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1.
World J Gastroenterol ; 27(40): 6927-6938, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34790015

RESUMO

BACKGROUND: Quantitative hepatitis B core-related antigen (qHBcrAg) has a better correlation with intrahepatic hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) than HBV DNA or hepatitis B e antigen (HBeAg), but data are still lacking for its clinical application. AIM: The aim was to investigate serum qHBcrAg levels in patients with chronic hepatitis B and assess the correlation of serum qHBcrAg with pregenomic RNA (pgRNA), cccDNA, and HBeAg seroconversion. METHODS: This study was a secondary analysis of patients who underwent percutaneous liver biopsy between July 2014 and June 2019 in two multicenter randomized controlled clinical trials of peginterferon vs nucleos(t)ide analog (NUC)-based therapy (NCT03509688 and NCT03546530). Serum qHBcrAg, pgRNA, HBV DNA, hepatitis B core antigen, HBeAg, liver cccDNA, and HBV DNA were measured. The correlations of serum qHBcrAg with other biomarkers were analyzed. RESULTS: A total of 139 patients were included. The mean qHBcrAg levels were 5.32 ± 1.18 log10 U/mL at baseline and decreased during treatment (all P < 0.0001). Serum qHBcrAg levels were positively correlated with pgRNA (r = 0.597, P < 0.0001) and cccDNA (r = 0.527, P < 0.0001) levels. The correlation of serum qHBcrAg level and intrahepatic HBV DNA levels at baseline was weak but significant (r = 0.399, P < 0.0001). HBcrAg predicted HBeAg seroconversion, with areas under the receiver operating characteristics curve of 0.788 at 24 wk and 0.825 at 48 wk. Log HBcrAg at wk 24 and 48 was independently associated with HBeAg seroconversion [odds ratio (OR) = 2.402, 95% confidence interval (CI): 1.314-4.391, P = 0.004; OR = 3.587, 95%CI: 1.315-9.784, P = 0.013]. CONCLUSION: Serum HBcrAg levels were correlated with HBV virological markers and could be used to predict HBeAg seroconversion.


Assuntos
Antígenos E da Hepatite B , Hepatite B Crônica , Antivirais/uso terapêutico , Biomarcadores , DNA Viral/uso terapêutico , Antígenos do Núcleo do Vírus da Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/tratamento farmacológico , Humanos , Soroconversão
2.
Oncol Lett ; 18(6): 6385-6396, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31807162

RESUMO

The poor prognosis of patients with osteosarcoma remains a persistent problem, in particular for patients with unresectable tumors or metastasis. Therefore, combination of radiotherapy and chemotherapy has been considered for patients with metastasis or recurrence, patients unsuitable for surgery and patients refusing surgery. The present study aimed to investigate the effect of the combined treatment with cisplatin and radiation therapy on the biological characteristics of the osteosarcoma cell line MG-63 and the breast cancer 1 (BRCA1)-associated signaling pathways. Cell proliferation was determined using Cell Counting kit-8 assay, and cell apoptosis and cell cycle were assessed by flow cytometry. Cell migration was examined by Transwell assay. The mRNA and protein expression levels of candidate genes, including BRCA1 and p53, were determined by reverse transcription-quantitative PCR and western blotting, respectively. The results demonstrated that combined treatment with radiation and cisplatin significantly inhibited MG-63 cell proliferation compared with radiation or cisplatin treatment alone. Furthermore, radiation, cisplatin or the combined treatment with radiation and cisplatin increased the apoptosis rate of MG-63 cells, which resulted in G2 phase arrest, and significantly decreased the migratory capacity of MG-63 cells. In addition, the apoptosis rate of MG-63 cells following combined radiation and cisplatin treatment was higher compared with the cisplatin group, but lower compared with the radiation group. Furthermore, combined treatment with radiation and cisplatin decreased the mRNA and protein expression levels of BRCA1 and p53. Additionally, combined treatment with radiation and cisplatin had a more potent inhibitory effect on p53 expression than on BRCA1 expression. In addition, combination of radiation and cisplatin had a higher inhibitory effect on Bax protein level and a higher inductive effect on Bcl-2 protein level compared with treatments with radiation and cisplatin alone. The results demonstrated that combined treatment of radiation and cisplatin exhibited superior therapeutic effects on osteosarcoma MG-63 cells compared with radiation or cisplatin treatment alone, which may be mediated by the BRCA1-p53 signaling pathway.

