Comprehensive and updated review on anti-oxidant effects of Nigella sativa and its constituent, thymoquinone, in various disorders.

Several pharmacological effects were described for Nigella sativa (N. sativa) seed and it has been used traditionally to treat various diseases. In this review article, the updated and comprehensive anti-oxidant effects of N. sativa and its main constituent, thymoquinone (TQ), on various disorders are described. The relevant articles were retrieved through PubMed, Science Direct, and Scopus up to December 31, 2023. Various extracts and essential oils of N. sativa showed anti-oxidant effects on cardiovascular, endocrine, gastrointestinal and liver, neurologic, respiratory, and urogenital diseases by decreasing and increasing various oxidant and anti-oxidant marketers, respectively. The main constituent of the plant, TQ, also showed similar anti-oxidant effects as the plant itself. The anti-oxidant effects of different extracts and essential oils of N. sativa were demonstrated in various studies which were perhaps due to the main constituent of the plant, TQ. The findings of this review article suggest the possible therapeutic effect of N. sativa and TQ in oxidative stress disorders.

An overview of pharmacological effects of Crocus sativous and its constituents.

Crocus sativus L. was used for the treatment of a wide range of disorders in traditional medicine. Due to the extensive protective and treatment properties of C. sativus and its constituents in various diseases, the purpose of this review is to collect a summary of its effects, on experimental studies, both in vitro and in vivo. Databases such as PubMed, Science Direct, and Scopus were explored until January 2023 by employing suitable keywords. Several investigations have indicated that the therapeutic properties of C. sativus may be due to its anti-oxidant and anti-inflammatory effects on the nervous, cardiovascular, immune, and respiratory systems. Further research has shown that its petals also have anticonvulsant properties. Pharmacological studies have shown that crocetin and safranal have anti-oxidant properties and through inhibiting the release of free radicals lead to the prevention of disorders such as tumor cell proliferation, atherosclerosis, hepatotoxicity, bladder toxicity, and ethanol induced hippocampal disorders. Numerous studies have been performed on the effect of C. sativus and its constituents in laboratory animal models under in vitro and in vivo conditions on various disorders. This is necessary but not enough and more clinical trials are needed to investigate unknown aspects of the therapeutic properties of C. sativus and its main constituents in different disorders.

Protective effects of 4-methylumbelliferone on myocardial ischemia/reperfusion injury in rats through inhibition of oxidative stress and downregulation of TLR4/NF-κB/NLRP3 signaling pathway.

Myocardial ischemia-reperfusion injury (MI/R) has been found to be one of the important risk factors for global cardiac mortality and morbidity. The study was conducted to inquire into the protective effect of 4-methylumbilliferon (4-MU) against MI/R in rats and clarify its potential underlying mechanism. Animals were divided into four groups (n = 15) including sham, MI/R, MI/R + vehicle, and MI/R + 4-MU. MI/R was established in Wistar rats by occluding the left anterior descending (LAD) coronary artery for 30 min. 4-MU (25 mg/kg) was injected intraperitoneally before the induction of reperfusion. Cardiac function, fibrosis, oxidant/antioxidant markers, and inflammatory cytokines were evaluated using echocardiography, ELISA, and Western blot assay. As a result of MI/R induction, a decrease in left ventricular contractile function occurred along with increased cardiac fibrosis and tissue damage. The serum levels of TNF-α, IL-1ß, and IL-18 increased, while IL-10 decreased. Oxidant/antioxidant changes were evident with increased MDA levels and decreased GSH, SOD, and CAT in the MI/R group. Furthermore, the protein levels of TLR4, NF-κB, and NLRP3 were significantly increased in the heart tissue of MI/R group. Treatment with 4-MU significantly prevented the reduction of cardiac contractile function and its pathological changes as a result of MI/R by inhibiting the increase of serum inflammatory factors and improving the oxidant/antioxidant balance probably through the TLR4/NF-κB/NLRP3 axis. The results of a current study showed that 4-MU had a potential ability to attenuate the cardiac injury by reducing oxidative stress and inflammation in a TLR4/NF-κB/NLRP3-dependent mechanism.

