Search

Brain inflammation, a pathological feature of neurodegenerative disorders, exhibits elevated microglial activity and increased levels of inflammatory factors. The present study was aimed at assessing the anti-inflammatory response of tetrahydrocurcumin (THC), the primary hydrogenated metabolite of curcumin, which was applied to treat Pseudomonas aeruginosa ( P.a. ) lipopolysaccharide- (LPS-) stimulated BV2 microglial cells. THC reduced P.a. LPS-induced mortality and the production of inflammatory mediators IL-6, TNF- α , MIP-2, IP-10, and nitrite. A further investigation revealed that THC decreased these inflammatory cytokines synergistically with JAK/STAT signaling inhibitors. THC also increased Nrf2/HO-1 signaling transduction which inhibits iNOS/COX-2/pNF κ B cascades. Additionally, the presence of the HO-1 inhibitor Snpp increased the levels of IP-10, IL-6, and nitrite while THC treatment reduced those inflammatory factors in P.a. LPS-stimulated BV2 cells. In summary, we demonstrated that THC exhibits anti-inflammatory activities in P.a. LPS-induced inflammation in brain microglial cells by inhibiting STAT1/3-dependent NF- κ B activation and inducing Nrf2-mediated HO-1 expression., Competing Interests: The authors reported no proprietary or commercial interest in any product mentioned or concept discussed in this article., (Copyright © 2022 Hui-Wen Lin et al.)

Luteolin is a common dietary flavonoid present in Chinese herbal medicines that has been reported to have important anti-inflammatory properties. Previous studies have shown that luteolin is an anti-inflammatory and anti-oxidative agent. In this study, the anti-virus inflammatory capacity of luteolin and its molecular mechanisms of action were analyzed. The cytotoxic effects of luteolin were assessed in the presence or absence of pseudorabies virus (PRV) via LDH and MTT assays. The results showed that luteolin (<10μM) had no toxic effects and there were tendencies toward higher cell survival. In PRV-infected RAW264.7 cells, luteolin potently inhibited the production of NO, iNOS, COX-2 and inflammatory cytokine production. Luteolin did not inhibit the phosphorylation of ERK 1/2, p38, and JNK 1/2 either. We found that PRV-induced NF-κB activation is regulated through inhibition of STAT1and STAT3 phosphorylation in response to luteolin. Additionally, luteolin caused the induction of HO-1 via upregulation of Nrf2, both of which are involved in the secretion of proinflammatory mediators. The blockade of HO-1 expression with SnPP, a HO-1 inhibitor, attenuated HO-1 induction by luteolin and thus mitigated its anti-inflammatory effects during PRV-infected RAW264.7 cells. Taken together, our data indicate that luteolin diminishes the proinflammatory mediators NO, inflammatory cytokines and the expression of their regulatory genes, iNOS and COX-2, in PRV-infected RAW264.7 cells by inhibiting STAT1/3 dependent NF-κB activation and inducing Nrf2mediated HO-1 expression., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Previous reports have suggested that many constituents within various algal samples are able to attenuate LPS-induced inflammatory effects. To date no report has been published on the regulation of virus-induced inflammatory response of Dunaliella salina carotenoid extract. In the present study, the anti-inflammatory effect of D. salina carotenoid extract on pseudorabies virus (PRV)-infected RAW 264.7 macrophages was investigated. We evaluated the anti-inflammatory effect of D. salina carotenoid extract on PRV-infected RAW 264.7 cells by measuring cell viability, cytotoxicity, production of inflammatory mediators such as NO, iNOS, COX-2, pro-inflammatory cytokines and anti-virus replication by plaque assay. We found down-regulation of the expression of the iNOS, COX-2 and pro-inflammatory genes IL-1β, IL-6, TNF-α, and MCP-1 in a dose-dependent manner. Although there was no effect on viral replication, there were tendencies toward lower virus titer and tendencies toward higher cell survival. Most importantly, we found that inhibition of TLR9, PI3K and Akt phosphorylation plays a crucial role in the extract-mediated NF-κB regulation by modulating IKK-IκB signaling in PRV-infected RAW264.7 cells. These results indicate that D. salina carotenoid extracts inhibited inflammation by inhibition of NF-κB activation by TLR9 dependent via PI3K/Akt inactivation., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Litchi (Litchi chinensis Sonn.) flower ethanolic extract (LFEE) was found to contain five flavanoids [total amount, 102.73 ± 5.50 mg/g of dried extract (gDE)], nine phenolic acids (total amount, 60.31 ± 4.52 mg/gDE), and proanthocyanidin A2 (79.31 ± 2.95 mg/gDE). LFEE was used to evaluate the inhibitory effects on lipopolysaccharide- (LPS-) induced pro-inflammatory mediators in RAW264.7 cells. The results showed that LFEE treatment could suppress the expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), the productions of nitric oxide (NO) and prostaglandin E2 (PGE2), and the secretions of pro-inflammatory cytokines [interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α)] in the LPS-mediated RAW264.7 cells. The attenuation of LPS-induced inflammatory responses by LFEE was found to be closely related to the inhibition of the translocation of nuclear factor κB (NF-κB) p50/p65 subunits correlated with suppression of the activation of the inhibitor of κB kinase (IKK) α/β and downregulation of activation of extracellular signal-regulated kinase (ERK) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3).

