Cocoa polyphenols suppress TNF-α-induced vascular endothelial growth factor expression by inhibiting phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase kinase-1 (MEK1) activities in mouse epidermal cells

Cocoa polyphenols have antioxidant and anti-inflammatory effects. TNF-α is a pro-inflammatory cytokine that has a vital role in the pathogenesis of inflammatory diseases such as cancer and psoriasis. Vascular endothelial growth factor (VEGF) expression is associated with tumorigenesis, CVD, rheumatoid arthritis and psoriasis. We tested whether cocoa polyphenol extract (CPE) inhibited TNF-α-induced VEGF expression in promotion-sensitive JB6 mouse epidermal cells. CPE significantly inhibited TNF-α-induced up-regulation of VEGF via reducing TNF-α-induced activation of the nuclear transcription factors activator protein-1 (AP-1) and NF-κB, which are key regulators of VEGF expression. CPE also inhibited TNF-α-induced phosphorylation of protein kinase B (Akt) and extracellular signal-regulated kinase. CPE blocked activation of their downstream kinases, p70 kDa ribosomal protein S6 kinase and p90 kDa ribosomal protein S6 kinase. CPE suppressed phosphoinositide 3-kinase (PI3K) activity via binding PI3K directly. CPE did not affect TNF-α-induced phosphorylation of mitogen-activated protein kinase kinase-1 (MEK1) but suppressed TNF-α-induced MEK1 activity. Collectively, these results indicate that CPE reduced TNF-α-induced up-regulation of VEGF by directly inhibiting PI3K and MEK1 activities, which may contribute to its chemopreventive potentia

Estimating remineralized phosphate and its remineralization rate in the northern East China Sea during Summer 1997 : a snapshot study before Three-Gorges Dam construction

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Terrestrial, Atmospheric and Oceanic Sciences 27 (2016): 955-963, doi:10.3319/TAO.2016.01.24.01(Oc).The northern East China Sea (a.k.a., “The South Sea”) is a dynamic zone that exerts a variety of effects on the marine ecosystem due to Three-Gorges Dam construction. As the northern East China Sea region is vulnerable to climate forcing and anthropogenic impacts, it is important to investigate how the remineralization rate in the northern East China Sea has changed in response to such external forcing. We used an historical hydrographic dataset from August 1997 to obtain a baseline for future comparison. We estimate the amount of remineralized phosphate by decomposing the physical mixing and biogeochemical process effect using water column measurements (temperature, salinity, and phosphate). The estimated remineralized phosphate column inventory ranged from 0.8 to 42.4 mmol P m-2 (mean value of 15.2 ± 12.0 mmol P m-2). Our results suggest that the Tsushima Warm Current was a strong contributor to primary production during the summer of 1997 in the study area. The estimated summer (June - August) remineralization rate in the region before Three-Gorges Dam construction was 18 ± 14 mmol C m-2 d-1.T. Lee was supported by 2-Year Research Grant of Pusan National University. H.-C. Kim was partly supported by KOPRI project (PG15010). I.-N. Kim was partly supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2015R1C1A1A01052051). K.-T. Park was partly supported by KOPRI project (PE17010). J.-H. Kim was partly supported by the program of “Management of Marine Organisms Causing Ecological Disturbance and Harmful Effects” funded by KIMST/MOF. A.M. Macdonald’s contribution was supported by NOAA grant: #NA110AR4310063 and NSF grant: #OCE-1059881

Colonic Mucosal Necrosis Following Administration of Calcium Polystryrene Sulfonate (Kalimate) in a Uremic Patient