Chest computed tomography severity score is a reliable predictor of mortality in patients with chronic obstructive pulmonary disease co-infected with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) pandemic is considered a global health crisis. The data related to chronic obstructive pulmonary disease (COPD) patients with COVID-19 are incomplete, especially the findings of the chest computed tomography (CT). The aim of the current study was to investigate the severity of the disease of COVID-19 in patients with COPD based on CT severity score and to evaluate its predictive power in the mortality of patients. METHODS: In a retrospective study, demographic, clinical, and CT scan findings of COPD patients with COVID-19 were extracted from March 2020 to February 2022. CT severity score was determined based on the extent and nature of involvement of lungs in CT scan findings. By performing receiver operating characteristics (ROC) and Kaplan-Meier survival analysis were determined the disease severity and survival probability. RESULTS: The most frequent radiological findings in chest CT scan included ground glass opacities (89.3%), consolidations (51.8%), crazy-paving pattern (46.4%), and septal thickening (35.7%). The mean CT severity score of deceased patients (34.61 ± 18.73) was significantly higher than recovered patients (16.71 ± 14.01, p < 0.001). Based on the ROC and Kaplan-Meier survival curves, it was revealed that CT severity score was a valuable criteria in the diagnosis of mortality in COPD patients with COVID-19. CONCLUSION: The findings of this study revealed that the CT severity scoring in COPD patients with COVID-19 was valuable in identifying poor prognosis, although further studies are needed.

Potential role of saffron and its components on miRNA levels in various disorders, a comprehensive review.

The potential therapeutic benefits of saffron and its active constituents have been investigated for the treatment of numerous illnesses. In this review, the impacts of saffron and its essential components on the levels of microRNAs (miRNAs) in different diseases have been delineated. Relevant articles were obtained through databases such as PubMed, Web of Sciences, Scopus, and Google Scholar up to the end of November 2022. miRNA expression has been altered by saffron and its active substances (crocin, crocetin, and safranal) which has been of great advantage in treating diseases such as cardiovascular, type 2 diabetes, cancers, gastrointestinal and liver disorders, central and peripheral nervous system disorders, asthma, osteoarthritis, ischemic-reperfusion induced injury conditions, and renal disorder. This study uncovered the potential restorative advantages of saffron and its derivatives, in miRNA imbalances in a variety of diseases.

Prognostic Value of Admission Neutrophil Count in Asthma Patients with COVID-19: A Comparative Analysis with other Systemic Inflammation Indices for In-Hospital Mortality Prediction.

Despite studies indicating that asthma patients do not exhibit a higher mortality rate or severity compared to the general population when infected with COVID-19, there have been few reports on predictive factors for mortality in this context. This study aimed to assess the predictive value of systemic inflammation indices including neutrophil-to-lymphocyte (NLR), monocyte-to-lymphocyte (MLR), platelet-to-lymphocyte (PLR), systemic inflammation response index (SIR-I), and systemic inflammation index (SII) in determining mortality rate among patients with COVID-19 and asthma. In this prospective study, the laboratory parameters of 1792 COVID-19 patients were examined, with a subgroup consisting of 112 patients with asthma and 1680 patients without asthma. Receiver operating characteristic (ROC) analysis was employed to assess the potential of inflammatory indices in indicating COVID-19 severity, while Kaplan-Meier curves were utilized to analyze the survival probability with death as the outcome. In deceased non-asthma patients, the levels of leukocyte and differential cell counts, and the values of PLR, NLR, MLR, SII, and SIR-I were higher than in survivors. In contrast, all the above values except PLR and MLR were significant in the asthma groups. The Kaplan-Meier survival curves were consistent with the ROC analysis. However, a multivariate Cox regression analysis revealed that neutrophil counts in non-asthma subjects and leukocyte and neutrophil counts in asthma patients remained significant for survival. In conclusion, while numerous inflammatory indices were associated with mortality in COVID-19 patients without asthma, neutrophil counts could independently predict mortality risk in asthma COVID-19 patients.

