RESUMEN
BACKGROUND: Acute liver injury is liver cell injury that occurs rapidly in a short period of time. Caffeine has been shown to maintain hepatoprotective effect with an unclear mechanism. Endoplasmic reticulum stress (ERS) has significant effects in acute liver injury. Induction of GRP78 is a hallmark of ERS. Whether or not caffeine's function is related to GRP78 remains to be explored. METHODS: Acute liver injury model was established by LPS-treated L02 cells and in vivo administration of LPS/D-Gal in mice. Caffeine was pre-treated in L02 cells or mice. Gene levels was determined by real-time PCR and western blot. Cell viability was tested by CCK-8 assay and cell apoptosis was tested by flow cytometry. The interaction of GRP78 and NEDD4L was determined by Pull-down and co-immunoprecipitation (Co-IP) assay. The ubiquitination by NEDD4L on GRP78 was validated by in vitro ubiquitination assay. RESULTS: Caffeine protected liver cells against acute injury induced cell apoptosis and ERS both in vitro and in vivo. Suppression of GRP78 could block the LPS-induced cell apoptosis and ERS. NEDD4L was found to interact with GRP78 and ubiquitinate its lysine of 324 site directly. Caffeine treatment induced the expression of NEDD4L, resulting in the ubiquitination and inhibition of GRP78. CONCLUSION: Caffeine mitigated the acute liver injury by stimulating NEDD4L expression, which inhibited GRP78 expression via ubiquitination at its K324 site. Low dose of caffeine could be a promising therapeutic treatment for acute liver injury.
Asunto(s)
Cafeína , Enfermedad Hepática Inducida por Sustancias y Drogas , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Ubiquitina-Proteína Ligasas Nedd4 , Animales , Ratones , Apoptosis , Cafeína/farmacología , Cafeína/uso terapéutico , Chaperón BiP del Retículo Endoplásmico/metabolismo , Lipopolisacáridos/farmacología , Hígado/efectos de los fármacos , Ubiquitinación , Ubiquitina-Proteína Ligasas Nedd4/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológicoRESUMEN
BACKGROUND AND AIM: Various all-oral direct-acting antiviral (DAA) regimens are being widely used in the treatment of human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infected patients; however, the comparative efficacy and safety of different types and combinations of DAAs are not completely clear. There is still a lack of integration of evidence for optimized therapies for HIV/HCV co-infection. METHODS: We conducted a systematic literature search in several databases up to January 1, 2020. All the studies that reported the sustained virologic response (SVR) and adverse events of DAAs in HIV/HCV co-infected patients were included. The Bayesian Markov Chain Monte Carlo method was used for the pooled estimates of network meta-analysis. RESULTS: We identified 33 eligible articles with 7 combinations of all-oral DAAs for the analyses of efficacy and safety. Grazoprevir-elbasvir ± ribavirin (GZR/EBR ± RBV: 95.6%; 95% CrI, 91.7-98.1%), ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin (3D ± RBV: 95.3%; 95% CrI, 93.4-96.9%), sofosbuvir-ledipasvir ± ribavirin (SOF/LDV ± RBV: 95.2%; 95% CrI, 93.7-96.6%), and sofosbuvir-daclatasvir ± ribavirin (SOF/DCV ± RBV: 94.8%; 95% CrI, 92.5-96.6%) were the most effective combinations for HIV/HCV co-infected patients, with SVR rates of approximately 94% and above while severe adverse events were rare. However, the SVR rates of sofosbuvir-ribavirin (SOF/RBV) and sofosbuvir-simeprevir ± ribavirin (SOF/SMV ± RBV) both failed to reach 90%, and the incidences of adverse events were higher than 5%. CONCLUSIONS: Efficacy and safety of all-oral DAAs were in prospect for HIV/HCV co-infection patients. GZR/EBR ± RBV was the optimal combination recommended for HIV/HCV co-infected patients based on the excellent treatment effects and insignificant adverse events.