Colonic necrosis is known as a rare complication following the administration of Kayexalate (sodium polystryrene sulfonate) in sorbitol. We report a rare case of colonic mucosal necrosis following Kalimate (calcium polystryrene sulfonate), an analogue of Kayexalate without sorbitol in a 34-yr-old man. He had a history of hypertension and uremia. During the management of intracranial hemorrhage, hyperkalemia developed. Kalimate was administered orally and as an enema suspended in 20% dextrose water to treat hyperkalemia. Two days after administration of Kalimate enema, he had profuse hematochezia, and a sigmoidoscopy showed diffuse colonic mucosal necrosis in the rectum and sigmoid colon. Microscopic examination of random colonic biopsies by two consecutive sigmoidoscopies revealed angulated crystals with a characteristic crystalline mosaic pattern on the ulcerated mucosa, which were consistent with Kayexalate crystals. Hematochezia subsided with conservative treatment after a discontinuance of Kalimate administration

Quercetin, the active phenolic component in kiwifruit, prevents hydrogen peroxide-induced inhibition of gap-junction intercellular communication

We evaluated the effects of the two main kiwifruit cultivars (gold kiwifruit (GOK) and green kiwifruit (GRK)) and their active phenolic compound, quercetin, on H2O2-induced inhibition of gap-junction intercellular communication (GJIC) in WB-F344 rat liver epithelial cells. We found that both GOK and GRK protect WB-F344 cells from H2O2-induced inhibition of GJIC. The extracellular signal-regulated protein kinase 1/2 (ERK1/2)-connexin 43 (Cx43) signalling pathway is crucial for the regulation of GJIC, and both GOK and GRK blocked the H2O2-induced phosphorylation of Cx43 and ERK1/2 in WB-F344 cells. Quercetin alone attenuated the H2O2-mediated ERK1/2-Cx43 signalling pathway and consequently reversed H2O2-mediated inhibition of GJIC in WB-F344 cells. A free radical-scavenging assay using 1,1-diphenyl-2-picrylhydrazyl showed that the scavenging activity of quercetin was higher than that of a synthetic antioxidant, butylated hydroxytoluene, per mol, suggesting that the chemopreventive effect of quercetin on H2O2-mediated inhibition of ERK1/2-Cx43 signalling and GJIC may be mediated through its free radical-scavenging activity. Since the carcinogenicity of reactive oxygen species such as H2O2 is attributable to the inhibition of GJIC, GOK, GRK and quercetin may have chemopreventive potential by preventing the inhibition of GJI

MMP-Inhibitory Effects of Flavonoid Glycosides from Edible Medicinal Halophyte Limonium tetragonum

Limonium tetragonum has been well-known for its antioxidative properties as a halophyte. This study investigated the antimetastasis effect of solvent-partitioned L. tetragonum extracts (LTEs) and isolated compounds on HT1080 mouse melanoma cell model with a focus on matrix metalloproteinase (MMP) activity and TIMP and MAPK pathways. Upregulation and stimulation of MMPs result in elevated degradation of extracellular matrix which is part of several complications such as metastasis, cirrhosis, and arthritis. The anti-MMP capacity of LTEs was confirmed by their MMP-inhibitory effects, regulation of MMP and TIMP expression, and suppression of MAPK pathway. Among all tested LTEs, 85% aq. MeOH and n-BuOH were found to be most active fractions which later yielded two known flavonoid glycosides, myricetin 3-galactoside and quercetin 3-o-beta-galactopyranoside. Anti-MMP potential of the compounds was confirmed by their ability to regulate MMP expression through inhibited MAPK pathway activation. These results suggested that L. tetragonum might serve as a potential source of bioactive substances with effective anti-MMP properties

Tidal Effects on Intermediate Waters: A Case Study in the East/Japan Sea

Although tides are believed to be the most important source for diapycnal mixing in the ocean, few studies have directly simulated open-ocean circulation including tides. Because the East/Japan Sea (EJS) has been considered to be a “miniature ocean,” tidal effects on the intermediate water of the EJS are investigated by using an eddy-resolving ocean general circulation model that can take account of M2 and K1 tides as well as oceanic flows. The simulated temperature and salinity in the intermediate layer are significantly improved by including tides. The improvement results from the combined effect of two internal tides. The M2 internal tide, propagating into the interior of the EJS, enhances vertical mixing and brings watermass characteristics closer to those observed. The K1 internal tide, trapped along the coast, induces southwestward flow along the Russian coast in the upper layer and thereby enhances the so-called Liman Current, which transports fresh waters with density conducive to the ventilation of intermediate waters in the EJS

