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1.
Carbohydr Polym ; 336: 122080, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38670772

ABSTRACT

Traditional Chinese medicine polysaccharides have numerous biological activities with broad applications in the biomedical industries. However, a clear understanding of the pharmacological activities of compound polysaccharides with multi-component structures remain challenging. This study aimed to investigate the immune boosting effect of compound polysaccharides on the influenza vaccine and assess the preliminary structure-activity relationship. The compound polysaccharide (CP) was isolated from the combined Chinese herbs lentinan, pachymaran and tremellan, and purified by gradient ethanol precipitation to obtain its subcomponents of CP-20, CP-40, CP-60, and CP-80 with decreasing molecular weights. These polysaccharides were mainly composed of glucans with different linkage patterns, including α-(1 â†’ 3)-glucan, α-(1 â†’ 4)-glucan and ß-(1 â†’ 6)-glucan. A significant improvement was observed in the survival of mice vaccinated with inactivated (IAV) vaccine and the isolated polysaccharides as adjuvants. A reduction in the pulmonary virus titer and weight loss were also observed. Moreover, CP-40 and CP-60, as well as the original CP, significantly enhanced the serum anti-IAV antibody titers and interleukin IL-2, IL-5, and IL-6 concentrations. These preliminary results indicate the immune boosting effect of the compound polysaccharides is highly relevant to the specific structural properties of the subcomponent, and CP-40 is worthy of further exploration as a glycan adjuvant for the IAV vaccine.


Subject(s)
Adjuvants, Immunologic , Influenza Vaccines , Mice, Inbred BALB C , Polysaccharides , Vaccines, Inactivated , Influenza Vaccines/immunology , Influenza Vaccines/chemistry , Influenza Vaccines/pharmacology , Animals , Vaccines, Inactivated/immunology , Mice , Polysaccharides/pharmacology , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Adjuvants, Immunologic/pharmacology , Adjuvants, Immunologic/chemistry , Female , Antibodies, Viral/blood , Antibodies, Viral/immunology , Orthomyxoviridae Infections/prevention & control , Orthomyxoviridae Infections/immunology , Cytokines/metabolism
2.
NPJ Biofilms Microbiomes ; 9(1): 97, 2023 Dec 11.
Article in English | MEDLINE | ID: mdl-38081891

ABSTRACT

Understanding how dietary polysaccharides affect mucin O-glycosylation and gut microbiota could provide various nutrition-based treatments. Here, the O-glycan profile of the colonic mucosa and gut microbiome were investigated in C57BL/6J mice fed six structurally diverse dietary polysaccharides and a mixture of six fibers. Dietary polysaccharides increased total O-glycans, mainly by stimulating neutral glycans. Highly branched arabinogalactan promoted terminally fucosylated core 1 O-glycans; whereas linear polysaccharides, including pectin, konjac glucomannan, inulin, and the fiber mixture, favored terminally di-fucosylated O-glycans. The last three polysaccharides also lowered the level of sulfated O-glycans and sialylated mono-fucosylated O-glycans. Varied monosaccharide composition in mixed polysaccharides had a synergistic beneficial effect, boosting fucosylated neutral glycans, decreasing acidic glycans, and stimulating microbial richness and diversity. Dietary polysaccharides containing arabinose and sulfate groups enhanced the relative abundances of Akkermansia and Muribaculaceae, respectively. The present comparison reveals the relationship between dietary polysaccharide structure, mucin O-glycan composition, and intestinal microorganisms.


Subject(s)
Gastrointestinal Microbiome , Mucins , Animals , Mice , Mucins/chemistry , Mucins/metabolism , Glycosylation , Mice, Inbred C57BL , Polysaccharides
3.
Medicine (Baltimore) ; 102(48): e36355, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-38050281

