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1.
J Gastroenterol Hepatol ; 39(2): 224-230, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37939704

RESUMEN

Liver ischemia/reperfusion injury (IRI) is a major complication after partial hepatectomy and liver transplantation and during hypovolemic shock and hypoxia-related diseases. Liver IRI is a current research hotspot. The early stage of liver IRI is characterized by injury and dysfunction of liver sinusoidal endothelial cells (LSECs), which, along with hepatocytes, are the major cells involved in liver injury. In this review, we elaborate on the roles played by LSECs in liver IRI, including the pathological features of LSECs, LSECs exacerbation of the sterile inflammatory response, LSECs interactions with platelets and the promotion of liver regeneration, and the activation of LSECs autophagy. In addition, we discuss the study of LSECs as therapeutic targets for the treatment of liver IRI and the existing problems when applying LSECs in liver IRI research.


Asunto(s)
Células Endoteliales , Daño por Reperfusión , Humanos , Células Endoteliales/fisiología , Hígado/patología , Hepatocitos/fisiología , Daño por Reperfusión/patología , Isquemia/patología
2.
Dig Dis Sci ; 57(4): 935-42, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22215519

RESUMEN

BACKGROUND AND AIM: Proliferation and activation of myofibroblastic hepatic stellate cells (HSCs) in response to growth factors is essential for the development of liver fibrosis. As one of the most potent factors, platelet-derived growth factor (PDGF) activates intracellular signals and contributes to sustained HSCs activation. Growing evidence has suggested that the Ca(2+) signal is involved in PDGF pathways. We showed previously for the first time that Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) is essential for human HSC proliferation. The inhibition of CaMKII by its specific inhibitor, KN-93, significantly decreased the HSC growth and increased expression of cell cycle suppressive regulators P53 and P21. METHODS: In the present study, we investigated the role of CaMKII in PDGF-induced HSC proliferation and underlying mechanisms. RESULTS: We confirmed that in human HSCs, PDGF significantly increased CaMKII mRNA levels, protein expression, and phosphorylation. The interruption of CaMKII by KN-93, specific inhibitory peptide (AIP), or specific CaMKII knockdown by its siRNA not only attenuated PDGF-induced HSC proliferation but also ERK1/2 phosphorylation. However, CaMKII had no effect on JNK phosphorylation. In addition, inhibitors of ERK1/2 (PD98059) and JNK (SP600125) did not affect CaMKII expression. Interruption of CaMKII-ERK cascade, not JNK signal, inhibited PDGF-induced HSC proliferation. CONCLUSION: We confirmed that CaMKII mediated PDGF-induced human HSC proliferation through ERK1/2 but not the JNK mechanism. Our study shed light on CaMKII as a crucial signal in PDGF-activated HSCs and a potential therapeutic point in hepatic fibrosis.


Asunto(s)
Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Proliferación Celular/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Factor de Crecimiento Derivado de Plaquetas/farmacología , Bencilaminas/farmacología , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/antagonistas & inhibidores , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/genética , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/farmacología , Células Cultivadas , ADN/biosíntesis , Técnicas de Silenciamiento del Gen , Células Estrelladas Hepáticas/citología , Células Estrelladas Hepáticas/efectos de los fármacos , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , ARN Interferente Pequeño/genética , Sulfonamidas/farmacología , Transfección
3.
Saudi Med J ; 27(2): 161-4, 2006 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16501668

