Oxidative Stress Conditions Research Articles

The Potential of Selenium-Based Therapies for Ocular Oxidative Stress.

Oxidative stress plays a critical role in the development of chronic ocular conditions including cataracts, age-related macular degeneration, and diabetic retinopathy. There is a need to explore the potential of topical antioxidants to slow the progression of those conditions by mediating oxidative stress and maintaining ocular health. Selenium has attracted considerable attention because it is a component of selenoproteins and antioxidant enzymes. The application of selenium to a patient can increase selenoprotein expression, counteracting the effect of reactive oxygen species by increasing the presence of antioxidant enzymes, and thus slowing the progression of chronic ocular disorders. Oxidative stress effects at the biomolecular level for prevalent ocular conditions are described in this review along with some of the known defensive mechanisms, with a focus on selenoproteins. The importance of selenium in the eye is described, along with a discussion of selenium studies and uses. Selenium's antioxidant and anti-inflammatory qualities may prevent or delay eye diseases. Recent breakthroughs in drug delivery methods and nanotechnology for selenium-based ocular medication delivery are enumerated. Different types of selenium may be employed in formulations aimed at managing ocular oxidative stress conditions.

Intracellular and extracellular Cyclophilin a promote cardiac fibrosis through TGF-β signaling in response to angiotensin Ⅱ

Cardiac fibrosis is characterized by abnormal proliferation of cardiac fibroblasts (CFs) and ventricular remodeling, which finally leads to heart failure. Inflammation and oxidative stress play a central role in the development of cardiac fibrosis. CyPA (Cyclophilin A) is a main proinflammatory cytokine secreted under the conditions of oxidative stress. The mechanisms by which intracellular and extracellular CyPA interact with CFs are unclear. Male C57BL/6 J mice received angiotensin Ⅱ (Ang Ⅱ) or vehicle for 4 weeks. Inhibition of CyPA significantly reversed Ang Ⅱ-induced cardiac hypertrophy and fibrosis. Mechanically, TGF-β (Transforming growth factor-β) signaling was found to be an indispensable downstream factor of CyPA-mediated myofibroblast differentiation and proliferation. Furthermore, intracellular CyPA and extracellular CyPA activate TGF-β signaling through NOD-like receptor protein 3 (NLRP3) inflammasome and nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, respectively. Pharmacological inhibition of CyPA and its receptor CD147 implemented by Triptolide also attenuated the expression of TGF-β signaling and cardiac fibrosis in Ang Ⅱ-model. These studies elucidate a novel mechanism by which CyPA promotes TGF-β and its downstream signaling in CFs and identify CyPA (both intracellular and extracellular) as plausible therapeutic targets for preventing or treating cardiac fibrosis induced by chronic Ang Ⅱ stimulation.

Screening mitochondria-related biomarkers in skin and plasma of atopic dermatitis patients by bioinformatics analysis and machine learning.

There is a significant imbalance of mitochondrial activity and oxidative stress (OS) status in patients with atopic dermatitis (AD). This study aims to screen skin and peripheral mitochondria-related biomarkers, providing insights into the underlying mechanisms of mitochondrial dysfunction in AD. Public data were obtained from MitoCarta 3.0 and GEO database. We screened mitochondria-related differentially expressed genes (MitoDEGs) using R language and then performed GO and KEGG pathway analysis on MitoDEGs. PPI and machine learning algorithms were also used to select hub MitoDEGs. Meanwhile, the expression of hub MitoDEGs in clinical samples were verified. Using ROC curve analysis, the diagnostic performance of risk model constructed from these hub MitoDEGs was evaluated in the training and validation sets. Further computer-aided algorithm analyses included gene set enrichment analysis (GSEA), immune infiltration and mitochondrial metabolism, centered on these hub MitoDEGs. We also used real-time PCR and Spearman method to evaluate the relationship between plasma circulating cell-free mitochondrial DNA (ccf-mtDNA) levels and disease severity in AD patients. MitoDEGs in AD were significantly enriched in pathways involved in mitochondrial respiration, mitochondrial metabolism, and mitochondrial membrane transport. Four hub genes (BAX, IDH3A, MRPS6, and GPT2) were selected to take part in the creation of a novel mitochondrial-based risk model for AD prediction. The risk score demonstrated excellent diagnostic performance in both the training cohort (AUC = 1.000) and the validation cohort (AUC = 0.810). Four hub MitoDEGs were also clearly associated with the innate immune cells' infiltration and the molecular modifications of mitochondrial hypermetabolism in AD. We further discovered that AD patients had considerably greater plasma ccf-mtDNA levels than controls (U = 92.0, p< 0.001). Besides, there was a significant relationship between the up-regulation of plasma mtDNA and the severity of AD symptoms. The study highlights BAX, IDH3A, MRPS6 and GPT2 as crucial MitoDEGs and demonstrates their efficiency in identifying AD. Moderate to severe AD is associated with increased markers of mitochondrial damage and cellular stress (ccf=mtDNA). Our study provides data support for the variation in mitochondria-related functional characteristics of AD patients.

