Materials and Methods: Dried root of P. glabra was extracted under reflux with methyl alcohol, fractionated through the vacuum liquid chromatography technique, and evaporated and then purified the compounds using column chromatography and preparative thin-layer chromatography. THP-1 cells were treated with amentoflavone, 5,7,4'-hydroxyflavonoid, and stigmasterol with various concentrations (0-30 µg/mL) and then incubated with MTS reagent for 2h. Treatment was done for 24, 48, and 72h. Then, effects of these compounds were also tested on PGE2, TNF-α, and IL-6 expression in human THP-1-derived macrophage cells for 24h.
Results: Three new compounds such as amentoflavone, 5,7,4'-hydroxyflavonoid, and stigmasterol were isolated. After 24h of incubation, a significant decrease in cell viability was reported with IC50 values of amentoflavone, 5,7,4'- hydroxyflavonoid, and stigmasterol (21 µg/mL ≡ 38 M), (18 µg/mL ≡ 66 M) and (20 µg/mL ≡ 48.5 M), respectively. Whereas for 48 and 72h treatment showed a less decreased cell viability compared with 24h treatment. These compounds also showed a significant reduction in the production of TNF-α, IL-6, and PGE2 in a dose-dependent manner.
Conclusions: The isolated new compounds showed significant cytotoxicity and anti-inflammatory effects.
METHODS: Microscopic agglutination test (MAT)-positive and MAT-negative human serum samples (n=30) from patients with leptospirosis were obtained from the Public Health Laboratory, Kota Kinabalu, Sabah, Malaysia and control serum samples (n=10) were obtained from healthy student volunteers. We estimated the levels of IL-1β, IL-6, IL-8, IL-10, and TNF-α in serum samples by a Luminex assay.
RESULTS: The levels of IL-6, IL-8, and IL1-β were significantly higher in 13% of the patients with leptospirosis compared to the healthy controls, while the levels of IL-10 and TNF-α were not elevated in either group.
CONCLUSION: Our data suggest that elevated levels of IL-6, IL- 8, and IL1-β may be associated with leptospirosis disease severity, which requires patient follow-up for confirmation.
Methods: This comparative cross-sectional study was conducted among healthy women. The cases included those women exposed to SHS, and the controls included those women not exposed to SHS. SHS exposure was defined as being exposed to SHS for at least 15 min for 2 days per week. Venous blood was taken to measure the metabolic markers (high molecular weight adiponectin, insulin level, insulin resistance, and nonesterified fatty acids), oxidative stress markers (oxidized low density lipoprotein cholesterol and 8-isoprostane), and inflammatory markers (high-sensitivity C-reactive protein and interleukin-6). A hair nicotine analysis was also performed. An analysis of covariance and a simple linear regression analysis were conducted.
Results: There were 101 women in the SHS exposure group and 91 women in the non-SHS exposure group. The mean (with standard deviation) of the hair nicotine levels was significantly higher in the SHS exposure group when compared to the non-SHS exposure group [0.22 (0.62) vs. 0.04 (0.11) ng/mg; P = 0.009]. No significant differences were observed in the high molecular weight adiponectin, insulin and insulin resistance, nonesterified fatty acids, 8-isoprostane, oxidized low density lipoprotein cholesterol, interleukin-6, and high-sensitivity C-reactive protein between the two groups. The serum high molecular weight adiponectin was negatively associated with the insulin level and insulin resistance in the women exposed to SHS. However, no significant relationships were seen between the high molecular weight adiponectin and nonesterified fatty acids, 8-isoprostane, oxidized low density lipoprotein cholesterol, high-sensitivity C-reactive protein in the SHS group.
Discussion: There were no significant differences in the metabolic, oxidative stress, and inflammatory markers between the SHS exposure and non-SHS exposure healthy women. A low serum level of high molecular weight adiponectin was associated with an increased insulin level and resistance in the women exposed to SHS.
AIM: To investigate the endothelial activation, inflammation, monocyte-endothelial cell binding and oxidative stress effects of four FD varieties.
