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1.
Parasite Immunol ; 44(9): e12938, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35689825

RESUMEN

The chemokine receptor CCR7 is a well-established homing receptor for dendritic cells (DCs) and T-cells. Interaction with the CCL19 and CCL21 ligands promotes priming of immune responses in lymphoid tissues; however, the mechanism underlying CCR7-induced immune responses against helminth parasite infection remains unknown. Thus, we examined the role of CCR7 in generating protective immune responses against intracellular Trichinella spiralis infection. The results showed significantly increased CCR7, CCL19 and CCL21 expression in the muscle tissue compared to that in the intestinal tissue in T. spiralis-infected mice. The CCR7-expressing DC population increased in the mesenteric and peripheral lymph nodes (PLNs) during T. spiralis infection. Notably, the number of CCR7-expressing cells in PLNs increased by more than 30% at 28 days post-infection; however, this increase was significantly inhibited in CCR7-blocked mice treated with CCR7-specific antibodies. T helper 2 (Th2)-and regulatory T (Treg )-related cytokine levels were also reduced by CCR7-specific antibody treatment. CCR7-blocked mice lost their resistance to T. spiralis infection in the muscle phase but not in the intestinal phase. Furthermore, fewer eosinophils around the nurse cells and reduced total and T. spiralis-specific IgE in the serum were observed in CCR7-blocked mice compared to those infected with only T. spiralis. CCR7 blockade led to the T. spiralis infection-induced suppression of Th2- and Treg -related cytokine production in vitro. These results suggest that CCR7 in DCs might play an essential role in host defence mechanisms against T. spiralis infection, particularly in the muscle stage of the infection, by accelerating Th2 and Treg cell responses.


Asunto(s)
Trichinella spiralis , Triquinelosis , Animales , Citocinas/metabolismo , Células Dendríticas , Ratones , Receptores CCR7/metabolismo
2.
Nanomedicine ; 11(1): 99-108, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25109662

RESUMEN

Respiratory syncytial virus (RSV) is an important human pathogen. Expression of virus structural proteins produces self-assembled virus-like nanoparticles (VLP). We investigated immune phenotypes after RSV challenge of immunized mice with VLP containing RSV F and G glycoproteins mixed with F-DNA (FdFG VLP). In contrast to formalin-inactivated RSV (FI-RSV) causing vaccination-associated eosinophilia, FdFG VLP immunization induced low bronchoalveolar cellularity, higher ratios of CD11c(+) versus CD11b(+) phenotypic cells and CD8(+) T versus CD4(+) T cells secreting interferon (IFN)-γ, T helper type-1 immune responses, and no sign of eosinophilia upon RSV challenge. Furthermore, RSV neutralizing activity, lung viral clearance, and histology results suggest that FdFG VLP can be comparable to live RSV in conferring protection against RSV and in preventing RSV disease. This study provides evidence that a combination of recombinant RSV VLP and plasmid DNA may have a potential anti-RSV prophylactic vaccine inducing balanced innate and adaptive immune responses.


Asunto(s)
Vacunas contra el Cáncer/química , Nanopartículas/química , Infecciones por Virus Sincitial Respiratorio/prevención & control , Vacunas contra Virus Sincitial Respiratorio/química , Vacunas de ADN/química , Animales , Líquido del Lavado Bronquioalveolar , Antígeno CD11b/metabolismo , Antígeno CD11c/metabolismo , Linfocitos T CD4-Positivos/citología , Linfocitos T CD8-positivos/citología , Ensayo de Inmunoadsorción Enzimática , Eosinofilia/virología , Femenino , Glicoproteínas/química , Inmunización , Inmunoglobulina G/química , Inflamación , Ratones , Ratones Endogámicos BALB C , Nanotecnología , Fenotipo , Vacunas contra Virus Sincitial Respiratorio/inmunología , Virus Sincitiales Respiratorios
3.
Exp Parasitol ; 146: 71-7, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25300761