3.
Food Sci Nutr ; 6(6): 1387-1393, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30258580

RESUMO

Response surface methodology based on Box-Behnken was used to assess the effects of three kinds of texture-improving ingredients, namely, mixed starch (MS) (6%-8%) of sweet potato starch and glutinous rice flour, k-carrageenan (CG) (0.4%-0.6%), and konjac flour (KF) (0.8%-1.2%), on the firmness, elasticity, and water holding capacity (WHC) of emulsified sausage (ES) made from pork and salted egg white (SEW). The three kinds of texture-improving ingredients individually presented different effects on firmness, elasticity, and WHC. Their synergistic effects were significant. The three response models obtained by ANOVA were suitable to predict firmness, elasticity, and WHC. These models can also be used to design formulations for different types of sausage with different firmness and elasticity. The combination of MS (7.36%), CG (0.60%), and KF (1.20%) can produce SEW-containing ES with remarkable firmness (224.04 g), elasticity (8.62), and WHC (8.41).

4.
Int J Oncol ; 53(5): 2269-2277, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30226600

RESUMO

Although radiation therapy is a powerful anticancer modality, radiation- induced stress response and gene expression with adaptive resistance may severely compromise the effectiveness of radiation. The function of rotundic acid (RA) on inducing apoptosis in the human breast cancer cell line MCF-7 has been investigated in a previous study. In the present study, the combined effect of chemotherapy and radiotherapy on reducing side effects was examined. The results of an MTT assay revealed that radiation (0.5, 2 and 10 Gy) effectively inhibit MCF-7 cell viability in a dose-dependent manner, consistent with the effects of RA (2, 5 and 12.5 µM). Interestingly, a lower dose of radiation (1 Gy) combined with RA (5 µM) exhibited a greater inhibition efficiency compared with a high dose of radiation alone. Flow cytometry revealed that radiation combined with RA induced the apoptosis of MCF-7 cells. Using western blotting, it was demonstrated that radiation induced the expression of ataxia-telangiectasia mutated (ATM) and p53 protein, and that RA enhanced this effect. On examining the potential underlying mechanism, it was revealed that radiation and RA combined induce Bcl-2-associated X protein expression and cell apoptosis in MCF-7 cells. An ATM inhibitor was able to restore the effect of radiation and RA on inducing MCF-7 cell apoptosis. These results suggest that the ATM/p53 pathway directly participates in radiation and RA-induced apoptosis in MCF-7 cells. RA has the potential for development as a novel drug for the treatment of human breast cancer combined with radiation therapy, given that the combined side effects are reduced.


Assuntos
Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Neoplasias da Mama/terapia , Tolerância a Radiação/efeitos dos fármacos , Triterpenos/farmacologia , Proteína Supressora de Tumor p53/metabolismo , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Neoplasias da Mama/patologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Relação Dose-Resposta à Radiação , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Humanos , Células MCF-7 , Medicina Tradicional Chinesa/métodos , Doses de Radiação , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/efeitos da radiação , Resultado do Tratamento , Triterpenos/uso terapêutico , Proteína X Associada a bcl-2/metabolismo
5.
Mol Med Rep ; 18(3): 3211-3218, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30085342

RESUMO

Chitosan is a linear polysaccharide that is made by treating the chitin shells of shrimp and crustaceans with an alkaline substance, for example sodium hydroxide. Due to its unique physical and chemical properties, chitosan has a wide range of applications in the medical field. Currently, there are no effective treatments for liver fibrosis; therefore, the aim of the present study was to investigate the therapeutic effect of chitosan in a CCl4­induced hepatic fibrosis (HF) rat model. The serum levels of aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) were measured by ELISA. Collagen (COL) 3 and α­smooth muscle actin (SMA) expression levels in the rat liver were detected by reverse transcription­semiquantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that treatment with chitosan significantly improved HF, by decreasing the serum levels of AST, ALT, and ALP; improving liver histology; and decreasing the expression levels of COL3 and α­SMA. Chitosan may offer an alternative approach for the clinical treatment of HF.


