ABSTRACT
PURPOSE: To investigate the association of food insecurity with overall and disease-specific mortality among US cancer survivors. METHODS: Data from the National Health and Nutrition Examination Survey (NHANES 1999-2018) were used to examine the impact of food insecurity on mortality risks among cancer survivors in the US. Study participants aged ≥ 20 years who had a history of cancer and completed the Adult Food Security Survey Module were included. Mortality data [all-cause, cancer, and cardiovascular (CVD) specific] through December 31, 2019 were obtained through linkage to the National Death Index. Using multivariable Cox proportional hazard regression, hazard ratios of mortality based on food security status were estimated. RESULTS: Among 5032 cancer survivors (mean age 62.5 years; 58.0% women; 86.2% non-Hispanic White), 596 (8.8%) reported food insecurity. Overall, 1913 deaths occurred (609 cancer deaths and 420 CVD deaths) during the median follow-up of 6.8 years. After adjusting for age, food insecurity was associated with a higher risk of overall (HR = 1.93; 95% CI = 1.56-2.39), CVD-specific (HR = 1.95; 95% CI = 1.24-3.05), and cancer-specific (HR = 1.70; 95% CI = 1.20-2.42) mortality (P < 0.001). However, after adjusting for socioeconomic characteristics and health-related factors (physical activity, diet quality measured by healthy eating index), the association between food insecurity and overall mortality was no longer statistically significant. CONCLUSIONS: Food insecurity was associated with a greater risk of overall mortality among cancer survivors. Further studies are needed to confirm these findings and evaluate whether the observed association represents a causal phenomenon and, if so, whether the effect is modifiable with food assistance programs.
Subject(s)
Cancer Survivors , Food Insecurity , Neoplasms , Nutrition Surveys , Humans , Female , Male , Middle Aged , Cancer Survivors/statistics & numerical data , United States/epidemiology , Aged , Neoplasms/mortality , Adult , Cardiovascular Diseases/mortality , Cardiovascular Diseases/epidemiology , Proportional Hazards ModelsABSTRACT
Introduction: Diabetes is a common comorbidity among people with cancer. The objective of our study was to examine patterns of health care use among patients with cancer and either type 2 diabetes or prediabetes. Methods: We used data from the National Health and Nutrition Examination Survey (NHANES) for 2017-2020. The study population included US adults aged 18 years or older who were diagnosed with any cancer and type 2 diabetes or prediabetes (established by self-report and/or hemoglobin A1c measurement). We used Poisson and multivariate logistic regression models to determine the effect of comorbidity on health care use, defined as health care visits and overnight stays in a hospital. Results: Of 905 cancer patients representing 27,180,715 people in the US, 24.4% had a type 2 diabetes diagnosis, and 25.8% had a prediabetes diagnosis. Patients with cancer and prediabetes had a significantly higher rate of health care visits (incidence rate ratio = 1.11; 95% CI, 1.01-1.22; P = .03) than patients with cancer only. We found no significant association between having cancer and type 2 diabetes and the number of health care visits or overnight hospital stays compared with patients with cancer only. Conclusion: More emphasis should be placed on optimal care coordination among people with cancer and other conditions, such as diabetes and prediabetes, to reduce the impact of comorbidity on health care use. Interventions integrated with technology to provide timely access to education on preventing or managing diabetes and prediabetes among cancer patients are warranted.
