An investigation into haloarchaea's potential as a novel source of natural antioxidants and anti-inflammatory compounds is the focus of this study. At the Odiel Saltworks (OS), a carotenoid-generating haloarchaeal strain was isolated, and its 16S rRNA gene sequence analysis revealed it to be a novel member of the Haloarcula genus. Specific to the Haloarcula genus, a particular species is identified. The OS acetone extract (HAE), originating from the biomass, displayed potent antioxidant properties in the ABTS assay, and contained bacterioruberin, with C18 fatty acids being the main component. This study provides, for the first time, compelling evidence that treating lipopolysaccharide (LPS)-stimulated macrophages with HAE beforehand leads to a decrease in reactive oxygen species (ROS) generation, a reduction in pro-inflammatory cytokine concentrations of TNF-alpha and IL-6, and an upregulation of the Nrf2 factor and its related heme oxygenase-1 (HO-1) gene. This suggests a potential therapeutic role for HAE in oxidative stress-associated inflammatory diseases.
Diabetic wound healing stands as a global medical predicament requiring attention. Several investigations pointed to the complex reasons behind the prolonged healing times in diabetic individuals. While other aspects may play a role, the primary cause of chronic wounds in diabetes stems from the overproduction of reactive oxygen species (ROS) and the compromised detoxification of these species. Certainly, the enhancement of reactive oxygen species (ROS) encourages the production and function of metalloproteinases, leading to a substantial proteolytic condition in the wound, causing significant degradation of the extracellular matrix. This breakdown prevents the healing process. ROS accumulation acts synergistically with NLRP3 inflammasome activation and macrophage hyperpolarization, driving the pro-inflammatory M1 profile. Oxidative stress acts as a catalyst in the activation mechanism of NETosis. The wound's pro-inflammatory state, elevated by this factor, impedes the crucial process of inflammation resolution, essential for wound healing. Medicinal plants and natural compounds can enhance diabetic wound healing by directly addressing oxidative stress and the transcription factor Nrf2, which controls the antioxidant response, or by affecting mechanisms altered by increased reactive oxygen species (ROS), such as the NLRP3 inflammasome, macrophage polarization, and the expression or activation of metalloproteinases. The diabetic pro-healing activity of nine plants from the Caribbean, this study reveals, is particularly influenced by the presence of five polyphenolic compounds. Following this review, research perspectives are elaborated upon.
The human body is home to the ubiquitous, multifunctional protein Thioredoxin-1 (Trx-1). The crucial function of Trx-1 in cellular processes involves maintaining redox homeostasis, controlling proliferation, facilitating DNA synthesis, influencing transcription factors, and regulating cell death. Ultimately, Trx-1 plays a critical role as one of the most important proteins for the correct and consistent operation of cells and organs. Hence, the modulation of Trx gene expression or the modulation of Trx activity via methods including post-translational modifications and protein-protein interactions could instigate a transition from the natural state of cells and organs into various pathologies, such as cancer, neurodegenerative and cardiovascular diseases. Beyond discussing current knowledge of Trx in health and disease, this review also spotlights its prospective use as a biomarker.
The pharmacological effects of a callus extract from the pulp of Cydonia oblonga Mill., better known as quince, were assessed in murine macrophage (RAW 2647) and human keratinocyte (HaCaT) cell lines. A significant aspect of *C. oblonga Mill* is its anti-inflammatory activity. The Griess test was utilized to evaluate the pulp callus extract's effect on lipopolysaccharide (LPS)-stimulated RAW 2647 cells, while the expression of inflammatory genes, such as nitric oxide synthase (iNOS), interleukin-6 (IL-6), interleukin-1 (IL-1), nuclear factor-kappa-B inhibitor alpha (IkB), and intercellular adhesion molecule (ICAM), was measured in LPS-treated HaCaT human keratinocytes. The antioxidant activity was determined via quantification of reactive oxygen species (ROS) generation in HaCaT cells that were injured by hydrogen peroxide and tert-butyl hydroperoxide. C. oblonga callus, derived from fruit pulp extract, exhibits anti-inflammatory and antioxidant effects, suggesting potential applications in the management of age-related acute or chronic diseases, and as a wound dressing component.
