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Leishmania major (L. major) applies several mechanisms to escape the immune system. Interleukin-10 (IL-10) and Transforming Growth Factor (TGF-ß) downregulate nitric oxide synthase (iNOS) leading to the survival of Leishmania within macrophages. The miRNAs are known as the modulators of the immune system. The present study was conducted to assess the effect of synthetic miR-340 mimic on cytokines (IL-10 and TGF-ß1) involved in L. major infected macrophages. The miRNAs targeting of IL-10 and TGF-ß1 was predicted using bioinformatic tools. Relative expression of predicted miRNA, IL-10, and TGF-ß1 was measured by RT-qPCR before and after synthetic miRNA mimic transfection. Concentration of IL-10 and TGF-ß was measured in posttreatment condition using ELISA method. Also, infectivity was assessed by Giemsa staining. mmu-miR-340 received the highest score for targeting cytokines. The expression of miR-340 was downregulated in L. major infected macrophages. By contrast, expression of IL-10 and TGF-ß1 was upregulated in infected macrophages. After miRNA transfection, TGF-ß1 and IL-10 were both downregulated and interestingly, the combination of miR-340 and miR-27a had a stronger effect on the downregulation of target genes. This research revealed that transfection of infected macrophages with miR-340 alone or in combination with miR-27a mimic can reduce macrophage infectivity and might be introduced as a novel therapeutic agent for cutaneous leishmaniasis.
Assuntos
Leishmania major , MicroRNAs , Anti-Inflamatórios , Citocinas , Interleucina-10/genética , Macrófagos , MicroRNAs/genética , Fator de Crescimento Transformador betaRESUMO
Alzheimer is a progressive neurological disease that results in irreversible loss of neurons and includes about two thirds of all cases of dementia. Toxoplasma gondii may be an important infectious agent involved in neurodegenerative diseases. The aim of this study was to investigate the correlation between Toxoplasma as an etiologic agent in the progress of Alzheimer's disease. This case control study was conducted on 75 Alzheimer's patients and 75 healthy volunteers. Blood samples were obtained and anti-Toxoplasma IgG and IgM tests were done by using ELISA technique. DNA was extracted from buffy coat and then GRA6 gene and SAG2 loci were amplified by PCR and nested PCR, respectively. Chi-square, Fisher's test, and binary logistic regression were used for data analysis. A percentage of 61.3 % of Alzheimer's patients and 62.6 % of healthy volunteers were positive for anti-Toxoplasma IgG but all participants were negative for anti-Toxoplasma IgM. There were no significant differences between Alzheimer's patients with their controls in terms of anti-Toxoplasma IgG antibody (P = 0.5). Due to lack of positive IgM sample, results of the molecular methods were negative by GRA6 and SAG2 fragments amplification. This result shows that, infection with T. gondii cannot be considered as a risk factor for etiology and developing Alzheimer's disease.
Assuntos
Doença de Alzheimer/etiologia , Anticorpos Antiprotozoários/imunologia , Antígenos de Protozoários/genética , Proteínas de Protozoários/genética , Toxoplasma/genética , Toxoplasma/imunologia , Toxoplasmose/sangue , Anticorpos Antiprotozoários/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Reação em Cadeia da Polimerase/métodos , Fatores de Risco , Toxoplasmose/parasitologiaRESUMO
BACKGROUND: miRNAs are known as non-coding RNAs that can regulate gene expression. They are reported in many microorganisms and their host cells. Parasite infection can change or shift host miRNAs expression, which can aim at both parasite eradication and infection. PURPOSE: This study dealt with examination of miRNA expressed in intestinal protozoan, coccidia , as well as profile changes in host cell miRNA after parasitic infection and their role in protozoan clearance/ survival. METHODS: The authors searched ISI Web of Sciences, Pubmed, Scholar, Scopus, another databases and articles published up to 2024 were included. The keywords of miRNA, intestinal protozoa, toxoplasma and some words associated with topics were used in this search. RESULTS: Transfection of miRNA mimics or inhibitors can control parasitic diseases, and be introduced as a new therapeutic option in parasitology. CONCLUSION: This review can be used to provide up-to date knowledge for future research on these issues.
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This systematic review and meta-analysis study aimed to evaluate global Trichuris infection prevalence, assessing progress towards the WHO's 2030 target. We searched international databases from 2010-2023, categorizing data by regions and socio-economic variables using a random-effects model. Analyzing 757 articles covering 7154,842 individuals from 78 countries, the study found a pooled global prevalence of (6.64-7.57%), with the highest rates in the Caribbean (21.72%; 8.90-38.18%) and South-East Asia (20.95; 15.71-26.71%) regions. Southern Africa (9.58; 2.11-21.46%), Latin America (9.58; 2.11-21.46%), and Middle Africa Middle Africa (8.94; 6.31-11.98%) also exhibited high prevalence. Eastern Europe had the lowest prevalence at 0.16% (0.09-0.24). Approximately 513 (480-547) million people worldwide were estimated to harbor Trichuris. Moreover â¼1.5% of people tested worldwide (2010-2023) had a moderate to heavy intensity of infection. The study emphasizes the persistent global health threat of Trichuris infection, urging tailored strategies for effective control and prevention on a global scale.
