Identification of integrin ß6 gene promoter and analysis of its transcription regulation in colon cancer cells.

BACKGROUND: The integrin ß6 gene, which is expressed in epithelial cancer, plays a pivotal role in various aspects of cancer progression. The present research for integrin ß6 regulation mainly focuses on the post-transcription and translation related regulation mechanism and its role in tumorigenesis. The mechanisms of how the integrin ß6 gene is regulated transcriptionally, and the promoter and transcription factors responsible for basic transcription of integrin ß6 gene remain unknown. AIM: To clone and characterize the integrin ß6 promoter. METHODS: Software analysis was used to predict the region of integrin ß6 promoter. Luciferase reporter plasmids, which contained the integrin ß6 promoter, were constructed. Element deletion analysis was performed to identify the location of core promoter and binding sites for transcription factors. RESULTS: The regulatory elements for the transcription of the integrin ß6 gene were located between -286 and -85 and contained binding sites for transcription factors such as STAT3 and Ets-1. CONCLUSION: For the first time, we found the region of ß6 core promoter and demonstrated the binding sites for transcription factors such as Ets-1 and STAT3, which are important for integrin ß6 promoter transcription activity. These findings are important for investigating the mechanism of integrin ß6 activation in cancer progression.

Protective effects of a novel drug RC28-E blocking both VEGF and FGF2 on early diabetic rat retina.

AIM: To investigate protective effects of a novel recombinant decoy receptor drug RC28-E on retinal damage in early diabetic rats. METHODS: The streptozotocin (STZ)-induced diabetic rats were randomly divided into 6 groups: diabetes mellitus (DM) group (saline, 3 µL/eye); RC28-E at low (0.33 µg/µL, 3 µL), medium (1 µg/µL, 3 µL), and high (3 µg/µL, 3 µL) dose groups; vascular endothelial growth factor (VEGF) Trap group (1 µg/µL, 3 µL); fibroblast growth factor (FGF) Trap group (1 µg/µL, 3 µL). Normal control group was included. At week 1 and 4 following diabetic induction, the rats were intravitreally injected with the corresponding solutions. At week 6 following the induction, apoptosis in retinal vessels was detected by TUNEL staining. Glial fibrillary acidic protein (GFAP) expression was examined by immunofluorescence. Blood-retinal barrier (BRB) breakdown was assessed by Evans blue assay. Ultrastructural changes in choroidal and retinal vessels were analyzed by transmission electron microscopy (TEM). Content of VEGF and FGF proteins in retina was measured by enzyme linked immunosorbent assay (ELISA). The retinal expression of intercellular cell adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), VEGF and FGF genes was examined by quantitative polymerase chain reaction (qPCR). RESULTS: TUNEL staining showed that the aberrantly increased apoptotic cells death in diabetic retinal vascular network was significantly reduced by treatments of medium and high dose RC28-E, VEGF Trap, and FGF Trap (all P<0.05), the effects of medium and high dose RC28-E or FGF Trap were greater than VEGF Trap (P<0.01). GFAP staining suggested that reactive gliosis was substantially inhibited in all RC28-E and VEGF Trap groups, but the inhibition in FGF Trap group was not as prominent. Evans blue assay demonstrated that only high dose RC28-E could significantly reduce vascular leakage in early diabetic retina (P<0.01). TEM revealed that the ultrastructures in choroidal and retinal vessels were damaged in early diabetic retina, which was ameliorated to differential extents by each drug. The expression of VEGF and FGF2 proteins was significantly upregulated in early diabetic retina, and normalized by RC28-E at all dosages and by the corresponding Traps. The upregulation of ICAM-1 and TNF-α in diabetic retina was substantially suppressed by RC28-E and positive control drugs. CONCLUSION: Dual blockade of VEGF and FGF2 by RC28-E generates remarkable protective effects, including anti-apoptosis, anti-gliosis, anti-leakage, and improving ultrastructures and proinflammatory microenvironment, in early diabetic retina, thereby supporting further development of RC28-E into a novel and effective drug to diabetic retinopathy (DR).

Von Hippel-Lindau disease involving pancreas and biliary system: A rare case report.

RATIONALE: Von Hippel-Lindau (VHL) disease is a rare inherited, autosomal-dominant syndrome caused by heterozygous germline mutations in the VHL gene. VHL patients are prone to develop benign and malignant tumors and cysts in multiple organ systems involving kidneys, pancreas and central nervous system (CNS). The varied and complex clinical manifestations and radiological findings of VHL are of interest. PATIENT CONCERNS: We report a 38-year-old woman with a ten-year history of VHL disease involving both pancreas and biliary system. To the best of our knowledge, direct involvement of the biliary system in VHL disease has never been reported. DIAGNOSES: The diagnosis was established via computed tomography scan and was confirmed by genetic testing. INTERVENTIONS: The patient chose to receive conservative treatment and was followed up by magnetic resonance cholangiopancreatography and magnetic resonance imaging examination. OUTCOMES: Renal angiomas and cysts were found during follow-up and there were no evidence of malignant change of the pancreas and biliary system. LESSONS: We described the first case of VHL-associated choledochal cysts and may present new visceral manifestations of VHL disease. Gastroenterologists should be aware of the clinical presentations of this rare disease for early detection of its life-threatening manifestations.

Reversible posterior encephalopathy syndrome associated with late onset postpartum eclampsia: A case report.

Late onset postpartum eclampsia (LPE) is defined by its onset at >48 h after delivery. Reversible posterior encephalopathy syndrome (RPES) associated with LPE is uncommon, with the majority of RPES cases having a late postpartum onset within 4 weeks after childbirth. The present study reported the case of a 15-year old female presenting with convulsions that began 5 weeks after delivery. A magnetic resonance imaging scan of the brain revealed multiple lesions in the cortex, subcortical region and deep white matter of the bilateral cerebellum, and occipital, frontal and parietal lobes. The clinical manifestations and radiological abnormalities were readily resolved subsequent to antihypertension and anticonvulsion treatment. In conclusion, the present rare case indicates that LPE should be considered as a potential diagnosis even at 4 weeks after delivery. Furthermore, clinicians should familiarize with the reversible radioimaging features of RPES, since early recognition and adequate treatment are important to the outcome of patients.

Resveratrol pre-treatment reduces early inflammatory responses induced by status epilepticus via mTOR signaling.

Resveratrol is indicated to be involved in neuroprotection and anti-inflammation in epileptic rats. The molecular mechanism is still not fully understood. In this study, we investigated the role of resveratrol in nuclear factor-kappa B associated inflammatory responses induced by status epilepticus. Our data showed that seizures activated mammalian target of rapamycin (mTOR), increased the activity of nuclear factor-kappa B and promoted the expressions of inflammatory molecules including inducible nitric oxide synthase, cyclooxygenase-2 and interleukin-1ß. Futhermore, resveratrol significantly inhibited the activation of nuclear factor-kappa B and the production of proinflammatory molecules via mTOR pathway. Additionally, we also proved that the inhibition of mTOR signal by resveratrol was mostly attributed to AMP-activated kinase (AMPK) activation. Altogether, our results suggest that resveratrol suppresses inflammatory responses induced by seizures partially via AMPK/mTOR pathway.