ROS-scavenging Properties Research Articles

Multifunctional SEBS/AgNWs Nanocomposite Films with Antimicrobial, Antioxidant, and Anti-Inflammatory Properties Promote Infected Wound Healing.

Wound healing is a complex biological process that can trigger inflammation and oxidative stress and impair myofibrillogenesis and angiogenesis. Several advanced wound-dressing nanocomposite materials have been designed to address these issues. Here, we designed a new multifunctional styrene-ethylene-butylene-styrene/silver nanowire (SEBS/AgNWs)-based nanocomposite film with antimicrobial, antioxidant, and anti-inflammatory properties to promote wound healing. The porous morphological structure of SEBS/AgNWs enhances their antimicrobial, antioxidant, and anti-inflammatory properties. SEBS/AgNWs significantly inhibited the growth of Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and Escherichia coli strains, effectively wiping out ABTS•+, DPPH•, hydrogen peroxide (H2O2), and hydroxyl (•OH) radicals, showing their effective ROS-scavenging properties. It further showed significant antioxidant properties by increasing the levels of enzyme-like catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH), while decreasing malonaldehyde (MDA) levels. Additionally, SEBS/AgNWs reduced the expression of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), while increasing levels of transforming growth factor- β (TGF-β), vascular endothelial growth factor-A (VEGF), and CD31 in wound healing. This suggests that applying a multifunctional nanoplatform based on SEBS/AgNWs could enhance wound healing and improve patient outcomes in wound care management.

Leveraging adrenergic receptor blockade for enhanced nonalcoholic fatty liver disease treatment via a biomimetic nanoplatform

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation, steatosis and fibrosis. Sympathetic nerves play a critical role in maintaining hepatic lipid homeostasis and regulating fibrotic progression through adrenergic receptors expressed by hepatocytes and hepatic stellate cells; however, the use of sympathetic nerve-focused strategies for the treatment of NAFLD is still in the infancy. Herein, a biomimetic nanoplatform with ROS-responsive and ROS-scavenging properties was developed for the codelivery of retinoic acid (RA) and the adrenoceptor antagonist labetalol (LA). The nanoplatform exhibited improved accumulation and sufficient drug release in the fibrotic liver, thereby achieving precise codelivery of drugs. Integration of adrenergic blockade effectively interrupted the vicious cycle of sympathetic nerves with hepatic stellate cells (HSCs) and hepatocytes, which not only combined with RA to restore HSCs to a quiescent state but also helped to reduce hepatic lipid accumulation. We demonstrated the excellent ability of the biomimetic nanoplatform to ameliorate liver inflammation, fibrosis and steatosis. Our work highlights the tremendous potential of a sympathetic nerve-focused strategy for the management of NAFLD and provides a promising nanoplatform for the treatment of NAFLD.

Cyanocobalamin-loaded dissolving microneedles diminish skin inflammation in vivo

Inflammatory diseases of the skin have a considerable high prevalence worldwide and negatively impact the patients' quality of life. First-line standard therapies for these conditions inherently entail important side effects when used long-term, particularly complicating the management of chronic cases. Therefore, there is a need to develop novel therapeutic strategies to offer reliable alternative treatments. Abnormally high reactive oxygen species (ROS) levels are characteristic of this kind of illnesses, and therefore a reasonable therapeutic goal. Cyanocobalamin, also known as Vitamin B12, possesses notable antioxidant and ROS-scavenging properties which could make it a possible therapeutic alternative. However, its considerable molecular weight restricts passive diffusion through the skin and forces the use of an advanced transdermal delivery system. Here, we present several prototypes of Cyanocobalamin-loaded Dissolving Microarray Patches (B12@DMAPs) with adequate mechanical properties to effectively penetrate the stratum corneum barrier, allowing drug deposition into the skin structure. Ex vivo penetration and permeability studies noted an effective drug presence within the dermal skin layers; in vitro compatibility studies in representative cell skin cell lines such as L929 fibroblasts and HaCaT keratinocytes ensured their safe use. The in vivo efficacy of the selected prototype was tested in a delayed-type hypersensitivity murine model that mimics an inflammatory skin process. Several findings such as a reduction of MPO-related photon emission in a bioluminescence study, protection against histological damage, and decrease of inflammatory cytokines levels point out the effectivity of B12@DMAPs to downregulate the skin inflammatory environment. Overall, B12@DMAPs offer a cost-effective translational alternative for improving patients' skin healthcare.

