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1.
J Food Sci ; 89(6): 3847-3857, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38767860

RESUMO

Egg allergy is one of the most common food allergies globally. This study aimed to assess the impact of four traditional cooking methods on the allergenicity of egg proteins using a comprehensive strategy, including simulated gastrointestinal digestion in vitro, serology experiments, a rat basophilic leukemia (RBL)-2H3 cell degranulation model, and a passive cutaneous anaphylaxis (PCA) mice model, and the structure changes were detected by circular dichroism (CD) spectra and ultraviolet (UV) spectra. The results showed that the processed egg proteins were more readily digested compared to raw egg proteins. The serological experiments revealed a significant reduction in immunoglobulin E binding of egg proteins after thermal treatments (p < 0.05), particularly after frying. Subsequently, the RBL-2H3 cell degranulation experiment demonstrated a marked decrease in the level of egg allergens-induced ß-hexosaminidase release after cooking (p < 0.05). Moreover, the results from the PCA mice model indicated that the increase in vascular permeability was effectively relieved in the treated groups, especially in frying group (p < 0.05). Additionally, the α-helix and ß-turn contents of processed egg proteins were significantly decreased (p < 0.05) compared with native egg proteins. The UV spectra findings showed that all cooking treatments caused significant alterations in the tertiary structure, and fluorescence analysis indicated that cooking decreased the surface hydrophobicity of egg proteins. In conclusion, four traditional cooking methods reduced the allergenicity of egg proteins, particularly frying, and this reduction was associated with structural changes that could contribute to the destruction or masking of epitopes of egg allergens. PRACTICAL APPLICATION: Egg allergy has a serious impact on public health, and there is no ideal treatment method at present. This study demonstrated that four traditional cooking methods (boiling, steaming, baking, and frying) reduced the allergenicity of egg proteins, especially frying, and the results will provide a basis for the development of hypoallergenic egg products.


Assuntos
Alérgenos , Culinária , Hipersensibilidade a Ovo , Proteínas do Ovo , Imunoglobulina E , Culinária/métodos , Animais , Hipersensibilidade a Ovo/imunologia , Camundongos , Alérgenos/imunologia , Imunoglobulina E/imunologia , Ratos , Proteínas do Ovo/imunologia , Proteínas do Ovo/química , Anafilaxia Cutânea Passiva , Camundongos Endogâmicos BALB C , Temperatura Alta , Feminino , Humanos , Modelos Animais de Doenças
2.
J Sci Food Agric ; 104(10): 5955-5963, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38415860

RESUMO

BACKGROUND: Food allergy has become a global public health problem. This study aimed to explore the possible anti-allergic effect of vitamin C (VC). A rat basophilic leukemia (RBL)-2H3 cell degranulation model was used to assess the effect of VC on degranulation in vitro, and an ovalbumin (OVA)-induced BALB/c mouse allergy model was used to assess the anti-allergy effect of VC in vivo. RESULTS: In vitro, VC significantly attenuated the release of ß-hexosaminidase, tryptase and histamine, and also reduced cytokine production (interleukins 4 and 6, tumor necrosis factor α) significantly (P < 0.05), with the inhibitory effect demonstrating a positive correlation with VC dose. In vivo, compared with the OVA group, the levels of serum immunoglobulins E and G1 of the VC low-dose (VCL) group (50 mg kg-1) and high-dose (VCH) group (200 mg·kg-1) were significantly reduced (P < 0.05). Furthermore, the plasma histamine level was also significantly decreased (P < 0.05). Moreover, TH2 cell polarization in mice of the VCL and VCH groups was significantly inhibited (P < 0.05), promoting the TH1/TH2 cell polarization balance. Additionally, VC treatment enhanced the expression of CD80 (P < 0.05) in spleen and small intestine tissues, while significantly inhibiting the expression of CD86 (P < 0.05); notably, high-dose VC treatment was more effective. CONCLUSION: VC exerted an anti-allergic effect through inhibiting degranulation and regulating TH1/TH2 cell polarization balance. © 2024 Society of Chemical Industry.


