In recent decades, biotechnology produced a growth of knowledge on the causes and mechanisms of metabolic diseases that have formed the basis for their study, diagnosis and treatment. Unfortunately, it is well known t...In recent decades, biotechnology produced a growth of knowledge on the causes and mechanisms of metabolic diseases that have formed the basis for their study, diagnosis and treatment. Unfortunately, it is well known that the clinical features of metabolic diseases can manifest themselves with very different characteristics and escape early detection. Also, it is well known that the prognosis of many metabolic diseases is excellent if diagnosed and treated early. In this editorial we briefly summarized two groups of inherited metabolic diseases, the defects of cholesterol biosynthesis and those of bile acids. Both groups show variable clinical manifestations but some clinical signs and symptoms are common in both the defects of cholesterol and bile acids. The differential diagnosis can be made analyzing sterol profiles in blood and/or bile acids in blood and urine by chromatographic techniques(GC-MS and LC-MS/MS). Several defects of both biosynthetic pathways are treatable so early diagnosis is crucial. Unfortunately their diagnosis is made too late, due either to the clinical heterogeneity of the syndromes(severe, mild and very mild) that to the scarcity of scientific dissemination of these rare diseases. Therefore, the delay in diagnosis leads the patient to the medical observation when the disease has produced irreversible damages to the body. Here, we highlighted simple clinical and laboratory descriptions that can potentially make you to suspect a defect in cholesterol biosynthesis and/or bile acids, as well, we suggest appropriate request of the laboratory tests that along with common clinical features can help to diagnose these defects.展开更多
Hepatitis B virus X protein （HBx） plays a crucial role in the development of hepatocellular carcinoma. Here, we sought to identify the mechanisms by which HBx mediates liver cell proliferation. We found that HBx upr...Hepatitis B virus X protein （HBx） plays a crucial role in the development of hepatocellular carcinoma. Here, we sought to identify the mechanisms by which HBx mediates liver cell proliferation. We found that HBx upregulated the levels of cyclooxygenase-2 （COX-2）, 5-1ipoxygenase （5-LOX） and phosphorylated extracellular signal-regulated protein kinases 1/2 （p-ERK1/2） in liver cells. HBx-induced p-ERK1/2 was abolished by inhibition of Gi/o proteins, COX or LOX. In addition, HBx increased the amounts of prostaglandin E2 （PGE2） and leukotriene B4 （LTB4） released from cell lines derived from hepatocytes. Moreover, these released arachidonic acid metabolites were able to activate ERK1/2. Interestingly, activated ERK1/2 could upregulate the expression of COX-2 and 5-LOX in a positive feedback manner. In conclusion, HBx enhances and maintains liver cell proliferation via a positive feedback loop involving COX-2, 5-LOX, released arachidonic acid metabolites, Gi/o proteins and p-ERK1/2.展开更多
文摘In recent decades, biotechnology produced a growth of knowledge on the causes and mechanisms of metabolic diseases that have formed the basis for their study, diagnosis and treatment. Unfortunately, it is well known that the clinical features of metabolic diseases can manifest themselves with very different characteristics and escape early detection. Also, it is well known that the prognosis of many metabolic diseases is excellent if diagnosed and treated early. In this editorial we briefly summarized two groups of inherited metabolic diseases, the defects of cholesterol biosynthesis and those of bile acids. Both groups show variable clinical manifestations but some clinical signs and symptoms are common in both the defects of cholesterol and bile acids. The differential diagnosis can be made analyzing sterol profiles in blood and/or bile acids in blood and urine by chromatographic techniques(GC-MS and LC-MS/MS). Several defects of both biosynthetic pathways are treatable so early diagnosis is crucial. Unfortunately their diagnosis is made too late, due either to the clinical heterogeneity of the syndromes(severe, mild and very mild) that to the scarcity of scientific dissemination of these rare diseases. Therefore, the delay in diagnosis leads the patient to the medical observation when the disease has produced irreversible damages to the body. Here, we highlighted simple clinical and laboratory descriptions that can potentially make you to suspect a defect in cholesterol biosynthesis and/or bile acids, as well, we suggest appropriate request of the laboratory tests that along with common clinical features can help to diagnose these defects.
文摘Hepatitis B virus X protein （HBx） plays a crucial role in the development of hepatocellular carcinoma. Here, we sought to identify the mechanisms by which HBx mediates liver cell proliferation. We found that HBx upregulated the levels of cyclooxygenase-2 （COX-2）, 5-1ipoxygenase （5-LOX） and phosphorylated extracellular signal-regulated protein kinases 1/2 （p-ERK1/2） in liver cells. HBx-induced p-ERK1/2 was abolished by inhibition of Gi/o proteins, COX or LOX. In addition, HBx increased the amounts of prostaglandin E2 （PGE2） and leukotriene B4 （LTB4） released from cell lines derived from hepatocytes. Moreover, these released arachidonic acid metabolites were able to activate ERK1/2. Interestingly, activated ERK1/2 could upregulate the expression of COX-2 and 5-LOX in a positive feedback manner. In conclusion, HBx enhances and maintains liver cell proliferation via a positive feedback loop involving COX-2, 5-LOX, released arachidonic acid metabolites, Gi/o proteins and p-ERK1/2.
