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Anti-inflammatory effect of KW-2449 on autoimmune encephalomyelitis: An experimental study on mice
No full textBackground: The KW-2449 is a novel multikinase inhibitor that inhibits FLT3, ABL, ABL-T315I, and Aurora A. FLT3 and Aurora A kinases play an important role in the pathogenesis of multiple sclerosis (MS). KW-2449 could modulate immune cells, but the immunomodulatory effects of KW-2449 on experimental autoimmune encephalomyelitis (EAE) have not been investigated yet. The aim of the present study is to investigate the effects of KW-2449 on EAE mouse model. Methods: In this study, C57BL/6 EAE mice were orally treated with (10 mg/kg/day) KW-2449 solution and compared with EAE and control mice. Following the treatment, histological analyses were performed on the brain and cerebellum to evaluate the pathological score. The gene expression levels of tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), and chemokine (C-C motif) ligand 2 (CCL2) were measured using qRT-PCR. The serum levels of TNF-α, IL-6, CCL-2 and MMP-2 were determined by using quantitative enzyme-linked immunosorbent assay (ELISA). Results: The results indicated that the clinical score, the infiltration of inflammatory cells and the demyelination in EAE mice treated with KW-2449 decreased significantly compared to control groups. KW-2449 also decreased TNF-α, IL-6, CCL-2 inflammatory cytokines, and MMP-2 in both brain mRNA expressions and serum levels of EAE mice. Conclusion: The KW-2449, aging as a multi-kinase inhibitor, modulates the inflammatory responses of cytokine cascades either in the brain or in plasma and reduces EAE pathogenesis manifestation. © 2021 Bentham Science Publishers
A multicenter retrospective study of clinical features, laboratory characteristics, and outcomes of 166 hospitalized children with coronavirus disease 2019 (COVID-19): A preliminary report from Iranian Network for Research in Viral Diseases (INRVD)
No full textBackground: The objectives of this study were to analyze the clinical features and laboratory profiles and risk factors associated with critical illness of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: One hundred and sixty-six coronavirus disease 2019 (COVID-19) Iranian pediatric patients were recruited through a collaborative research network between March and May 2020. Demographics, clinical, laboratory, and radiological results were obtained from patient files. Results: Of 166 patients, 102 (61) and 64 (39) were males and females, respectively. Ninety-six (57.8) and 70 (42.2), had moderate and severe conditions, respectively. Thirty (18) of patients died. The common symptoms were fever (73), cough (54), and shortness of breath, headache decrease in neutrophil and platelet counts; increase values in lactate dehydrogenase, decrease in the blood pH and HCO3 were significantly associated with the disease severity. 54 and 56 of patients showed abnormal radiographic appearance in Chest X-ray and in chest computed tomography scan, respectively. Sixty-one (36.7) of patients were referred to intensive care unit (ICU). The coexistence of comorbidity was the main factor associated with ICU admission, shock, arrhythmia, acute kidney injury, acute respiratory distress syndrome, acute cardiac injury, and death. Conclusions: We describe a higher than previously recognized rate of COVID-19 mortality in Iranian pediatric patients. Epidemiological factors, such as the relatively high case fatality rate in the country and the presence of underlying diseases were the main factors for the high death rate. © 2021 Wiley Periodicals LL
Antiviral therapeutic potential of curcumin: An update
No full textThe treatment of viral disease has become a medical challenge because of the increasing incidence and prevalence of human viral pathogens, as well as the lack of viable treatment alternatives, including plant-derived strategies. This review attempts to investigate the trends of research on in vitro antiviral effects of curcumin against different classes of human viral pathogens worldwide. Various electronic databases, including PubMed, Scopus, Web of Science, and Google Scholar were searched for published English articles evaluating the anti-viral activity of curcumin. Data were then extracted and analyzed. The forty-three studies (published from 1993 to 2020) that were identified contain data for 24 different viruses. The 50 cytotoxic concentration (CC50), 50 effective/inhibitory concentration (EC50/IC50), and stimulation index (SI) parameters showed that curcumin had antiviral activity against viruses causing diseases in humans. Data presented in this review highlight the potential antiviral applications of curcumin and open new avenues for further experiments on the clinical applications of curcumin and its derivatives. © 2021 by the authors. Licensee MDPI, Basel, Switzerland
