Search Results (161)

Background/Objectives: To study the efficacy and pharmacological mechanism of the dual-target liposome complex AD808 in the treatment of Alzheimer’s disease. Methods: Using APP/PS1 mouse models, the therapeutic efficacy and pharmacological mechanism of AD808 on Alzheimer’s disease were studied through water maze tests, brain tissue staining, immunofluorescence, and ELISA for inflammatory and neurotrophic factors. Results: AD808 exhibited significant pharmacodynamic effects in improving behavioral and cognitive abilities (70% reduction in escape latency) and repairing damaged nerve cells (90% reduction in Aβ plaque) in Alzheimer’s disease mice. The efficacy of the liposome complex AD808 was significantly better than that of ST707 or gh625-Zn₇MT3 alone. AD808 significantly reduced brain inflammation (57.3% and 61.5% reductions in TNF-α and IL-1β, respectively) in AD (Alzheimer’s disease) mouse models and promoted the upregulation of neurotrophic factors and nerve growth factors (142.8% increase in BDNF, 275.9% in GDNF, and 111.3% in NGF-1) in brain homogenates. By activating the PI3K/AKT signaling pathway in brain microglia, AD808 upregulated TREM2 protein expression and removed Aβ amyloid plaques in the brain. Additionally, it promoted the transition of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, regulated the M1/M2 balance, released anti-inflammatory and neurotrophic factors, reduced chronic inflammation, and enhanced neurological repair. Based on these results, the potential pharmacological mechanism of AD808 against Alzheimer’s disease was proposed. Conclusions: As a dual-target liposome complex, AD808 has shown promising therapeutic potential in the treatment of Alzheimer’s disease, providing a new strategy for innovative drug development. Full article

The systematics and phylogeny of the most speciose genus (Leopardus) of the felidae have historically been contentious and problematic. These issues have been compounded with the recent advancement of genetic techniques that make it possible to detect events such as incomplete lineage sorting (ILS), punctual historical ancestral introgression (PHAI), and repetitive introgression or recent hybridization (RI-RH). Each of these events have noteworthily affected the Leopardus genus. One Leopardus taxon (Leopardus tigrinus, herein called tigrina) has been especially complex from a phylogenetic point of view. In the last decade, one new species has been reported (L. guttulus) and two other new species likely exist within the tigrinas (L. emiliae and L. pardinoides). However, the most surprising find was the discovery of a new and not previously reported tigrina, the Nariño cat, from the southern Andean region of Colombia (2023). Later that same year, a new paper criticized the discovery. In response to that criticism, herein, we provide new molecular genetics results of the Nariño cat as well as new insights into the molecular phylogeny of the tigrinas inside the Leopardus genus: (1) In this new work, we analyzed the mtND5 gene of Nariño cat samples collected over four years (2001, 2007, 2017, 2023) as well as analyzed mitogenomes of Nariño cat samples collected in three different years (2001, 2017, 2023). The temporal Nariño cat samples (2001, 2007, 2017, 2023) refer to samples taken from a single specimen across different years. Based on these analyses, data from 2001 and 2007 represent the most reliable information. In contrast, samples from 2017 and 2023 may be contaminated with DNA from the Pampas cat and tigrina, respectively. (2) On the other hand, based on sequencing the mtND5 gene of 164 specimens of Leopardus, northern Andean and Central American tigrinas (37 specimens) are divided into at least six different groups (without counting the Nariño cat). Based on our analysis of sequenced mitogenomes of 102 specimens (including 34 northern Andean and Central American tigrinas) of the Leopardus genus, there are at least eight different groups of tigrinas (without counting the Nariño cat). Henceforth, there are strong datasets which support the existence of multiple lineages within the presumed “a priori” northern Andean tigrina and thus much of the genetic diversity of this wild cat has gone unnoticed. There are a series of potential taxa that have gone unnoticed due to a lack of sampling of this polyphyletic Andean feline. Full article

