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??????????????? ????????? ???????????? ???????????? ?????? ?????????????????? ??????????????? ?????? ???????????? ??????. ??? ??????????????? ??????????????? ??? ?????? ????????? ???????????? ????????? ??????????????? ????????? ???????????????. ?????? ??????????????? ????????? ??? ?????? ????????? ???????????????, ??? ?????? ????????? diethylnitrosamine (DEN)??? C3H/HeN ?????? ?????? ?????? ???????????? ??? ?????? ????????? ????????? ???????????????. DEN?????? ????????? ???????????? ?????? alkaline phosphatase (ALP) ??????, TUNEL positive ???????????? ??????, ??? ???????????? ?????? ???????????? duct??? ??????, ?????????????????? ????????????, Masson???s trichrome ???????????? ????????? ???????????? ???, ?????? ?????? ?????? ??? ????????? ????????? ???????????? ?????? ???????????? ?????? ?????? ????????? ??? ?????????. ?????????, ??????????????? ?????? ???????????? ????????? ?????? ?????????????????? ??????, ?????? ?????? ??? ????????? ???????????? ??????????????? ???????????? ???????????? ???????????? ?????? ?????? ????????? ??? ?????????. ???????????? ???????????? ????????? ???????????? ??????, ???????????? ???????????? ???????????? ?????? ????????? ???, solvent partition ????????? ???????????? ????????? ???????????? hexane, ethyl acetate, water ???????????? ???????????????. ?????? ??????????????? ?????? ????????? ??????????????? ??????????????? ???, ethyl acetate ???????????? ??????????????? ????????? ?????????????????? ??????????????? ?????? ??????????????? ???????????? ????????? ????????? ????????? ??? ?????????. ????????? ethyl acetate???????????? ???????????? ????????? ????????? ??? ?????????, ??????????????? ????????? ??? ?????? ????????? ????????? ?????????. ???????????????, ??????????????? ????????? ????????????????????? ?????? ????????? ??? ?????? ????????? ???????????? ?????? ??????????????? ????????? ??? ?????? ????????? ????????? ????????? ?????? ???????????????. ?????????, ?????? ??????????????? ?????? ???????????? ?????? ??? ?????? ?????? ???????????? ??????????????? ?????? ????????? ????????? ??? ?????? ????????? ???????????? ??????.clos

Overexpression of the miR-141/200c cluster promotes the migratory and invasive ability of triple-negative breast cancer cells through the activation of the FAK and PI3K/AKT signaling pathways by secreting VEGF-A

Migration in miR-141/200c-transduced HCC-38 and Hs578T cells treated with an anti-VEGF-A-neutralizing antibody. (A, D) Migration in miR-141/200c-transduced HCC-38 and Hs578T cells. Images of the crystal violet-stained cells that migrated horizontally in the trans-well migration assay (upper). The absorbance values of extracted crystal violet in migrated cells (lower). The migratory abilities of the miR-200c cells (~1.6-fold and ~1.7-fold, HCC-38 and Hs578T, respectively) were significantly increased compared with those of the control cells. (B, E) Measurement of the secreted levels of cytokines and growth factors (IL-2, IL-4, IL-5, IL-10, IL-12, IL-13, GM-CSF, IFN-γ, TNF-α, and VEGF-A). Transduction of miR-141/200c into HCC-38 and Hs578T cells promoted significantly higher VEGF-A secretion than that of control cells. (C, F) Trans-well migration of anti-VEGF-A-neutralizing antibody-treated cells. The enhanced migration of the miR-141/200c-transduced HCC-38 cells were significantly suppressed by treatment with anti-VEGF-A-neutralizing antibodies, but miR-141/200c-transduced Hs578T cells still showed increased migratory ability compared with control cells. *p < 0.05, **p < 0.001. (JPG 188 kb

Respiratory Syncytial Virus-Like Nanoparticle Vaccination Induces Long-Term Protection Without Pulmonary Disease by Modulating Cytokines and T-cells Partially Through Alveolar Macrophages