Assuntos
Antialérgicos , Ácido Ascórbico , Degranulação Celular , Hipersensibilidade Alimentar , Camundongos Endogâmicos BALB C , Células Th1 , Células Th2 , Animais , Células Th2/imunologia , Células Th2/efeitos dos fármacos , Antialérgicos/farmacologia , Camundongos , Ácido Ascórbico/farmacologia , Degranulação Celular/efeitos dos fármacos , Células Th1/imunologia , Células Th1/efeitos dos fármacos , Ratos , Hipersensibilidade Alimentar/tratamento farmacológico , Hipersensibilidade Alimentar/imunologia , Imunoglobulina E/imunologia , Humanos , Feminino , Masculino , Ovalbumina/imunologia , Ovalbumina/efeitos adversos , Citocinas/metabolismo , Citocinas/imunologia , beta-N-Acetil-Hexosaminidases/metabolismo
3.
BMC Surg ; 24(1): 43, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38297276

RESUMO

BACKGROUND: The new-onset postoperative atrial fibrillation (NOPAF) following pulmonary resection is a common clinical concern. The aim of this study was to construct a nomogram to intuitively predict the risk of NOPAF and offered protective treatments. METHODS: Patients who underwent pulmonary resection between January 2018 and December 2020 were consecutively enrolled. Forward stepwise multivariable logistic regression analyses were used to screen independent predictors, and a derived nomogram model was built. The model performance was evaluated in terms of calibration, discrimination and clinical utility and validated with bootstrap resampling. RESULTS: A total of 3583 patients who met the research criteria were recruited for this study. The incidence of NOPAF was 1.507% (54/3583). A nomogram, composed of five independent predictors, namely age, admission heart rate, extent of resection, laterality, percent maximum ventilation volume per minute (%MVV), was constructed. The concordance index (C-index) was 0.811. The nomogram showed substantial discriminative ability, with an area under the receiver operating characteristic curve of 0.811 (95% CI 0.758-0.864). Moreover, the model shows prominent calibration performance and higher net clinical benefits. CONCLUSION: We developed a novel nomogram that can predict the risk of NOPAF following pulmonary resection, which may assist clinicians predict the individual probability of NOPAF and perform available prophylaxis. By using bootstrap resampling for validation, the optimal discrimination and calibration were demonstrated, indicating that the nomogram may have clinical practicality.


Assuntos
Fibrilação Atrial , Nomogramas , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Estudos Retrospectivos , Curva ROC , Incidência
5.
Food Res Int ; 168: 112771, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37120220

RESUMO

Sesame allergy is a growing concern worldwide. In this study, sesame proteins was glycated with glucose, galactose, lactose and sucrose respectively, and the allergenicity of different glycated sesame proteins were assessed by a comprehensive strategy, including simulated gastrointestinal digestion in vitro, a BALB/c mice model, a rat basophilic leukemia (RBL)-2H3 cell degranulation model and a serological experiment. Firstly, simulated gastrointestinal digestion in vitro showed that glycated sesame proteins were more easily to digest than raw sesame. Subsequently, the allergenicity of sesame proteins was assessed in vivo by detecting the allergic indexes of mice, and results showed that the levels of total immunoglobulin E (IgE) and histamine were reduced in glycated sesame proteins treated mice. Meanwhile, the Th2 cytokines (IL-4, IL-5, and IL-13) were downregulated significantly, demonstrating that sesame allergy was relieved in glycated sesame treated mice. Thirdly, the RBL-2H3 cell degranulation model results showed that the release of ß-hexosaminidase and histamine were decreased to different degrees in glycated sesame proteins treated groups. Notably, the monosaccharide glycated sesame proteins exhibited lower allergenicity both in vivo and in vitro. Furthermore, the study also analyzed the structure alteration of sesame proteins, and the results showed that the secondary structure of glycated sesame proteins were changed (the content of α-helix and ß-sheet were reduced), and the tertiary structure of sesame proteins after glycation modification was also changed (microenvironment around aromatic amino acids was altered). Besides, the surface hydrophobicity of glycated sesame proteins was also reduced except sucrose glycated sesame proteins. In conclusion, this study demonstrated that glycation reduced the allergenicity of sesame proteins effectively, especially glycation with monosaccharides, and the allergenicity reduction might be related to structural changes. The results will provide a new reference for developing hypoallergenic sesame products.


Assuntos
Hipersensibilidade , Sesamum , Ratos , Camundongos , Animais , Alérgenos , Reação de Maillard , Histamina/metabolismo
6.
Clin Exp Pharmacol Physiol ; 50(7): 573-582, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36987398