Aggregate index of systemic inflammation (AISI) in admission as a reliable predictor of mortality in COPD patients with COVID-19.

BACKGROUND: The role of leukocytes and systemic inflammation indicators in predicting the severity and mortality of inflammatory diseases has been well reported, such as the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), neutrophil/lymphocyte*platelet ratio (NLPR), derived neutrophil/lymphocyte ratio (dNLR), aggregate index of systemic inflammation (AISI), as well as systemic inflammation response index (SIRI) and systemic inflammation index (SII). The purpose of the present study was to investigate the prognostic role of systemic inflammatory indicators in the mortality of chronic obstructive pulmonary disease (COPD) patients with COVID-19. METHODS: This retrospective study included 169 COPD patients hospitalized with COVID-19. Demographic, clinical, and laboratory data were obtained from the patients' electronic records. The ability of systemic inflammation indeces to distinguish the severity of COVID-19 was determined by receiver operating characteristic (ROC) analysis, and survival probability was determined by the mean of Kaplan-Meier curves, with the endpoint being death. RESULTS: ROC curves showed that the AUD level was significant for WBC, MLR, SIRI, and AISI. Interestingly, Kaplan-Meier survival curves revealed that survival was lower with higher MLR (HR = 2.022, 95% CI = 1.030 to 3.968, P < 0.05) and AISI (HR = 2.010, 95% CI = 1.048 to 3.855, P < 0.05) values. However, the multivariate Cox regression model showed that only AISI was significantly associated with survival. CONCLUSION: AISI in COPD patients with COVID-19 was a reliable predictor of mortality.

Role of Lipid Profile and Its Relative Ratios (Cholesterol/HDL-C, Triglyceride/HDL-C, LDL-C/HDL-C, WBC/HDL-C, and FBG/HDL-C) on Admission Predicts In-Hospital Mortality COVID-19.

Background: Lipid profile and its related ratios such as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), TG/HDL-C ratio, TC/HDL-C ratio, LDL-C/HDL-C ratio, white blood cell (WBC)/HDL-C ratio, and fasting blood glucose (FBG)/HDL-C ratio are valuable indicators that have been studied in various disorders to predict mortality. The present study was conducted with the aim of investigating the role of lipid profile ratios in predicting mortality in COVID-19 patients. Methods: At the beginning of hospitalization, laboratory tests were taken from all patients (n = 300). The ability of lipid profile ratios to determine the COVID-19 severity was evaluated using receiver-operating characteristic (ROC). In addition, survival probability was determined with the average of Kaplan-Meier curves, so that the end point was death. Results: In deceased patients, TG, TC, LDL-C, HDL-C, TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C parameters were significantly lower than those of surviving patients, while WBC/HDL-C and FBG/HDL-C were significantly higher. TC (HR = 3.178, 95%CI = 1.064 to 9.491, P < 0.05), TG (HR = 3.276, 95%CI = 1.111 to 9.655, P < 0.05), LDL-C (HR = 3.207, 95%CI = 1.104 to 9.316, P < 0.05), and HDL-C (HR = 3.690, 95%CI = 1.290 to 10.554, P < 0.05), as well as TC/HDL-C (HR = 3.860, 95%CI = 1.289 to 11.558, P < 0.05), TG/HDL-C (HR = 3.860, 95%CI = 1.289 to 11.558, P < 0.05), LDL-C/HDL-C (HR = 3.915, 95%CI = 1.305 to 11.739, P < 0.05), WBC/HDL-C (HR = 3.232, 95%CI = 1.176 to 8.885, P < 0.05), and FBG/HDL-C ratios (HR = 4.474, 95%CI = 1.567 to 12.777, P < 0.01), were detectably related to survival. The multivariate Cox regression models showed that only FBG/HDL-C ratio (HR = 5.477, 95%CI = 1.488 to 20.153, P < 0.01) was significantly related to survival. Conclusion: The results suggested that FBG/HDL-C ratio in hospital-admitted COVID-19 patients was a reliable predictor of mortality.