RESUMEN

Anisakis (Anisakidae) is one of the most important causes of helminth-induced allergic reactions and elicits clinical responses that include urticaria, rhinitis, bronco-constriction, cough, and/or gastrointestinal symptoms. More than 13 reactive allergens have been identified in the serum of Anisakis allergy patients, but the allergenicity of only a few of these have been evaluated in vivo using a mouse model. To evaluate the allergenicity of two important allergens, Ani s 1 and Ani s 9, we induced experimental allergic airway inflammation in a mouse model by repeated intranasal administration of the allergens. Both recombinant proteins (rAni s 1 and rAni s 9) elicited increased airway hyperresponsivity, airway infiltration by inflammatory cells (especially eosinophils), bronchial epithelial cell hyperplasia, all of which are characteristic of allergic airway inflammation. These allergens significantly increased the levels of Th2-related cytokines (IL-4, IL-5, IL-13, and IL-25) and Th17 related cytokines (IL-6 and IL-17) in both splenocytes and airway (except IL-17 in airway by rAni s 9). OVA-specific IgE and total IgE were increased in rAni s 1 and rAni s 9 treated mice as compared with controls treated with OVA alone. In addition, these two allergens induced gene expression of thymic stromal lymphopoietin (TSLP) and IL-25 (initiators of the Th2 response), as well as CXCL1 (initiator of the Th17 response) in mouse lung epithelial cells. In conclusion, repeated intranasal treatments with rAni s 1 and rAni s 9 induced airway inflammation in mice by elevating of Th2 and Th17 responses in the lung.


Asunto(s)
Alérgenos/inmunología , Anisakis/inmunología , Sistema Respiratorio/inmunología , Alérgenos/genética , Animales , Anisakis/genética , Hiperreactividad Bronquial/etiología , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/análisis , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Proteínas del Helminto/genética , Proteínas del Helminto/inmunología , Inflamación/etiología , Inflamación/inmunología , Pulmón/inmunología , Pulmón/patología , Ratones , Ratones Endogámicos C57BL , Proteínas Recombinantes/inmunología , Sistema Respiratorio/patología , Organismos Libres de Patógenos Específicos , Bazo/citología , Bazo/inmunología
4.
Exp Mol Med ; 56(5): 1137-1149, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38689087

RESUMEN

Osimertinib, a selective third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), effectively targets the EGFR T790M mutant in non-small cell lung cancer (NSCLC). However, the newly identified EGFR C797S mutation confers resistance to osimertinib. In this study, we explored the role of pyruvate dehydrogenase kinase 1 (PDK1) in osimertinib resistance. Patients exhibiting osimertinib resistance initially displayed elevated PDK1 expression. Osimertinib-resistant cell lines with the EGFR C797S mutation were established using A549, NCI-H292, PC-9, and NCI-H1975 NSCLC cells for both in vitro and in vivo investigations. These EGFR C797S mutant cells exhibited heightened phosphorylation of EGFR, leading to the activation of downstream oncogenic pathways. The EGFR C797S mutation appeared to increase PDK1-driven glycolysis through the EGFR/AKT/HIF-1α axis. Combining osimertinib with the PDK1 inhibitor leelamine helped successfully overcome osimertinib resistance in allograft models. CRISPR-mediated PDK1 knockout effectively inhibited tumor formation in xenograft models. Our study established a clear link between the EGFR C797S mutation and elevated PDK1 expression, opening new avenues for the discovery of targeted therapies and improving our understanding of the roles of EGFR mutations in cancer progression.


Asunto(s)
Acrilamidas , Compuestos de Anilina , Carcinoma de Pulmón de Células no Pequeñas , Resistencia a Antineoplásicos , Receptores ErbB , Neoplasias Pulmonares , Mutación , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora , Humanos , Acrilamidas/farmacología , Acrilamidas/uso terapéutico , Receptores ErbB/genética , Receptores ErbB/metabolismo , Resistencia a Antineoplásicos/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Compuestos de Anilina/farmacología , Compuestos de Anilina/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/metabolismo , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/genética , Animales , Línea Celular Tumoral , Ratones , Ensayos Antitumor por Modelo de Xenoinjerto , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Femenino , Masculino , Indoles , Pirimidinas
5.
Korean J Parasitol ; 51(5): 583-8, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24327787