Subject(s)
Diabetes Mellitus, Type 2 , Neoplasms , Nutrition Surveys , Prediabetic State , Humans , Male , Female , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/therapy , Neoplasms/epidemiology , Middle Aged , United States/epidemiology , Adult , Prediabetic State/epidemiology , Patient Acceptance of Health Care/statistics & numerical data , Aged , Comorbidity , Young AdultABSTRACT
Media exposed to atmospheric pressure plasma (APP) produce reactive oxygen and nitrogen species (RONS), with hydrogen peroxide (H2O2), nitrite (NO2-), and nitrate (NO3-) being among the most detected species due to their relatively long lifetime. In this study, a standardized microwave-excited (ME) APP jet (APPJ) source was employed to produce gaseous RONS to treat liquid samples. The source was a commercially available plasma jet, which generated argon plasma utilizing a coaxial transmission line resonator at the operating frequency of 2.45 GHz. An ultraviolet-visible spectrophotometer was used to measure the concentrations of H2O2 and NO3- in plasma-activated media (PAM). Three different types of media (deionized water, Hank's balanced salt solution, and cell culture solution Dulbecco's modified eagles medium [DMEM]) were utilized as liquid samples. Among these media, the plasma-treated DMEM was observed to have the highest levels of H2O2 and NO3-. Subsequently, the feasibility of using argon ME-APPJ-activated DMEM (PAM) as an adjuvant to enhance the therapeutic effects of cisplatin on human bladder cancer cells (T-24) was investigated. Various cancer cell lines, including T-24 cells, treated with PAM were observed in vitro for changes in cell viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. A viability reduction was detected in the various cancer cells after incubation in PAM. Furthermore, the study's results revealed that PAM was effective against cisplatin-resistant T-24 cells in vitro. In addition, a possible connection between HER expression and cell viability was sketched.
Subject(s)
Plasma Gases , Urinary Bladder Neoplasms , Humans , Cisplatin/pharmacology , Hydrogen Peroxide/pharmacology , Microwaves , Atmospheric Pressure , Reactive Oxygen Species/metabolism , Reactive Nitrogen Species/metabolism , Urinary Bladder Neoplasms/drug therapy , Plasma Gases/pharmacologyABSTRACT
BACKGROUND: Allergic rhinitis (AR) is characterized by airway inflammation in nasal mucosa from inhaled allergens and interleukin (IL)-33 is the potent inducer of Th2 inflammation in allergic nasal epithelium. Staphylococcus epidermidis is one of the most abundant colonizers of the healthy human nasal mucosa and might impact the allergen-induced inflammatory responses in the nasal epithelium. Thus, we sought to characterize the mechanism of S. epidermidis regulating Th2 inflammation and IL-33 production in AR nasal mucosa. RESULTS: The AR symptoms were alleviated and eosinophilic infiltration, serum IgE levels, and Th2 cytokines were significantly decreased in OVA-sensitized AR mice in response to human nasal commensal S. epidermidis. The inoculation of S. epidermidis to normal human nasal epithelial cells reduced IL-33 and GATA3 transcriptions and also reduced IL-33 and GATA3 expression in AR nasal epithelial (ARNE) cells and the nasal mucosa of AR mice. Our data exhibited that the cellular necroptosis of ARNE cells might be involved in IL-33 production and inoculation of S. epidermidis decreased the phosphorylation of necroptosis enzymes in ARNE cells, which was related to the reduction of IL-33 production. CONCLUSIONS: We present that human nasal commensal S. epidermidis reduces allergic inflammation by suppressing IL-33 production in nasal epithelium. Our findings indicate that S. epidermidis serves a role in blocking allergen-induced cellular necroptosis in allergic nasal epithelium which might be a key mechanism of reduction of IL-33 and Th2 inflammation.
Subject(s)
Rhinitis, Allergic , Staphylococcus epidermidis , Humans , Animals , Mice , Interleukin-33 , Necroptosis , Immunoglobulin E/metabolism , Th2 Cells , Nasal Mucosa , Allergens , Inflammation , Cytokines/metabolism , Disease Models, Animal , Mice, Inbred BALB CABSTRACT
Neutrophils are important effector cells of the innate immune response that fight pathogens by phagocytosis and degranulation. Neutrophil extracellular traps (NETs) are released into the extracellular space to defend against invading pathogens. Although NETs play a defensive role against pathogens, excessive NETs can contribute to the pathogenesis of airway diseases. NETs are known to be directly cytotoxic to the lung epithelium and endothelium, highly involved in acute lung injury, and implicated in disease severity and exacerbation. This review describes the role of NET formation in airway diseases, including chronic rhinosinusitis, and suggests that targeting NETs could be a therapeutic strategy for airway diseases.