Assuntos
Antioxidantes/uso terapêutico , Quitosana/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Actinas/genética , Actinas/metabolismo , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Antioxidantes/química , Aspartato Aminotransferases/sangue , Tetracloreto de Carbono , Quitosana/química , Colágeno Tipo III/genética , Colágeno Tipo III/metabolismo , Expressão Gênica/efeitos dos fármacos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , Masculino , Ratos , Ratos Sprague-Dawley
6.
Sheng Li Xue Bao ; 69(5): 685-692, 2017 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-29063116

RESUMO

Endocannabinoid receptor system is extensively expressed in the vertebrate retina. There are two types of cannabinoid receptors, CB1 and CB2. Activation of these two receptors by endocannabinoids N-arachidonoylethanolamide (anandamine, AEA) and 2-arachidonyl glycerol (2-AG) regulates multiple neuronal and glial ion channels, thus getting involved in retinal visual information processing. In this review, incorporating our results, we discuss the modulation of cannabinoid CB1 and CB2 receptors on retinal neuronal and glial ion channels and retinal synaptic transmission.


Assuntos
Canais Iônicos/fisiologia , Receptores de Canabinoides/fisiologia , Retina/fisiologia , Transmissão Sináptica/fisiologia , Animais , Ácidos Araquidônicos/farmacologia , Endocanabinoides/farmacologia , Glicerídeos/farmacologia , Humanos , Alcamidas Poli-Insaturadas/farmacologia
7.
Exp Ther Med ; 13(6): 2812-2818, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28588665

RESUMO

The fifth most common cancer worldwide is hepatocellular carcinoma (HCC), which has an annual mortality rate of ~800,000. Although surgical procedures for HCC, such as hepatic resection and liver transplantation, have progressed and the outcomes of patients have improved, HCC is still characterized by frequent recurrence, even after liver transplantation. In the present study the expression of the protein coding gene, S100 calcium binding protein A3 (S100A3), was observed in 62 HCC tissues and tumor-surrounding tissues. The present study indicated that S100A3 activation was involved in tumorigenesis and tumor aggressiveness. The protein and mRNA expression levels of S100A3 in the human HCC cell line (HepG2) were investigated using western blotting and reverse transcription-quantitative polymerase chain reaction analysis, respectively. The function of sodium cantharidinate in inducing HCC cell apoptosis was also investigated. Sodium cantharidinate inhibited the protein and gene expression of S100A3 in HepG2 cells in vitro. These data suggested that S100A3 has an important role in human HCC. The present study indicates that the functional properties of sodium cantharidinate are promising for the development of a novel drug that may control the expression of S100A3 and improve the treatment of human HCC in the near future.

8.
Oncotarget ; 8(26): 42030-42042, 2017 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-28159932

RESUMO

Spinal muscular atrophy (SMA) is a devastating motor neuron disease caused by mutations of the survival motor neuron 1 (SMN1) gene. SMN2, a paralogous gene to SMN1, can partially compensate for the loss of SMN1. On the basis of age at onset, highest motor function and SMN2 copy numbers, childhood-onset SMA can be divided into three types (SMA I-III). An inverse correlation was observed between SMN2 copies and the differential phenotypes of SMA. Interestingly, this correlation is not always absolute. Using SMA induced pluripotent stem cells (iPSCs), we found that the SMN was significantly decreased in both SMA III and SMA I iPSCs derived postmitotic motor neurons (pMNs) and γ-aminobutyric acid (GABA) neurons. Moreover, the significant differences of SMN expression level between SMA III (3 copies of SMN2) and SMA I (2 copies of SMN2) were observed only in pMNs culture, but not in GABA neurons or iPSCs. From these findings, we further discovered that the neurite outgrowth was suppressed in both SMA III and SMA I derived MNs. Meanwhile, the significant difference of neurite outgrowth between SMA III and SMA I group was also found in long-term cultures. However, significant hyperexcitability was showed only in SMA I derived mature MNs, but not in SMA III group. Above all, we propose that SMN protein is a major factor of phenotypic modifier. Our data may provide a new insight into recognition for differential phenotypes of SMA disease.


