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1.
BMC Pediatr ; 24(1): 51, 2024 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-38229006

RESUMEN

OBJECTIVE: The study aimed to explore the effectiveness of bedside lung ultrasound (LUS) combined with the PaO2/FiO2 (P/F) ratio in evaluating the outcomes of high-flow nasal cannula (HFNC) therapy in infants with severe pneumonia. METHODS: This retrospective study analyzed the clinical data of 150 infants diagnosed with severe pneumonia and treated with HFNC therapy at our hospital from January 2021 to December 2021. These patients were divided into two groups based on their treatment outcomes: the HFNC success group (n = 112) and the HFNC failure group (n = 38). LUS was utilized to evaluate the patients' lung conditions, and blood gas results were recorded for both groups upon admission and after 12 h of HFNC therapy. RESULTS: At admission, no significant differences were observed between the two groups in terms of age, gender, respiratory rate, partial pressure of oxygen, and partial pressure of carbon dioxide. However, the P/F ratios at admission and after 12 h of HFNC therapy were significantly lower in the HFNC failure group (193.08 ± 49.14, 228.63 ± 80.17, respectively) compared to the HFNC success group (248.51 ± 64.44, 288.93 ± 57.17, respectively) (p < 0.05). Likewise, LUS scores at admission and after 12 h were significantly higher in the failure group (18.42 ± 5.3, 18.03 ± 5.36, respectively) than in the success group (15.09 ± 4.66, 10.71 ± 3.78, respectively) (p < 0.05). Notably, in the success group, both P/F ratios and LUS scores showed significant improvement after 12 h of HFNC therapy, a trend not observed in the failure group. Multivariate regression analysis indicated that lower P/F ratios and higher LUS scores at admission and after 12 h were predictive of a greater risk of HFNC failure. ROC analysis demonstrated that an LUS score > 20.5 at admission predicted HFNC therapy failure with an AUC of 0.695, a sensitivity of 44.7%, and a specificity of 91.1%. A LUS score > 15.5 after 12 h of HFNC therapy had an AUC of 0.874, with 65.8% sensitivity and 89.3% specificity. An admission P/F ratio < 225.5 predicted HFNC therapy failure with an AUC of 0.739, 60.7% sensitivity, and 71.1% specificity, while a P/F ratio < 256.5 after 12 h of HFNC therapy had an AUC of 0.811, 74.1% sensitivity, and 73.7% specificity. CONCLUSION: Decreased LUS scores and increased P/F ratio demonstrate a strong correlation with successful HFNC treatment outcomes in infants with severe pneumonia. These findings may provide valuable support for clinicians in managing such cases.


Asunto(s)
Neumonía , Insuficiencia Respiratoria , Lactante , Humanos , Cánula , Estudios Retrospectivos , Terapia por Inhalación de Oxígeno/métodos , Pulmón/diagnóstico por imagen , Neumonía/diagnóstico por imagen , Neumonía/terapia , Oxígeno , Insuficiencia Respiratoria/terapia
2.
Microcirculation ; 30(4): e12803, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36916460

RESUMEN

BACKGROUND: Impaired microcirculation in acute coronary syndrome (ACS) patients manifests inadequate recovery and adverse clinical outcome. Here, we analyzed correlations between peripheral microcirculation and heart function in ACS patients. METHODS: Opisthenar microvessel area (OMA) were measured with optical coherence tomography angiography (OCTA), cardiac functional indexes (echocardiograph) were assessed 48-72 h after therapeutic interventions. RESULTS: Results showed that OMA normalized with heart rate (OMA-HR) were significantly greater in ACS patients with percutaneous intervention (ACS-PCI, n = 25, stenosis >80%) compared to those with pharmacological intervention (ACS-PI, n = 23, stenosis <50%, p = .02). Ejection fraction (EF) and fractional shortening (FS), which were not different between two groups, showed negative correlations with OMA-HR in ACS-PCI (EF: r = -0.512, p = .009; FS: r = -0.594, p = .002). Cardiac output (CO) inversely correlated with OMA-HR in both groups (r = -0.697, p < .0001; r = -0.527, p = .01). Neutrophil to lymphocyte ratio (NLR) on admission was greater in ACS-PCI group. NLR, which was negatively associated with EF or FS, was positively associated with OMA-HR in all patients. The area under the curve (AUC) for OMA-HR was 0.683 (specificity 0.696 and sensitivity 0.72, p = .02). OMA-HR at >376.5 µm2 predicts reduced FS and CO (p = .002, p = .005, respectively). Summary OMA-HR predicts inadequate recovery of the heart in severe ACS patients post-PCI.