Subject(s)
Extracellular Traps , Respiration Disorders , Humans , Respiration Disorders/pathology , Neutrophils , Immunity, Innate , Chronic DiseaseABSTRACT
BACKGROUND: l-Leucine powder (LP) was added to green Robusta coffee beans in order to reduce the difference in flavour between Robusta and Arabica coffee. l-Leucine was selected as an additive based on the Maillard reaction. The pre-treatment method conducted in this study was a short soaking (M1) or spraying procedure (M2), then LP was added at varying levels up to 3% (w/w, 30 g kg-1 ). All samples were roasted (240 °C for 15 min) and extracted using an espresso machine. Volatile compounds were analysed by solid-phase microextraction-gas chromatography-mass selective detection. RESULTS: Thirty volatile compounds (six pyrroles, eight pyrazines, three phenols, nine furans, two ketones, two aldehydes) were analysed. In 15 coffee samples, the levels of total volatile compounds (based on peak area ratios) ranged from 8.9 (M1-1) to 15. Non-treated Robusta had higher levels of bitter aroma compounds than Arabica coffee, and Robusta coffee had lower levels of bitter aroma compounds when pre-treated with LP. The sum of bitter volatiles (phenols, pyrroles, pyrazines) was lowest in M1-5 (3% LP), M2-1 (1% LP; both dried at 50 °C for 15 min) and M2-7 (3% LP, dried at 70 °C for 15 min) compared with non-treated Robusta (P < 0.05). CONCLUSION: From the results of this study it can be shown that pre-treatment with LP can improve the flavour of Robusta. © 2023 Society of Chemical Industry.
Subject(s)
Coffea , Leucine , Powders , Coffea/chemistry , Odorants/analysis , Maillard ReactionABSTRACT
High-resolution 3D-printable hydrogels with high mechanical strength and biocompatibility are in great demand because of their potential applications in numerous fields. In this study, a material system comprising Pluronic F-127 dimethacrylate (FDMA) is developed to function as a direct ink writing (DIW) hydrogel for 3D printing. FDMA is a triblock copolymer that transforms into micelles at elevated temperatures. The transformation increases the viscosity of FDMA and preserves its structure during DIW 3D printing, whereupon the printed structure is solidified through photopolymerization. Because of this viscosity shift, various functionalities can be incorporated through the addition of other materials in the solution state. Acrylic acid is incorporated into the pregel solution to enhance the mechanical strength, because the carboxylate group of poly(acrylic acid) ionically crosslinks with Fe3+ , increasing the toughness of the DIW hydrogel 37 times to 2.46 MJ m-3 . Tough conductive hydrogels are also 3D printed by homogenizing poly(3,4-ethylenedioxythiophene) polystyrene sulfonate into the pregel solution. Furthermore, the FDMA platform developed herein uses DIW, which facilitates multicartridges 3D printing, and because all the materials included are biocompatible, the platform may be used to fabricate complex structures for biological applications.
Subject(s)
Hydrogels , Poloxamer , Ink , Polymers , Printing, Three-DimensionalABSTRACT
Pesticides and veterinary drugs are generally employed to control pests and insects in crop and livestock farming. However, remaining residues are considered potentially hazardous to human health and the environment. Therefore, regular monitoring is required for assessing and legislation of pesticides and veterinary drugs. Various approaches to determining residues in various agricultural and animal food products have been reported. Most analytical methods involve sample extraction, purification (cleanup), and detection. Traditional sample preparation is time-consuming labor-intensive, expensive, and requires a large amount of toxic organic solvent, along with high probability for the decomposition of a compound before the analysis. Thus, modern sample preparation techniques, such as the quick, easy, cheap, effective, rugged, and safe method, have been widely accepted in the scientific community for its versatile application; however, it still requires a laboratory setup for the extraction and purification processes, which also involves the utilization of a toxic solvent. Therefore, it is crucial to elucidate recent technologies that are simple, portable, green, quick, and cost-effective for onsite and infield residue detections. Several technologies, such as surface-enhanced Raman spectroscopy, quantum dots, biosensing, and miniaturized gas chromatography, are now available. Further, several onsite techniques, such as ion mobility-mass spectrometry, are now being upgraded; some of them, although unable to analyze field sample directly, can analyze a large number of compounds within very short time (such as time-of-flight and Orbitrap mass spectrometry). Thus, to stay updated with scientific advances and analyze organic contaminants effectively and safely, it is necessary to study all of the state-of-art technology.
