The expression of the products of IGF-Ⅱ,IGF-Ⅱ receptors(IGF-Ⅱ-R)and CSF-Ⅰ re-ceptors(CSF-Ⅰ-R)was observed in 17 cases of human primary hepatocellular carcinoma(PHC)and the juxtacancerous liver tissue with immunoh...The expression of the products of IGF-Ⅱ,IGF-Ⅱ receptors(IGF-Ⅱ-R)and CSF-Ⅰ re-ceptors(CSF-Ⅰ-R)was observed in 17 cases of human primary hepatocellular carcinoma(PHC)and the juxtacancerous liver tissue with immunohistochemistry(ABC),Western blot and North-ern blot technique,It was found that the expression of IGF-Ⅱ,IGF-Ⅱ-R and CSF-Ⅰ-R was signif-icantly higher in PHC than in normal liver tissue and the expression of IGF-Ⅱ and IGF-Ⅱ-R wasremarkably higher in the juxtacancerous liver tissue from PHC patients than in PHC proper.Itwas noteworthy that the expression of IGF-Ⅱ in both the cancer proper and the juxtacancerousliver tissue was characterized by its fetal type.Besides,the expression of CSF-Ⅰ-R was signifi-cantly higher in PHC than in the juxtacancerous liver tissue.It is believed that the abnormal ex-pression of IGF-Ⅱ,IGF-Ⅱ-R and CSF-I-R in PHC and the juxtacaneerous liver tissue might berelated to the autocrine mechanism of human PHC.展开更多
AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant...AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant hepatic failure （FHF）. METHODS： FHF was induced by lipopolysaccharide （LPS） in D-galactosamine （GAIN） sensitized BALB/c mice. There were 20 mice in normal saline （NS）-treated group, 20 mice in LPS-treated group, 20 mice in GaIN- treated group, and 60 mice in GalN/LPS-treated group （FHF group）. Liver and kidney tissues were obtained at 2, 6, and 9 h after administration. The liver and kidney specimens were stained with hematoxylin-eosin for studying morphological changes under light microscope. The expression of IP3R I in kidney tissue was tested by immunohistochemistry, Western blot and reverse transcription （RT）-PCR. RESULTS： Kidney tissues were morphologically normal at all time points in all groups. IP3R I proteins were found localized in the plasma region of glomerular mesangial cells （GMC） and vascular smooth muscle cells （VSMC） in kidney by immunohistochemical staining. In kidney of mice with FHF at 6 h and 9 h IP3R I staining was upregulated. Results from Western blot demonstrated consistent and significant increment of IP3R I expression in mice with FHF at 6 h and 9 h （t = 3.16, P 〈 0.05; t = 5.43, P 〈 0.01）. Furthermore, we evaluated IP3R I mRNA expression by RT-PCR and observed marked upregulation of IP3R I mRNA in FHF samples at 2 h, 6 h and 9 h compared to controls （t = 2.97, P 〈 0.05; t = 4.42, P 〈 0.01; t = 3.81, P 〈 0.01）. CONCLUSION： The expression of IP3R I protein increased in GMC and renal VSMC of mice with FHF, possibly caused by up-regulation of IP3R I mRNA.展开更多
Retinoic acid-inducible gene Ⅰ (RIG-Ⅰ) and melanoma differentiation-associated protein 5 (MDA5) sense viral RNA and activate antiviral immune responses.Herein we investigate their functions in human epithelial cells...Retinoic acid-inducible gene Ⅰ (RIG-Ⅰ) and melanoma differentiation-associated protein 5 (MDA5) sense viral RNA and activate antiviral immune responses.Herein we investigate their functions in human epithelial cells,the primary and initial target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).A deficiency in MDA5,RIG-Ⅰ or mitochondrial antiviral signaling protein (MAVS) enhanced viral replication.The expression of the type I/III interferon(IFN) during infection was impaired in MDA5;and MAVS;,but not in RIG-Ⅰ;,when compared to wild type (WT) cells.The mRNA level of full-length angiotensin-converting enzyme 2 (ACE2),the cellular entry receptor for SARS-CoV-2,was approximately 2.5-fold higher in RIG-Ⅰ;than WT cells.These data demonstrate MDA5 as the predominant SARS-CoV-2 sensor,IFN-independent induction of ACE2 and anti-SARS-CoV-2 role of RIG-Ⅰ in epithelial cells.展开更多