Assuntos
Saúde Global , Tricuríase , Trichuris , Humanos , Tricuríase/epidemiologia , Prevalência , Saúde Global/estatística & dados numéricos , Trichuris/isolamento & purificação , AnimaisRESUMO
Background: Immune cells and their secreted cytokines are known as the first barrier against pathogens. Leishmania major as an intracellular protozoan produces anti-inflammatory cytokines that lead to proliferation and survival of the parasite in the macrophages. miRNAs are small non-coding RNA molecules that regulate mRNAs expression. We aimed to investigate the relationship between the expression of TGF-ß and a bioinformatically candidate miRNA, in leishmaniasis as a model of TGF-ß overexpression. Methods: The miRNAs that target TGF-ß -3'UTR were predicted and scored by bioinformatic tools. After cloning of TGF-ß-3'UTR in psi-CHECK ™- 2 vector, targeting validation was confirmed using Luciferase assay. After miRNA mimic transfection, the expression of miR-27a, TGF-ß, as well as Nitric Oxide concentration was evaluated. Results: miR-27a received the highest score for targeting TGF-ß in bioinformatic predictions. Luciferase assay confirmed that miR-27a is targeting TGF-ß-3'UTR, since miR-27a transfection decreased the luciferase activity. After miRNA transfection, TGF-ß expression and Nitric Oxide concentration were declined in L. major infected macrophages. Conclusion: Bioinformatic prediction, luciferase assay, and miRNA transfection results showed that miR-27a targets TGF-ß. Since miRNA and cytokine-base therapies are developing in infectious diseases, finding and validating miRNAs targeting regulatory cytokines can be a novel strategy for controlling and treating leishmaniasis.
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Due to the growth of diabetic mellitus (DM) and diabetic nephropathy as a significant complication for diabetic patients, study on effective treatment with fewer side effects has been fascinated. In this study for the first time carvedilol effects on both function and structure of kidney in diabetic nephropathy treatment were evaluated. Diabetes was induced by injection of streptozotocin (STZ) intravenously in rats and three groups including control, diabetic, and treatment with carvedilol were considered. Biochemical parameters such as, blood glucose level, BUN, creatinine, uric acid, Na+, K+ was determined. Results showed that glucose (516 to 291 mg/dl), BUN (42 to 21.67 mg/dl), creatinine (0.75 to 0.6 mg/dl), uric acid (4.45 to 1.36 mg/dl), and K+ (7.433 to 5.433 mEq/l) level reduced. Decrease in glucose, BUN, creatinine, uric acid, and K+ and increase in Na+ level (138 to 146.33 mEq/l) confirmed therapeutic effect of carvedilol. Furthermore, the histopathological study was done for each group. Histopathological results confirmed the data obtained by biochemical parameters. For further investigation, SPECT imaging with 99mTc-DMSA, which is a gold standard in diabetic nephropathy detection, was done. SPECT imaging showed that accumulation of 99mTc-DMSA was increased in treated group (5 to 25 kcpm) which means the improvement in renal structure in the treated group compare to the diabetic group (5 kcpm). Finally, obtained results confirmed our hypothesis that carvedilol had a therapeutic effect on diabetic nephropathy.
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BACKGROUND: Cutaneous Leishmaniasis (CL) is an emerging uncontrollable and neglected infectious disease worldwide including Iran. The aim of this study was to investigate the expression profile of apoptosis-related miRNA and its target gene in macrophages. METHODS: This study was carried out in the Department of Medical Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran from January 2016 to November 2018. Applying literature reviews, bioinformatics software, and microarray expression analysis, we selected miRNA-24-3p interfering in apoptosis pathway. The expression profile of this miRNA and target gene were investigated in Leishmania major (MRHO/IR/75/ER)-infected primary and RAW 264.7 macrophages (IBRC-C10072) compared with non-infected macrophages (control group) using quantitative Real-time PCR. RESULTS: Results of bioinformatics analysis showed that miR-24-3p as anti-apoptotic miRNA inhibits pro-apoptotic genes (Caspases 3 and 7). Microarray expression data presented in Gene Expression Omnibus (GEO) revealed a significant difference in the expression level of selected miRNA and its target gene between two groups. QRT-PCR results showed that the expression of miR-24-3p was upregulated in L. major infectioned macrophages that approved the results of bioinformatics and microarray analysis. CONCLUSION: Parasite can alter miRNAs expression pattern in the host cells to establish infection and its survival. Alteration in miRNAs levels likely plays an important role in regulating macrophage functions following L. major infection. These results could highlight current understanding and new insights concerning the gene expression in macrophages during leishmaniasis and will help to development of novel strategies for control and treatment of CL.