Assuntos
Células-Tronco Pluripotentes Induzidas/citologia , Neurônios Motores/citologia , Neurônios Motores/metabolismo , Atrofia Muscular Espinal/metabolismo , Atrofia Muscular Espinal/patologia , Fenótipo , Biomarcadores , Diferenciação Celular , Reprogramação Celular , Fenômenos Eletrofisiológicos , Feminino , Neurônios GABAérgicos/metabolismo , Humanos , Immunoblotting , Imuno-Histoquímica , Masculino , Atrofia Muscular Espinal/genética , Mutação , Neuritos/metabolismo , Linhagem , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Proteína 1 de Sobrevivência do Neurônio Motor/metabolismo
9.
Nutr Neurosci ; 20(3): 172-179, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26796989

RESUMO

OBJECTIVE: Pathophysiology of spinal cord injury (SCI) causes primary and secondary effects leading to loss of neuronal function. The aim of the present study was to investigate the role of rosmarinic acid (RA) in protection against SCI. METHODS: The experimental study was carried out in male wistar rats categorized into three groups. Group I - sham operated rats; Group II - SCI; Group III - SCI followed by RA treatment (10 mg/kg). The spinal tissues after treatment schedule were analyzed for oxidative stress status through determination of reactive oxygen species (ROS), lipid peroxidation, protein damage (carbonyl and sulfhydryl contents), and antioxidant enzyme activities. The expression of oxidative stress factors NF-κB and Nrf-2 was determined by Western blot analysis. Further pro-inflammatory cytokines (TNF-α, IL-6, MCP-1, and IL-1ß) were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The results show that treatment with RA significantly enhances the antioxidant status and decrease the oxidative stress in wistar rats post-SCI. RA effectively ameliorated inflammatory mechanisms by downregulation of NF-κB and pro-inflammatory cytokines post-SCI. CONCLUSION: The study demonstrates for the first time on the role of RA in protecting the spinal cord from injury and demonstrates its neuroprotection in wistar rats.


Assuntos
Cinamatos/uso terapêutico , Depsídeos/uso terapêutico , Modelos Animais de Doenças , Neurônios Motores/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Medula Espinal/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Biomarcadores/metabolismo , Cinamatos/administração & dosagem , Depsídeos/administração & dosagem , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Injeções Intraperitoneais , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Neurônios Motores/imunologia , Neurônios Motores/metabolismo , Neurônios Motores/patologia , NF-kappa B/metabolismo , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Carbonilação Proteica/efeitos dos fármacos , Ratos Wistar , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Medula Espinal/imunologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Traumatismos da Medula Espinal/imunologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia
10.
Sheng Li Xue Bao ; 68(4): 483-91, 2016 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-27546508

RESUMO

Glaucoma, the second leading cause of blindness, is a neurodegenerative disease characterized by optic nerve degeneration related to apoptotic death of retinal ganglion cells (RGCs). In the pathogenesis of RGC death following the onset of glaucoma, functional changes of glutamate receptors are commonly regarded as important risk factors. During the past several years, we have explored the mechanisms underlying RGC apoptosis and retinal Müller cell reactivation (gliosis) in a rat chronic ocular hypertension (COH) model. We demonstrated that elevated intraocular pressure in COH rats may induce changes of various signaling pathways, which are involved in RGC apoptosis by modulating glutamate NMDA and AMPA receptors. Moreover, we also demonstrated that over-activation of group I metabotropic glutamate receptors (mGluR I) by excessive extracellular glutamate in COH rats could contribute to Müller cell gliosis by suppressing Kir4.1 channels. In this review, incorporating our results, we discuss glutamate receptor- mediated RGC apoptosis and Müller cell gliosis in experimental glaucoma.


