BACKGROUND/OBJECTIVES: Soy isoflavones are expected to improve menopausal symptoms and osteoporosis in women. However, their efficacy is still inconclusive, and there was limited data for postmenopausal women in South Korea. We examined the effects of soy isoflavones on climacteric symptoms, bone biomarkers, and quality of life in Korean postmenopausal women. SUBJECTS/METHODS: A randomized, double-blind study design was used. Eighty-seven participants who had undergone natural menopause were randomly administered either 70 mg/day isoflavones (n = 43) or placebo (n = 41) for 12 weeks. We assessed the Kupperman index for climacteric symptoms and the menopause-specific quality of life (MENQOL) questionnaire for quality of the life. Biomarkers of bone metabolism were also measured in serum bone-specific alkaline phosphatase (BALP), osteocalcin (OC), N- and C-terminal cross-linking telopeptides of type I collagen (NTx, CTx), and urine-deoxypyridinolin (u-DPD). RESULTS: Scores of the Kupperman index were decreased in both the isoflavones group (−7.0 ± 15.8, P = 0.0074) and placebo group (−6.3 ± 14.6, P = 0.0064) during the intervention, but no significant difference was noted between the groups. Regarding the bone formation markers, the level of serum BALP increased by 6.3 ± 4.1% (P = 0.004) and OC increased by 9.3 ± 6.2% (P < 0.001), meanwhile those of the placebo were not changed. For the bone resorption markers, NTx, CTx, and u-DPD were not significantly different in either group. MENQOL was significant decreased in the isoflavone group (−0.6 ± 0.5) and placebo group (−0.6 ± 0.4), with a significant difference between groups (P = 0.0228). CONCLUSIONS: Our study suggests that 70 mg isoflavones supplement has beneficial effects on bone formation markers; however, it showed no benefit compared to the placebo on climacteric symptoms or quality of life.
Alkaline Phosphatase ; Biomarkers* ; Bone Resorption ; Climacteric* ; Collagen Type I ; Double-Blind Method ; Female ; Humans ; Isoflavones* ; Korea ; Menopause ; Metabolism ; Osteocalcin ; Osteogenesis ; Osteoporosis ; Postmenopause ; Quality of Life*

PURPOSE: Our aim to assess clinical significance of the relation between inferior mesenteric vein ligation and collateral blood supply (meandering mesenteric artery) to the splenic flexure with elaboration more in anatomical landmarks and technical tips. MATERIALS AND METHODS: We review the literature regarding the significance of the collateral vessels around inferior mesenteric vein (IMV) root and provide our prospective operative findings, anatomical landmarks and technical tips. We analyzed the incidence and pattern of anatomic variation of collateral vessels around the IMV. RESULTS: A total of 30 consecutive patients have been prospectively observed in a period between June 25-2012 and September 7-2012. Nineteen males and eleven females with mean age of 63 years. Major colorectal procedures were included. There were three anatomical types proposed, based on the relation between IMV and the collateral vessel. Type A and B in which either the collateral vessel crosses or runs close to the IMV with incidence of 43.3% and 13.3%, respectively, whereas type C is present in 43.3%. There was no definitive relation between the artery and vein. No intra or postoperative ischemic events were reported. CONCLUSION: During IMV ligation, inadvertent ligation of Arc of Riolan or meandering mesenteric artery around the IMV root "in type A&B" might result in compromised blood supply to the left colon, congestion, ischemia and different level of colitis or anastomotic dehiscence. Therefore, careful dissection and skeletonization at the IMV root "before ligation if necessary" is mandatory to preserve the collateral vessel for the watershed area and to avoid further injury.
Duodenum/anatomy & histology ; Female ; Humans ; Ligation/*methods ; Male ; Mesenteric Veins/*surgery ; Middle Aged ; Pancreas/anatomy & histology ; Prospective Studies