Background: The etiopathogenesis of atopic dermatitis is complicated, and it includes aspects such as dysfunction of the skin barrier, changes in immune responses, IgE-mediated hypersensitivity, and many characteristics of the environment. Regarding skin barrier dysfunction, a number of genetic changes have been described. This genetic predisposition could be related to the phenotypes of atopic dermatitis. Aim: In this study, several polymorphisms in five proinflammatory genes were associated with certain phenotypes of AD patients (genotype–phenotype study). Methods: In total, 89 unrelated AD Czech (Caucasian) patients were genotyped regarding five proinflammatory gene polymorphisms (angiotensinogen AGT M235T, AGT-6 G/A, TNF-α-238 G/A, TNF-β Fok1, IL-6-174 C/G and IL-6-596 G/A). Genotyping was performed using PCR and restriction analysis. For phenotypes, patients’ sex, age and personal and family history of atopy, aero- and food allergies and other complex diseases were evaluated. Results: A significant association with transepidermal water loss (TEWL) measured on the forearm was found with the AGT M235T polymorphism (p = 0.02). For the AG genotype of TNF-α-238 G/A, a six-times higher risk for a family history of diabetes mellitus compared to other examined aspects of family history was found (p = 0.02). A family history of thyreopathy was associated with the IL-6-174 G/C polymorphism when compared to a family history of other complex diseases. The GG genotype had a ten-times higher risk for a family history of thyreopathy compared to the other genotypes (p = 0.004). This result was highly specific (0.914). The GG genotype of IL-6-596 G/A was associated with a family history of thyreopathy, with the same result (p = 0.004). Moreover, the G allele of IL-6-174 G/C was associated with a family history of thyreopathy compared to AD patients without a positive family history of complex diseases (p = 0.03). In AD men, the MM genotype of the AGT M235T gene was found to be associated with food allergies (p = 0.004). This result was highly sensitive (0.833). A family history of cardiovascular disease in AD men was associated with AGT-6 G/A variability. The A allele was found to be six times more frequent in patients with a positive family history of cardiovascular disease (p = 0.02, with high sensitivity and specificity (0.700 and 0.735, respectively)). A family history of diabetes mellitus was associated with the TNF-β Fok1 polymorphism, where the B1 allele was almost six times more frequent in AD men with a positive family history of diabetes mellitus (p = 0.02), with high sensitivity (0.85). A significant association between TEWL measured on the forearm and the AGT M235T polymorphism was found when AD women were carriers of the MM genotype, with a median of 25 and range 4–61; those patients with the MT genotype had a median of 10 and range of 0.3–39; and patients with the TT genotype had a median of 5 and range of 3–40, p = 0.003. The polymorphism AGT-6 G/A was associated with different ages of eczema onset. The AG genotype was almost nine times more risky for the youngest group (0–7 years) compared to the oldest group (more than 18 years) (p = 0.02), with high specificity for this result. Conclusions: Our results in the field of cytokine signaling in the immune system in patients with atopic dermatitis are in agreement with those of GWASs. We suggest that cost-effective and simple PCR tests may be the best approach for the rapid and optimal collection of valid genetic information in clinical practice. Full article

Background/Objectives: Pestalotic acid A (PAA), a polyketide derived from Pestalotiopsis vismiae, an endophyte of the Japanese holly (Ilex crenata), is known to exhibit known antimicrobial activity, but its anti-inflammatory properties remain uncharacterized. This study aimed to investigate the anti-inflammatory effects of PAA in lipopolysaccharide (LPS)-stimulated murine macrophages, RAW264.7 cells. Methods: PAA was isolated from P. vismiae endophytes of Ilex crenata, and its structure was confirmed. RAW264.7 macrophages were treated with 0–50 μM of PAA in the presence of 100 ng/mL LPS. Cell viability was assessed by MTS assay; nitric oxide (NO) production was measured via Griess reagent; interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF) were quantified by enzyme-linked immunosorbent assay. Protein expression of inducible NO synthase (iNOS), nuclear factor (NF)-κB p65 phosphorylation, and related signaling proteins was evaluated by Western blot analysis and immunofluorescence staining. Results: PAA significantly increased macrophage viability and dose-dependently inhibited the release of NO by alleviating the protein expression of iNOS in LPS-treated RAW264.7 cells. Furthermore, PAA suppressed the release of IL-6, IL-1β, and TNF induced by LPS. Western blot and immunofluorescence results also indicated that PAA blocked the p65 subunit phosphorylation of NF-κB, which is one of the underlying mechanisms of the anti-inflammatory action of pestalotic acid A. Conclusions: PAA exerts potent anti-inflammatory effects in LPS-stimulated macrophages via inhibition of the NF-κB pathway, highlighting its potential as a natural therapeutic agent for inflammatory diseases. Full article

