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The aim of the present study is to explore the effect of retinoic acid (RA) on cardiac injury induced by gestational diabetes mellitus (GDM). GDM mice were given 3 mg/kg RA once daily until the 19th day of pregnancy or the 7th day of post-partum. Compared to normal control and normal pregnant control mice, GDM mice before and after delivery showed significantly cardiac injury. RA treatment attenuated cardiac injury as evidenced by decreased heart mass and left ventricular mass, mRNA expressions of ANP and BNP, and cardiac fibrosis compared with that in GDM mice. The protective effect of RA on GDM cardiomyopathy was related to the decreased MDA content and ROS generation, the increased GSH-Px and SOD content as well as the reduced TNF-[alpha] and IL-1[beta] content and inhibition of NF-[kappa]B signaling. In addition, RA treatment delayed the continuous rise of blood glucose before delivery and decreased the higher level of glucose after delivery. In conclusion, RA treatment could increase the activity of the antioxidant enzyme and suppress the oxidative stress, inflammation response, and activation of NF-[kappa]B signaling, thereby improving blood glucose level and cardiac injury of GDM mice before and after delivery. Key words: retinoic acid, gestational diabetes mellitus, oxidative stress, inflammation. Cette etude avait pour but d'explorer l'effet de l'acide retinoique (AR) sur les lesions cardiaques engendrees par le diabete sucre gestationnel (DSG). Nous avons administre de l'AR a des souris DSG a raison de 3 mg/kg une fois par jour jusqu'au 19e jour de gestation ou jusqu'au 7e jour apres la mise bas. Les souris DSG presentaient avant et apres la mise bas des lesions cardiaques marquees par rapport aux souris temoins normales et aux souris gravides temoins normales. L'administration d'AR entrainait une attenuation des lesions cardiaques mises en evidence par une diminution du poids du creur et de la masse du ventricule gauche, de l'expression en ARNm de l'ANP et du BNP, ainsi que par de la fibrose cardiaque par rapport aux souris DSG. L'effet protecteur de l'AR sur la cardiomyopathie DSG etait lie a la diminution des taux de malondialdehyde et de la production de derives reactifs de l'oxygene, a une augmentation des taux de GSH-Px et de superoxyde dismutase, ainsi qu'a une diminution des taux de facteur de necrose tumorale a et d'interleukine ip, avec une inhibition de la voie de signalisation du facteur nucleaire kB. De plus, l'administration d'AR entrainait des retards dans la hausse continue de la glycemie avant la mise bas, avec un abaissement des glycemies maximales apres la mise bas. En conclusion, l'administration d'AR pourrait entrainer une augmentation de l'activite de l'enzyme antioxydante, avec une inhibition du stress oxydatif, de la reaction inflammatoire et de l'activation des voies de signalisation du facteur nucleaire kB, ce qui pourrait avoir des effets positifs sur la glycemie et les lesions cardiaques chez les souris DSG avant et apres la mise bas. [Traduit par la Redaction] Mots-cles: acide retinoique, diabete sucre gestationnel, stress oxydatif, inflammation., Introduction Gestational diabetes mellitus (GDM), a common metabolic disorder, occurs during pregnancy and is estimated to affect 2%-5% of pregnant women (Capobianco et al. 2018; CEMACH 2002; Wendland et al. [...]

Extensive genetic changes as well as related gene function and activity disorders occur in the development of malignant tumors. DNA methylation in epigenetics is one of the best-characterized epigenetic modifications. It affects gene expression and genome stability, having an important impact on the development of malignant tumors. Most of these epigenetic changes occur in the early stages of malignant tumors and are widespread in the entire malignant tumor. DNA methylation biomarkers are important methods for early tumor diagnosis,prognosis and treatment detection. Cancer-related DNA methylation changes can be detected in blood, feces, urine and other biological samples. It is a non-invasive, rapid and reproducible alternative to tissue biopsy. DNA methylation is a simple, economical and highly specific malignant tumor detection method that can be applied to population screening. Although it faces many challenges, DNA methylation biomarkers have unique advantages, having the prospect of clinical translational application and value. This article reviews the characteristics of DNA methylation, the mechanism of action as well as the latest research progress in early diagnosis, clinical treatment effects,and prognosis determination in bladder cancer, breast cancer, colorectal cancer and other malignant tumors, discussing the problems and prospects of clinical translation.

