Dysfunctional hepatic metabolism has been linked to numerous diseases, including non-alcoholic fatty liver disease, the most common chronic liver disorder worldwide, which can progress to hepatic fibrosis, and is closely associated with insulin resistance and cardiovascular diseases. In addition, the liver secretes a wide array of metabolites, biomolecules, and microRNAs (miRNAs) and many of these secreted factors exert significant effects on metabolic processes both in the liver and in peripheral tissues. In this review, we summarize the involvement of liver-derived miRNAs in biological processes with an emphasis on delineating the communication between the liver and other tissues associated with metabolic disease progression. Furthermore, the review identifies the primary molecular targets by which miRNAs act. These consolidated findings from numerous studies provide insight into the underlying mechanism of various metabolic disease progression and suggest the possibility of using circulatory miRNAs as prognostic predictors and therapeutic targets for improving clinical intervention strategies.

The acute manifestations of coronavirus disease 2019 (COVID-19) exhibit the hallmarks of sepsis-associated complications that reflect multiple organ failure. The inflammatory cytokine storm accompanied by an imbalance in the pro-inflammatory and anti-inflammatory host response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to severe and critical septic shock. The sepsis signature in severely afflicted COVID-19 patients includes cellular reprogramming and organ dysfunction that leads to high mortality rates, emphasizing the importance of improved clinical care and advanced therapeutic interventions for sepsis associated with COVID-19. Phytochemicals of functional foods and nutraceutical importance have an incredible impact on the healthcare system, which includes the prevention and/or treatment of chronic diseases. Hence, in the present review, we aim to explore the pathogenesis of sepsis associated with COVID-19 that disrupts the physiological homeostasis of the body, resulting in severe organ damage. Furthermore, we have summarized the diverse pharmacological properties of some potent phytochemicals, which can be used as functional foods as well as nutraceuticals against sepsis-associated complications of SARS-CoV-2 infection. The phytochemicals explored in this article include quercetin, curcumin, luteolin, apigenin, resveratrol, and naringenin, which are the major phytoconstituents of our daily food intake. We have compiled the findings from various studies, including clinical trials in humans, to explore more into the therapeutic potential of each phytochemical against sepsis and COVID-19, which highlights their possible importance in sepsis-associated COVID-19 pathogenesis. We conclude that our review will open a new research avenue for exploring phytochemical-derived therapeutic agents for preventing or treating the life-threatening complications of sepsis associated with COVID-19.

The heparin anti-Xa assay is affected by the use of direct oral anticoagulants (DOACs) and is utilized in the management of intravenous unfractionated heparin. Patients with non-ST-segment myocardial infarction (NSTEMI) receive intravenous unfractionated heparin with prior administration of DOACs poses challenges given these laboratory abnormalities. On this background, we evaluate if an elevated heparin anti-Xa assay may lead to the decision to delay heparin in the management of NSTEMI patients and the outcome of in-hospital mortality. This is a single-center chart review study with patients admitted between January 2019 and December 2020. Patients with a documented DOAC home medication and a diagnosis of NSTEMI were included. Data was collected for heparin anti-Xa levels at baseline, after 6 and 12 hours of hospitalization, in addition to the reason for the delay in the administration of heparin. Statistical analysis included the determination of r-squared correlation and one-way ANOVA using GraphPad Prism 8.0. A total of 44 patients were divided into three groups based on baseline Xa levels of patients. Elevated Xa level was noted more in patients who were taking apixaban. Heparin infusion was delayed among this sub-group of patients. Elevated baseline heparin anti-Xa levels were significantly improved after 12 hours. There was no correlation between elevated anti-Xa levels and activated partial thromboplastin time. No in-hospital mortality was observed among any of the subgroups. Collectively, this study demonstrates that the high sensitivity of heparin anti-Xa assay to DOACs affect assay accuracy and result in elevated heparin anti-Xa level with the use of DOACs resulting in delayed start of heparin therapy in treating NSTEMI patients.

Dementia is a progressive neurodegenerative disorder that represents a growing challenge to global health, especially in aging populations. The burden of dementia is high in rural communities, where access to healthcare services, nutritional resources, and educational opportunities is significantly limited. A critical knowledge gap exists regarding how rural-specific nutritional disparities mechanistically interact with gut–brain axis dysfunction to influence dementia risk. The gut-brain axis mediates neuroimmune communication, metabolic regulation, and microbial signaling, and nutritional insufficiency is associated with reduced microbial diversity, impaired short-chain fatty acid (SCFAs) production, increased intestinal permeability, and heightened systemic inflammatory activity, all of which contribute to neurodegenerative processes. This review delineates the mechanistic pathways linking malnutrition-induced gut dysregulation to neuronal injury and cognitive decline, with a specific focus on rural populations. We further evaluate the biological actions of key nutraceutical classes, including phytochemicals (curcumin, resveratrol, sulforaphane, ginkgo biloba), vitamins (B12, C, E, and D), and metabolic/dietary interventions (omega-3 fatty acids, ketogenic diet, Mediterranean diet, trehalose). By consolidating preclinical and clinical evidence, we identify the molecular targets through which these nutraceuticals modulate oxidative stress, inflammatory signaling networks, blood-brain barrier (BBB) integrity, and microRNA regulation. In summary, our findings suggest that nutraceutical-based approaches targeting gut-brain axis dysfunction may provide a feasible and biologically informed strategy for mitigating dementia disparities in rural settings.

Exosomes have emerged as key mediators of intercellular and inter-organ communication. Although substantial advances have expanded the understanding of the biology of extracellular vesicles, exosome biogenesis and their role in the disease progression of systemic diseases have not yet been fully elucidated. In this review, we present a comprehensive overview of the molecular pathways responsible for exosome biogenesis, emphasizing how the selective incorporation of proteins, lipids, metabolites, messenger RNAs, and microRNAs (miRs) determines the composition and biological activity of exosomes. We also discuss how exosome-mediated inter-organ communication functions as an integrated biological network that connects the kidney, the cardiovascular system, the brain, the liver, the immune system, and tumors, thereby coordinating the pathological responses underlying the progression of chronic diseases. Additionally, we demonstrate the recent advances in the potential of exosomes as minimally invasive biomarkers and clinical translational implantation. Finally, we discussed the methodological and biological challenges that limit the clinical application of exosomes. Overall, this review presents an integrated framework for understanding exosome biology and supports the concept that exosomes function as dynamic platforms for systemic signaling that link molecular mechanisms to disease pathogenesis and translational medicine.