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Cytokine gene expression alterations in human macrophages infected by leishmania major
No full textObjective: Leishmaniasis is caused by members of the Leishmania species and constitute a group of infective diseases that range from cutaneous lesions to lethal visceral forms. In infected persons, macrophages recognize and eliminate the parasites via phagocytosis. In order to change a hostile environment into an environment adequate for survival and reproduction, the engulfed Leishmania species needs to modulate the function of its host macrophage. The expression patterns of cytokine genes such as interleukin-12 (IL-12), tumour necrosis factor-alpha (TNF-α), IL-1, and interferon-gamma (IFNγ) represent the immune response. In this study, we employed an RNA-seq approach for human monocyte-derived macrophages infected with Leishmania major (L. major) to decipher cytokine gene expression alterations in host macrophages. Materials and Methods: In this descriptive study, human monocytes were isolated by magnetic activated cell sorting (MACS) and cultured in the presence of monocyte colony stimulating factor (M-CSF) to obtain the macrophages. Monocyte-derived macrophages were then co-cultured with metacyclic promastigotes of L. major for 4 hours. RNA isolation was performed using TRIzol reagent. RNA sequencing was performed using the Illumina sequencing platforms. Gene expression analysis was performed using a Bioconductor DESeq2 package. Results: Our data revealed significant changes in immune response gene expressions in macrophages infected with L. major, with an up-regulation of cytokines and mostly down-regulation of their receptors. Conclusion: The obtained data could shed more light on the biology of L. major and how the host cell responds to leishmaniasis. © 2021 Royan Institute (ACECR). All rights reserved
Preconditioning and anti-apoptotic effects of Metformin and Cyclosporine-A in an isolated bile duct-ligated rat heart
No full textDespite all previous studies relating to the mechanism of cirrhotic cardiomyopathy (CCM), the role of cirrhosis on Ischemic Preconditioning (IPC) has not yet been explored. The present study strives to assess the cardioprotective role of IPC in bile duct ligated (BDL) rats as well as the cardioprotective role of Cyclosporin-A (CsA) and Metformin (Met) in CCM. Cirrhosis was induced by bile duct ligation (BDL). Rats� hearts were isolated and attached to a Langendorff Apparatus. The pharmacological preconditioning with Met and CsA was done before the main ischemia. Myocardial infarct size, hemodynamic and electrophysiological parameters, biochemical markers, and apoptotic indices were determined at the end of the experiment. Infarct size, apoptotic indices, arrhythmia score, and incidence of VF decreased significantly in the IPC group in comparison with the I/R group. These significant decreases were abolished in the IPC (BDL) group. Met significantly decreased the infarct size and apoptotic indices compared with I/R (BDL) and normal groups, while CsA led to similar decreases except in the level of caspase-3 and -8. Met and CsA decreased and increased the arrhythmia score and incidence of VF in the BDL groups, respectively. Functional recovery indices decreased in the I/R (BDL) and IPC (BDL) groups. Met improved these parameters. Therefore, the current study depicted that the cardioprotective effect of Met and CsA on BDL rats is mediated through the balance between pAMPK and apoptosis in the mitochondria. © 2020 Elsevier B.V
The concentration and probabilistic risk assessment of potentially toxic elements in fillets of silver pomfret (Pampus argenteus): A global systematic review and meta-analysis
No full textThe contamination of fish type products such as silver pomfret fish fillets by potentially toxic elements (PTEs) has raised global health concerns. Related studies regarding the concentration of PTEs in fillets of silver pomfret fish were retrieved among some international databases such as Scopus, PubMed and Embase between 1 January 1983 and 10 March 2020. The pooled (mean) concentration of PTEs in fillets of silver pomfret fish was meta-analyzed with the aid of a random-effect model (REM). Also, the non-carcinogenic risk was estimated via calculating the 95th percentile of the total target hazard quotient (TTHQ). The meta-analysis of 21 articles (containing 25 studies or data reports) indicated that the ranking of PTEs in fillets of silver pomfret fish was Fe (11,414.81 µg/kg wet weight, ww) > Zn (6055.72 µg/kg ww) > Cr (1825.79 µg/kg ww) > Pb (1486.44 µg/kg ww) > Se (1053.47 µg/kg ww) > Cd (992.50 µg/kg ww) > Ni (745.23 µg/kg ww) > Cu (669.71 µg/kg ww) > total As (408.24 µg/kg ww) > Co (87.03 µg/kg ww) > methyl Hg (46.58 µg/kg ww). The rank order of health risk assessment by country based on the TTHQ for adult consumers was Malaysia (2.500) > Bangladesh (0.886) > Iran (0.144) > China (0.045) > Pakistan (0.020) > India (0.015), while the corresponding values for child consumers was Malaysia (11.790) > Bangladesh (4.146) > Iran (0.675) > China (0.206) > Pakistan (0.096) > India (0.077). The adult consumers in Malaysia and children in Malaysia and Bangladesh were at considerable non-carcinogenic risk. Therefore, following the recommended control plans in order to reduce the health risk associated with the ingestion of PTEs via consumption of silver pomfret fish fillets is crucial. © 202
