Neutrophils are the most abundant innate immune cells. The pathogenic roles of neutrophils are related to chronic inflammation and autoimmune diseases. Psoriasis is a chronic systemic inflammatory disease affecting ∼2-3% of the world population. The abundant presence of neutrophils in the psoriatic skin lesions serves as a typical histopathologic hallmark of psoriasis. Recent reports indicated that oxidative stress, granular components, and neutrophil extracellular traps from psoriatic neutrophils are related to the initial and maintenance phases of psoriasis. This review provides an overview on the recent (up to 2019) advances in understanding the role of neutrophils in the pathophysiology of psoriasis, including the effects of respiratory burst, degranulation, and neutrophil extracellular trap formation on psoriatic immunity and the clinical relationships.
Neutrophil infiltration plays a significant pathological role in inflammatory diseases. NADPH oxidase type 2 (NOX2) is a respiratory burst oxidase that generates large amounts of superoxide anion (O 2 •− ) and subsequent other reactive oxygen species (ROS). NOX2 is an emerging therapeutic target for treating neutrophilic inflammatory diseases. Herein, we show that 4-[(4-(dimethylamino)butoxy)imino]-1-methyl-1 H -benzo[ f ]indol-9(4 H )-one (CYR5099) acts as a NOX2 inhibitor and exerts a protective effect against complete Freund's adjuvant (CFA)-induced inflammatory arthritis in mice. CYR5099 restricted the production of O 2 •− and ROS, but not the elastase release, in human neutrophils activated with various stimulators. The upstream signaling pathways of NOX2 were not inhibited by CYR5099. Significantly, CYR5099 inhibited NOX2 activity in activated human neutrophils and in reconstituted subcellular assays. In addition, CYR5099 reduced ROS production, neutrophil infiltration, and edema in CFA-induced arthritis in mice. Our findings suggest that CYR5099 is a NOX2 inhibitor and has therapeutic potential for treating neutrophil-dominant oxidative inflammatory disorders.
Polycystic ovary syndrome (PCOS) is a common endocrine disease of reproductive-age women, accounting for about 9% to 18% of all women in this age group. Hyperandrogenemia, oligomenorrhea, or amenorrhea or anovulation, and polycystic ovary morphology are the 3 main criteria used to diagnose PCOS currently. Substantial scientific evidence and consensus on treating Taiwanese PCOS was lacking. The aim of this study is to investigate the characteristics and utilization of traditional Chinese medicine (TCM) among Taiwanese women with PCOS. The data used in this study were derived from the Longitudinal Health Insurance Database (LHID 2000 and LHID 2005). Demographic characteristics, TCM usage, the frequency, as well as average daily dose of Chinese herbal formulas and the single herbs prescribed for patients with PCOS, were analyzed. Chinese herbal formulas and the single herbs prescribed for PCOS women during 1999 to 2013 were extracted to build up Chinese Herbal Medicine prescription database. In our study, 66.43% (n = 8205) women sought TCM treatment because of PCOS for infertility or menstrual disorders. The most commonly prescribed Chinese herbal formula was Jia-wei-xiao-yao-san (Supplemented Free Wanderer Powder). The most commonly prescribed single herb was Yi-mu-cao ( Leonuri herba ). Among top 20 Chinese herbal formulas, Si-wu-tang has the largest average daily dosage (9.60 g). Our study identified the characteristics and prescription patterns of TCM for patients with PCOS in Taiwan. We may need do further longitudinal research for TCM and its long-term response for improvement of pregnancy rate and reduction of metabolic disease rate.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint deformity and disability. Deer velvet antler (DA), a traditional Chinese medicine, has been used to treat various types of arthritis for several thousands of years, but the underlying mechanisms are unknown. Herein, we investigated the anti-arthritic and anti-inflammatory effects of DA in vitro and in vivo. The ethyl acetate layer of DA ethanol extract (DA-EE-EA) was used to treat tumor necrosis factor (TNF)-[Formula: see text]-stimulated fibroblast-like synoviocyte MH7A cells, collagen-induced arthritis DBA/1 mice, and SKG mice with zymosan-induced arthritis. DA-EE-EA reduced nitric oxide production, prostaglandin E2 levels, and levels of pro-inflammatory cytokines including interleukin (IL)-1[Formula: see text], IL-6, and IL-8 in MH7A cells. DA-EE-EA also downregulated the phosphorylation of mitogen-activated protein kinase p38 and c-Jun N-terminal kinase and the translocation of nuclear factor kappa B p65. Intraperitoneal injection of DA-EE-EA for 3 weeks substantially reduced clinical arthritis scores in vivo models. Pathohistological images of the hind paws showed that DA-EE-EA reduced immune cell infiltration, synovial hyperplasia, and cartilage damage. The levels of pro-inflammatory cytokines, such as tumor necrosis factor alpha, IL-1[Formula: see text], IL-6, IL-8, IL-17A, and interferon-gamma, decreased in the hind paw homogenates of DA-EE-EA-treated mice. We also identified several potential components, such as hexadecanamide, oleamide, erucamide, and lysophosphatidylcholines, that might contribute to the anti-inflammatory effects of DA-EE-EA. In conclusion, DA-EE-EA has the potential to treat RA by regulating inflammatory responses. However, the individual components of DA-EE-EA and the underlying anti-inflammatory mechanisms need further investigation in future studies.