RESUMO

This study aimed to explore the anti-inflammatory effect of stachyose, a tetrasaccharide extracted from Stachys sieboldii Miq. A lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages model and a dextran sodium sulfate (DSS)-induced ulcerative colitis BALB/C mice model was used to assess the anti-inflammatory effect of stachyose both in vitro and in vivo. The levels of nitric oxide (NO) and cytokines (interleukin-1ß, interleukin-6 and tumour necrosis factor-α) were detected using enzyme-linked immunosorbent assay methods; moreover, haematoxylin-eosin staining was used to observe changes in intestinal morphology of mice. In addition, the possible mechanisms were explored by reverse transcription-polymerase chain reaction and western blot. Results showed that stachyose and four other oligosaccharides (galacto-oligosaccharides, xylo-oligosaccharides, inulin and resistant dextrin) inhibited NO secretion and the production of pro-inflammatory cytokines in LPS-stimulated RAW264.7 macrophages in a dose-dependent manner, whereas stachyose was most effective in vitro. In mice, different doses of stachyose significantly alleviated the symptoms of DSS-induced ulcerative colitis and stachyose also significantly inhibited the production of inflammatory cytokines and myeloperoxidase in vivo. In addition, our findings illustrated that stachyose inhibited expression of toll-like receptor 4 (TLR4) and suppressed the phosphorylation of nuclear factor (NF)-κB p65 both in vitro and in vivo. Taken together, results demonstrated that stachyose exerted anti-inflammatory effect through inhibition of the TLR4/NF-κB signalling pathway.


Assuntos
Colite Ulcerativa , NF-kappa B , Camundongos , Animais , NF-kappa B/metabolismo , Receptor 4 Toll-Like/metabolismo , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos BALB C , Oligossacarídeos , Citocinas/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Sulfato de Dextrana
7.
Life Sci ; 311(Pt A): 121013, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36257460

RESUMO

AIMS: As an essential indicator of allergic reactions, mast cell (MC) activation involves FcεRI-mediated signaling and the release of allergic mediators. In FcεRI signaling, Ca2+ is located at the intersection of multiple cellular signaling pathways. However, the effect of extracellular Ca2+ (exCa2+) on MCs during anaphylaxis remains unclear, along with its exact mechanisms. Therefore, we sought to determine whether and how elevated exCa2+ amplifies allergic reactions. MAIN METHODS: In vitro experiments used immunoglobulin E (IgE)/antigen (Ag)-induced activation of rat and mouse MCs in vitro. The levels of MC degranulation mediators were used to evaluate the effect of exCa2+. In vivo experiments used MC-mediated passive systemic anaphylaxis (PCA) Balb/c mice. After stimulation, anaphylaxis indexes such as rectal temperature and allergic symptom score were detected. KEY FINDINGS: In vitro experiments revealed that exCa2+ is a stimulus signal for the aggravation of allergic reactions in MCs. When antagonists or siRNA inhibited GPRC6, MCs released fewer inflammatory mediators. Moreover, in vivo experiments confirmed in vitro results. Allergic symptoms were alleviated by antagonists NPS2143 in PCA mice, demonstrating that exCa2+ aggravates allergic reactions through GPRC6A. SIGNIFICANCE: Our study provides an essential theoretical basis for targeting Ca2+ and GPRC6A as therapeutic options for allergies.


Assuntos
Anafilaxia , Cálcio , Mastócitos , Receptores Acoplados a Proteínas G , Animais , Camundongos , Ratos , Anafilaxia/metabolismo , Degranulação Celular , Imunoglobulina E , Mastócitos/imunologia , Camundongos Endogâmicos BALB C , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Cálcio/metabolismo
8.
Foods ; 11(9)2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35563950

RESUMO

In this study, an obese C57BL/6J mice model was induced to compare the effect of different high protein diets (soybean protein and pork protein) on obesity. The obese mice were randomly divided into four groups: natural recovery (NR), high-fat diet (HF), high soybean protein diet (HSP), and high pork protein diet (HPP) groups. After 12 weeks of dietary intervention, the obesity-related indexes of mice were measured, such as body weight, fat coefficients, blood lipid indexes and so on. Results showed that HSP and HPP decreased the weight and fat coefficients of mice, the levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and leptin (p < 0.05). Soybean protein was shown to be more effective in reducing the weight and fat mass of obese mice, although pork protein seemed to have a better effect on regulating serum triglyceride (TG). In addition, the two high protein diets both alleviated hepatic fat deposition effectively. Furthermore, HPP and HSP decreased the expression of hepatic peroxisome proliferator-activated receptor-γ (PPAR-γ) and increased the protein expression of phosphorylated AMP-activated protein kinase (pAMPK), phosphorylated acetyl CoA carboxylase (pACC), and uncoupling protein 2 (UCP2) (p < 0.05). In conclusion, the study shows that high protein diets based on both pork protein and soybean protein alleviated abdominal obesity in mice effectively by regulating lipid metabolism, probably via the UCP2-AMPK-ACC signaling pathway.