Synthesis of zinc oxide / reduced graphene oxide nanocatalyst and its efficiency in photocatalytic degradation of paraquat herbicide
No full textBackground and purpose: Paraquat (PQ) is the third most widely used herbicide in the world. This herbicide has the potential to damage cell membranes by lipid peroxidation and free radical attack. In this study, ZnO /rGO (ZG) heterogeneous photocatalyst was used for oxidation of PQ herbicide in aqueous solution under ultraviolet light irradiation. Materials and methods: In this experimental study, EDS, FE-SEM, BET, XRD, and FTIR analyzes were performed to determine the characteristics of synthesized catalyst. Effect of operating parameters, including solution pH, catalyst concentration, rGO percentage loading, PQ concentration, and UV-light intensity on degradation of PQ was studied in batch mode. Residual concentration of PQ and type and toxicity of intermediate compounds were measured by HPLC and GC-MS, respectively and toxicity test was done by Daphnia Magna. Studies on reusability of catalysts, effect of radical scavengers, and inorganic anions were also performed. Results: Under optimum conditions (pH=7, catalyst loading=10, catalyst concentration=0.5 g/l, PQ concentration= 10mg/l, and UV-light intensity=220 mw/cm2), degradation and mineralization rate were 91.61 and 51 in 120 minutes, respectively. Radical scavenger experiments showed electron as the most effective factor in PQ oxidation process in ZG/UV system. In samples of agricultural run-off, degradation efficiency was 58.27. Biotoxicity test also showed that toxic unit in pesticide-containing samples was 61.72 in raw samples that decreased to 12.19 in treated samples after 96 hours. Conclusion: ZG/UV process has high efficiency and excellent catalytic activity, so, it the can be successfully used to degrade organic pollutants, especially pesticides, in wastewater. © 2021, Mazandaran University of Medical Sciences. All rights reserved
Molecular Characterization, Virulence Determinants, and Antimicrobial Resistance Profile of Methicillin-Resistant Staphylococcus aureus in the North of Iran; a High Prevalence of ST239-SCC mec III/t037 Clone
No full textObjectives: Emergence and prevalence of methicillin-resistant Staphylococcus aureus (MRSA) have become a major universal health concern, limiting therapeutic options. Methods: A total number of 37 MRSA isolates, including 19 clinical isolates from hospitalized patients and 18 colonizing isolates from health care workers were identified from 3 hospitals, in Gorgan, North of Iran. Antimicrobial susceptibility test was performed using the disk diffusion method and E-test. The presence of virulence and antibiotic resistance determinants were evaluated by PCR. The genotypical characterization was further analyzed using multi-locus sequence, spa, staphylococcal cassette chromosome, mec (SCCmec), and agr typing. Results: The frequency of MRSA among S. aureus isolates was 38.14 (37/97). The most frequent S. aureus resistant isolates were found to be obstinate against penicillin (98) and gentamicin (82.5). Additionally, the lowest resistance rates were found against daptomycin (0), vancomycin (2.7), and quinupristin-dalfopristin (5.4). All MRSA isolates were susceptible to daptomycin with minimum inhibitory concentration (MIC)50/MIC90 of 0.25/0.5 μg/mL. One isolate belonging to sequence type 239 (ST239)-SCCmecIII/t037 clone (MIC �16 μg/mL) was resistant to vancomycin. All but 1 isolate that shares ST22-SCCmec IV/t790 strain were positive for both tsst and pvl genes. The most predominant MRSA isolates (27) were associated with ST239-SCCmec III/t037, and ST239-SCCmec III/t924 (16.2) clones, subsequently. In our study, circulating MRSA strains were genetically diverse with a high prevalence of ST239-SCCmec III/t037 clone. Conclusion: These findings emphasize the need for future and continuous surveillance studies on MRSA to prevent the dissemination of existing multidrug resistance MRSA clones in an effective manner. © 2021 S. Karger AG, Basel. All rights reserved
Epidemiological characteristics and outcomes of COVID-19 in asymptomatic versus symptomatic patients