Effect of saffron supplementation on oxidative stress markers (MDA, TAC, TOS, GPx, SOD, and pro-oxidant/antioxidant balance): An updated systematic review and meta-analysis of randomized placebo-controlled trials.

Introduction: This study aimed to perform an updated systematic review and meta-analysis to evaluate the effectiveness of saffron supplementation on oxidative stress markers [malondialdehyde (MDA), total antioxidant capacity (TAC), total oxidant status (TOS), glutathione peroxidase (GPx), superoxide dismutase (SOD), and prooxidant/antioxidant balance (PAB)] in randomized controlled trials (RCTs). Methods: We searched PubMed/Medline, Web of Science, Scopus, Cochrane CENTRAL, and Google Scholar until December 2022. Trial studies investigating the effects of oral saffron supplements on MDA, TAC, TOS, GPx, SOD, and PAB concentrations were included in the study. To analyze the results, mean differences (SMD) and 95% confidence intervals (CI) were pooled using a random effects model. Heterogeneity was assessed using the Cochrane Q and I 2 values. Sixteen cases were included in the meta-analysis (468 and 466 subjects in the saffron and control groups, respectively). Results: It was found that saffron consumption caused a significant decrease in MDA (SMD: -0.322; 95% CI: -0.53, -0.16; I 2 = 32.58%) and TOS (SMD: -0.654; 95% CI: -1.08, -0.23; I 2 = 68%) levels as well as a significant increase in TAC (SMD: 0.302; 95% CI: 0.13, 0.47; I 2 = 10.12%) and GPx (SMD: 0.447; 95% CI: 0.10, 0.80; I 2 = 35%). Subgroup analysis demonstrated a significant reduction in MDA levels in studies with a saffron dosage of >30 mg/day, age of <50 years, and study duration of <12 weeks. Among the limitations of the study, we can point out that the studies were from Iran, the different nature of the diseases included, and were not considered of some potential confounders such as smoking, physical activity, and diet in the studies. Discussion: In summary, the results showed that saffron has beneficial effects on oxidative stress markers.

Effect of crocin of Crocus sativus L. on serum inflammatory markers (IL-6 and TNF-α) in chronic obstructive pulmonary disease patients: a randomised, double-blind, placebo-controlled trial.

Different factors, such as inflammation, oxidative stress, extracellular matrix degradation and apoptosis, affect the pathophysiology of chronic obstructive pulmonary disease (COPD), as a progressive disease characterised by permanent airflow limitation. Herbal supplements with anti-inflammatory and antioxidant properties can help treat certain chronic diseases. The current study aimed at investigating the preventive effects of crocin supplementation on the serum concentrations of IL-6, TNF-α, exercise capacity and pulmonary function tests (PFT) in patients with COPD. The present prospective randomised clinical trial equally divided fifty-seven patients with COPD into a placebo and an intervention group, who respectively received a placebo and crocin (15 mg twice day for 12 weeks) as a supplement. ELISA was used to measure serum levels of IL-6 and TNF-α, also PFT and exercise capacity based on 6-min walking distance test (6MWD), which was performed at the beginning and end of the study. Crocin improved the results of PFT (P < 0·05) and 6-MWD (P < 0·001) and exerted preventive effects by increasing the serum levels of IL-6 in patients with COPD compared with those in the placebo group (P < 0·05). Intervention with crocin significantly lowered serum levels of TNF-α at the end of the study (P < 0·01). The present findings suggest crocin supplementation improves exercise capacity and PFT in patients with COPD by reducing serum levels of inflammatory factors.

Effects of crocin on T-bet/GATA-3 ratio, and miR-146a and miR-106a expression levels in lung tissue of ovalbumin-sensitized mice.