Novel Sprayable Antioxidative Dressing Based on Fullerene and Curdlan for Accelerating Chronic Wound Healing.

The effective treatment of chronic wounds represents a critical global medical challenge demanding urgent attention. Persistent inflammation, driven by an excess of reactive oxygen radicals, sets in motion a detrimental cycle leading to chronic wounds and impeding the natural healing process. This study develops a sprayable wound dressing by covalently grafting amino fullerene to carboxymethylated curdlan (CMC-C). This novel dressing exhibits excellent biocompatibility, antioxidant, and reactive oxygen species scavenging properties. Furthermore, it demonstrates a targeted affinity for HEK-a cells, efficiently reducing the inflammatory response while promoting cell proliferation and migration in vitro. Moreover, the animal experiment investigations reveal that CMC-C significantly accelerates chronic wounds healing by regulating the inflammatory process, promoting collagen deposition, and improving vascularization. These results demonstrate the potential of the sprayable dressing (CMC-C) in curing the healing of chronic wounds through the modulation of the inflammatory microenvironment. Overall, the sprayable hydrogel dressing based on water-soluble derivative of fullerene and curdlan emerges as a potential approach for clinical applications in the treatment of chronic wounds.

Enhancing diabetic wound healing: A two-pronged approach with ROS scavenging and ROS-independent antibacterial properties

The intricate microenvironment often hinders diabetic wounds from following a normal healing process, marked by prolonged low-grade inflammation, thereby slowing or stalling wound healing. Nanomedicine stands as a pivotal branch in the evolution of therapeutic strategies, yet grapples with inherent conflicting traits – the ROS-dependent antibacterial properties of most materials and the anti-inflammatory ROS-scavenging capabilities. This study introduces a multifunctional MOF-199/GO nanocomposite designed to promote diabetic wound healing by its robust ROS scavenging capacity, ROS-independent antibacterial and anti-biofilm properties, and the ability to modulate wound microenvironments. In a skin wound model on type I diabetes rats, the addition of MOF-199/GO efficiently orchestrates the healing process into the defined phases of inflammation, proliferation, and remodeling, achieving a remarkable 96 % wound closure by day 10. When employed as a drug, MOF-199/GO exhibits minimal biological toxicity in vivo. Moreover, when combined with various dressing materials, the drug’s performance remains unchanged, indicating its practical application value.

Protective Role of Nanoceria-Infused Nanofibrous Scaffold toward Bone Tissue Regeneration with Senescent Cells.

The presence of oxidative stress in bone defects leads to delayed regeneration, especially in the aged population and patients receiving cancer treatment. This delay is attributed to the increased levels of reactive oxygen species (ROS) in these populations due to the accumulation of senescent cells. Tissue-engineered scaffolds are emerging as an alternative method to treat bone defects. In this study, we engineered tissue scaffolds tailored to modulate the adverse effects of oxidative stress and promote bone regeneration. We used polycaprolactone to fabricate nanofibrous mats by using electrospinning. We exploited the ROS-scavenging properties of cerium oxide nanoparticles to alleviate the high oxidative stress microenvironment caused by the presence of senescent cells. We characterized the nanofibers for their physical and mechanical properties and utilized an ionization-radiation-based model to induce senescence in bone cells. We demonstrate that the presence of ceria can modulate ROS levels, thereby reducing the level of senescence and promoting osteogenesis. Overall, this study demonstrates that ceria-infused nanofibrous scaffolds can be used for augmenting the osteogenic activity of senescent progenitor cells, which has important implications for engineering bone tissue scaffolds for patients with low regeneration capabilities.