Assuntos
Glaucoma , Retina , Animais , Modelos Animais de Doenças , Hipertensão Ocular , Receptores de Glutamato , Células Ganglionares da Retina
11.
Stem Cells Int ; 2016: 2452985, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26770203

RESUMO

Somatic cells can be directly converted into functional neurons by ectopic expression of defined factors and/or microRNAs. Since the first report of conversion mouse embryonic fibroblasts into functional neurons, the postnatal mouse, and human fibroblasts, astroglia, hepatocytes, and pericyte-derived cells have been converted into functional dopaminergic and motor neurons both in vitro and in vivo. However, it is invasive to get all these materials. In the current study, we provide a noninvasive approach to obtain directly reprogrammed functional neurons by overexpression of the transcription factors Ascl1, Brn2, NeuroD, c-Myc, and Myt1l in human urine cells. These induced neuronal (iN) cells could express multiple neuron-specific proteins and generate action potentials. Moreover, urine cells from Wilson's disease (WD) patient could also be directly converted into neurons. In conclusion, generation of iN cells from nonneural lineages is a feasible and befitting approach for neurological disease modeling.

12.
Zhongguo Gu Shang ; 29(11): 1049-1052, 2016 Nov 25.
Artigo em Chinês | MEDLINE | ID: mdl-29292644

RESUMO

OBJECTIVE: To explore the clinical therapeutic effect and safety of application of Ilizarov technique combined with flap instant expansion technique in correcting tibia angular deformity combined with skin contracture by one stage. METHODS: From January 2010 to January 2013, 30 cases of tibial deformity with skin contracture were corrected by Ilizarov technique combined with flap instant expansion technique at one stage, including 21 males and 9 females with an average age of(40.2±5.5) years ranging from 25 to 60 years. All patients underwent regular reexamination of X-ray. After removal of the Ilizarov external fixation, knee joint function were assessed by American Hospital for Special Surgery (HSS) scoring criteria, and the pain was evaluated by visual simulation score(VAS). RESULTS: All patients were followed up for 6 to 35 months with an average of 22 months. Among them, the incision of 29 patients were primary healing, 1 patient had wound infection complicated by osteomyelitis, 2 patients complicated with fixed screw loosening, there were no expanded skin flap necrosis and neurovascular injury symptoms. The external fixators were removed at 4 to 7 months after operation with an average of(5.2±1.1) months. Correction angle was 10° to 35° degrees with an average of (25.5±3.5)°. HSS total score was 92.5±6.6 and the result was excellent in 25 cases, good in 4 cases, fair in 1 case; the VAS score was 1.2±1.5. CONCLUSIONS: The application of Ilizarov technique combined with flap instant expansion technique is a good method for correction of tibial angular deformity with skin contracture by one stage, with a shorter time of external fixation frame, without skin necrosis and neurological symptoms, early load exercise and improve the limb function.


Assuntos
Amputação Traumática/cirurgia , Fixadores Externos , Traumatismos dos Dedos/cirurgia , Técnica de Ilizarov , Reimplante/métodos , Retalhos Cirúrgicos , Adulto , Contratura/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
13.
Int J Ophthalmol ; 8(6): 1101-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26682155

RESUMO

AIM: To investigate the effect of DSX, an active component extracted from Erigeron breviscapus, on the voltage-gated outward K(+) channel currents in rat retinal ganglion cells (RGCs) by using electrophysiological method, and to explore the possible mechanisms of DSX on optic nerve protection. METHODS: Outward K(+) currents were recorded by using whole-cell patch-clamp techniques on acutely isolated rat RGCs. Outward K(+) currents were induced by a series of depolarizing voltage pulses from a holding potential of -70 mV to +20 mV in an increment of 10 mV. RESULTS: Extracellular application of DSX voltage-dependently suppressed both the steady-state and peak current amplitudes of outward K(+) currents in rat RGCs. Furthermore, DSX reversibly and dose-dependently inhibited the amplitudes of outward K(+) currents of the cells. At +20 mV membrane potential DSX at the concentrations of 0.02 g/L and 0.05 g/L showed no significant effects on the currents. In contrast, DSX at higher concentrations (0.1 g/L, 0.2 g/L and 0.5 g/L) significantly suppressed the current amplitudes. CONCLUSION: These results suggest that DSX reversibly and dose-dependently suppress outward K(+) channel currents in rat RGCs, which may be one of the possible mechanisms underlying Erigeron breviscapus prevents vision loss and RGC damage caused by glaucoma.