RESUMEN

To determine alteration of immune responses during visceral larva migrans (VLM) caused by Toxascaris leonina at several time points, we experimentally infected mice with embryonated eggs of T. leonina and measured T-helper (Th) cell-related serial cytokine production after infection. At day 5 post infection (PI), most larvae were detected from the lungs, spleen, intestine, and muscle. Expression of thymic stromal lymphopoietin (TSLP) and CCL11 (eotaxin) showed a significant increase in most infected organs, except the intestine. However, expression of the CXCL1 (Gro-α) gene was most highly enhanced in the intestine at day 14 PI. Th1-related cytokine secretion of splenocytes showed increases at day 28 PI, and the level showed a decrease at day 42 PI. Th2-related cytokine secretion of splenocytes also showed an increase after infection; in particular, IL-5 level showed a significant increase at day 14 PI, and the level showed a decrease at day 28 PI. However, levels of Th17-related cytokines, IL-6 and IL-17A, showed gradual increases until day 42 PI. In conclusion, Th1, Th2, and Th17-related cytokine production might be important in immune responses against T. leonina VLM in experimental mice.


Asunto(s)
Citocinas/metabolismo , Interleucinas/metabolismo , Larva Migrans Visceral/inmunología , Toxascaris/inmunología , Animales , Encéfalo/parasitología , Femenino , Regulación de la Expresión Génica , Corazón/parasitología , Intestinos/parasitología , Larva Migrans Visceral/parasitología , Hígado/parasitología , Pulmón/parasitología , Pulmón/patología , Ratones , Ratones Endogámicos C57BL , Músculos/parasitología , Bazo/parasitología , Células TH1/inmunología , Células Th17/inmunología , Células Th2/inmunología , Linfopoyetina del Estroma Tímico
6.
Korean J Parasitol ; 51(1): 139-42, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23468007

RESUMEN

Pinworm infection can occur through contact with contaminated surfaces followed by ingestion or even through inhalation of infective eggs. We have limited information regarding environmental contamination by eggs of Enterobius vermicularis. In order to determine environmental risk factors associated with the rate of E. vermicularis infection, we investigated possible environmental risk factors using a questionnaire from 46 kindergartens in 3 different cities of the southeast area of Korea. In total, using the cellotape anal swab technique, 3,422 children were examined for E. vermicularis infection. We evaluated E. vermicularis egg of books, educational materials, toys, room door handles, dusts of window edges, desks, chairs, tables, and dusts of classrooms. The overall egg-positive rate for E. vermicularis was 6.0%, and the prevalence of enterobiasis in each kindergarten ranged between 0% and 16.9%. We found that 78.9% of egg positive kindergartens were managed by private foundations, which was significantly higher, compared with kindergartens managed by public foundations or the nation. Compared with public or national kindergartens, most private kindergartens were located in residential areas and the number of children in these areas was significantly higher. In conclusion, numbers of children in kindergartens was found to be an environmental risk factor associated with transmission of enterobiasis in Korea.


Asunto(s)
Guarderías Infantiles , Enterobiasis/epidemiología , Enterobius/aislamiento & purificación , Exposición a Riesgos Ambientales , Animales , Preescolar , Enterobiasis/parasitología , Femenino , Humanos , Corea (Geográfico)/epidemiología , Masculino , Medición de Riesgo , Encuestas y Cuestionarios
7.
Korean J Parasitol ; 51(5): 525-30, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24327777

RESUMEN

The ascarids, Toxocara canis and Toxascaris leonina, are probably the most common gastrointestinal helminths encountered in dogs. In order to understand biological differences of 2 ascarids, we analyzed gene expression profiles of female adults of T. canis and T. leonina using CLC Genomics Workbench, and the results were compared with those of free-living nematode Caenorhabditis elegans. A total of 2,880 and 7,949 ESTs were collected from T. leonina and T. canis, respectively. The length of ESTs ranged from 106 to 4,637 bp with an average insert size of 820 bp. Overall, our results showed that most functional gene annotations of 2 ascarids were quite similar to each other in 3 major categories, i.e., cellular component, biological process, and molecular function. Although some different transcript expression categories were found, the distance was short and it was not enough to explain their different lifestyles. However, we found distinguished transcript differences between ascarid parasites and free-living nematodes. Understanding evolutionary genetic changes might be helpful for studies of the lifestyle and evolution of parasites.