9.
Life Sci ; 286: 120038, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34653427

RESUMO

AIMS: To explore the effect on food allergy of stachyose. MAIN METHODS: The egg allergen ovalbumin (OVA) was used to induce a food allergy model of BALB/c mice, and different doses of stachyose were given in process. Using enzyme-linked immunosorbent assay (ELISA) methods to detect the levels of IgE, IgG1, histamine and cytokines. And flow cytometry was used to analyze TH1/TH2 balance further. Besides, Hematoxylin-eosin (HE) staining was used to observe changes of intestinal morphology. Lastly, Reverse Transcription-Polymerase Chain Reaction (RT-qPCR) and western Blot was conducted to explore the possible mechanism. KEY FINDINGS: Compared with OVA group, serum IgE and IgG1 levels in the low-dose (1mg/mouse) group and high-dose (5mg/mouse) group of stachyose were significantly reduced (P < 0.05); the level of plasma histamine was also decreased significantly (P < 0.05) and the body temperature were decreased. In all, allergic symptoms were alleviated after stachyose treatment. Furthermore, TH1/TH2 balance was improved after stachyose treatment. Lastly, the expression of TLR2 and NF-κB were increased significantly (P < 0.05) in both mRNA and protein levels after stachyose treatment. SIGNIFICANCE: Food allergy was alleviated through improving TH1/TH2 balance by activating TLR2/NF-κB signal by stachyose.


Assuntos
Hipersensibilidade Alimentar/tratamento farmacológico , Oligossacarídeos/farmacologia , Alérgenos/metabolismo , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Hipersensibilidade Alimentar/metabolismo , Histamina/metabolismo , Imunoglobulina E/sangue , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Oligossacarídeos/metabolismo , Ovalbumina/imunologia , Ovalbumina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Th1/imunologia , Células Th2/imunologia , Receptor 2 Toll-Like/metabolismo
10.
Sci Total Environ ; 757: 143748, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33267994

RESUMO

Currently, numerous challenges such as excessive irrigation water consumption, labor shortage, lower economic and environmental benefits pose serious threats to rice cultivation systems. Therefore, more water- and labor-efficient irrigation technologies are needed in rice production for minimal environmental hazards and greater economic benefits. After the screening experiment of water-saving cultivation technologies and cultivars, a two-year field experiment was conducted to further explore the effects of efficient water-saving technologies and rice cultivars on the comprehensive benefits, global warming potential (GWP), grain yield, economic benefits, water productivity, nitrogen partial factor productivity, radiation, accumulated temperature and energy use efficiency (EUE) of a rice-wheat rotation system. Conventional flooding irrigation (F), intermittent irrigation (IR), transplanting rainfed (TR) and rice dry cultivation (D) were implemented with two rice cultivars, including Hanyou73 (HY) and Huanghuazhan (HH). After rice harvest, a winter wheat cultivar (Huamai 2566) was planted with traditional methods. The system of rice dry cultivation and wheat rotation had higher comprehensive benefits, which were attributed to greater water productivity, economic benefits and EUE and lower GWP, especially in the rice growing season. D treatment enhanced the comprehensive and economic benefits by 2.5% and 26.8%, 1.6% and 11.3%, 3.3% and 0.6%, and reduced the GWP by 3.4%, 56.7% and 30.2% compared with F, IR and TR treatments in the rotation system, respectively. During the rice season, D treatment significantly (P < 0.05) increased the economic benefits, water productivity and EUE, but slight decreased the grain yield than other treatments. Overall, rice dry cultivation (especially with the HY cultivar) can achieve higher comprehensive benefits in rice growing season as well as in the whole rotation system.

11.
Life Sci ; 263: 118514, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33010283

RESUMO

AIMS: Cholera toxin is often used to induce food allergies. However, its exact mode of action and effect remain ambiguous. In this study, we established a BALB/c mouse cholera toxin/ovalbumin-induced food allergy model to determine the molecular basis and signaling mechanisms of the immune regulation of cholera toxin during food allergy. MATERIALS AND METHODS: The adjuvant activity of cholera toxin was analyzed by establishing mouse allergy model, and the allergic reaction of each group of mice was evaluated. The effect of cholera toxin on Th1/Th2 cell differentiation was analyzed to further explore the role of cholera toxin in allergen immune response. We stimulated bone marrow-derived dendritic cells (BMDCs) with cholera toxin in vitro to investigate the effect of cholera toxin on Notch ligand expression. BMDCs and naive CD4+T cells were co-cultured in vitro, and their cytokine levels were examined to investigate whether cholera toxin regulates Th cell differentiation via the Jagged2 Notch signaling pathway. KEY FINDINGS: The results showed that in the presence of allergens, cholera toxin promotes Th2 cell differentiation and enhances the body's immune response. Cholera toxin induces expression of the Notch ligand Jagged2, but Jagged2 Notch signaling pathway is not required to promote BMDCs-mediated differentiation of Th2 cells. SIGNIFICANCE: This study initially revealed the mechanism by which cholera toxin plays an adjuvant role in food allergy, and provides reference for future related research.


