Intranodal Hemangioma in the Pelvic Cavity: A Case Report.

Hemangiomas are benign tumours that commonly develop in the skin, mucosal surfaces, and soft tissues. However, intranodal hemangiomas are extremely rare and are among the benign primary vascular abnormalities of the lymph nodes that include lymphangioma, hemangioendothelioma, angiomyomatous hamartoma and hemangiomas. The hemangioma in the pelvic lymph node has never been reported in the English literature. Herein, we described an extremely rare case of hemangioma in the pelvic lymph node, simulating a benign metastasizing leiomyoma.

Prognostic effects of histology-based tumour microenvironment scores in resected distal bile duct cancer.

AIMS: Histology-based tumour microenvironment (TME) scores are useful in predicting the prognosis of gastrointestinal cancer. However, their prognostic roles in distal bile duct cancer (DBDC) have not been previously studied. This study aimed to evaluate the prognostic significance of the TME scores using the Klintrup-Mäkinen (KM) grade, tumour stroma percentage (TSP) and the Glasgow microenvironment score (GMS) in resected DBDC. METHODS AND RESULTS: Eighty-one patients with DBDC who underwent curative resection were enrolled. DBDC was graded according to KM grade, TSP and GMS. A high KM grade was found in 19 patients (24%) and a high TSP was found in 47 patients (58%). A high TSP was significantly correlated with a low KM grade (P < 0.001). The distribution of the GMS, which was developed by combining the KM grade and TSP, was as follows: 0 (n = 19, 24%), 1 (n = 19, 24%) and 2 (n = 43, 52%). A low KM grade, high TSP and high GMS were significantly associated with short overall survival (OS) (P < 0.001) and relapse-free survival (RFS) (P < 0.001). Furthermore, multivariate analysis showed that a low KM grade [hazard ratio (HR) = 3.826; confidence interval (CI) = 1.650-8.869; P = 0.014], high TSP (HR = 2.193; CI = 1.173-4.100, P = 0.002) and high GMS (HR = 7.148; CI = 2.811-18.173) were independent prognostic factors for short RFS; a low KM grade (HR = 4.324; CI = 1.594-11.733) and high GMS (HR = 6.332; CI = 2.743-14.594) were independent prognostic factors for short OS. CONCLUSION: Histology-based TME scores, including the KM grade, TSP and GMS, are useful for predicting the survival of patients with resected DBDC.

A prospective association between dietary folate intake and type 2 diabetes risk among Korean adults aged 40 years or older: the Korean Multi-Rural Communities Cohort (MRCohort) Study.

It has not been well established whether dietary folate intake reduces the risk of diabetes development. We aimed to clarify the prospective association between dietary folate intake and type 2 diabetes (T2D) risk among 7333 Korean adults aged 40 years or older who were included in the Multi-Rural Communities Cohort. Dietary folate intake was estimated from all 106 food items listed on a FFQ, not including folate intake from supplements. Two different measurements of dietary folate intake were used: the baseline consumption and the average consumption from baseline until just before the end of follow-up. The association between folate intake and T2D risk was determined through a modified Poisson regression model with a robust error estimator controlling for potential confounders. For 29 745 person years, 319 cases of diabetes were ascertained. In multivariable analyses, dietary folate intake was inversely associated with risk of T2D for women, not for men. For women, the incidence rate ratio of diabetes in the third tertile compared with the first tertile was 0·57 (95 % CI 0·38-0·87, P for trend=0·0085) in the baseline consumption model and 0·64 (95 % CI 0·43-0·95, P for trend=0·0244) in the average consumption model. These inverse associations was found in both normal fasting blood glucose group and impaired fasting glucose group among women. Among non-users of multinutrients and vitamin supplements, the significant inverse association remained. Thus, higher dietary intake of folate is prospectively associated with lower risk of diabetes for women.

Association between serum stromal cell-derived factor-1α and long-term outcome of acute ischemic stroke.

BACKGROUND: Stromal cell-derived factor-1α (SDF-1α) provides neurotrophic support to neurons. In this prospective study, we investigated the association between SDF-1α and long-term outcome in patients with acute ischemic stroke. METHODS: This study included 104 patients with first-ever ischemic stroke, identified within 24 h of symptom onset. Serum samples were collected immediately after admission and 3 months thereafter, as well as from age- and sex-matched normal controls. The correlation between acute-stage serum SDF-1α and stroke severity were analyzed. Finally, the relationship between serum SDF-1α and long-term outcome was evaluated by multivariate analysis. RESULTS: Serum SDF-1α levels were only higher in acute-stage stroke patients compared with the normal control group (p = 0.011). The serum SDF-1α level was increased in proportion to infarct volume (r = 0.220, p = 0.025) and initial National Institutes of Health Stroke Scale score (r = 0.275, p = 0.005). After adjustment for covariates, a high initial serum SDF-1α level (OR 1.167, p = 0.023) or second and third tertiles of SDF-1α level compared to first tertile (OR 4.644, p = 0.044 and OR 9.396, p = 0.025, respectively) were significantly associated with a favorable long-term outcome. CONCLUSIONS: This prospective study demonstrated a correlation between serum SDF-1α and favorable long-term outcome in patients with acute ischemic stroke.