Asunto(s)
Enfermedades de los Perros/parasitología , Genómica , Toxascariasis/veterinaria , Toxascaris/genética , Toxocara canis/genética , Toxocariasis/parasitología , Animales , Perros , Femenino , Anotación de Secuencia Molecular , Toxascariasis/parasitología , Toxascaris/metabolismo , Toxocara canis/metabolismo
8.
Heliyon ; 9(2): e13615, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36852026

RESUMEN

A shared personal mobility device (PMD) is a transportation model that rents personal transportation devices, such as bicycles and kickboards, through a sharing platform. The use of shared PMD has increased, but related complaints and traffic accidents are doubling with it every year. This study applied an analytic network process (ANP) methodology for the multi-criteria analysis. A survey including normal citizens was conducted to evaluate the importance of safety regarding shared PMD experience. The evaluation factors differ according to the experience of using the shared PMD device, although 'driving continuity' and 'separation of sidewalks and roadways' were the most important. PMD users gave greater priority to 'removal of the road gap', 'traffic safety signs', 'dedicated parking area' and 'management of obstacles' compared to non-users. On the other hand, for non-PMD users, 'bicycle lane width', 'strengthening enforcement', and 'user safety education' were more important. The results showed that importance differed depending on the participant's experience of using a shared PMD or the lack of it. In the case of users, factors that have a direct effect on driving were prioritised, and in the case of non-users, auxiliary operations and management, such as crackdowns and education, were prioritised.

9.
Oncol Rep ; 49(4)2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36825595

RESUMEN

Metabolic disorder is a major characteristic of cancer cells, and controlling genes involved in metabolic shifts can be an effective strategy for cancer treatment. Andrographolide (AG), a diterpenoid lactone, is widely recognized as a natural anticancer drug due to its ability to inhibit cancer growth. The present study aimed to investigate the mechanism underlying the mitochondrial­mediated anticancer effect of AG by inhibiting pyruvate dehydrogenase kinase 1 (PDK1) expression in lung cancer cells. Cells were treated with AG and PDK1 mRNA and protein expression was determined using reverse transcription­quantitative PCR and western blotting, respectively. As a result, AG significantly inhibited the viability of human lung cancer cells and suppressed aerobic glycolysis by decreasing lactate generation. AG further decreased the PDK1 protein and mRNA levels in a dose­dependent manner. AG­induced cell death was assessed by flow cytometry and fluorescence microscopy. AG induced apoptotic cell death that was associated with the cleavage of poly (ADP ribose) polymerase, activation of caspase­3, and mitochondrial damage, which was associated with an increase in reactive oxygen species and loss of mitochondrial membrane potential. AG­induced cell death was partially suppressed via PDK1 overexpression in lung cancer cells. Therefore, the anticancer effects of AG on human lung cancer cells may negatively regulate the expression of PDK1.


Asunto(s)
Diterpenos , Neoplasias Pulmonares , Humanos , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Apoptosis , Diterpenos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Glucólisis , Línea Celular Tumoral , Proliferación Celular
10.
Integr Med Res ; 12(2): 100947, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37168676

RESUMEN

Background: Frankincense, a resin derived from trees of the Boswellia genus, has been used as an incense and a type of herbal medicine for treating inflammatory diseases such arthritis, chronic bowel illness, and asthma. While endometriosis is a well-known inflammatory gynecological illness caused by the ectopic attachment and development of uterine tissue over the menstrual cycle, the impact of frankincense on this illness is poorly understood. The purpose of this study was to explore the effects of frankincense on endometriosis. Methods: We used a network pharmacological assessment, in vitro and in vivo investigations with a human endometriotic cell line as well as a syngeneic uterine transfer mouse model. High-performance liquid chromatographic analysis was used to compare water-extracted frankincense (Fr) to its reference compounds and validate the sample. Results: A network pharmacological analysis suggested a positive effect of Fr on endometriosis. Fr relieved endometriosis by reducing ectopic endometrial adherence and development, according to both in vivo and in vitro models. We suggested that the ER stress/p53-apoptosis and chemokine-migration/adhesion pathways underlie Fr's anti-endometriotic action using RNA sequencing and bioinformatic analysis. Conclusion: This study revealed the potential effect of Fr on endometriosis using an experimental investigation. Fr may have the potential to be an effective and safe treatment for endometriosis.