Asunto(s)
Síndrome Coronario Agudo , Intervención Coronaria Percutánea , Humanos , Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/etiología , Microcirculación , Intervención Coronaria Percutánea/efectos adversos , Constricción Patológica/etiología , Corazón/diagnóstico por imagen
3.
Chin J Integr Med ; 29(1): 3-9, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35915317

RESUMEN

OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS: Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).


Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Quimioembolización Terapéutica/efectos adversos , Hepatectomía , Supervivencia sin Enfermedad , Resultado del Tratamiento , Estudios Retrospectivos
4.
Hepatogastroenterology ; 54(79): 2092-8, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-18251166

RESUMEN

BACKGROUND/AIMS: To study the effects of interleukin-10 on hepatic stellate cells and liver tissue in experimental rats hepatic fibrosis. METHODOLOGY: Rat hepatic fibrosis model induced by carbon tetrachloride was established. Liver tissues were harvested from the rats administered CCl4 with or without IL-10 treatment and the animals of the control group. The expression of TGF-beta1, MMP-2 and TIMP-1 in the liver tissues was measured by S-P immunohistochemistry. In addition, another model was established; HSCs in rats in each group were isolated. RT-PCR was employed to analyze TGF-beta1, MMP-2 and TIMP-1 mRNA expression in cells and immunocytochemistry was performed to detect protein expression of alpha-SMA, NF-kappaB, TGF-beta1, MMP-2 and TIMP-1 in HSCs. RESULTS: Rat hepatic fibrosis was developed successfully. The fibrosis changes were partially reversed by simultaneous administration of IL-10. The positive signals of TGF-beta1, MMP-2 and TIMP-1 were observed more frequently (P<0.05) in the CCl4-treated group compared to those in the IL-10-treated group and the control group. HSCs were successfully isolated. TGF-beta1, MMP-2 and TIMP-1 mRNA in HSCs increased obviously during the course of hepatic fibrosis, and their levels were decreased after the treatment with IL-10 (P<0.05). The immunocytochemistry positive levels for TGF-beta1, MMP-2, TIMP-1, alpha-SMA and NF-kappaB in the fibrogenesis group were increased significantly compared to the normal group (P<0.01). The positive signals decreased significantly (P<0.05) after the treatment with IL-10. CONCLUSIONS: The expression of TGF-beta1, MMP-2 and TIMP-1 increased in liver or in HSC of hepatic fibrosis rats and decreased after treatment with IL-10. The IL-10 could inhibit the activation of HSCs and make an antifibrogenic process come into effect in this way.


Asunto(s)
Fibrinólisis/fisiología , Interleucina-10/fisiología , Cirrosis Hepática Experimental/metabolismo , Actinas/metabolismo , Animales , Modelos Animales de Enfermedad , Electroforesis , Inmunohistoquímica , Hígado/citología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo
5.
World J Gastroenterol ; 12(12): 1918-23, 2006 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-16609999

RESUMEN

AIM: To study the effects of interleukin-10 (IL-10) on the expression of alpha-smooth muscle actin (alpha-SMA), nuclear factor- kappa B(NF- kappa B) and Fas/Fas ligand (FasL) in hepatic stellate cells of experimental rats with hepatic fibrosis. METHODS: Sixty clean SD rats were randomly divided into control group (group N), liver fibrotic group (group C) and IL-10 treatment group (group I). Control group received intraperitoneal injection of saline (2 mL/kg), twice a week. Fibrotic group was injected intraperitoneally with 50% carbon tetrachloride (CCl(4)) (2 mL/kg), twice a week. IL-10 treatment group was given IL-10 at a dose of 4 microg/kg 20 minutes before CCl(4) administration from the third week. Hepatic stellate cells (HSCs) were isolated from these rats at the seventh and eleventh weeks during the course of liver fibrosis, respectively. The expression of alpha-SMA and NF- kappa B in HSCs was measured by S-P immunohistochemistry. The expression of Fas and FasL mRNA was measured by RT-PCR. Furthermore, liver tissues were harvested from three groups at the same time. RESULTS: The CCl(4)- induced experimental rat hepatic fibrosis model was established successfully. The purity of extracted hepatic stellate cells was about 95% and the yield of hepatic stellate cells was 1.2-2.3 x 10(6)/g liver tissue averagely. The positive expression of alpha-SMA and NF- kappa B was 36.5% and 28.5% respectively in group N. The positive levels of alpha-SMA and NF- kappa B were increased significantly in group C compared to group N (P<0.01). The positive signals decreased significantly (P<0.05) in group I. In the 11th week, the HSCs of group I became round with visible pyknotic nuclei. The expression of NF- kappa B in group C was significantly increased in a time-dependent manner (P<0.01), but there was no difference in the alpha-SMA expression (P>0.05). The mRNA of Fas and FasL in group C was significantly increased in a time-dependent manner compared to that in control group. After treated with IL-10, the expression level of Fas and FasL was higher in group I than in group C. CONCLUSION: The positive expression of alpha-SMA and NF- kappa B in hepatic stellate cells is decreased by ectogenic IL-10 in liver fibrosis induced by CCl(4). The expression of Fas and FasL is increased in the course of liver fibrosis, and is further increased by IL-10. IL-10 could inhibit the activation of HSCs and cause apoptosis of activated HSCs.