ABSTRACT

RATIONALE: To describe the diagnostic and treatment approaches of renal abscesses complicated with acute pyelonephritis in children. PATIENT CONCERNS: Two children presented with fever, vomiting, and abdominal pain with no typical manifestations, like frequent urination, urgency, dysuria, hematuria, foam urine, and lumbago. Renal abscess complicating acute pyelonephritis was diagnosed by B-ultrasound and computed tomography enhancement. Moreover, inflammatory markers were elevated significantly, but routine blood and urine cultures were repeatedly negative. The empirical anti-infection therapy had no obvious effect. A pathogenic diagnosis was confirmed in case two, and macro gene detection in blood and urine guided the follow-up treatment. DIAGNOSES: Both children were diagnosed with acute gastroenteritis on admission, but renal abscess complicating acute pyelonephritis were diagnosed by imaging examination. INTERVENTIONS: Both children were given anti-infection therapy of third-generation cephalosporin, which had no obvious effect. Routine blood and urine cultures were repeatedly negative. Case one was changed to piperacillin sodium tazobactam. We further carried out blood and urinary metagenomic next-generation sequencing detection for case two. Meanwhile, meropenem and linezolid anti-infection treatment was given. The results showed overlapping infection with Escherichia coli and Enterococcus faecalis. According to the genetic test results, amoxicillin clavulanate potassium combined with nitrofurantoin were prescribed after discharge. OUTCOMES: Clinical symptoms of the 2 children disappeared, the infection was controlled, and imaging showed that renal abscess complicated with acute pyelonephritis disappeared. LESSONS: The clinical spectrum of renal abscess complicating acute pyelonephritis is vague, with no specific manifestations, and can be easily misdiagnosed. B-ultrasound and computed tomography enhancement are helpful in making a definite diagnosis. Moreover, the sensitivity of routine culture is low, and metagenomic next-generation sequencing might be helpful to detect pathogenic microorganisms and guided treatment. Early treatment with broad-spectrum antibiotics might have favorable outcomes.


Subject(s)
Kidney Diseases , Peritoneal Diseases , Pyelonephritis , Urinary Tract Infections , Child , Humans , Abscess/complications , Abscess/diagnosis , Abscess/drug therapy , Pyelonephritis/complications , Pyelonephritis/diagnosis , Pyelonephritis/drug therapy , Urinary Tract Infections/diagnosis , Kidney Diseases/complications , Anti-Bacterial Agents/therapeutic use , Escherichia coli , Tomography, X-Ray Computed , Peritoneal Diseases/complications
4.
Food Res Int ; 165: 112498, 2023 03.
Article in English | MEDLINE | ID: mdl-36869507

ABSTRACT

Konjac is a high-quality dietary fiber rich in ß-glucomannan, which has been reported to possess anti-obesity effects. To explore the effective components and the structure-activity relationships of konjac glucomannan (KGM), three different molecular weight components (KGM-1 (90 kDa), KGM-2 (5 kDa), KGM-3 (1 kDa)) were obtained, and systematical comparisons of their effects on high-fat and high-fructose diet (HFFD)-induced obese mice were investigated in the present study. Our results indicated that KGM-1, with its larger molecular weight, reduced mouse body weight and improved their insulin resistance status. KGM-1 markedly inhibited lipid accumulation in mouse livers induced by HFFD by downregulating Pparg expression and upregulating Hsl and Cpt1 expressions. Further investigation revealed that dietary supplementation with konjac glucomannan at different molecular weights caused ß-diversity changes in gut microbes. The potential weight loss effect of KGM-1 maybe attributed to the abundance of changes in Coprobacter, Streptococcus, Clostridium IV, and Parasutterella. The results provide a scientific basis for the in-depth development and utilization of konjac resources.


Subject(s)
Amorphophallus , Gastrointestinal Microbiome , Animals , Mice , Mice, Obese , Molecular Weight , Diet , Fructose
6.
Sci Rep ; 13(1): 1505, 2023 Jan 27.
Article in English | MEDLINE | ID: mdl-36707687

ABSTRACT

The noise from other sources is inevitably mixed in the vibration information of CNC machine tools obtained using the sensors. In this work, a de-noising method based on joint analysis is proposed. The variational mode decomposition (VMD), correlation analysis (CA), and wavelet threshold (WT) denoising are used to denoise the original signal. First, VMD decomposes noisy signals into multiple intrinsic mode functions (IMFs). The penalty factor and decomposition level of VMD parameters are selected by the optimization algorithm by combining the whale optimization algorithm (WOA) and tabu search (TS). The minimum permutation entropy of IMF is used as the fitness function of the proposed fusion algorithm. Then, the IMF is divided into three categories by using the cross-correlation number. They include the pure components, signals containing noise, and complete noise components. Then, the WT method is used to further denoise the signals, and signal reconstruction is performed with the pure component to obtain the denoised signal. This joint analysis denoising method is named TS-WOA-VMD-CA-WT. The simulation results show that the fusion optimization algorithm proposed in this work has better performance as compared to the single optimization algorithm. It performs effectively when applied to the actual machine tool vibration signal denoising. Therefore, the proposed TS-WOA-VMD-CA-WT method is superior to other existing denoising techniques and has good generality, which is expected to be popularized and applied more widely.