11.
J Asthma ; 49(1): 10-5, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22149098

RESUMEN

BACKGROUND: In a previous study, we demonstrated that the human macrophage migration inhibitory factor (MIF)-like protein (As-MIF) isolated from helminths could inhibit allergic airway inflammation via the recruitment of CD4(+)CD25(+)Foxp3(+) T cells. OBJECTIVE: To evaluate the clinical importance of As-MIF as an antiasthma drug, we evaluated immune responses after recombinant As-MIF (rAs-MIF) treatment in peripheral blood mononuclear cell (PBMC) cultures. METHODS: PBMC was isolated from 10 patients with atopic asthma, 8 patients with nonatopic asthma, and 12 nonatopic healthy subjects, and various concentrations of rAs-MIF were transferred into the PBMC culture medium. After 3 days, we measured the levels of T helper 2 and T helper 1 cytokines via ELISA. RESULTS: In atopic asthma, IL-4 and IL-5 production was significantly reduced in the PBMC cultures after rAs-MIF treatment. These inhibitory effects were not observed in the nonatopic asthma group. By way of contrast, IL-10 production in the PMBC cultures was significantly increased after rAs-MIF treatment in all experimental groups. CONCLUSION: The results of this study are similar to those previously reported in a mouse study, suggesting that As-MIF might be a candidate for the specific treatment of asthma.


Asunto(s)
Asma/tratamiento farmacológico , Citocinas/metabolismo , Helmintos/química , Leucocitos Mononucleares/efectos de los fármacos , Factores Inhibidores de la Migración de Macrófagos/aislamiento & purificación , Factores Inhibidores de la Migración de Macrófagos/farmacología , Células Th2/efectos de los fármacos , Adulto , Animales , Asma/sangre , Asma/inmunología , Estudios de Casos y Controles , Células Cultivadas , Citocinas/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Hipersensibilidad Inmediata/tratamiento farmacológico , Hipersensibilidad Inmediata/inmunología , Interleucina-10/análisis , Interleucina-10/metabolismo , Interleucina-4/análisis , Interleucina-4/metabolismo , Interleucina-5/análisis , Interleucina-5/metabolismo , Leucocitos Mononucleares/inmunología , Factores Inhibidores de la Migración de Macrófagos/inmunología , Masculino , Persona de Mediana Edad , Células Th2/inmunología , Células Th2/metabolismo , Adulto Joven
12.
Exp Parasitol ; 130(1): 69-72, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22001446

RESUMEN

A gene coding for a 24 kDa protein (22 U homologous; As22U) was isolated from the Anisakis simplex third-stage larvae cDNA library during expressed sequence tag analysis. As22U was 636 bp long, and was found to code for 212 amino acid residues with a calculated mass of 23.5 kDa and a PI of 9.06. The As22U deduced amino acid sequence harbored a signal peptide region and 16 highly conserved cysteine residues, and it was identified in both the total extracts and excretory secretory (ES) protein of A. simplex. Its molecular weight was measured at 24 kDa via western blot analysis. The expression levels of thymic stromal lymphopoietin, IL-25, and CXCL1 (Gro-α) genes were increased at 6h after recombinant As22U treatment in mouse intestinal epithelial cells. Additionally, thymus and activation-regulated chemokine gene levels were increased at 14 h after treatment. Although we do not currently have sufficient evidence to determine whether As22U plays a role as an allergen, this remains possible. Further in vivo studies may provide some insight as to the allergenic properties of As22U.


Asunto(s)
Alérgenos/aislamiento & purificación , Anisakis/metabolismo , Proteínas del Helminto/aislamiento & purificación , Alérgenos/química , Alérgenos/genética , Secuencia de Aminoácidos , Animales , Anisakiasis/parasitología , Anisakis/genética , Secuencia de Bases , Western Blotting , Línea Celular , Citocinas/genética , Citocinas/metabolismo , Gadiformes , Regulación de la Expresión Génica , Proteínas del Helminto/química , Proteínas del Helminto/genética , Larva/química , Larva/genética , Ratones , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/aislamiento & purificación , Células Th2/efectos de los fármacos , Células Th2/inmunología
13.
Korean J Parasitol ; 50(4): 385-90, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-23230342