Objectives: Although various studies have revealed the beneficial effects of crocin (derived from saffron), such as anti-inflammatory, anti-cancer, antioxidant, and immune modulator, however, its exact mechanism is unknown. The present study aimed to investigate the effect of crocin on the expression ratio of T-bet/GATA-3 as an indicator of altered immune responses in the lung tissue of ovalbumin (OVA)-sensitized mice. In addition, the effect of crocin on the expression level of miR-146a and miR-106a in the lung tissue OVA-sensitized mice was investigated. Materials and Methods: Mice were randomly divided into five groups (n=6): Control; OVA, OVA + Crocin 25, OVA + Cro 50, and OVA + Cro100 groups. Crocin was administrated intraperitoneally at doses of 25, 50, and 100 mg/kg for five consecutive days. One day after asthma induction, animals were euthanized, and lungs were sampled for pathological and gene expression analysis. Results: OVA-sensitization led to increased inflammation and histopathological changes in the lung tissue of mice. In addition, GATA-3 expression increased (P<0.001) and T-bet expression decreased (P<0.001) in OVA-sensitized groups. The T-bet/GATA3 ratio was also reduced markedly in asthma groups (P<0.001). Furthermore, increased expression of miR-146a and miR-106a levels was evident in the lung tissue of OVA-sensitized mice (P<0.001 for both). Intervention with high concentrations of crocin (50 and 100 mg/kg) significantly reduced airway inflammation, GATA-3 expression, miR-146a expression, and miR-106a expression and corrected the T-bet/GATA-3 ratio (P<0.05 to P<0.001). Conclusion: Treatment with crocin led to a decrease in the severity of lung inflammation in OVA-sensitized mice, which is probably through the reduction of the T-bet/GATA-3 ratio, and mir-146a and mir-106a expression level.

Role of leukocytes and systemic inflammation indexes (NLR, PLR, MLP, dNLR, NLPR, AISI, SIR-I, and SII) on admission predicts in-hospital mortality in non-elderly and elderly COVID-19 patients.

Background: Systemic inflammation indices, including neutrophil/lymphocyte ratio (NLR), monocyte/lymphocyte ratio (MLR), platelet/lymphocyte ratio (PLR), derived neutrophil/lymphocyte ratio (dNLR), neutrophil/lymphocyte*platelet ratio (NLPR), aggregate index of systemic inflammation (AISI), systemic inflammation response index (SIR-I), and systemic inflammation index (SII) are well-expressed inflammatory indices that have been used to predict the severity and mortality of various inflammatory diseases. This study aimed to investigate the role of systemic inflammatory markers in predicting mortality in non-elderly and elderly COVID-19 patients. Methods: In a retrospective study, laboratory parameters were examined for 1,792 COVID-19 patients (elderly = 710 and non-elderly = 1,082). The ability of inflammatory markers to distinguish the severity of COVID-19 was determined by receiver operating characteristic (ROC) analysis, and survival probability was determined by the mean of Kaplan-Meier curves, with the endpoint being death. Results: In the non-survivor non-elderly and elderly patients, the parameters PLR, MLR, dNLR, NLPR, AISI, SIR-I, and SII were significantly higher than in the surviving patients. WBC count (HR = 4.668, 95% CI = 1.624 to 13.413, P < 0.01), neutrophil count (HR = 6.395, 95% CI = 2.070 to 19.760, P < 0.01), dNLR (HR = 0.390, 95% CI = 0.182 to 0.835, P < 0.05), and SII (HR = 10.725, 95% CI = 1.076 to 106.826, P < 0.05) were significantly associated with survival. On the other hand, in elderly patients, it was found that WBC count (HR = 4.076, 95% CI = 2.176 to 7.637, P < 0.001) and neutrophil count (HR = 2.412, 95% CI = 1.252 to 4.647, P < 0.01) were significantly associated with survival. Conclusion: WBC count and neutrophil count in non-elderly and elderly patients, were reliable predictors of mortality.

Adipolin and IL-6 Serum Levels in Chronic Obstructive Pulmonary Disease.

