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International Journal of Nanomedicine 2024Idiopathic pulmonary fibrosis (IPF) poses a formidable clinical challenge, characterized by the thickening of alveolar septa and the onset of pulmonary fibrosis. The... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) poses a formidable clinical challenge, characterized by the thickening of alveolar septa and the onset of pulmonary fibrosis. The pronounced activation of oxidative stress emerges as a pivotal hallmark of inflammation. Traditional application of exogenous antioxidants proves inadequate in addressing oxidative stress, necessitating exploration into strategies to augment their antioxidant efficacy. Exosomes, nano-sized extracellular vesicles harboring a diverse array of bioactive factors, present as promising carriers with the potential to meet this challenge. Recent attention has been directed towards the clinical applications of exosomes in IPF, fueling the impetus for this comprehensive review. We have compiled fresh insights into the role of exosomes in modulating oxidative stress in IPF and delved into their potential as carriers for regulating endogenous reactive oxygen species generation. This review endeavors to bridge the divide between exosome research and IPF, traversing from bedside to bench. Through the synthesis of recent findings, we propose exosomes as a novel and promising strategy for improving the outcomes of IPF therapy.
Topics: Humans; Exosomes; Oxidative Stress; Idiopathic Pulmonary Fibrosis; Reactive Oxygen Species; Antioxidants; Animals
PubMed: 38911503
DOI: 10.2147/IJN.S453739 -
Nature and Science of Sleep 2024Mental stress induced myocardial ischemia (MSIMI) is regarded as the primary cause of the angina with no obstructive coronary artery disease (ANOCA). Obstructive sleep...
PURPOSE
Mental stress induced myocardial ischemia (MSIMI) is regarded as the primary cause of the angina with no obstructive coronary artery disease (ANOCA). Obstructive sleep apnea (OSA) is autonomously linked to obstructive coronary heart disease, hypertension, and sudden cardiac death. Similar to the impact of psychological stress on the cardiovascular system, individuals with OSA experience periodic nocturnal hypoxia, resulting in the activation of systemic inflammation, oxidative stress, endothelial dysfunction, and sympathetic hyperactivity. The contribution of OSA to MSIMI in ANOCA patients is unclear. To explore the prevalence of OSA in ANOCA patients and the correlation between OSA and MSIMI, a prospective cohort of female ANOCA patients was recruited.
PATIENTS AND METHODS
We recruited female patients aged 18 to 75 years old with ANOCA and evaluated MSIMI using positron emission tomography-computed tomography. Subsequently, Level III portable monitors was performed to compare the relationship between OSA and MSIMI.
RESULTS
There is higher REI (7.8 vs 2.6, =0.019), ODI (4.7 vs 9.2, =0.028) and percentage of OSA (67.74% vs 33.33%, =0.004) in MSIMI patients. The patients diagnosed with OSA demonstrated higher myocardial perfusion imaging scores (SSS: 1.5 vs 3, = 0.005, SDS: 1 vs 3, P = 0.007). Adjusted covariates, the risk of developing MSIMI remained 3.6 times higher in OSA patients (β=1.226, OR = 3.408 (1.200-9.681), = 0.021).
CONCLUSION
Patients with MSIMI exhibit a greater prevalence of OSA. Furthermore, the myocardial blood flow perfusion in patients with OSA is reduced during mental stress.
PubMed: 38911317
DOI: 10.2147/NSS.S445219 -
Frontiers in Genetics 2024Osteoporosis (OP) is typically diagnosed by evaluating bone mineral density (BMD), and it frequently results in fractures. Here, we investigated the causal relationships...
BACKGROUND
Osteoporosis (OP) is typically diagnosed by evaluating bone mineral density (BMD), and it frequently results in fractures. Here, we investigated the causal relationships between diet-derived circulating antioxidants and the risk of OP using Mendelian randomization (MR).
METHODS
Published studies were used to identify instrumental variables related to absolute levels of circulating antioxidants like lycopene, retinol, ascorbate, and β-carotene, as well as antioxidant metabolites such as ascorbate, retinol, α-tocopherol, and γ-tocopherol. Outcome variables included BMD (in femoral neck, lumbar spine, forearm, heel, total body, total body (age over 60), total body (age 45-60), total body (age 30-45), total body (age 15-30), and total body (age 0-15)), fractures (in arm, spine, leg, heel, and osteoporotic fractures), and OP. Inverse variance weighted or Wald ratio was chosen as the main method for MR analysis based on the number of single nucleotide polymorphisms (SNPs). Furthermore, we performed sensitivity analyses to confirm the reliability of the findings.