14.
Biol Open ; 4(12): 1744-52, 2015 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-26621826

RESUMO

Paroxysmal kinesigenic dyskinesia (PKD) is a monogenic movement disorder with autosomal dominant inheritance. We previously identified the proline-rich transmembrane protein 2 (PRRT2) as a causative gene of PKD. However, the pathogenesis of PKD remains largely unknown so far. In addition, applicable modeling tools to investigate the underlying mechanisms of PKD are still lacking. The combination of disease-specific human induced pluripotent stem cells (iPSCs) and directed cell differentiation offers an ideal platform for disease modeling. In this study, we generated two iPSC lines from the renal epithelial cells of one PKD patient with the hotspot c.649dupC mutation (PKD-iPSCs). These cell lines were positive for alkaline phosphatase Nanog, Tra-1-80, Tra-1-60, SSEA-3 and SSEA-4. Teratomas with three blastoderms including ectoderm, mesoderm, and endoderm were obtained two months after injection of PKD-iPSCs into NOD/SCID mice. The expression of PRRT2 mRNA was decreased in PKD-iPSCs compared with that of the control iPSCs. Furthermore, PKD-iPSCs possessed the differentiation potential of functional glutamatergic, dopaminergic and motor neurons in vitro. Electrophysiological examinations revealed that the current densities of fast activated and deactivated sodium channels as well as voltage gated potassium channels were not different between the neurons from PKD-iPSCs and control iPSCs. Thus, PKD-iPSCs are a feasible modeling tool to investigate the pathogenic mechanisms of PKD.

15.
Antioxid Redox Signal ; 23(2): 129-47, 2015 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-25756524

RESUMO

AIMS: The mechanisms underlying numerous biological roles of hydrogen sulfide (H2S) remain largely unknown. We have previously reported an inhibitory role of H2S in the L-type calcium channels in cardiomyocytes. This prompts us to examine the mechanisms underlying the potential regulation of H2S on the ion channels. RESULTS: H2S showed a novel inhibitory effect on Ito potassium channels, and this effect was blocked by mutation at the Cys320 and/or Cys529 residues of the Kv4.2 subunit. H2S broke the disulfide bridge between a pair of oxidized cysteine residues; however, it did not modify single cysteine residues. H2S extended action potential duration in epicardial myocytes and regularized fatal arrhythmia in a rat model of myocardial infarction. H2S treatment significantly increased survival by ∼1.4-fold in the critical 2-h time window after myocardial infarction with a protection against ventricular premature beats and fatal arrhythmia. However, H2S did not change the function of other ion channels, including IK1 and INa. INNOVATION AND CONCLUSION: H2S targets the Cys320/Cys529 motif in Kv4.2 to regulate the Ito potassium channels. H2S also shows a potent regularizing effect against fatal arrhythmia in a rat model of myocardial infarction. The study provides the first piece of evidence for the role of H2S in regulating Ito potassium channels and also the specific motif in an ion channel labile for H2S regulation.


Assuntos
Motivos de Aminoácidos/efeitos dos fármacos , Arritmias Cardíacas/metabolismo , Cisteína/metabolismo , Sulfeto de Hidrogênio/farmacologia , Infarto do Miocárdio/metabolismo , Canais de Potássio Shal/metabolismo , Animais , Arritmias Cardíacas/tratamento farmacológico , Dissulfetos/metabolismo , Células HEK293 , Humanos , Sulfeto de Hidrogênio/uso terapêutico , Masculino , Mutação , Infarto do Miocárdio/tratamento farmacológico , Miócitos Cardíacos/metabolismo , Ratos , Canais de Potássio Shal/antagonistas & inibidores , Canais de Potássio Shal/genética
16.
Sheng Li Xue Bao ; 66(5): 511-8, 2014 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-25331996