Comparative evaluation of amniotic fluid as an alternative to fetal bovine serum in the maintenance of Leishmania major and Toxoplasma gondii
No full textThis study aimed to evaluate the efficacy of amniotic fluid (AF) as an alternative to fetal bovine serum (FBS) in the maintenance of Leishmania major promastigotes and Toxoplasma gondii tachyzoites. AF was collected by an obstetrician using sterile syringes during a cesarean section. The culture medium was supplemented with 5 different concentrations of FBS or AF including 2, 5, 10, 20, and 30. These concentrations were used to maintain both mentioned parasites. L. major was maintained at temperatures 4 and 24 °C and examined once a week for 4 weeks, while T. gondii was maintained at temperatures 4, 24, and 37 °C and examined at hours 24, 48, 72, and 96. For L. major, at both 4 and 24 °C, we observed no significant difference between FBS and AF on day 7. However, on days 14, 21, and 28, the difference between FBS and AF was significant at both temperatures. For T. gondii, no significant difference was observed between FBS and AF at hour 24 and all temperatures. However, this difference was significant at hours 48, 72, and 96 and all temperatures. According to our results, although FBS had a greater efficacy than AF in the growth of L. major and the survival of T. gondii, the number of promastigotes increased over time in AF-containing medium and the number of tachyzoites reduced slowly with a mild slop. Therefore, AF can be a potential alternative to FBS. © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature
The use of bio-active compounds of citrus fruits as chemopreventive agents and inhibitor of cancer cells viability
No full textCommon therapy of cancer, such as chemotherapy, has various side effects for the patients. In recent studies, new therapeutic approaches in cancer treatment are adjuvant therapy, along with a reduction in side effects of chemotherapy drugs. Treatment by herbal medicines may have some advantages over treatment with single purified chemicals, also in terms of side effects, the use of plants in cancer treatment is a more secure method. Citrus fruits are one of the most consumed natural products in the world due to the presence of various metabolites and bioactive compounds, such as phenols, flavonoids and, carotenoids. Bioactive compounds of citrus modulate signaling pathways and interact with signaling molecules such as apoptotic and cell cycle (P53, P21, etc.) and thus have a wide range of pharmacological activities, including anti-inflammatory, anti-cancer and oxidative stress. The findings discussed in this review strongly support their potential as anti-cancer agents. Therefore, the purpose of this review was to examine the effects of active compounds in citrus as a therapy agent in cancer treatment. © 2021 Bentham Science Publishers
Bedaquiline: Current status and future perspectives
No full textThe development of drug-resistant tuberculosis (TB) is a major threat worldwide. Based on World Health Organization (WHO) reports, it is estimated that more than 500 000 new cases of drug-resistant TB occur annually. In addition, there are alarming reports of increasing multidrug-resistant TB (MDR-TB) and the emergence of extensively drug-resistant TB (XDR-TB) from different countries of the world. Therefore, new options for TB therapy are required. Bedaquiline (BDQ), a novel anti-TB drug, has significant minimum inhibitory concentrations (MICs) both against drug-susceptible and drug-resistant TB. Moreover, BDQ was recently approved for therapy of MDR-TB. The current narrative review summarises the available data on BDQ resistance, describes its antimicrobial properties, and provides new perspectives on clinical use of this novel anti-TB agent. © 2021 The Author(s
Characteristics of Clostridioides difficile colonization in Ilamian children
No full textBackground: The increasing colonization with Clostridioides difficile in paediatric hospitalized population is a well known event; however, its prevalence in Iranian children has not effectively been identified yet. Objective: The objective of this study was to determine the intestinal-carriage rates of C. difficile and molecular characterization of C. difficile in the Ilamian pediatric population from May 22, 2018, until September 22, 2018. Materials and Methods: Eighty samples were obtained from 40 children aged <5 years, at day 0 of their hospitalization (N=40 samples), to determine community-associated colonization, and then at day 5 days after hospitalization (N=40 samples), to determine healthcare associated colonization. The stool samples were examined for C. difficile, and isolated strains were evaluated for production of Clostridial toxins A/B and molecular characterizations. Results: The colonization rates of C. difficile and toxigenic C. difficile were 10 (8/80) and 3.75 (3/80), respectively. Based on the age group, the intestinal-carriage rates of C. difficile were 37.5, 50, and 12.5 in children � 1, 1-3, and 3-5 years old, respectively. Our findings have revealed eight distinct ribotypes. Our findings have revealed eight distinct ribotypes of C. difficile isolates. Three out of 8 (37.5) of C. difficile isolates were considered as community-associated colonization and belonged to ribotypes 7, 8, and 9. Conclusion. Our findings suggest the need of confirmation by further epidemiological studies in Iranian children. Given that the 37.5 of cases observed were community-associated, estimates of the incidence of C. difficile infections, that include only hospitalized children, may largely underestimate the burden of disease in children