RESULTS
We found a causal relationship between absolute retinol levels and heel BMD ( = 7.6E-05). The results of fixed effects IVW showed a protective effect of absolute retinol levels against heel BMD, with per 0.1 ln-transformed retinol being associated with a 28% increase in heel BMD (OR: 1.28, 95% CI: 1.13-1.44). In addition, a sex-specific effect of the absolute circulating retinol levels on the heel BMD has been observed in men. No other significant causal relationship was found.
CONCLUSION
There is a positive causal relationship between absolute retinol levels and heel BMD. The implications of our results should be taken into account in future studies and in the creation of public health policies and OP prevention tactics.
PubMed: 38911297
DOI: 10.3389/fgene.2024.1346367 -
Open Medicine (Warsaw, Poland) 2024Parkinson's disease (PD), characterized by tremor, slowness of movement, stiffness, and poor balance, is due to a significant loss of dopaminergic neurons in the... (Review)
Review
Parkinson's disease (PD), characterized by tremor, slowness of movement, stiffness, and poor balance, is due to a significant loss of dopaminergic neurons in the substantia nigra pars compacta and dopaminergic nerve terminals in the striatum with deficit of dopamine. To date the mechanisms sustaining PD pathogenesis are under investigation; however, a solid body of experimental evidence involves neuroinflammation, mitochondrial dysfunction, oxidative stress, and apoptotic cell death as the crucial factors operating in the pathogenesis of PD. Nutrition is known to modulate neuroinflammatory processes implicated in the pathogenesis and progression of this neurodegenerative disorder. Consistent with this notion, the Burseraceae family, which includes the genera and , are attracting emerging interest in the treatment of a wide range of pathological conditions, including neuroinflammation and cognitive decline. Bioactive components present in these species have been shown to improve cognitive function and to protect neurons from degeneration in , animal, as well as clinical research. These effects are mediated through the anti-inflammatory, antiamyloidogenic, anti-apoptotic, and antioxidative properties of bioactive components. Although many studies have exploited possible therapeutic approaches, data from human studies are lacking and their neuroprotective potential makes them a promising option for preventing and treating major neurodegenerative disorders.
PubMed: 38911256
DOI: 10.1515/med-2024-0988 -
Open Medicine (Warsaw, Poland) 2024Mitochondria-derived reactive oxygen species production at a moderate physiological level plays a fundamental role in the anti-aging signaling, due to their action as... (Review)
Review
Mitochondria-derived reactive oxygen species production at a moderate physiological level plays a fundamental role in the anti-aging signaling, due to their action as redox-active sensors for the maintenance of optimal mitochondrial balance between intracellular energy status and hormetic nutrients. Iron regulatory protein dysregulation, systematically increased iron levels, mitochondrial dysfunction, and the consequent oxidative stress are recognized to underlie the pathogenesis of multiple neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. Central to their pathogenesis, Nrf2 signaling dysfunction occurs with disruption of metabolic homeostasis. We highlight the potential therapeutic importance of nutritional polyphenols as substantive regulators of the Nrf2 pathway. Here, we discuss the common mechanisms targeting the Nrf2/vitagene pathway, as novel therapeutic strategies to minimize consequences of oxidative stress and neuroinflammation, generally associated to cognitive dysfunction, and demonstrate its key neuroprotective and anti-neuroinflammatory properties, summarizing pharmacotherapeutic aspects relevant to brain pathophysiology.
PubMed: 38911254
DOI: 10.1515/med-2024-0986 -
Iranian Journal of Basic Medical... 2024The present study aimed to explore the mechanisms underlying the potency of the renoprotective effect of the EtOAc fraction of (EALD) (Plumbaginaceae) against...
OBJECTIVES
The present study aimed to explore the mechanisms underlying the potency of the renoprotective effect of the EtOAc fraction of (EALD) (Plumbaginaceae) against cyclosporine A (CsA), in comparison to vitamin E (Vit. E).