BACKGROUND/OBJECTIVES: Hyperglycemia-induced hepatic damage has been recognized as one of the major cause of complications in diabetes. Hepatic complications are associated with inflammation and oxidative stress in diabetes. In this study, we investigated the hypothesis that gamma-tocopherol (GT) supplementation ameliorates NLRP3 inflammasome associated hepatic inflammation in diabetes. MATERIALS/METHODS: Diabetes was induced by the intraperitoneal injection of alloxan (150 mg/kg. BW) in ICR mice. All mice were fed with a control diet (AIN-76A). After diabetes was induced (fasting glucose level ≥ 250 mg/dL), the mice were treated with tocopherol-stripped corn oil or GT-supplemented (35 mg/kg) corn oil, respectively, by gavage for 2 weeks. RESULTS: GT supplementation reduced fasting blood glucose levels in diabetic mice relative to non-treated diabetic mice. Moreover, GT supplementation ameliorated hyperglycemia-induced hepatic damage by regulation of NOD-like receptor protein 3 (NLRP3)-inflammasome associated inflammation represented by NLRP3, apoptosis-associated speck-like protein containing a caspase-recruitment domain, caspase-1, nuclear factor-κB pathway as well as oxidative stress demonstrated by nuclear factor erythroid 2-related factor 2, NAD(P)H dehydrogenase quinone 1, catalase and glutathione-dependent peroxidase in diabetic mice. CONCLUSION: The findings suggested that GT supplementation ameliorated hepatic damage by attenuating inflammation and oxidative stress in alloxan-induced diabetic mice. Taken together, GT could be a beneficial nutrient that can ameliorate inflammatory responses associated with NLRP3 inflammasome in hyperglycemia-induced hepatic damage.

The action of observing can be used as an effective rehabilitation paradigm, because it activates the mirror neuron system. However, it is difficult to fully use this paradigm because it is difficult to get patients to engage in watching video clips of exercise. In this study, we proposed a steady state visually evoked potential (SSVEP) based paradigm that could be used in a Brain Computer Interface, and examined its feasibility by investigating whether flickering video could activate the mirror neuron system and evoke SSVEPs at the same time. Twenty subjects were recruited and asked to watch the flickering videos at a rate of 20 Hz of upper limb motion and visual white noise, while an EEG signal was recorded. The mu rhythm (8–13 Hz) suppression and the SSVEP (19–21 Hz) evocation were analyzed from recorded EEG. The results showed that SSVEPs, evoked by the flickering stimulus, was observed in both conditions on O1 and O2, but the mu rhythm suppression on C3 and C4 was observed only in the exercise video condition. These results could signify that the flickering video is applicable for the BCI rehabilitation game, activating the mirror neuron system at the same time.
Brain-Computer Interfaces ; Electroencephalography ; Evoked Potentials* ; Humans ; Mirror Neurons* ; Noise ; Rehabilitation ; Stroke ; Upper Extremity

BACKGROUND: This study investigates the effects of a neuropeptide, secretoneurin (SN), on bone regeneration in an experimental mouse model. METHODS: The effects of SN on cell proliferation, osteoblast marker genes expression, and mineralization were evaluated using the CCK-8 assay, quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and alizarin red S staining, respectively. To examine the effects of SN on bone regeneration in vivo, bone defects were created in the calvaria of ICR mice, and 0.5 or 1 lg/ml SN was applied. New bone formation was analyzed by micro-computed tomography (micro-CT) and histology. New blood vessel formation was assessed by CD34 immunohistochemistry. RESULTS: SN had no significant effect on proliferation and mineralization of MC3T3-E1 cells. However, SN partially induced the gene expression of osteoblast differentiation markers such as runt-related transcription factor 2, alkaline phosphatase, collagen type I alpha 1, and osteopontin. A significant increase of bone regeneration was observed in SN treated calvarial defects. The bone volume (BV), BV/tissue volume, trabecular thickness and trabecular number values were significantly increased in the collagen sponge plus 0.5 or 1 lg/ml SN group (p < 0.01) compared with the control group. Histologic analysis also revealed increased new bone formation in the SN-treated groups. Immunohistochemical staining of CD34 showed that the SN-treated groups contained more blood vessels compared with control in the calvarial defect area. CONCLUSION SN increases new bone and blood vessel formation in a calvarial defect site. This study suggests that SN may enhance new bone formation through its potent angiogenic activity.