Psoriasis, a chronic inflammatory skin disorder, is driven by dysregulated immune responses and keratinocyte dysfunction. Here, we explore the therapeutic potential of Astilbin (AST), a flavonoid with potent anti-inflammatory properties, in modulating ferroptosis and the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway in IL-17-stimulated HaCaT keratinocytes. Our psoriatic cell model recapitulated key pathological features, including hyperproliferation, membrane integrity loss, mitochondrial dysfunction, and heightened oxidative stress, alongside elevated proinflammatory cytokine levels. Ferroptosis-related biomarkers were significantly altered, with increased malondialdehyde (MDA) accumulation, reduced glutathione (GSH) levels, iron overload (Fe²⁺), and enhanced lipid peroxidation (detected via C11-BODIPY). Mechanistically, mitochondrial damage triggered cytoplasmic leakage of mitochondrial DNA (mtDNA), activating the cGAS-STING pathway, as evidenced by upregulated pathway-associated protein expression. AST intervention effectively mitigated these pathological changes by suppressing ferroptosis and modulating cGAS-STING signaling. These findings reveal a dual-pathway regulatory mechanism, positioning AST as a promising therapeutic candidate for psoriasis. By elucidating the interplay between ferroptosis and the cGAS-STING pathway, this study provides new insights into psoriatic inflammation and offers a rationale for targeting these pathways in therapeutic strategies. Full article

Caulebra okamurae (C. okamurae), a green seaweed, has been reported to exhibit pharmacological properties, including anti-obesity and anti-diabetic effects. This study investigated the anti-inflammatory effects of C. okamurae extracts on periodontal health. The cell viability of RAW 264.7 macrophages was dose-dependently assessed using an MTS assay. The anti-inflammatory activity of C. okamurae on Porphyromonas gingivalis (P. gingivalis)-stimulated RAW 264.7 macrophages was evaluated by measuring nitric oxide (NO) production. mRNA expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β were quantified via quantitative real-time PCR (qRT-PCR). The protein expression of iNOS, p-IKKα/β, p-IκBα, and NF-κB p65 was examined using Western blot and immunofluorescence. The results demonstrated that C. okamurae extracts exhibited no cytotoxicity in RAW 264.7 macrophages at concentrations of 0.2, 2, 20, and 200 μg/mL. The extracts dose-dependently reduced NO production, downregulated mRNA levels of proinflammatory cytokines, and inhibited iNOS expression in P. gingivalis-stimulated RAW 264.7 macrophages, a model commonly used to study periodontal inflammation. Furthermore, the extracts suppressed the phosphorylation of IKKα/β and IκBα and prevented the NF-κB p65 nuclear translocation. These findings suggest that C. okamurae extracts inhibit NF-κB signaling activation triggered by the periodontal pathogen, highlighting their potential anti-inflammatory effects, relevant to periodontal disease. Full article

Pancreatic cancer (PaCa) is among the most aggressive malignancies of the digestive system. Inflammation plays a critical role in tumor growth and dissemination, with soluble cytokines serving as messengers that facilitate interactions between immune and cancer cells. The release of cell-free mitochondrial DNA (cf-mtDNA) into the bloodstream has been identified as a potent proinflammatory trigger, acting as a mitochondrial-derived damage-associated molecular pattern (mtDAMP). Whether a relationship exists between circulating cf-mtDNA (ccf-mtDNA) unloading and inflammation in PaCa remains unclear. In this study, we quantified ccf-mtDNA levels in plasma/serum samples from PaCa patients and healthy controls and examined their association with inflammatory markers. Analyses were conducted on 14 participants: 3 controls (mean age: 52.0 ± 16.0 years, 67% women) and 11 PaCa patients (mean age: 69.1 ± 10.0 years, 27% women). Circulating levels of ccf-mtDNA in PaCa patients did not show differences compared to controls (p = 0.06). In contrast, concentrations of interleukin (IL)-8, IL-17, and interferon-gamma were significantly higher in PaCa patients. Stratification of PaCa patients based on the median ccf-mtDNA concentration revealed significantly higher levels of IL-4, IL-9, monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein 1-beta in those with ccf-mtDNA levels above the median (p < 0.05). Significant positive associations were also observed between levels of ccf-mtDNA and IL-8, fibroblast growth factor, and MCP-1. These results suggest a potential association between elevated ccf-mtDNA levels and increased concentrations of proinflammatory cytokines, especially in PaCa patients with an unfavorable prognosis. Further research with larger cohorts is required to validate these findings and assess the prognostic value of these biomarkers. Full article