Purpose: To investigate the therapeutic effect and underlying mechanism of a traditional Chinese medicine (TCM) mixture consisting of Astragalus, rhubarb, and saffron in a mouse model of diabetic kidney disease (DKD). Methods: Forty-eight db/db mice received no TCM (DKD model), low-dose TCM, medium-dose TCM, or high-dose TCM, and an additional 12 db/m mice received no TCM (normal control). Intragastric TCM or saline (controls) was administered daily for 24 weeks. Blood glucose, body weight, serum creatinine (SCr), blood urea nitrogen (BUN), blood lipids, and urinary microalbumin were measured every four weeks, and the urinary albumin excretion rate (UAER) was calculated. After 24 weeks, kidney tissues were collected for transcriptome sequencing, and the main functions of these genes were determined via functional enrichment analysis. Results: Compared with the DKD model group, the medium-dose and high-dose TCM groups had significantly decreased levels of SCr, BUN, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and UAER (all p< 0.05). We identified 42 genes that potentially functioned in this therapeutic response, and the greatest effect on gene expression was in the high-dose TCM group. We also performed functional enrichment analysis to explore the potential mechanisms of action of these different genes. Conclusion: A high-dose of the Astragalus-rhubarb-saffron TCM provided the best prevention of DKD. Analysis of the kidney transcriptome suggested that this TCM mixture may prevent DKD by altering immune responses and oxygen delivery by hemoglobin. [ABSTRACT FROM AUTHOR]

We previously reported that simvastatin, an inhibitor of HMG-CoA reductase, inhibits atherosclerosis in rats. The present study was designed to investigate the effect of simvastatin on mouse peritoneal macrophage foam cell formation, the early feature of atherosclerosis, and explore its mechanisms. The results showed that simvastatin decreased cholesterol content and DiI-oxLDL (1,1'-didodecyl 3,3,3',3'-indocarbocyanine perchlorate--oxidized low-density lipoprotein) uptake, reduced the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the medium, down-regulated the mRNA and protein expression of CD36 (a fatty acid receptor), and reduced the mRNA expressions of peroxisome proliferator-activated receptor gamma (PPARγ), TNF-α, and IL-6 in macrophages treated with oxLDL. However, PPARγ agonist troglitazone partly abolished the effects of simvastatin on foam cells. In addition, simvastatin reduced the protein expression of calpain-1, a [Ca.sup.2+]-sensitive cysteine protease, in oxLDL-treated macrophages. Furthermore, PD150606, a specific calpain inhibitor, reduced mRNA expressions of PPAR^ and CD36 in macrophages treated with oxLDL. Combination of simvastatin and PD150606 had no further effect on mRNA expression of PPARγ and CD36 compared with either alone. However, over-expression of calpain-1 in macrophages partly reversed the simvastatin effects, including cell cholesterol content, mRNA expressions of PPARγ, and CD36. The results suggested that simvastatin inhibits foam cell formation of oxLDL-treated macrophages through a calpain-1-PPARγ-CD36 pathway. Key words: simvastatin, foam cells, CD36, calpain inhibitor, PPARγ. Nous avons rapporte precedemment que la simvastatine, un inhibiteur de l'HMG-CoA reductase, inhibe l'atherosclerose chez le rat. Les presents travaux ont ete concus en vue d'etudier chez la souris l'effet de la simvastatine sur la formation de cellules spumeuses de macrophages peritoneaux, caracteristique precoce de l'atherosclerose, et d'en explorer les mecanismes. Les resultats ont montre que la simvastatine permettait de diminuer les taux de cholesterol et l'utilisation de DiI-oxLDL (<>) ainsi que les taux de facteur de necrose tumorale-α (TNF-α) et d'interleukine-6 (IL-6) dans la substance, de reguler a la baisse l'expression de la proteine CD36 et de l'ARNm relatif, de reduire l'expression du recepteur gamma active par les proliferateurs des peroxysomes (PPARγ), de TNF-α et d'IL-6 dans des macrophages exposes a l' oxLDL. Cependant, la troglitazone, un agoniste du PPARγ, contrait partiellement les effets de la simvastatine sur les cellules spumeuses. De plus, la simvastatine a permis de reduire l'expression de la calpaine-1, une protease a cysteine sensible a l'ion [Ca.sup.2+], dans les macrophages exposes aux oxLDL. En outre, le PD150606, un inhibiteur specifique de la calpaine, entrainait une diminution de l'expression de l'ARNm du PPARγ et du CD36 dans des macrophages exposes aux oxLDL. L'association de simvastatine avec le PD150606 n'a eu aucun effet supplementaire sur l'expression de l'ARNm du PPARγ et du CD36 comparativement a l'exposition a l'un ou a l'autre individuellement. Cependant, la surexpression de la calpaine-1 dans les macrophages a partiellement contre les effets de la simvastatine, y compris sur les taux intracellulaires de cholesterol et sur l'expression de l'ARNm du PPARγ et du CD36. Les resultats laissaient entendre que la simvastatine inhiberait la formation de cellules spumeuses a partir de macrophages exposes aux oxLDL par l'intermediaire de la voie de signalisation calpaine-1-PPARγ-CD36. [Traduit par la Redaction] Mots-cles: simvastatine, cellules spumeuses, CD36, inhibiteur de la calpaine, PPARγ., Introduction Atherosclerotic cardiovascular disease is the prime cause of mortality in developed countries, and its incidence in developing countries has been increasing recently (Zelicoff 2015). Oxidative stress has been involved [...]