Injectable Thermosensitive Gel CH-BPNs-NBP for Effective Periodontitis Treatment through ROS-Scavenging and Jaw Vascular Unit Protection.

Periodontitis, a prevalent inflammatory condition in the oral cavity, is closely associated with oxidative stress-induced tissue damage mediated by excessive reactive oxygen species (ROS) production. The jaw vascular unit (JVU), encompassing both vascular and lymphatic vessels, plays a crucial role in maintaining tissue fluid homeostasis and contributes to the pathological process in inflammatory diseases of the jaw. This study presents a novel approach for treating periodontitis through the development of an injectable thermosensitive gel (CH-BPNs-NBP). The gel formulation incorporates black phosphorus nanosheets (BPNs), which are notable for their ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator that promotes lymphatic vessel function within the JVU. These results demonstrate that the designed thermosensitive gel serve as a controlled release system, delivering BPNs and NBP to the site of inflammation. CH-BPNs-NBP not only protects macrophages and human lymphatic endothelial cells from ROS attack but also promotes M2 polarization and lymphatic function. In in vivo studies, this work observes a significant reduction in inflammation and tissue damage, accompanied by a notable promotion of alveolar bone regeneration. This research introduces a promising therapeutic strategy for periodontitis, leveraging the unique properties of BPNs and NBP within an injectable thermosensitive gel.

Dynamic hydrogel-integrated microneedle patch with extracellular vesicles encapsulation for wound healing

Excessive reactive oxygen species (ROS) generated by wounds and bacterial infection are the great obstacles for diabetic wound closure. Here, we present a novel dual ROS-scavenging and antibacterial microneedle array patch with M2 macrophage-derived extracellular vesicles (M2-EVs) encapsulation for diabetic wound healing. The microneedle patch with a core–shell structure is composed of hyaluronic acid (HA) and PFP hydrogel crosslinked by polyvinyl alcohol (PVA)/2-formylphenylboronic acid (2-FPBA)/polyetherimide (PEI). When exposed to high levels of ROS existed in the wound, the dynamic covalent bonds of the hydrogel network can dissociate and subsequently release M2-EVs from the HA core. Benefitting from ROS-scavenging properties, antibacterial activities, and macrophage polarization driven by M2-EVs, the microneedle patch could effectively promote wound closure in diabetic animal models. These results indicated that the proposed ROS-scavenging microneedle patches with EVs delivery are promising for variety of difficult-to-heal wounds in clinical application.

An Injectable Black Phosphorus Hydrogel for Rapid Tooth Extraction Socket Healing.

The excess production of reactive oxygen species (ROS) will delay tooth extraction socket (TES) healing. In this study, we developed an injectable thermosensitive hydrogel (NBP@BP@CS) used to treat TES healing. The hydrogel formulation incorporated black phosphorus (BP) nanoflakes, recognized for their accelerated alveolar bone regeneration and ROS-scavenging properties, and dl-3-n-butylphthalide (NBP), a vasodilator aimed at enhancing angiogenesis. In vivo investigations strongly demonstrated that NBP@BP@CS improved TES healing due to antioxidation and promotion of alveolar bone regeneration by BP nanoflakes. The sustained release of NBP from the hydrogel promoted neovascularization and vascular remodeling. Our results demonstrated that the designed thermosensitive hydrogel provided great opportunity not only for ROS elimination but also for the promotion of osteogenesis and angiogenesis, reflecting the "three birds with one stone" concept, and has tremendous potential for rapid TES healing.

Ruthenium(II) Polypyridyl Complexes with Benzoxazole Derivatives and Non-Innocent Ligands as Effective Antioxidants in Human Neuroblasts.