7.
J Ethnopharmacol ; 300: 115699, 2023 Jan 10.
Article in English | MEDLINE | ID: mdl-36113679

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Periodontal disease is a complex inflammatory disease that seriously affects peoples' lives. Scutellaria radix (SR) is traditionally used as a folk medicine to clear away heat and dampness, purge fire and detoxification. Although it has been extensively used as a medicinal plant to treat a variety of inflammatory illnesses, the efficacy and active ingredient for topical administration in the treatment of periodontitis is unknown. AIM OF STUDY: The aim of this study was to screen and validate the active ingredients in SR for the prevention and treatment of periodontitis. MATERIALS AND METHODS: A ligature-induced periodontitis in rats was used to investigate the efficacy of topical administration of SR for the treatment of periodontitis, and the active fraction was screened after separation of the aqueous extract of SR into fractions of different polarities using a lipopolysaccharide (LPS)-induced cell model. Chromatographic fingerprints were established for 18 batches of SR by high performance liquid chromatography. The potential active components were screened using spectral effect relationship analysis and the target cell extraction method. RESULTS: SR has good efficacy in the topical treatment of periodontitis, according to animal experiments. Five active ingredients were screened out and their anti-inflammatory activity was confirmed in vitro. CONCLUSION: The main active compounds in the treatment of periodontitis via topical administration of SR were found and this provides an experimental basis for further studies on the pharmacodynamic material basis of SR, as well as reference for the comprehensive evaluation of SR quality and the development of substitute resources.


Subject(s)
Periodontitis , Scutellaria baicalensis , Administration, Topical , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Lipopolysaccharides , Periodontitis/drug therapy , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Rats , Scutellaria baicalensis/chemistry
8.
BMC Infect Dis ; 22(1): 814, 2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36319953

ABSTRACT

BACKGROUND: There is little evidence about consistency between nasopharyngeal and pulmonary pathogens in children with severe pneumonia. This study aims to compare the difference of pathogens between nasopharyngeal aspirates (NPAs) collected before bronchoscopy and bronchoalveolar lavage fluids (BALFs) in children with severe community-acquired pneumonia (SCAP). METHODS: NPAs and BALFs were collected form pediatric SCAP cases hospitalized from January 2018 to March 2019. NPAs were colleced within 3 days before bronchoscopy. Samples were detected by direct immunofluorescence assay (DFA) for seven respiratory viruses and by routine bacterial culture in the clinical microbiology laboratory. Respiratory syncytial virus (RSV), Adenovirus (ADV), Influenza virus types A, B (IV-A and IV-B), Parainfluenza virus 1-3 (PIV1-3) were detected with a commercial assay. The virological and bacteriological detention results of NPAs were compared with the results of BALFs. RESULTS: In total 204 cases with mean age of 3.4 ± 2.8 years (IQR, 1 month-14 years) were included in the study. Both NPA and BALF were collected from those cases. The positive rates of pathogen in NPAs and BALFs were 25.0% (51/204) and 36.7% (75/204), respectively (x2 = 6.614, P = 0.010). Respiratory viruses were found in 16.1% (33/204) from NPAs and 32.3% (66/204) from BALFs (x2 = 14.524, P < 0.001). RSV and ADV were the two most frequent detected viruses in NPAs and BALFs. High consistentcy of pathogens between NPAs and BALFs was observed, and 96.9% (32/33) viruses detected in NPAs were also found in BALFs. While bacteria were isolated from 12.7% (26/204) and 10.7% (22/204) of the two kinds of samples, respectively (x2 = 0.378, P = 0.539). In addition, Haemophilus influenzae (HI) was the dominant germ in both samples. CONCLUSION: The DFA method used to detect seven respiratory viruses from NPAs collected within 3 days before bronchoscopy can partially reflect the pathogens in the lungs in children with SCAP.