Asunto(s)
Apoptosis/efectos de los fármacos , Interleucina-10/farmacología , Cirrosis Hepática/tratamiento farmacológico , Hígado/efectos de los fármacos , Actinas/análisis , Animales , Tetracloruro de Carbono , Proteína Ligando Fas , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/patología , Masculino , Glicoproteínas de Membrana/análisis , FN-kappa B/análisis , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Receptores del Factor de Necrosis Tumoral/análisis , Transducción de Señal , Factores de Necrosis Tumoral/análisis , Receptor fas
6.
World J Gastroenterol ; 12(9): 1386-91, 2006 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-16552806

RESUMEN

AIM: To study the therapeutic effect of exogenous interleukin-10 on CCl4-induced hepatic fibrosis in rats and its possible mechanisms. METHODS: Fourty-seven SD rats were randomly divided into control group (group N) and CCl4-induced hepatic fibrosis model group (group C). After CCl4 was given for 9 wk, the model group was divided into three groups. Rats in group M were put to death immediately,rats in group T were treated with IL-10 for another three wk and then put to death, rats in group R recovered after three weeks and were then killed. The degree of hepatic fibrosis was measured by HE staining and histological activity index (HAI). Histological activity index (HAI), change of collagen types I and III were measured by Picrosirius staining. The expression of TNF-alpha, MMP-2 and TIMP-1 in liver tissue was measured by S-P immunohistochemistry. RESULTS: CCl4- induced experimental rat hepatic fibrosis model was established successfully. The degree of hepatic fibrosis was markedly lower in group T than in groups M and R, and there was no difference between the two groups. The expression of collagen types I and III was significantly suppressed in group T and was slightly suppressed in groups M and R. The positive levels of TNF-alpha, MMP-2 and TIMP-1 in group M increased significantly compared to those in group N (P<0.01). The positive signals decreased significantly in groups T and R (P<0.01),but positive score was significantly lower in group T than in group R (P<0.01). CONCLUSION: Exogenous IL-10 can reverse CCl4-induced hepatic fibrosis in rats. IL-10 may exert its reversible effects on hepatic fibrosis by blocking CCl4-induced inflammation,inhibiting expression of MMP-2 and TIMP-1 and promoting resolution of collagen types I and III.


Asunto(s)
Interleucina-10/uso terapéutico , Cirrosis Hepática/tratamiento farmacológico , Animales , Tetracloruro de Carbono , Colágeno Tipo I/análisis , Colágeno Tipo III/análisis , Inmunohistoquímica , Hígado/química , Hígado/efectos de los fármacos , Hígado/patología , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/patología , Masculino , Metaloproteinasa 2 de la Matriz/análisis , Ratas , Ratas Sprague-Dawley , Inhibidor Tisular de Metaloproteinasa-1/análisis , Factor de Necrosis Tumoral alfa/análisis
7.
World J Gastroenterol ; 12(15): 2357-62, 2006 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-16688825