Myocardial ischemia/reperfusion (I/R) injury is marked by rapid increase in inflammation and not only results in myocardial apoptosis but also compromises the myocardial function. Dunaliella salina (D. salina), a halophilic unicellular microalga, has been used as a provitamin A carotenoid supplement and color additive. Several studies have reported that D. salina extract could attenuate lipopolysaccharides-induced inflammatory effects and regulate the virus-induced inflammatory response in macrophages. However, the effects of D. salina on myocardial I/R injury remain unknown. Therefore, we aimed to investigate the cardioprotection of D. salina extract in rats subjected to myocardial I/R injury that was induced by occlusion of the left anterior descending coronary artery for 1 h followed by 3 h of reperfusion. Compared with the vehicle group, the myocardial infarct size significantly decreased in rats that were pre-treated with D. salina. D. salina significantly attenuated the expressions of TLR4, COX-2 and the activity of STAT1, JAK2, IκB, NF-κB. Furthermore, D. salina significantly inhibited the activation of caspase-3 and the levels of Beclin-1, p62, LC3-I/II. This study is the first to report that the cardioprotective effects of D. salina may mediate anti-inflammatory and anti-apoptotic activities and decrease autophagy through the TLR4-mediated signaling pathway to antagonize myocardial I/R injury. [ABSTRACT FROM AUTHOR]

To explore the involved mechanisms and possible treatments of ambient PM2.5 exposure-induced lung inflammation, this work studied the activity of luteolin, a natural flavonoid which widely presents in many plant species, in murine alveolar macrophage MH S cells exposed to PM2.5. Results showed PM2.5 induced an inflammatory response, as evidenced by significantly increased TNF-α, IL-6, MCP-1 and Rantes levels. and induced iNOS, COX-2, and NF-κB protein expressions in MH-S cells. Moreover, luteolin pre-treatment reduced JAK2 and STAT1 but not STAT3 protein expressions in PM2.5-stimulated MH-S cells. Performing JAK2 inhibitor AG490 further showed reduced TNF-α and IL-6 productions as well as iNOS, COX-2, and NF-κB protein expressions. In addition, although PM2.5 exposure could elevate HO-1 expression basically, luteolin pre-treatment and AG490 administration further significantly enhanced HO-1 expression additionally. Collectively, these results revealed that luteolin inhibits inflammation through suppressing JAK2/STAT1/NF-κB pathway and enhancing HO-1 expression in PM2.5-challenged alveolar macrophage MH-S cells. [ABSTRACT FROM AUTHOR]