Subject(s)
Community-Acquired Infections , Pneumonia , Respiratory Syncytial Virus, Human , Respiratory Tract Infections , Viruses , Child , Humans , Infant , Child, Preschool , Bronchoalveolar Lavage Fluid , Bronchoscopy , Nasopharynx/microbiology
9.
Front Pediatr ; 10: 830897, 2022.
Article in English | MEDLINE | ID: mdl-35450107

ABSTRACT

Background: Increasing evidence indicated that ozone (O3) exposure could trigger asthma attacks in children. However, the effect of O3 at low concentrations is uncertain. Purpose: This study aimed to explore the effects of O3 exposure at low concentrations on asthma attacks in children. Methods: A total of 3,475 children with asthma attacks from the First Affiliated Hospital of Xiamen University were available for the analyses. Air pollution data and meteorological data in Xiamen during 2016-2019 were also collected. A case-crossover design and conditional logistic regression models were conducted to evaluate the association between asthma attacks and outdoor air pollution with lag structures (from lag 0 to lag 6) in both single and multi-pollutant models. Furthermore, we estimated the influence of various levels of O3 exposure on an asthma attack in three groups categorized by maximum daily 8-h sliding average ozone (O3-8 h) (O3-8 h ≥ 100 µg/m3, O3-8 h: 80-99 µg/m3, O3-8 h < 80 µg/m3). Results: For both single-pollutant models and multi-pollutant models, when O3-8 h was higher than 80 µg/m3, O3 exposure was increased the risk of acute asthma attacks on each day of lag. The effect of O3 on children with asthma was significant when O3 concentration was higher than 100 µg/m3. Conclusion: O3 concentration above 80 µg/m3 contributed to an increased risk of asthma attacks in children.

10.
Sci Rep ; 12(1): 5602, 2022 04 04.
Article in English | MEDLINE | ID: mdl-35379865

ABSTRACT

In recent years, Hybrid Cellular Automata Method (HCAM) has been successfully applied to solve structural topology optimization problems. However, there was no report on HCAM research of three-dimensional composite structure composed of multiple materials and multiple bodies. Therefore, in this paper, three-dimensional non-cube cells of irregular size (such as tetrahedral cells with adaptive changes inside length) and Finite Element Method (FEM) are introduced to extend HCAM, which is better and more flexibly to fit complex geometric shapes. Furthermore, a better structure configuration of multi-material and multi-body structure is obtained. The typical example study showed that the proposed topology optimization method could effectively remove the redundant materials of multi-material and multi-body structure, and the optimized structure configuration could still meet the requirements of the original condition after geometric reconstructed. Thus it provided a reference for the intelligent design of other products.


Subject(s)
Cellular Automata , Research Design
11.
Respir Res ; 21(1): 123, 2020 May 24.
Article in English | MEDLINE | ID: mdl-32448264

ABSTRACT

BACKGROUND: Particulate Matter (PM) is known to cause inflammatory responses in human. Although prior studies verified the immunogenicity of PM in cell lines and animal models, the effectors of PM exposure in the respiratory system and the regulators of the immunogenicity of PM is not fully elucidated. METHODS: To identify the potential effector of PM exposure in human respiratory system and to better understand the biology of the immunogenicity of PM, We performed gene-expression profiling of peripheral blood mononuclear cells from 171 heathy subjects in northern China to identify co-expressed gene modules associated with PM exposure. We inferred transcription factors regulating the co-expression and validated the association to T-cell differentiation in both primary T-cells and mice treated with PM. RESULTS: We report two transcription factors, IRF4 and STAT3, as regulators of the gene expression in response to PM exposure in human. We confirmed that the activation of IRF4 and STAT3 by PM is strongly associated with imbalanced differentiation of T-cells in the respiratory tracts in a time-sensitive manner in mouse. We also verified the consequential inflammatory responses of the PM exposure. Moreover, we show that the protein levels of phosphorylated IRF4 and STAT3 increase with PM exposure. CONCLUSIONS: Our study suggests the regulatory activities of IRF4 and STAT3 are associated with the Th17-mediated inflammatory responses to PM exposure in the respiratory tracts, which informs the biological background of the immunogenicity of particulate matters.


Subject(s)
Cell Differentiation/physiology , Interferon Regulatory Factors/biosynthesis , Particulate Matter/administration & dosage , STAT3 Transcription Factor/biosynthesis , Th17 Cells/metabolism , Administration, Inhalation , Adult , Aged , Aged, 80 and over , Animals , Cell Differentiation/drug effects , China/epidemiology , Female , Humans , Interferon Regulatory Factors/genetics , Male , Mice , Mice, Inbred BALB C , Middle Aged , Particulate Matter/adverse effects , STAT3 Transcription Factor/genetics , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , Th17 Cells/drug effects , Young Adult
12.
Pediatr Pulmonol ; 55(6): 1440-1447, 2020 06.
Article in English | MEDLINE | ID: mdl-32297710