Assuntos
Diferenciação Celular , Toxina da Cólera/toxicidade , Modelos Animais de Doenças , Hipersensibilidade Alimentar/etiologia , Proteína Jagged-2/metabolismo , Células Th2/imunologia , Adjuvantes Imunológicos/toxicidade , Animais , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Feminino , Hipersensibilidade Alimentar/metabolismo , Hipersensibilidade Alimentar/patologia , Proteína Jagged-2/genética , Camundongos , Camundongos Endogâmicos BALB C , Receptores Notch/metabolismo , Células Th2/efeitos dos fármacos , Células Th2/metabolismo
12.
Food Chem ; 322: 126711, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32283362

RESUMO

Jug r 1, the major allergen of walnut, triggers severe allergic reactions through epitopes. Hence, research on the efficient strategy for analyzing the linear epitopes of Jug r 1 are necessary. In this work, bioinformatics analysis was used to predict the linear epitopes of Jug r 1. Overlapping peptide synthesis was used to map linear epitopes. In vitro simulated gastrointestinal digestion and HPLC-MS/MS were used to identify digestion-resistant peptides. The results showed that six predicted linear epitopes were AA28-35, AA42-49, AA55-62, AA65-73, AA97-104, and AA109-121. AA16-30 and AA125-139 were identified by the sera of walnut allergic patients. Five digestion-resistant peptides were AA19-33, AA40-45, AA54-74, AA96-106, and AA117-137. The predicted results only included one of the linear epitopes identified by sera, while the digestion-resistant peptides covered all. Therefore, the digestion-resistant property of food allergens may be a promising direction for studying the linear epitopes of Jug r 1.


Assuntos
Alérgenos/química , Epitopos/química , Juglans/química , Peptídeos/química , Alérgenos/genética , Alérgenos/imunologia , Sequência de Aminoácidos , Mapeamento de Epitopos , Epitopos/genética , Epitopos/imunologia , Hipersensibilidade Alimentar/imunologia , Humanos , Juglans/genética , Juglans/imunologia , Nozes/química , Nozes/genética , Nozes/imunologia , Peptídeos/imunologia , Análise de Sequência , Espectrometria de Massas em Tandem
13.
J Agric Food Chem ; 67(31): 8626-8631, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31287307

RESUMO

An almond allergen with two known short peptide sequences was reported as the almond 2S albumin but was later suspected to be almond vicilin. However, this allergen was not designated by the World Health Organization/International Union of Immunological Societies. This study aimed to determine the true identity of this elusive almond allergen. cDNAs were synthesized from total RNA of the Nonpareil almond. The complete sequence of the previously reported almond allergen was determined from its coding sequence. The deduced protein was produced recombinantly and was confirmed to be a food allergen by testing with 18 almond-allergic sera. The allergen is a potential cysteine-rich antimicrobial protein with characteristic C[X]3C-[X]10-12-C[X]3C motifs of the hairpinin antimicrobial protein. This first member of a novel family of food allergens was named Pru du 8. The signature motif of the hairpinin antimicrobial protein can be found in the N-terminal region of some vicilin allergens (e.g., Ara h 1). It can also be found in the signal peptide of other vicilin allergens (e.g., Car i 2). In many species, however, vicilins do not contain such a motif, indicating that the presence of the signature motifs of the hairpinin antimicrobial protein in vicilins might be a result of translocation during evolution.