Ruthenium(II) polypyridyl complexes continue to raise increasing interest for the encouraging results in several biomedical areas. Considering their vast chemical-physical repertoire, in particular the possibility to switch from the sensitization of reactive oxygen species (ROS) to ROS-scavenging abilities by tuning the nature of their ligands, it is therefore surprising that their potential as antioxidants has not been largely investigated so far. Herein, we explored the antioxidant behaviour of the novel ruthenium compound [Ru(dbpy)(2,3-DAN)Cl]PF6 (Ru1), featuring a benzoxazole derivative (dpby=2,6-bis(4-methyl-2-benzoxazolyl)pyridine) and the non-innocent 2,3-diamminonaftalene (2,3-DAN) ligand, along with the reference tpy-containing analogue [Ru(tpy)(2,3-DAN)Cl]PF6 (Ru2) (tpy=2,2':6',2''-terpyridine). Following the synthesis and the electrochemical characterization, chemical antioxidant assays highlighted the beneficial role of dpby for the ROS-scavenging properties of Ru1. These data have been corroborated by the highest protective effect of Ru1 against the oxidative stress induced in SH-SY5Y human neuroblastoma, which exerts pro-survival and anti-inflammatory actions. The results herein reported highlight the potential of Ru1 as pharmacological tool in neurodegenerative diseases and specially prove that the antioxidant properties of such compounds are likely the result of a non-trivial synergetic action involving the bioactive ligands in their chemical architectures.

Oxidative stress in the remaining muscle after volumetric muscle loss contributes to impaired mitochondrial bioenergetics and is attenuated by SS-31

Volumetric muscle loss (VML) injury results in the non-recoverable loss of muscle mass and function. Our previous studies indicate mitochondrial dysfunction in the remaining muscle fibers after VML injury, marked by changes in mitochondrial respiration, membrane potential, and enzyme activities. In particular, mitochondrial membrane potential is hyperpolarized during the first 14-days post-injury, a condition that could lead to the production of reactive oxygen species (ROS). When ROS emissions exceed the antioxidant buffering capacity, cellular damage can ensue. The primary objective of this study was to determine ROS production, ROS emission, and antioxidant buffering capacity of remaining muscle fibers after VML injury in the first month after injury. The secondary objective of this study was to determine if a mitochondrial antioxidant (SS-31) could mitigate mitochondrial dysfunction after VML injury. We hypothesized that VML injury will alter the redox status of the remaining muscle. Study 1: Male C57BL/6J mice (n=40) were randomized to Uninjured or VML-injured cohorts. ROS (H2O2) emission/production and endogenous antioxidant buffering capacity were analyzed fluorometrically during live muscle fiber respiration (Oroboros O2k) at 3-, 7-, 14-, 21-, and 30-days post-injury. Study 2: Male C57BL/6J mice (n=32) were randomized into two groups: VML and VML+SS-31. SS-31 is a mitochondrial-targeted peptide with ROS-scavenging properties. VML+SS-31 received SS-31 (8mg/kg/day) for 14 days, and the VML received equal volume saline injections. At 14- and 28-days post-VML, mitochondrial respiration and electron conductance, ROS emission, and antioxidant buffering capacity were assessed in permeabilized gastrocnemius muscle fibers from the muscle remaining after the initial injury. Group differences were detected through ANOVA and unpaired t-test. ROS emission and antioxidant buffering capacity were different between VML-injured and Uninjured mice through 14-days post-injury, specifically at 3-, 7-, and 14-days, mitochondrial ROS emission was significantly higher (+28%, p<0.001), and antioxidant buffering capacity was less (-28%, p=0.002) in VML mice compared to Uninjured mice. Two weeks of SS-31 treatment lead to greater muscle fiber respiration and electron conductance (p≤0.008) at both 14- and 28-days post-VML. Importantly, at 14-days post-injury, mitochondrial ROS emission was 71% lower in VML+SS-31 than VML. At both 14- and 28-days post-injury, antioxidant buffering capacity was 12% greater in VML+SS-31 (p≤0.003) compared to VML. Oxidative stress is a feature of early VML pathophysiology marked by greater ROS emission and less antioxidant buffering capacity. Attenuating oxidative stress during the first two-weeks post-VML injury improves mitochondrial respiration. W81XWH-20-1-0885 and R01AR078903 to SG and JC. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Characterization of AICAR transformylase/IMP cyclohydrolase (ATIC) bifunctional enzyme from Candidatus Liberibacer asiaticus

