1.MicroRNA Dysregulations in Gastrointestinal Cancers: Pathophysiological and Clinical Perspectives.
William KK WU ; Joseph JY SUNG
Intestinal Research 2012;10(4):324-331
Two common gastrointestinal cancers, namely, gastric and colorectal cancers, cause high mortality and morbidity. The development of gastrointestinal cancers usually follows stepwise processes with recognizable pre-neoplastic changes. A class of noncoding RNA known as microRNA (miRNA) is increasingly recognized to play pleiotropic functions in the multistep development of gastrointestinal cancers. Abnormal patterns of miRNA expression in gastric and colorectal cancers have been widely reported. These dysregulated miRNAs function as novel proto-oncogenes and tumor-suppressor genes by controlling cellular malignant phenotypes, including unchecked cell proliferation, resistance to apoptosis, enhanced invasiveness and metastasis, and angiogenesis. Moreover, certain polymorphisms in miRNA genes or miRNA-binding sites are associated with disease risks whereas detection of circulating or fecal miRNAs may facilitate early diagnosis. The prognostic functions of a number of dysregulated miRNAs in gastrointestinal cancers have also been established. Delineating the pathophysiological basis of miRNA dysregulation will further our understanding of the pathogenesis of these two potentially fatal diseases. Such efforts will also result in the development of miRNA-based biomarkers and therapeutics for the risk stratification, diagnosis, prognostication, and treatment of gastrointestinal cancers.
Apoptosis
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Biomarkers
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Cell Proliferation
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Colorectal Neoplasms
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Early Diagnosis
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Gastrointestinal Neoplasms
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MicroRNAs
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Neoplasm Metastasis
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Phenotype
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Prognosis
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Proto-Oncogenes
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RNA, Untranslated
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Stomach Neoplasms
2.Multiple organ dysfunction scoring system: comparison and evaluation of correlation and accuracy of the three scoring systems in predicting the outcome of multiple organ dysfunction syndrome on highland
SF, ZHANG ; DH, ZHANG ; W, GAO ; HP, LIU ; XH, LUO ; G, DA ; JY, WU ; SX, LIN ; NB, LI ; TD, CHEN ; TY, WU
Chinese Critical Care Medicine 2005;17(6):346-352
OBJECTIVE: To study the characteristics of the diagnostic parameters of acute respiratory distress syndrome/multiple organ dysfunction syndrome on plateau (H-ARDS/MODS) and compare the accuracy of the three MODS scoring criteria in predicting the outcome of syndrome. METHODS: Five hundred and forty cases fulfilling the criteria of MODS were divided into four groups according to the altitude of their inhabitation area: control group (on plain, CG, n=113, altitude: <430 m), moderate high altitude group 1 (H1G, n=314, altitude: 1,517 m), moderate high altitude group 2 (H2G, n=78, altitude: 2,261 m to 2,400 m) and high altitude group (HG, n=35, altitude: 2 808 m to 3 400 m). According to the diagnostic criteria of Lushan conference and Marshall (1995) commonly used on plain, and Lanzhou criteria drafted by the authors, three data analyzing models were set up to draw the receiver operating characteristic (ROC) curves, the Yordon Index and the optimum cutoff points of the parameters were calculated and the accuracy of the three respective diagnostic criteria was evaluated in predicting the outcome of ARDS/MODS. Multiple factors affecting the outcome of MODS were analyzed using the method of stepwise forward regress model. RESULTS: Following the increase in altitude, Lanzhou criteria was clearly superior to the other two criteria in the area of ROC, the sensitivity, the specificity, and also for the optimum cutoff points of MODS. Multi-variable regression analysis showed that the impacting factor of Lanzhou criteria was the highest (P<0.05). CONCLUSION: (1)Some parameters of the current diagnostic criteria of ARDS/MODS are not suitable in moderately high or high altitude areas. It is necessary to set up the diagnostic criteria of H-ARDS/MODS. (2)Some clinical characteristics might change in areas 1,500 m altitude or higher. The pathophysiological mechanism might be attributable to peculiar biologic reactions due to hypoxia stress reaction, and it is worth further study.
Altitude
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Multiple Organ Failure/*diagnosis
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Prognosis
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ROC Curve
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Regression Analysis
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Respiratory Distress Syndrome, Adult/*diagnosis
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Severity of Illness Index
3.Effect of Electroacupuncture on Visceral Hyperalgesia, Serotonin and Fos Expression in an Animal Model of Irritable Bowel Syndrome.
Justin CY WU ; Eric TC ZIEA ; Lixing LAO ; Emma FC LAM ; Catherine SM CHAN ; Angela YQ LIANG ; Sunny LH CHU ; David TW YEW ; Brian M BERMAN ; Joseph JY SUNG
Journal of Neurogastroenterology and Motility 2010;16(3):306-314
BACKGROUND/AIMS: While it is well established that acupuncture relieves somatic pain, its therapeutic effect on visceral pain such as irritable bowel syndrome (IBS) is unclear. We evaluated the effect of acupuncture in treating visceral hyperalgesia in an animal model. METHODS: Sprague-Dawley rats (n = 8 per group) with prior neonatal maternal separation stress were randomly allocated to receive 3-day treatment of either electroacupuncture (EA) or sham acupuncture at acupoint ST-36. Another group of rats without prior maternal separation was included as non-handled controls. Colorectal distension was performed on the day after acupuncture treatment. The 3 groups were compared for pain threshold as determined by abdominal withdrawal reflex and visceromotor response as measured by electromyogram. Colon, spinal cord, and brainstem were sampled for topographic distribution and quantitative assessment of serotonin and Fos expression by immunohistochemistry. RESULTS: Rats in EA group had significantly higher pain threshold compared to those in sham acpuncture group (25.0 +/- 5.7 mmHg vs 18.7 +/- 5.2 mmHg, p = 0.01) and it was comparable with that of non-handled treatment naive controls (29.4 +/- 9.3 mmHg, p = 0.28). They also had lower visceromotor response as measured by electromyogram compared to those received sham acupuncture at all colorectal distension pressures. EA significantly suppressed Fos expression in doral raphe nuclei of brainstem, superficial dorsal horn of spinal cord and colonic epithelium but suppressed 5-HT expression only in brainstem and spinal cord. CONCLUSIONS: Electro acupuncture attenuates visceral hyperlagesia through down-regulation of central serotonergic activities in the brain-gut axis.
Acupuncture
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Acupuncture Points
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Animals
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Axis, Cervical Vertebra
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Benzodiazepines
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Brain Stem
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Colon
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Down-Regulation
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Electroacupuncture
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Epithelium
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Horns
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Hyperalgesia
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Immunohistochemistry
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Irritable Bowel Syndrome
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Models, Animal
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Nociceptive Pain
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Pain Threshold
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Raphe Nuclei
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Rats
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Rats, Sprague-Dawley
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Reflex
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Salicylamides
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Serotonin
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Spinal Cord
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Visceral Pain