Endothelial cell injury caused by reactive oxygen species (ROS) plays a critical role in the pathogenesis of cardiovascular disorders. Astragaloside IV (AslV) possesses potent antioxidant properties against oxidative stress through undefined mechanism(s). We sought to investigate whether AsIV protects human umbilical vein endothelial cells (HUVECs) from hydrogen peroxide ([H.sub.2][O.sub.2]) induced oxidative stress focusing on eNOS uncoupling and the NADPH oxidase--ROS--NF-κB pathway. Compared with HUVECs incubated with [H.sub.2][O.sub.2] alone, pretreatment with AsIV significantly increased the viability of HUVECs, which was accompanied with apparent increase in nitric oxide (NO) production and decrease in intracellular superoxide anion production. Furthermore, pretreatment with AsIV increased endothelial nitric oxide synthase (eNOS) dimer/monomer ratio and its critical cofactor tetrahydrobiopterin (B[H.sub.4]) content, decreased Nox4 protein expression (the most abundant Nox isoform in HUVECs), inhibited translocation of NF-κB p65 subunit into nuclear fraction while enhanced the protein expression of IkB-o (the inhibitor of NF-κB p65), reduced the levels of IL-1β, IL-6, and TNF-a in HUVECs medium, and decreased iNOS protein expression. These results suggest that AsIV may protect HUVECs from [H.sub.2][O.sup.2]-induced oxidative stress via inhibiting NADPH oxidase--ROS NF-κB pathway and eNOS uncoupling. Key words: Astragaloside IV, human umbilical vein endothelial cells, hydrogen peroxide, eNOS uncoupling, NF-κB, NADPH oxidase, tetrahydrobiopterin, superoxide anion. Les dommages causes aux cellules endotheliales par les derives reactifs de l'oxygene (ROS) jouent un role essentiel dans la pathogenese des troubles cardiovasculaires. L'astragaloside IV(AsIV) dispose de puissantes proprietes anti-oxydantes contre le stress oxydatif qui sont portees par des mecanismes toujours indetermines. Nous nous sommes employes a etudier si l'AsIV permet de proteger les cellules endotheliales des veines ombilicales humaines (HUVEC) du stress oxydatif provoque par le peroxyde d'hydrogene ([H.sub.2][O.sub.2]) en centrant nos efforts sur le decouplage de l'oxyde nitrique synthase endotheliale (eNOS) et la voie de signalisation NADPH oxydase--ROS--NF-κB. Comparativement a l'incubation avec le [H.sub.2][O.sub.2] seul, le pretraitement des cellules HUVEC avec de l'AsIV a permis d'augmenter nettement leur viabilite, ce qui etait accompagne d'une augmentation apparente de la production d'oxyde nitrique (NO) et d'une diminution de la production d'anions superoxyde dans le milieu intracellulaire. En outre, le pretraitement avec de l'AsIV a permis d'augmenter le ratio dimeres/monomeres de l'eNOS et les taux de tetrahydrobiopterine (B[H.sub.4]) (son cofacteur essentiel), de diminuer l'expression de la proteine Nox4 (l'isoforme des proteines Nox la plus abondante dans les cellules HUVEC) et d'inhiber la translocation de la sous-unite p65 du facteur NF-κB dans la fraction nucleaire. Ces phenomenes etaient accompagnes d'une augmentation de l'expression de la proteine IκB-α (la proteine inhibitrice de la sous-unite p65 du NF-κB) ainsi que d'une diminution des taux d'IL-1β, d'IL-6 et de TNF-α dans le milieu des cellules HUVEC; l'expression de la proteine iNOS etait aussi diminuee. Ces resultats laissent entendre que l'AsIV pourrait proteger les cellules HUVEC du stress oxydatif cause par le [H.sub.2][O.sub.2] par l'intermediaire de l'inhibition de la voie de signalisation NADPH oxydase--ROS NFκB et du decouplage de l'eNOS. [Traduit par la Redaction] Mots-cles : astragaloside IV, cellules endotheliales des veines ombilicales humaines, peroxyde d'hydrogen, decouplage de l'eNOS, NF-κB, NADPH oxydase, tetrahydrobiopterine, anion superoxyde., Introduction It has been demonstrated that oxidative stress plays a pivotal role in the development of the endothelial dysfunction associated with many cardiovascular disease (Hermida and Balligand 2014; Makarenko et [...]