The bifunctional enzyme, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase/inosine monophosphate (IMP) cyclohydrolase (ATIC) is involved in catalyzing penultimate and final steps of purine de novo biosynthetic pathway crucial for the survival of organisms. The present study reports the characterization of ATIC from Candidatus Liberibacer asiaticus (CLasATIC) along with the identification of potential inhibitor molecules and evaluation of cell proliferative activity. CLasATIC showed both the AICAR Transformylase (AICAR TFase) activity for substrates, 10-f-THF (Km, 146.6 μM and Vmax, 0.95 μmol/min/mg) and AICAR (Km, 34.81 μM and Vmax, 0.56 μmol/min/mg) and IMP cyclohydrolase (IMPCHase) activitiy (Km, 1.81 μM and Vmax, 2.87 μmol/min/mg). The optimum pH and temperature were also identified for the enzyme activity. In-silico study has been conducted to identify potential inhibitor molecules through virtual screening and MD simulations. Out of many compounds, HNBSA, diosbulbin A and lepidine D emerged as lead compounds, exhibiting higher binding energy and stability for CLasATIC than AICAR. ITC study reports higher binding affinities for HNBSA and diosbulbin A (Kd, 12.3 μM and 34.2 μM, respectively) compared to AICAR (Kd, 83.4 μM). Likewise, DSC studies showed enhanced thermal stability for CLasATIC in the presence of inhibitors. CD and Fluorescence studies revealed significant conformational changes in CLasATIC upon binding of the inhibitors. CLasATIC demonstrated potent cell proliferative, wound healing and ROS scavenging properties evaluated by cell-based bioassays using CHO cells. This study highlights CLasATIC as a promising drug target with potential inhibitors for managing CLas and its unique cell protective, wound-healing properties for future biotechnological applications.

Regulation of Photophysical Behaviors in Hyperbranched Aggregation-Induced Emission Polymers for Reactive Oxygen Species Scavenging.

Developing nonconjugated materials with large Stokes shifts is highly desired. In this work, three kinds of hyperbranched aggregation-induced emission (AIE) polymers with tunable n/π electronic effects were synthesized. HBPSi-CBD contains alkenyl groups in the backbone and possesses a promoted n-π* transition and red-shifted emission wavelength with a large Stokes shift of 186 nm. Experiments and theoretical simulations confirmed that the planar π electrons in the backbone are responsible for the red-shifted emission due to the strong through-space n···π interactions and restricted backbone motions. Additionally, the designed HBPSi-CBD could be utilized as an ROS scavenger after coupling with l-methionine. The HBPSi-Met exhibits remarkable ROS scavenging properties with a scavenging capacity of 77%. This work not only gains further insight into the structure-property relationship of nonconjugated hyperbranched AIE polymers but also provides a promising ROS-scavenging biomaterial for the treatment of ROS-related diseases.

A Curcumin-Decorated Nanozyme with ROS Scavenging and Anti-Inflammatory Properties for Neuroprotection.

