Type 2 diabetes (T2D) is a metabolic disorder characterized by hyperglycemia and insulin resistance in which oxidative stress is thought to be a primary cause. Considering that mitochondria are the main source of ROS, we have set out to provide a general overview on how oxidative stress is generated and related to T2D. Enhanced generation of reactive oxygen species (ROS) and oxidative stress occurs in mitochondria as a consequence of an overload of glucose and oxidative phosphorylation. Endoplasmic reticulum (ER) stress plays an important role in oxidative stress, as it is also a source of ROS. The tight interconnection between both organelles through mitochondrial-associated membranes (MAMs) means that the ROS generated in mitochondria promote ER stress. Therefore, a state of stress and mitochondrial dysfunction are consequences of this vicious cycle. The implication of mitochondria in insulin release and the exposure of pancreatic β-cells to hyperglycemia make them especially susceptible to oxidative stress and mitochondrial dysfunction. In fact, crosstalk between both mechanisms is related with alterations in glucose homeostasis and can lead to the diabetes-associated insulin-resistance status. In the present review, we discuss the current knowledge of the relationship between oxidative stress, mitochondria, ER stress, inflammation, and lipotoxicity in T2D.

Relationship between Oxidative Stress, ER Stress, and Inflammation in Type 2 Diabetes: The Battle Continues

A new strain of a novel infectious disease affecting millions of people, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently been declared as a pandemic by the World...

An investigation into the identification of potential inhibitors of SARS-CoV-2 main protease using molecular docking study.

Polyphenols are a group of phytochemicals with potential health-promoting effects. They are classified as flavonoid (flavonols, flavanols, flavones, flavanones, isoflavones, and anthocyanins) and non-flavonoid molecules (phenolic acids, hydroxycinnamic acids, lignans, stilbenes, and tannins). Although an increasing number of trials have shown a correlation among polyphenol consumption and a reduction in risk factors for chronic diseases, discrepancies in explaining their positive effects have been found in terms of the bioavailability. In fact, polyphenols show a low bioavailability due to several factors: interaction with the food matrix, the metabolic processes mediated by the liver (phase I and II metabolism), intestine and microbiota. On the other hand, the biological activities of phenol compounds may be mediated by their metabolites, which are produced in vivo, and recent studies have confirmed that these molecules may have antioxidant and anti-phlogistic properties. This review discusses the studies performed in vivo, which consider the polyphenol bioavailability and their different food sources. Factors influencing the biological effects of the main classes of polyphenols are also considered.

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Polyphenols and Human Health: The Role of Bioavailability

Phenolic compounds are parts of secondary metabolites mostly found in plant species with enormous structural diversities. They can exist as glycosides or aglycones; matrix or free-bound compounds; and comprising mostly polymerized or monomer structures. Additionally, these compounds are not universally dispensed within plants with varied stability. This has contributed to challenging extraction processes; implying that employing a single step or inappropriate extraction technique might change the recovery of phenolic components from the plant samples. Hence, it is important to select an appropriate extraction method so as to recover the targeted phenolic compounds. This is will helps to recover substantial yields from the sample matrix. Therefore, this review mainly focuses on the phenolic compounds and several methods of extraction that are used to obtaining them from plant materials. These extraction methods includes both conventional and unconventional techniques.

Extraction of phenolic compounds: A review.

Phenolic compounds are broadly represented in plant kingdom, and their occurrence in easily accessible low-cost sources like wastes from agri-food processing have led in the last decade to an increase of interest in their recovery and further exploitation. Indeed, most of these compounds are endowed with beneficial properties to human health (e.g., in the prevention of cancer and cardiovascular diseases), that may be largely ascribed to their potent antioxidant and scavenging activity against reactive oxygen species generated in settings of oxidative stress and responsible for the onset of several inflammatory and degenerative diseases. Apart from their use as food supplements or as additives in functional foods, natural phenolic compounds have become increasingly attractive also from a technological point of view, due to their possible exploitation in materials science. Several extraction methodologies have been reported for the recovery of phenolic compounds from agri-food wastes mostly based on the use of organic solvents such as methanol, ethanol, or acetone. However, there is an increasing need for green and sustainable approaches leading to phenolic-rich extracts with low environmental impact. This review addresses the most promising and innovative methodologies for the recovery of functional phenolic compounds from waste materials that have appeared in the recent literature. In particular, extraction procedures based on the use of green technologies (supercritical fluid, microwaves, ultrasounds) as well as of green solvents such as deep eutectic solvents (DES) are surveyed.

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Bioactive Phenolic Compounds From Agri-Food Wastes: An Update on Green and Sustainable Extraction Methodologies.

This narrative mini- review summarizes current knowledge of the role of polyphenols in health outcomes-and non-communicable diseases specifically-and discusses the implications of this evidence for public health, and for future directions for public health practice, policy, and research The publications cited originate mainly from animal models and feeding experiments, as well as human cohort and case-control studies Hypothesized protective effects of polyphenols in acute and chronic diseases, including obesity, neurodegenerative diseases, type 2 diabetes, and cardiovascular diseases, are evaluated Potential harmful effects of some polyphenols are also considered, counterbalanced with the limited evidence of harm in the research literature Recent international governmental regulations are discussed, as the safety and health claims of only a few specific polyphenolic compounds have been officially sanctioned The implications of food processing on the bioavailability of polyphenols are also assessed, in addition to the health claims and marketing of polyphenols as a functional food Finally, this mini-review asserts the need for increased regulation and guidelines for polyphenol consumption and supplementation in order to ensure consumers remain safe and informed about polyphenols

/pdf/the-role-of-polyphenols-in-human-health-and-food-systems-a-51jpy40zvl.pdf

The Role of Polyphenols in Human Health and Food Systems: A Mini-Review.

Abstract Preclinical mechanistic studies have pointed towards RNA interference-mediated off-target effects as a major driver of hepatotoxicity for GalNAc–siRNA conjugates. Here, we demonstrate that a single glycol nucleic acid or 2′–5′-RNA modification can substantially reduce small interfering RNA (siRNA) seed-mediated binding to off-target transcripts while maintaining on-target activity. In siRNAs with established hepatotoxicity driven by off-target effects, these novel designs with seed-pairing destabilization, termed enhanced stabilization chemistry plus (ESC+), demonstrated a substantially improved therapeutic window in rats. In contrast, siRNAs thermally destabilized to a similar extent by the incorporation of multiple DNA nucleotides in the seed region showed little to no improvement in rat safety suggesting that factors in addition to global thermodynamics play a role in off-target mitigation. We utilized the ESC+ strategy to improve the safety of ALN-HBV, which exhibited dose-dependent, transient and asymptomatic alanine aminotransferase elevations in healthy volunteers. The redesigned ALN-HBV02 (VIR-2218) showed improved specificity with comparable on-target activity and the program was reintroduced into clinical development.

/pdf/from-bench-to-bedside-improving-the-clinical-safety-of-3ea69wl4.pdf

John Szeto

Papers

The Role of Polyphenols in Human Health and Food Systems: A Mini-Review.

From bench to bedside: Improving the clinical safety of GalNAc–siRNA conjugates using seed-pairing destabilization