AIM: To investigate the molecular mechanisms underlying the reversal effect of emodin on platinum resistance in hepatocellular carcinoma. METHODS: After the addition of 10 μmol/L emodin to HepG2/oxaliplatin (OXA) cel...AIM: To investigate the molecular mechanisms underlying the reversal effect of emodin on platinum resistance in hepatocellular carcinoma. METHODS: After the addition of 10 μmol/L emodin to HepG2/oxaliplatin (OXA) cells, the inhibition rate (IR), 50% inhibitory concentration (IC 50 ) and reversal index (IC 50 in experimental group/IC 50 in control group) were calculated. For HepG2, HepG2/OXA, HepG2/OXA/T, each cell line was divided into a control group, OXA group, OXA + fibroblast growth factor 7 (FGF7) group and OXA + emodin group, and the final concentrations of FGF7, emodin and OXA in each group were 5 ng/mL, 10 μg/mL and 10 μmol/L, respectively. Single-cell gel electrophoresis was conducted to detect DNA damage, and the fibroblast growth factor receptor 2 (FGFR2), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and excision repair cross-complementing gene 1 (ERCC1) protein expression levels in each group were examined by Western blotting. RESULTS: Compared with the IC50 of 120.78 μmol/L in HepG2/OXA cells, the IC 50 decreased to 39.65 μmol/L after treatment with 10 μmol/L emodin; thus, the reversal index was 3.05. Compared with the control group, the tail length and Olive tail length in the OXA group, OXA + FGF7 group and OXA + emodin group were significantly increased, and the differences were statistically significant (P < 0.01). The tail length and Olive tail length were lower in the OXA + FGF7 group than in the OXA group, and this difference was also statistically significant. Compared with the OXA + FGF7 group, the tail extent, the Olive tail moment and the percentage of tail DNA were significantly increased in the OXA + emodin group, and these differences were statistically significant (P < 0.01). In comparison with its parental cell line HepG2, the HepG2/OXA cells demonstrated significantly increased FGFR2, p-ERK1/2 and ERCC1 expression levels, whereas the expression of all three molecules was significantly inhibited in HepG2/ OXA/T cells, in which FGFR2 was silenced by FGFR2 shRNA. In the examined HepG2 cells, the FGFR2, p-ERK1/2 and ERCC1 expression levels demonstrated increasing trends in the OXA group and OXA + FGF7 group. Compared with the OXA group and OXA + FGF7 group, the FGFR2, p-ERK1/2, and ERCC1 expression levels were significantly lower in the OXA + emodin group, and these differences were statistically significant. In the HepG2/OXA/T cell line that was transfected with FGFR2 shRNA, the FGFR2, p-ERK1/2 and ERCC1 expression levels were significantly inhibited, but there were no significant differences in these expression levels among the OXA, OXA + FGF7 and OXA + emodin groups. CONCLUSION: Emodin markedly reversed OXA resistance by enhancing OXA DNA damage in HepG2/OXA cells, and the molecular mechanism was related to the inhibitory effect on ERCC1 expression being mediated by the FGFR2/ERK1/2 signaling pathway.展开更多
Objective To study the effect of Asparagus officinalis polysaccharide on the number and activity of erythrocyte complement receptor 1 in S180 mice.Methods Red blood cells from mice venous blood were labeled by rat ant...Objective To study the effect of Asparagus officinalis polysaccharide on the number and activity of erythrocyte complement receptor 1 in S180 mice.Methods Red blood cells from mice venous blood were labeled by rat anti-mouse CD35 monoclonal antibody and FITC-conjugated goat anti-mouse antibody.Using flow cytometry,we determined the number of ECR1.Using microscope,we studied the adherence between erythrocyte immunity and C3b receptor or tumor-cell by RBC-C3bRR and DTER.Results Comparing the mean value of the number of CR1 on each RBC of high and middle groups with control groups,the mean value of the number of CR1,RBC-C3bRR and DTER of Asparagus officinalis polysaccharide groups are increased significantly.Conclusions Asparagus officinalis polysaccharide can improve the erythrocyte function of S180 mice,which may be one of its most important antitumor mechanisms.展开更多