MATERIALS AND METHODS
In the experiment, a model of CsA-induced nephrotoxicity was established by dosing male Wistar rats with 25 mg/kg, for 14 days. The protective effect of EALD was investigated through pretreatment of rats with a dose of 200 mg/kg for 14 days, compared to the oral administration of Vit. E at 100 mg/kg. Renal function and markers of oxidative stress were then assessed. Furthermore, a complementary study was carried out to evaluate CsA-induced endoplasmic reticulum stress (ERS) and inflammation on cell culture (3T3 cells and MCT cells) using western blot and quantitative RT-PCR..
RESULTS
Pretreatment of rats with EALD significantly attenuated the elevated levels of renal dysfunction markers (BUN, creatinine) and suppressed malondialdehyde (MDA) levels; It also significantly regulated the changes in superoxide dismutase (SOD), reduced glutathione (GSH), glutathione peroxydase (GPx), and glutathione S-transferase (GST) levels as compared to Vit. E, demonstrating a more effective recovery in renal tissues. Treatment of cells with CsA was linked to the expression of ERS and inflammatory markers activating transcription factor (ATF4), inositol-requiring enzyme 1α (IRE1α), binding immunoglobulin protein (BiP), and monocyte chemoattractant protein-1 (MCP1). In contrast, pretreatment of cells with EALD resulted in a significant decrease in both ERS and inflammatory markers.
CONCLUSION
These findings indicate the renoprotective potential of , as it demonstrated the ability to ameliorate CsA-induced renal dysfunction through its distinctive antioxidant properties.
PubMed: 38911250
DOI: 10.22038/IJBMS.2024.77052.16661 -
Iranian Journal of Basic Medical... 2024Several pharmacological effects were described for () seed and it has been used traditionally to treat various diseases. In this review article, the updated and... (Review)
Review
Several pharmacological effects were described for () seed and it has been used traditionally to treat various diseases. In this review article, the updated and comprehensive anti-oxidant effects of and its main constituent, thymoquinone (TQ), on various disorders are described. The relevant articles were retrieved through PubMed, Science Direct, and Scopus up to December 31, 2023. Various extracts and essential oils of showed anti-oxidant effects on cardiovascular, endocrine, gastrointestinal and liver, neurologic, respiratory, and urogenital diseases by decreasing and increasing various oxidant and anti-oxidant marketers, respectively. The main constituent of the plant, TQ, also showed similar anti-oxidant effects as the plant itself. The anti-oxidant effects of different extracts and essential oils of were demonstrated in various studies which were perhaps due to the main constituent of the plant, TQ. The findings of this review article suggest the possible therapeutic effect of and TQ in oxidative stress disorders.
PubMed: 38911247
DOI: 10.22038/IJBMS.2024.75985.16453 -
Iranian Journal of Basic Medical... 2024Polycystic ovary syndrome (PCOS) is a complex metabolic and endocrine disorder associated with chronic inflammation. However, the effect of ∆ tetrahydrocannabinol-9...
Revitalizing polycystic ovary syndrome: The therapeutic impact of low-dose ∆ tetrahydrocannabinol-9 through reduction of oxidative stress and modulation of macrophage polarization.
OBJECTIVES
Polycystic ovary syndrome (PCOS) is a complex metabolic and endocrine disorder associated with chronic inflammation. However, the effect of ∆ tetrahydrocannabinol-9 (THC) on PCOS has not been evaluated. Therefore, this study aimed to investigate the immunomodulatory effects of THC in an animal model of PCOS.
MATERIALS AND METHODS
Twenty female Sprague-Dawley rats, aged 4 weeks, were divided into four groups. The control group received a normal diet, the sham group received a vehicle (carboxymethyl cellulose), the PCOS group received a high-fat diet (HFD) for 16 weeks followed by letrozole for 4 weeks, and the THC group received an HFD for 16 weeks followed by letrozole+THC (0.02 mg/kg) for 4 weeks.
RESULTS
The PCOS animals exhibited significantly higher levels of testosterone, insulin, triglycerides, and total cholesterol, along with elevated inflammatory and oxidative stress markers compared to the control group. Flow cytometry and real-time PCR analysis revealed an increase in M1 macrophage markers and a decrease in M2 macrophage markers compared to the control group. However, the administration of a low dose of THC mitigated these disturbances.
