccharide (LPS)-activated endothelial cells, following the DFB exposure. Starting from differentially regulated gene expression datasets, we utilized the Ingenuity Pathway Analysis (IPA) to infer novel information about the activity of this drug. We found that effects elicited by LPS deeply differ depending on cells were exposed to DFB and LPS at the same time, or if the DFB priming occurs before the LPS exposure. Only in the second case, we observed a significant down-regulation of various pathways activated by LPS. In IPA, the pathways most affected by DFB were leukocyte migration and activation, vasculogenesis, and inflammatory response. Furthermore, the activity of DFB seemed to be associated with the modulation of six key genes, including matrix-metalloproteinases 2 and 9, thrombin receptor, sphingosine-kinase1, alpha subunit of collagen XVIII, and endothelial-protein C receptor. Overall, our findings support a role for DFB in a wide range of diseases associated with an exaggerated inflammatory response of endothelial cells.

Isolation and Molecular Diagnosis of Leishmania major and Study Activity of Aqueous Extract of Plant Nigella sativa Against the Parasite In Vitro

2019 ◽  
Vol 10 (01) ◽  
Author(s):  
Enas Abdul Kareem Jabbar ◽  
Bassad A. AL-Aboody ◽  
Basim Abdulhussein Jarullah ◽  
Nada Noori
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Molecular Diagnosis ◽  
Aqueous Extract ◽  
Teaching Hospital ◽  
Exposure Time ◽  
Leishmania Major ◽  
Nigella Sativa ◽  
Study Activity ◽  
Leishmania Spp

The current study included isolating and diagnosing the cutaneous leishmaniasis parasite from patients with Baghdad boil and the reviewers of Al Hussein Teaching Hospital in Thi-Qar province for the period from November to December 2016 and then studying the effect of aqueous extract of the plant Nigella sativa in the vitality of isolated parasite in vitro. Through the results, the isolated parasite was diagnosed depend on lesions appearance and characterization then confirm the diagnosis by KDNA- PCR which revealed that leishmania spp. was Leishmania major . In this study three different concentrations from aqueous extract of the Nigella sativa plant were used (50, 100 and 150 mg / ml), the parasite growing in NNN medium (3 replicates used)It was observed that the percentage of parasite destruction increased with prolong exposure time of the extract and increased concentration of the extract, results also exhibited that the percentage of the destruction was 100% after four hours of exposure to the concentration of 150 mg / ml which was the highly killed percentage compared to control, which was 5. 98%.

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