Clear cell hepatocellular carcinoma: origin,metabolic traits and fate of glycogenotic clear and ground glass cells

Clear cell hepatocellular carcinoma(CCHCC)has hitherto been considered an uncommon, highly differentiated variant of hepatocellular carcinoma(HCC) with a relatively favorable prognosis. CCHCC is composed of mixtures of clear and/or acidophilic ground glass hepatocytes with excessive glycogen and/or fat and shares histology, clinical features and etiology with common HCCs. Studies in animal models of chemical, hormonal and viral hepatocarcinogenesis and observations in patients with chronic liver diseases prone to develop HCC have shown that the majority of HCCs are preceded by, or associated with, focal or diffuse excessive storage of glycogen(glycogenosis) which later may be replaced by fat(lipidosis/steatosis). In ground glass cells, the glycogenosis is accompanied by proliferation of the smooth endoplasmic reticulum, which is closely related to glycogen particles and frequently harbors the hepatitis B surface antigen(HBs Ag).From the findings in animal models a sequence of changes has been established, commencing with preneoplastic glycogenotic liver lesions, often containing ground glass cells, and progressing to glycogen-poor neoplasms via various intermediate stages, including glycogenotic/lipidotic clear cell foci, clear cell hepatocellular adenomas(CCHCA) rich in glycogen and/or fat, and CCHCC. A similar process seems to take place in humans, with clear cells frequently persisting in CCHCC and steatohepatitic HCC, which presumably represent intermediate stages in the development rather than particular variants of HCC. During the progression of the preneoplastic lesions,the clear and ground glass cells transform into cells characteristic of common HCC. The sequential cellular changes are associated with metabolic aberrations, which start with an activation of the insulin signaling cascade resulting in preneoplastic hepatic glycogenosis. The molecular and metabolic changes underlying the glycogenosis/lipidosis are apparently responsible for the dramatic metabolic shift from gluconeogenesis to the pentose phosphate pathway and Warburg-type glycolysis, which provide precursors and energy for an ever increasing cell proliferation during progression.

Single Cellular Algae Digestive Supplement Designed by Yeast &Lactobacillus Rearranged Leukocyte Subsets through Activation of Complement Components

A plant fermentation was carried out by Yeast and Lactobacilli against single cellular algae (f-Chlorella). These materials were proved by as safe in animal safety experiment. We sought to look into changes of immune-competent cells that commonly utilized f-Chlorella including after administration of immno-suppressed animals. The effects by f-Chlorella on the regurational effect to the host were measured. Our results showed that f-Chlorella regulated the level of lymphocytes, while conventional-Chlorella worked to adjust the level of granulocytes. In our clinical study with 20 healthy volunteers, granulocyte and lymphocyte ratio was obtained as neutral in the peripheral blood. In rodents, immune-compromised host as well as normal animal were prepared with cancer chemotherapeutic agent (Mytomycin-C), and then tried to rescue the immune-competent rebel. Our observations showed that both Chlorella derivatives regulated in number and functions. The effect was more prominent in f-Chlorella than that of conventional one. We discussed the significance and mechanism of f-Chlorella on the level of leukocyte subsets in number and function. These effects were considered to bring the potential elevation of antibody secreting cell by the localized heamolysis in gel method. We also proposed an idea that exhibited tonic effects were brought via activating the complement components in the serum. Moreover, we tried to access further to the anti-oxidative activities of this f-Chlorella. This modification brought to the significant lifted up for immune competent cells and anti-oxidative activity for phagocytic cells.

The role of CYP1A1/2 in cholesterol ester accumulation provides a new perspective for the treatment of hypercholesterolemia

Cholesterol is an important precursor of many endogenous molecules.Disruption of cholesterol homeostasis can cause many pathological changes,leading to liver and cardiovascular diseases.CYP1A is widely involved in cholesterol metabolic network,but its exact function has not been fully elucidated.Here,we aim to explore how CYP1A regulates cholesterol homeostasis.Our data showed that CYP1A1/2 knockout(KO)rats presented cholesterol deposition in blood and liver.The serum levels of low-density lipoprotein cholesterol,high-density lipoprotein cholesterol and total cholesterol were significantly increased in KO rats.Further studies found that the lipogenesis pathway(LXRa-SREBP1-SCD1)of KO rats was activated,and the key protein of cholesterol ester hydrolysis(CES1)was inhibited.Importantly,lansoprazole can significantly alleviate rat hepatic lipid deposition in hypercholesterolemia models by inducing CYP1A.Our findings reveal the role of CYP1A as a potential regulator of cholesterol homeostasis and provide a new perspective for the treatment of hypercholesterolemia.