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Protective Effect of Thymoquinone Against Fluoxetine-Induced Liver Damage Through Enhancing Antioxidant and Anti-Inflammatory System in Male Rats
No full textIntroduction: Fluoxetine is a drug used to treat depression and has toxic effects on liver cells. Thymoquinone, the most important active ingredient in black seed (Nigella sativa), has several pharmacological effects, including sedation, reduced motor activity, and muscle relaxation. This study aimed to investigate the effect of thymoquinone on reducing the hepatotoxicity effects of fluoxetine. Methods: A total of forty Wistar rats were treated with fluoxetine, thymoquinone, and silymarin for four weeks. Different techniques, including biochemical analysis, qRT-PCR, and histopathological examination, were performed to investigate the effect of drugs on the oxidant/antioxidant system and inflammatory responses. Results: Our results revealed that fluoxetine increased lipid peroxidation and protein oxidation and inhibited antioxidant systems in rat hepatocytes. In addition, fluoxetine increased the expression of the proinflammatory cytokine TNF-α and also the migration of lymphocytes to liver cells. In contrast, thymoquinone (10, 20, and 40 mg/kg) significantly decreased MDA, PC, and TNF-α levels. Moreover, thymoquinone enhanced the catalytic activity of antioxidant enzymes, including catalase, superoxide dismutase, glutathione peroxidase, and GSH. Thymoquinone only at a dose of 40 mg/kg can inhibit the infiltration of lymphocytes into the liver. Conclusion: Thymoquinone exerted liver protective effects against fluoxetine hepatotoxicity by inducing antioxidant and anti-inflammatory activities. This study suggests that thymoquinone, in combination with fluoxetine, can be used to reduce liver damage
Expression of Brucella abortus Omp25 Protein in Lactococcus lactis Probiotic Bacteria
No full textBackground and purpose: The sequence of Omp25 is conserved in all Brucella species. The high antigenicity of the product of this gene stimulates the host’s immune system. Using engineered probiotic bacteria is an appropriate method for vaccine transport. The aim of this study was to express the Omp25 of the Brucella abortus pathogenic bacterium in Lactococcus lactis probiotic bacterium. Materials and methods: In this experimental study, the required vector was designed and synthesized to include the gene of interest and a signal peptide (pNZ8148-Usp45-Omp25). E. coli strain TOP10F was transformed using the pNZ8148-Usp45-Omp25 expression vector based on induction by nisin. The recombinant plasmid was extracted from the transformed bacteria using a plasmid extraction kit. The L. lactis was transformed by pNZ8148-Usp45-Omp25 vector using electroporation. Evaluation of the expression of Omp25 gene at the RNA level was assessed by reverse transcription method and confirming the presence of recombinant Omp25 protein in the engineered bacteria using SDS-PAGE method. Results: Successful expression of B. abortus Omp25 in L. lactis was verified by RT-PCR. Subsequently, the proteins were separated based on molecular weight using sodium dodecyl sulfate– polyacrylamide gel electrophoresis (SDS-PAGE). The protein expression analysis showed the expression of Omp25 as a 25kDa extra band in transformed L. lactis compared to the L. lactis receiving the vector lacking the target gene. Conclusion: This study shows that Omp25 is expressed in L. lactis transformed via pNZ8148-Usp45-Omp25 by electroporation. Transformed L. lactis can be successfully used as a subunit oral vaccine in prevention of Brucellosis
Systemic lupus erythematosus following SARS-CoV-2 vaccination; a review of literature
No full textFrom March 2020, the coronavirus disease 2019 (COVID-19) pandemic challenged public health and healthcare systems worldwide. Viral infection is one of the environmental factors that has been associated with the development, relapse, or exacerbation of systemic lupus erythematosus (SLE). SLE patients are at an increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) because of immune system dysfunction related to their disease as well as immunosuppression medications. So far, the most effective way to reduce SARS-CoV-2 infection-induced hospitalization and death is vaccination. On the other hand, SLE patients present distinct challenges related to the safety and effectiveness of SARS-CoV-2 vaccination. We have reviewed some reports on the onset or flare of SLE post-COVID-19 vaccination. Of note, the mRNA COVID-19 vaccines are associated with increased SLE disease activity, more frequently than the other types of COVID-19 vaccines