Subject(s)
Pesticides/analysis , Veterinary Drugs/analysis , Gas Chromatography-Mass Spectrometry , Quantum Dots/chemistry , Spectrum Analysis, RamanABSTRACT
IL-17 family cytokines are directly involved in host immune responses and the critical mediators for host defense against infection or inflammation. IL-17C is highly expressed in respiratory epithelium and is induced after acute bacterial lung infection. However, the definite function of IL-17C induced by Pseudomonas aeruginosa (PAO1 strain) is not fully understood, and our study was designed to demonstrate IL-17C-induced immune response against PAO1 infection in nasal epithelium. Passage-2 normal human nasal epithelial (NHNE) cells were infected with PAO1 and the relationship between IL-17C-related immune responses and the iron absorption of PAO1, depending on inoculation of recombinant human IL-17C (rhIL-17C), was assessed by measuring the siderophore activity of PAO1. Microarray data showed that IL-17C expression increased 34.7 times at 8 hours postinfection (hpi) in NHNE cells, and IL-17C mRNA levels increased until 48 hpi. The PAO1 colonies significantly increased from 8 hpi in NHNE cells, and siderophore activity of PAO1 was enhanced in the supernatants of PAO1-infected NHNE cells. Interestingly, PAO1 colonies were reduced in PAO1-infected NHNE cells treated with rhIL-17C, and supernatants from NHNE cells treated with rhIL-17C also exhibited decreased PAO1 colonies. We found that the siderophore activity of PAO1 was significantly reduced in the supernatants of NHNE cells treated with rhIL-17C where LCN2 expression was highly elevated. Our findings indicate that IL-17C mediates an antibacterial effect against PAO1 by inhibiting siderophore activity in nasal epithelium. We propose that IL-17C might be an efficient mediator to suppress PAO1 infection through disturbing iron absorption of PAO1 in nasal epithelium.
Subject(s)
Interleukin-17/immunology , Nasal Mucosa/immunology , Pseudomonas Infections/immunology , Pseudomonas aeruginosa/immunology , Respiratory Mucosa/immunology , Cell Line , Epithelial Cells/immunology , Humans , RNA, Messenger/immunology , Siderophores/immunologyABSTRACT
BACKGROUND: The host-microbial commensalism can shape the innate immune responses in respiratory mucosa and nasal microbiome also modulates front-line immune mechanism in the nasal mucosa. Inhaled allergens encounter the host immune system first in the nasal mucosa, and microbial characteristics of nasal mucus directly impact the mechanisms of initial allergic responses in nasal epithelium. However, the roles of the nasal microbiome in allergic nasal mucosa remain uncertain. We sought to determine the distribution of nasal microbiomes in allergic nasal mucosa and elucidate the interplay between nasal microbiome Staphylococcus species and Th2 cytokines in allergic rhinitis (AR) models. RESULTS: Staphylococcus aureus (AR-SA) and S. epidermidis (AR-SE) were isolated from the nasal mucosa of patients with AR. The influence of nasal microbiome Staphylococcus species on allergic nasal mucosa was also tested with in vitro and in vivo AR models. Pyrosequencing data showed that colonization by S. epidermidis and S. aureus was more dominant in nasal mucus of AR subjects. The mRNA and protein levels of IL-33 and TSLP were significantly higher in AR nasal epithelial (ARNE) cells which were cultured from nasal mucosa of AR subjects, and exposure of ARNE cells to AR-SA reduced IL-33 mRNA and secreted protein levels. Particularly, ovalbumin-driven AR mice inoculated with AR-SA by intranasal delivery exhibited significantly reduced IL-33 in their nasal mucosa. In the context of these results, allergic symptoms and Th2 cytokine levels were significantly downregulated after intranasal inoculation of AR-SA in vivo AR mice. CONCLUSION: Colonization by Staphylococcus species was more dominant in allergic nasal mucosa, and nasal commensal S. aureus from subjects with AR mediates anti-allergic effects by modulating IL-33-dependent Th2 inflammation. The results demonstrate the role of host-bacterial commensalism in shaping human allergic inflammation.