Neutrophil-to-Lymphocyte Ratio as a Poor Prognostic Factor in Iranian COVID-19 Patients
No full textBackground: We aimed to accumulate evidence that suggests the potential role of neutrophil-to-lymphocyte ratio (NLR) in determining the prognostic factor for COVID-19 patients. Methods: A cohort of COVID-19 hospitalized patients at the Ilam University of Medical Sciences was analyzed. Logistic regression models were performed to identify the potential role of NLR in determining the prognostic factor for COVID-19 patients. Results: The total number of in-hospital mortality was 43/328 (13.1). Multivariate analysis identified that there was a 26 higher risk of in-hospital death for each unit increase in NLR (Odds ratio OR = 1.08; 95% confidence interval 95% CI, 1.01 to 1.14; p = 0.0147). Multivariate analysis identified that there was an 8% higher risk of in-hospital death for each unit increase in NLR (Odds ratio OR = 1.08; 95% confidence interval 95% CI, 1.01 to 1.14; p = 0.0147). Compared with patients in the NLR < 5 group, the NLR of patients in the NLR � 5 group had a 16-fold higher risk of mortality (OR = 16.04; 95% CI, 1.14 to 224.95; p = 0.0395) after adjustment for potential confounders. Conclusions: NLR is an independent risk factor of mortality COVID-19 patients. © 2021 Verlag Klinisches Labor GmbH. All rights reserved
Melatonin and doxorubicin co-delivered via a functionalized graphene-dendrimeric system enhances apoptosis of osteosarcoma cells
No full textA functionalized graphene-dendrimeric system was designed via Fe3O4 nanoparticle (NP) as a magnetic nanocarrier for co-delivery of doxorubicin (DOX) and melatonin (MLT). Accordingly, β-Cyclodextrin (β-CD) was modified by creating amine functional groups. The modified β-CD was grafted with Graphene oxide (GO), and the resulting platform gain many functional groups, including the hydroxyl (-OH), carboxylic acid (-COOH), and amine functional groups (�NH2). Finally, magnetic NPs were synthesized on the prepared platform to efficiently controlling and targeting drugs to tumor sites. The human osteosarcoma cell lines including Saos-2 and MG-63, as well as Human Bone Marrow Mesenchymal Stem Cells (hBM-MSC) line, were used to determine the in vitro biological effects of the functionalized graphene-dendrimeric system. The magnetic nanocarrier has encapsulation efficiency (EE) values of 99.92 for DOX and 21.5 for MLT. The biocompatibility tests of the nanocarrier revealed that the magnetic nanocarrier was appropriate as a drug carrier. Co-delivery of DOX and MLT with an efficiently anticancer performance was also was confirmed by cellular uptake, 4�,6-diamidino-2-phenylindole (DAPI) staining, and apoptosis analysis in comparison with free DOX and MLT. Moreover, there was a synergy in the antitumor effect when MLT was combined with DOX, especially in the nano-formulation form, which may be due to the down-regulation of X-linked Inhibitor of Apoptosis (XIAP), survivin, and human telomerase catalytic subunit (hTERT) (p < 0.0001). Overall, the result of our study suggests that the designed carrier is a promising nanocarrier for targeted co-delivery of DOX and MLT with improved anticancer efficacy in cancer cells and thus reduced toxicity in normal cells. © 2020 Elsevier B.V
Cytotoxic effect of define concentration of yarrow (achillea millefolium) extract used in iranian traditional medicine on ags human gastric cancer cell-line
No full textGastric cancer is one of the main cancer-related death causes in the world threatening almost 12 million human lives by 2020. Achillea millefolium L. (yarrow) with domestic Iranian name of Bumadaran, has been as a curative plant for several medical conditions for a long time. Its antimicrobial and wound healing effects have been reported and in this study, we aimed to survey the in-vitro cytotoxic and anti-cancer effects of this plant. After taxonomically identification of Achillea millefolium L., its hydroalcoholic extract was extracted and the AGS gastric cancer and L-929 normal fibroblastic cell-lines with treated by the different concentrations of extract in 3 time periods (24, 48, and 72 hrs). MTT assay was performed for the evaluation of cytotoxic effects. The 24 hrs treatment did not affect cell survival, notably, while the concentrations of 64 and 16 µg/ml were determined as IC50 concentrations at 48 and 72 hrs incubation times respectively. The 72 hrs incubation time with 16 µg/ml showed the best effectiveness on cancerous cell-line while being safe for normal cell-line. The long-term treatment of AGS cancer cell-line by low concentrations of yarrow extract could be useful for the cytotoxicity upon this type of cancerous cells. © 2021 Assiut University. All rights reserved