ABSTRACT

Airway inflammation of eosinophilic asthma (EA) attributes to Th2 response, leaving the role of Th17 response unknown. Signal transducer and activator of transcription 3 (STAT3) induce both suppressors of cytokine signaling 3 (SOCS3) and retinoic acid receptor-related orphan nuclear receptor γ (RORγt) to initiate Th17 cell differentiation which is inhibited by SOCS3, a negative feedback regulator of STAT3. Heme oxygenase-1 (HO-1) is a stress-responsive, cytoprotective, and immunoregulatory molecular. Two other isoforms of the enzyme includes HO-2 and HO-3. Because HO-2 does not exhibit stress-related upregulation and distributes mainly in nervous system and HO-3 shows a low enzymatic activity, we tested a hypothesized anti-inflammatory role for HO-1 in EA by inhibiting STAT3-SOCS3 signaling. Animal model was established with Ovalbumin in wild type Balb/C mice. Hemin or SNPP was intraperitoneally (IP) injected ahead of the animal model to induce or inhibit HO-1 expression. Airway inflammation was evaluated by bronchoalveolar lavage, hematoxyline and eosin staining, enzyme-linked immunosorbent assay, and Western blot analysis. In vivo results showed that HO-1 induction inhibited phosphorylation of STAT3 and expression of SOCS3 and RORγt, decreased Th2 and Th17 immune responses, and alleviated airway inflammation. In vitro results revealed that HO-1 inhibited phosphorylation of STAT3 and expression of SOCS3 in naive CD4+ T cells. These findings identify HO-1 induction as a potential therapeutic strategy for EA treatment by reducing STAT3 phosphorylation, STAT3-SOCS3-mediated Th2/Th17 immune responses, and ultimate allergic airway inflammation.


Subject(s)
Asthma/immunology , Eosinophilia/immunology , Heme Oxygenase-1/immunology , Membrane Proteins/immunology , STAT3 Transcription Factor/immunology , Suppressor of Cytokine Signaling 3 Protein/immunology , Allergens , Animals , Mice, Inbred BALB C , Ovalbumin , Phosphorylation , Signal Transduction , Th17 Cells/immunology , Th2 Cells/immunology
13.
BMC Pediatr ; 19(1): 194, 2019 06 13.
Article in English | MEDLINE | ID: mdl-31196028

ABSTRACT

BACKGROUND: The short-term effects of particulate matter (PM) exposure on childhood asthma exacerbation and disease control rate is not thoroughly assessed in Chinese population yet. The previous toxic effects of PM exposure are either based on long-term survey or experimental data from cell lines or mouse models, which also needs to be validated by real-world evidences. METHODS: We evaluated the short-term effects of PM exposure on asthma exacerbation in a Chinese population of 3106 pediatric outpatientsand disease control rate (DCR) in a population of 3344 children using case-crossover design. All the subjects enrolled are non-hospitalized outpatients. All data for this study were collected from the electronic health record (EHR) in the period between January 1, 2016 and June 30, 2018 in Xiamen, China. RESULTS: We found that exposure to PM2.5 and PM10 within the past two weeks was significantly associated with elevated risk of exacerbation (OR = 1.049, p < 0.001 for PM2.5and OR = 1.027, p < 0.001 for PM10). In addition, exposure to PM10 was associated with decreased DCR (OR = 0.976 for PM10, p < 0.001). CONCLUSIONS: Our results suggest that exposure to both PM10 and PM2.5 has significant short-term effects on childhood asthma exacerbation and DCR, which serves as useful epidemiological parameters for clinical management of asthma risk in the sensitive population.


Subject(s)
Asthma/complications , Asthma/prevention & control , Disease Progression , Environmental Exposure/adverse effects , Particulate Matter/toxicity , Adolescent , Child , Child, Preschool , China , Cross-Over Studies , Female , Humans , Infant , Infant, Newborn , Male , Meteorological Concepts , Odds Ratio
14.
J Biol Chem ; 293(48): 18454-18465, 2018 11 30.
Article in English | MEDLINE | ID: mdl-30333233