Neutrophils are the primary immune cells in innate immunity, which are related to various inflammatory diseases. Astragalus mongholicus Bunge is a Chinese medicinal herb used to treat various oxidative stress-related inflammatory diseases. However, there are limited studies that elucidate the effects of Astragalus mongholicus Bunge in human neutrophils. In this study, we used isolated human neutrophils activated by various stimulants to investigate the anti-inflammatory effects of Astragalus mongholicus Bunge water extract (AWE). Cell-free assays were used to examine free radicals scavenging capabilities on superoxide anion, reactive oxygen species (ROS), and nitrogen-centered radicals. Imiquimod (IMQ) induced psoriasis-like skin inflammation mouse model was used for investigating anti-psoriatic effects. We found that AWE inhibited superoxide anion production, ROS generation, and elastase release in human neutrophils, which exhibiting a direct anti-neutrophil effect. Moreover, AWE exerted a ROS scavenging ability in the 2,2’-Azobis (2-amidinopropane) dihydrochloride assay, but not superoxide anion in the xanthine/xanthine oxidase assay, suggesting that AWE exhibited anti-oxidation and anti-inflammatory capabilities by both scavenging ROS and by directly inhibiting neutrophil activation. AWE also reduced CD11b expression and adhesion to endothelial cells in activated human neutrophils. Meanwhile, in mice with psoriasis-like skin inflammation, administration of topical AWE reduced both the affected area and the severity index score. It inhibited neutrophil infiltration, myeloperoxidase release, ROS-induced damage, and skin proliferation. In summary, AWE exhibited direct anti-inflammatory effects by inhibiting neutrophil activation and anti-psoriatic effects in mice with IMQ-induced psoriasis-like skin inflammation. Therefore, AWE could potentially be a pharmaceutical Chinese herbal medicine to inhibit neutrophilic inflammation for anti-psoriasis.
Background: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in Taiwan. Chronic obstructive pulmonary disease (COPD) is associated with CRC mortality in several population-based studies. However, this effect of COPD on CRC shows no difference in some studies and remains unclear in Taiwan’s population. Methods: We conducted a retrospective cohort study using Taiwan’s nationwide database. Patients newly diagnosed with CRC were identified from 2007 to 2012 via the Taiwan Cancer Registry dataset and linked to the National Health Insurance research database to obtain their medical records. Propensity score matching (PSM) was applied at a ratio of 1:2 in COPD and non-COPD patients with CRC. The 5-year overall survival (OS) was analyzed using the Cox regression method. Results: This study included 43,249 patients with CRC, reduced to 13,707 patients after PSM. OS was lower in the COPD group than in the non-COPD group. The adjusted hazard ratio (aHR) for COPD was 1.26 (95% confidence interval (CI), 1.19–1.33). Moreover, patients with CRC plus preexisting COPD showed a higher mortality risk in all stage CRC subgroup analysis. Conclusions: In this 5-year retrospective cohort study, patients with CRC and preexisting COPD had a higher mortality risk than those without preexisting COPD, suggesting these patients need more attention during treatment and follow-up.
This cross-sectional study aimed to explore the influence of the COVID-19 pandemic on physical activity (PA) and dietary habits, and their impact on body weight changes during the Level 3 alert period that resulted in the lockdown in Taiwan. The study was conducted between 1 July 2021 and 15 July 2021, using a Google Forms online survey platform. Personal data, anthropometric information, PA information, and dietary habit information were collected before and during the alert period. Exactly 374 respondents, aged between 20 and 66, were included in the study. The results indicate that the lockdown during the alert period negatively impacted all levels of PA, including vigorous and moderate activities and walking. Additionally, respondents showed a sedentary lifestyle, with an increased daily sitting time of 22%. However, body weight and dietary behavior were not significantly affected, and some dietary questions achieved significant differences, including eating three meals less regularly, among others. During the pandemic, exercise was still one of the most important ways to maintain health; therefore, we hope to bring more attention to the prevention of sedentary lifestyles and dietary abnormalities in Taiwan during a pandemic.
Background: Kan-Lu-Hsiao-Tu-Tan (KLHTT) exhibits anti-psoriatic effects through anti-inflammatory activity in mice. However, the therapeutic effects of KLHTT on rheumatoid arthritis (RA), another significant autoimmune inflammatory disorder, have not been elucidated. Herein, we explored the anti-arthritic effects of KLHTT on collagen-induced arthritis (CIA) in mice. Methods: KLHTT was extracted by boiling water and subjected to spectroscopic analysis. Chicken collagen type II (CII) with complete Freund’s adjuvant was intradermally injected to induce CIA in DBA/1J mice. Anti-CII antibody, cytokines, malondialdehyde (MDA), and hydrogen peroxide (H2O2) were measured using ELISA, thiobarbituric acid reactive substances, and a hydrogen peroxide assay kit. Splenocyte proliferation was tested using thymidine incorporation. Th1 and Th17 cells were analyzed by flow cytometry. Results: Oral KLHTT treatment (50 and 100 mg/kg) ameliorated mouse CIA by decreasing the levels of interleukin (IL)-1β, IL-6, IL-17A, and tumour necrosis factor-α in the paw homogenates and serum. KLHTT also suppressed anti-CII antibody formation, splenocyte proliferation, and splenic Th1 and Th17 cell numbers. Additionally, KLHTT showed antioxidant activity by reducing the concentrations of MDA and H2O2 in paw tissues. Conclusions: The therapeutic effects of KLHTT in CIA mice were through regulating oxidative stress and inflammatory responses. Our results suggest that KLHTT has potential to treat RA.
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