Apigenin attenuates serum concentrations of TNF-a, interleukin 1b and interleukin 6 in lipopolysaccharide-stimulated rats.

Objective: The use of flavonoids is increasing due to their cost-effectiveness and less adverse reaction. Therefore, the effect of apigenin on lipopolysaccharide (LPS)-induced inflammation was investigated by measuring IL-1b, IL-6, and TNF-a, of serum in the male rats. Materials and Methods: Ninety male wistar rats were divided in 6 groups included; control, sham, dexamethasone 15 mg/kg, intraperitoneally (i.p.), and apigenin (5, 15, and 30 mg/kg, i.p). Thirty minutes after the administration of solvent or apigenin, LPS (30 µg/kg, i.p) was injected. At time intervals of 4, 12 and 24 hr after injection, blood samples were taken and the concentrations of TNF-a, IL-1b and IL-6 were measured by enzyme-linked immunosorbent assay. Results: Compared to the control, apigenin (5 mg/kg) decreased the level of TNF-a, and IL-1b in a period of 24 hr (p<0.05). The concentration of IL-6 decreased significantly by apigenin (15 mg/kg) 24 hr after injection (p<0.05). Apigenin (30 mg/kg) decreased the level of TNF-a, at all three time points (4 hr; p<0.05, 12 hr; p<0.01, and 24 hr; p<0.01), and the level of IL-1b (p<0.01), 24 hr and the level of IL-6 at 4 hr (p<0.05), and 24 hr (p<0.01) after LPS injection. Conclusion: Apigenin can suppress serum inflammatory cytokines, similar to dexamethasone.

Effect of cold atmospheric plasma on changing of biomolecular structures involved in apoptosis pathways of melanoma cancer.

BACKGROUND: Cold atmospheric plasma (CAP), is a technology based on non-thermal ionized gas that is used for cancer therapy in research. We evaluated the effect of CAP on malignant melanoma cancer cell line (B16) in comparison with normal cells (L929). METHODS: The effect of CAP on the cytotoxicity of B16 and L929 cell lines was assayed by the MTT method and inverted microscopy. The induction of apoptosis in cells was evaluated using a fluorescence microscope. FTIR monitored the CAP effect in biomacromolecules changes in these cell lines. QPCR assayed gene expression of BAX, BCL-2, and Caspase-3 (CASP-3). RESULTS: The results of the MTT test showed CAP has a cytotoxic effect on the B16 cancer cell line more than L929 normal cells (p < 0.0001). The results of invert and fluorescence microscopy showed CAP-induced apoptotic morphology on cancerous cells. FTIR spectroscopy indicated CAP changes biomacromolecules structure. Evaluation of gene expression showed CAP increased BAX and CASP-3 gene expression. Also, it decreased BCL-2 gene expression. CONCLUSIONS: Taken together, CAP may change biomacromolecule structures involved in apoptosis pathways, decrease proliferation and induce apoptosis in cancer cells.

Promising Modulatory Effects of Cenicriviroc on the Progression of Mouse Colorectal Cancer through Inhibition of CCR2_CCL2 Signaling Pathway.

The study was designed to assay the efficacy of cenicriviroc (CVC) on the progression of mouse colorectal cancer by downregulation of CCR2_CCL2. In this study, CVC was used to inhibit the CCR2 receptor. Next, an MTT assay was performed to evaluate the cytotoxic effects of CVC on the CT26 cell line. CT26 cells were implanted subcutaneously in BALB/c mice. After tumor implantation, one group of animals received 20 mg/kg of CVC several times. The mRNA levels of CCR2, CCL2, VEGF, NF-κB, c-Myc, vimentin, and IL33 were determined in the CT26 cell line and then tumor tissues (after 21 days), by qRT-PCR. Protein levels of the above-mentioned targets were determined by western blot and ELISA. Flow cytometry was performed to assess the changes in apoptosis. Tumor growth inhibition was measured on the 1st, 7th, and 21st days after the first treatment. In both cell line and tumor cells treated with CVC, expression levels of the markers of our interest in mRNA and protein levels were significantly reduced compared to controls. A significantly higher apoptotic index was observed in CVC-treated groups. The rates of tumor growth were significantly decreased on the 7th and 21st days after the first injection. To our knowledge, this was the first time that we demonstrated the promising effect of CVC on the development of CRC through inhibition of the CCR2_CCL2 signaling and its downstream biomarkers.

Higher Intake of Dietary Magnesium Is Inversely Associated With COVID-19 Severity and Symptoms in Hospitalized Patients: A Cross-Sectional Study.

Background and Aims: Magnesium is an anti-inflammatory mineral that plays a role in the innate immune system, and the relaxation of bronchial smooth muscle warrants additional attention in COVID-19. This study examined the association between magnesium intake and COVID-19 severity and related symptoms in hospitalized patients. Methods: A cross-sectional study was done enrolling 250 COVID-19 patients aged 18 to 65 years. A validated 168-item online food frequency questionnaire (FFQ) was used to assess dietary magnesium intake. COVID-19 Treatment Guidelines were used to determine COVID-19 severity, and symptoms were evaluated using a standard questionnaire. Crude and adjusted analyses were performed (Model 1: age, sex, and energy intake; Model 2: Model 1 + physical activity, supplements, corticosteroids, and antiviral drugs; Model 3: Model 2 + body mass index). Results: The mean age of participants was 44.1 ± 12.1 years, and 46% of them had severe COVID-19. Patients at the highest tertile of dietary magnesium intake had lower serum levels of inflammatory biomarkers, including CRP (11.8 ± 2.2 vs. 29.5 ± 2.1 mg/L, p < 0.001) and ESR (15.8 ± 2.4 vs. 34.7 ± 2.4 mm/hr, p < 0.001), than those at the lowest tertile. After controlling for potential confounders, we observed that a higher dietary magnesium intake was associated with a lower odds of severe COVID-19 (OR: 0.32; 95% CI: 0.15-0.70). Also, we found a significant inverse association between dietary magnesium intake and odds of COVID-19 symptoms. Conclusion: We found that higher intake of dietary magnesium was inversely associated with COVID-19 severity and symptoms.