Assuntos
Alérgenos/imunologia , Antígenos de Plantas/imunologia , Prunus dulcis/imunologia , Alérgenos/química , Alérgenos/genética , Motivos de Aminoácidos , Sequência de Aminoácidos , Antígenos de Plantas/química , Antígenos de Plantas/genética , DNA Complementar/genética , Hipersensibilidade Alimentar/imunologia , Humanos , Prunus dulcis/química , Prunus dulcis/genética , Proteínas de Armazenamento de Sementes/química , Proteínas de Armazenamento de Sementes/genética , Proteínas de Armazenamento de Sementes/imunologia , Alinhamento de Sequência , Análise de Sequência de DNA
14.
J Allergy Clin Immunol ; 144(3): 720-728.e4, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31071340

RESUMO

BACKGROUND: Environmental factors, as well as genetic predisposition, are known to be critical for the development of autoimmunity. However, the environmental agents that trigger autoimmune responses have remained elusive. One possible explanation is the "hit-and-run" mechanism in which the inciting antigens that initiate autoimmune responses are not present at the time of overt autoimmune disease. OBJECTIVE: After our previous findings that some allergens can incite autoimmune responses, we investigated the potential role of environmental allergens in triggering autoantibody development in patients with an autoimmune skin disease, pemphigus vulgaris (PV). METHODS: Revertant/germline mAbs (with mutations on variable regions of heavy and light chains reverted to germline forms) of 8 anti-desmoglein (Dsg) 3 pathogenic mAbs from patients with PV were tested for reactivity against a panel of possible allergens, including insects, pollens, epithelia, fungi, and food antigens. RESULTS: All the PV germline mAbs were reactive to antigens from walnut, including the well-known allergen Jug r 2 and an uncharacterized 85-kDa protein component. Sera from patients with PV contained significantly greater levels of anti-Dsg3 autoantibodies than walnut-specific antibodies, suggesting that the autoreactive B-cell response in patients with PV might be initially triggered by walnut antigens but is subsequently driven by Dsg3. CONCLUSION: Our findings suggest that walnut antigens/allergens can initiate autoantibody development in patients with PV through a "hit-and-run" mechanism. The revertant/germline mAb approach might provide a paradigm for the etiological study of other allergic and autoimmune diseases.


Assuntos
Alérgenos/imunologia , Antígenos de Plantas/imunologia , Autoanticorpos/imunologia , Juglans/imunologia , Pênfigo/imunologia , Anticorpos Monoclonais/imunologia , Desmogleína 3/imunologia , Humanos , Imunoglobulina G/imunologia
15.
Zhonghua Wei Chang Wai Ke Za Zhi ; 21(1): 79-82, 2018 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-29354904

RESUMO

OBJECTIVE: To investigate the safety and clinical significance of pelvic floor reconstruction in extralevator abdominoperineal excision(ELAPE) for advanced low rectal cancer. METHODS: The clinical efficacy was retrospectively analyzed in 30 patients with low rectal cancer who underwent ELAPE from January 2013 to December 2016 in Nanjing Drum Tower Hospital, the affiliated Hospital of Nanjing University Medical School. There were 21 male patients and 9 female, with an average age of 61.7 years old. We used 13*15 cm Biodesign biologic meshes(Cook, China) for the reconstruction and the procedure involved soaking in saline solution for 5 minutes and fixation of the mesh to the cut edges of the levators by non-absorbable 2-0 sutures. A perineal drain was used and was removed when drainage was minimal. Potassium permanganate was used for hip bath after removing the stitches. The surgical procedure, postoperative complications, prognosis and follow-up of all these patients were documented. RESULTS: The operations of all patients were completed successfully. ELAPE could remove more para cancer tissues in the distant rectum. There was no rectum perforation, and the circumferential resection margins of all specimens were proved to be negative. During the follow-up of 21 months, only 2 patients suffered incision infection and healed uneventfully after strengthening the dressing. No one developed perineal breakdown, bulge or intestinal obstruction, as well as local recurrence and pelvic floor hernia. There was also no complication related to mesh. The average hospitalization time was 10 days (9-15 days). CONCLUSIONS: The ELAPE could render a low occurrence of intraoperative perforations and circumferential resection margins. Reconstruction of pelvic floor with biologic meshmight lower the complication incidences associated with the perineal region.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Diafragma da Pelve/cirurgia , Procedimentos de Cirurgia Plástica , Neoplasias Retais/cirurgia , Abdome , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Períneo , Estudos Retrospectivos , Resultado do Tratamento
16.
Immunol Res ; 66(1): 87-96, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29181775