Infection with influenza A virus (IAV) may trigger excessive inflammatory responses, leading to severe viral pneumonia and accelerating disease progression. Therefore, controlling these excessive inflammatory responses is crucial for the prevention and treatment of pneumonia caused by IAV. Berberine (BBR), an isoquinoline alkaloid extracted from traditional Chinese medicine, possesses extensive pharmacological activities. However, its immunoregulatory effects and molecular mechanisms in the context of IAV infection require further investigation. This study explored the impact of BBR on macrophage pyroptosis and inflammatory responses induced by IAV infection. Our findings revealed that BBR effectively inhibits the release of IL-1β and TNF-α induced by IAV infection and suppresses gasdermin D (GSDMD)-mediated pyroptosis in a dose-dependent manner. Further research indicates that BBR alleviates macrophage pyroptosis and inflammatory responses in IAV-infected cells by reducing the release of mitochondrial reactive oxygen species (mtROS), inhibiting mitochondrial antiviral signaling protein (MAVS) expression and blocking the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome. Experiments using siRNA to knockdown MAVS further confirmed the pivotal role of MAVS in BBR’s inhibition of IAV-induced macrophage pyroptosis. This study provides a scientific basis for the application of BBR as an anti-inflammatory drug in the treatment of inflammatory diseases caused by IAV infection and directs future research endeavors. Full article

Monoterpenes (MTs) are plants’ secondary metabolites and major components of essential oils (EOs), widely used in the pharmaceutical industry. However, its neuroprotective effects, particularly in Parkinson’s disease (PD) have not been fully demonstrated. PD is a progressive neurological disorder marked by dopaminergic neuron loss in the substantia nigra, motor symptoms being the most reported ones. This review evaluates the evidence supporting the use of MTs as potential neuroprotective agents. PubMed, SCOPUS, Google Scholar, and ScienceDirect databases were searched for articles on MTs in murine models with any type of administration. The PRISMA guidelines were followed. After screening 405 records, 32 were included in the systematic review and 30 were included in the meta-analysis. Fifteen MTs, commonly found in EOs, were identified as potential therapeutic agents for PD. The meta-analysis revealed that MTs administration improved motor performance, increased tyrosine hydroxylase levels, reduced oxidative stress markers (malondialdehyde) and proinflammatory cytokines (IL-6, IL-1, TNF-α), and enhanced antioxidant enzymes (catalase, superoxide dismutase) in parkinsonian animals. The antioxidant and anti-inflammatory properties of MTs appear to be key mechanisms in mitigating dopaminergic neurodegeneration. However, further clinical research is essential to translate these findings into practical applications. Full article

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects approximately one-quarter of the world’s adult population, and no effective therapeutic drugs are available. Poria cocos is a fungus used as a herb and food nutrient for centuries as well as for MAFLD treatment. Exosome-like nanovesicles have many pharmacological activities; however, studies on the effects of Poria cocos-derived exosome-like nanovesicles (PCELNs) on MAFLD are lacking. Therefore, our study aimed at identifying the effects and mechanism of action of PCELNs on MAFLD. PCELNs were isolated by ultracentrifugation and their morphology was characterized, such as particle size, zeta potential, protein distributions, as well as lipid and miRNA compositions. Then, the absorption and distribution of PCELNs were observed in vivo and in vitro. Finally, L02 cell steatosis model induced by fat emulsion and MAFLD mouse model induced by high-fat diet (HFD) were used to evaluate the effect and mechanism of PCELNs on MAFLD. PCELNs were membrane structured vesicles, with a particle size of 161.4 ± 1.7 nm, a zeta potential of −3.20 ± 0.37 mV, and contained a range of proteins, lipids, and miRNAs. PCELNs were absorbed by L02 cells and targeted the liver and spleen after intraperitoneal injection. PCELNs inhibited body weight gain and improved the index of heart, liver, spleen, and various fats, as well as decreased lipid accumulation and lipid level. They also protected mitochondrial ultrastructure and regulated oxidative stress and energy metabolism disorder. Furthermore, PCELNs increased PTEN induced kinase 1 (PINK1), E3 ubiquitin ligase (Parkin) and microtubule associated protein light chain-3 (LC3) protein expression in the liver, reduced oxidized mitochondrial DNA (Ox-mtDNA) content in mitochondria and cytoplasm of the liver, reduced nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3), pro-cysteinyl aspartate specific proteinase-1 (caspase-1), cleared-caspase-1, and mature-interleukin-1β (IL-1β) protein expression in the liver, and reduced the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and interleukin-18 (IL-18) in serum and liver. In conclusion, we demonstrated that PCELNs may alleviate HFD-induced MAFLD by promoting mitochondrial autophagy and inhibiting NLRP3 inflammasome activation. Full article