METHODS: Human coronary artery endothelial cells (HCAEC) were incubated with different concentrations of aqueous ethanolic extracts of FD var. trengganuensis (FDT), var. kunstleri (FDK), var. deltoidea (FDD) and var. intermedia (FDI), together with LPS. Protein and gene expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), endothelial-leukocyte adhesion molecule-1 (E-selectin), interleukin-6 (IL-6), Nuclear factor-κB (NF-κB) p50 and p65 and endothelial nitric oxide synthase (eNOS) were measured using ELISA and QuantiGene plex, respectively. Adhesion of monocyte to HCAEC and formation of reactive oxygen species (ROS) were detected by Rose Bengal staining and 2'-7'-dichlorofluorescein diacetate (DCFH-DA) assay.
RESULTS: FDK exhibited the highest inhibition of biomarkers in relation to endothelial activation and inflammation, second in reducing monocyte binding (17.3%) compared to other varieties. FDK (25.6%) was also the most potent at decreasing ROS production.
CONCLUSION: FD has anti-atherogenic effects, possibly mediated by NF-κB and eNOS pathways; with FDK being the most potent variety. It is potentially beneficial in mitigating atherogenesis.
Methods: Ascites and respective peripheral blood sera were collected from 18 patients with advanced EOC and soluble biomarkers, including IL-6, sTNFR2, IL-10, TGF-β, and TNF, were quantified using multiplexed bead-based immunoassay. Peripheral blood mononuclear cells (PBMC) from healthy donors were incubated with cell-free ascites for 48 h (or media as a negative control). In some experiments, IL-6 or TNF within the ascites were neutralized by using monoclonal antibodies. The phenotype of TNFR2(+) Tregs and TNFR2(-) Tregs were characterized post incubation in ascites. In some experiments, cell sorted Tregs were utilized instead of PBMC.
Results: High levels of immunosuppressive (sTNFR2, IL-10, and TGF-β) and pro-inflammatory cytokines (IL-6 and TNF) were present in malignant ascites. TNFR2 expression on all T cell subsets was higher in post culture in ascites and highest on CD4(+)CD25(hi)FoxP3(+) Tregs, resulting in an increased TNFR2(+) Treg/effector T cell ratio. Furthermore, TNFR2(+) Tregs conditioned in ascites expressed higher levels of the functional immunosuppressive molecules programmed cell death ligand-1, CTLA-4, and GARP. Functionally, TNFR2(+) Treg frequency was inversely correlated with interferon-gamma (IFN-γ) production by effector T cells, and was uniquely able to suppress TNFR2(+) T effectors. Blockade of IL-6, but not TNF, within ascites decreased TNFR2(+) Treg frequency. Results indicating malignant ascites promotes TNFR2 expression, and increased suppressive Treg activity using PBMC were confirmed using purified Treg subsets.
Conclusion: IL-6 present in malignant ovarian cancer ascites promotes increased TNFR2 expression and frequency of highly suppressive Tregs.
DATA SYNTHESIS: We searched the following international databases from inception to January 2022: PubMed, Scopus, Web of Science and Embase, and Google Scholar. Our findings of eleven meta-analyses showed that cinnamon consumption can significantly improve total cholesterol (TC) (WMD = -1.01 mg/dL; 95% CI: -2.02, -0.00, p = 0.049), low-density lipoprotein-cholesterol (LDL-C) (WMD = -0.82 mg/dL; 95% CI: -1.57, -0.07, p = 0.032), and high-density lipoprotein-cholesterol (HDL-C) (WMD = 0.47 mg/dL; 95% CI: 0.17, 0.77, p = 0.002) levels but not triglyceride (TG) levels (WMD = -0.13 mg/dL; 95% CI: -0.58, 0.32, p = 0.570). Our results did not show any significant effect of cinnamon on malondialdehyde (MDA) levels (WMD = -0.47; 95% CI: -0.99, 0.05, p = 0.078) and C-reactive protein (CRP) levels (WMD = -1.33; 95% CI: -2.66, 0.00, p = 0.051) but there was enhanced total antioxidant capacity (TAC) in patients with type 2 diabetes (T2DM) and polycystic ovary syndrome (PCOS) (WMD = 0.34; 95% CI: 0.04, 0.64, p = 0.026) and increased levels of interleukin-6 (WMD = -1.48; 95% CI: -2.96, -0.01, p = 0.049).
CONCLUSIONS: Our results support the usefulness of cinnamon intake in modulating an imbalanced lipid profile in some metabolic disorders, particularly PCOS, as well as in improving TAC and interleukin-6. The review protocol was registered on PROSPERO as CRD42022358827.