ABSTRACT

Asthma is thought to be caused by malfunction of type 2 T helper cell (Th2)-mediated immunity, causing excessive inflammation, mucus overproduction, and apoptosis of airway epithelial cells. Heme oxygenase-1 (HO-1) functions in heme catabolism and is both cytoprotective and anti-inflammatory. We hypothesized that this dual function may be related to asthma's etiology. Using primary airway epithelial cells (pAECs) and an asthma mouse model, we demonstrate that severe lung inflammation is associated with rapid pAEC apoptosis. Surprisingly, NOD-like receptor protein 3 (NLRP3) inhibition, retinoid X receptor (RXR) deficiency, and HO-1 induction were associated with abrogated apoptosis. MCC950, a selective small-molecule inhibitor of canonical and noncanonical NLRP3 activation, reduced RXR expression, leading to decreased pAEC apoptosis that was reversed by the RXR agonist adapalene. Of note, HO-1 induction in a mouse model of ovalbumin-induced eosinophilic asthma suppressed Th2 responses and reduced apoptosis of pulmonary pAECs. In vitro, HO-1 induction desensitized cultured pAECs to ovalbumin-induced apoptosis, confirming the in vivo observations. Critically, the HO-1 products carbon monoxide and bilirubin suppressed the NLRP3-RXR axis in pAECs. Furthermore, HO-1 impaired production of NLRP3-RXR-induced cytokines (interleukin [IL]-25, IL-33, thymic stromal lymphopoietin, and granulocyte-macrophage colony-stimulating factor) in pAECs and lungs. Finally, we demonstrate that HO-1 binds to the NACHT domain of NLRP3 and the RXRα and RXRß subunits and that this binding is not reversed by Sn-protoporphyrin. Our findings indicate that HO-1 and its products are essential for pAEC survival to maintain airway epithelium homeostasis during NLRP3-RXR-mediated apoptosis and inflammation.


Subject(s)
Apoptosis/physiology , Asthma/metabolism , Asthma/pathology , Bronchi/pathology , Heme Oxygenase-1/physiology , Inflammation/pathology , Membrane Proteins/physiology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Retinoid X Receptors/metabolism , Animals , Cytokines/biosynthesis , Enzyme Induction , Epithelium/pathology , Heme Oxygenase-1/biosynthesis , Heme Oxygenase-1/metabolism , Inflammation/metabolism , Inflammation Mediators/metabolism , Membrane Proteins/biosynthesis , Membrane Proteins/metabolism , Metalloporphyrins/metabolism , Mice, Inbred C57BL , Protoporphyrins/metabolism
15.
Eur J Immunol ; 48(11): 1838-1850, 2018 11.
Article in English | MEDLINE | ID: mdl-30184256

ABSTRACT

Epithelial cells (ECs)-derived cytokines are induced by different stimuli through pattern recognition receptors (PRRs) to mount a type-2-cell-mediated immune response; however, the underlying mechanisms are poorly characterized. Here, we demonstrated asthmatic features in both primary bronchial epithelial cells (pBECs) and mouse model using several allergens including ovalbumin (OVA), house dust mite (HDM), or Alternaria alternata. We found that toll-like receptor 2 (TLR2) was highly induced in ECs but not dendritic cells (DCs) by various allergens, leading to recruitment of circulating basophils into the lung via C-C chemokine ligand-2 (CCL2). TLR2 expression increased thymic stromal lymphopoietin (TSLP) production through the NF-κB and JNK signaling pathways to extend the survival of recruited basophils and resident DCs in the lung, predisposing a type-2-cell-mediated airway inflammation. Conversely, TLR2 deficiency impaired secretion of TSLP and CCL2, decreased infiltration of lung basophils, and increased resistance to Th2 response. Blocking TSLP also phenocopied these phenomena. Our findings reveal a pro-inflammatory role of airway ECs through a TLR2-dependent TSLP production, which may have implication for treating allergic asthma.


Subject(s)
Allergens/immunology , Bronchi/immunology , Epithelial Cells/immunology , Inflammation/immunology , Lung/immunology , Alternaria/immunology , Animals , Asthma/immunology , Basophils/immunology , Cells, Cultured , Chemokine CCL2/immunology , Cytokines/immunology , Dendritic Cells/immunology , Disease Models, Animal , Mice , Mice, Inbred C57BL , Ovalbumin/immunology , Pyroglyphidae/immunology , Th2 Cells/immunology , Toll-Like Receptor 2/immunology , Thymic Stromal Lymphopoietin
16.
Br J Pharmacol ; 175(9): 1439-1450, 2018 05.
Article in English | MEDLINE | ID: mdl-29315511

