AIM: To examine the efficacy of the radial flow bioreactor (RFB) as an extracorporeal bioartificial liver (BAL) and the reconstruction of liver organoids using embryonic pig liver cells. METHODS: We reconstructe...AIM: To examine the efficacy of the radial flow bioreactor (RFB) as an extracorporeal bioartificial liver (BAL) and the reconstruction of liver organoids using embryonic pig liver cells. METHODS: We reconstructed the liver organoids using embryonic porcine liver cells in the RFB. We also determined the gestational time window for the optimum growth of embryonic porcine liver cells. Five weeks of gestation was designated as embryonic day (E) 35 and 8 wk of gestation was designated as E56. These cells were cultured for one week before morphological and functional examinations. Moreover, the efficacy of pulsed adminisbation of a high concentration hepatocyte growth factor (HGF) was examined. RESULTS: Both cell growth and function were excellent after harvesting on E35. The pulsed administration of a high concentration of HGF promoted the differentiation and maturation of these fetal hepatic cells. Microscopic examination of organoids in the RFB revealed palisading and showed that bile duct-like structures were well developed, indicating that the organoids were mini livers. Transmission electron microscopy revealed microvilli on the luminal surfaces of bile duct-like structures and junctional complexes, which form the basis of the cytoskeleton of epithelial tissues. Furthermore, strong expression of connexin (Cx) 32, which is the main protein of hepatocyte gap junctions, was observed. With respect to liver function, ammonia detoxification and urea synthesis were shown to be performed effectively. CONCLUSION: Our system can potentially be applied in the fields of BAL and transplantation medicine.展开更多
Constitutive activation of the insulin-like growth factor (IGF)-signaling axis is frequently observed in human hepatocellular carcinoma(HCC).Especially the over- expression of the fetal growth factor IGF-Ⅱ,IGF-Ⅰ rec...Constitutive activation of the insulin-like growth factor (IGF)-signaling axis is frequently observed in human hepatocellular carcinoma(HCC).Especially the over- expression of the fetal growth factor IGF-Ⅱ,IGF-Ⅰ receptor(IGF-IR),and cytoplasmic downstream effectors such as insulin-receptor substrates(IRS)contribute to proliferation,anti-apoptosis,and invasive behavior. This review focuses on the relevant alterations in this signaling pathway and independent in vivo models that support the central role IGF-Ⅱsignaling during HCC development and progression.Since this pathway has become the center of interest as a target for potential anti-cancer therapy in many types of malignancies,various experimental strategies have been developed,including neutralizing antibodies and selective receptor kinase inhibitors,with respect to the specific and efficient reduction of oncogenic IGF-Ⅱ/IGF-IR-signaling.展开更多
Objective: To observe the effect of acupuncture-moxibustion on the expression of insulin-like growth factor-I (IGF-I) and suppressor of cytokine signaling-2 (SOCS2) in colonic mucosa of rat models of ulcerative...Objective: To observe the effect of acupuncture-moxibustion on the expression of insulin-like growth factor-I (IGF-I) and suppressor of cytokine signaling-2 (SOCS2) in colonic mucosa of rat models of ulcerative colitis (UC), and explore the mechanism of acupuncture- moxibustion therapy in treating UC. Methods: The rats were randomized into a normal control (NC) group, a model control (MC) group, an herb-partitioned moxibustion (HPM) group and an electroacupuncture (EA) group, 8 in each group. The rat models of UC were established by immunological methods combined with local stimulation. The rats in the HPM and EA groups were given herb-partitioned moxibustion and electroacupuncture treatments respectively, once every day, lasting for 14 d. The morphological variations of rat's colonic mucosa were observed under light microscope; the colonic mucosal mucin was detected by PAS-AB and HID-AB staining methods; the expression of IGF-1 and SOCS2 was assayed by the immunohistochemical method. Results: In the rat models of UC, ulceration and inflammation of the colon were revealed by light microscope. The concentration of colonic mucosal mucin was reduced (P〈0.01), while the expression of IGF-1 had an increase (P〈0.01), and the expression of SOCS2 was reduced (P〈0.01). After HPM or EA treatment, the pathological injuries of colonic mucosa had improved, the concentration of mucin increased (P〈0.01), the expression of IGF-1 decreased (P〈0.01), and the expression of SOCS2 increased (P〈0.01). Conclusion: The secretion of mucosal mucin in rat UC decreased, the expression of IGF-1 was significantly higher, while the expression of SOCS2 was remarkably lower; both HPM and EA can help improve the damage of colonic mucosa in rat UC, and modulate the secretion of mucin, as well as regulate the expression of IGF-1 and SOCS2 in the colonic mucosa.展开更多