RESUMEN

In order to know the effect of pre-existing Trichinella spiralis infection on experimentally induced intestinal inflammation and immune responses, we induced colitis in T. spiralis-infected mice and observed the severity of colitis and the levels of Th1, Th2, and regulatory cytokines and recruitment of CD4(+)CD25(+)Foxp3(+) T (regulatory T; T(reg)) cells. Female C57BL/6 mice were infected with 250 muscle larvae; after 4 weeks, induction of experimental colitis was performed using 3% dextran sulfate sodium (DSS). During the induction period, we observed severity of colitis, including weight loss and status of stool, and evaluated the disease activity index (DAI). A significantly low DAI and degree of weight loss were observed in infected mice, compared with uninfected mice. In addition, colon length in infected mice was not contracted, compared with uninfected mice. We also observed a significant increase in production of pro-inflammatory cytokines, IL-6 and IFN-γ, in spleen lymphocytes treated with DSS; however, such an increase was not observed in infected mice treated with DSS. Of particular interest, production of regulatory cytokines, IL-10 and transforming growth factor (TGF)-ß, in spleen lymphocytes showed a significant increase in mice infected with T. spiralis. A similar result was observed in mesenteric lymph nodes (MLN). Subsets of the population of T(reg) cells in MLN and spleen showed significant increases in mice infected with T. spiralis. In conclusion, T. spiralis infection can inhibit the DSS-induced colitis in mice by enhancing the regulatory cytokine and T(reg) cells recruitment.


Asunto(s)
Colitis/inmunología , Citocinas/inmunología , Regulación de la Expresión Génica , Linfocitos T Reguladores/inmunología , Trichinella spiralis/inmunología , Triquinelosis/inmunología , Animales , Colitis/inducido químicamente , Colitis/patología , Citocinas/genética , Citocinas/metabolismo , Sulfato de Dextran/efectos adversos , Modelos Animales de Enfermedad , Femenino , Factores de Transcripción Forkhead/inmunología , Factores de Transcripción Forkhead/metabolismo , Larva , Ratones , Ratones Endogámicos C57BL , Bazo/inmunología , Triquinelosis/parasitología
14.
J Allergy Clin Immunol Pract ; 10(10): 2685-2692.e2, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35413472

RESUMEN

BACKGROUND: An optimal strategy for choosing safe alternative low osmolar contrast media (LOCM) has not yet been established in patients with a history of LOCM-induced anaphylaxis. OBJECTIVES: To validate the practical pathway in patients with anaphylaxis to LOCMs and to compare 2 different doses of challenge testing with skin test-negative LOCM. METHODS: A retrospective cohort study was performed in patients with LOCM-induced anaphylaxis. Patients were challenged with intravenous LOCMs showing negativity in the skin test according to 2 different protocols: low-dose and high-dose (maximum dose 10 and 30 mL, respectively). Challenge-negative LOCMs were selected for use during computed tomography scans, and patients received intravenous pretreatment with 4 mg chlorpheniramine and 40 mg methylprednisolone. RESULTS: Of the 110 challenge tests, there were 4 (3.6%) positive challenges. Among 106 enhanced computed tomography scans performed using challenge-negative LOCMs, breakthrough reactions occurred in 8 (7.6%). Breakthrough reaction rates were not statistically different between the 2 protocols (8.9% and 6.0% in the low-dose challenge and the high-dose challenge, respectively). Compared with the low-dose protocol, the number needed to test of the high-dose challenge test decreased 2.5-fold. Moreover, none of the patients in the high-dose challenge group incurred severe reactions during computed tomography scans with challenge-negative LOCM, whereas 80% of reactions were severe in the low-dose challenge group. CONCLUSIONS: We validated a pathway consisting of a battery of skin testing to LOCMs and challenge with skin test-negative LOCM in patients with LOCM-induced anaphylaxis.


Asunto(s)
Anafilaxia , Medios de Contraste , Anafilaxia/inducido químicamente , Anafilaxia/diagnóstico , Clorfeniramina , Medios de Contraste/efectos adversos , Humanos , Metilprednisolona , Concentración Osmolar , Estudios Retrospectivos
15.
Front Pharmacol ; 13: 872810, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35444541