ABSTRACT

BACKGROUND AND PURPOSE: Increasing energy expenditure through adipocyte thermogenesis is generally accepted as a promising strategy to mitigate obesity and its related diseases. However, few clinically effective and safe agents are known to promote adipocyte thermogenesis. In this study, 20 traditional Chinese herbal medicines were screened to examine whether they induced adipocyte thermogenesis. EXPERIMENTAL APPROACH: The effects of Chinese herbal medicines or components isolated from extracts of A. membranaceus, on adipocyte thermogenesis were analysed by assessing expression of uncoupling protein 1 (UCP1) by qPCR. Eight-week-old C57BL6/J male mice were fed a high-fat diet for 8 weeks and then randomized to two groups treated with vehicle or formononetin for another 8 weeks. Glucose tolerance tests and staining of adipose tissue with haematoxylin and eosin were carried out. Whole-body oxygen consumption was measured with an open-circuit indirect calorimetry system. KEY RESULTS: Extracts of A. membranaceus increased expression of Ucp1 in primary cultures of mouse adipocytes. Formononetin was the only known component of A. membranaceus extracts to increase adipocyte Ucp1 expression. Diet-induced obese mice treated with formononetin gained less weight and showed higher energy expenditure than untreated mice. In addition, formononetin binds directly with PPARγ. CONCLUSIONS AND IMPLICATION: Taken together, our study demonstrates that the Chinese herbal medicine from A. membranaceus and its constituent formononetin have the potential to reduce obesity and associated metabolic disorders. Our results suggest that formononetin regulates adipocyte thermogenesis as a non-classical PPARγ agonist.


Subject(s)
Adipocytes/drug effects , Astragalus propinquus/chemistry , Isoflavones/isolation & purification , Isoflavones/pharmacology , PPAR gamma/metabolism , Thermogenesis/drug effects , Adipocytes/metabolism , Animals , Body Weight/drug effects , Diet, High-Fat , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/pharmacology , Energy Metabolism/drug effects , Glucose Tolerance Test , Male , Mice , Obesity/chemically induced , Obesity/prevention & control , Oxygen Consumption/drug effects , PPAR gamma/physiology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Primary Cell Culture , RNA, Small Interfering/pharmacology , Thermogenesis/physiology , Uncoupling Protein 1/biosynthesis
17.
Diabetes ; 66(2): 407-417, 2017 02.
Article in English | MEDLINE | ID: mdl-28108609

ABSTRACT

Both mammals and adult humans possess classic brown adipocytes and beige adipocytes, and the amount and activity of these adipocytes are considered key factors in combating obesity and its associated metabolic diseases. Uncoupling protein 1 (Ucp1) is the functional marker of both brown and beige adipocytes. To facilitate a reliable, easy, and sensitive measurement of Ucp1 expression both in vivo and in vitro, we generated a Ucp1-2A-luciferase knock-in mouse by deleting the stop codon for the mouse Ucp1 gene and replacing it with a 2A peptide. This peptide was followed by the luciferase coding sequence to recapitulate the expression of the Ucp1 gene at the transcriptional and translational levels. With this mouse, we discovered a cold-sensitive brown/beige adipose depot underneath the skin of the ears, which we named uBAT. Because of the sensitivity and high dynamic range of luciferase activity, the Ucp1-2A-luciferase mouse is useful for both in vitro quantitative determination and in vivo visualization of nonshivering thermogenesis. With the use of this model, we identified and characterized axitinib, an oral small-molecule tyrosine kinase inhibitor, as an effective browning agent.


Subject(s)
Adipocytes, Beige/metabolism , Adipocytes, Brown/metabolism , Subcutaneous Fat/metabolism , Adipocytes, Beige/drug effects , Adipocytes, Brown/drug effects , Animals , Axitinib , Blotting, Western , Ear , Gene Knock-In Techniques , Glucose Tolerance Test , Imidazoles/pharmacology , Immunohistochemistry , In Vitro Techniques , Indazoles/pharmacology , Luciferases/genetics , Luminescent Measurements , Male , Mice , Models, Animal , Oxygen Consumption , Protein Kinase Inhibitors/pharmacology , Reverse Transcriptase Polymerase Chain Reaction , Subcutaneous Fat/drug effects , Thermogenesis/drug effects , Uncoupling Protein 1/genetics
18.
Article in English | MEDLINE | ID: mdl-28115972

ABSTRACT

Overweight or obese adults aged 20~55 years and living in Beijing more than one year were randomly divided into different management groups. A one-year integrated health management intervention was applied in the health management groups. The physical indicators and metabolic indicators changed after one-year intervention on the overweight and obese adults. The annual reduction of the physical indicators was significant in all groups (p < 0.05) except the weight loss in the placebo + general management group. The health management and the dietary supplement have statistically significant (p < 0.001, p < 0.001) effects on the annual reduction of these indicators and interactive effect between them was found on some of these indicators such as bodyweight, body mass index (BMI), body fat ratio (BFR), and hipline (p < 0.05). The dietary supplement + health management group had the best annual reduction effects for the indicators among the groups. Integrated health management interventions including both dietary supplements intervention and health management could improve metabolic indicators in overweight and obese adults together with the physical indicators, suggesting the intermediated role of metabolic indictors in controlling obesity.