RESUMO

The knowledge about electrophysiological properties of retinal ganglion cells (RGCs), as well as modulation of these properties, is important not only for understanding the unique physiological functions of RGCs under normal conditions, but also for exploring the cellular mechanisms of retinal neurodegeneration diseases, such as glaucoma. In this paper, we reviewed the progress in electrophysiological studies of RGCs by using patch-clamp techniques, concerning the voltage-gated ion channels, the ligand-gated ion channels and the effects of neuromodulators on these channels.


Assuntos
Fenômenos Eletrofisiológicos , Células Ganglionares da Retina/fisiologia , Animais , Humanos , Canais Iônicos/fisiologia , Técnicas de Patch-Clamp
17.
J Med Virol ; 86(8): 1296-306, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24760738

RESUMO

Human beta2-glycoprotein I (beta2-GPI) binds to recombinant hepatitis B surface antigen (rHBsAg) and can bind specifically to annexin II, which is located on the cell membrane of human hepatoma SMMC-7721 cells. Viral envelope proteins are essential for mediating cellular entry. The aim of this study was to investigate the role of beta2-GPI in the early stages of hepatitis B virus (HBV) infection. Western blot and qRT-PCR analyses revealed that beta2-GPI expression was upregulated in HepG2.2.15 cells at both the mRNA and protein level and was almost non-existent in 293T and CHO cells. Furthermore, annexin II was expressed at lower levels in HepG2.2.15 cells compared to L02, HepG2, and SMMC-7721 cells. Additionally, ELISA analyses demonstrated that beta2-GPI enhanced the ability of HBsAg to bind to cell surfaces, and there was differential adhesion to L02, HepG2, HepG2.2.15, and 293T cells. Western blot and ELISA were then performed to assess the effects of HBV and the HBsAg domain on beta2-GPI expression in co-transfected 293T cells. This study revealed that HBV and the large HBV envelope protein increased beta2-GPI expression. Further investigation indicated that beta2-GPI colocalized with HBsAg in the cytosol of HepG2.2.15 cells, with sodium taurocholate co-transporting polypeptide (NTCP) on the cell membrane in NTCP-complemented HepG2 cells, and with annexin II in the cytosol of HepG2 and HepG2.2.15 cells. These data suggest that high expression of beta2-GPI enhances HBsAg binding to cell surfaces, thus contributing to virus particle transfer to the NTCP receptor and interaction with annexin II for viral membrane fusion.


Assuntos
Vírus da Hepatite B/fisiologia , Hepatócitos/fisiologia , Hepatócitos/virologia , Interações Hospedeiro-Patógeno , Ligação Viral , beta 2-Glicoproteína I/biossíntese , Western Blotting , Linhagem Celular , Ensaio de Imunoadsorção Enzimática , Humanos , Reação em Cadeia da Polimerase em Tempo Real
18.
Sheng Li Xue Bao ; 65(6): 654-63, 2013 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-24343724

RESUMO

In the vertebrate retina, Müller cells are principal glial cells which stretch across the whole thickness of the retina and contact with the somata and processes of all retinal neurons, thus forming an anatomical and functional link between glial cells and retinal neurons. Numerous studies have shown that Müller cells express various neurotransmitter receptors, transporters, ion channels and enzymes that are relative to cellular activities. In addition, the cells also release factors, such as D-serine and glutamate etc., to regulate the neuron excitability. Therefore, retinal Müller cells may play more curious roles in addition to supporting the retinal neurons. The information exchange and interaction between Müller cells and neurons may regulate and maintain retinal neuronal functions. In the glaucomatous retina, Müller cells are reactivated (gliosis). Reactivated Müller cells undergo a variety of changes in cellular physiology, biochemistry and morphological features. Meanwhile, the reactivated Müller cells may produce and release cytotoxic factors, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), reactive oxygen species (ROS) and prostaglandin E2 (PGE2), thus involving in the induction of retinal ganglion cell apoptosis and death. Here, we reviewed the physiological properties of retinal Müller cells, and the functional changes of Müller cells in the glaucomatous retina.


