Cross-Talk of NADPH Oxidases and Inflammation in Obesity

Obesity is a major risk factor for cardiovascular and metabolic diseases. Multiple experimental and clinical studies have shown increased oxidative stress and inflammation linked to obesity. NADPH oxidases are major sources of reactive oxygen species in the cardiovascular system and in metabolically active cells and organs. An impaired balance due to the increased formation of reactive oxygen species and a reduced antioxidative capacity contributes to the pathophysiology of cardiovascular and metabolic diseases and is linked to inflammation as a major pathomechanism in cardiometabolic diseases. Non-alcoholic fatty liver disease is particularly characterized by increased oxidative stress and inflammation. In recent years, COVID-19 infections have also increased oxidative stress and inflammation in infected cells and tissues. Increasing evidence supports the idea of an increased risk for severe clinical complications of cardiometabolic diseases after COVID-19. In this review, we discuss the role of oxidative stress and inflammation in experimental models and clinical studies of obesity, cardiovascular diseases, COVID-19 infections and potential therapeutic strategies

Peritoneal VEGF-A expression is regulated by TGF-β1 through an ID1 pathway in women with endometriosis

VEGF-A, an angiogenic factor, is increased in the peritoneal fluid of women with endometriosis. The cytokine TGF-β1 is thought to play a role in the establishment of endometriosis lesions. Inhibitor of DNA binding (ID) proteins are transcriptional targets of TGF-β1 and ID1 has been implicated in VEGF-A regulation during tumor angiogenesis. Herein, we determined whether peritoneal expression of VEGF-A is regulated by TGF-β1 through the ID1 pathway in women with endometriosis. VEGF-A was measured in peritoneal fluid by ELISA (n = 16). VEGF-A and ID1 expression was examined in peritoneal biopsies (n = 13), and primary peritoneal and immortalized mesothelial cells (MeT5A) by immunohistochemistry, qRT-PCR and ELISA. VEGF-A was increased in peritoneal fluid from women with endometriosis and levels correlated with TGF-β1 concentrations (P < 0.05). VEGF-A was immunolocalized to peritoneal mesothelium and TGF-β1 increased VEGFA mRNA (P < 0.05) and protein (P < 0.05) in mesothelial cells. ID1 was increased in peritoneum from women with endometriosis and TGF-β1 increased concentrations of ID1 mRNA (P < 0.05) in mesothelial cells. VEGF-A regulation through ID1 was confirmed by siRNA in MeT5A cells (P < 0.05). Our data supports role for ID1 in the pathophysiology of endometriosis, as an effector of TGFβ1 dependent upregulation of VEGF-A, and highlights a novel potential therapeutic target

Optimum design of steel bridges including corrosion effect using TLBO

This study presents optimum design of plane steel bridges considering corrosion effect by using teaching-learning based optimization (TLBO) method. Optimum solutions of three different bridge problems are linearly carried out including and excluding corrosion effect. The member cross sections are selected from a pre-specified list of 128 W profiles taken from American Institute of Steel Construction (AISC). A computer program is coded in MATLAB to carry out optimum design interacting with SAP2000 using OAPI (Open Application Programming Interface). The stress constraints are incorporated as indicated in AISC Allowable Stress Design (ASD) specifications and also displacement constraints are applied in optimum design. The results obtained from analysis show that the corrosion effect on steel profile surfaces causes a crucial increase on the minimum steel weight of bridges. Moreover, the results show that the method proposed is applicable and robust to reach the destination even for complex problems. Copyright © 2017 Techno-Press, Ltd

Cross-Talk of NADPH Oxidases and Inflammation in Obesity

Obesity is a major risk factor for cardiovascular and metabolic diseases. Multiple experimental and clinical studies have shown increased oxidative stress and inflammation linked to obesity. NADPH oxidases are major sources of reactive oxygen species in the cardiovascular system and in metabolically active cells and organs. An impaired balance due to the increased formation of reactive oxygen species and a reduced antioxidative capacity contributes to the pathophysiology of cardiovascular and metabolic diseases and is linked to inflammation as a major pathomechanism in cardiometabolic diseases. Non-alcoholic fatty liver disease is particularly characterized by increased oxidative stress and inflammation. In recent years, COVID-19 infections have also increased oxidative stress and inflammation in infected cells and tissues. Increasing evidence supports the idea of an increased risk for severe clinical complications of cardiometabolic diseases after COVID-19. In this review, we discuss the role of oxidative stress and inflammation in experimental models and clinical studies of obesity, cardiovascular diseases, COVID-19 infections and potential therapeutic strategies

Sex-specific mTOR signaling determines sexual dimorphism in myocardial adaptation in normotensive DOCA-salt model

The deoxycorticosterone acetate (DOCA)-salt mouse model exhibits adverse cardiac remodeling in male mice and cardiac protection in female mice, even when blood pressure is normalized. We hypothesized that intact mammalian target of rapamycin (mTOR) signaling is necessary for cardiac protection in females. We first tested sex differences and intracellular signaling after mTOR targeting with rapamycin in wild-type mice. Radio-telemetric blood pressure was maintained at normal for 6 weeks. Rapamycin significantly reduced left ventricular hypertrophy, preserved ejection fraction, inhibited fibrosis, and maintained capillary structure in male mice. Decreased mTORC1 and increased mTORC2 activity were detected in rapamycin-treated male mice compared with vehicle controls. In contrast, female mice developed dilative left ventricular hypertrophy, cardiac fibrosis, and capillary loss similar to DOCA-salt females lacking the estrogen receptor {beta} (ER{beta}(-/-)) that we described earlier. Because rapamycin downregulated ER{beta} in female mice, we next studied ER{beta}(-/-) normotensive DOCA-salt females. Vehicle-treated wild-type females maintained their high constitutive mTORC1 and mTORC2 in response to DOCA-salt. In contrast to males, both mTORCs were decreased by rapamycin, in particular mTORC2 by 60%. ER{beta}(-/-) DOCA-salt females showed similar mTORC1 and mTORC2 response patterns. We suggest that ERβ-dependent regulation involves sex-specific use of mTOR signaling branches. Maintenance of both mTORC1 and mTORC2 signaling seems to be essential for adaptive cardiac remodeling in females and supports a rationale for sex-specific therapeutic strategies in left ventricular hypertrophy