The mechanisms of protection against respiratory syncytial virus (RSV) are poorly understood. Virus-like nanoparticles expressing RSV glycoproteins (eg, a combination of fusion and glycoprotein virus-like nanoparticles [FG VLPs]) have been suggested to be a promising RSV vaccine candidate. To understand the roles of alveolar macrophages (AMs) in inducing long-term protection, mice that were 12 months earlier vaccinated with formalin-inactivated RSV (FI-RSV) or FG VLPs were treated with clodronate liposome prior to RSV infection. FI-RSV immune mice with clodronate liposome treatment showed increases in eosinophils, plasmacytoid dendritic cells, interleukin (IL)-4+ T-cell infiltration, proinflammatory cytokines, chemokines, and, in particular, mucus production upon RSV infection. In contrast to FI-RSV immune mice with severe pulmonary histopathology, FG VLP immune mice showed no overt sign of histopathology and significantly lower levels of eosinophils, T-cell infiltration, and inflammatory cytokines, but higher levels of interferon-γ, which are correlated with protection against RSV disease. FG VLP immune mice with depletion of AMs showed increases in inflammatory cytokines and chemokines, as well as eosinophils. The results in this study suggest that FG nanoparticle vaccination induces long-term protection against RSV and that AMs play a role in the RSV protection by modulating eosinophilia, mucus production, inflammatory cytokines, and T-cell infiltration

Ginseng Protects Against Respiratory Syncytial Virus by Modulating Multiple Immune Cells and Inhibiting Viral Replication

Ginseng has been used in humans for thousands of years but its effects on viral infection have not been well understood. We investigated the effects of red ginseng extract (RGE) on respiratory syncytial virus (RSV) infection using in vitro cell culture and in vivo mouse models. RGE partially protected human epithelial (HEp2) cells from RSV-induced cell death and viral replication. In addition, RGE significantly inhibited the production of RSV-induced pro-inflammatory cytokine (TNF-α) in murine dendritic and macrophage-like cells. More importantly, RGE intranasal pre-treatment prevented loss of mouse body weight after RSV infection. RGE treatment improved lung viral clearance and enhanced the production of interferon (IFN-γ) in bronchoalveolar lavage cells upon RSV infection of mice. Analysis of cellular phenotypes in bronchoalveolar lavage fluids showed that RGE treatment increased the populations of CD8+ T cells and CD11c+ dendritic cells upon RSV infection of mice. Taken together, these results provide evidence that ginseng has protective effects against RSV infection through multiple mechanisms, which include improving cell survival, partial inhibition of viral replication and modulation of cytokine production and types of immune cells migrating into the lung

Electroacupuncture Delays Hypertension Development through Enhancing NO/NOS Activity in Spontaneously Hypertensive Rats

Using spontaneously hypertensive rats (SHR), this study investigated whether electroacupuncture (EA) could reduce early stage hypertension by examining nitric oxide (NO) levels in plasma and nitric oxide synthase (NOS) levels in the mesenteric resistance artery. EA was applied to the acupuncture point Governor Vessel 20 (GV20) or to a non-acupuncture point in the tail twice weekly for 3 weeks under anesthesia. In conscious SHR and normotensive Wistar Kyoto (WKY) rats, blood pressure was determined the day after EA treatment by the tail-cuff method. We measured plasma NO concentration, and evaluated endothelial NO syntheses (eNOS) and neuronal NOS (nNOS) protein expression in the mesenteric artery. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were lower after 3 weeks of GV20 treatment than EA at non-acupuncture point and no treatment control in SHR. nNOS expression by EA was significantly different between both WKY and no treatment SHR control, and EA at GV20 in SHR. eNOS expression was significantly high in EA at GV 20 compared with no treatment control. In conclusion, EA could attenuate the blood pressure elevation of SHR, along with enhancing NO/NOS activity in the mesenteric artery in SHR

A Case of More Abundant and Dysplastic Adenomas in the Interposed Colon than in the Native Colon

We report a 60-year-old woman with intramucosal adenocarcinoma arising in the interposed colon, 40 years after the esophageal reconstruction for lye induced esophageal stricture. Although synchronous adenomas were also found in the native colon where the graft was taken, the number of adenomas was greater in the interposed colon and more dysplastic, even progressed to adenocarcinoma, than that of the native colon. The microsatellite instability-testing performed in the intramucosal carcinoma from interposed colon showed absence of microsatellite instability. Changing of location and functional deman]d of colonic segment, and the exposure to different intraluminal contents might have facilitated the adenomacarcinoma transformation in the interposed colon