RESUMO

Food allergy includes sensitization phase and effect phase, and effect cells degranulate and secrete cytokines in the effect phase, causing allergic clinical symptoms. We have demonstrated that Notch signaling plays an important role in the sensitization phase, but its role in effect phases still remains unclear. In this study, we investigated the role of Notch signaling in degranulation and cytokine production of the effect phase response. A RBL-2H3 cell model was used and Notch signaling was induced by priming with Notch ligands. Our results showed after priming with Notch ligand, Delta-like1(Dll1)-Fc, ß-hexosaminidase release, and cytokines production, including TGF-ß, IL-1ß, IL-4, IL-6, and IL-13, were increased significantly, and the enhancement was abolished after DAPT treatment, a γ-secretase inhibitor, indicating that Dll1 Notch signaling enhanced RBL-2H3 cell degranulation and cytokine production. Western blot analysis showed that Dll1 Notch signaling augmented high-affinity IgE receptors-mediated phosphorylation of MAPKs through suppressing the expression of downstream tyrosine kinases 1 (Dok-1). Besides, a passive systemic anaphylaxis mouse model was used to confirm the role of Notch signaling. And our data showed that allergic clinical features of mice were alleviated, and the level of degranulation was decreased significantly after inhibiting Notch signaling in vivo. Therefore, we demonstrated Notch ligand Dll1 enhanced RBL-2H3 cell degranulation and cytokine production through a novel Notch/Dok-1/MAPKs pathway, suggesting Notch signaling played a key role in the effect phase of food allergy.


Assuntos
Anafilaxia/imunologia , Basófilos/imunologia , Hipersensibilidade Alimentar/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/metabolismo , Receptores Notch/metabolismo , Animais , Degranulação Celular , Linhagem Celular , Citocinas/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Ratos , Proteínas Recombinantes de Fusão/genética , Transdução de Sinais
17.
Oncotarget ; 8(5): 8818-8824, 2017 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-27732566

RESUMO

GOAL: To share our experience of extra-levator abdominoperineal excision (ELAPE) for low rectal cancer, focusing on perineal repair with biological mesh. METHODS: We retrospectively analyzed medical records of all patients with low rectal cancer who underwent the ELAPE procedure using biological mesh for perineal repair at the Gastrointestinal Surgery of Nanjing Drum Power Hospital between January 2013 and September 2015. All patients were closely followed up to now. RESULTS: A total of 17 patients underwent ELAPE for low rectal cancer was screened. Of these, 15 patients had primary rectal cancer, 1 had local recurrent rectal cancer, and 1 had malignant melanoma. All patients underwent ELAPE successfully without intestinal perforation and got stage I healing in perineum wound without incision infection, dehiscence, cystocele perinealis, urethral dysfunction or intestinal obstruction. Perineum wound hematoma developed in just one patient and had successful percutaneous drainage in one week. During the follow-up, there was no recurrence, perineal hernia, sexual dysfunction, urinary retention, or bowel obstruction. Two patients described slight pain in the sacrococcygeal region without special handling. CONCLUSION: ELAPE is applicable to low rectal cancer. Biological mesh reconstruction of perineal defect seems to be safe and effective, with high patient compliance.


Assuntos
Diafragma da Pelve/cirurgia , Procedimentos de Cirurgia Plástica/instrumentação , Neoplasias Retais/cirurgia , Telas Cirúrgicas , Adulto , Idoso , Idoso de 80 Anos ou mais , China , Desenho de Equipamento , Feminino , Humanos , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Diafragma da Pelve/patologia , Complicações Pós-Operatórias/etiologia , Procedimentos de Cirurgia Plástica/efeitos adversos , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Cicatrização
18.
Ann Allergy Asthma Immunol ; 118(1): 94-102, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28007091

RESUMO

BACKGROUND: Notch signaling regulates proliferation, differentiation, and function of dendritic cells, T cells, and mast cells, as well as many other immune cells, which act as important parts in food allergy, Notch signaling may play an important role in food allergy. OBJECTIVE: To investigate the role of Notch signaling in IgE-mediated food allergy. METHODS: An ovalbumin-induced food allergy mouse model was built (cholera toxin as adjuvant) and Notch signaling was blunted by FLI-06 and MW167, which inhibited Notch receptor-expressing phase and the γ-secretase-affecting phase, respectively. Then food allergy indicators, including levels of serum antibodies, cytokines, and degranulation, were examined. Meanwhile, clinical features, such as vascular permeability changes, intestinal permeability changes, body temperature changes, and symptoms, were also observed. RESULTS: After blunting Notch signaling, the levels of serum ovalbumin specific IgE and IgG1 were decreased significantly, suggesting that blunting Notch signaling inhibited antibody responses. The levels of TH1 cytokines (interferon-γ) were increased significantly, whereas the levels of TH2 cytokines (interleukin-4, -5, and -13) were decreased significantly, suggesting TH2 polarization was suppressed after blunting Notch signaling. The expression of T-bet was significantly increased, whereas the expression of Gata-3 was significantly reduced in both messenger RNA and protein levels, indicating TH2 polarization was inhibited and TH1 polarization was enhanced after blunting Notch signaling. Moreover, allergic clinical features of mice were alleviated after blunting Notch signaling. CONCLUSION: Food allergy was inhibited by blunting Notch signaling through suppressing TH2 polarization, enhancing TH1 cell differentiation and promoting TH1/TH2 balance in mice. Notch signaling plays a key role in IgE-mediated food allergy.