Subject(s)
Immunity, Innate , Nasal Mucosa/immunology , Rhinitis, Allergic/immunology , Staphylococcus aureus/immunology , Staphylococcus epidermidis/immunology , Symbiosis/immunology , Animals , Corynebacterium/growth & development , Cytokines/genetics , Cytokines/immunology , Disease Models, Animal , Enterobacter aerogenes/growth & development , Epithelial Cells/immunology , Epithelial Cells/microbiology , Female , Gene Expression , Humans , Interleukin-33/genetics , Interleukin-33/immunology , Mice, Inbred BALB C , Micrococcus luteus/growth & development , Mucus/immunology , Mucus/microbiology , Nasal Mucosa/microbiology , Ovalbumin/administration & dosage , Primary Cell Culture , RNA, Messenger/genetics , RNA, Messenger/immunology , Rhinitis, Allergic/chemically induced , Rhinitis, Allergic/microbiology , Rhinitis, Allergic/pathology , Staphylococcus aureus/growth & development , Staphylococcus epidermidis/growth & developmentABSTRACT
Lycopodium clavatum has been used in traditional medicine for the treatment of kidney disorders, rheumatic arthritis, cystitis, and gastritis. We isolated a new serratane triterpenoid (2), and five known triterpenoids (1, 3-6) from the ethyl acetate fraction of L. clavatum by bioactivity-guided fractionation based on their suppression of inflammatory cytokines. Two different cell lines, RAW 264.7 and HT-29 were used to determine the anti-inflammatory activity of the isolated compounds. Among them, compounds 1, 2, 4, and 5 significantly inhibited the production of lipopolysaccharide (LPS)-induced NO in macrophages. Compounds 1, 2, 4, and 5 reduced inducible nitric oxide (iNOS) expression in RAW 264.7 cells and compounds 1 and 6 downregulated COX-2, which correlated with the reduced expression of PGE2. Compounds 1, 2, 4, and 5 downregulated pro-inflammatory cytokines, such as interleukin-1ß (IL-1ß) in macrophages, and additionally suppressed the levels of IL-8 in HT-29 cells. To determine the signaling pathways involved in the suppression of NO production by these compounds, we investigated ERK1/2 and nuclear factor-kappa B (NF-κB) expression by western blot analysis. We observed that these compounds downregulated the expression of LPS-induced NF-κB and pERK 1/2 in RAW 264.7 cells. Our results demonstrate that serratane triterpenoids isolated from L. clavatum may be used as potential candidates for treating inflammatory bowel disease (IBD) due to their anti-inflammatory effects.