Bee venom attenuates neuroinflammatory events and extends survival in amyotrophic lateral sclerosis models

<p>Abstract</p> <p>Background</p> <p>Amyotrophic lateral sclerosis (ALS) is a disease affecting the central nervous system that is either sporadic or familial origin and causing the death of motor neurons. One of the genetic factors contributing to the etiology of ALS is mutant SOD1 (mtSOD1), which induces vulnerability of motor neurons through protein misfolding, mitochondrial dysfunction, oxidative damage, cytoskeletal abnormalities, defective axonal transport, glutamate excitotoxicity, inadequate growth factor signaling, and neuroinflammation. Bee venom has been used in the practice of Oriental medicine and evidence from the literature indicates that BV plays an anti-inflammatory or anti-nociceptive role against inflammatory reactions associated with arthritis and other inflammatory diseases. The purpose of the present study was to determine whether bee venom suppresses motor neuron loss and microglial cell activation in hSOD1^G93Amutant mice.</p> <p>Methods</p> <p>Bee venom (BV) was bilaterally injected (subcutaneously) into a 14-week-old (98 day old) male hSOD1^G93Aanimal model at the Zusanli (ST36) acupoint, which is known to mediate an anti-inflammatory effect. For measurement of motor activity, rotarod test was performed and survival statistics were analyzed by Kaplan-Meier survival curves. The effects of BV treatment on anti-neuroinflammation of hSOD1^G93Amice were assessed via immunoreactions using Iba 1 as a microglia marker and TNF-α antibody. Activation of ERK, Akt, p38 MAP Kinase (MAPK), and caspase 3 proteins was evaluated by western blotting.</p> <p>Results</p> <p>BV-treated mutant hSOD1 transgenic mice showed a decrease in the expression levels of microglia marker and phospho-p38 MAPK in the spinal cord and brainstem. Interestingly, treatment of BV in symptomatic ALS animals improved motor activity and the median survival of the BV-treated group (139 ± 3.5 days) was 18% greater than control group (117 ± 3.1 days). Furthermore, we found that BV suppressed caspase-3 activity and blocked the defects of mitochondrial structure and cristae morphology in the lumbar spinal cord of hSOD1^G93Amice at the symptomatic stage.</p> <p>Conclusion</p> <p>From these findings, our research suggests BV could be a potential therapeutic agent for anti-neuroinflammatory effects in an animal model of ALS.</p

Attributable fraction of tobacco smoking on cancer using population-based nationwide cancer incidence and mortality data in Korea

Smoking is by far the most important cause of cancer that can be modified at the individual level. Cancer incidence and mortality rates in Korea are the highest among all Asian countries, and smoking prevalence in Korean men is one of the highest in developed countries. The purpose of the current study was to perform a systematic review and provide an evidence-based assessment of the burden of tobacco smoking-related cancers in the Korean population. Sex- and cancer-specific population-attributable fractions (PAF) were estimated using the prevalence of ever-smoking and second-hand smoking in 1989 among Korean adults, respectively, and the relative risks were estimated from the meta-analysis of studies performed in the Korean population for ever-smoking and in the Asian population for passive smoking. National cancer incidence data from the Korea Central Cancer Registry and national cancer mortality data from Statistics Korea for the year 2009 were used to estimate the cancer cases and deaths attributable to tobacco smoking. Tobacco smoking was responsible for 20,239 (20.9%) cancer incident cases and 14,377 (32.9%) cancer deaths among adult men and 1,930 (2.1%) cancer incident cases and 1,351 (5.2%) cancer deaths among adult women in 2009 in Korea. In men, 71% of lung cancer deaths, 55%-72% of upper aerodigestive tract (oral cavity, pharynx, esophagus and larynx) cancer deaths, 23% of liver, 32% of stomach, 27% of pancreas, 7% of kidney and 45% of bladder cancer deaths were attributable to tobacco smoking. In women the proportion of ever-smoking-attributable lung cancer was 8.1%, while that attributable to second-hand smoking among non-smoking women was 20.5%. Approximately one in three cancer deaths would be potentially preventable through appropriate control of tobacco smoking in Korean men at the population level and individual level. For Korean women, more lung cancer cases and deaths were attributable to second-hand than ever-smoking. Effective control programs against tobacco smoking should be further developed and implemented in Korea to reduce the smoking-related cancer burden