Mitochondria's life cycle is intrinsically linked to their dual roles in producing and defending against reactive oxygen species (ROS). PGC-1, the transcriptional activator, is essential for the maintenance of energy metabolism homeostasis, thereby directly affecting mitochondrial function. PGC-1, responding to environmental and intracellular signals, is subject to control by SIRT1/3, TFAM, and AMPK, all of which are key determinants of mitochondrial biogenesis and performance. This review examines PGC-1's functions and regulatory mechanisms, particularly its role in mitochondrial processes and reactive oxygen species (ROS) management, within this framework. Post infectious renal scarring We present the example of PGC-1's role in eliminating reactive oxygen species within an inflammatory environment. One observes a reciprocal regulatory interplay between PGC-1 and the immune response regulator NF-κB, a stress response factor. Inflammation leads to decreased PGC-1 expression and activity, a consequence of NF-κB activation. A lower-than-optimal PGC-1 activity results in the downregulation of genes essential for antioxidant defense, thereby fostering an oxidative stress state. Additionally, low PGC-1 levels, along with oxidative stress, promote NF-κB activation, escalating the inflammatory reaction.
Heme, a complex of iron and protoporphyrin, is fundamental to all cellular processes, especially in proteins such as hemoglobin, myoglobin, and the cytochromes within mitochondria, acting as an indispensable prosthetic group. Recognizing heme's dual nature, its capacity to contribute to pro-oxidant and pro-inflammatory responses is evident, leading to cytotoxic effects in organs like the kidney, brain, heart, liver, and immune cells. In fact, heme, freed upon tissue damage, has the potential to ignite inflammatory reactions, both in the immediate area and further afield. These factors can activate innate immunity, leading to responses that, if uncontrolled, can amplify initial damage and precipitate organ failure. Unlike other membrane elements, a specific set of heme receptors line the plasma membrane, serving either to import heme or activate particular signaling routes. In this way, free heme can be either a harmful molecule or a director and initiator of highly specific cellular responses which are fundamentally important for continued survival. The interplay of heme metabolism and signaling pathways, encompassing the stages of heme synthesis, degradation, and scavenging, are reviewed in this paper. Our investigation into trauma and inflammatory diseases will emphasize traumatic brain injury, trauma-related sepsis, cancer, and cardiovascular diseases, where current studies have indicated heme's possible paramount significance.
By unifying diagnostics and therapeutics, theragnostics presents a personalized strategy, demonstrating promise. Vevorisertib datasheet Accurate replication of in vivo conditions in an in vitro setting is a fundamental requirement for the conduct of meaningful theragnostic investigations. Within the context of personalized theragnostic strategies, this review delves into the importance of redox homeostasis and mitochondrial function. Protein localization, density, and degradation constitute crucial cellular responses to metabolic stress, pathways that ultimately contribute to cell survival. Nevertheless, the disruption of redox equilibrium can trigger oxidative stress and cellular injury, conditions associated with various diseases. The development of models illustrating oxidative stress and mitochondrial dysfunction in metabolically-conditioned cells is necessary to further the understanding of the root causes of diseases and the subsequent design of new therapies. Selecting an appropriate cellular model, fine-tuning cell culture parameters, and verifying the model's accuracy enable the identification of the most promising therapeutic avenues and the customization of treatments for individual patients. We conclude by stressing the paramount importance of precise and individualized theragnostic methodologies and the imperative for developing accurate in vitro models which faithfully reflect in vivo conditions.
Maintaining redox homeostasis is crucial for a healthy state; conversely, its impairment gives rise to a variety of pathological conditions. Polyphenols, polyunsaturated fatty acids (PUFAs), and carbohydrates accessible to the microbiota (MACs), which are bioactive food components, are best characterized for their beneficial effects on human health. Notably, a growing body of evidence demonstrates that their ability to combat oxidative stress contributes to the prevention of several human diseases. biologic drugs Empirical evidence points to a possible role for the activation of the nuclear factor erythroid 2-related 2 (Nrf2) pathway, the fundamental mechanism of maintaining redox homeostasis, in the advantageous impacts of including polyunsaturated fatty acids and polyphenols in one's diet. Nonetheless, the latter compound requires metabolic alteration to attain activity, and the gut microbiota is essential in the biotransformation of some ingested food constituents. Additionally, recent investigations showcasing the impact of MACs, polyphenols, and PUFAs in increasing the microbial communities producing biologically active metabolites (such as polyphenol metabolites and short-chain fatty acids, or SCFAs), corroborate the hypothesis that these factors are responsible for the antioxidant influence on the host's physiology.