MATERIALS AND METHODS: A total of 24 male rats were randomly divided into six groups: control, DM 1.5 month (DM1.5), DM 2 months (DM2) and the group with three different doses of CGA 12.5 (CGA1), 25 (CGA2), and 50 (CGA3) mg/KgBW. Frontal lobe tissue is taken for analysis of mRNA expression for NF-κB, MCP-1, IL-6, and GFAP using Reverse Transcriptase PCR (RT-PCR). Samples were also taken for histopathology preparation and stained by immunohistochemistry method using anti-GFAP antibodies to observe glial cell activation in frontal lobe tissue.
RESULTS: The group that was given CGA at all doses have statistically significant better memory function, i.e. DM2 versus CGA1 (p = 0.036), CGA2 (p = 0.040), and CGA3 (p = 0.021). The result of mRNA expression in NF-κB was lower in the group given CGA, i.e. DM2 compared to CGA2 (p = 0.007). mRNA expression of MCP-1 was significantly lower in all CGA treatment groups compared to the non-CGA group (p = 0.000). IL-6 mRNA expression was lower than the group not given CGA, DM compared to CGA2 (p = 0.028). GFAP mRNA expression was lower than the group given CGA in DM, DM2 group compared to CGA1 (p = 0.04) and CGA3 (p = 0.004).
CONCLUSION: Administration of CGA can improve memory function at all doses given, and can reduce brain inflammatory activity, especially in the CGA2 group.
METHODS: SPF grade 4-6-week-old Kunming rats were randomly divided into 5 groups including a blank group, sham-operated group, model group, acupuncture, and moxibustion (AnM) group, and positive group. A total of 10 rats were included in each group. The model group, the AnM group, and the positive group were prepared by ligating the left sciatic nerve. AnM group was used for acupuncture and moxibustion therapy intervention, and the positive group was rendered to quick-acting sciatica pills once a day for 7 days (3 courses of treatment). The blank group, sham-operated group, and model group were not treated. The changes in thermal and mechanical pain thresholds were observed before and after the operation, and the morphological changes of the dorsal horn of the spinal cord in the lumbosacral region of the rats in each group were observed by HE staining after the courses of treatment finished. The contents of IL-1β, IL-6, IL-18, and TNF-α were measured by ELISA and the expressions of NOX1, NOX2, NOX4, and NLRP3 genes were detected by RT-qPCR while the protein expressions of NOX1, NOX2, NOX4 and NLRP3 were analyzed by Western blotting.
RESULTS: The AnM and positive group showed a significant increase in thermal and mechanical pain thresholds after treatment, while there was no significant change in the model group. As compared to the control group, the contents of IL- 1β, IL-6, IL-18, and TNF-α, as well as the relative expressions of NOX1, NOX2, NOX4, and NLRP3 genes were significantly increased in the model group (P 6, IL-18, and TNF-α, as well as the relative expressions of NOX1, NOX2, NOX4, and NLRP3 genes significantly decreased in the AnM and positive groups (P
METHODS AND ANALYSIS: Initially, during Phase I of the study, the serum level of IL-1β, IL-6 and TNF-α; ERP changes in the EEG and fecal microbiota content will be compared between 120 AUD patients and 120 healthy controls. Subsequently in Phase II of the study, 120 AUD patients will be randomized by stratified permuted block randomization into the probiotic, ACT and placebo groups in a 1:1:1 ratio. Participants in the probiotic and placebo groups will be administered one sachet per day of Lactobacillus spp. probiotic and placebo, respectively for 12 weeks. While those in the ACT group will receive one session per week of ACT for 8 weeks. Outcome measures will be administered at four timepoints, such as t0 = baseline assessment prior to intervention, t1 = 8 weeks after intervention began, t2 = 12 weeks after intervention and t3 = 24 weeks after intervention. Primary outcomes are the degrees of alcohol craving, alcohol withdrawal during abstinence and AUD. Secondary outcomes to be assessed are the severity of co-morbid depression and anxiety symptoms; the serum levels of IL-1β, IL-6 and TNF-α; changes in ERP and fecal microbiota content.
TRIAL REGISTRATION NUMBER: NCT05830708 (ClinicalTrials.gov). Registered on April 25, 2023.