I3MT-3 (HMPSNE) has been identified as a selective inhibitor of the supersulfide-producing enzyme 3-MST. In this study, we found that I3MT-3 inhibits inflammatory responses, including the secretion of the pro-inflammatory cytokine interleukin-1β (IL-1β) and inflammatory cell death pyroptosis, induced by the activation of the inflammasomes composed of NLRP1, NLRP3, or AIM2. However, interestingly, the knockdown of 3-MST did not affect the activation of the inflammasomes, suggesting that the inhibitory effect of I3MT-3 on inflammasome activation is mediated by alternative ways rather than the inhibition of 3-MST. Interestingly, an in vitro caspase assay revealed that I3MT-3 directly inhibits caspase-1 activation, and molecular docking simulations raised the possibility that the pyrimidone ring in I3MT-3 stabilizes direct interaction of I3MT-3 with caspase-1. Taken together, our data suggest that I3MT-3 inhibits inflammasome activation by targeting caspase-1, and show I3MT-3 as a potent inhibitor of caspase-1. Full article

In rats, a fructose-rich diet triggers endocrine-metabolic disturbances similar to those present in human prediabetes. We evaluated the protective effect of isoespintanol, a monoterpene isolated from Oxandra cf. xylopioides (Annonaceae), on pancreatic islet. Rats were kept for three weeks with a standard commercial diet and tap water (C), plus 10% fructose (F), or F plus isoespintanol (I; 10 mg/kg, i.p.). Glycemia, triglyceridemia, total cholesterol, HDL-cholesterol, insulin resistance index (IRX), and glucose tolerance tests were determined. Glucose-stimulated insulin secretion (GSIS) and gene expression of insulin signalling mediators (insulin receptor -IR-, IRS1/2, PI3K), oxidative stress (SOD-2, GPx, GSR, 3’-nitrotyrosine), inflammation (TNF-α, IL-1β, PAI-1), mitochondrial function (Bcl-2, mtTFA, PGC-1α), and apoptosis markers were evaluated in pancreatic islets. The F group increased triglyceridemia, non-HDL-cholesterol, and IRX, and decreased HDL-cholesterol and impaired glucose tolerance, with alterations reversed by isoespintanol administration (p < 0.05). Isoespintanol normalized higher GSIS recorded in the F group. F decreased mRNA levels of insulin signalling mediators and mitochondrial function markers, and increased the expression of inflammatory, apoptotic, and oxidative stress markers, alterations that were significantly reversed by isoespintanol. Current results suggest that isoespintanol improved insular oxidative stress and inflammation by affecting the IR-PI3K pathway, which plays a pivotal role in insulin resistance development, underlying its therapeutic potential for the prevention of type 2 diabetes before its onset (prediabetes). Full article

Neurotoxic damage resulting from lead pollution exposure constitutes a significant public health concern. The regulatory impact of lead (Pb) exposure on neuronal dendritic spine plasticity, a crucial mechanism for neuronal adaptation, warrants further investigation. To elucidate the role and mechanism of the Mitofilin–mtDNA axis in hippocampal synaptic plasticity and learning and memory impairment induced by lead exposure, in this study, both in vivo and in vitro models were subjected to chronic lead exposure. The results showed that the spatial learning and memory abilities of lead-exposed mice were significantly reduced. Furthermore, Western blotting and RT-PCR analyses demonstrated a significant down-regulation in the expression of the mitochondrial inner membrane protein Mitofilin. Extended exposure to lead has the potential to compromise the plasticity of dendritic spines within the CA1 region of hippocampal neurons and disrupt the structural integrity of neuronal mitochondria. Furthermore, lead exposure was associated with elevated levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in neurons. The study additionally demonstrated that the overexpression of Mitofilin ameliorated deficits in spatial learning and memory in mice subjected to chronic lead exposure. This overexpression also facilitated the normal formation of neuronal dendritic spines, preserved the structural integrity of the mitochondrial inner membrane, and mitigated mitochondrial damage. The study further revealed that the overexpression of Mitofilin markedly suppressed the release of mitochondrial DNA (mtDNA) in neurons subjected to chronic lead exposure, while concurrently reducing the expression levels of the inflammasome Nlrp3 and the inflammatory cytokine IL-1β. Additionally, there was a significant reduction in the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) in lead-exposed neurons with Mitofilin overexpression. These findings suggest that the mitochondrial inner membrane protein Mitofilin may play a role in mediating synaptic plasticity impairment following chronic lead exposure through the regulation of mitochondrial function. Full article