RESUMEN

OBJECTIVE: To investigate the relationship of serum lipids and apolipoprotein (apoE) gene polymorphism to colorectal adenomas. METHODS: This study took place in the Department of Gastroenterology, Renmin Hospital of Wuhan University, PR China from June 2003 to March 2005. Ninety-eight patients with colorectal adenomas and 40 healthy subjects were enrolled, and their serum levels of triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and low density lipoprotein cholesterol (LDL-C) were determined. The apoE gene polymorphism was identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Serum TC levels of colorectal adenomas group (5.32 +/- 0.85 mmol/L), distal colorectal adenomas group (5.58 +/- 0.63 mmol/L), and villous adenoma group (5.49 +/- 0.69 mmol/L) were higher than the control group (4.28 +/- 0.62 mmol/L, p=0.016), proximal colorectal adenomas group (4.82 +/- 0.58 mmol/L, p=0.038) and non-villous adenoma group (4.76 +/- 0.58 mmol/L, p=0.03). Serum HDL-C levels of colorectal adenomas group (1.39 +/- 0.25 mmol/L) were lower than the control group (1.51 +/- 0.29 mmol/L) (p=0.035). Serum lipids levels of each genotype in colorectal adenomas group were not statistically significant. Apolipoprotein E3/E4 genotypic frequency in colorectal adenomas group (7.1%) was lower than the control group (17.5%) (p=0.012). CONCLUSION: The findings suggest that altered lipid metabolism may be differentially associated with colorectal adenomas and the persons with apoE E3/E4 genotype have lower risk suffering from colorectal adenomas than those with other genotypes.


Asunto(s)
Adenoma/sangre , Adenoma/genética , Apolipoproteínas E/genética , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/genética , Lípidos/sangre , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Triglicéridos/sangre
4.
Artículo en Inglés | MEDLINE | ID: mdl-26379752

RESUMEN

Gastric cancer is the fourth commonest cancer in the world and the second leading cause of cancer-related death. Investigation of gastric cancer metastasis is one of the hottest and major focuses in cancer research. Growing evidence manifested that primo vascular system (PVS) is a new kind of circulatory system beyond vascular and lymphatic system. Previous researches revealed that PVS is a specific tissue between endothelium and mesenchyme and is involved in cancer, especially in tumor metastasis and regeneration. In current study, we investigated the role of primo vessels in gastric cancer metastasis and its possible relationship to vascular vessels formation. Our results indicated that primo vessels were involved in gastric cancer metastasis. We observed blood vessel-mediated metastasis, primo vessel-mediated metastasis, and an intermediate state between them. We deduced that primo vessels may be precursors of blood vessels. These results possibly provided a thoroughly new theoretic development in cancer metastasis.

5.
Artículo en Inglés | MEDLINE | ID: mdl-23662116

RESUMEN

Recent evidences demonstrated that endothelial-to-mesenchymal transition (EndMT) has a crucial role in cancer and is recognized as a unique source of cancer-associated fibroblasts (CAFs). Primo vascular system (PVS) is a new circulatory system which may play an important role in cancer metastasis and regeneration. In the current study, we applied previously established time-saving method to identify primo vessels and further investigated the immunocytochemical properties of primo vessels. Both primo vessels and primary primo vessel cells in the mesentery expressed endothelial markers and fibroblast markers. Double-labeling experiments demonstrated that endothelial and fibroblast markers are coexpressed in primo vessels. In addition, under the stimulation of TGF-ß1 in vitro, primary primo vessel cells differentiated into fibroblasts. Therefore, we found that primo vessels in the mesentery had a transitional structure between endothelium and mesenchymal. This is a new finding of EndMT in normal postnatal animals.

