Hemes and heme proteins are vital components of essentially every cell of virtually every eukaryote organism. Previously, we demonstrated accumulation of the heme precursor protoporphyrin-IX (PpIX) in gastrointestinal tumor tissues. To elucidate the mechanisms of PpIX accumulation by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we studied expression of the relevant enzymes of the heme synthetic pathway. Here, we describe a significant down-regulation of ferrochelatase (FECH) mRNA expression in gastric, colonic, and rectal carcinomas. Accordingly, in an in vitro model of several carcinoma cell lines, ferrochelatase down-regulation and loss of enzymatic activity corresponded with an enhanced PpIX-dependent fluorescence. Direct detection of PpIX in minute amounts was achieved by a specifically developed pulsed solid-state laser dual delay fluorimetry setup. Silencing of FECH using small interfering RNA (siRNA) technology led to a maximum 50-fold increased PpIX accumulation, imageable by a specifically adapted two-photon microscopy unit. Our results show that in malignant tissue a transcriptional down-regulation of FECH occurs, which causes endogenous PpIX accumulation. Furthermore, accumulation of intracellular PpIX because of FECH siRNA silencing provides a small-molecule-based approach to molecular imaging and molecular therapy.
Patients with cirrhosis are known to develop small bowel mucosal lesions. However, the occurrence of mucosal lesions in patients with abnormal liver function test results in the absence of chronic liver disease has not been fully evaluated. This study aims to examine the association between small bowel endoscopic lesions and liver dysfunction in patients without confirmed chronic liver disease.
Two hundred ninety six consecutive patients who met the selection criteria underwent capsule endoscopy. The severity of the small intestinal mucosal lesions was evaluated quantitatively using the Lewis scoring system, and hepatic dysfunction was evaluated using an algorithm-based combination scoring system with 8 individual serological markers.
Small bowel lesions were observed in 121 patients (40.88%). Hepatic dysfunction was significantly more prevalent in patients with small bowel lesions than in those without lesions (33.1%; 40/121 and 5.7%; 10/175, respectively; P < .001). The mean serum ALT and AST levels were significantly higher in patients with small bowel lesions than in those without lesions (P = .007 and P = .004, respectively). The mean scores for AST to Platelet Ratio Index, Forns Index, S-Index, Fibrosis-4 Index and BARD were significantly higher in patients with small bowel lesions than those without lesions. The Lewis score significantly and positively correlated with the Forns Index (P = .008) and the FIB-4 Index (P = .006).
There is a close correlation between small intestinal mucosal lesions and hepatic dysfunction. The severity of hepatic dysfunction is directly proportional to the severity of the small intestinal mucosal lesions in patients without confirmed chronic liver disease.
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