Nateglinide and acarbose for postprandial glucose control after optimizing fasting glucose with insulin glargine in patients with type 2 diabetes.

AIMS: Basal insulin treatment is frequently used in type 2 diabetes, but the successful control of postprandial glucose is challenging. We compared the effect of preferential postprandial glucose targeting drugs for postprandial glucose control after optimizing fasting glucose with basal insulin. METHODS: This study was performed in 58, insulin naïve type 2 diabetes. After fasting glucose was optimized by insulin glargine, nateglinide or acarbose was initiated and then crossed over after second wash out period. 75 g oral glucose tolerance test and 7 point self monitoring blood glucose for 3 days at the end of each period was performed. RESULTS: Both drugs effectively reduced postprandial glucose levels compared with the insulin glargine monotherapy. No significant differences were found between nateglinide and acarbose in terms of mean glucose level, standard deviation of glucose levels, mean average glucose excursion and average daily risk range. Homeostasis model analysis (HOMA)% ß, corrected insulin response and insulin-to-glucose ratio were significantly higher in the responder group compared with the non-responder. There was no episode of severe hypoglycemia. CONCLUSIONS: Nateglinide and acarbose are equally effective in type 2 diabetes for postprandial glucose excursions during basal insulin treatment. The markers of beta cell function might be used for predicting response. (Clinical trial reg. no. NCT 00437918, clinicaltrial.gov.).

The effect of chromium on rat insulinoma cells in high glucose conditions.

AIMS: it has been suggested that Chromium (Cr), one of the essential minerals, can be beneficial to type 2 diabetic patients because it lowers blood glucose levels by improving various steps in insulin action. A few studies reported that Cr might also have some beneficial effects in people with type 1 diabetes mellitus and in streptozotocin-treated rats, but direct beneficial effects of Cr on pancreatic beta cells have not been proven. We performed this study to determine whether Cr could have direct protective effects on INS-1 cells in high glucose conditions that mimic the actual diabetic state. MAIN METHODS: INS-1 cells were cultured for 48h in RPMI medium with 33mM glucose as the stress condition and 11mM glucose as a control. CrCl(3) was used to verify whether Cr could protect INS-1 cells from glucotoxic stress. Cell viability and apoptosis were evaluated by MTT assay and FACS. The level of insulin mRNA, by semi-quantitative RT-PCR, was significantly reduced at 33mM glucose concentration after 48h of incubation. KEY FINDINGS: cell viability was reduced by 50%, and 35% of the cells underwent apoptosis at the same culture condition. Addition of various concentrations of CrCl(3) to INS-1 cells in 33mM glucose for different durations of time did not reveal any beneficial effects on cell viability, degree of apoptosis, insulin mRNA levels, and glucose stimulated insulin secretion. SIGNIFICANCE: we could not find any evidence that Cr had direct beneficial effects on INS-1 cells in high glucose induced stress conditions.

EGCG and quercetin protected INS-1 cells in oxidative stress via different mechanisms.

EGCG and quercetin are known as beneficial dietary flavonoid for various diseases including diabetes mellitus. But it is not certain whether they could protect pancreatic beta cell directly. We performed this study to test both EGCG and quercetin could directly protect beta cell line under oxidative stress, and verify the action mechanisms. The protective effect of quercetin on INS-1 cells against oxidative stress was concentration dependent, but EGCG showed specific concentration zone for the protection. The protective effect of EGCG was more pronounced in pre-treatment before oxidative stress, while quercetin showed dramatic improvement of viability in simultaneous incubation with H2O2. In EGCG pre-treatment, antioxidant enzymes and activity were decreased, but the phosphorylated PI3K and Akt were significantly increased. PI3K inhibitor significantly reduced cell viability in EGCG pre-treatment. In conclusion, EGCG and quercetin have protective effect on INS-1 cells against oxidative stress through both antioxidant effect and anti-apoptosis signaling. In EGCG, pre-treatment make its effect better by the enhancement of anti-apoptosis signaling. Quercetin protected INS-1 cells more in simultaneous incubation via strong antioxidant defense.

Human neural stem cells genetically modified to overexpress Akt1 provide neuroprotection and functional improvement in mouse stroke model.

