Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Más filtros











Intervalo de año de publicación
1.
Biol Res ; 57(1): 3, 2024 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-38217055

RESUMEN

BACKGROUND: Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. RESULTS: Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. CONCLUSIONS: In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.


Asunto(s)
Exosomas , Neomicina , Neomicina/toxicidad , Neomicina/metabolismo , Exosomas/metabolismo , Células Ciliadas Auditivas , Autofagia/fisiología
2.
Biol. Res ; 57: 3-3, 2024. ilus, graf, tab
Artículo en Inglés | LILACS | ID: biblio-1550058

RESUMEN

BACKGROUND: Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. RESULTS: Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. CONCLUSIONS: In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.


Asunto(s)
Neomicina/metabolismo , Neomicina/toxicidad , Exosomas/metabolismo , Autofagia/fisiología , Células Ciliadas Auditivas
3.
Braz. j. infect. dis ; Braz. j. infect. dis;20(1): 1-7, Jan.-Feb. 2016. tab, graf
Artículo en Inglés | LILACS | ID: lil-776471

RESUMEN

Abstract Background The mechanism underlying the coexistence of hepatitis B surface antigen and antibodies to HBsAg in chronic hepatitis B patients remains unknown. Aims This research aimed to determine the clinical and virological features of the rare pattern. Methods A total of 32 chronic hepatitis B patients infected by HBV genotype C were included: 15 carrying both HBsAg and anti-HBs (group I) and 17 solely positive for HBsAg (group II). S gene and reverse transcriptase region sequences were amplified, sequenced and compared with the reference sequences. Results The amino acid variability within major hydrophilic region, especially the “a” determinant region, and within reverse transcriptase for regions overlapping the major hydrophilic region in group I is significantly higher than those in group II. Mutation sI126S/T within the “a” determinant was the most frequent change, and only patients from group I had the sQ129R, sG130N, sF134I, sG145R amino acid changes, which are known to alter immunogenicity. Conclusions In chronic patients, the concurrent HBsAg/anti-HBs serological profile is associated with an increased aa variability in several key areas of HBV genome. Additional research on these genetic mutants are needed to clarify their biological significance for viral persistence.


Asunto(s)
Adulto , Femenino , Humanos , Masculino , Adulto Joven , Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B Crónica/genética , Hepatitis B Crónica/inmunología , ADN Polimerasa Dirigida por ARN/genética , Proteínas del Envoltorio Viral/genética , China , ADN Viral , Genotipo , Virus de la Hepatitis B/inmunología , Mutación , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN
4.
Braz J Infect Dis ; 20(1): 1-7, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26613893

RESUMEN

BACKGROUND: The mechanism underlying the coexistence of hepatitis B surface antigen and antibodies to HBsAg in chronic hepatitis B patients remains unknown. AIMS: This research aimed to determine the clinical and virological features of the rare pattern. METHODS: A total of 32 chronic hepatitis B patients infected by HBV genotype C were included: 15 carrying both HBsAg and anti-HBs (group I) and 17 solely positive for HBsAg (group II). S gene and reverse transcriptase region sequences were amplified, sequenced and compared with the reference sequences. RESULTS: The amino acid variability within major hydrophilic region, especially the "a" determinant region, and within reverse transcriptase for regions overlapping the major hydrophilic region in group I is significantly higher than those in group II. Mutation sI126S/T within the "a" determinant was the most frequent change, and only patients from group I had the sQ129R, sG130N, sF134I, sG145R amino acid changes, which are known to alter immunogenicity. CONCLUSIONS: In chronic patients, the concurrent HBsAg/anti-HBs serological profile is associated with an increased aa variability in several key areas of HBV genome. Additional research on these genetic mutants are needed to clarify their biological significance for viral persistence.


Asunto(s)
Anticuerpos contra la Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/genética , Hepatitis B Crónica/genética , Hepatitis B Crónica/inmunología , ADN Polimerasa Dirigida por ARN/genética , Proteínas del Envoltorio Viral/genética , Adulto , China , ADN Viral , Femenino , Genotipo , Virus de la Hepatitis B/inmunología , Humanos , Masculino , Mutación , Reacción en Cadena de la Polimerasa , Análisis de Secuencia de ADN , Adulto Joven
5.
Ann Hepatol ; 14(2): 175-80, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25671826

RESUMEN

INTRODUCTION: Among the available nucleos(t)ide analogues adefovir dipivoxil (ADV) is relatively cheap and widely used in rural area in China. However, there are insufficient data on recommendation for patients with suboptimal response to ADV after 48 weeks of treatment in order to reduce the resistance rate in the long term. The aim of this study was to compare the efficacy and safety of LAM add-on combination therapy versus ETV monotherapy for patients with suboptimal response to ADV. MATERIAL AND METHODS: 136 patients with suboptimal response to ADV were randomly assigned to the add-on LAM with ADV combination therapy (68 patients) group and the ETV monotherapy (68 patients) group. Patients in the add-on group were prescribed 100 mg LAM and 10 mg ADV per day, while the monotherapy group received 0.5 mg ETV per day for 48 weeks. Tests for liver and kidney function, HBV serum markers, HBV DNA load, were performed every 3 months. RESULTS: The mean patient age in LAM add-on group and ETV monotherapy was 38.59 ± 7.65 and 37.56 ± 8.67 years respectively. The HBV DNA undetectable rate in the LAM add-on group and the ETV group were not significant difference at week 4, 12 and 24 (P > 0.05). However, the HBV undetectable rate in the ETV group was higher than that in the LAM add-on group at week 36 and 48 (P = 0.043 for week 36 and P = 0.038 for week 48). There was no significant difference both for HBeAg loss and HBeAg seroconversion between two groups (P > 0.05) at 48 weeks. Meanwhile, our study also demonstrated that the mean eGFR levels in LAM add-on group was decreased from 99.6 ± 8.71 at baseline to 86.4 ± 9.83 at the end of 48 weeks, which was significantly higher than that in the ETV monotherapy group (P < 0.05). 8.8% of patients in LAM add-on group experienced eGFR reduction by 20-30% from baseline at 48 weeks. No patients developed hyposphosphatemia in our study. CONCLUSION: Our study clearly showed that switch to ETV monotherapy was the more effective and more safe than that of LAM add-on combination therapy for patients with suboptimal response to ADV.


Asunto(s)
Adenina/análogos & derivados , Antivirales/uso terapéutico , Sustitución de Medicamentos , Guanina/análogos & derivados , Hepatitis B Crónica/tratamiento farmacológico , Lamivudine/uso terapéutico , Organofosfonatos/uso terapéutico , Adenina/efectos adversos , Adenina/uso terapéutico , Adulto , Antivirales/efectos adversos , Biomarcadores/sangre , China , Quimioterapia Combinada , Femenino , Guanina/efectos adversos , Guanina/uso terapéutico , Hepatitis B Crónica/sangre , Hepatitis B Crónica/diagnóstico , Humanos , Lamivudine/efectos adversos , Masculino , Persona de Mediana Edad , Organofosfonatos/efectos adversos , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento , Carga Viral
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA