• Pediatric Gastroenterology, Hepatology & Nutrition
• /
• v.9 no.1
• /
• pp.39-47
• /
• 2006

Purpose: We proposed a new classification of pediatric intussusception based on clinical and radiologic findings. Methods: Data from 88 consecutive patients with intussusception were reviewed. We retrospectively analyzed six factors; patient age, sites of intussusception, symptoms, therapeutic methods, existence of enlarged mesenteric lymph nodes, and ultrasonographic (US) findings from clinical records. Results: 1) There was one neonatal case (1.1%), the others (98.9%) were infants and children. 2) These 87 infant and child cases consisted of 14 cases (16.1%) of small bowel intussusception (SBI) and 73 cases (83.9%) of ileo-colic intussusception (ICI). Of the 14 SBI cases, 12 cases were symptomatic and 2 cases were asymptomatic. The symptomatic group comprised 8 transient cases (66.7%), 3 operative cases (25.0%), and 1 enema-reduction case (8.3%). Two asymptomatic cases were incidentally captured by computed tomography. Of the 73 ICI cases, 19 cases (26.0%) required operation, and 54 (74.0%) enema-reduction. 3) When transient SBI cases were compared with operated SBI cases, enema-reduced and operated ICI cases, the age ($38.0{\pm}22.9$ months) of transient SBI cases were significantly higher than those of the others (p=0.003). Mean mass size ($20.8{\pm}2.7mm$) in transient SBI was significantly smaller than in the others (p=0.0001). 4) No correlation was found between the existence of enlarged mesenteric lymph nodes and therapeutic method or concomitant illness. 5) Most of the target types observed by US were in transient SBI cases, the remainder were in the enema-reduced ICI cases. In terms of the doughnuts type, all 8 cases (34.8%) with an external hypoechoic rim thickness of >8.9mm were treated surgically. Conclusion: Pediatric intussusception may be classified based on clinical and radiologic findings, which are likely to indicate appropriate therapies.

• Journal of Physiology & Pathology in Korean Medicine
• /
• v.25 no.6
• /
• pp.1008-1013
• /
• 2011

Osteoporosis is the leading underlying cause of fractures, particularly in postmenopausal women, due to the loss of estrogen-mediated suppression of bone resorption. More than 50% of adults 50 years of age or older are estimated to have osteoporosis. Osteoclast which is main target for treatment of osteoporosis is originated from hematopoietic cell line. Aloe has been widely used in worldwide country as a coadjuvant medicine. Extracts of the leaves of Aloe have been used in condition to improve dermatologic problem such as seborrheic dermatitis, aphthous stomatitis, xerosis, lichen planus and has been known to exert anti-inflammatory, anti-oxidant and anti-tumor effects. However, despite the popularity of aloe as a plant food supplements, the evaluation of its efficacy as a possible therapeutic option for osteoporosis remains scarce. Thus, we evaluated the effect of Aloe on receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation. Here we found that Aloe significantly inhibited osteoclast differentiation induced by RANKL. Aloe suppressed the activation of p38 pathway and $NF{\kappa}B$ in bone marrow macrophages (BMMs) treated with RANKL. Also, Aloe significantly inhibited the mRNA expression of c-Fos, tartrate-resistant acid phosphatase (TRAP), osteoclast-associated receptor (OSCAR), nuclear factor of activated T cells (NFAT)c1 and cathepsin K in BMMs treated with RANKL. Particularly, Aloe greatly inhibited the protein expression of c-fos and NFATc1. Taken together, our results suggested that Aloe may be useful tool for treatment of osteoporosis by inhibition of osteoclast differentiation.

• Journal of Life Science
• /
• v.23 no.9
• /
• pp.1126-1132
• /
• 2013

Cytochrome P450 2J2 (CYP2J2) is an enzyme mainly found in human extrahepatic tissues, with predominant expression in the cardiovascular system. CYP2J2 plays important roles in the metabolism of endogenous metabolites and therapeutic drugs, such as arachidonic acid, astemizole, ebastine, and terfenadine. CYP2J2 is also overexpressed in human cancer tissues and cancer cell lines and may represent a potential target for therapy of human cancers. In this study, 10 natural products obtained from plants and microorganisms were screened as potential CYP2J2 inhibitors. Among them, thelephoric acid showed strong inhibition of astemizole O-demethylation activity ($IC_{50}=3.23{\mu}M$) in a dose-dependent manner. Evaluation of the substrate dependency of the inhibitory activity of thelephoric acid showed that it strongly inhibited CYP2J2-mediated ebastine hydroxylation ($IC_{50}=5.32{\mu}M$) and terfenadine hydroxylation ($IC_{50}=3.27{\mu}M$) in a substrate nondependent manner. The present data suggest that this compound might be a potential candidate for further evaluation for anticancer activity.

