RESUMEN
Angiostrongylus cantonensis is the major cause of human eosinophilic meningoencephalitis. C57BL/6 mice were experimentally infected with 35 infectious larvae. Two groups of infected mice received intraperitoneal injections of mouse IL-33 (1µg) or anti-IL-33 monoclonal antibody (mAb) (10µg) 3days post infection (dpi) and subsequent booster shots of the same dose at 5day intervals. Blood samples from each group were collected weekly for assays. IgE levels were significantly increased in all infected mice. The eosinophil percentage and levels of IL-5 and IL-13 significantly increased in the IL-33-treated group relative to infected but non-treated animals. The level of IL-5 decreased in the mAb-treated group. The severity of eosinophilic meningitis was exacerbated in the IL-33 injected group. Taken together, these results suggest that IL-33 mediates the expressions of IL-5 and IL-13, and plays a crucial role in the pathogenesis of angiostrongylosis.
Asunto(s)
Angiostrongylus cantonensis/inmunología , Infecciones Protozoarias del Sistema Nervioso Central/inmunología , Interleucina-13/metabolismo , Interleucina-5/metabolismo , Interleucinas/administración & dosificación , Infecciones por Strongylida/inmunología , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/inmunología , Biomphalaria , Encéfalo/patología , Citocinas/sangre , Eosinofilia/inmunología , Eosinofilia/parasitología , Inmunoglobulina E/sangre , Inyecciones Intraperitoneales , Interleucina-33 , Interleucinas/inmunología , Interleucinas/fisiología , Recuento de Leucocitos , Masculino , Meninges/patología , Ratones , Ratones Endogámicos C57BL , Distribución Aleatoria , Ratas , Ratas Wistar , Organismos Libres de Patógenos EspecíficosRESUMEN
A cDNA library was constructed from an Angiostrongylus cantonensis young adult and the encoded proteins were expressed in Escherichia coli. One reactive antigen, a RAB-2 protein, was selected using an immunoscreening technique. The expression of the Th1-type cytokine IFN-γ was elicited in mouse splenic cells that were co-cultured with the recombinant RAB-2 protein and in the sera of mice that were immunised with this protein and adjuvant (50 µg at 2-week intervals). In the A. cantonensis-infected groups, the mice were orally infected with 35 infective larvae, and a subset of the infected mice were immunised with the recombinant RAB-2 protein in adjuvant. Serum samples were collected every week for ELISA, and the pathological examinations were performed at 14 days post infection (dpi). An increase in IFN-γ expression was noted in the blood, and the brain sections revealed moderate eosinophilic meningitis in the immunised mice. The RAB-2 antigen of A. cantonensis induced a Th1-type immune response both in vitro and in vivo.
Asunto(s)
Angiostrongylus cantonensis/inmunología , Antígenos Helmínticos/inmunología , Infecciones por Strongylida/inmunología , Células TH1/inmunología , Proteína de Unión al GTP rab2/inmunología , Angiostrongylus cantonensis/genética , Animales , Antígenos Helmínticos/genética , Biomphalaria , Encéfalo/parasitología , Encéfalo/patología , Células Cultivadas , Proteínas del Helminto/genética , Proteínas del Helminto/inmunología , Interferón gamma/sangre , Interferón gamma/genética , Interferón gamma/metabolismo , Interleucina-13/genética , Interleucina-13/metabolismo , Interleucina-4/genética , Interleucina-4/metabolismo , Interleucina-5/genética , Interleucina-5/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , Conejos , Distribución Aleatoria , Ratas , Ratas Wistar , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología , Bazo/citología , Bazo/inmunología , Infecciones por Strongylida/parasitología , Proteína de Unión al GTP rab2/genéticaRESUMEN
As people in the 21st century become increasingly environmentally aware, environmentally friendly products have come into focus. As such, environmentally friendly textiles and eco-textiles have become an international trend in research and development. Poly(lactic acid) fiber, which is biodegradable, holds much promise, but it is difficult to deep dye. This study used chitosan, succine anhydride, siloxane, and polyethylene glycol to produce a series of chitosan/siloxane polyesters that have a hydrophilic component (chitosan) and a hydrophobic component (siloxane), and this chitosan/siloxane polyester can be coated on poly(lactic acid) fiber, which we had subjected to Argon plasma treatment to increase their antimicrobial properties and to increase the fibers dyeing efficiency. The study shows that, after the surface plasma treatment, longer PEG chain lengths resulted in higher K/S values. This result suggests that the surface plasma pretreatment and chitosan/siloxane polyesters coating showed that lower ∆E values result in more leveling dyeing of poly(lactic acid) fiber.