RESUMEN

Endometriosis is a chronic inflammatory disorder caused by abnormal adhesion of endometrial tissue to the outside of the uterus. The combination of surgery, non-steroidal anti-inflammatory drugs, and hormone treatment is well established therapy for endometriosis, however, case reports have showed that high rates of relapse and unpleasant side effect. For these reasons, recently, the studies have been focused on the Warburg-like metabolic shift of endometriosis. Prunella vulgaris is one of traditionally used herbal medicine for inflammatory disease and the anti-estrogenic effects of P. vulgaris is well-established. Therefore, in this work, we evaluated water-extracted P. vulgaris (PV) as a potential treatment for endometriosis. To this, we artificially induced endometriosis in ovarectomized mice by intra-peritoneal inoculation of uterus extracts. PV was orally administered, and PV significantly alleviated endometriosis, particularly the growth of ectopic endometrial lesions in artificially endometriosis-induced mice. For the mechanism study of anti-endometriosis by PV, we designed an in vitro study using human normal endometrial stromal cells (T-HESCs) and human endometrial cell (12Z) obtained from patients with endometriosis. PV strongly induced the apoptosis of 12Z cells rather than T-HESCs by control the activity or expression of aerobic glycolysis enzymes, such as lactate dehydrogenase A (LDHA), pyruvate dehydrogenase A, and pyruvate dehydrogenase kinase 1/3. In addition, lactate production was enhanced, and oxygen consumption rate was suppressed in 12Z cells upon PV treatment. These changes in aerobic glycolysis eventually caused mitochondrial damage following decreased mitochondrial membrane potential and excessive mitochondrial ROS production. Especially, ulsolic acid (UA), one of the compounds in PV considerably led 12Z cell apoptosis with inhibition of LDHA activity. Therefore, UA could be a major active substance of PV in terms of endometriosis inhibitors. In conclusion, this study provides the evidence that the beneficial efficacy of PV for the prevention/treatment of endometriosis.

16.
Front Endocrinol (Lausanne) ; 13: 942368, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36339397

RESUMEN

Endometriosis is a gynecological disease prevalent in women of reproductive age, and it is characterized by the ectopic presence and growth of the eutopic endometrium. The pathophysiology and diagnostic biomarkers of endometriosis have not yet been comprehensively determined. To discover molecular markers and pathways underlying the pathogenesis of endometriosis, we identified differentially expressed genes (DEGs) in three Gene Expression Omnibus microarray datasets (GSE11691, GSE23339, and GSE7305) and performed gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network analyses. We also validated the identified genes via immunohistochemical analysis of tissues obtained from patients with endometriosis or healthy volunteers. A total of 118 DEGs (79 upregulated and 39 downregulated) were detected in each dataset with a lower (fold change) FC cutoff (log2|FC| > 1), and 17 DEGs (11 upregulated and six downregulated) with a higher FC cutoff (log2|FC| > 2). KEGG and GO functional analyses revealed enrichment of signaling pathways associated with inflammation, complement activation, cell adhesion, and extracellular matrix in endometriotic tissues. Upregulation of seven genes (C7, CFH, FZD7, LY96, PDLIM3, PTGIS, and WISP2) out of 17 was validated via comparison with external gene sets, and protein expression of four genes (LY96, PDLIM3, PTGIS, and WISP2) was further analyzed by immunohistochemistry and western blot analysis. Based on these results, we suggest that TLR4/NF-κB and Wnt/frizzled signaling pathways, as well as estrogen receptors, regulate the progression of endometriosis. These pathways may be therapeutic and diagnostic targets for endometriosis.


Asunto(s)
Endometriosis , Humanos , Femenino , Endometriosis/diagnóstico , Endometriosis/genética , Endometriosis/metabolismo , Biología Computacional/métodos , Mapas de Interacción de Proteínas/genética , Biomarcadores/metabolismo , Vía de Señalización Wnt
17.
Front Pharmacol ; 13: 1112004, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36582524

RESUMEN

[This corrects the article DOI: 10.3389/fphar.2022.872810.].

18.
J Immunol ; 182(11): 6907-14, 2009 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-19454687

RESUMEN

We have cloned the macrophage migration inhibitory factor (MIF)-like protein (Anisakis simplex (As)-MIF) from larvae of the whale worm (Anisakis simplex third-stage larvae). Asthma was induced in the mice using OVA/alum, with or without various concentrations of rAs-MIF treatment before OVA/alum challenge. Treatment with rAs-MIF coupled with OVA/alum during the challenge period induced a complete inhibition of eosinophilia and goblet cell hyperplasia within the lung and profoundly ameliorated the development of lung hyperreactivity. Also, rAs-MIF was shown to reduce profoundly the quantity of Th2-related cytokines (IL-4, IL-5, and IL-13) in the bronchial alveolar lavage fluid and allergen-specific IgG2a in sera. IL-10 and TGF-beta levels in the bronchoalveolar lavage fluid of the rAs-MIF-treated group were significantly higher than in the other groups. Additionally, CD4(+)CD25(+)Foxp3(+) T cells (regulatory T) were recruited to the spleen and lungs of the rAs-MIF-treated mice, but this recruitment was inhibited by anti-rAs-MIF Ab.


