Single anthocyanins effectiveness modulating inflammation markers in obesity: dosage and matrix composition analysis.

Anthocyanins (ACNs) are phytochemicals with numerous bioactivities, e.g., antioxidant and anti-inflammatory. Health benefits from consuming ACN-rich foods, extracts, and supplements have been studied in clinical trials (CT). However, the individual effect of single ACNs and their correlation with doses and specific bioactivities or molecular targets have not been thoroughly analyzed. This review shows a recompilation of single anthocyanins composition and concentrations used in CT, conducted to investigate the effect of these anti-inflammatory derivatives in obese condition. Single anthocyanin doses with changes in the levels of frequently monitored markers were correlated. In addition, the analysis was complemented with reports of studies made in vitro with single ACNs. Anthocyanins' efficacy in diseases with high baseline obesity-related inflammation markers was evidenced. A poor correlation was found between most single anthocyanin doses and level changes of commonly monitored markers. Correlations between cyanidin, delphinidin, and pelargonidin derivatives and specific molecular targets were proposed. Our analysis showed that knowledge of specific compositions and anthocyanin concentrations determined in future studies would provide more information about mechanisms of action.

Nutritional, bioactive components and health properties of the milpa triad system seeds (corn, common bean and pumpkin).

The milpa system is a biocultural polyculture technique. Heritage of Mesoamerican civilizations that offers a wide variety of plants for food purposes. Corn, common beans, and pumpkins are the main crops in this agroecosystem, which are important for people's nutritional and food security. Moreover, milpa system seeds have great potential for preventing and ameliorating noncommunicable diseases, such as obesity, dyslipidemia, type 2 diabetes, among others. This work reviews and analyzes the nutritional and health benefits of milpa system seeds assessed by recent preclinical and clinical trials. Milpa seeds protein quality, vitamins and minerals, and phytochemical composition are also reviewed. Evidence suggests that regular consumption of milpa seeds combination could exert complementing effect to control nutritional deficiencies. Moreover, the combination of phytochemicals and nutritional components of the milpa seed could potentialize their individual health benefits. Milpa system seeds could be considered functional foods to fight nutritional deficiencies and prevent and control noncommunicable diseases.

The CCAAT box in the proximal SERCA2 gene promoter regulates basal and stress-induced transcription in cardiomyocytes.

The cardiac sarco/endoplasmic reticulum Ca2+-ATPase-2a (SERCA2a) is vital for the correct handling of calcium concentration in cardiomyocytes. Recent studies showed that the induction of endoplasmic reticulum (ER) stress (ERS) with the SERCA2 inhibitor Thapsigargin (Tg) increases the mRNA and protein levels of SERCA2a. The SERCA2 gene promoter contains an ERS response element (ERSE) at position -78 bp that is conserved among species and might transcriptionally regulate SERCA2 gene expression. However, its involvement in SERCA2 basal and calcium-mediated transcriptional activation has not been elucidated. In this work, we show that in cellular cultures of neonatal rat ventricular myocytes, the treatment with Tg or the calcium ionophore A23187 increases the SERCA2a mRNA and protein abundance, as well as the transcriptional activity of two chimeric human SERCA2 gene constructs, containing -254 and -2579 bp of 5'-regulatory region cloned in the pGL3-basic vector and transiently transfected in cultured cardiomyocytes. We found that the ERSE present in the SERCA2 proximal promoter contains a CCAAT box that is involved in basal and ERS-mediated hSERCA2 transcriptional activation. The EMSA results showed that the CCAAT box present in the ERSE recruits the NF-Y transcription factor. Additionally, by ChIP assays, we confirmed in vivo binding of NF-Y and C/EBPß transcription factors to the SERCA2 gene proximal promoter.

Lovastatin Differentially Affects Neuronal Cholesterol and Amyloid-ß Production in vivo and in vitro.