Subject(s)
Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Inflammation Mediators/metabolism , Lycopodium/chemistry , Triterpenes/chemistry , Triterpenes/pharmacology , Animals , HT29 Cells , Humans , Inflammation Mediators/antagonists & inhibitors , Mice , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/metabolism , RAW 264.7 CellsABSTRACT
BACKGROUND: The 4G4G genotype of plasminogen activator inhibitor 1 (PAI-1) is associated with increased plasma PAI-1 levels and poor asthma control. Previous studies suggest that soy isoflavones can reduce PAI-1 levels. OBJECTIVE: We sought to investigate PAI-1 genotype-specific differences of the soy isoflavone response in asthma outcomes. METHODS: A PAI-1 functional polymorphism (rs1799768, 4G5G) was characterized in subjects with poorly controlled asthma enrolled in a randomized clinical trial of soy isoflavones (n = 265). Genotype-specific treatment responses on asthma outcomes were compared between soy isoflavones and placebo. Normal human bronchial epithelial cells were cultured with or without TGF-ß1, genistein, or both, and PAI-1 levels were measured. RESULTS: The 4G4G/4G5G genotype was associated with a greater risk for allergy-related worsened asthma symptoms and eczema at baseline compared with the 5G5G genotype. There was a significant interaction between the genotype and soy isoflavone intervention on oral corticosteroid use for asthma exacerbation (P = .005). In a subgroup analysis soy isoflavones significantly reduced the use of oral corticosteroids (number of events/person-year) by 4-fold compared with placebo in the 4G4G/4G5G genotype (0.2 vs 0.8; relative risk, 0.28; P < .001) but not in the 5G5G genotype. Soy isoflavones reduced plasma PAI-1 levels compared with placebo. Genistein treatment reduced TGF-ß1-induced PAI-1 production in normal human bronchial epithelial cells. CONCLUSIONS: This study demonstrates that soy isoflavone treatment provides a significant benefit in reducing the number of severe asthma exacerbations in asthmatic patients with the high PAI-1-producing genotype. PAI-1 polymorphisms can be used as a genetic biomarker for soy isoflavone-responsive patients with asthma.
Subject(s)
Asthma/drug therapy , Glycine max , Isoflavones/therapeutic use , Plasminogen Activator Inhibitor 1/genetics , Adolescent , Adrenal Cortex Hormones/therapeutic use , Adult , Asthma/blood , Asthma/genetics , Biomarkers , Bronchi/cytology , Cell Line , Epithelial Cells/metabolism , Female , Genotype , Humans , Isoflavones/pharmacology , Male , Middle Aged , Plasminogen Activator Inhibitor 1/metabolism , Polymorphism, Single Nucleotide , Young AdultABSTRACT
The possibility has been suggested that interferon (IFN)-λs can be induced rapidly for restricting respiratory viral infection in asthmatic mice and may modulate Th2-related immune responses that underlie the pathogenesis of asthma. We sought to determine the in vivo contribution of IFN-λs on decrease of Th2 cytokines in the respiratory tract of in vivo asthma. Lungs of asthmatic mice were severely inflamed, with extensive inflammatory cell infiltration and increased goblet cell metaplasia with higher total lung resistance. The mean protein levels of TSLP and IL-33 from BAL fluid of asthmatic mice were significantly higher until 7â¯days. Following the collection of lung tissue of 20 asthmatic mice, TSLP and IL-33 gene expressions inversely correlated with mRNA levels of IFN-λ2/3. Asthmatic mice were administered recombinant IFN-λ2/3 via the intranasal route and the mRNA levels of IFN-stimulated genes were elevated to an even greater extent in the lung tissue of the mice without intranasal IFN-λ2/3. Asthma-related histopathologic lung inflammation was significantly improved and total lung resistance was maintained within normal range in IFN-λ2/3-treated asthmatic mice. Moreover, IFN-λ2/3-treated asthmatic mice exhibited significant decrease of secreted protein levels of TSLP and IL-33 in the BAL fluid until 7â¯days after IFN administration. The current data provide compelling evidence that the compensation of IFN-λs can restrict the secretion of epithelial-derived Th2 cytokines, accompanied with reduced asthmatic immunopathology and IFN-λs are critical for limiting Th2-mediated allergic responses in allergic asthma.
Subject(s)
Asthma/immunology , Cytokines/immunology , Epithelial Cells/immunology , Inflammation/drug therapy , Inflammation/immunology , Th2 Cells/immunology , Animals , Bronchoalveolar Lavage Fluid/immunology , Interleukin-33/immunology , Mice , Mice, Inbred C57BL , Ovalbumin/immunologySubject(s)
Asthma , Interleukin-33 , Respiratory Mucosa , Asthma/drug therapy , Asthma/immunology , Interleukin-33/metabolism , Respiratory Mucosa/metabolism , Respiratory Mucosa/immunology , Respiratory Mucosa/drug effects , Animals , Mice , Administration, Inhalation , Interferons , Humans , Disease Models, AnimalABSTRACT
By means of electrospinning with the thermal annealing process, we investigate a highly efficient sensing platform driven by a hierarchical hetero-nanostructure for the sensitive detection of biologically relevant molecules, consisting of single crystalline ruthenium dioxide nanorods (RuO2 NRs) directly grown on the surface of electrospun tungsten trioxide nanofibers (WO3 NFs). Electrochemical measurements reveal the enhanced electron transfer kinetics at the prepared RuO2 NRs-WO3 NFs hetero-nanostructures due to the incorporation of conductive RuO2 NRs nanostructures with a high surface area, resulting in improved relevant electrochemical sensing performances for detecting H2O2 and L-ascorbic acid with high sensitivity.