Disordered reactive oxygen/nitrogen species are a common occurrence in various diseases, which usually cause cellular oxidative damage and inflammation. Despite the wide range of applications for biomimetic nanoparticles with antioxidant or anti-inflammatory properties, designs that seamlessly integrate these two abilities with a synergistic effect in a simple manner are seldom reported. In this study, we developed a novel PEI-Mn composite nanoparticle (PM NP) using a chelation method, and the curcumin was loaded onto PM NPs via metal-phenol coordination to form PEI-Mn@curcumin nanoparticles (PMC NPs). PMC NPs possessed excellent dispersibility and cytocompatibility, was engineered to serve as an effective nanozyme, and exhibited specific SOD-like and CAT-like activities. In addition, the incorporation of curcumin granted PMC NPs the ability to effectively suppress the expression of inflammatory cytokines in microglia induced by LPS. As curcumin also has antioxidant properties, it further amplified the synergistic efficiency of ROS scavenging. Significantly, PMC NPs effectively scavenged ROS triggered by H2O2 in SIM-A9 microglia cells and Neuro-2a cells. PMC NPs also considerably mitigated DNA and lipid oxidation in Neuro-2a cells and demonstrated an increase in cell viability under various H2O2 concentrations. These properties suggest that PMC NPs have significant potential in addressing excessive ROS and inflammation related to neural diseases.

Accelerating Diabetic Wound Healing by Modulating the Inflammatory Environment Using Quercetin–Rosemary Oil Lipid Nanoemulsions with Artificial Intelligence‐Based Wound Closure Analysis

AbstractDiabetic wounds are a significant complication of diabetes that is characterized by delayed wound healing and a high risk of amputation. The overexpression of pro‐inflammatory macrophages (M1) and matrix metallo protease‐9 (MMP‐9) plays a crucial role in the extended inflammatory phase, which is characteristic of these wounds. This study develops multifunctional lipid nanoemulsions known as Quercetin and Rosemary Oil Lipid Nanoemulsions (Q‐RLNEs) that can effectively convert M1 to M2 macrophages, inhibit MMP‐9 and prevent microbial infections, thereby expediting the healing of diabetic wounds. Q‐RLNEs exhibit excellent biocompatibility, cellular uptake, ROS scavenging, macrophage polarization, MMP‐9 inhibition, and potent antimicrobial properties against Staphylococcus aureus in vitro. In vivo experiments further reveal Q‐RLNE's ability to accelerate complete wound healing in diabetic‐induced rats by reducing inflammation, promoting angiogenesis, and facilitating proper collagen deposition and dermal projection regeneration. This study introduces the application of the Segment Anything Model (SAM). SAM combines attention‐fusion and hybrid fusion strategies for accurate segmentation, enabling comprehensive analysis of wound attributes over time and guiding treatment decisions. The SAM analysis results also align with Q‐RLNE in vitro and in vivo. The findings of this study suggest that Q‐RLNE is a promising new therapeutic agent for accelerating diabetic wound healing.

The mechanism of adipose mesenchymal stem cells to stabilize the immune microenvironment of pelvic floor injury by regulating pyroptosis and promoting tissue repair

Pelvic organ prolapse (POP) has a high incidence rate among Chinese women. Repeated mechanical stimulation is an important factor causing POP, but the injury mechanism has not yet been elucidated. The purpose of this study is to explore the related mechanisms of pelvic floor supporting tissue damage caused by mechanical force and the application of stem cell therapy. First, we obtained vaginal wall and sacral ligament tissue samples from clinical patients for examination. Pelvic floor support tissues of POP patients displayed high expression of inflammation and immune disorders. Then, we constructed a rat model of childbirth injury. In vivo and in vitro experiments investigated the key mechanism of pelvic floor support tissue injury caused by mechanical force. We discovered that after mechanical force, a large number of reactive oxygen species (ROS) and macrophages rapidly accumulated in pelvic floor tissues. ROS stimulated macrophages to produce NLRP3 inflammatory complex, induced the release of interleukin (IL-1β) and pyroptosis and exacerbated the inflammatory state of damaged tissues, persisting chronic inflammation of fibroblasts in supporting tissues, thus causing the pelvic floor's extracellular matrix (ECM) collagen metabolic disorder. Resultingly impeding the repair process, thereby causing the onset and progression of the disease. Through their paracrine ability, we discovered that adipose mesenchymal stem cells (ADSCs) could inhibit this series of pathological processes and promote tissue repair, asserting a good therapeutic effect. Simultaneously, to overcome the low cell survival rate and poor therapeutic effect of directly injecting cells, we developed a ROS-responsive PVA@COLI hydrogel with ADSCs. The ROS-scavenging properties of the gel could reshape the site of inflammation injury, enhance cell survival, and play a role in subsequent treatment. The findings of this study could serve as a basis for early, targeted intervention therapy for POP and representing a promising approach.