BACKGROUND: This study investigates the effects of a neuropeptide, secretoneurin (SN), on bone regeneration in an experimental mouse model. METHODS: The effects of SN on cell proliferation, osteoblast marker genes expression, and mineralization were evaluated using the CCK-8 assay, quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and alizarin red S staining, respectively. To examine the effects of SN on bone regeneration in vivo, bone defects were created in the calvaria of ICR mice, and 0.5 or 1 lg/ml SN was applied. New bone formation was analyzed by micro-computed tomography (micro-CT) and histology. New blood vessel formation was assessed by CD34 immunohistochemistry. RESULTS: SN had no significant effect on proliferation and mineralization of MC3T3-E1 cells. However, SN partially induced the gene expression of osteoblast differentiation markers such as runt-related transcription factor 2, alkaline phosphatase, collagen type I alpha 1, and osteopontin. A significant increase of bone regeneration was observed in SN treated calvarial defects. The bone volume (BV), BV/tissue volume, trabecular thickness and trabecular number values were significantly increased in the collagen sponge plus 0.5 or 1 lg/ml SN group (p < 0.01) compared with the control group. Histologic analysis also revealed increased new bone formation in the SN-treated groups. Immunohistochemical staining of CD34 showed that the SN-treated groups contained more blood vessels compared with control in the calvarial defect area. CONCLUSION SN increases new bone and blood vessel formation in a calvarial defect site. This study suggests that SN may enhance new bone formation through its potent angiogenic activity.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Although advances have been made in the treatment of MS, such as the use of IFN-β, glucocorticoids and stem cells, the therapeutic effects of these treatments are not sufficient. In the present study, we evaluated whether the combination of methylprednisolone (MP) and human bone marrow-derived mesenchymal stem cells (BM-MSCs) could enhance the therapeutic effectiveness in experimental autoimmune encephalomyelitis (EAE), a model for MS. EAE was induced by immunizing C57BL/6 mice with myelin oligodendrocyte glycoprotein 35-55 (MOG 35-55). The immunized mice received an intraperitoneal injection of MP (20 mg/kg), an intravenous injection of BM-MSCs (1 × 10⁶ cells) or both on day 14 after immunization. Combination treatment significantly ameliorated the clinical symptoms, along with attenuating inflammatory infiltration and demyelination, compared to either treatment alone. Secretion of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-17) was significantly reduced, and anti-inflammatory cytokines (IL-4, IL-10) was significantly increased by the combination treatment as compared to either treatment alone. Flow cytometry analysis of MOG-reactivated T cells in spleen showed that combination treatment reduced the number of CD4⁺CD45⁺ and CD8⁺ T cells, and increased the number of CD4⁺CD25⁺Foxp3⁺ regulatory T cells. Furthermore, combination treatment enhanced apoptosis in MOG-reactivated CD4⁺ T cells, a key cellular subset in MS pathogenesis. Combination treatment with MP and BM-MSCs provides a novel treatment protocol for enhancing therapeutic effects in MS.
Animals ; Apoptosis ; Central Nervous System ; Clinical Protocols ; Cytokines ; Demyelinating Diseases ; Encephalomyelitis, Autoimmune, Experimental* ; Flow Cytometry ; Glucocorticoids ; Humans* ; Immunization ; Injections, Intraperitoneal ; Injections, Intravenous ; Mesenchymal Stromal Cells* ; Methylprednisolone* ; Mice ; Multiple Sclerosis ; Myelin-Oligodendrocyte Glycoprotein ; Spleen ; Stem Cells ; T-Lymphocytes ; T-Lymphocytes, Regulatory ; Therapeutic Uses

In the previous version of this article, two important references [47-2, 173] were missing. The authors would like to make corrections in the original version of the article.