Background: Phytocarriers are advanced drug delivery systems that use biocompatible and biodegradable materials to enhance the efficacy, stability, and bioavailability of natural products. The sea buckthorn (Hippophae rhamnoides L.) berry extract is rich in essential fatty acids and antioxidants, including vitamin C, vitamin E, and anthocyanins, which contribute to its wide-ranging health benefits. In this study, we assessed the morphology, intracellular delivery, and anti-inflammatory effect of sodium cholate (NaC) and sodium deoxycholate (NaDC)-based phytocarriers loaded with ethanolic extract from sea buckthorn berries (sea buckthorn carrier nanostructures, further defined as phytocarriers). Methods: Negative and electron cryo-microscopy were used to analyze hollow and loaded nanocarriers. The cyto-compatibility of nanocarriers was assessed by endpoint (LDH and MTS) and real-time cell assays, on both human fibroblasts (HS27) and human normal monocytes (SC). The anti-inflammatory effect of hollow and loaded nanocarriers was tested by multiplexing. Results: The negative and electron cryo-microscopy analyses showed that NaC-based phytocarriers were spherical, whilst NaDC-based phytocarriers were predominantly polymorphic. Moreover, the NaDC-based phytocarriers frequently formed large lipid networks or “plaques”. Although 24 h cytotoxicity testing showed both types of nanocarriers are biocompatible with human fibroblasts and monocytes, based on a long-term real-time assay, NaDC delayed fibroblast proliferation. NaC sea buckthorn phytocarriers did not impair fibroblast proliferation in the long term and they were uptaken by cells, as shown by hyperspectral microscopy. NaC nanocarriers and NaC sea buckthorn phytocarriers induced an anti-inflammatory effect, lowering IL-8 cytokine production in normal human monocytes as soon as 4 h of treatment lapsed. Conclusions: NaC-derived phytocarriers loaded with sea buckthorn alcoholic extract are a cell-compatible delivery system with anti-inflammatory properties. Full article

In a recent clinical trial, beetroot juice supplementation for 14 days yielded positive effects on systemic inflammation in adults with long COVID. Here, we explored the relationship between circulating markers of mitochondrial quality and inflammation in adults with long COVID as well as the impact of beetroot administration on those markers. We conducted secondary analyses of a placebo-controlled randomized clinical trial testing beetroot juice supplementation as a remedy against long COVID. Analyses were conducted in 25 participants, 10 assigned to placebo (mean age: 40.2 ± 11.5 years, 60% women) and 15 allocated to beetroot juice (mean age: 38.3 ± 7.7 years, 53.3% women). Extracellular vesicles were purified from serum by ultracentrifugation and assayed for components of the electron transport chain and mitochondrial DNA (mtDNA) by Western blot and droplet digital polymerase chain reaction (ddPCR), respectively. Inflammatory markers and circulating cell-free mtDNA were quantified in serum through a multiplex immunoassay and ddPCR, respectively. Beetroot juice administration for 14 days decreased serum levels of interleukin (IL)-1β, IL-8, and tumor necrosis factor alpha, with no effects on circulating markers of mitochondrial quality control. Significant negative associations were observed between vesicular markers of mitochondrial quality control and the performance on the 6 min walk test and flow-mediated dilation irrespective of group allocation. These findings suggest that an amelioration of mitochondrial quality, possibly mediated by mitochondria-derived vesicle recycling, may be among the mechanisms supporting improvements in physical performance and endothelial function during the resolution of long COVID. Full article