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Antivirales/administración & dosificación , Benzofuranos/administración & dosificación , Coinfección/tratamiento farmacológico , Infecciones por VIH/diagnóstico por imagen , Hepatitis C Crónica/tratamiento farmacológico , Imidazoles/administración & dosificación , Quinoxalinas/administración & dosificación , Ribavirina/administración & dosificación , Administración Oral , Adulto , Anciano , Amidas , Antivirales/efectos adversos , Benzofuranos/efectos adversos , Carbamatos , Ciclopropanos , Quimioterapia Combinada , Femenino , Infecciones por VIH/virología , Hepatitis C Crónica/virología , Humanos , Imidazoles/efectos adversos , Masculino , Persona de Mediana Edad , Quinoxalinas/efectos adversos , Ribavirina/efectos adversos , Seguridad , Sulfonamidas , Respuesta Virológica Sostenida , Resultado del TratamientoRESUMEN
BACKGROUND: The pattern of changes in the cervical spine and the spinal cord and their dynamic characteristics in patients with cervical spinal cord injury without fracture and dislocation remain unclear. This study aimed to evaluate the dynamic changes in the cervical spine and spinal cord from C2/3 to C7/T1 in different positions by using kinematic magnetic resonance imaging in patients with cervical spinal cord injury without fracture and dislocation. This study was approved by the ethics committee of Yuebei People's Hospital. METHODS: Using median sagittal T2-weighted images for 16 patients with cervical spinal cord injury without fracture and dislocation who underwent cervical kinematic MRI, the anterior space available for the cord, spinal cord diameter, posterior space available for the cord from C2/3 to C7/T1, and Muhle's grade were determined. The spinal canal diameter was calculated by adding the anterior space available for the cord, spinal cord diameter, and posterior space available for the cord. RESULTS: The anterior space available for the cord, posterior space available for the cord, and spinal canal diameters at C2/3 and C7/T1 were significantly higher than those from C3/4 to C6/7. Muhle's grades at C2/3 and C7/T1 were significantly lower than those at the other levels. Spinal canal diameter was lower in extension than in the neutral and flexion positions. In the operated segments, significantly lesser space was available for the cord (anterior space available for the cord + posterior space available for the cord), and the spinal cord diameter/spinal canal diameter ratio was higher than those in the C2/3, C7/T1, and non-operated segments. CONCLUSION: Kinematic MRI demonstrated dynamic pathoanatomical changes, such as canal stenosis in different positions, in patients with cervical spinal cord injury without fracture and dislocation. The injured segment had a small canal diameter, high Muhle's grade, low space available for the cord, and high spinal cord diameter/spinal canal diameter ratio.
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Médula Cervical , Fracturas Óseas , Luxaciones Articulares , Traumatismos de los Tejidos Blandos , Traumatismos de la Médula Espinal , Humanos , Médula Cervical/diagnóstico por imagen , Fenómenos Biomecánicos , Traumatismos de la Médula Espinal/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Vértebras Cervicales/diagnóstico por imagenRESUMEN
Background: Extracellular vesicles (EVs) were reported to participate in various cellular processes based on the biomolecules, particularly microRNAs. Numerous commercial EVs isolation reagents are available. However, whether these reagents are suitable for separating EVs from the culture medium supernatant supernatant of model cell lines, such as HepG2, and whether the isolated products are suitable for High-throughput sequencing remains unclear. Methods: We examined three commonly used EVs isolation kits: the ExoQuick-TC exosome precipitation solution (EQ), Total Exosome Isolation from cell culture medium (EI), and exoEasy Maxi Kit (EM), to isolate EVs from HepG2 cell culture medium supernatants. EVs were identified based on marker proteins, particle size measurements, and electron microscopy analysis. The total amounts of microRNA and microRNA High-throughput sequencing data quality from EVs isolated by each kit were compared. Results: The total amount of EVs' microRNA isolated from the EI and EM groups were higher than that obtained from the EQ group (EQ/EI: p = 0.036, EI/EM: p = 0.024). High-throughput sequencing data quality evaluation showed that the EI group possessed higher quality than those in the EM group. Conclusion: For the cell culture medium from HepG2, EVs' microRNA isolated by EI reagents might be more suitable for High-throughput sequencing applications.
RESUMEN
Approximately 34-86% of neoplasms of the salivary glands are located in the parotid gland and parotidectomy is the first-line treatment for parotid gland tumors. Frey syndrome and cosmetic deformity are common complications experienced by patients following parotidectomy and the sternocleidomastoid muscle flap (SCMF) is used to prevent them. Numerous studies have been performed to examine the effectiveness of the SCMF for the prevention of cosmetic deformity and Frey syndrome, however, they provide contradictory results and possess small sample sizes with consequently low statistical power. In order to evaluate the effectiveness of the SCMF for the prevention of Frey syndrome and cosmetic deformity following parotidectomy, we performed a systematic review and meta-analysis based on published randomized controlled trials (RCTs), which were identified using PubMed and CNKI databases, and references of studies up to August 2012 were included. Using these criteria, we yielded 11 RCTs. Following an independent assessment of the methodological quality of these studies and the extraction of data, a systematic review and meta-analysis was conducted. The results of the meta-analysis demonstrated that there was a significant trend towards a lower risk of objective incidence [67%; risk ratio (RR), 0.33; 95% confidence interval (CI), 0.16-0.67; P<0.01] and subjective incidence (66%; RR, 0.34; 95% CI, 0.16-0.75; P= 0.01) of Frey syndrome in the SCMF group. The sensitivity analysis also indicated that this result was significant. Due to the considerable variation between the included studies, a meta-analysis was not applicable to assess cosmetic deformity. Two RCTs demonstrated that the difference between the SCMF and no SCMF group was not statistically significant, while the other seven RCTs detected a statistically significant difference between the two groups. Publication bias was detected. In conclusion, based on currently available evidence, the use of the SCMF is benefical for the prevention of Frey syndrome, however, whether it is also benefical for cosmetic deformity remains inconclusive.