No full textBackground. The clinical manifestations of COVID-19 are different, which can be attributed to asymptomatic carriers, acute respiratory disease and pneumonia with different severities. The aim of this study was to compare the epidemiological characteristics and outcomes of COVID-19 in patients with clinical symptoms versus asymptomatic patients. Methods. In this retrospective cohort study, the epidemiological characteristics of two groups of patients, with clinical symptoms (n = 38,630) and without clinical symptoms who were definitive cases of COVID-19 (n = 2,327) were investigated in the southwestern of Iran. Chi-square test was used to evaluate the differences between qualitative variables in the two study groups. Results. Of 40,957 patients with COVID-19, 2,327 (5.68) were asymptomatic, of whom 1391 (59.77) were males, 1841 patients (79.11) had a history of contact with definite or suspected cases of COVID-19. Asymptomatic patients were older than symptomatic cases. Patients with clinical symptoms had higher mortality rate than asymptomatic patients (2.68 in symptomatic patients vs 0 in asymptomatic patients). Conclusion. According to the results of our study, the detected viral load in asymptomatic individuals was similar to that of symptomatic patients, indicating that asymptomatic infections can potentially transmit the disease. Therefore, screening and detection of asymptomatic cases is an important and key measure in prevention and early control of COVID-19 worldwide. © 2021 Pacini Editore S.p.A.. All rights reserved
Toxin gene profiles and antimicrobial resistance of Clostridioides difficile infection: a single tertiary care center study in Iran
No full textBackground and Objectives: Due to the reduced susceptibility of clinical Clostridioides difficile strains in hospitals to various antimicrobial agents, the importance of antimicrobial susceptibility testing (ASTs) has increased. This study aimed to investigate the toxin gene profiles and the antimicrobial resistance of C. difficile isolated from hospitalized patients suspected of having Clostridioides difficile infection (CDI) in Tehran, Iran. Materials and Methods: The stool samples were obtained from a hospitalized patients. The samples were shocked by al-cohol and the patients cultured on cycloserine-cefoxitin-fructose agar in anaerobic Conditions. Toxin assay was performed for detection of toxinogenic isolates. An antibiotic susceptibility test was done. Furthermore, their genome was extracted for PCR to confirm C. difficile and detect toxin gene profile. Results: Toxigenic C. difficile were identified in 21 of the 185 stool samples (11.3). PCR detected seven toxin gene profiles; the highest prevalence was related to tcdA+B+, cdtA+B- toxin gene profile (57.1). There were 14.3 and 28.6 resistant rates of the isolates towards vancomycin and metronidazole with the toxin gene profiles; tcdA+B+, cdtA±B+; and tc-dA+B-, cdtA-B+. All resistant isolates to moxifloxacin, clindamycin, and tetracycline were belonged to the toxin gene profiles; tcdA+B+, cdtA+B+; tcdA+B+, cdtA+B-, and tcdA-B+, cdtA+B-. Conclusion: Relative high resistance was detected towards metronidazole and vancomycin, although, still have acceptable activity for CDI treatment. However, a proper plan for the use of antibiotics and more regular screening of C. difficile antibiotic resistance seems necessary. © 2021 The Authors. Published by Tehran University of Medical Sciences
Evaluation of the effect of co-administration of irak inhibitor and pioglitazone on ppar-γ, glut-4, tnf-α, and leptin genes expression in adipose tissue of insulin-resistant mice
No full textBackground: The worldwide prevalence of diabetes is increasing. Diabetes is a complex disease that results from impaired secretion of insulin or insulin resistance. In adipose tissue, insulin increases glucose uptake by stimulating the transfer of glucose transporter type 4 (GLUT-4) to the plasma membrane. In this study, the effect of IRAK inhibitor (IRAKi) and pioglitazone on genes expression in adipose tissue of insulin resistant mice was evaluated. Methods: Mice were randomly divided into 6 groups (n= 8 each), five groups of which were fed a high-fat diet and one group received a normal diet for 12 weeks. The treatment with pioglitazone and IRAKi was performed for 2 weeks. At the end of the study, the animals were sacrificed and the adipose tissue and blood samples were collected. The expression of GLUT4, TNF-α, peroxisome proliferator-activated receptor gamma (PPARγ), and Lepin were determined by real-time PCR in the adipose tissue. The malondialdehyde (MDA) level and total antioxidant capacity (TAC) in serum were measured. Results were analyzed by SPSS 22. Results: The data showed that the combination of IRAKi and pioglitazone increased PPARγ expression, leptin and TAC levels in serum, and reduced TNF-α expression and MDA levels. The GLUT4 expression in adipose tissue was not significant between studied groups. Pioglitazone and IRAKi improved insulin function by inhibiting inflammation signaling. Conclusion: According to the results of this study, IRAKi may be an appropriate target for inhibiting inflammation and related disorders, including insulin resistance. © 2021 The Author(s); Published by Kerman University of Medical Sciences