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BACKGROUND: We aimed to investigate the effect of miR-15a mimic and inhibitor of miR-155 expression on apoptosis induction in macrophages infected with Iranian strain of Leishmania major in-vitro and in-vivo. METHODS: RAW 264.7 cells were infected with L. major promastigotes (MRHO/IR/75/ER), and then were treated with miRNAs. For in-vivo experiment, BALB/c mice were inoculated with L. major promastigotes, and then they were treated with miRNAs. For evaluation of miRNA therapeutic effect, in-vitro and in-vivo studies were performed using quantitative Real-time PCR, Flow cytometry, lesion size measurement, and Limiting Dilution Assay (LDA). This study was performed in Shahid Beheshti University of Medical Sciences in 2019. RESULTS: In-vitro results of flow cytometry showed that using miR-15a mimic, miR-155 inhibitor or both of them increased apoptosis of macrophages. In in-vivo, size of lesion increased during experiment in control groups (P<0.05) while application of both miR-155 inhibitor and miR-15a mimic inhibited the increase in the size of lesions within 6 wk of experiment (P=0.85). LDA results showed that microRNA therapy could significantly decrease parasite load in mimic or inhibitor receiving groups compared to the control group (P<0.05). CONCLUSION: miR-155 inhibitor and miR-15a mimic in L. major infected macrophages can induce apoptosis and reduce parasite burden. Therefore, miRNA-based therapy can be proposed as new treatment for cutaneous leishmaniasis.
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BACKGROUND: Toxoplasma gondii, the obligate, intracellular parasite afflicts human in diverse ways such as ingestion of tissue cysts in undercooked meat. The aim of this study was to assess the prevalence and genotyping of Toxoplasma isolated from meat samples being consumed in East Azerbaijan, Northwest of Iran. METHODS: Overall, 150 samples including chicken, beef and lamb meat were collected from retailers in different regions of Tabriz, northwestern Iran during April to September 2014. Molecular detection was done by amplifying B1 gene and T. gondii surface antigen 2 (SAG2) loci. For genotyping of T. gondii, restriction fragment length polymorphism (RFLP) was performed using Sau3AI and HhaI restriction enzymes. Finally, three positive isolate from each host was sequenced to evaluate and phylogenetic analysis. RESULTS: Overall, 26 (17.33%) samples were positive for T. gondii including 4 (8%) isolate from chicken, 8 (16%) isolates from cattle and 14 (28%) isolates from sheep. According to the RFLP patterns, sequencing and phylogenetic results, all of the samples were identified as genotype I. CONCLUSION: The results indicated a potential risk of transmission of the disease through the consumption of infected meat. This is particularly important especially for pregnant women and immuno-compromised patients and this suggests that the training on the prevention of infection is necessary.
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Toxoplasma gondii is an obligate intracellular parasite that infects all nucleate cells of vertebrates. Human infected by vertical transmission and also using raw or undercooked meat or food and water that contaminated with mature oocysts. Parkinson's disease as neurodegenerative disease affects people above 60 years. Due to high prevalence of toxoplasmosis in Iran and evidence about effects of T. gondii on neurodegenerative diseases, this study has been conducted to investigate possible correlation between Toxoplasma and Parkinson's disease in Iran. Seventy five Parkinson's patients and equal healthy volunteers were enrolled. After obtaining informed consent and sociodemographic features, 5 ml blood sample were collected and then anti-Toxoplasma IgG and IgM levels were examined by ELISA method. Data was analyzed with Chi-squre and Fisher's test by usig stata 11 software. Binary logistic regression was used for multivariate analysis in assessing the correlation between toxoplasmosis and Parkinson. Eighty five percent of Parkinson's group and 90.3 % of control group were positive for anti-Toxoplasma IgG antibody. In this investigation no statically differences were observed between groups and age, gender, residency and using raw or undercooked meat. There is no significant association between IgG positive titer and Parkinson's disease. However, statistically significant association was found between Parkinson and keeping cat (P = 0.03) as well as the using of undercooked egg (P = 0.004). Although there is high level of anti-Toxoplasma IgG antibody in Parkinson's patients which reflects chronic Toxoplasma infection; we couldn't detect any statistical association between T. gondii infection and Parkinson's disease.
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BACKGROUND: Hydatidosis, as the most important zoonotic parasitic disease in Iran, has posed many health and economic losses. This study was conducted to investigate the demographic characteristics of hydatid cyst surgeries in hospitals of East Azerbaijan Province, Northwest of Iran. METHODS: Demographic characteristics of all patients with hydatid cyst surgery in hospitals of the province, during 2009-2011 were gathered including age, gender, occupation, number and location of the cyst, clinical symptoms, place of residence and history of contact with dog. They were extracted from reports of health center and were analyzed using STATA 11 software. RESULTS: Out of 52 hydatid cyst surgeries, 27 cases were females. Mean age of patients was 38.3 yr. Liver was reported as the most involved organ. The most clinical symptoms were abdominal and liver pain. Housewives comprised the most victims of the disease. Forty seven percent of patients had one cyst and 59% had the history of contact with dog. The majority of the patients were living in rural areas. CONCLUSION: Due to the high costs of diagnosis and treatment of hydatidosis, collecting data on the prevalence and transmission of the disease as well as on vulnerable groups seems to be essential as the first step in controlling and preventing the disease.