Background: Patients with chronic obstructive pulmonary disease (COPD) are at a higher risk of many types of cancer. However, specific investigation of the risk of prostate cancer and the influence of COPD pharmacotherapy in patients with COPD is lacking. This study investigated the risk and influence of COPD pharmacotherapy on risk of prostate cancer in patients with COPD. Methods: This retrospective cohort study used data from Taiwan’s Longitudinal Health Insurance Database 2005 (LHID2005). The study cohort comprised COPD patients who received treatment between 2004 and 2008, and who were identified from the LHID2005. The control cohort comprised patients without COPD and was matched to the study cohort by age and sex. Two-stage propensity score calibration with the National Health Interview Survey 2005 was performed to obtain the missing confounders of smoking, alcohol drinking, and body mass index in the LHID. The hazard ratio (HR) and adjusted HR were estimated. Moreover, the influence of inhaled medications and other related medication on the risk of prostate cancer was analyzed by Cox proportional hazard regression. Results: The COPD cohort comprised 12,774 patients, and the control cohort comprised 38,322 patients (1:3). The incidence of prostate cancer was 633 per 100,000 person-years in the COPD cohort and 361 per 100,000 person-years in the control cohort. The propensity score calibration-adjusted HR was 1.62 (95% CI, 1.40–1.87, p < 0.001) in the COPD cohort. Further analysis revealed that the adjusted HR for the risk of prostate cancer was 1.61 (95% CI, 1.19–2.16, p = 0.002) in patients with COPD who used short-acting muscarinic antagonists (SAMAs) and 1.89 (95% CI, 1.40–2.54, p < 0.001) in patients with COPD who used short-acting beta-agonists (SABAs). COPD patients had lower risk of prostate cancer when using statin (HR = 0.63, 95% CI, 0.45–0.89, p = 0.010) or aspirin (HR = 0.55, 95% CI, 0.35–0.85, p = 0.008). Conclusion: Patients with COPD are at a higher risk of prostate cancer, particularly those using SAMAs or SABAs. This finding suggests that inflammation control may be an effective strategy for decreasing the risk of prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: We have previously described the association of rheumatoid arthritis (RA) prevalence and two epidermal growth factor receptor (EGFR) SNPs (rs17337023 and rs2227983) among the Taiwanese population. This present study aimed to elucidate whether the SNPs can alter the expression of EGFR in the progression of RA. Methods: The cohort study included 366 Taiwan’s Han Chinese RA patients and 326 age and gender matched healthy controls. Blood samples collected from the participants were analyzed to determine their serum EGFR levels and to identify EGFR SNPs from their genomic DNA. Genotyping for EGFR SNPs was performed by restriction fragment length polymorphism (RFLP) assay. The relationship between EGFR SNP and the clinical manifestations of RA was evaluated. Results: Our results showed that a statistically significant difference in genotype frequency distributions at rs17337023 SNP for RA patients and controls (p ˂ 0.05). In addition, compared with the haplotype frequencies between case and control groups, the RA patient with the GT haplotype appeared to be a significant “protective” haplotype compared with other haplotypes (OR: 0.73, 95% CI: 0.59–0.91; p = 0.005). Furthermore, the increased serum level of EGFR was also observed in RA patients (p ˂ 0.001). Conclusion: Our study showed that RA is associated with rs17337023 SNP in EGFR gene and increased serum level of the EGFR protein. These findings suggest EGFR is worthy of further investigation as a therapeutic target for RA. [ABSTRACT FROM AUTHOR]

Background Excessive reactive oxygen species (ROS) can result in inflammation and cytokine secretion in the liver, and then activate hepatic stellate cells that cause the accumulation of extracellular matrix proteins, especially collagen, in liver tissue. Naturally fermented noni juice (NJ; Morinda citrifolia ) has been used for decades as a nutraceutical in humans. In this study, we intended to examine if NJ can ameliorate ROS-induced liver fibrosis via a thioacetamide (TAA)-induced rat model. Methods The 50 rats used in this study were separated into five groups of 10 rats each for 8 weeks as follows: (1) control group; (2) TAA; (3) TAA + low-dose NJ (2.51 mL NJ/kg); (4) TAA + medium-dose NJ (5.02 mL NJ/kg); and (5) TAA + high-dose NJ (7.52 mL NJ/kg). Results Treatment with TAA resulted in lower body weight and serum lipid levels ( p < 0.05), while liver weight and collagen contents, and serum alanine aminotransferase and aspartate aminotransferase values were increased ( p < 0.05). The protective effects of NJ on TAA treatment resulted from decreased endoplasmic reticulum stress-related gene expressions ( p < 0.05), inflammatory cytokines, collagen accumulation, and matrix metalloproteinase (MMP-2 and MMP-9) activities, as well as upregulated ( p < 0.05) tissue inhibitors of metalloproteinase (TIMP-1 and TIMP-3) in livers. NJ also increased hepatic antioxidant capacities ( p < 0.05). Conclusion Naturally fermented NJ manifests a protective potential on liver fibrosis via the enhancement of antioxidant capacities, as well as decreasing endoplasmic-reticulum stress and MMP-2/MMP-9 activities. [ABSTRACT FROM AUTHOR]