CONCLUSION
Low-dose THC improved inflammatory responses and shifted the balance of M1/M2 macrophage markers towards M2 macrophages in the animal model of PCOS.
PubMed: 38911246
DOI: 10.22038/IJBMS.2024.73892.16061 -
Iranian Journal of Basic Medical... 2024Polycystic ovary syndrome (PCOS) is one of the main causes of infertility in women. This study was conducted to uncover the effects of lupeol as an anti-androgenic...
OBJECTIVES
Polycystic ovary syndrome (PCOS) is one of the main causes of infertility in women. This study was conducted to uncover the effects of lupeol as an anti-androgenic triterpene on experimentally-induced PCOS in mice.
MATERIALS AND METHODS
Eighty immature female mice were divided into 4 groups: Control (C), PCOS (P), Lupeol (L), and Flutamide (F). PCOS was induced in test groups by injection of Dehydroepiandrosterone (60 mg/kg/day, IP) for twenty days. Following the PCOS induction, the two groups of L and F were treated with lupeol (40 mg/kg/day) and/or flutamide (10 mg/kg/day) respectively and the two groups of C and P received sesame oil (0.1 ml/mouse/day) for 15 days. After the treatment period, ten animals in each group were selected for collecting blood and ovary samples. fertilization assessment was carried out on 10 remaining mice in each group. The hormonal assays and oxidative stress biomarker determination were performed on serum and tissue samples. Moreover, histopathological analyses were conducted on the ovaries.
RESULTS
PCOS-elevated concentration of LH and Testosterone was significantly (<0.05) lowered in lupeol and flutamide-received animals. Lupeol and flutamide both reduced PCOS-induced fibrosis and the number of atretic follicles. Both compounds declined the PCOS-increased lipid peroxidation and protein oxidation in serum and the ovaries. Lupeol increased the PCOS-reduced fertility rate and decreased the number of arrested embryos by 12%.
CONCLUSION
These findings indicate that lupeol could be a novel compound in the treatment of PCOS as it reduced PCOS-induced structural and also functional disorders.
PubMed: 38911242
DOI: 10.22038/IJBMS.2024.77602.16783 -
Iranian Journal of Basic Medical... 2024Rhabdomyolysis, a potentially life-threatening condition, occurs when myoglobin is released from damaged muscle cells, leading to acute kidney injury (AKI). Alpha lipoic...
OBJECTIVES
Rhabdomyolysis, a potentially life-threatening condition, occurs when myoglobin is released from damaged muscle cells, leading to acute kidney injury (AKI). Alpha lipoic acid (ALA), an organosulfur compound known for its anti-oxidant and anti-inflammatory properties, was examined in this study for its potential impact on rhabdomyolysis-induced AKI in rats.
MATERIALS AND METHODS
Six groups of rats were included in the study, with each group consisting of six rats (n=6): Control, rhabdomyolysis, rhabdomyolysis treated with different doses of ALA (5, 10, and 20 mg/kg), and ALA alone (20 mg/kg) groups. Rhabdomyolysis was induced by intramuscular injection of glycerol on the first day of the experiment, while ALA was administered intraperitoneally for four consecutive days. Renal function parameters, oxidative stress markers, and histological changes in the kidneys were evaluated. Western blot analysis was performed to measure the levels of neutrophil gelatinase-associated lipocalin (NGAL) and tumor necrosis factor-alpha (TNF-α) proteins.
RESULTS
A significant increase in serum urea, creatinine, renal malondialdehyde, NGAl, and TNF-α protein levels was observed in glycerol-injected rats. In addition, a significant decrease in glutathione was recorded. Compared to the rhabdomyolysis group, treatment with ALA recovered kidney histological and biochemical abnormalities.
CONCLUSION
Results suggest that rhabdomyolysis-induced AKI is associated with increased oxidative stress and inflammation. Treatment with ALA improved kidney histological abnormalities and reduced oxidative stress markers in rats. Therefore, ALA may have a potential protective effect against rhabdomyolysis-induced AKI.
PubMed: 38911241
DOI: 10.22038/IJBMS.2024.74864.16252