RESUMEN

AIM: To study the effect of interleukin-10 (IL-10) on the expression of transforming growth factor beta1 (TGF-beta1) in hepatic fibrosis rats and the anti-fibrotic role of exogenous IL-10. METHODS: Hepatic fibrosis was induced by carbon tetrachloride administered (CCl(4)) intraperitoneally. The experiment was performed in two stages. In the first stage, 60 SD rats were divided randomly into normal control group 1 (GN(1), n=8), hepatic fibrosis group (GC, n=28)and IL-10 intervened group (GI, n=24). At the beginning of the 7(th) and 11(th) wk, hepatic stellate cells (HSCs) were isolated, reverse transcription-polymerase chain reaction (RT-PCR) and immunocytochemistry were performed to detect the expression of TGF-beta1 in HSCs. Histological examination was used to determine the degree of hepatic fibrosis. In the second stage, 47 SD rats were divided randomly into normal control group 2 (GN(2), n=6)and CCl(4) group(GZ, n=41). At the end of the 9(th) wk, rats in GZ group were allocated randomly into model group(GM, n=9), IL-10 treatment group (GT, n=9)and recovered group (GR, n=9). At the end of the 12(th) wk, all rats were sacrificed. RT-PCR and immunohistochemistry were performed to detect the expression of TGF-beta1 in liver tissue. ELISA was used to assay serum TGF-beta1 levels. RESULTS: Hepatic fibrosis developed in rats with the increase of the injection frequency of CCl(4). In the first stage, hepatic fibrosis developed and HSCs were isolated successfully. At the 7(th) and 11(th) wk, TGF-beta1 mRNA in GC group increased significantly compared with that in GN(1) (P=0.001/0.042) and GI groups (P=0.001/0.007), whereas there was no significant difference between the two groups. The levels of TGF-beta1 at the beginning of the 7(th) wk was higher than that of the 11(th) wk (P=0.049). Immunocytochemistry results of TGF-beta1 were consistent with the above findings. In the second stage, TGF-beta1 increased significantly in GM group compared to GN(2). After treatment with IL-10, TGF-beta1 declined obviously. The expression of TGF-beta1 decreased in GR group but was still higher than that in GT group. CONCLUSION: The levels of TGF-beta1 are increased in hepatic fibrosis rats and decreased after treatment with exogenous IL-10. IL-10 may play an anti-fibrotic role by suppressing TGF-beta1 expression.


Asunto(s)
Interleucina-10/farmacología , Cirrosis Hepática/tratamiento farmacológico , Factor de Crecimiento Transformador beta/metabolismo , Animales , Secuencia de Bases , Tetracloruro de Carbono/toxicidad , Expresión Génica/efectos de los fármacos , Inmunohistoquímica , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Masculino , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta1
8.
World J Gastroenterol ; 11(31): 4788-93, 2005 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-16097045

RESUMEN

AIM: To study the effect of IL-10 on the expression of growth factors--transforming growth factor-beta1 (TGF-beta1), epidermal growth factor (EGF), hepatocyte growth factor (HGF) and platelet-derived growth factor (PDGF) of hepatic stellate cells (HSCs) of hepatic fibrosis rat and the anti-fibrogenic role of exogenous IL-10. METHODS: Hepatic fibrosis was induced by CCl(4) administration intra-peritoneally. Sixty clean male Sprague-Dawley (SD) rats were randomly divided into three groups: normal control group (GN, 8 rats), hepatic fibrosis model group (GC, 28 rats) and IL-10 treated group (GI, 24 rats). At the beginning of the 7th and 11th wk, rats in each group were routinely perfused with pronase E and type IV collagenase through a portal vein catheter and the suspension obtained from the liver was spun by centrifugation with 11% Nycodenz density gradient to isolate HSCs. Histological examination was used to determine the degree of hepatic fibrosis. RT-PCR was employed to analyze mRNA expression from freshly isolated cells. Immunocytochemistry was performed to detect protein expression in primary cultured HSCs. RESULTS: Rat hepatic fibrosis was developed with the increase of injection frequency of CCl(4), and HSCs were successfully isolated. At the 7th and 11th wk, TGF-beta1, EGF, and HGF mRNA in GC increased obviously compared with GN (P = 0.001/0.042, 0.001/0.001, 0.001/0.001) and GI (P = 0.001/0.007, 0.002/0.001, 0.001/0.001). For TGF-beta1, no difference was observed between GI and GN. For EGF, mRNA level in GI increased compared with GN during the 7th wk (P = 0.005) and 11th wk (P = 0.049). For HGF, mRNA level in GI decreased compared with GN at the 7th wk (P = 0.001) and 11th wk (P = 0.021). Between these two time points, TGF-beta1 expression at the 7th wk was higher than that of the 11th wk (P = 0.049), but for EGF, the former was lower than the latter (P = 0.022). As for PDGF mRNA, there was no significant difference between these groups, but difference seemed to exist in protein levels. Results by immunocytochemistry of TGF-beta1 and EGF were paralleled with the above findings. CONCLUSION: The expression of TGF-beta1, EGF and HGF increased in HSC of hepatic fibrosis rat and decreased after treatment with IL-10. IL-10 plays an anti-fibrogenic role by suppressing growth factors expression.