Assuntos
Células Ependimogliais/patologia , Células Ependimogliais/fisiologia , Glaucoma/fisiopatologia , Humanos , Neurônios/fisiologia , Retina/citologia
19.
Sheng Li Xue Bao ; 65(4): 355-62, 2013 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-23963066

RESUMO

Activation of cannabinoid CB1 receptors (CB1Rs) regulates a variety of physiological functions in the vertebrate retina through modulating various types of ion channels. The aim of the present study was to investigate the effects of this receptor on cell excitability of rat retinal ganglion cells (RGCs) in retinal slices using whole-cell patch-clamp techniques. The results showed that under current-clamped condition perfusing WIN55212-2 (WIN, 5 µmol/L), a CB1R agonist, did not significantly change the spontaneous firing frequency and resting membrane potential of RGCs. In the presence of cocktail synaptic blockers, including excitatory postsynaptic receptor blockers CNQX and D-APV, and inhibitory receptor blockers bicuculline and strychnine, perfusion of WIN (5 µmol/L) hardly changed the frequencies of evoked action potentials by a series of positive current injection (from +10 to +100 pA). Phase-plane plot analysis showed that both average threshold voltage for triggering action potential and delay time to reach threshold voltage were not affected by WIN. However, WIN significantly decreased +dV/dtmax and -dV/dtmax of action potentials, suggestive of reduced rising and descending velocities of action potentials. The effects of WIN were reversed by co-application of SR141716, a CB1R selective antagonist. Moreover, WIN did not influence resting membrane potential of RGCs with synaptic inputs being blocked. These results suggest that activation of CB1Rs may regulate intrinsic excitability of rat RGCs through modulating evoked action potentials.


Assuntos
Potenciais de Ação , Receptor CB1 de Canabinoide/fisiologia , Células Ganglionares da Retina/fisiologia , Animais , Benzoxazinas/farmacologia , Potenciais Evocados , Técnicas In Vitro , Potenciais da Membrana , Morfolinas/farmacologia , Naftalenos/farmacologia , Técnicas de Patch-Clamp , Piperidinas/farmacologia , Pirazóis/farmacologia , Ratos , Rimonabanto
20.
Brain Res ; 1391: 102-13, 2011 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-21420392

RESUMO

An animal model for clip spinal cord injury (SCI) was used to determine whether Neurotrophin-3 (NT-3) genetically modified human umbilical mesenchymal stem cells (NT-3-HUMSCs) could promote the morphologic and functional recovery of injured spinal cords. Using the Basso, Beattie, and Bresnahan scores and a grid test, the rats in the HUMSC-treated and NT-3-HUMSCs groups had significantly improved locomotor functional recovery more than the control group. In comparison, the NT-3-HUMSCs group achieved better functional recovery than the HUMSCs group at the end of 12 weeks after SCI. The functional recovery was accompanied by increased intensity of 5-HT fibers, increased volume of spared myelination, and decreased area of the cystic cavity in the NT-3-HUMSCs group compared with the HUMSCs group. Moreover, transplanted NT-3-HUMSCs survived and produced larger amounts of NT-3 than the HUMSCs in the host spinal cord. These results show that NT-3 enhanced the therapeutic effects of HUMSCs after clip injury of the spinal cord.


Assuntos
Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Neurotrofina 3/metabolismo , Traumatismos da Medula Espinal/cirurgia , Cordão Umbilical/citologia , Análise de Variância , Animais , Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Sobrevivência Celular/fisiologia , Células Cultivadas , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática/métodos , Citometria de Fluxo/métodos , Humanos , Locomoção/fisiologia , Bainha de Mielina/metabolismo , Regeneração Nervosa/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/fisiologia , Neurotrofina 3/biossíntese , Desempenho Psicomotor/fisiologia , Ratos , Serotonina/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Transdução Genética/métodos , Tirosina 3-Mono-Oxigenase/metabolismo
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