Millets, cereals and grains play an important role in providing adequate nutrition and as well shown to possess beneficial effects on lifestyle disorders. Several studies on millet seed proteins and their hydrolysates, have demonstrated their physiological role in the prevention of chronic diseases by acting on various molecular targets. In recent years, the importance of food derived bioactive peptides is surging at an exponential rate in both nutraceutical and pharmaceutical research. A considerable number of earlier reviews have discussed their role in improving the human health. However, a concise review on millet-derived peptides and their purported role in human health is still lacking. Thus, this review provides an extensive survey of key bioactive millet peptides (BAMPs) reported till date in a succinct form. BAMPs are derived through enzymatic hydrolysis of the seed proteins and are known to perform several regulatory functions in vitro and in vivo. Several in silico and in vitro studies have demonstrated the antimicrobial, antioxidant, antihypertensive, anticancer and antidiabetic properties of BAMPs. Even though, the biological application of these peptides profoundly depends on the size and structure, the absorption in target tissues and bioavailability also play a critical role. Thus, the aim of this review is to discuss and summarize several key BAMPs from various millets reported so far, focusing on their proposed multifaceted biochemical activity, production, purification and mechanism of action. In addition, some of the key parameters for the successful delivery and bioavailability of these peptides are also highlighted. Nevertheless, in-depth investigations on the in vivo mode of action of BAMPs crucial in future to validate and translate these observed effects to human health benefits.

Cardiac fibrosis is a pathological condition characterized by excessive deposition of collagen and other extracellular matrix components in the heart. It is recognized as a major contributor to the development and progression of heart failure. Despite significant research efforts in characterizing and identifying key molecular mechanisms associated with myocardial fibrosis, effective treatment for this condition is still out of sight. In this regard, bioactive compounds have emerged as potential therapeutic antifibrotic agents due to their anti-inflammatory and antioxidant properties. These compounds exhibit the ability to modulate fibrogenic processes by inhibiting the production of extracellular matrix proteins involved in fibroblast to myofibroblast differentiation, or by promoting their breakdown. Extensive investigation of these bioactive compounds offers new possibilities for preventing or reducing cardiac fibrosis and its detrimental consequences. This comprehensive review aims to provide a thorough overview of the mechanisms underlying cardiac fibrosis, address the limitations of current treatment strategies, and specifically explore the potential of bioactive compounds as therapeutic interventions for the treatment and/or prevention of cardiac fibrosis.

Diabetic cardiomyopathy is a major complication of diabetes mellitus, characterised by impaired calcium homeostasis, insulin resistance, and metabolic dysregulation. Notably, the expression and activity of sarco/endoplasmic reticulum Ca²⁺-ATPase 2a (SERCA2a) are diminished in diabetic heart failure, contributing to both systolic and diastolic dysfunction. Although enhancing SERCA2a function has shown beneficial cardiac effects, the underlying metabolic mechanisms remain unclear. The objective of this study was to investigate the effect of pharmacological activation of SERCA2a in the diabetic heart. This study aimed to evaluate the impact of pharmacological activation of SERCA2a on cardiac function and metabolism in a diabetic context. Leptin-deficient (Ob/ob) diabetic mice were treated using two strategies: a novel SERCA2a allosteric agonist (CDN1163) and cardiac-specific overexpression via AAV9-mediated gene delivery. Both approaches attenuated the expression of genes involved in lipid synthesis and fatty acid oxidation, thereby improving lipid homeostasis. Enhanced SERCA2a activity promoted mitochondrial biogenesis, increased mitochondrial DNA content, improved oxidative phosphorylation, and elevated ATPase activity in diabetic hearts. In vitro, SERCA2a restoration in high glucose and H₂O₂-treated H9C2 myocytes normalised mitochondrial membrane potential and improved mitochondrial function. Additionally, SERCA2a activation mitigated lipotoxicity and cell injury through upregulation of antioxidant enzymes and suppression of ROS by inhibiting NADPH oxidase activity. Crucially, these molecular improvements translated into enhanced diastolic function in diabetic mice following both CDN1163 and AAV9-SERCA2a treatments. Collectively, our findings suggest SERCA2a activation may offer a promising therapy for diabetic cardiomyopathy by improving cardiac energetics, lipid metabolism, and mitochondrial function.

This review highlights the emerging functional implications of nonsense-mediated mRNA decay (NMD) in human diseases, with a focus on its therapeutic potential for cardiovascular disease. NMD, conserved from yeast to humans, is involved in apoptosis, autophagy, cellular differentiation, and gene expression regulation. NMD is a highly conserved surveillance mechanism that degrades mRNAs containing premature termination codons (PTCs) located upstream of the final exon-exon junction. NMD serves to prevent the translation of aberrant mRNA and prevents the formation of defective protein products that could result in diseases. Key players in this pathway include up-frameshift proteins (UPFs), nonsense-mediated mRNA decay associated with p13K-related kinases (SMGs), and eukaryotic release factors (eRFs), among others. Dysregulation of NMD has been linked to numerous pathological conditions such as dilated cardiomyopathy, cancer, viral infections, and various neurodevelopmental and genetic disorders. This review will examine the regulatory mechanisms by which NMD regulation or dysregulation may contribute to disease mitigation or progression and its potential for cardiovascular disease therapy. We will further explore how modulating NMD could prevent the outcomes of mutations underlying genetically induced cardiovascular conditions and its applications in personalized medicine due to its role in gene regulation. While recent advances have provided valuable insights into NMD machinery and its therapeutic potential, further studies are needed to clarify the precise roles of key NMD components in cardiovascular disease prevention and treatment.