Efficacy of Bioactive Compounds in the Regulation of Metabolism and Pathophysiology in Cardiovascular Diseases.

PURPOSE OF REVIEW: An imbalance in reactive oxygen species (ROS) homeostasis can wreak damage to metabolic and physiological processes which can eventually lead to an advancement in cardiovascular diseases (CVD). Mitochondrial dysfunction is considered as a key source of ROS. The purpose of the current review is to concisely discuss the role of bioactive compounds in the modulation of cardiovascular metabolism and their potential application in the management of cardiovascular diseases. RECENT FINDINGS: Recently, it has been shown that bioactive compounds exhibit immunomodulatory function by regulating inflammatory pathways and ROS homeostasis. It has also been reported that bioactive compounds regulate mitochondria dynamics, thus modulating the autophagy and energy metabolism in the cells. In the present article, we have discussed the roles of different bioactive compounds in the modulation of different inflammatory drivers. The functional properties of bioactive compounds in mitochondrial dynamics and its impact on cardiac disease protection have been briefly summarized. Furthermore, we have also discussed various aspects of bioactive compounds with respect to metabolism, immune modulation, circadian rhythm, and its impact on CVD's pathophysiology.

Integrative network analyses of wilt transcriptome in chickpea reveal genotype dependent regulatory hubs in immunity and susceptibility.

Host specific resistance and non-host resistance are two plant immune responses to counter pathogen invasion. Gene network organizing principles leading to quantitative differences in resistant and susceptible host during host specific resistance are poorly understood. Vascular wilt caused by root pathogen Fusarium species is complex and governed by host specific resistance in crop plants, including chickpea. Here, we temporally profiled two contrasting chickpea genotypes in disease and immune state to better understand gene expression switches in host specific resistance. Integrative gene-regulatory network elucidated tangible insight into interaction coordinators leading to pathway determination governing distinct (disease or immune) phenotypes. Global network analysis identified five major hubs with 389 co-regulated genes. Functional enrichment revealed immunome containing three subnetworks involving CTI, PTI and ETI and wilt diseasome encompassing four subnetworks highlighting pathogen perception, penetration, colonization and disease establishment. These subnetworks likely represent key components that coordinate various biological processes favouring defence or disease. Furthermore, we identified core 76 disease/immunity related genes through subcellular analysis. Our regularized network with robust statistical assessment captured known and unexpected gene interaction, candidate novel regulators as future biomarkers and first time showed system-wide quantitative architecture corresponding to genotypic characteristics in wilt landscape.

Interplay of neuronal and non-neuronal genes regulates intestinal DAF-16-mediated immune response during Fusarium infection of Caenorhabditis elegans.

Although precisely controlled innate immune response is governed by conserved cellular events in phylogenetically diverse hosts, the underlying molecular mechanisms by which this process is regulated against a multi-host pathogen remain unknown. Fusarium oxysporum is a model multi-host pathogen, known to be associated with neuronal stress in humans and vascular wilt in plants. The interaction between innate immune and neuronal pathways is the basis of many diverse biological responses. How these processes are coordinated in response to fungal disease is not well understood. Here, we show that F. oxysporum f. sp. ciceri causes neuronal stress and intestinal disintegration, ultimately leading to the death of Caenorhabditis elegans. To explore the regulatory framework of Fusarium-associated disease, we analysed the gene expression during infection, integrated temporal gene expression, and network analysis with genetic inactivation data in Caenorhabditis elegans. We identified 1024 genes showing significant changes in expression (corrected P-values <0.05) in response to Fusarium infection. Co-expression network analysis of our data identified prognostic genes related to disease progression. These genes were dynamically expressed in various neuronal and non-neuronal tissues exhibiting diverse biological functions, including cellular homeostasis, organ patterning, stress response, and lipid metabolism. The RNA-seq analysis further identified shared and unique signalling pathways regulated by DAF-16/FOXO and SIR-2.1 linking neuronal stress, which facilitates negative regulation of intestinal innate immunity. Genetic analysis revealed that GCY-5 in ASE functions upstream of DAF-16, whereas ASI-specific SRD-1 regulates behavioural immunity. Overall, our results indicate that a ubiquitous response occurs during Fusarium infection mediated by highly conserved regulatory components and pathways, which can be exploited further for the identification of disease-responsive genes conserved among animals and plants. Finally, this study provided a novel insight into cross-species immune signalling and may facilitate the discovery of cellular therapeutic targets for Fusarium-associated disease.

Reduction of oxalate levels in tomato fruit and consequent metabolic remodeling following overexpression of a fungal oxalate decarboxylase.

The plant metabolite oxalic acid is increasingly recognized as a food toxin with negative effects on human nutrition. Decarboxylative degradation of oxalic acid is catalyzed, in a substrate-specific reaction, by oxalate decarboxylase (OXDC), forming formic acid and carbon dioxide. Attempts to date to reduce oxalic acid levels and to understand the biological significance of OXDC in crop plants have met with little success. To investigate the role of OXDC and the metabolic consequences of oxalate down-regulation in a heterotrophic, oxalic acid-accumulating fruit, we generated transgenic tomato (Solanum lycopersicum) plants expressing an OXDC (FvOXDC) from the fungus Flammulina velutipes specifically in the fruit. These E8.2-OXDC fruit showed up to a 90% reduction in oxalate content, which correlated with concomitant increases in calcium, iron, and citrate. Expression of OXDC affected neither carbon dioxide assimilation rates nor resulted in any detectable morphological differences in the transgenic plants. Comparative proteomic analysis suggested that metabolic remodeling was associated with the decrease in oxalate content in transgenic fruit. Examination of the E8.2-OXDC fruit proteome revealed that OXDC-responsive proteins involved in metabolism and stress responses represented the most substantially up- and down-regulated categories, respectively, in the transgenic fruit, compared with those of wild-type plants. Collectively, our study provides insights into OXDC-regulated metabolic networks and may provide a widely applicable strategy for enhancing crop nutritional value.