PI3K/AKT/mTOR signaling pathway modulation by circular RNAs in breast cancer progression
No full textThe PI3K/Akt/mTOR signaling pathway is responsible for many cellular behaviors, including survival, growth, and proliferation. A newly identified RNA, circular RNA (circRNA), plays a crucial role in the regulation of gene expression. The upregulation of the PI3K/Akt pathway through dysregulated circRNAs promotes breast tumor initiation, growth, and progression. The dysregulation of PI3K/Akt-regulating circRNAs seems to be directly correlated with breast cancer clinical features, including overall survival, tumor size, cancer stage, and lymph node metastasis. In addition, targeting these circRNAs may be a promising option in cancer-targeted therapy. Understanding the molecular pathogenesis of the circRNA-PI3K/AKT axis may give the insight to develop new therapeutic and diagnostic approaches for breast cancer therapy. Here we reviewed the expression and functions of PI3K/AKT-regulating circRNAs, and their correlation with breast cancer clinical features. In addition, the potential of PI3K/AKT-regulating circRNAs as diagnostic/prognostic biomarkers or therapeutic targets was discussed
Ethnic differences in the lifestyle behaviors and premature coronary artery disease: a multi-center study
No full textBackground: Diverse ethnic groups that exist in Iran may differ regarding the risk factors such as hypertension, hyperlipidemia, dyslipidemia, diabetes mellitus, and family history of non-communicable disease. Premature Coronary Artery Disease (PCAD) is more endemic in Iran than before. This study sought to assess the association between ethnicity and lifestyle behaviors in eight major Iranian ethnic groups with PCAD. Methods: In this study, 2863 patients aged ≤ 70 for women and ≤ 60 for men who underwent coronary angiography were recruited in a multi-center framework. All the patients’ demographic, laboratory, clinical, and risk factor data were retrieved. Eight large ethnicities in Iran, including the Farses, the Kurds, the Turks, the Gilaks, the Arabs, the Lors, the Qashqai, and the Bakhtiari were evaluated for PCAD. Different lifestyle components and having PCAD were compared among the ethnical groups using multivariable modeling. Results: The mean age of the 2863 patients participated was 55.66 ± 7.70 years. The Fars ethnicity with 1654 people, was the most subject in this study. Family history of more than three chronic diseases (1279 (44.7%) was the most common risk factor. The Turk ethnic group had the highest prevalence of ≥ 3 simultaneous lifestyle-related risk factors (24.3%), and the Bakhtiari ethnic group had the highest prevalence of no lifestyle-related risk factors (20.9%). Adjusted models showed that having all three abnormal lifestyle components increased the risk of PCAD (OR = 2.28, 95% CI: 1.04–1.06). The Arabs had the most chance of getting PCAD among other ethnicities (OR = 2.26, 95%CI: 1.40–3.65). While, the Kurds with a healthy lifestyle showed the lowest chance of getting PCAD (OR = 1.96, 95%CI: 1.05–3.67)). Conclusions: This study found there was heterogeneity in having PACD and a diverse distribution in its well-known traditional lifestyle-related risk factors among major Iranian ethnic groups
Targeting the vital non-structural proteins (NSP12, NSP7, NSP8 and NSP3) from SARS-CoV-2 and inhibition of RNA polymerase by natural bioactive compound naringenin as a promising drug candidate against COVID-19