Asunto(s)
Intoxicación por Tetracloruro de Carbono/patología , Factor de Crecimiento Epidérmico/genética , Factor de Crecimiento de Hepatocito/genética , Interleucina-10/farmacología , Hepatopatías/metabolismo , Factor de Crecimiento Transformador beta/genética , Animales , Secuencia de Bases , Intoxicación por Tetracloruro de Carbono/metabolismo , Cartilla de ADN , Regulación de la Expresión Génica/efectos de los fármacos , Hepatopatías/patología , Masculino , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Factor de Crecimiento Transformador beta1
9.
World J Gastroenterol ; 11(12): 1753-8, 2005 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-15793858

RESUMEN

AIM: To investigate the expression of matrix metallopr-oteinase-2 and tissue inhibitor of metalloproteinase-1 in hepatic fibrosis and the antifibrogenic role of exogenous interleukin-10 (IL-10). METHODS: Hepatic fibrosis was induced by CCl(4) administration and 60 male Sprague-Dawley rats were randomly divided into normal control group (group N, 8 rats), CCl(4)-induced group (group C, 28 rats) and IL-10-treated group (group I, 24 rats). At the beginning of the 7(th) and 11(th) wk, rats in each group were routinely perfused with pronase E and type IV collagenase through portal vein catheter and the suspension was centrifuged by 11% Nycodenz density gradient to isolate hepatic stellate cells (HSCs). RT-PCR was used to analyze mRNA of MMP-2 and TIMP-1 from freshly isolated cells. Densitometric data were standardized with beta-actin signals. Immunocytochemistry was performed to detect MMP-2 and TIMP-1 expression in HSC cultured for 72 h. RESULTS: Compared to group N in the 7(th) wk, MMP-2 and TIMP-1 mRNA increased in group C (P = 0.001/0.001) and group I (P = 0.001/0.009). The level of MMP-2 and TIMP-1 mRNA in group I was significantly lower than that in group C (P = 0.001/0.001). In the 11(th) wk, MMP-2 mRNA in group I was still lower than that in group C (P = 0.005), but both dropped compared with that in the 7(th) week (P = 0.001/0.004). TIMP-1 mRNA in group I was still lower than that in group C (P = 0.001), and increased in group C (P = 0.001) while decreased in group I (P = 0.042) compared with that in the 7(th) wk. Same results were found by immunocytochemistry. CONCLUSION: Expression of MMP-2 and TIMP-1 is increased in hepatic fibrosis. IL-10 exhibits an antifibrogenic effect by suppressing MMP-2 and TIMP-1 expression.


Asunto(s)
Interleucina-10/farmacología , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/fisiopatología , Metaloproteinasa 2 de la Matriz/genética , Inhibidor Tisular de Metaloproteinasa-1/genética , Animales , Tetracloruro de Carbono , Inmunohistoquímica , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/patología , Masculino , Metaloproteinasa 2 de la Matriz/metabolismo , ARN Mensajero/análisis , Ratas , Ratas Sprague-Dawley , Inhibidor Tisular de Metaloproteinasa-1/metabolismo
10.
Mol Med Rep ; 7(2): 371-8, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23232951

RESUMEN

Activation of hepatic stellate cells (HSCs) plays a key role in the progression of liver fibrosis. Interleukin-10 (IL-10), a potential anti-fibrosis cytokine, has an unfavorable pharmacokinetic profile, which limits its clinical applications. A liver-targeting gene delivery system may maintain a longer-lasting concentration in hepatic tissue with fewer side­effects in non-target tissues. In the present study, when delivered by asialoglycoprotein receptor-mediated liposomes, the IL-10 gene was highly expressed in BRL cells (a rat hepatocyte line) and attenuated the apoptosis of BRL cells induced by plasmid transfection. In a co-culture system, BRL cells demonstrated a marked ability to stimulate the proliferation of primary HSCs and their expression of α-SMA and procollagen type I. Following modification of the BRL cells with the IL-10 gene, this stimulation was attenuated and an accelerated apoptosis of the HSCs was induced. These results suggest that hepatocyte­targeting gene delivery may be an ideal technique for the IL-10 gene therapy of liver fibrosis, which requires further confirmation by in vivo studies.