Subject(s)
Ascorbic Acid/isolation & purification , Biosensing Techniques , Electrochemical Techniques , Hydrogen Peroxide/isolation & purification , Ascorbic Acid/chemistry , Hydrogen Peroxide/chemistry , Nanofibers/chemistry , Nanostructures/chemistry , Nanotubes/chemistry , Oxides/chemistry , Ruthenium Compounds/chemistry , Tungsten/chemistryABSTRACT
Nandina domestica (Berberidaceae) has been used in traditional medicine for the treatment of cough. This plant is distributed in Korea, Japan, China, and India This study aimed to investigate the anti-inflammatory phytochemicals obtained from the N. domestica fruits. We isolated a biflavonoid-type phytochemical, robustaflavone (R), from N. domestica fruits through bioactivity-guided fractionation based on its capacity to inhibit inflammation. The anti-inflammatory mechanism of R isolated from N. domestica has not yet been studied. In the present study, we evaluated the anti-inflammatory activities of R using lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We have shown that R reduces the production of nitric oxide (NO), pro-inflammatory cytokine interleukin-1 beta (IL-1ß), and IL-6. Western blot analysis showed that R suppresses the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and downregulates the expression of LPS-induced nuclear factor-kappa B (NF-κB) and the phosphorylation of extracellular-regulated kinases (pERK 1/2). Moreover, R inhibited IL-8 release in LPS-induced human colonic epithelial cells (HT-29). These results suggest that R could be a potential therapeutic candidate for inflammatory bowel disease (IBD).
Subject(s)
Berberidaceae/chemistry , Biflavonoids/isolation & purification , Biflavonoids/pharmacology , Down-Regulation , Inflammation Mediators/metabolism , Animals , Biflavonoids/chemistry , Cell Death/drug effects , Cell Survival/drug effects , Chemical Fractionation , Cyclooxygenase 2/metabolism , Down-Regulation/drug effects , Enterocytes/drug effects , Enterocytes/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , HT29 Cells , Humans , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Interleukin-8/biosynthesis , Lipopolysaccharides/pharmacology , Macrophages/drug effects , Macrophages/metabolism , Mice , NF-kappa B/metabolism , Nitric Oxide/biosynthesis , Nitric Oxide Synthase Type II/metabolism , Phosphorylation/drug effects , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Extracts/pharmacology , RAW 264.7 CellsABSTRACT
Citrus junos Tanaka is a traditional medicine for treating coughs, dyspepsia, diabetes, asthma, neuralgia, and inflammatory disorders, and is distributed in Asia, especially in Korea, Japan, and China. This study aimed to use bioactivity-guided fractionation to find therapeutic phytochemicals from C. junos seeds, which can attenuate inflammatory responses. Nine coumarins (1-9) were isolated from the methanolic extract of C. junos seed shells and the inhibitory effects against inflammatory mediators were investigated using murine macrophages. Among the coumarins, compound 3, isogosferol (ISO), more potently attenuated the production of nitric oxide (NO) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. ISO also inhibited the expression of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated macrophages. Additionally, the phosphorylation of extracellular-regulated kinases (pERK)1/2 was reduced by ISO. We confirmed that ISO attenuated the release of interleukin-1 beta (IL-1ß), which is a central mediator of the inflammatory response. These results demonstrate that ISO from C. junos seed shells may be a potent therapeutic candidate for the treatment of inflammatory diseases.