基金Supported by Grants-In-Aid from the University Start-Up Creation Support Systemthe Promotion and Mutual Aid Corporation for Private School of Japanthe Japan Health Sciences Foundation, Research on Health Science on Drug Innovation, No. KH 71068
文摘AIM: To examine the efficacy of the radial flow bioreactor (RFB) as an extracorporeal bioartificial liver (BAL) and the reconstruction of liver organoids using embryonic pig liver cells. METHODS: We reconstructed the liver organoids using embryonic porcine liver cells in the RFB. We also determined the gestational time window for the optimum growth of embryonic porcine liver cells. Five weeks of gestation was designated as embryonic day (E) 35 and 8 wk of gestation was designated as E56. These cells were cultured for one week before morphological and functional examinations. Moreover, the efficacy of pulsed adminisbation of a high concentration hepatocyte growth factor (HGF) was examined. RESULTS: Both cell growth and function were excellent after harvesting on E35. The pulsed administration of a high concentration of HGF promoted the differentiation and maturation of these fetal hepatic cells. Microscopic examination of organoids in the RFB revealed palisading and showed that bile duct-like structures were well developed, indicating that the organoids were mini livers. Transmission electron microscopy revealed microvilli on the luminal surfaces of bile duct-like structures and junctional complexes, which form the basis of the cytoskeleton of epithelial tissues. Furthermore, strong expression of connexin (Cx) 32, which is the main protein of hepatocyte gap junctions, was observed. With respect to liver function, ammonia detoxification and urea synthesis were shown to be performed effectively. CONCLUSION: Our system can potentially be applied in the fields of BAL and transplantation medicine.
文摘Constitutive activation of the insulin-like growth factor (IGF)-signaling axis is frequently observed in human hepatocellular carcinoma(HCC).Especially the over- expression of the fetal growth factor IGF-Ⅱ,IGF-Ⅰ receptor(IGF-IR),and cytoplasmic downstream effectors such as insulin-receptor substrates(IRS)contribute to proliferation,anti-apoptosis,and invasive behavior. This review focuses on the relevant alterations in this signaling pathway and independent in vivo models that support the central role IGF-Ⅱsignaling during HCC development and progression.Since this pathway has become the center of interest as a target for potential anti-cancer therapy in many types of malignancies,various experimental strategies have been developed,including neutralizing antibodies and selective receptor kinase inhibitors,with respect to the specific and efficient reduction of oncogenic IGF-Ⅱ/IGF-IR-signaling.
文摘Objective: To observe the effect of acupuncture-moxibustion on the expression of insulin-like growth factor-I (IGF-I) and suppressor of cytokine signaling-2 (SOCS2) in colonic mucosa of rat models of ulcerative colitis (UC), and explore the mechanism of acupuncture- moxibustion therapy in treating UC. Methods: The rats were randomized into a normal control (NC) group, a model control (MC) group, an herb-partitioned moxibustion (HPM) group and an electroacupuncture (EA) group, 8 in each group. The rat models of UC were established by immunological methods combined with local stimulation. The rats in the HPM and EA groups were given herb-partitioned moxibustion and electroacupuncture treatments respectively, once every day, lasting for 14 d. The morphological variations of rat's colonic mucosa were observed under light microscope; the colonic mucosal mucin was detected by PAS-AB and HID-AB staining methods; the expression of IGF-1 and SOCS2 was assayed by the immunohistochemical method. Results: In the rat models of UC, ulceration and inflammation of the colon were revealed by light microscope. The concentration of colonic mucosal mucin was reduced (P〈0.01), while the expression of IGF-1 had an increase (P〈0.01), and the expression of SOCS2 was reduced (P〈0.01). After HPM or EA treatment, the pathological injuries of colonic mucosa had improved, the concentration of mucin increased (P〈0.01), the expression of IGF-1 decreased (P〈0.01), and the expression of SOCS2 increased (P〈0.01). Conclusion: The secretion of mucosal mucin in rat UC decreased, the expression of IGF-1 was significantly higher, while the expression of SOCS2 was remarkably lower; both HPM and EA can help improve the damage of colonic mucosa in rat UC, and modulate the secretion of mucin, as well as regulate the expression of IGF-1 and SOCS2 in the colonic mucosa.