AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of...AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.展开更多
AIM:To determine whether mitochondrial dysfunction resulting from high-fat diet is related to impairment of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt,also known as PKB) pathway. METHODS:Rat models...AIM:To determine whether mitochondrial dysfunction resulting from high-fat diet is related to impairment of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt,also known as PKB) pathway. METHODS:Rat models of nonalcoholic fatty liver were established by high-fat diet feeding. The expression of total and phosphorylated P13K and Akt proteins in hepatocytes was determined by Western blotting. Degree of fat accumulation in liver was measured by hepatic triglyceride. Mitochondrial number and size were determined using quantitative morphometric analysis under transmission electron microscope. The permeability of the outer mitochondrial membrane was assessed by determining the potential gradient across this membrane.RESULTS:After Wistar rats were fed with high-fat diet for 16 wk,their hepatocytes displayed an accumulation of fat (103.1 ± 12.6 vs 421.5 ± 19.7,P < 0.01),deformed mitochondria (9.0% ± 4.3% vs 83.0% ± 10.9%,P < 0.05),and a reduction in the mitochondrial membrane potential (389.385% ± 18.612% vs 249.121% ± 13.526%,P < 0.05). In addition,the expression of the phosphorylated P13K and Akt proteins in hepatocytes was reduced,as was the expression of the anti-apoptotic protein Bcl-2,while expression of the pro-apoptotic protein caspase-3 was increased. When animals were treated with pharmacological inhibitors of P13K or Akt,instead of high-fat diet,a similar pattern of hepatocellular fat accumulation,mitochondrial impairment,and change in the levels of PI3K,Akt,Bcl-2 was observed. CONCLUSION:High-fat diet appears to inhibit the PI3K/Akt signaling pathway,which may lead to hepa-tocellular injury through activation of the mitochondrial membrane pathway of apoptosis.展开更多
Abundant studies have been conducted to identify how B-cell translocation gene 1 protein(BTG1)gene affects the differentiation,proliferation,metastasis of cancer cells,and how it further regulates the generation or de...Abundant studies have been conducted to identify how B-cell translocation gene 1 protein(BTG1)gene affects the differentiation,proliferation,metastasis of cancer cells,and how it further regulates the generation or development of diseases to influence the prognosis of patients.However,the data from single research were not powerful enough.The correlations between BTG1 expression and mechanisms of tumorigenesis or prognosis of patients are still in controversial.Our system review and meta-analysis provided a complete explanation about the association between BTG1 expression and clinicopathological features or prognosis of patients,which further laid a foundation for future research on BTG1.Fifteen eligible studies consisting of 1992 participants were included.We uncovered that BTG1 expression in solid tumors was associated w让h lymph node status(RR=0.66,95%CI:0.58-0.75,P=0.142),TMN stage status(RR=2.13,95%CI:1.71-2.65,P=0.001),T category(RR=1.90,95%CI:1.20-3.00,P=0.000),histological differentiation(RR-1.91,95%CI:1.55-2.37,7=0.012),vascular invasion(RR=0.90,95%CI:0.57-1.41,P=0.001).BTG1 low expression was significantly associated with overall survival(OS)(HR=0.47,95%CI:0.38-0.67,P=0.000).It concluded that BTG1 possessed the potential value for future research and could be recommended as a significant biomarker in solid tumor.展开更多
Microphthalmia-associated transcription factor family(transcription factor E3 or transcription factor EB)translocation renal cell carcinomas(RCCs)are rare neoplasms.These renal neoplasms can be either asymptomatic and...Microphthalmia-associated transcription factor family(transcription factor E3 or transcription factor EB)translocation renal cell carcinomas(RCCs)are rare neoplasms.These renal neoplasms can be either asymptomatic and incidentally discovered on imaging or symptomatic,with the most common presenting symptoms being hematuria,pain,and abdominal mass,or paraneoplastic event.In conventional RCCs,hypertension is considered a risk factor and a possible paraneoplastic event,whereas,in translocation RCCs,prior exposure to cytotoxic chemotherapy is the only known risk factor,and hypertension as an isolated associated paraneoplastic event has never been reported.Interestingly,hypertension as the only presenting symptom in RCC is extremely rare.We report a case of transcription factor E3 positive RCC in a young adult presenting only with hypertension that normalized after radical nephrectomy.To the best of our knowledge,this is the first reported case of hypertension secondary to microphthalmia-associated transcription translocation RCC.展开更多
基金Supported by National Natural Science Foundation of China(No.81273212,81100651)Project of Science and Technology of Shandong Province(No.2014GSF118044)
文摘AIM: To investigate into the potential involvement of pyrin containing 3 gene(NLRP3), a member of the nucleotide-binding oligomerization domain-like receptors with cytosolic pattern recognition, in the host defense of corneas against viruses.METHODS: The herpes viral keratitis model was utilized in BALB/c mice with inoculation of herpes simplex virus-1(HSV-1). Corneal tissues removed during therapy of patients with viral keratitis as well as a Simian vacuolating virus 40(SV40)-immortalized human corneal epithelial cell line were also examined.Immunohistochemistry was used to detect NLRP3 in these subjects, focusing on their distribution in tissue or cells. Western blot was used to measure the level of NLRP3 and another two related molecules in NLPR3 inflammasome, namely caspase-1 and IL-1β.RESULTS: The NLRP3 activation induced by HSV-1infection in corneas was accompanied with redistribution of NLRP3 from the cytoplasm to the nucleus in both murine and human corneal epithelial cells. Furthermore,in the SV40-immortalized human corneal epithelial cells,NLRP3 was exclusively located in the nucleus, and treatment of the cells with high concentration of extracellular potassium(known as an inhibitor of NLRP3activation) effectively drove NLRP3 back to the cytoplasm as reflected by both immunohistochemistry and Western blot.· CONCLUSION: It is proposed that herpes virus infection activates and causes redistribution of NLRP3 to nuclei. Whether this NLRP3 translocation occurs with other viral infections and in other cell types merit further study.