• Journal of Life Science
• /
• v.21 no.10
• /
• pp.1494-1499
• /
• 2011

${\beta}$-lapachone, a quinone of lapachol extracted from the bark of the lapacho tree, has been found to induce apoptosis in various human cancer cells. In the present study, we investigated further possible mechanisms by which ${\beta}$-lapachone exerts its pro-apoptotic action in cultured human lung cancer A549 cells. ${\beta}$-lapachone treatment resulted in inhibition of growth and induction of apoptosis in a concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of apoptosis by ${\beta}$-lapachone was associated with up-regulation of the expression of p53 and p21 in both transcriptional and translational levels, and the phosphorylation of p53. In addition, ${\beta}$-lapachone activated caspase-3 and -9, and induced degradation of caspase-3 target proteins such as poly (ADP-ribose) polymerase (PARP) and ${\beta}$-catenin. Furthermore, ${\beta}$-lapachone treatment caused a progressive decrease in the expression levels of cyclooxygenase (COX)-2 without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E2 synthesis. Taken together, these results indicated that ${\beta}$-lapachone may have therapeutic potential in human lung cancer treatment.

• The Korean Journal of Physiology and Pharmacology
• /
• v.21 no.4
• /
• pp.377-384
• /
• 2017

Activation of protein kinase C (PKC) is closely linked with endothelial dysfunction. However, the effect of $PKC{\beta}II$ on endothelial dysfunction has not been characterized in cultured endothelial cells. Here, using adenoviral $PKC{\beta}II$ gene transfer and pharmacological inhibitors, the role of $PKC{\beta}II$ on endothelial dysfucntion was investigated in cultured endothelial cells. Phorbol 12-myristate 13-acetate (PMA) increased reactive oxygen species (ROS), p66shc phosphorylation, intracellular adhesion molecule-1, and monocyte adhesion, which were inhibited by $PKC{\beta}i$ (10 nM), a selective inhibitor of $PKC{\beta}II$. PMA increased the phosphorylation of CREB and manganese superoxide dismutase (MnSOD), which were also inhibited by $PKC{\beta}i$. Gene silencing of CREB inhibited PMA-induced MnSOD expression, suggesting that CREB plays a key role in MnSOD expression. Gene silencing of $PKC{\beta}II$ inhibited PMA-induced mitochondrial ROS, MnSOD, and ICAM-1 expression. In contrast, overexpression of $PKC{\beta}II$ using adenoviral $PKC{\beta}II$ increased mitochondrial ROS, MnSOD, ICAM-1, and p66shc phosphorylation in cultured endothelial cells. Finally, $PKC{\beta}II$-induced ICAM-1 expression was inhibited by Mito-TEMPO, a mitochondrial ROS scavenger, suggesting the involvement of mitochondrial ROS in PKC-induced vascular inflammation. Taken together, the results suggest that $PKC{\beta}II$ plays an important role in PMA-induced endothelial dysfunction, and that the inhibition of $PKC{\beta}II$-dependent p66shc signaling acts as a therapeutic target for vascular inflammatory diseases.

• Toxicological Research
• /
• v.33 no.1
• /
• pp.63-69
• /
• 2017

Transmembrane protein 39A (TMEM39A) belongs to the TMEM39 family. TMEM39A gene is a susceptibility locus for multiple sclerosis. In addition, TMEM39A seems to be implicated in systemic lupus erythematosus. However, any possible involvement of TMEM39A in cancer remains largely unknown. In the present report, we provide evidence that TMEM39A may play a role in brain tumors. Western blotting using an anti-TMEM39A antibody indicated that TMEM39A was overexpressed in glioblastoma cell lines, including U87-MG and U251-MG. Deep-sequencing transcriptomic profiling of U87-MG and U251-MG cells revealed that TMEM39A transcripts were upregulated in such cells compared with those of the cerebral cortex. Confocal microscopic analysis of U251-MG cells stained with anti-TMEM39A antibody showed that TMEM39A was located in dot-like structures lying close to the nucleus. TMEM39A probably located to mitochondria or to endosomes. Immunohistochemical analysis of glioma tissue specimens indicated that TMEM39A was markedly upregulated in such samples. Bioinformatic analysis of the Rembrandt knowledge base also supported upregulation of TMEM39A mRNA levels in glioma patients. Together, the results afford strong evidence that TMEM39A is upregulated in glioma cell lines and glioma tissue specimens. Therefore, TMEM39A may serve as a novel diagnostic marker of, and a therapeutic target for, gliomas and other cancers.