6.
Dig Dis Sci ; 50(10): 1898-903, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16187194

RESUMEN

Stress ulcer occurs primarily in severe conditions, with a high incidence and mortality in intensive care units. However, studies on the association between stress ulcer and bile reflux to the stomach with stress ulcer are still inconclusive. Therefore, our research aimed to determine whether or not bile reflux exists during stress ulcer and then to investigate the effects and mechanism of changes of pyloric local neurotransmitters on bile reflux in such circumstances so as to provide a new pathway for clinical intervention. Cold water immersion was used to copy the stress ulcer model of rats. Sixty-five adult Sprague-Dawley rats of either sex were randomly divided into three groups: the normal control group (n = 10), the stress group (n = 30), and the antagonist group (n = 25). The gastric ulcer index, pH, and bile acid of gastric juice were measured before and after stress. Radio Immunoassay Detection Kit and Biochemic Detection Kit were used to measure local contents of CGRP (calcitonin gene-related peptide) and nitric oxide, respectively, in rats' pylorus. The local contents of nitric oxide in rats' pylorus reached a maximum at 1 hr after stress. The bile acid and pH of gastric juice peaked at 2 hr after stress and the ulcer index peaked at 4 hr after stress. But the local contents of CGRP in rats' pylorus decreased to the minimum at 4 hr after stress. The bile acid and ulcer index in the L-NAME group were significantly lower than in the antagonist control group. However, the bile acid in the hCGRP8-37 group was less than in the antagonist control group. Compared with hCGRP8-37 group, there was a significant reduction in bile acid in the L-NAME group. There was a significant reduction in the ulcer index of the hCGRP8-37 group compared with the L-NAME group and the antagonist control group. There was a certain kind of positive correlation between nitric oxide in rats' pylorus and bile acid to the stomach, for nitric oxide could loosen the pyloric sphincter and increase the bile acid to the stomach. L-NAME might reduce the local nitric oxide contents in rats' pylorus so that bile acid to the stomach might be decreased, obviously with a looser tight pyloric sphincter. Meanwhile, the CGRP in rats' pylorus was negatively associated with the ulcer index, hence CGRP might protect gastric mucosa under stress conditions.


Asunto(s)
Reflujo Biliar/etiología , Péptido Relacionado con Gen de Calcitonina/fisiología , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico Sintasa/antagonistas & inhibidores , Fragmentos de Péptidos/fisiología , Píloro/efectos de los fármacos , Úlcera Gástrica/complicaciones , Animales , Ácidos y Sales Biliares/fisiología , Reflujo Biliar/metabolismo , Reflujo Biliar/fisiopatología , Femenino , Determinación de la Acidez Gástrica , Masculino , Óxido Nítrico/metabolismo , Píloro/metabolismo , Ratas , Ratas Sprague-Dawley , Úlcera Gástrica/metabolismo , Úlcera Gástrica/fisiopatología , Estrés Fisiológico/complicaciones , Estrés Fisiológico/metabolismo , Estrés Fisiológico/fisiopatología
7.
Dig Dis Sci ; 49(6): 948-53, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15309882

RESUMEN

Nonsteroidal antiinflammatory drugs (NSAIDs) have been reported to have antiproliferative effects in neoplastic cells of different origin during the past few decades. We aimed to study the effects of the selective COX-2 inhibitor, nimesulide, on cell viability and telomerase and Akt/PKB activity in the human gastric cancer cell line MKN-45 and to explore the molecular mechanism for the antitumor activity of the selective COX-2 inhibitor. We tested the influence of nimesulide on the gastric cancer cell line MKN-45 in vitro. Trypan blue exclusion was used to determine the cell viability after incubation for 0, 12, 24, and 48 hr in different concentrations of nimesulide 0, 25, 50, 100, 200 microM). After treatment or no treatment with 100 microM nimesulide for 0, 12, 24, or 48 hr in the presence or absence of 300 nM okadaic acid for 2 hr, telomerase and Akt/PKB activity was measured using TRAP PCR-ELISA and nonradioactive IP kinase assays, respectively. In the gastric cancer cell line MKN-45 nimesulide caused a time- and dose-dependent reduction in cell numbers and significantly inhibited telomerase and Akt/PKB activity; the inhibition of telomerase activity was partly associated with the attenuation of Akt/PKB activity. These results demonstrate that the selective COX-2 inhibitor suppresses the telomerase activity of gastric cancer cells, in part by blocking the activation of protein kinase B, which provides a new signaling mechanism responsible for the anticancer effects of the selective COX-2 inhibitor.


Asunto(s)
Inhibidores de la Ciclooxigenasa/farmacología , Isoenzimas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/efectos de los fármacos , Proteínas Proto-Oncogénicas/efectos de los fármacos , Neoplasias Gástricas/enzimología , Sulfonamidas/farmacología , Telomerasa/efectos de los fármacos , Línea Celular Tumoral/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2 , Relación Dosis-Respuesta a Droga , Activación Enzimática/efectos de los fármacos , Humanos , Proteínas de la Membrana , Prostaglandina-Endoperóxido Sintasas , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas c-akt , Telomerasa/metabolismo , Factores de Tiempo
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