Assuntos
Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Células Th1/imunologia , Células Th1/metabolismo , Equilíbrio Th1-Th2 , Células Th2/imunologia , Células Th2/metabolismo , Animais , Biomarcadores , Permeabilidade Capilar , Degranulação Celular/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Expressão Gênica , Isotipos de Imunoglobulinas/sangue , Isotipos de Imunoglobulinas/imunologia , Contagem de Linfócitos , Mastócitos/imunologia , Mastócitos/metabolismo , Camundongos , Peptídeos/farmacologia , Quinolinas/farmacologia
19.
Zhonghua Wei Chang Wai Ke Za Zhi ; 18(2): 135-8, 2015 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-25656121

RESUMO

OBJECTIVE: To study the clinicopathological features and prognosis of multifocal gastric cancer. METHODS: Clinicopathological data of 30 cases with multifocal gastric cancer from January 2003 to March 2014 in our department were retrospectively analyzed. Random selection of 100 cases of single focal gastric cancer patients admitted in the same period was used as control group. Clinicopathological features and prognosis were compared between two groups. RESULTS: Six(20.0%) multifocal gastric cancer patients had 3 or more focuses with different differentiation degrees at the same time. The age of multifocal gastric cancer patients was younger than that of single focal gastric cancer [(56.8±16.4) year vs. (63.3±10.8) year, P<0.05]. The TNM stage of multifocal gastric cancer was mainly stage I((73.3%, 22/30), and the TNM stage of single focal gastric cancer was mainly stage III((64.0%, 64/100). As compared to single focal gastric cancer group, multifocal gastric cancer group had smaller tumors, lower ratio of nerve invasion and lymphatic vascular invasion(all P<0.01). Five-year survival rate was higher in multifocal gastric cancer group as compared to single focal gastric cancer group(76.0% vs. 48.8%, P<0.05). The prognosis of multifocal gastric cancer patients was associated with tumor size, nerve invasion, vascular invasion, depth of tumor invasion, lymphatic metastasis and TNM staging(all P<0.05), which was similar to single focal gastric cancer patients. Differences of 5-year survival rate under various clinicopathological conditions were not significant between two groups(all P>0.05). CONCLUSION: Multifocal gastric cancer patients have earlier staging tumor and overall advantage as compared to those with single focal gastric cancer.


Assuntos
Neoplasias Gástricas , Humanos , Metástase Linfática , Vasos Linfáticos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
20.
Asian Pac J Cancer Prev ; 15(8): 3659-65, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24870774

RESUMO

To assess inhibition mechanisms of a Phellinus igniarius (PI) extract on cancer, C57BL/6 mice were orally treated with PI extractive after or before implanting H22 (hepatocellular carcinoma ) or B16 (melanoma) cells. Mice were orally gavaged with different doses of PI for 36 days 24h after introduction of H22 or B16 cells. Mice in another group were orally treated as above daily for 42 days and implanted with H22 cells on day 7. Then the T lymphocyte, antibody, cytokine, LAK, NK cell activity in spleen, tumor cell apoptosis status and tumor inhibition in related organs, as well as the expression of iNOS and PCNA in tumor tissue were examined. The PI extract could improve animal immunity as well as inhibit cancer cell growth and metastasis with a dose-response relationship. Notably, PI's regulation with the two kinds of tumor appeared to occur in different ways, since the antibody profile and tumor metastasis demonstrated variation between animals implanted with hepatocellular carcinoma and melanoma cells.


Assuntos
Agaricales/imunologia , Anticorpos/efeitos dos fármacos , Carcinoma Hepatocelular , Citocinas/efeitos dos fármacos , Neoplasias Hepáticas , Melanoma Experimental , Linfócitos T/efeitos dos fármacos , Animais , Anticorpos/imunologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral/transplante , Proliferação de Células/efeitos dos fármacos , Citocinas/imunologia , Células Matadoras Ativadas por Linfocina/efeitos dos fármacos , Células Matadoras Ativadas por Linfocina/imunologia , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico Sintase Tipo II/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/imunologia , Antígeno Nuclear de Célula em Proliferação/efeitos dos fármacos , Antígeno Nuclear de Célula em Proliferação/imunologia , Linfócitos T/imunologia , Ensaios Antitumorais Modelo de Xenoenxerto
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