In a previous study, we have shown that human neural stem cells (hNSCs) transplanted in brain of mouse intracerebral hemorrhage (ICH) stroke model selectively migrate to the ICH lesion and induce behavioral recovery. However, low survival rate of grafted hNSCs in the brain precludes long-term therapeutic effect. We hypothesized that hNSCs overexpressing Akt1 transplanted into the lesion site could provide long-term improved survival of hNSCs, and behavioral recovery in mouse ICH model. F3 hNSC was genetically modified with a mouse Akt1 gene using a retroviral vector. F3 hNSCs expressing Akt1 were found to be highly resistant to H(2)O(2)-induced cytotoxicity in vitro. Following transplantation in ICH mouse brain, F3.Akt1 hNSCs induced behavioral improvement and significantly increased cell survival (50-100% increase) at 2 and 8 weeks post-transplantation as compared to parental F3 hNSCs. Brain transplantation of hNSCs overexpressing Akt1 in ICH animals provided functional recovery, and survival and differentiation of grafted hNSCs. These results indicate that the F3.Akt1 human NSCs should be a great value as a cellular source for the cellular therapy in animal models of human neurological disorders including ICH.

Comparison of the efficiency and toxicity of sonoporation with branched polyethylenimine-mediated gene transfection in various cultured cell lines.

OBJECTIVE: The objective of this study is to evaluate transfection efficiency and safety for gene delivery by sonoporation in comparison with cationic polymer gene carrier branched polyethylenimine (BPEI). METHODS: The cDNA expressing VEGF(165) was cloned under chicken beta-actin promoter. The plasmid DNA was transfected into the CHO, HEK293, and NIH3T3 cells using microbubble-based sonoporation and BPEI (25 kDa) under various conditions. Enzyme-linked immunosorbent assay (ELISA) was used to determine the expressed protein level. Cytotoxicities of transfection methods were compared by Cell Counting Kit-8. RESULTS: At 1 MHz intensity, transfection efficiency of sonoporation was enhanced by microbubble concentration with no detrimental effects. By contrast, BPEI exacerbated cell viability, despite its high transgene expression efficiency. CONCLUSION: Sonoporation gene therapy might be the safest technique to be used in actual clinical practice.

Ursodeoxycholic acid prevents apoptosis of mouse sensory neurons induced by cisplatin by reducing P53 accumulation.

Ursodeoxycholic acid (UDCA), a component of bile acid, which is abundant in the gall bladder of bears, has been used in clinical medicine for cholestatic liver diseases. Recently, it was demonstrated that UDCA and its derivative tauroursodeoxycholic acid block apoptotic cell death in both hepatic and non-hepatic cells. Cisplatin, an effective anti-cancer drug, is known to cause sensory neuropathy in patients receiving the drug. In the present study, whether UDCA is effective in blocking cisplatin-induced cell death in mouse hybrid sensory neurons was conducted. N18D3 mouse hybrid sensory neurons exposed to cisplatin were found to undergo apoptotic cell death. Preincubation with UDCA completely blocked cisplatin-induced apoptotic cell death in the sensory neurons, and cisplatin-induced p53 accumulation was suppressed by UDCA treatment. These results indicate that UDCA has a neuroprotective effect on the cisplatin-induced neuronal cell death of sensory neurons via the downregulation of the p53 signaling pathway.

Upregulation of endothelial adhesion molecules by lysophosphatidylcholine. Involvement of G protein-coupled receptor GPR4.

Lysophosphatidylcholine induces expression of adhesion molecules; however, the underlying molecular mechanisms of this are not well elucidated. In this study, the intracellular signaling by which lysophosphatidylcholine upregulates vascular cell adhesion molecule-1 and P-selectin was delineated using YPEN-1 and HEK293T cells. The results showed that lysophosphatidylcholine dose-dependently induced expression of vascular cell adhesion molecule-1 and P-selectin, accompanied by the activation of transcription factor nuclear factor kappaB. However, the nuclear factor kappaB inhibitor caffeic acid phenethyl ester (CAPE) and the antioxidant N-acetylcysteine only partially blocked lysophosphatidylcholine-induced adhesion molecules. Subsequently, we found that the lysophosphatidylcholine receptor G protein-coupled receptor 4 (GPK4) was expressed in YPEN-1 cells and triggered the cAMP/protein kinase A/cAMP response element-binding protein pathway, resulting in upregulation of adhesion molecules. Further evidence showed that overexpression of human GPK4 enhanced lysophosphatidylcholine-induced expression of adhesion molecules in YPEN-1 cells, and enabled HEK293T cells to express adhesion molecules in response to lysophosphatidylcholine. In conclusion, the current study suggested two pathways by which lysophosphatidylcholine regulates the expression of adhesion molecules, the lysophosphatidylcholine/nuclear factor-kappaB/adhesion molecule and lysophosphatidylcholine/GPK4/cAMP/protein kinase A/cAMP response element-binding protein/adhesion molecule pathways, emphasizing the importance of the lysophosphatidylcholine receptor in regulating endothelial cell function.