Objective(s): One of the adipokines that have insulin-sensitizing properties is adipolin, whose reduced levels have been reported in obesity, oxidative stress, and inflammation. The present study investigated serum interleukin-6 (IL-6) and adipolin levels in chronic obstructive pulmonary disease (COPD) patients. Method: A control case study included 60 COPD patients and 30 healthy subjects in the research and measured adipolin and IL-6 serum levels. In addition, serum adipolin levels in COPD patients were assessed according to the GOLD grade. The relationship between serum adipolin levels and study variables were also analyzed. Results: The results showed reduced adipolin levels in COPD patients compared with healthy individuals (p < 0.001). Furthermore, increased levels of IL-6 were evident in the COPD group compared to the control group (p < 0.001). Adipolin serum levels were positively correlated with PFTs and negatively correlated with IL-6 levels. Conclusion: Decreased adipolin levels enhanced disease severity in COPD patients. It seems that the existence of a significant relationship between adipolin and IL-6 may indicate the role of adipolin in the pathophysiology of COPD.

Urinary concentrations of BTEX in waterpipe smokers and nonsmokers: Investigating the influence of conventional activities and multiple factors.

The aim of this study was to compare the concentrations of the benzene, toluene, ethylbenzene, and xylene (BTEX) compounds in the urine of smokers and the control group considering the role of age, weight, job, history of waterpipe and cigarette smoking, and driving time. The chemicals in the urine of 99 smokers and 31 nonsmokers were extracted by liquid-liquid extraction method and their concentrations were measured by liquid injection GC/MS. The mean concentration of benzene, toluene, ethylbenzene, m-xylene, o-xylene, p-xylene, and total BTEX in waterpipe smokers were found to be 471.40, 670.90, 127.91, 167.64, 90.62, 46.04, and 1574.50 ng/g. creatinine, respectively. For the waterpipe&cigarette smokers, the concentration of the compounds were 708.00, 959.00, 146.40, 192.50, 93.30, 53.07, and 2152.00 ng/g.creatinine, respectively. For nonsmokers the concentrations of these compounds were 88.12, 140.40, 36.68, 57.29, 31.53, 26.21, and 380.30 ng/g.creatinine, respectively. Driving time, waterpipe smoking and cigarette smoking were positively associated with BTEX concentration (p < 0.05). Fruity tobacco showed higher concentrations of BTEX compared to the regular tobacco, and athlete persons had les urinary BTEX than the non-athletes. There was not significant correlation between the BTEX and age, height, weight, and BMI. High concentrations of BTEX compounds in the urine of waterpipe and cigarette smokers compared to nonsmokers indicate that waterpipe and cigarette can be an important source of exposure to these compounds and the known adverse effects of these compounds, especially carcinogenicity, threaten the health of smokers.

Effect of Crocin From Saffron (Crocus sativus L.) Supplementation on Oxidant/Antioxidant Markers, Exercise Capacity, and Pulmonary Function Tests in COPD Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

Background: Chronic obstructive pulmonary disease (COPD) is a progressive and chronic respiratory disorder characterized by reversible airflow limitation and lung parenchyma destruction. The main feature of COPD is inflammation and disturbance of the oxidant/antioxidant balance in the airways. The therapeutic use of herbal supplements with antioxidant and anti-inflammatory properties seems to be very useful in the medical management of patients with COPD. Method: COPD patients were divided into placebo and intervention groups (each group n = 23) in a clinical trial study. The intervention group received crocin supplementation (30 mg/day for 12 weeks), and the control group received a placebo. Pre- and after the intervention, pulmonary function tests (PFTs), exercise capacity (using a 6-min walking distance test (6MWD)), and serum levels of total oxidant status (TOS), total antioxidant capacity (TAOC), and NF-kB were assessed using the ELISA test. Results: Intervention with crocin for 12 weeks in COPD patients decreased serum levels of TOS and NF-κB as well as increased TAOC. In addition, the results of the 6MWD test reveal an improvement in patients' exercise capacity. Conclusion: Crocin supplementation appears to effectively establish oxidant/antioxidant balance and improve inflammatory conditions in patients with COPD.