The study was carried out to observe the effects of heparin,dexamethasone and ibuprofen on the clearance function of the Kupffer cell complement receptors(KCCR) in experimental acute obstructive cholangitis (AOC) in r...The study was carried out to observe the effects of heparin,dexamethasone and ibuprofen on the clearance function of the Kupffer cell complement receptors(KCCR) in experimental acute obstructive cholangitis (AOC) in rats.It was found that in AOC,the mortality rate was far higher in not treated group and dexamethasone treated group than in ibuprofen and heparin treated groups and the clearance function of KCCR was significantly decreased 48h after the onset of AOC but it was strengthened with the administration of heparin and ibuprofen.The prominent pathological changes of AOC were the damages on the hepatocytes,degeneration of Kupffer cells with reduction of their functions and damages of the pulmonary alveolar walls. The phagocytic function of Kupffer cells were restored and damages of the liver and lungs abated after the administration of heparin.This study was financially suppoited by the National Funds for Natural Science of China (Approval certificate numberof NSFC 38870770).展开更多
Atypical hemolytic-uremic syndrome(a HUS) is a rare disease of complement dysregulation leading to thrombotic microangiopathy(TMA). Renal involvement and progression to end-stage renal disease are common in untreated ...Atypical hemolytic-uremic syndrome(a HUS) is a rare disease of complement dysregulation leading to thrombotic microangiopathy(TMA). Renal involvement and progression to end-stage renal disease are common in untreated patients. We report a 52-year-old female patient who presented with severe acute kidney injury, microangiopathic hemolytic anemia, and thrombocytopenia. She was managed with steroid, plasma exchange, and dialysis. Kidney biopsy shows TMA and renal cortical necrosis. Genetic analysis reveals heterozygous complement factor Ⅰ(CFI) mutation. Eculizumab was initiated after 3 mo of presentation, continued for 9 mo, and stopped because of sustained hematologic remission, steady renal function, and cost issues. Despite this, the patient continued to be in hematologic remission and showed signs of renal recovery, and peritoneal dialysis was stopped 32 mo after initiation. We report a case of a HUS due to CFI mutation, which, to the best of our knowledge, has not been reported before in Saudi Arabia. Our case illustrates the challenges related to the diagnosis and management of this condition, in which a high index of suspicion and prompt treatment are usually necessary.展开更多
基金This project was financially aided by the National"Seven-Five"Research Funds of China
文摘The expression of the products of IGF-Ⅱ,IGF-Ⅱ receptors(IGF-Ⅱ-R)and CSF-Ⅰ re-ceptors(CSF-Ⅰ-R)was observed in 17 cases of human primary hepatocellular carcinoma(PHC)and the juxtacancerous liver tissue with immunohistochemistry(ABC),Western blot and North-ern blot technique,It was found that the expression of IGF-Ⅱ,IGF-Ⅱ-R and CSF-Ⅰ-R was signif-icantly higher in PHC than in normal liver tissue and the expression of IGF-Ⅱ and IGF-Ⅱ-R wasremarkably higher in the juxtacancerous liver tissue from PHC patients than in PHC proper.Itwas noteworthy that the expression of IGF-Ⅱ in both the cancer proper and the juxtacancerousliver tissue was characterized by its fetal type.Besides,the expression of CSF-Ⅰ-R was signifi-cantly higher in PHC than in the juxtacancerous liver tissue.It is believed that the abnormal ex-pression of IGF-Ⅱ,IGF-Ⅱ-R and CSF-I-R in PHC and the juxtacaneerous liver tissue might berelated to the autocrine mechanism of human PHC.