No full textThe prevalence of SARS-CoV-2-induced respiratory infections is now a major challenge worldwide. There is currently no specific antiviral drug to prevent or treat this disease. Infection with COVID-19 seriously needs to find effective therapeutic agents. In the present study, naringenin, as a potential inhibitor candidate for RNA Polymerase SARS-CoV-2 was compared with remdesivir (FDA-approved drug) and GS-441,524 (Derivative of the drug remdesivir) by screening with wild-type and mutant SARS-CoV-2 NSP12 (NSP7-NSP8) and NSP3 interfaces, then complexes were simulated by molecular dynamics (MD) simulations to gain their stabilities. The docking results displayed scores of -3.45 kcal/mol and -4.32 kcal/mol against NSP12 and NSP3, respectively. Our results showed that naringenin had ΔG values more negative than the ΔG values of Remdesivir (RDV) and GS-441,524. Hence, naringenin was considered to be a potential inhibitor. Also, the number of hydrogen bonds of naringenin with NSP3 and later NSP12 are more than Remdesivir and its derivative. In this research, Mean root mean square deviation (RMSD) values of NSP3 and NSP12with naringenin ligand (5.55±1.58 nm to 3.45±0.56 nm and 0.238±0.01 to 0.242±0.021 nm, respectively showed stability in the presence of ligand. The root mean square fluctuations (RMSF) values of NSP3 and NSP12 amino acid units in the presence of naringenin in were 1.5 ± 0.31 nm and 0.118±0.058, respectively. Pharmacokinetic properties and prediction of absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of naringenin and RDV showed that these two compounds had no potential cytotoxicity
Investigation of the therapeutic role of native plant compounds against colorectal cancer based on system biology and virtual screening
No full textThis study investigated the anticancer effects of compounds extracted from native plants on colon cancer following drug–target-network analysis and molecular docking. Based on the ChEBI database, compounds were identified in medicinal plants and weeds in the Chaharmahal and Bakhtiari provinces of Iran. A drug–target network was constructed based on candidate colon cancer protein targets and selective compounds. Network pharmacology analysis was conducted against the identified compounds and subjected to molecular docking studies. Based on molecular dynamics simulations, the most efficient compounds were evaluated for their anticancer effects. Our study suggests that TREM1, MAPK1, MAPK8, CTSB, MIF, and DPP4 proteins may be targeted by compounds in medicinal plants for their anti-cancer effects. Multiorthoquinone, Liquiritin, Isoliquiritin, Hispaglabridin A, Gibberellin A98, Cyclomulberrin, Cyclomorusin A, and Cudraflavone B are effective anticancer compounds found in targeted medicinal plants and play an important role in the regulation of important pathways in colon cancer. Compounds that inhibit MIF, CTSB, and MAPK8-16 appear to be more effective. Additional in vitro and in vivo experiments will be helpful in validating and optimizing the findings of this study
Demographic and clinical features of patients suffering acute intoxication with an emphasis on cardiovascular complications; an observational case series
No full textIntroduction: Acute intoxication is an ongoing health issue worldwide and one of the most prevalent causes of hospital admission. Investigation of the features of acute intoxication occurrence allows for effectively planning preventive measures and required health resources. Objectives: The current study investigated acute intoxication’s demographic and clinical characteristics in an Iranian province. Patients and Methods: An observational case-series study was designed to investigate patients suffering from acute intoxication and admitted to two referral tertiary teaching hospitals over six months. Demographic data, vital parameters comprising neurologic, respiratory, and hemodynamic status, clinical symptoms, and blood analysis data were prospectively recorded. Data analysis was conducted using SPSS version 21 software. Results: In total, 447 patients were included in the study (3.5% of all emergency admission). The mean age of patients was 33 ± 16 (4-88) years, and 190 (42.6%) patients were female. Seventy percent of patients were under 40 years. The male patients were significantly older than the female ones (P = 0.001). Hospital mortality was 2.7%. Circulatory shock and respiratory apnea occurred separately in 13 (2.9%) patients, and alteration in consciousness affected 30%. Reduced arterial