Asunto(s)
Células Estrelladas Hepáticas/citología , Hepatocitos/citología , Interleucina-10/genética , Actinas/metabolismo , Animales , Apoptosis , Proliferación Celular , Células Cultivadas , Técnicas de Cocultivo , Colágeno Tipo I/metabolismo , Hepatocitos/metabolismo , Liposomas/química , Liposomas/metabolismo , Ratas , Ratas Sprague-Dawley , Transfección
11.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 24(4): 332-4, 2008 Apr.
Artículo en Zh | MEDLINE | ID: mdl-18394335

RESUMEN

AIM: To construct eukaryotic expression vector of rat IL-10 gene and observe its expression in hepatocyte cell line BRL. METHODS: Total RNA was extracted from rat peripheral blood mononuclear cells. The full length coding region of IL-10 was amplified by RT- nested PCR and cloned into eukaryotic expression vector pcDNA3.0. The recombinant plasmid was transfected into BRL cells with either liposome Transfast or asialoglycoprotein receptor mediated liposome PEIjet-gal respectively. The expression of IL-10 mRNA was detected with PCR and that of IL-10 secreted from BRL cells transfected by liposome PEIjet-gal was detected with ELISA. RESULTS: The recombinant plasmid was identified and confirmed with digestion of restriction endonuclease and DNA sequencing. Receptor mediated liposome PEIjet-gal exhibited significantly higher transfection efficiency than liposome Transfast and higher level secretory IL-10 expressed in BRL cells. CONCLUSION: The eukaryotic expression vector of IL-10 gene was successfully constructed. Asialoglycoprotein receptor-mediated liposome had high transfection efficiency on hepatocytes, suggesting that it could be a potential hepatocyte-targeting delivery system for IL-10 gene therapy.


Asunto(s)
Vectores Genéticos/genética , Interleucina-10/metabolismo , Transfección/métodos , Animales , Línea Celular , Ensayo de Inmunoadsorción Enzimática , Vectores Genéticos/química , Hepatocitos/metabolismo , Interleucina-10/genética , Liposomas/química , Plásmidos , Reacción en Cadena de la Polimerasa , Ratas
12.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 24(12): 1150-3, 2008 Dec.
Artículo en Zh | MEDLINE | ID: mdl-19068197

RESUMEN

AIM: To investigate the effect of IL-10 on proliferation of rat primary cultured hepatocytes. METHODS: Rat hepatocytes were isolated from rat liver by in situ digestion of collagenase IV and cryopreserved, resuscitated, cultured in vitro. Reverse-transcription polymerase chain reaction (RT-PCR) was used to characterize the purity of hepatocytes and analyze IL-10/IL10Ralpha mRNA from freshly isolated cells. The primary cultured hepatocytes were divided into 3 groups and treated with nothing (group N), Insulin (group C), and IL-10 in combination with Insulin (group I), respectively. Nuclear cell cycle analysis, MTT, and Trypan Blue cell count was assayed. RESULTS: RT-PCR showed expression of characterization genes in primary hepatocytes group and liver tissue are different. RT-PCR showed an expression of IL-10/IL10Ralpha mRNA in rat primary hepatocytes. Trypan Blue cell count showed an depression of cell quantity in group I at 48h (71.96% contrast to group C, P<0.05). MTT analyse also showed absorbance of group I was declined contrast to group C at 24 h and 48 h (88.41% and 90.24%, P<0.05). Cell cycle analysis via FCM showed a decline at 24h in group I than group C and group N (59.06% and 70.18%, P<0.01). CONCLUSION: The primary hepatocytes we isolated is quite purity. Rat primary hepatocytes express IL-10/IL10Ralpha mRNA. IL-10 has an suppression effect on proliferation of primary cultured hepatocytes.


Asunto(s)
Hepatocitos/citología , Hepatocitos/efectos de los fármacos , Interleucina-10/farmacología , Animales , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Hepatocitos/metabolismo , Insulina/farmacología , Interleucina-10/genética , Subunidad alfa del Receptor de Interleucina-10/genética , Masculino , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
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