Type 2 Diabetes Mellitus Provokes Rat Immune Cells Recruitment into the Pulmonary Niche by Up-regulation of Endothelial Adhesion Molecules.

Purpose: Diabetes mellitus, especially type 2, is conceived as a devastating chronic metabolic disease globally. Due to the existence of an extensive vascular network in the pulmonary tissue, it is suggested that lungs are sensitive to the diabetic condition like other tissues. This study was designed to address the possible effect of type 2 diabetes mellitus on the promotion of pathological changes via vascular injury. Methods: Sixteen male Wistar rats were randomly allocated to the two of control and T2D groups. To induce type 2 diabetes (T2D), rats were received high-fat and a single dose of streptozotocin (STZ). On week 12, rats were euthanized and lungs samples were taken. Using hematoxylin and eosin (H&E) staining, the pathological changes were monitored. The expression of intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and interleukin 10 (IL-10) was monitored using real-time PCR assay. The level of tumor necrosis factor-α (TNF-α) was detected using ELISA assay. Nitrosative stress was monitored using the Griess assay. Results: Pathological examination in bronchoalveolar discharge revealed the existence of mild to moderate interstitial bronchopneumonia and increased neutrophilic leukocytosis compared to the control. Enhanced ICAM-1 and VCAM-1 expression and suppression of IL-10 was found using real-time PCR analysis (P < 0.05). The levels of TNF-α and NO were increased with diabetic changes compared to the control rats (P < 0.05). Conclusion: T2D could promote pulmonary tissue injury via the production of TNF-α and up-regulation of vascular ICAM-1 and VCAM-1. The inflammatory status and vascular ICAM-1 and VCAM-1 increase immune cell recruitment into the pulmonary niche.

Effects of crocin supplementation on inflammatory markers, lipid profiles, insulin and cardioprotective indices in women with PCOS: A randomized, double-blind, placebo-controlled trial.

Polycystic ovary syndrome (PCOS) is a multifactorial reproductive condition common in women of reproductive age. Hyperlipidemia, insulin resistance, obesity, and chronic low-grade inflammation are associated with PCOS. In a clinical trial study, women with PCOS were divided into two groups (n = 25 each): the intervention group receiving crocin (15 mg, twice daily) and the control group receiving a placebo. The duration of intervention in both groups was 12 weeks. Pre- and postintervention, demographic information, lipid profile, fasting blood glucose (FBG), fasting insulin, and inflammatory markers (interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-α]) were measured. Intervention with crocin significantly increased the mean high-density lipoprotein cholesterol postintervention compared to the placebo group, while exerting a suppressive effect on the increase in mean low-density lipoprotein cholesterol, triglycerides, and cholesterol levels. Intervention with crocin also exerted inhibitory effects on changes in FBG and insulin, so that crocin improved insulin and cardioprotective indices. Finally, despite the increased inflammatory markers (IL-6 and TNF-α) in the placebo group, crocin treatment had protective effects on their increased changes. Thus, crocin supplementation could be considered in the therapeutic targets of women with PCOS.

Altered gene expression levels of IL-17/TRAF6/MAPK/USP25 axis and pro-inflammatory cytokine levels in lung tissue of obese ovalbumin-sensitized rats.

AIMS: The association between asthma and obesity has been shown but its accurate mechanism is unknown. In the current study, we sought to investigate the gene expression levels of IL-17/TRAF6/MAPK/USP25 axis and pro-inflammatory cytokine level (IL-6, IL-1ß, and TNF-α) in obese Ovalbumin (OVA)-sensitized female and male Wistar rats lung tissue. MAIN METHODS: Animals in both males and females were divided into eight groups (four groups in each sex) based on diet and OVA-sensitization: normal diet, a normal diet with OVA-sensitization, high-fat diet (HFD), and OVA-sensitization with an HFD. KEY FINDINGS: In both sexes, obese OVA-sensitized rats, the methacholine concentration-response curve shifted to the left and EC50 methacholine decreased. Increased pro-inflammatory cytokines as well as elevated IL-17/TRAF6/MAPK axis genes and decreased USP25 gene expression were identified in obese OVA-sensitized groups. SIGNIFICANCE: The results indicate that in obese OVA-sensitized rats, the IL-17 axis were involved in the pathogenesis of the disease and can be considered as a therapeutic target in subjects with obesity-related asthma.