BACKGROUND AND AIMS: Epidemiological and experimental studies indicate that high cholesterol may increase susceptibility to age-associated neurodegenerative disorders, such as Alzheimer's disease (AD). Thus, it has been suggested that statins, which are inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), may be a useful therapeutic tool to diminish the risk of AD. However, several studies that analyzed the therapeutic benefits of statins have yielded conflicting results. Herein, we investigated the role of lovastatin on neuronal cholesterol homeostasis and its effects on amyloid ß protein production in vivo and in vitro. METHODS AND RESULTS: Lovastatin effects were analyzed in vitro using differentiated human neuroblastoma cells and in vivo in a lovastatin-fed rat model. We demonstrated that lovastatin can differentially affect the expression of APP and Aß production in vivo and in vitro. Lovastatin-induced HMGCR inhibition was detrimental to neuronal survival in vitro via a mechanism unrelated to the reduction of cholesterol. We found that in vivo, dietary cholesterol was associated with increased Aß production in the cerebral cortex, and lovastatin was not able to reduce cholesterol levels. However, lovastatin induced a remarkable increase in the mature form of the sterol regulatory element-binding protein-2 (SREBP-2) as well as its target gene HMGCR, in both neuronal cells and in the brain. CONCLUSIONS: Lovastatin modifies the mevalonate pathway without affecting cholesterol levels in vivo and is able to reduce Aß levels only in vitro.

Regulation of sarco(endo)plasmic reticulum Ca2+-ATPase and calsequestrin gene expression in the heart.

The precise control of Ca(2+) levels during the contraction-relaxation cycle in cardiac myocytes is extremely important for normal beat-to-beat contractile activity. The sarcoplasmic reticulum (SR) plays a key role controlling calcium concentration in the cytosol. The SR Ca(2+)-ATPase (SERCA2) transports Ca(2+) inside the SR lumen during relaxation of the cardiac myocyte. Calsequestrin (Casq2) is the main protein in the SR lumen, functioning as a Ca(2+) buffer and participating in Ca(2+) release by interacting with the ryanodine receptor 2 (RyR2) Ca(2+)-release channel. Alterations in normal Ca(2+) handling significantly contribute to the contractile dysfunction observed in cardiac hypertrophy and in heart failure. Transcriptional regulation of the SERCA2 gene has been extensively studied and some of the mechanisms regulating its expression have been elucidated. Overexpression of Sp1 factor in cardiac hypertrophy downregulates SERCA2 gene expression and increased levels of thyroid hormone up-regulates its transcription. Other hormones such norepinephrine, angiotensin II, endothelin-1, parathyroid hormone, prostaglandin-F2α, as well the cytokines tumor necrosis factor-α and interleukin-6 also downregulate SERCA2 expression. Calcium acting through the calcineurin-NFAT (nuclear factor of activated T cells) pathway has been suggested to regulate SERCA2 and CASQ2 gene expression. This review focuses on the current knowledge regarding transcriptional regulation of SERCA2 and CASQ2 genes in the normal and pathologic heart.

Calcium-regulated transcriptional pathways in the normal and pathologic heart.

The cytosolic calcium concentration ([Ca(2+)](c)) is key for the regulation of many cellular processes, such cell signaling and proliferation, metabolism, and muscle contraction. In cardiomyocytes, Ca(2+) is an important regulator in many cellular functions such electrophysiological processes, excitation-contraction coupling, regulation of contractile proteins activity, energy metabolism, cell death, and transcriptional regulation by the activation of Ca(2+)-dependent transcriptional pathways. In cardiomyocytes, the two main Ca(2+) -dependent pathways are the Ca(2+)/calmodulin-calcineurin-NFAT and the Ca(2+) /calmodulin-dependent kinases-MEF2. Both pathways are involved in the transcriptional control of many cardiac genes. Cardiac hypertrophy (CH) and heart failure (HF) are characterized by alterations in calcium handling such a low sarcoplasmic reticulum Ca(2+) content, decreased rate of Ca(2+) removal from the sarcoplasm, increased diastolic [Ca(2+)](c), and decreased systolic [Ca(2+)](c), all of them contributing to diminished contractibility and force generation in failing heart. At gene expression level, there are also many changes such decreased levels of SERCA2a and activation of a fetal gene expression program in cardiomyocytes. A variety of Ca(2+)-dependent signaling pathways have been implicated in CH and HF, but whether these pathways are interrelated and whether there is specificity among them are still unclear and under investigation. The focus of this review is to make an analysis of the current knowledge about the role of Ca(2+) signaling pathways in the regulation of cardiac gene expression making special emphasis in novel strategies to correct Ca(2+) handling alterations by means of SERCA2a gene therapy.