High-intensity focused ultrasound(HIFU)is a noninvasive modality that uses an extracorporeal source of focused ultrasound energy.This technique was introduced by Lynn et al and is able to induce coagulative necrosis i...High-intensity focused ultrasound(HIFU)is a noninvasive modality that uses an extracorporeal source of focused ultrasound energy.This technique was introduced by Lynn et al and is able to induce coagulative necrosis in selected tissues without damaging adjacent structures.Although HIFU has been studied for 50years,recent technological developments now allow its use for tumours of the liver,prostate and other sites.In liver disease,HIFU has been used to treat unresectable,advanced stages of hepatocellular carcinoma(HCC)and liver metastases.Hepatocellular carcinoma is a serious health problem worldwide and is endemic in some areas because of its association with hepatitis B and C viruses(in 20%of cases).Liver transplantation(LT)has become one of the best treatments available because it removes both the tumour and the underlying liver disease such as cirrhosis(which is present in approximately 80%of cases).The prerequisite for longterm transplant success depends on tumour load and strict selection criteria regarding the size and number of tumour nodules.The need to obtain the optimal benefit from the limited number of organs available has prompted strict selection criteria limited to only those patients with early HCC who have a better long-term outcome after LT.The so-called"bridging therapy"has the aim of controlling disease burden for patients who are on the organ transplant waiting list.Amongst various treatment options,transarterial chemoembolisation and radiofrequency ablation are the most popular treatment choices.Recently,Cheung et al demonstrated that HIFU ablation is a safe and effective method for the treatment of HCC patients with advanced cirrhosis as a bridging therapy and that it reduced the dropout rate from the liver transplant waiting list.In this commentary,we discuss the current value of HIFU in the treatment of liver disease,including its value as a bridging therapy,and examine the potential advantages of other therapeutic strategies.展开更多
In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal eco...In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome(IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial(Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful(Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required.展开更多
AIM: To investigate whether the farnesoid X receptor (FXR) regulates expression of liver cystathionase (CSE), a gene involved in hydrogen sulfi de (H2S) generation. METHODS: The regulation of CSE expression in respons...AIM: To investigate whether the farnesoid X receptor (FXR) regulates expression of liver cystathionase (CSE), a gene involved in hydrogen sulfi de (H2S) generation. METHODS: The regulation of CSE expression in response to FXR ligands was evaluated in HepG2 cells and in wild-type and FXR null mice treated with 6-ethyl chenodeoxycholic acid (6E-CDCA), a synthetic FXR ligand. The analysis demonstrated an FXR responsive element in the 5'-flanking region of the human CSE gene. The function of this site was investigated by luciferase reporter assays, chromatin immunoprecipitation and electrophoretic mobility shift assays. Livers obtained from rats treated with carbon tetrachloride alone, or in combination with 6-ethyl chenodeoxycholic acid, were studied for hydrogen sulphide generation and portal pressure measurement. RESULTS: Liver expression of CSE is regulated by bile acids by means of an FXR-mediated mechanism. Western blotting, qualitative and quantitative polymerase chain reaction, as well as immunohistochemical analysis, showed that expression of CSE in HepG2 cells and in mice is induced by treatment with an FXR ligand. Administration of 6E-CDCA to carbon tetrachloride treated rats protected against the down-regulation of CSE expression, increased H2S generation, reduced portal pressure and attenuated the endothelial dysfunction of isolated and perfused cirrhotic rat livers. CONCLUSION: These results demonstrate that CSE is an FXR-regulated gene and provide a new molecular explanation for the pathophysiology of portal hypertension.展开更多
文摘High-intensity focused ultrasound(HIFU)is a noninvasive modality that uses an extracorporeal source of focused ultrasound energy.This technique was introduced by Lynn et al and is able to induce coagulative necrosis in selected tissues without damaging adjacent structures.Although HIFU has been studied for 50years,recent technological developments now allow its use for tumours of the liver,prostate and other sites.In liver disease,HIFU has been used to treat unresectable,advanced stages of hepatocellular carcinoma(HCC)and liver metastases.Hepatocellular carcinoma is a serious health problem worldwide and is endemic in some areas because of its association with hepatitis B and C viruses(in 20%of cases).Liver transplantation(LT)has become one of the best treatments available because it removes both the tumour and the underlying liver disease such as cirrhosis(which is present in approximately 80%of cases).The prerequisite for longterm transplant success depends on tumour load and strict selection criteria regarding the size and number of tumour nodules.The need to obtain the optimal benefit from the limited number of organs available has prompted strict selection criteria limited to only those patients with early HCC who have a better long-term outcome after LT.The so-called"bridging therapy"has the aim of controlling disease burden for patients who are on the organ transplant waiting list.Amongst various treatment options,transarterial chemoembolisation and radiofrequency ablation are the most popular treatment choices.Recently,Cheung et al demonstrated that HIFU ablation is a safe and effective method for the treatment of HCC patients with advanced cirrhosis as a bridging therapy and that it reduced the dropout rate from the liver transplant waiting list.In this commentary,we discuss the current value of HIFU in the treatment of liver disease,including its value as a bridging therapy,and examine the potential advantages of other therapeutic strategies.
文摘In the last decade the impressive expansion of our knowledge of the vast microbial community that resides in the human intestine, the gut microbiota, has provided support to the concept that a disturbed intestinal ecology might promote development and maintenance of symptoms in irritable bowel syndrome(IBS). As a correlate, manipulation of gut microbiota represents a new strategy for the treatment of this multifactorial disease. A number of attempts have been made to modulate the gut bacterial composition, following the idea that expansion of bacterial species considered as beneficial(Lactobacilli and Bifidobacteria) associated with the reduction of those considered harmful(Clostridium, Escherichia coli, Salmonella, Shigella and Pseudomonas) should attenuate IBS symptoms. In this conceptual framework, probiotics appear an attractive option in terms of both efficacy and safety, while prebiotics, synbiotics and antibiotics still need confirmation. Fecal transplant is an old treatment translated from the cure of intestinal infective pathologies that has recently gained a new life as therapeutic option for those patients with a disturbed gut ecosystem, but data on IBS are scanty and randomized, placebo-controlled studies are required.
文摘AIM: To investigate whether the farnesoid X receptor (FXR) regulates expression of liver cystathionase (CSE), a gene involved in hydrogen sulfi de (H2S) generation. METHODS: The regulation of CSE expression in response to FXR ligands was evaluated in HepG2 cells and in wild-type and FXR null mice treated with 6-ethyl chenodeoxycholic acid (6E-CDCA), a synthetic FXR ligand. The analysis demonstrated an FXR responsive element in the 5'-flanking region of the human CSE gene. The function of this site was investigated by luciferase reporter assays, chromatin immunoprecipitation and electrophoretic mobility shift assays. Livers obtained from rats treated with carbon tetrachloride alone, or in combination with 6-ethyl chenodeoxycholic acid, were studied for hydrogen sulphide generation and portal pressure measurement. RESULTS: Liver expression of CSE is regulated by bile acids by means of an FXR-mediated mechanism. Western blotting, qualitative and quantitative polymerase chain reaction, as well as immunohistochemical analysis, showed that expression of CSE in HepG2 cells and in mice is induced by treatment with an FXR ligand. Administration of 6E-CDCA to carbon tetrachloride treated rats protected against the down-regulation of CSE expression, increased H2S generation, reduced portal pressure and attenuated the endothelial dysfunction of isolated and perfused cirrhotic rat livers. CONCLUSION: These results demonstrate that CSE is an FXR-regulated gene and provide a new molecular explanation for the pathophysiology of portal hypertension.