RESUMEN
BACKGROUND/PURPOSE: Interleukin-33 (IL-33) could play an important role in the pathogenesis of angiostrongylosis. However, the role of IL-33/ST2 pathway in this parasitic infection is uncertain. METHODS: C57BL/six mice were each infected with 35 Angiostrongylus cantonensis larvae. One group of mice received an intraperitoneal injection of anti-ST2 monoclonal antibody (mAb; 50 µg) 3 days postinfection and subsequent booster shots of the same dose at 5-day intervals. Blood samples from each group were collected every week for assays. RESULTS: The level of IL-5 significantly decreased in the mAb-treated group, and the infiltration of eosinophils in the meninges was also significantly reduced. CONCLUSION: The IL-33/ST2 axis may play a crucial role in the pathogenesis of angiostrongylosis and the results of this study could be useful for the development of strategies to reduce the neurological damage caused by this parasitic infection.
Asunto(s)
Angiostrongylus cantonensis/inmunología , Anticuerpos Monoclonales/administración & dosificación , Eosinófilos/inmunología , Meninges/patología , Receptores de Interleucina/antagonistas & inhibidores , Infecciones por Strongylida/patología , Animales , Proteína 1 Similar al Receptor de Interleucina-1 , Masculino , Ratones Endogámicos C57BL , Resultado del TratamientoRESUMEN
@#BACKGROUND. Sensorineural hearing impairment (SNHI) is the most common inherited sensory defect, affecting about 3 per 1000 children. More than 50% of these patients have a genetic cause (i.e. hereditary hearing impairment; HHI). Mutations in certain genes were noted to be extraordinarily popular in the deaf patients across different populations, making molecular screening feasible for these common deafness genes. One of the most important characteristics that we have learned concerning hereditary hearing loss is that common deafness genes and their mutations are usually different according to the ethnic background. As demonstrated in our previous studies performed in Taiwanese patients, the mutation spectrums of common deafness genes, such as the GJB2 gene and the SLC26A4 gene, are different from those in the Caucasian or even other Asian populations. These findings further underscore the indispensability of the collection of local data in terms of genetic counseling. In the collaborative project, we have successfully established a cohort of >100 hearingimpaired families, and clarified the genetic epidemiology of deafness in the Mongolian population. We identified several special deafness mutations such as GJB2 c.23+1G>A, c.559_604dup, and SLC26A4 c.919-2A>G, and our results revealed that Mongolian patients demonstrate a unique genetic profile in deafness as compared to other East Asian populations (paper in preparation). Meanwhile, by organizing a seminar at National Taiwan University Hospital in March 2017, we have transferred crucial concepts and techniques regarding how to perform genetic testing for deafness to the Mongolian colleagues. In the future, we plan to strengthen the mutual collaboration by expanding the clinical cohort and upgrading the genetic examination platform using the NGS techniques.
RESUMEN
@#BACKGROUND. Sensorineural hearing impairment (SNHI) is the most common inherited sensory defect, affecting about 3 per 1000 children. More than 50% of these patients have a genetic cause (i.e. hereditary hearing impairment; HHI). Mutations in certain genes were noted to be extraordinarily popular in the deaf patients across different populations, making molecular screening feasible for these common deafness genes. One of the most important characteristics that we have learned concerning hereditary hearing loss is that common deafness genes and their mutations are usually different according to the ethnic background. As demonstrated in our previous studies performed in Taiwanese patients, the mutation spectrums of common deafness genes, such as the GJB2 gene and the SLC26A4 gene, are different from those in the Caucasian or even other Asian populations. These findings further underscore the indispensability of the collection of local data in terms of genetic counseling. In the collaborative project, we have successfully established a cohort of >100 hearing-impaired families, and clarified the genetic epidemiology of deafness in the Mongolian population. We identified several special deafness mutations such as GJB2 c.23+1G>A, c.559_604dup, and SLC26A4 c.919-2A>G, and our results revealed that Mongolian patients demonstrate a unique genetic profile in deafness as compared to other East Asian populations (paper in preparation). Meanwhile, by organizing a seminar at National Taiwan University Hospital in March 2017, we have transferred crucial concepts and techniques regarding how to perform genetic testing for deafness to the Mongolian colleagues. In the future, we plan to strengthen the mutual collaboration by expanding the clinical cohort and upgrading the genetic examination platform using the NGS techniques.
RESUMEN
ICR mice were each infected with 35 Angiostrongylus cantonensis larvae. One group of mice received an intraperitoneal injection of anti-CCR3 monoclonal antibody (mAb) (50 microg) at 10 days post-infection (dpi), while another similarly-treated group also received a booster injection (25 microg) at 12 dpi. All the mice were sacrificed at 14 dpi for pathological examination, enzyme-linked immunosorbent assay analysis and RNA extraction. The infiltration of eosinophils and the severity of eosinophilic meningitis were reduced in both the mAb-treated groups, relative to infected but untreated animals. The levels of CCL11 (eotaxin) in the peripheral circulation and the expression of the Th2-type cytokine interleukin-5 in the brains were significantly reduced. A. cantonensis infection is the major cause of eosinophilic meningoencephalitis in Taiwan, and the results of this study could be useful for the development of strategies to reduce the neurological damage caused by this infection.