基金Supported by The Natural Science Foundation of Heilongjiang Province, No. 2005-13
文摘AIM:To determine whether mitochondrial dysfunction resulting from high-fat diet is related to impairment of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt,also known as PKB) pathway. METHODS:Rat models of nonalcoholic fatty liver were established by high-fat diet feeding. The expression of total and phosphorylated P13K and Akt proteins in hepatocytes was determined by Western blotting. Degree of fat accumulation in liver was measured by hepatic triglyceride. Mitochondrial number and size were determined using quantitative morphometric analysis under transmission electron microscope. The permeability of the outer mitochondrial membrane was assessed by determining the potential gradient across this membrane.RESULTS:After Wistar rats were fed with high-fat diet for 16 wk,their hepatocytes displayed an accumulation of fat (103.1 ± 12.6 vs 421.5 ± 19.7,P < 0.01),deformed mitochondria (9.0% ± 4.3% vs 83.0% ± 10.9%,P < 0.05),and a reduction in the mitochondrial membrane potential (389.385% ± 18.612% vs 249.121% ± 13.526%,P < 0.05). In addition,the expression of the phosphorylated P13K and Akt proteins in hepatocytes was reduced,as was the expression of the anti-apoptotic protein Bcl-2,while expression of the pro-apoptotic protein caspase-3 was increased. When animals were treated with pharmacological inhibitors of P13K or Akt,instead of high-fat diet,a similar pattern of hepatocellular fat accumulation,mitochondrial impairment,and change in the levels of PI3K,Akt,Bcl-2 was observed. CONCLUSION:High-fat diet appears to inhibit the PI3K/Akt signaling pathway,which may lead to hepa-tocellular injury through activation of the mitochondrial membrane pathway of apoptosis.
基金Natural Science Foundation of Hubei Province of China(No.2018CFB611).
文摘Abundant studies have been conducted to identify how B-cell translocation gene 1 protein(BTG1)gene affects the differentiation,proliferation,metastasis of cancer cells,and how it further regulates the generation or development of diseases to influence the prognosis of patients.However,the data from single research were not powerful enough.The correlations between BTG1 expression and mechanisms of tumorigenesis or prognosis of patients are still in controversial.Our system review and meta-analysis provided a complete explanation about the association between BTG1 expression and clinicopathological features or prognosis of patients,which further laid a foundation for future research on BTG1.Fifteen eligible studies consisting of 1992 participants were included.We uncovered that BTG1 expression in solid tumors was associated w让h lymph node status(RR=0.66,95%CI:0.58-0.75,P=0.142),TMN stage status(RR=2.13,95%CI:1.71-2.65,P=0.001),T category(RR=1.90,95%CI:1.20-3.00,P=0.000),histological differentiation(RR-1.91,95%CI:1.55-2.37,7=0.012),vascular invasion(RR=0.90,95%CI:0.57-1.41,P=0.001).BTG1 low expression was significantly associated with overall survival(OS)(HR=0.47,95%CI:0.38-0.67,P=0.000).It concluded that BTG1 possessed the potential value for future research and could be recommended as a significant biomarker in solid tumor.
文摘Microphthalmia-associated transcription factor family(transcription factor E3 or transcription factor EB)translocation renal cell carcinomas(RCCs)are rare neoplasms.These renal neoplasms can be either asymptomatic and incidentally discovered on imaging or symptomatic,with the most common presenting symptoms being hematuria,pain,and abdominal mass,or paraneoplastic event.In conventional RCCs,hypertension is considered a risk factor and a possible paraneoplastic event,whereas,in translocation RCCs,prior exposure to cytotoxic chemotherapy is the only known risk factor,and hypertension as an isolated associated paraneoplastic event has never been reported.Interestingly,hypertension as the only presenting symptom in RCC is extremely rare.We report a case of transcription factor E3 positive RCC in a young adult presenting only with hypertension that normalized after radical nephrectomy.To the best of our knowledge,this is the first reported case of hypertension secondary to microphthalmia-associated transcription translocation RCC.