Abstract: Research has indicated that inflammation promote all phases of atherosclerosis. The current study tested the hypothesis that rhinosinusitis is a risk marker for myocardial infarction (MI). Data on the general population were obtained from the Taiwan Longitudinal Health Insurance Database 2005 (LHID2005). The study cohort comprised patients who had received a recorded diagnosis of rhinosinusitis (N = 52,930) between January 1, 2004 and December 31, 2004. The comparison group consisted of patients who had not received a rhinosinusitis diagnosis, and who were matched for age and sex with the study group at a ratio of 4 controls to 1 study patient (1:4) (N = 211,720). Each patient''s condition was followed using database entries until the end of 2006. Cox proportional hazard regressions were used to evaluate the 3-year MI-free survival rates, after adjusting for known confounding factors. We found that patients with rhinosinusitis were more likely than the control group to have MI, after adjusting for potential confounders [adjusted hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.44 ∼ 2.40]. Of the total 264 650 patients, 290 experienced MI during the 3-year follow-up period, including 8 acute sinusitis patients, 77 chronic sinusitis patients, and 205 control patients. The incidence rate of MI was 6.19 (95% CI 5.01–7.65) per 10,000 person-years for rhinosinusitis patients, compared to 3.51 (95% CI, 3.06–4.02) for the control patients. From this study, rhinosinusitis may be associated with MI. Further research in this important area of public health is warranted. [Copyright &y& Elsevier]

Abstract: Carotenoids are effective antioxidants, which can quench singlet oxygen, suppress lipid peroxidation, and prevent oxidative damage. Both Pseudorabies virus (PRV) and human Herpes simplex virus (HSV) are DNA viruses, and their pathogenesis and immunobiology are similar. However, PRV does not infect humans. Therefore, PRV was used to infect murine macrophages (RAW264.7 cells), to mimic HSV-induced inflammation. Meanwhile, the influence of β-carotene on PRV-induced inflammation was also investigated. Results indicated that β-carotene inhibited (p <0.05) NO, IL-1β, IL-6, and MCP-1 production in PRV-infected RAW264.7 cells. β-Carotene also suppressed (p <0.05) NF-κB (p50 and p65), phosphorylation of extracellular-signal-related kinase (ERK), p38, and c-Jun N-terminal kinase (JNK) expression. It could be concluded that the anti-inflammatory effect of β-carotene is mainly through a suppression of cytokine expression in PRV-induced inflammation, which results from NF-κB inactivation. β-Carotene can be considered a potential anti-inflammatory agent for DNA-virus infection. [Copyright &y& Elsevier]