Asunto(s)
Angiostrongylus cantonensis/inmunología , Anticuerpos Monoclonales/inmunología , Eosinófilos/inmunología , Factores Inmunológicos/inmunología , Meningitis/patología , Receptores CCR3/antagonistas & inhibidores , Infecciones por Strongylida/patología , Animales , Anticuerpos Monoclonales/administración & dosificación , Quimiocina CCL11/sangre , Modelos Animales de Enfermedad , Factores Inmunológicos/administración & dosificación , Inyecciones Intraperitoneales , Interleucina-5/biosíntesis , Masculino , Meningitis/inmunología , Meningitis/parasitología , Ratones , Ratones Endogámicos ICR , Infecciones por Strongylida/inmunologíaRESUMEN
Angiostrongylus cantonensis is the major cause of human eosinophilic meningoencephalitis. ICR mice were infected orally with 35 infective larvae and sacrificed at 4-14 days, 25 days or 32 days post infection (dpi) for pathological and immunocytochemical examinations. In the non-treated group, no apoptosis signal was found in the meninges or parenchyma of the brains (4-14 dpi). Only a few apoptotic cells were noticed at 25 dpi (3%) and 32 dpi (10%). In the groups, the animals were given a single dose of mebendazole (20 mg/kg, per os at various times) or injections of interleukin 12 (IL-12) (10 ng/daily, intraperitoneally), all the animals were sacrificed at 14 dpi; the number of apoptotic cells was increased (17-21%). In the group that received a single dose of mebendazole (4 dpi) in combination with IL-12 injections (4-13 dpi), mild meningitis was observed, and most of the infiltrated inflammatory cells were in the apoptotic program (55%). Taken together, apoptosis of the inflammatory cells (most were eosinophils) could be induced when the infected mice were treated with mebendazole or/and IL-12.
Asunto(s)
Angiostrongylus cantonensis/efectos de los fármacos , Antinematodos/farmacología , Encéfalo/patología , Interleucina-12/farmacología , Mebendazol/farmacología , Infecciones por Strongylida/tratamiento farmacológico , Adyuvantes Inmunológicos/farmacología , Adyuvantes Inmunológicos/uso terapéutico , Angiostrongylus cantonensis/fisiología , Animales , Antinematodos/uso terapéutico , Apoptosis/efectos de los fármacos , Biomphalaria , Encéfalo/efectos de los fármacos , Encéfalo/parasitología , Caspasa 3/inmunología , Quimioterapia Combinada , Eosinofilia/tratamiento farmacológico , Eosinofilia/parasitología , Eosinofilia/patología , Inmunohistoquímica , Etiquetado Corte-Fin in Situ , Interleucina-12/uso terapéutico , Masculino , Mebendazol/uso terapéutico , Meningitis/tratamiento farmacológico , Meningitis/parasitología , Meningitis/patología , Meningoencefalitis/tratamiento farmacológico , Meningoencefalitis/parasitología , Meningoencefalitis/patología , Ratones , Ratones Endogámicos ICR , Proteínas Proto-Oncogénicas c-akt/inmunología , Ratas , Ratas Wistar , Infecciones por Strongylida/patologíaRESUMEN
Hepatitis D virus (HDV) encodes two proteins, the 24-kDa small delta antigen (S-HDAg) and 27-kDa large delta antigen (L-HDAg) in its single open reading frame. Both of them had been identified as nuclear phosphoproteins. Moreover, the phosphorylated form of S-HDAg was shown to be important for HDV replication. However, the kinase responsible for S-HDAg phosphorylation remains unknown. Therefore, we employed an in-gel kinase assay to search candidate kinases and indeed identified a kinase with a molecular mass of about 68 kDa. Much evidence demonstrated this kinase to be the double-stranded RNA-activated kinase, PKR. The immunoprecipitated endogenous PKR was sufficient to catalyze S-HDAg phosphorylation, and the kinase activity disappeared in the PKR-depleted cell lysate. The S-HDAg and PKR could be co-immunoprecipitated together, and both of them co-located in the nucleolus. The LC/MS/MS analysis revealed that the serine 177, serine 180, and threonine 182 of S-HDAg were phosphorylated by PKR in vitro. This result was consistent with previous phosphoamino acid analysis indicating that serine and threonine were phosphorylation targets in S-HDAg. Furthermore, serine 177 was also shown to be the predominant phosphorylation site for S-HDAg purified the from cell line. In dominant negative PKR-transfected cells, the level of phosphorylated S-HDAg was suppressed, but replication of HDV was enhanced. Other than human immunodeficiency virus type 1 trans-activating protein (Tat), S-HDAg is another viral protein phosphorylated by PKR that may regulates HDV replication and viral response to interferon therapy.