Serum levels and genetic variation of IL-35 are associated with multiple sclerosis: a population-based case-control study.

This study aimed to investigate the association between serum levels and polymorphic variants of IL-35 with susceptibility, clinical features, and disease severity in multiple sclerosis (MS) patients.This case-control study recruited 186 MS patients and 195 sex- and age-matched healthy controls. Serum levels and polymorphic variants of IL-35 were determined by ELISA and restriction fragment length polymorphism (RFLP)-PCR or high resolution melting (HRM) analysis methods, respectively. In addition, by in silico analysis, we evaluated the location and function of the polymorphism.Serum levels of IL-35 were significantly lower in the patients than those of healthy controls (49.3 ± 3.7 vs. 69.5 ± 7.8, p = 0.009). EBI3 rs4740 polymorphism of IL-35 was associated with 2.2-fold increased risk of MS susceptibility (95% CI, 1.3-3.9, p = 0.005). However, there were no differences in the genotype distribution and allele frequencies of IL-35 rs568408 between the patients and controls (p > 0.05). In silico results showed that variation in IL-12A and EBI3 may affect on protein pathways of the cells and different components of the immune system such as NF-κB and INF-γ.The results show that IL-35 polymorphisms might be a genetic risk factor for the development of MS.

Association of serum levels and receptor genes BsmI, TaqI and FokI polymorphisms of vitamin D with the severity of multiple sclerosis.

PURPOSE: Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease. Vitamin D has a major role in preventing inflammatory disorders. Therefore, any alteration in vitamin D receptor (VDR) might be a genetic risk factor for MS development. This study aimed to evaluate the effect of serum levels and VDR FokI, BsmI, and TaqI gene polymorphisms on the severity of MS. METHODS: This case-control study recruited 160 MS patients (71.9% females, mean age of 34.3 ± 8.3 years) and 162 (66.7% females, mean age 35.4 ± 7.9 year) age, sex, and ethnicity matched healthy controls. FokI (rs2228570), BsmI (rs1544410), and TaqI (rs731236) polymorphisms were carried out using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Demographic, clinical parameters, and the levels of vitamin D were compared between groups. RESULTS: We found that the frequency of FokI and TaqI polymorphisms significantly differed between the patients and the controls (p = 0.0127 and p = 0.0236, respectively). The MS patients had low levels of vitamin D compared to the controls (p = 0.011). In addition, TaqI T/C polymorphism significantly decreased the levels of vitamin D in the MS patients (p = 0.002). However, there was no significant association between FokI or BsmI SNPs and the levels of vitamin D in MS patients (p > 0.5). CONCLUSION: Our results suggest that FokI and TaqI polymorphisms of VDR are associated with MS risk and TaqI polymorphism is associated with Vitamin D levels in MS patients. Meanwhile, no difference was observed between VDR gene polymorphisms and any types of MS.

Association between Dietary Intakes of Tea, Coffee, and Soft Drinks in Patients Undergoing Coronary Angiography with Coronary Artery Stenosis.

BACKGROUND: Coronary artery disease (CAD) is one of the major causes of mortality that is related to the nutritional habits and lifestyle. The aim of this study was to examine the association between tea, coffee, and soft drink consumption and coronary artery stenosis in patients undergoing coronary angiography. METHODS: Out of all the patients, 208 cases (101 Female) with 57.81 ± 12.18 (mean ± SD) were assigned to participate in this cross-sectional study. In total, 168-items, semi-quantitative food frequency questionnaire collected for assessments of dietary intakes of black tea, coffee, caffeine, and soft drinks and record demographic and clinical questionnaire. RESULTS: There were negative association between arteries with stenosis of more than 50% number with dietary intakes of tea (P = 0.011, r = - 0.187), coffee (P = 0.069, r = - 0.098) intakes, and dietary caffeine intake (P = 0.043, r = -0.118). The high consumptions of soft drinks (P = 0.005, r = 0.387) were associated with an enhancement in arteries with stenosis of more than 50% number. In addition, dietary consumption of black tea have a negatively significant association with the history of previous angiography (P = 0.044, r = -0.121), the history of previous Stanton (P = 0.035, r = -0.132), and coronary artery bypass graft surgery nomination (P = 0.008, r = -0.216). Coffee consumption showed a significant negative relationship with engagement for coronary artery bypass graft surgery (P = 0.004, r = -0.598). CONCLUSIONS: Dietary intakes of tea, coffee, and caffeine may have a negative relationship with CAD and cardio vascular diseases. Healthy dietary lifestyle is an important issue for the prevention of chronic diseases.