15-keto-Prostaglandin E(2) exhibits bioactive role by modulating glomerular cytoarchitecture through EP2/EP4 receptors

AIMS: Prostaglandins are important signaling lipids with prostaglandin E(2) (PGE(2)) known to be the most abundant prostaglandin across tissues. In kidney, PGE(2) plays an important role in the regulation of kidney homeostasis through its EP receptor signaling. Catabolism of PGE(2) yields the metabolic products that are widely considered biologically inactive. Although recent in vitro evidence suggested the ability of 15-keto-PGE(2) (a downstream metabolite of PGE(2)) to activate EP receptors, the question whether 15-keto-PGE(2) exhibits physiological roles remains unresolved. MATERIALS AND METHODS: Pharmacological treatment was performed in transgenic zebrafish embryos using 500 µM 15-keto-PGE(2) and 20 µM EP receptors antagonists' solutions during zebrafish embryonic development. After the exposure period, the embryos were fixed for confocal microscopy imaging and glomerular morphology analysis. KEY FINDINGS: Here, we show that 15-keto-PGE(2) can bind and stabilize EP2 and EP4 receptors on the plasma membrane in the yeast model. Using lipidomic analysis, we demonstrate both PGE(2) and 15-keto-PGE(2) are present at considerable levels in zebrafish embryos. Our high-resolution image analysis reveals the exogenous treatment with 15-keto-PGE(2) perturbs glomerular vascularization during zebrafish development. Specifically, we show that the increased levels of 15-keto-PGE(2) cause intercalation defects between podocytes and endothelial cells of glomerular capillaries effectively reducing the surface area of glomerular filtration barrier. Importantly, 15-keto-PGE(2)-dependent defects can be fully reversed by combined blockade of the EP2 and EP4 receptors. SIGNIFICANCE: Altogether, our results reveal 15-keto-PGE(2) to be a biologically active metabolite that modulates the EP receptor signaling in vivo, thus playing a potential role in kidney biology

Nutrition and Public Health in Georgia: Reviewing the current status and inspiring improvements: A joint event of the Georgian Nutrition Society, The Nutrition Society of the UK and Ireland and the Sabri clker Foundation, October 2023

\ua9 2024 Cambridge University Press. All rights reserved.Georgia lies to the north east of T\ufcrkiye, having a western border on the Black Sea. With a population of some 3.73 million, Georgia has a tradition of gastronomic excellence dating back millennia. However, changing lifestyles and external influences have, as elsewhere, led to problems of suboptimal nutrition, and lifestyle related diseases and disorders prevail. There is considerable scope for improving the focus on public health and nutrition in Georgia. With this in mind, the Georgian Nutrition Society teamed up with The Nutrition Society of the United Kingdom and Ireland and the Sabri clker Foundation, a public health charity based in Istanbul, T\ufcrkiye, to host a conference and workshops in Tbilisi, Georgia. The primary purpose was to review the current status of public health and nutrition in Georgia with reference to the situation elsewhere, to share examples of best practice and to identify opportunities for improvement. A particular highlight was the presentation of a programme of nutrition education for family physicians recently implemented in T\ufcrkiye.This summary of the proceedings is intended as a blueprint for action in Georgia and also to inspire others to consider how public health might be improved via a focus on balanced nutrition

Estrogen receptor-β signals left ventricular hypertrophy sex differences in normotensive deoxycorticosterone acetate-salt mice

We found earlier that deoxycorticosterone acetate-salt treatment causes blood pressure-independent left ventricular hypertrophy, but only in male mice. To test the hypothesis that the estrogen receptor-beta (ERbeta) protects the females from left ventricular hypertrophy, we treated male and female ERbeta-deficient (ERbeta(-/-)) mice and their male and female littermates (wild-type [WT]) with deoxycorticosterone acetate-salt and made them telemetrically normotensive with hydralazine. WT males had increased (+16%) heart weight/tibia length ratios compared with WT females (+7%) at 6 weeks. In ERbeta(-/-) mice, this situation was reversed. Female WT mice had the greatest heart weight/tibia length ratio increases of all of the groups (+23%), even greater than ERbeta(-/-) males (+10%). Echocardiography revealed concentric left ventricular hypertrophy in male WT mice, whereas ERbeta(-/-) females developed dilative left ventricular hypertrophy. The hypertrophic response in female ERbeta(-/-) mice was accompanied by the highest degree of collagen deposition, indicating maladaptive remodeling. ERbeta(+/+) females showed robust protective p38 and extracellular signal-regulated kinase 1/2 signaling relationships compared with other groups. Calcineurin Abeta expression and its positive regulator myocyte-enriched calcineurin-interacting protein 1 were increased in deoxycorticosterone acetate-salt female ERbeta(-/-) mice, yet lower than in WT males. Endothelin increased murine cardiomyocyte hypertrophy in vitro, which could be blocked by estradiol and an ERbeta agonist. We conclude that a functional ERbeta is essential for inducing adaptive p38 and extracellular signal-regulated kinase signaling, while reducing maladaptive calcineurin signaling in normotensive deoxycorticosterone acetate female mice. Our findings address the possibility of sex-specific cardiovascular therapies