Lysophosphatidic acid (LPA) is known to regulate various biological responses by binding to LPA receptors. The serum level of LPA is elevated in diabetes, but the involvement of LPA in the development of diabetes and its complications remains unknown. Therefore, we studied LPA signaling in diabetic nephropathy and the molecular mechanisms involved. The expression of autotaxin, an LPA synthesis enzyme, and LPA receptor 1 was significantly increased in both mesangial cells (SV40 MES13) maintained in high-glucose media and the kidney cortex of diabetic db/db mice. Increased urinary albumin excretion, increased glomerular tuft area and volume, and mesangial matrix expansion were observed in db/db mice and reduced by treatment with ki16425, a LPA receptor 1/3 antagonist. Transforming growth factor (TGF)β expression and Smad-2/3 phosphorylation were upregulated in SV40 MES13 cells by LPA stimulation or in the kidney cortex of db/db mice, and this was blocked by ki16425 treatment. LPA receptor 1 siRNA treatment inhibited LPA-induced TGFβ expression, whereas cells overexpressing LPA receptor 1 showed enhanced LPA-induced TGFβ expression. LPA treatment of SV40 MES13 cells increased phosphorylated glycogen synthase kinase (GSK)3β at Ser9 and induced translocation of sterol regulatory element-binding protein (SREBP)1 into the nucleus. Blocking GSK3β phosphorylation inhibited SREBP1 activation and consequently blocked LPA-induced TGFβ expression in SV40 MES13 cells. Phosphorylated GSK3β and nuclear SREBP1 accumulation were increased in the kidney cortex of db/db mice and ki16425 treatment blocked these pathways. Thus, LPA receptor 1 signaling increased TGFβ expression via GSK3β phosphorylation and SREBP1 activation, contributing to the development of diabetic nephropathy.
Ecklonia stolonifera is a brown alga that was shown to have antioxidant, anti-inflammatory, tyrosinase inhibitory, and chemopreventive activities. However, the molecular mechanisms underlying its anti-inflammatory activity remain unclear. In this study, we investigated the molecular mechanism of the anti-inflammatory action of E. stolonifera ethanolic extracts (ESE) using lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. ESE inhibited LPS-induced nitric oxide (IC(50) = 72 ± 1.9 μg/mL) and prostaglandin E(2) (IC(50) = 98 ± 5.3 μg/mL) production in a dose-dependent manner and suppressed the expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 cells. ESE also reduced the production of pro-inflammatory cytokines in LPS-stimulated RAW 264.7 cells. LPS-induced nuclear factor-κB (NF-κB) transcriptional activity and NF-κB translocation into the nucleus were significantly inhibited by ESE treatment through the prevention of the degradation of inhibitor κB-α. Moreover, ESE inhibited the activation of Akt, ERK, JNK1/2, and p38 MAPK in LPS-stimulated RAW 264.7 cells. The main components with anti-inflammatory activity in ESE were identified as phlorofucofuroeckol A and B based on the inhibition of NO production. Our results indicate that ESE can be considered as a potential source of therapeutic agents for inflammatory diseases.
In case of bleeding control by hemostatic packing, there remains a risk of delayed hemorrhage from pseudoaneurysm. Postoperative vertebral angiography is helpful to avoid life-threatening complications. Endovascular treatment can be a good alternative in the treatment of VAI.
Consumers are very aware of contaminants that could pose potential health hazards. Most people drink tea as an infusion (adding hot water); however, in some countries, including India, China and Egypt, tea is drunk as a decoction (tea and water are boiled together). An infusion usually brings the soluble ingredients into solution, whereas a decoction brings all soluble and non-soluble constituents together. Therefore, a cup of tea may contain various kinds of contaminants. This review focuses on green and black tea because they are most commonly consumed. The target was to examine the transfer rate of contaminants - pesticides, environmental pollutants, mycotoxins, microorganisms, toxic heavy metals, radioactive isotopes (radionuclides) and plant growth regulators - from tea to infusion/brewing, factors contributing to the transfer potential and contaminants degradation, and residues in or on the spent leaves. It is concluded that most contaminants leaching into tea infusion are not detected or are detected at a level lower than the regulatory limits. However, the traditional practice of over-boiling tea leaves should be discouraged as there may be a chance for more transfer of contaminants from the tea to the brew.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.