19.
Zhonghua Liu Xing Bing Xue Za Zhi ; 37(4): 491-5, 2016 Apr.
Article in Chinese | MEDLINE | ID: mdl-27087212

ABSTRACT

OBJECTIVE: To explore the effect of weight-loss for overweight or obese population under the health management programs, and to provide evidence for the development of safe and effective weight-loss programs. METHODS: 738 participants who resided in Beijing longer than one year, under 22 to 55 years of age, with BMI≥24 kg/m(2) and without organic diseases were voluntarily recruited, from September 1(st) to October 15(th) 2013. All the participants were randomly divided into general management group or under health management group, in which all the subjects received intervention measures for 6 months. Anthropometry and body composition were measured at baseline and 6 months for all the subjects. Weight-loss effect from the health management programs was evaluated through analyzing the changes on weight and body fat. RESULTS: 618 participants completed the follow-up process, including 321 in the general management group and 297 in the health management group. 6 months after the intervention process, values of weight and body fat rate in the two groups appeared both significantly lower than that at the baseline levels. Difference before and after the intervention program was statistically significant (P<0.001). However, the differences of those with reduction value as 2.19 kg or 2.19% among health management group were higher than that in the general management group, which were 0.97 kg and 1.28% respectively, with difference statistically significant (P<0.001). The effective rate of 24.2% loss-weight and the 52.5% losing rate on body fat among the health management group were both higher than 11.8% and 34.3%, seen in the general management group, respectively, with difference statistically significant (P<0.001). CONCLUSION: The healthy management programs could effectively control the weight and body fate rate among the overweight or obese adults.


Subject(s)
Body Composition , Obesity/prevention & control , Risk Reduction Behavior , Weight Loss/physiology , Weight Reduction Programs/methods , Adipose Tissue , Adult , Behavior Therapy , Body Mass Index , China , Exercise , Feeding Behavior , Female , Humans , Middle Aged , Overweight , Treatment Outcome
20.
Immunology ; 147(3): 321-37, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26879758

ABSTRACT

The anti-inflammatory role of heme oxygenase-1 (HO-1) has been studied extensively in many disease models including asthma. Many cell types are anti-inflammatory targets of HO-1, such as dendritic cells and regulatory T cells. In contrast to previous reports that HO-1 had limited effects on basophils, which participate in T helper type 2 immune responses and antigen-induced allergic airway inflammation, we demonstrated in this study, for the first time, that the up-regulation of HO-1 significantly suppressed the maturation of mouse basophils, decreased the expression of CD40, CD80, MHC-II and activation marker CD200R on basophils, blocked DQ-ovalbumin uptake and promoted basophil apoptosis both in vitro and in vivo, leading to the inhibition of T helper type 2 polarization. These effects of HO-1 were mimicked by exogenous carbon monoxide, which is one of the catalytic products of HO-1. Furthermore, adoptive transfer of HO-1-modified basophils reduced ovalbumin-induced allergic airway inflammation. The above effects of HO-1 can be reversed by the HO-1 inhibitor Sn-protoporphyrin IX. Moreover, conditional depletion of basophils accompanying hemin treatment further attenuated airway inflammation compared with the hemin group, indicating that the protective role of HO-1 may involve multiple immune cells. Collectively, our findings demonstrated that HO-1 exerted its anti-inflammatory function through suppression of basophil maturation and activation, but promotion of basophil apoptosis, providing a possible novel therapeutic target in allergic asthma.


Subject(s)
Apoptosis/immunology , Asthma/immunology , Basophils/immunology , Heme Oxygenase-1/immunology , Hypersensitivity/immunology , Membrane Proteins/immunology , Th2 Cells/immunology , Adoptive Transfer , Animals , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Immunohistochemistry , Inflammation/immunology , Mice , Mice, Inbred BALB C , Real-Time Polymerase Chain Reaction
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