Revascularization of immature retinas with retinopathy of prematurity using combination therapy of deferred laser treatment after a single intravitreal bevacizumab injection

Background This study aimed to observe the extent of retinal vascularization in patients with retinopathy of prematurity (ROP) who underwent deferred laser treatment (LT) after a single intravitreal bevacizumab injection (IVB). Methods This study retrospectively evaluated 40 consecutive eyes in 21 infants who received a single IVB or LT. Deferred LT was performed in cases of ROP recurrence after a single IVB. To assess the amount of retinal vascularization between the initial IVB and deferred LT, the cases were divided into three groups based on treatment: single IVB, deferred LT after a single IVB, and prompt LT. The growth and associated complications were compared between groups. Results There were 12, 16, and 12 eyes in the single IVB, deferred LT, and prompt LT groups, respectively. Deferred LT was performed at an average of 7.9 weeks after a single IVB. In the single IVB group, retinal vascularization proceeded to zone III, whereas the prompt LT group did not show any growth of vascularization beyond the laser scars. In the deferred LT group, during the window period before LT, retinal vascularization progressed from zone I to zone II posterior and from zone II posterior to zone II anterior, respectively, without further ROP recurrence. Conclusions Retinal vascularization progressed during the deferred window period, thereby reducing the area of the retina ablated by LT. A single IVB followed by deferred LT can be an alternative treatment option to prevent ablation of zone I or multiple IVBs

A Case of Santorinicele without Pancreas Divisum: Diagnosis with Multi-detector Row Computed Tomography

A santorinicele is defined as a focal cystic dilatation of the terminal portion of the dorsal pancreatic duct at the minor papilla. Most cases reported previously were associated with pancreas divisum and a santorinicele without pancreas divisum is known to be rare. We recently experienced a typical case of a santorinicele without pancreas divisum in a 67-yr-old woman with abdominal pain and hematochezia, subsequently proven to be the result of an ischemic colitis. The santorinicele was diagnosed incidentally with multi-detector row computed tomography using a minimum intensity projection technique, which clearly showed a cystic dilatation of the terminal portion of the dorsal pancreatic duct and a communication between the ventral and dorsal pancreatic ducts. This finding was also confirmed by a magnetic resonance cholangiopancreatography

Assessment of the Prognostic Factors for a Local Recurrence of Rectal Cancer: the Utility of Preoperative MR Imaging

OBJECTIVE: To determine the utility of MR imaging in evaluating the prognostic factors for a local recurrence of rectal cancer following a curative resection. MATERIALS AND METHODS: The preoperative MR images obtained from 17 patients with a local recurrence and 54 patients without a local recurrence, who had undergone a curative resection, were independently evaluated by three radiologists. The following findings were analyzed: the direct invasion of the perirectal fat by the primary rectal carcinoma, involvement of the perirectal lymph nodes, perirectal spiculate nodules, perivascular encasement, and an enlargement of the pelvic wall lymph nodes. The clinical and surgical profiles were obtained from the patients' medical records. The association of a local recurrence with the MR findings and the clinicosurgical variables was statistically evaluated. RESULTS: Of the MR findings, the presence of perivascular encasement (p = 0.001) and perirectal spiculate nodules (p = 0.001) were found to be significant prognostic factors for a local recurrence. Of the clinicosurgical profiles, the presence of a microscopic vascular invasion (p = 0.005) and the involvement of the regional lymph nodes (p = 0.006) were associated with a local recurrence. Logistic regression analysis showed that the presence of perirectal spiculate nodules was an independent predictor of a local recurrence (odds ratio, 7.382; 95% confidence interval, 1.438, 37.889; p = 0.017). CONCLUSION: The presence of perirectal spiculate nodules and perivascular encasement on the preoperative MR images are significant predictors of a local recurrence after curative surgery for a rectal carcinoma. This suggests that preoperative MR imaging can provide useful information to help in the planning of preoperative adjuvant therapy.ope