基金Supported by National Natural Science Foundation of China, No. 30270607
文摘AIM： To delineate the mechanisms of renal vasoconstriction in hepatorenal syndrome （HRS）, we investigated the expression of type I inositol 1, 4, 5-triphosphate receptors （IP3R I） of kidney in mice with fulminant hepatic failure （FHF）. METHODS： FHF was induced by lipopolysaccharide （LPS） in D-galactosamine （GAIN） sensitized BALB/c mice. There were 20 mice in normal saline （NS）-treated group, 20 mice in LPS-treated group, 20 mice in GaIN- treated group, and 60 mice in GalN/LPS-treated group （FHF group）. Liver and kidney tissues were obtained at 2, 6, and 9 h after administration. The liver and kidney specimens were stained with hematoxylin-eosin for studying morphological changes under light microscope. The expression of IP3R I in kidney tissue was tested by immunohistochemistry, Western blot and reverse transcription （RT）-PCR. RESULTS： Kidney tissues were morphologically normal at all time points in all groups. IP3R I proteins were found localized in the plasma region of glomerular mesangial cells （GMC） and vascular smooth muscle cells （VSMC） in kidney by immunohistochemical staining. In kidney of mice with FHF at 6 h and 9 h IP3R I staining was upregulated. Results from Western blot demonstrated consistent and significant increment of IP3R I expression in mice with FHF at 6 h and 9 h （t = 3.16, P 〈 0.05; t = 5.43, P 〈 0.01）. Furthermore, we evaluated IP3R I mRNA expression by RT-PCR and observed marked upregulation of IP3R I mRNA in FHF samples at 2 h, 6 h and 9 h compared to controls （t = 2.97, P 〈 0.05; t = 4.42, P 〈 0.01; t = 3.81, P 〈 0.01）. CONCLUSION： The expression of IP3R I protein increased in GMC and renal VSMC of mice with FHF, possibly caused by up-regulation of IP3R I mRNA.
基金supported by a National Institutes of Health grant (No. R01AI132526)a UConn Health Startup fund to Wang P。
文摘Retinoic acid-inducible gene Ⅰ (RIG-Ⅰ) and melanoma differentiation-associated protein 5 (MDA5) sense viral RNA and activate antiviral immune responses.Herein we investigate their functions in human epithelial cells,the primary and initial target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).A deficiency in MDA5,RIG-Ⅰ or mitochondrial antiviral signaling protein (MAVS) enhanced viral replication.The expression of the type I/III interferon(IFN) during infection was impaired in MDA5;and MAVS;,but not in RIG-Ⅰ;,when compared to wild type (WT) cells.The mRNA level of full-length angiotensin-converting enzyme 2 (ACE2),the cellular entry receptor for SARS-CoV-2,was approximately 2.5-fold higher in RIG-Ⅰ;than WT cells.These data demonstrate MDA5 as the predominant SARS-CoV-2 sensor,IFN-independent induction of ACE2 and anti-SARS-CoV-2 role of RIG-Ⅰ in epithelial cells.
基金Supported by National Natural Sciences Foundation of China,No. 81001067the Ministry of Science and Technology International Cooperation Project, No. 2010DFA31870the AstraZeneca Special Research Foundation for Targeted Therapy of the Wu Jieping Medical Foundation, No. 320.6700.09068
文摘AIM: To investigate the molecular mechanisms underlying the reversal effect of emodin on platinum resistance in hepatocellular carcinoma. METHODS: After the addition of 10 μmol/L emodin to HepG2/oxaliplatin (OXA) cells, the inhibition rate (IR), 50% inhibitory concentration (IC 50 ) and reversal index (IC 50 in experimental group/IC 50 in control group) were calculated. For HepG2, HepG2/OXA, HepG2/OXA/T, each cell line was divided into a control group, OXA group, OXA + fibroblast growth factor 7 (FGF7) group and OXA + emodin group, and the final concentrations of FGF7, emodin and OXA in each group were 5 ng/mL, 10 μg/mL and 10 μmol/L, respectively. Single-cell gel electrophoresis was conducted to detect DNA damage, and the fibroblast growth factor receptor 2 (FGFR2), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) and excision repair cross-complementing gene 1 (ERCC1) protein expression levels in each group were examined by Western blotting. RESULTS: Compared with the IC50 of 120.78 μmol/L in HepG2/OXA cells, the IC 50 decreased to 39.65 μmol/L after treatment with 10 μmol/L emodin; thus, the reversal index was 3.05. Compared with the control group, the tail length and Olive tail length in the OXA group, OXA + FGF7 group and OXA + emodin group were significantly increased, and the differences were statistically significant (P < 0.01). The tail length and Olive tail length were lower in the OXA + FGF7 group than in