Background: Research has found evidence that chronic inflammation may promote atherosclerotic disease. The purpose of this study was to test the hypothesis that rhinosinusitis is a risk factor for stroke. Methods: This prospective cohort study comprised patients recorded on the Taiwan Longitudinal Health Insurance Database 2005 (LHID2005) who had received a diagnosis of rhinosinusitis (n = 53,653) between January 1, 2004 and December 31, 2005. A control group (1:4) drawn from the same database was matched for age and gender (n = 214,624). Each patient was followed up using data entered until the end of 2006. Cox proportional hazard regressions were performed to evaluate the hazard ratios (HRs) after adjusting for potential confounding factors. Results: We found that patients with rhinosinusitis were more likely to suffer strokes than the control population, after adjusting for potential confounders (adjusted HR, 1.39; 95% confidence interval [CI], 1.28∼1.50). The HR of stroke was 1.39 (95% CI, 1.28∼1.51) for acute sinusitis patients, and 1.34 (95% CI, 1.04∼1.74) for chronic sinusitis patients. Conclusion: Both acute and chronic sinusitis are risk factors or markers for stroke that is independent of traditional stroke risk factors. Further research in this important area of epidemiology is warranted. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) commonly causes inflammation in the joints and periarticular structures. The association between RA and rotator cuff (RC) has been reported; however, epidemiological studies on RA and RC tendons are scant. Therefore, we investigated RC disease (RCD) risk and analyzed the effects of RA medication, steroids, and methotrexate, on the risk of RCD for patients with RA. We conducted a retrospective cohort study with a 6-year longitudinal follow-up in Taiwan. Patients who received RA diagnoses between 2004 and 2008 were enrolled in the study cohort. The non-RA control cohort comprised age- and sex-matched controls. Propensity score matching was used for other comorbidities and treatments. The hazard ratios (HRs) and adjusted HRs (aHRs) were estimated after confounders were adjusted for. Effects of steroid and methotrexate use on RCD risk were also analyzed. We enrolled 4521 RA patients (study cohort) and 22,605 matched controls. RCD incidence was 145 and 91 per 100,000 person-years in the RA and control cohorts, respectively. In the RA cohort, the crude HR for RCD was 1.62 (95% confidence interval (CI), 1.41–1.86, p < 0.001), and the aHR was 1.56 (95% CI, 1.36–1.79, p < 0.001). The methotrexate nonusers exhibited an aHR (vs. controls) of 1.61 (95% CI, 1.40–1.85, p < 0.001), but the methotrexate users did not have a significantly higher aHR than the controls. The steroid nonusers had an aHR (vs. controls) of 1.69 (95% CI, 1.46–1.96, p < 0.001), but the aHR of the steroid users was not significantly higher than the control aHR. Patients with RA had a higher risk for RCD compared with the non-RA control cohort. Steroids or methotrexate use significantly reduces the risk of RCD occurrence in patients with RA. Treatment for RCD symptoms and controlling inflammatory process are important to ensure high-quality care for patients with RA. [ABSTRACT FROM AUTHOR]

Abstract: Background: There is evidence that chronic inflammation may promote atherosclerotic disease. The purpose of this study was to test the hypothesis that pelvic inflammatory disease (PID) is a risk marker for myocardial infarction (MI). Method: Using the Taiwan Longitudinal Health Insurance Database 2005 (LHID2005), this cohort study comprised patients with a recorded diagnosis of PID (N =68,668) between January 1, 2004 and December 31, 2005, with age-matched controls (1:2) (N =136,906). Each patient was followed-up using entry data until the end of 2006. Cox proportional hazard regressions were used to evaluate the up to 3-year MI-free survival rates, after adjusting for known confounding factors. Results: We found that patients with PID were more likely to have MI than the control population after adjusting for potential confounders [adjusted hazard ratio (HR), 1.86, 95% confidence interval (CI), 1.23–2.81]. When stratified by patient's age, the adjusted HR for MI was 2.09 (95% CI, 1.24–3.52) for patients with PID aged over 55years. However, the adjusted HR for MI occurring was not significant for patients with PID aged≤55years. Conclusions: PID is a risk marker for MI that is independent of traditional MI risk factors. Further research in this important area of public health is warranted. [Copyright &y& Elsevier]

Abstract: The effects of taurine (Tau) in regulation of lipid metabolism and decreasing inflammation in chronic alcohol-fed rats was investigated. Rats were randomly divided into three groups: (1) isocaloric solution; (2) 3g alcohol/kg BW/day; (3) 3g alcohol/kg BW/day+1g Tau/kg BW/day for 6weeks. Liver size and serum/liver lipids of alcohol-fed rats were decreased (p <0.05) by Tau supplementation, but daily fecal lipid/bile acid outputs were increased (p <0.05). Regarding de novo lipogenesis, Tau downregulated (p <0.05) fatty-acid biosynthesis and upregulated (p <0.05) cholesterol metabolism (CYP7A1) and energy expenditure (PPAR-α). Serum AST and ALT, and hepatic TNF-α levels and MMP-9 activity of alcohol-fed rats were decreased (p <0.05) by Tau supplementation which may be related to the maintenance of higher (p <0.05) antioxidant levels (lower thiobarbituric-acid-reactive-substances values and higher trolox equivalent antioxidant capacity) in serum and livers. Our study indicates that Tau downregulates lipogenesis, oxidative stress, and inflammation in chronic alcohol-fed rats. [Copyright &y& Elsevier]