• Journal of Life Science
• /
• v.28 no.9
• /
• pp.1100-1117
• /
• 2018

The Ras superfamily of small G-proteins acts as a molecular switch on the intracellular signaling pathway. Upon ligand stimulation, inactive GTPases (Ras-GDP) are activated (Ras-GTP) using guanine nucleotide exchange factor (GEF) and transmit signals to their downstream effectors. Following signal transmission, active Ras-GTP become inactive Ras-GDP and cease signaling. However, the intrinsic GTPase activity of Ras proteins is weak, requiring Ras GTPase-activating protein (RasGAP) to efficiently convert RAS-GTP to Ras-GDP. Since deregulation of the Ras pathway is found in nearly 30% of all human cancers, it might be useful to clarify the structural and physiological roles of Ras GTPases. Recently, RasGAP has emerged as a new class of tumor-suppressor protein and a potential therapeutic target for cancer. Therefore, it is important to clarify the physiological roles of the individual GAPs in human diseases. The first RasGAP discovered was RASA1, also known as p120 RasGAP. RASA1 is widely expressed, independent of cell type and tissue distribution. Subsequently, neurofibromatosis type 1 (NF1) was discovered. The remaining GAPs are affiliated with the GAP1 and synaptic GAP (SynGAP) families. There are more than 170 Ras GTPases and 14 Ras GAP members in the human genome. This review focused on the current understanding of Ras GTPase and RasGAP in human diseases, including cancers.

• Biomolecules & Therapeutics
• /
• v.17 no.4
• /
• pp.403-411
• /
• 2009

Thiacremonone, the main component isolated from heated garlic (Allium sativum L.), is interested for using as a cancer preventive or therapeutic agent since garlic has been known to be useful plant in the treatment of cancers. Nuclear factor kappaB (NF-${\kappa}B$) is constitutively activated in the prostate cancer and activation of NF-${\kappa}B$ is implicated in drug resistance in cancer cells. Docetaxel, a semisynthetic analog of paclitaxel, is an antineoplastic drug widely used for advanced various cancer. In previous studies, we found that thiacremonone inhibited activation of NF-${\kappa}B$ in cancer cells and marcrophages. In the present study, we investigated whether thiacremonone could increase susceptibility of prostate cancer cells (PC-3 and DU145) to docetaxel via inactivation of NF-${\kappa}B$. We found that the combination treatment of thiacremonone (50 ${\mu}g$/ml) with docetaxel (5 nM) was more effective in the inhibition of prostate cancer cell growth and induction of apoptosis accompanied with the significant inhibition of NF-${\kappa}B$ activity than those by the treatment of thiacremonone or docetaxel alone. It was also found that NF-${\kappa}B$ target gene expression of Bax, caspase-3 and caspase-9 was much more significantly enhanced, but the expression of Bcl-2 was also much more significantly inhibited by the combination treatment. These results indicate that thiacremonone inhibits NF-${\kappa}B$, and enhances the susceptibility of prostate cancer cells to docetaxel. Thus, thiacremonone could be useful as an adjuvant anti-cancer agent.

• Journal of Acupuncture Research
• /
• v.21 no.2
• /
• pp.57-71
• /
• 2004

Objective : Physiological evidence regarding acupuncture's effect in human patients is not yet well established, despite considerable evidence for its therapeutic efficacy. Besides target or disease specificity of acupuncture, acupuncture analgesia (AA) appears to be another large subclass that poses many questions, such as whether there is point specificity with respect to which acupoint is most effective for a particular condition. Methods : We observed brain activation with functional magnetic resonance imaging (fMRI) using a set of stimuli that consist of pain, pain following Meridian acupuncture, and pain following Sham acupuncture. Results : Among the new observations, the most interesting fact is that data sets of both Meridian acupuncture and Sham acupuncture show decreased activation of the same brain areas related to the pain processing signals. Present functional MRI study demonstrate two important biological observations that could elucidate AA mechanism in human participants: the effects of acupuncture occur through mediation of the higher brain areas. Sham acupuncture stimulation appears to be almost as effective as traditional Meridian acupoint stimulation, suggesting that acupuncture is not entirely point specific. Decreased activation in the limbic paleo cortical areas appears to be the probable neurological manifestation of AA and strongly implies that acupuncture stimulation inhibits the transmission of ascending pain signals to the higher cortical areas by the previously known descending pain inhibitory circuit. Conclusion : We, therefore, a hypothesized that this pain inhibitory circuit is initiated and mediated via the broad sense Hypothalamus Pituitary Adrenal (BS HPA) axis in conjunction to the "sensory stimulation."

• Therapeutic Science for Rehabilitation
• /
• v.7 no.3
• /
• pp.59-78
• /
• 2018

Objective : The purpose of this study was to investigate the effect of robot-assisted therapy on upper extremity function. Methods : This study used a single-subject experimental A-B-A' design. Three Parkinson's disease patients took part. Each subject received a robot-assisted therapy intervention (45 min/session, 5 sessions/week for 4 weeks). Upper extremity movement was evaluated with the Reo Assessment tool in Reogo. The Jebsen-Taylor hand motor function test, Fugle-Mayer Assessment score, Box and Block Test, and Nine-hole pegboard test were assessed pre- and post-intervention. Results : After intervention, all subjects underwent 3D motion analysis of reaching function. There was overall improvement in resistance, smoothness, direction accuracy, path efficiency, initiation time, and time to moving target with robot-assisted therapy. Robot-assisted therapy may have a positive effect on upper extremity movement in Parkinson's disease. Conclusion : Robot-assisted therapy is considered an alternative in clinical occupational therapy to improve upper extremity function in Parkinson's disease.