Application of magnetic activated carbon as a catalyst in catalytic ozonation process (Cop) for removal and mineralization of humic acid from aqueous solution
No full textHumic acid (HA) is a natural organic matter, which is naturally present in raw water sources due to the decomposition of dead animals and plants. Therefore, the catalytic properties of a carbonaceous nanocomposite in the catalytic ozonation process (COP) of HA were investigated, and the results were compared with those obtained from the single ozonation process (SOP). Magnetic carbona-ceous nanocomposite, as a novel catalyst, was applied to optimize the conditions for the removal of HA in the COP, and the influential parameters such as pH, retention time, catalyst dosage, and addition of radical scavengers were all evaluated. This is an experimental study in which the removal of HA by a COP was investigated in a cylindrical glass reactor (a useful volume of 250 mL) with a semi-continuous flow. Catalyst raw material was the granular activated carbon (GAC) that has been stabilized on Fe3 O4 nanoparticles by the calcination method. The results revealed that by increasing the retention time, pH, and catalyst dosage, HA and TOC removal efficiencies by both process (SOP and COP) was increased. The highest removal efficiencies of HA and TOC in the COP process were 95 and 87.67, respectively while their removal efficiencies in the SOP process were 76.8 and 67.1 under the conditions including pH of 9, contact time of 60 min, and HA concentrations of 15 mg/L. The highest removal of the HA by the SOP and catalyst adsorption was obtained to be 76 and 5.8 after 60 min, respectively; however, it was observed to be 95.7 in the COP, in the same contact time. The presence of tert-butanol alcohol (TBA) did not significantly affect the removal of the HA in the COP. Practically, this study revealed that the magnetically activated carbon catalyst could be potentially employed in the COP for the treatment of the water having average concentrations of HA substances. © 2021 Desalination Publications. All rights reserved
An intervention to increase hepatitis C virus diagnosis and treatment uptake among people in custody in Iran
No full textBackground: Iran is among countries with high opioid agonist therapy (OAT) coverage in prisons, which provides an infrastructure to increase feasibility of HCV programs. We aimed to evaluate the impact of an intervention to improve HCV screening, diagnosis, and treatment, including alongside the provision of OAT, in an Iranian prison. Methods: During July-December 2018, in the Gorgan prison, all incarcerated adults (>18 years) received HCV antibody rapid testing and, if positive, provided a venepuncture sample for HCV RNA testing. Participants with positive RNA received direct-acting antiviral (DAA) therapy (Sofosbuvir/Daclatasvir) for 24 or 12 weeks, respectively, for those with and without cirrhosis. Response to treatment was measured by the sustained virological response at 12 weeks post-treatment (SVR12). Results: Among 2015 incarcerated people with a median age of 35 years (IQR:29�41), the majority were male (97%), had not finished high school (68%), and had a history of drug use (71%), of whom 15% had ever injected drugs. A third of participants were receiving OAT, including 54% of those who had ever injected. HCV antibody prevalence was 6.7%, and RNA was detected in 4.6% of all participants; this prevalence was 32.6% and 24.7% among those with a history of injection, respectively. Treatment uptake was 82% (75/92) and was similar among people on OAT and those with a history of injection (81%). The majority completed treatment in prison and were available for SVR12 assessment (71%, 53/75). Achieved SVR12 was 100% (53/53) based on the available case analysis; those who did not have available SVR12 were released either prior to treatment initiation or completion (n = 39). Conclusion: The availability of OAT infrastructure should be considered as an opportunity for enhancing HCV care in prisons. Where resources are limited, the prison harm reduction network could be used to design targeted HCV programs among people who are at higher risk of infection. © 2021 Elsevier B.V