Subject(s)
Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Citrus/chemistry , Furocoumarins/isolation & purification , Furocoumarins/pharmacology , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Seeds/chemistry , Animals , Anti-Inflammatory Agents/chemistry , Cell Survival/drug effects , Chemical Fractionation , Cyclooxygenase 2/genetics , Cyclooxygenase 2/metabolism , Cytokines/metabolism , Extracellular Signal-Regulated MAP Kinases/metabolism , Furocoumarins/chemistry , Gene Expression Regulation/drug effects , Mice , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Phytochemicals/chemistry , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Extracts/chemistry , Plant Oils , RAW 264.7 CellsABSTRACT
OBJECTIVE: To develop and validate a risk assessment tool called the Prescription Medication Non-Adherence Prediction Tool (Rx-NAPT) to predict medication nonadherence in patients with fibromyalgia. METHODS: This was a retrospective cohort study using claims data from South Carolina Medicaid. Patients with fibromyalgia who were ≥18 years old and who had filled at least 1 prescription medication for pregabalin, duloxetine, or milnacipran from January 1, 2005, through June 30, 2011 were included. Medication possession ratios (MPRs) were calculated to classify patients as adherent (MPR ≥ 80%) or nonadherent (MPR < 80%). Multivariable logistic models using 100 bootstrap replications (with replacement) were used to identify factors associated with medication nonadherence, including age, gender, race, days' supply, medication type, and fibromyalgia-related comorbidity score. Weighted ß coefficients of the predictors were used to create the Rx-NAPT. Youden's J statistic was used to classify nonadherent patients into different levels of risk. RESULTS: The study sample comprised 6,626 patients with fibromyalgia, where 4,804 (72.50%) were non-adherent and 1,822 (27.50%) were adherent to their prescribed medication(s). Logistic regression models showed that 7 predictors (gender, age, race, fibromyalgia-related comorbidity score, medication type, health maintenance organization coverage, emergency room visit) were statistically significant in ≥50% of the bootstrapped samples. The final model demonstrated reasonable discrimination (area under the curve [AUC] = 0.6224) and calibration (Hosmer-Lemeshow goodness-of-fit; P > 0.05) statistics and was validated internally (AUC = 0.6372). CONCLUSION: Poor adherence with medication remains an important barrier to providing optimal care. Our risk prediction model provides an easy tool to help clinicians better identify patients with fibromyalgia who may not take their medications as prescribed.
Subject(s)
Fibromyalgia/drug therapy , Medicaid/statistics & numerical data , Medication Adherence/statistics & numerical data , Adolescent , Adult , Aged , Cohort Studies , Duloxetine Hydrochloride/therapeutic use , Female , Humans , Logistic Models , Male , Middle Aged , Pregabalin/therapeutic use , Prescription Drugs , Retrospective Studies , Risk Assessment , South Carolina , United StatesABSTRACT
Stimuli-responsive hydrogel microfibers and microtubes are in great demand for biomedical applications due to their similarity to the native extracellular matrix. In this study, we prepared pH- and temperature-responsive hydrogel microfibers and microtubes using a microfluidic device through alginate-templated photopolymerization. Hydrogel monomer solutions containing N-isopropylacrylamide (NIPAm) and sodium acrylate (SA) or allyl amine (AA) were irradiated with UV light to invoke in situ photopolymerization. A repulsive force between the ionized SA or AA groups caused by protonation/deprotonation of the acrylate or amine groups, respectively, led to changes in the diameters and wall thicknesses of the fibers and/or tubes depending on the pH of the medium. Poly(NIPAm) is a well-known thermally responsive polymer wherein the NIPAm-based copolymer microfibers exhibited a thermal behavior close to the lower critical solution temperature. We have demonstrated that these multistimuli-responsive volume changes are fully reversible and repeatable. Furthermore, the positively charged microfibers were shown to exhibit cell adhesion, and the number of cells attached to the microfibers could be further increased by supplying nutrients, presenting the possibility of their application in tissue engineering and other biomedical fields.