Study of Biological Behavior and Antimicrobial Properties of Cerium Oxide Nanoparticles.

(1) Background: An element that has gained much attention in industrial and biomedical fields is Cerium (Ce). CeO2 nanoparticles have been proven to be promising regarding their different biomedical applications for the control of infection and inflammation. The aim of the present study was to investigate the biological properties and antimicrobial behavior of cerium oxide (CeO2) nanoparticles (NPs). (2) Methods: The investigation of the NPs' biocompatibility with human periodontal ligament cells (hPDLCs) was evaluated via the MTT assay. Measurement of alkaline phosphatase (ALP) levels and alizarine red staining (ARS) were used as markers in the investigation of CeO2 NPs' capacity to induce the osteogenic differentiation of hPDLCs. Induced inflammatory stress conditions were applied to hPDLCs with H2O2 to estimate the influence of CeO2 NPs on the viability of cells under these conditions, as well as to reveal any ROS scavenging properties. Total antioxidant capacity (TAC) of cell lysates with NPs was also investigated. Finally, the macro broth dilution method was the method of choice for checking the antibacterial capacity of CeO2 against the anaerobic pathogens Porphyromonas gingivalis and Prevotella intermedia. (3) Results: Cell viability assay indicated that hPDLCs increase their proliferation rate in a time-dependent manner in the presence of CeO2 NPs. ALP and ARS measurements showed that CeO2 NPs can promote the osteogenic differentiation of hPDLCs. In addition, the MTT assay and ROS determination demonstrated some interesting results concerning the viability of cells under oxidative stress conditions and, respectively, the capability of NPs to decrease free radical levels over the course of time. Antimicrobial toxicity was observed mainly against P. gingivalis. (4) Conclusions: CeO2 NPs could provide an excellent choice for use in clinical practices as they could prohibit bacterial proliferation and control inflammatory conditions.

A Narrative Review: The Effect and Importance of Carotenoids on Aging and Aging-Related Diseases.

Aging is generally defined as a time-dependent functional decline that affects most living organisms. The positive increase in life expectancy has brought along aging-related diseases. Oxidative stress caused by the imbalance between pro-oxidants and antioxidants can be given as one of the causes of aging. At the same time, the increase in oxidative stress and reactive oxygen species (ROS) is main reason for the increase in aging-related diseases such as cardiovascular, neurodegenerative, liver, skin, and eye diseases and diabetes. Carotenoids, a natural compound, can be used to change the course of aging and aging-related diseases, thanks to their highly effective oxygen-quenching and ROS-scavenging properties. Therefore, in this narrative review, conducted using the PubMed, ScienceDirect, and Google Scholar databases and complying with the Scale for the Assessment of Narrative Review Articles (SANRA) guidelines, the effects of carotenoids on aging and aging-related diseases were analyzed. Carotenoids are fat-soluble, highly unsaturated pigments that occur naturally in plants, fungi, algae, and photosynthetic bacteria. A large number of works have been conducted on carotenoids in relation to aging and aging-related diseases. Animal and human studies have found that carotenoids can significantly reduce obesity and fatty liver, lower blood sugar, and improve liver fibrosis in cirrhosis, as well as reduce the risk of cardiovascular disease and erythema formation, while also lowering glycated hemoglobin and fasting plasma glucose levels. Carotenoid supplementation may be effective in preventing and delaying aging and aging-related diseases, preventing and treating eye fatigue and dry eye disease, and improving macular function. These pigments can be used to stop, delay, or treat aging-related diseases due to their powerful antioxidant, restorative, anti-proliferative, anti-inflammatory, and anti-aging properties. As an increasingly aging population emerges globally, this review could provide an important prospective contribution to public health.