the OXA group, and this difference was also statistically significant. Compared with the OXA + FGF7 group, the tail extent, the Olive tail moment and the percentage of tail DNA were significantly increased in the OXA + emodin group, and these differences were statistically significant (P < 0.01). In comparison with its parental cell line HepG2, the HepG2/OXA cells demonstrated significantly increased FGFR2, p-ERK1/2 and ERCC1 expression levels, whereas the expression of all three molecules was significantly inhibited in HepG2/ OXA/T cells, in which FGFR2 was silenced by FGFR2 shRNA. In the examined HepG2 cells, the FGFR2, p-ERK1/2 and ERCC1 expression levels demonstrated increasing trends in the OXA group and OXA + FGF7 group. Compared with the OXA group and OXA + FGF7 group, the FGFR2, p-ERK1/2, and ERCC1 expression levels were significantly lower in the OXA + emodin group, and these differences were statistically significant. In the HepG2/OXA/T cell line that was transfected with FGFR2 shRNA, the FGFR2, p-ERK1/2 and ERCC1 expression levels were significantly inhibited, but there were no significant differences in these expression levels among the OXA, OXA + FGF7 and OXA + emodin groups. CONCLUSION: Emodin markedly reversed OXA resistance by enhancing OXA DNA damage in HepG2/OXA cells, and the molecular mechanism was related to the inhibitory effect on ERCC1 expression being mediated by the FGFR2/ERK1/2 signaling pathway.
文摘Objective To study the effect of Asparagus officinalis polysaccharide on the number and activity of erythrocyte complement receptor 1 in S180 mice.Methods Red blood cells from mice venous blood were labeled by rat anti-mouse CD35 monoclonal antibody and FITC-conjugated goat anti-mouse antibody.Using flow cytometry,we determined the number of ECR1.Using microscope,we studied the adherence between erythrocyte immunity and C3b receptor or tumor-cell by RBC-C3bRR and DTER.Results Comparing the mean value of the number of CR1 on each RBC of high and middle groups with control groups,the mean value of the number of CR1,RBC-C3bRR and DTER of Asparagus officinalis polysaccharide groups are increased significantly.Conclusions Asparagus officinalis polysaccharide can improve the erythrocyte function of S180 mice,which may be one of its most important antitumor mechanisms.
文摘The study was carried out to observe the effects of heparin,dexamethasone and ibuprofen on the clearance function of the Kupffer cell complement receptors(KCCR) in experimental acute obstructive cholangitis (AOC) in rats.It was found that in AOC,the mortality rate was far higher in not treated group and dexamethasone treated group than in ibuprofen and heparin treated groups and the clearance function of KCCR was significantly decreased 48h after the onset of AOC but it was strengthened with the administration of heparin and ibuprofen.The prominent pathological changes of AOC were the damages on the hepatocytes,degeneration of Kupffer cells with reduction of their functions and damages of the pulmonary alveolar walls. The phagocytic function of Kupffer cells were restored and damages of the liver and lungs abated after the administration of heparin.This study was financially suppoited by the National Funds for Natural Science of China (Approval certificate numberof NSFC 38870770).
文摘Atypical hemolytic-uremic syndrome(a HUS) is a rare disease of complement dysregulation leading to thrombotic microangiopathy(TMA). Renal involvement and progression to end-stage renal disease are common in untreated patients. We report a 52-year-old female patient who presented with severe acute kidney injury, microangiopathic hemolytic anemia, and thrombocytopenia. She was managed with steroid, plasma exchange, and dialysis. Kidney biopsy shows TMA and renal cortical necrosis. Genetic analysis reveals heterozygous complement factor Ⅰ(CFI) mutation. Eculizumab was initiated after 3 mo of presentation, continued for 9 mo, and stopped because of sustained hematologic remission, steady renal function, and cost issues. Despite this, the patient continued to be in hematologic remission and showed signs of renal recovery, and peritoneal dialysis was stopped 32 mo after initiation. We report a case of a HUS due to CFI mutation, which, to the best of our knowledge, has not been reported before in Saudi Arabia. Our case illustrates the challenges related to the diagnosis and management of this condition, in which a high index of suspicion and prompt treatment are usually necessary.