BACKGROUND: The neural regulation of bone regeneration has emerged recently. Spexin (SPX) is a novel neuropeptide and regulates multiple biological functions. However, the effects of SPX on osteogenic differentiation need to be further investigated. Therefore, the aim of this study is to investigate the effects of SPX on osteogenic differentiation, possible underlying mechanisms, and bone regeneration. METHODS: In this study, MC3T3-E1 cells were treated with various concentrations of SPX. Cell proliferation, osteogenic differentiation marker expressions, alkaline phosphatase (ALP) activity, and mineralization were evaluated using the CCK-8 assay, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR), ALP staining, and alizarin red S staining, respectively. To determine the underlying molecular mechanism of SPX, the phosphorylation levels of signaling molecules were examined via western blot analysis. Moreover, in vivo bone regeneration by SPX (0.5 and 1 lg/ll) was evaluated in a calvarial defect model. New bone formation was analyzed using micro-computed tomography (micro-CT) and histology. RESULTS: The results indicated that cell proliferation was not affected by SPX. However, SPX significantly increased ALP activity, mineralization, and the expression of genes for osteogenic differentiation markers, including runt-related transcription factor 2 (Runx2), Alp, collagen alpha-1(I) chain (Col1a1), osteocalcin (Oc), and bone sialoprotein (Bsp). In contrast, SPX downregulated the expression of ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1). Moreover, SPX upregulated phosphorylated mitogen-activated protein kinase kinase (MEK1/2) and extracellular signal-regulated kinase (ERK1/2). in vivo studies, micro-CT and histologic analysis revealed that SPX markedly increased a new bone formation. CONCLUSION Overall, these results demonstrated that SPX stimulated osteogenic differentiation in vitro and increased in vivo bone regeneration via the MEK/ERK pathway.

PURPOSE: The aim of this study was to evaluate the diagnostic and prognostic role of metabolic parameters of FDG PET/CT in patients with intrahepatic cholangiocarcinoma (ICC).METHODS: From December 2008 to December 2013, 76 FDG PET/CT scans performed for initial staging of ICC in a single institution (57 male and 19 female; mean age 68 ± 9 years) were retrospectively reviewed. Patients with history of other known malignancy were excluded. Detection rates of regional lymph node and distant metastasis by FDG PET/CT were analyzed in comparison with conventional imaging modalities such as CT or MRI. Metabolic parameters including maximum, peak and mean standardized uptake values (SUVmax, SUVpeak, SUVmean), metabolic tumor volume (MTV), total lesion glycolysis (TLG), glucose corrected SUV (SUVgluc), and glucose corrected TLG (TLGgluc) were measured for the primary tumor. Cut-off values for the metabolic parameters were calculated by ROC curve analysis, and used to dichotomize the patient groups. The overall survival time (OS) was calculated and compared using the Cox proportional hazard regression analysis.RESULTS: The median duration of follow-up period was 5.4 months (interquartile range: 1.45~15.45). FDG PET/CT showed higher sensitivity than conventional imagingmodalities in detection of regional node involvement (74.5 % vs. 61.8 %, p = 0.013). In six patients, distant metastasis was identified only by FDG PET/CT. The mean SUVmax, SUVpeak, SUVmean, MTV, and TLG for the primary tumor were 8.2 ± 3.1, 6.8 ± 2.5, 4.0 ± 0.8, 192.7 ± 360.5 cm3, and 823.7 ± 1615.4, respectively. Patients with higher (≥7.3, HR: 4.280, p = 0.001), higher SUVpeak (≥6.5, HR: 2.333, p = 0.020), higher SUVmean (≥3.9, HR: 2.799, p = 0.004), higher SUVgluc (≥8.1, HR: 2.648, p = 0.012), and higher TLGgluc (≥431.6, HR: 2.186, p = 0.030) showed significantly shorter survival time. By multivariate study, operability was an independent prognostic factor for longer survival (HR: 4.113, p= 0.005).CONCLUSION: FDG PET/CT is an important diagnostic imaging tool in the nodal staging and detection of distant metastasis in ICC patients. Metabolic parameters may have a significant role as prognostic factors in patients with ICC.
Cholangiocarcinoma ; Diagnostic Imaging ; Female ; Follow-Up Studies ; Glucose ; Glycolysis ; Humans ; Lymph Nodes ; Magnetic Resonance Imaging ; Male ; Neoplasm Metastasis ; Positron-Emission Tomography ; Positron-Emission Tomography and Computed Tomography ; Prognosis ; Retrospective Studies ; ROC Curve ; Tumor Burden