Rhythm and ROS: Hepatic Chronotherapeutic Features of Grape Seed Proanthocyanidin Extract Treatment in Cafeteria Diet-Fed Rats.

Polyphenols play a key role in the modulation of circadian rhythms, while the cafeteria diet (CAF) is able to perturb the hepatic biological rhythm and induce important ROS production. Consequently, we aimed to elucidate whether grape seed proanthocyanidin extract (GSPE) administration recovers the CAF-induced hepatic antioxidant (AOX) misalignment and characterize the chronotherapeutic properties of GSPE. For this purpose, Fischer 344 rats were fed a standard diet (STD) or a CAF and concomitantly treated with GSPE at two time-points (ZT0 vs. ZT12). Animals were euthanized every 6 h and the diurnal rhythms of hepatic ROS-related biomarkers, hepatic metabolites, and AOX gene expression were examined. Interestingly, GSPE treatment was able to recover the diurnal rhythm lost due to the CAF. Moreover, GSPE treatment also increased the acrophase of Sod1, as well as bringing the peak closer to that of the STD group. GSPE also corrected some hepatic metabolites altered by the CAF. Importantly, the differences observed at ZT0 vs. ZT12 due to the time of GSPE administration highlight a chronotherapeutic profile on the proanthocyanin effect. Finally, GSPE could also reduce diet-induced hepatic oxidative stress not only by its ROS-scavenging properties but also by retraining the circadian rhythm of AOX enzymes.

Tropolones and Thailandepsin B as Lead-like Natural Compounds in the Development of Potent and Selective Histone Deacetylase Inhibitors.

Tropolone and thailandepsin B are naturally occurring substances that are primarily isolated from fungi and plants, although they can also be found in certain bacteria. Tropolones belong to an important class of aromatic compounds with a seven-membered nonbenzenoid ring structure. Thailandepsins are a group of natural products that were initially discovered in the culture broth of the Gram-negative bacterium Burkholderia thailandensis. Tropolonebased structures have been identified in over 200 natural compounds, ranging from simple tropolone derivatives to complex multicyclic systems like pycnidione and pyrerubrine A. These natural compounds exhibit a diverse range of pharmacological effects, including antibacterial, antifungal, insecticidal, phytotoxic, anti-inflammatory, antimitotic, anti-diabetic, enzyme inhibitory, anticancer, cytoprotective, and ROS scavenging properties. It is worth noting that thujaplicane, a compound similar to tropolone, displays all of the listed biological activities except for antimitotic action, which has only been observed in one natural tropolone compound, colchicine. Tropolone can be synthesized from commercially available seven-membered rings or derived through various cyclization and cycloaddition reactions. Thailandepsin B, on the other hand, can be synthesized by macro-lactonization of the corresponding secoacid, followed by the formation of internal disulfide bonds. It is important to mention that thailandepsin B exhibits different selective inhibition profiles compared to FK228. We investigated the HDAC inhibitory activity of the Tropolones and Thailandepsin B and discussed the biosynthesis of the naturally occurring compounds and their synthetic scheme. It has been observed that Tropolone derivatives act as isoenzyme-selective inhibitors of proven anticancer drug targets, histone deacetylases (HDACs). Some monosubstituted tropolones show remarkable levels of selectivity for HDAC2 and strongly inhibit the growth of T-lymphocyte cell lines. And Thailandepsins have different selective inhibition profiles than FK228. They exhibit comparable inhibitory activities to FK228 against human HDAC1, HDAC2, HDAC3, HDAC6, HDAC7, and HDAC9, but less potent inhibitory activities than FK228 toward HDAC4 and HDAC8, the latter of which may be useful. Thailandepsins possess potent cytotoxic activities toward some types of cell lines.