blood saturation and visual acuity were observed in 14% and 3.6% of the patients. A cumulative prevalence of electrocardiogram anomalies of 38% was also observed. The most prevalent electrolyte disorder was hypocalcemia (12%), followed by hypokalemia (10%); 17 % of patients were affected by severe blood acidosis. Conclusion: Acute intoxication is a medical emergency with a high risk of death. A multi-organ-based diagnosis and therapeutic approach should be implemented to manage the potentially lethal complications as soon as possible. Effective preventive planning for reducing acute intoxication should be performed concerning the socioeconomic status of the targeted population
The effects of gallic acid on inflammation and oxidative stress in valproic acid-induced hepatotoxicity in rats
No full textValproic acid (VPA) is one of the most broadly used drugs for epilepsy disorders worldwide. Despite its great effectiveness, this drug causes liver toxicity. In this work, the effects of gallic acid (GA) on hepatic injury caused by VPA were investigated. We randomly divided 48 Wistar rats into 6 groups. Group 1 was considered as control. The second group received only valproic acid. The third group was a positive control group which was administrated with VPA and then Silymarin. The fourth, fifth, and sixth groups also received GA after taking valproic acid. Then serum lipid profile, alkaline phosphatase (ALP), aspartate transaminase (AST), alanine aminotransferase (ALT), inflammatory factor interleukin-1beta (IL-1β), and liver biomarkers of oxidative stress were assessed. VPA caused a substantial increase (p < 0.05) in AST, ALP, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ALT, triglyceride (TG), blood urea nitrogen (BUN), very low-density lipoprotein cholesterol (VLDL-C), creatinine (Cr), urea, protein carbonyl (PC), and malondialdehyde (MDA) levels plus serum inflammatory factor IL-1β. This drug also caused an obvious decrease (p < 0.05) in high-density lipoprotein cholesterol (HDL-C), catalase (CAT), ferric-reducing antioxidant power (FRAP), vitamin (Vit) C, and superoxide dismutase (SOD). Exposure to GA not only leads to a considerable improvement (p < 0.05) against hepatic damage caused by valproic acid, but also increases the antioxidant system and reduces serum ALP, TC, AST, TG, ALT, BUN, LDL-C, Cr, VLDL-C, urea, PC, and MDA levels. GA with its antioxidant properties shows a protective effect against hepatotoxicity caused by valproic acid. This antioxidant reduces the toxicity induced by the VPA by reducing oxidative stress and inflammatory effects of IL-1β
Anticonvulsant effect of quercetin in pentylenetetrazole (PTZ)-induced seizures in male mice: The role of anti-neuroinflammatory and anti-oxidative stress
No full textBackground: Epilepsy is one of the major neurological disorders. The inflammatory process and oxidative stress are closely related to seizure progression. Quercetin is a flavonoid with anti-inflammatory and antioxidant properties as well as neuroprotective effects. We aimed to evaluate the effect of quercetin on pentylenetetrazole- (PTZ-) induced seizures in male mice focusing on its possible anti-neuroinflammatory and anti-oxidative stress. Methods: In this study, 50 male NMRI mice were divided into five groups (n = 10) and given the following treatments: normal saline, quercetin at doses of 10, 20, and 40 mg/kg, and diazepam at a dose of 10 mg/kg. In order to induce seizures, PTZ was administered intravenously. Drugs were administered intravenously 60 min before the seizure induction. The seizure threshold was measured, and finally, malondialdehyde (MDA), total antioxidant capacity (TAC), and the gene expression of IL-1β, TNF-α, NLRP3, and iNOS were determined in the prefrontal cortex. Results: It was confirmed that quercetin increased the seizure threshold. And quercetin increased TAC, and decreased levels of MDA as well as gene expression of TNF- α, NLRP3, IL-1β, and iNOS in the prefrontal cortex at the time of seizure induction. Conclusion: It was suggested that the anticonvulsant effect of quercetin in PTZ-induced seizures in mice may be due to the reduction of inflammatory responses and oxidative stress in the prefrontal cortex