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The increase in 19S subunits in L2AKO livers may explain the enhanced degradation of endogenous polyubiquitinated proteins (Fig. 3B) which depend on the 19S regulatory particle for access to the core protease, but not of the synthetic peptides used for analysis of catalytic activities that occurs independently of the 19S subunits.
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But the interplay between the intestinal tract and the liver may explain the increased association with autoimmune liver diseases and inflammatory bowel diseases.
In patients associating CMLNS, septicemia or malignant T-lymphocyte infiltration of the liver may explain the liver insufficiency [ 2, 3].
The male rat liver has been shown to be more susceptible than the female rat liver to the hepatocarcinogenic action of certain drugs, and it is conceivable that sex differences in the metabolic activation of the drugs in the liver may explain the greater sensitivity of male rats to chemically induced hepatocellular carcinoma.
VEGFR-1 has been reported to regulate VEGFR-2 activity 21 and we confirmed that in vitro stimulation of LSEC with VEGF-A induced VEGFR-1 expression (Supporting Fig. 5A), suggesting that elevated VEGFR-1 levels observed in the diseased liver may explain the reduction in phosphorylated VEGFR-2.
Improved treatment of advanced HBV-related liver disease may explain why HBV liver-related morbidity declined.
Hepatic dysfunction may alter multiple critical coagulation factors which are produced by the liver, which may explain some of the coagulation abnormalities associated with HIV infection.
Some experts [ 7] suggest that the hypervascularity of HCC and the underlying coagulopathy due to liver cirrhosis may explain this observation.
Finally, male and female secretory patterns of GH determine sex-dependent gene expression in the rodent liver that may explain adverse effects of IGF-1R+/− mutation on male survival at advanced ages (Ahluwalia et al., 2004; Waxman & Holloway, 2009).
This latter effect likely has implications for other hepatic disease states associated with TRAIL induced liver injury, and may explain why the course of such diseases is accelerated in HIV infected patients.
Frequent expression of CXCR4 and its ability to promote liver metastasis in PAC may explain the well-known, but poorly understood, predilection for PAC to metastasize to liver and why adjuvant chemotherapy provides only modest protection against liver recurrence.
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