Asunto(s)
Asma/inmunología , Quimiotaxis de Leucocito/inmunología , Factores Inhibidores de la Migración de Macrófagos/inmunología , Linfocitos T Reguladores/inmunología , Células Th2/inmunología , Animales , Anisakis , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/análisis , Modelos Animales de Enfermedad , Inflamación/inmunología , Pulmón/inmunología , Ratones , Bazo/inmunología
19.
Exp Parasitol ; 127(2): 539-44, 2011 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21044628

RESUMEN

In an effort to define the mechanism underlying the host immune downregulation inherent to Trichinella spiralis infection, we compared the levels of Th1, Th2, and regulatory cytokines and CD4(+)CD25(+) forkhead box P3 (FoxP3)(+) T (T(reg)) cell recruitment, as well as cellular pathology in the airway between T. spiralis infected and uninfected asthma-induced mice. After the induction of allergic airway inflammation, we noted influxes of inflammatory cells into the peribronchial tree. However, in the T. spiralis infection groups, cellular infiltration was minimal around the bronchial tree, with only a smattering of inflammatory cells. In the OVA-challenged group after T. spiralis infection, the numbers of macrophages and eosinophils in the bronchial alveolar lavage fluid were reduced by 23% and 52%, respectively, as compared to those of the OVA-challenged group. Airway hyperresponsiveness of OVA-challenged mice after T. spiralis infection was significantly suppressed as compared to the OVA-only challenged mice. The T. spiralis-infected mice exhibited a significant reduction in IL-5 concentrations relative to that noted in the OVA-challenged group (p<0.01). Nevertheless, the regulatory cytokines IL-10 and TGF-ß levels were increased significantly as the result of T. spiralis infection, and we verified the recruitment of T(reg) cells in lung draining lymph nodes via T. spiralis infection. Therefore, T(reg) cells, which were recruited by T. spiralis infection, might ameliorate lung function and reduce allergic airway inflammation.


Asunto(s)
Asma/inmunología , Trichinella spiralis , Triquinelosis/complicaciones , Animales , Asma/complicaciones , Asma/prevención & control , Citocinas/biosíntesis , Citocinas/inmunología , Modelos Animales de Enfermedad , Femenino , Inmunoglobulinas/sangre , Inflamación/inmunología , Inflamación/prevención & control , Pulmón , Ganglios Linfáticos/inmunología , Linfocitos/inmunología , Ratones , Ratones Endogámicos C57BL , Sistema Respiratorio/patología , Triquinelosis/inmunología
20.
Korean J Parasitol ; 49(2): 139-44, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21738269

RESUMEN

The present study was performed to estimate the seroprevalence of larval Anisakis simplex infection among the residents health-examined in 3 hospitals in southern parts of Korea. A total of 498 serum samples (1 serum per person) were collected in 3 hospitals in Busan Metropolitan city, Masan city, and Geoje city in Gyeongsangnam-do (Province) and were examined by IgE-ELISA and IgE-western blotting with larval A. simplex crude extract and excretory-secretory products (ESP). The prevalence of antibody positivity was 5.0% and 6.6% with ELISA against crude extracts and ESP, respectively. It was also revealed that infection occurred throughout all age groups and higher in females than in males. A specific protein band of 130 kDa was detected from 10 patients with western blot analysis against crude extract and ESP among those who showed positive results by ELISA. Our study showed for the first time the seroprevalence of anisakiasis in Korea. The allergen of 130 kDa can be a candidate for serologic diagnosis of anisakiasis.


Asunto(s)
Anisakiasis/epidemiología , Anisakis/inmunología , Anticuerpos Antihelmínticos/sangre , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Animales , Antígenos Helmínticos/química , Western Blotting , Niño , Ensayo de Inmunoadsorción Enzimática , Femenino , Hospitales , Humanos , Inmunoglobulina E/sangre , Corea (Geográfico)/epidemiología , Larva/inmunología , Masculino , Persona de Mediana Edad , Peso Molecular , Estudios Seroepidemiológicos , Distribución por Sexo , Adulto Joven
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