Crocin attenuates inflammation of lung tissue in ovalbumin-sensitized mice by altering the expression of endoplasmic reticulum stress markers.

Endoplasmic reticulum (ER) stress plays a pivotal role in the pathogenesis of asthma. The present study aimed to investigate the reducing or suppressing effects of crocin in ovalbumin (OVA)-sensitized mice on ER stress markers. Mice were divided into six groups (n = 5 per group) including control, OVA-sensitized (OVA), OVA-treated crocin (OVA-Cr25, OVA-Cr50, and OVA-Cr100 mg/kg), and OVA-treated dexamethasone (1 mg/kg), (OVA-Dexa) groups. Animals 5 later groups were sensitized to OVA and the treatment groups received intraperitoneally crocin/dexamethasone in the last 5 days of the model. At the end of the study, lung tissue was evaluated for airway inflammation, caspase 12 and CHOP protein levels, and expression of ER stress markers using real-time-PCR. Sensitization with OVA significantly caused airway inflammation and induction of ER stress in mice compared to the control group based on the elevated inflammatory cells and ER stress markers in the lung tissue. Treatment with crocin and dexamethasone reduced airway inflammation and suppressed ER stress markers. Interestingly, in the OVA-Cr100 group, the suppressive effects on ER stress apoptotic markers were comparable to the OVA-Dexa group. The results suggest that crocin mediates maladaptive ER stress conditions possibly by creating adaptive ER stress status and driving protein folding correctly.

Association of plasma visfatin with epicardial fat thickness and severity of coronary artery diseases in patients with acute myocardial infarction and stable angina pectoris.

BACKGROUND: Elevated serum visfatin levels have been reported in some chronic inflammatory diseases such as cardiovascular diseases (CVDs) and rheumatoid arthritis. The purpose of the present study was to investigate the correlation between visfatin and interleukin-6 (IL-6) and anthropometric, angiographic, echocardiographic, and biochemical parameters in patients with acute myocardial infarction (AMI). METHODS: In this case-control study, 90 patients who were candidates for angiography were divided into the following 3 groups: non-coronary artery disease group (non-CAD; n = 30) with a history of chest pain without angiographic changes, stable angina pectoris group (SAP; n = 30), and AMI group (n = 30). Anthropometric, angiographic, echocardiographic, and biochemical parameters were measured in all subjects. RESULTS: The mean age of patients in the non-CAD, SAP, and AMI groups was 62.26 ± 13.24, 62.93 ± 8.35, and 52.83 ± 10.26 years (P < 0.001) respectively. The results showed that the median [interquartile range] of visfatin level was higher in the AMI group [7 (6.30-9.30), pg/ml] compared with the SAP [5.85 (5.20-6.60); P < 0.001] and non-CAD [5.20 (3.30-5.70); P < 0.001] groups. In addition, median [interquartile range] IL-6 levels were higher in the AMI group [17.5 (16-21), pg/ml] compared with the SAP [15.50 (14-18); P < 0.01] and non-CAD [14 (11-17); P < 0.001] groups. Furthermore, there was a positive association between plasma level of visfatin, and epicardial fat thickness (EFT) and the Gensini score in the SAP and AMI patients. The results of multivariate linear regression analysis revealed that white blood cell ý(WBC) count and IL-6 were independently associated with plasma visfatin level. CONCLUSION: The current study showed an association between visfatin and EFT in AMI patients. Increased visfatin levels in patients with AMI may contribute to atherosclerosis; however, further studies should be conducted to confirm this finding.