Independent of their etiology, all chronic liver diseases ultimately lead to liver cirrhosis, which is a majorhealth problem worldwide. The underlying molecular mechanisms are still poorly understood and no efficient ...Independent of their etiology, all chronic liver diseases ultimately lead to liver cirrhosis, which is a majorhealth problem worldwide. The underlying molecular mechanisms are still poorly understood and no efficient treatment strategies are available. This paper introduces the sinusoidal pressure hypothesis(SPH), which identifies an elevated sinusoidal pressure(SP) as cause of fibrosis. SPH has been mainly derived from recent studies on liver stiffness. So far, pressure changes have been exclusively seen as a consequ-ence of cirrhosis. According to the SPH, however, an elevated SP is the major upstream event that initiates fibrosis via biomechanic signaling by stretching of perisinusoidal cells such as hepatic stellate cells or fibroblasts(SPH part?Ⅰ: initiation). Fibrosis progression is determined by the degree and time of elevated SP. The SPH predicts that the degree of extracellular matrix eventually matches SP with critical thresholds > 12 mmH g and > 4 wk. Elevated arterial flow and final arterialization of the cirrhotic liver represents the self-perpetuating key event exposing the low-pressure-organ to pathologically high pressures(SPH part?Ⅱ: perpetuation). It also defines the "point of no return" where fibrosis progression becomes irreversible. The SPH is able to explain the macroscopic changes of cirrhotic livers and the uniform fibrotic response to various etiologies. It also opens up new views on the role of fat and disease mechanisms in other organs. The novel concept will hopefully stimulate the search for new treatment strategies.展开更多
The static O-H bond parameters including O-H bond length, O-H charge difference, O-H Mulliken population and O-H bond stretching force constant (k) for 17 phenols were calculated by ab initio method HF/6-31G**. In com...The static O-H bond parameters including O-H bond length, O-H charge difference, O-H Mulliken population and O-H bond stretching force constant (k) for 17 phenols were calculated by ab initio method HF/6-31G**. In combination with the O-H bond dissociation enthalpies (BDE) of the phenols determined by experiment, it was found that there were poor correlationships between the static O-H bond parameters and O-H BDE. Considering the good correlationship bt tween O-H BDE and logarithm of free radical scavenging rate constant for phenolic antioxidant, it is reasonable to believe that the ineffectiveness of static O-H bond parameters in characterizing antioxidant activity arises from the fact that they cannot measure the O-H BDE.展开更多
文摘Independent of their etiology, all chronic liver diseases ultimately lead to liver cirrhosis, which is a majorhealth problem worldwide. The underlying molecular mechanisms are still poorly understood and no efficient treatment strategies are available. This paper introduces the sinusoidal pressure hypothesis(SPH), which identifies an elevated sinusoidal pressure(SP) as cause of fibrosis. SPH has been mainly derived from recent studies on liver stiffness. So far, pressure changes have been exclusively seen as a consequ-ence of cirrhosis. According to the SPH, however, an elevated SP is the major upstream event that initiates fibrosis via biomechanic signaling by stretching of perisinusoidal cells such as hepatic stellate cells or fibroblasts(SPH part?Ⅰ: initiation). Fibrosis progression is determined by the degree and time of elevated SP. The SPH predicts that the degree of extracellular matrix eventually matches SP with critical thresholds > 12 mmH g and > 4 wk. Elevated arterial flow and final arterialization of the cirrhotic liver represents the self-perpetuating key event exposing the low-pressure-organ to pathologically high pressures(SPH part?Ⅱ: perpetuation). It also defines the "point of no return" where fibrosis progression becomes irreversible. The SPH is able to explain the macroscopic changes of cirrhotic livers and the uniform fibrotic response to various etiologies. It also opens up new views on the role of fat and disease mechanisms in other organs. The novel concept will hopefully stimulate the search for new treatment strategies.
文摘The static O-H bond parameters including O-H bond length, O-H charge difference, O-H Mulliken population and O-H bond stretching force constant (k) for 17 phenols were calculated by ab initio method HF/6-31G**. In combination with the O-H bond dissociation enthalpies (BDE) of the phenols determined by experiment, it was found that there were poor correlationships between the static O-H bond parameters and O-H BDE. Considering the good correlationship bt tween O-H BDE and logarithm of free radical scavenging rate constant for phenolic antioxidant, it is reasonable to believe that the ineffectiveness of static O-H bond parameters in characterizing antioxidant activity arises from the fact that they cannot measure the O-H BDE.