Melatonin regulates the antioxidant capacity of sheep granulosa cells through a novel uORF-Nrf2aa mediated Nrf2/KEAP1 pathway

Ovarian dysfunction stands as a prevalent contributor to female infertility, with its etiology intertwined with genetic, autoimmune, and environmental factors. Within the ovarian follicles, granulosa cells (GCs) represent the predominant cell population. Alterations in GCs, notably oxidative stress (OS) and the consequential surge in reactive oxygen species (ROS), play pivotal roles in the orchestration of ovarian function. Nrf2aa, a newly identified upstream open reading frame (uORF), is situated within the 5′ untranslated region (5'UTR) of sheep Nrf2 mRNA and is regulated by melatonin, a crucial intrafollicular antioxidant. In this study, we have noted that Nrf2aa has the capacity to encode a peptide and exerts a negative regulatory effect on the translation efficiency (TE) of the Nrf2 CDs region. Further in vitro experiments, we observed that interfering with Nrf2aa can enhance the cellular functionality of GCs under 3-np-induced oxidative stress, while overexpressing Nrf2aa has the opposite effect. Furthermore, overexpression of Nrf2aa counteracts the rescuing effect of melatonin on the cellular functions of GCs under oxidative stress conditions, including estrogen secretion, proliferation, apoptosis, and many more. Finally, we confirmed that Nrf2aa, by regulating the expression of key proteins in the Nrf2/KEAP1 signaling pathway, further modulates the antioxidant levels in GCs.

Novel Approaches Used for Decreasing Apoptosis Rate in Ovarian Tissue Cryopreservation and Transplantation

Apoptosis is the main cause of atresia in ovarian follicles. In oxidative stress (OS) conditions, an imbalance between pro-apoptotic and anti-apoptotic genes can increase the apoptosis rate. In some diseases, such as cancers, patients lose fertility due to chemotherapy and radiotherapy. One way to maintain fertility in these patients is ovarian tissue cryopreservation and transplantation (OTC/T). Studies show that OTC/T also increases apoptosis due to hypoxia and ischemia but fortunately new findings show that applying new approaches could decrease apoptosis in these procedures considerably. This article reviewed follicular atresia, apoptosis during cryopreservation and transplantation, and factors affecting the reduction of apoptosis.

Biosurfactant assisted synthesis and characterization of silver nanoparticles: In vitro investigation of their anti-oxidant, anti-inflammatory, anti-infective and wound healing potential

Silver nanoparticles (AgNPs) hadshowen immense potential for managing inflammatory responses, oxidative stress, and severe microbial infections leading to chronic wounds by reducing environmental impact and resistance. Plant-mediated synthesis offers eco-friendly solutions, especially in degrading harmful textile dyes, benefiting ecosystems. Still, frequent aggregation and destabilization are the major limitations of metallic nanoparticles. Mannosylerythritol (MST), a lipid derived from microorganisms stabilises metallic nanoparticles. AgNPs were prepared by a chemical reduction method, characterized for optical, surface properties, and elemental analysis, and evaluated for ionic silver release, antioxidant effect, inhibition of ROS generation and NF-kB upregulation, anti-infective and wound closure potentials. The AgNPs comprised of 0.04% w/v AgNO3, 0.3% w/v sodium borohydride and 0.5% w/v MST exhibited nanosized (50–80 nm) orbicular particles with high purity and stability. EDX analysis portrayed the presence of 92.82% Ag by weight. Unlike acidified AgNPs, plane AgNPS showed consistent Ag+ release for 24 h, owing to which this group showed tremendous utility in scavenging DPPH-induced free radicals (20-fold lesser IC50 value) with a slight decrease in RAW 264.7 cell viability when tested by MTT assay. The MIC of AgNPs against C. albicans, S. aureus and P. aeruginosa was 10, 10 and 5 ppm, respectively. The microbial GI of AgNPs was found to be 62.44 ppm against C. albicans, 110.69 against S. aureus and 91.58 against P. aeruginosa. Flowcytometry showed a reduction in ROS generation, and NF-κβ upregulation justifies the safer use of AgNPs against oxidative stress and inflammatory conditions. The in vitro scratch test in RAW 264.7 cells justifies the rapid wound closure claim. Controlling a wide range of pathogens while mitigating oxidative stress and inflammation is the optimal strategy for expediting wound healing. Consequently, these AgNPs hold significant promise as innovative wound dressing materials for the future.

179 Effects of Saccharomyces yeast postbiotics on intestinal health of newly weaned pigs challenged with F18+ Escherichia coli.

Abstract The purpose of this study was to investigate the effects of Saccharomyces yeast postbiotics (celluTEIN, Puretein Biosecience LLC, Minneapolis, MN, USA) on the intestinal health and growth performance of newly weaned pigs challenged with F18+ Escherichia coli. Nursery pigs [n =36; initial body weight (BW) = 6.42 ± 0.33 kg BW] were allotted into three dietary treatments utilizing a randomized complete block design with sex and initial BW as blocks. The dietary treatments included a negative control (NC: basal diet, no challenge), a positive control (PC: basal diet, challenged with F18+ E. coli), and SYP (basal diet with Saccharomyces yeast postbiotics at 175 g/ton of feed, challenged with F18+ E. coli). Basal diets were formulated to meet NRC (2012) requirements with Saccharomyces yeast postbiotics replacing corn in the basal diet. Pigs were fed for 28 d in 3 phases (P1: 11 d, P2: 10 d, P3: 7 d). Pigs in PC and Saccharomyces yeast postbiotics were orally inoculated with F18+ E. coli (2.0 × 1010 CFU), whereas the NC group received sterile saline, given in 4 doses beginning on d 7 after weaning. Throughout, fecal score, BW, and feed intake were recorded to calculate average daily gain (ADG), average daily feed intake (ADFI), and gain to feed ratio (G:F). At d 28, all pigs were euthanized for sampling of the jejunal mucosa to analyze oxidative stress and immune status, as well as microbiota diversity and relative abundance. Data were analyzed using the Proc Mixed in SAS 9.4 (Cary, NC). Overall, PC reduced (P &amp;lt; 0.05) the BW, ADG, and ADFI of pigs. The SYP had a tendency (P = 0.098) to improve the ADFI of pigs challenged with F18+ E. coli. The fecal score of pigs fed SYP were improved (P &amp;lt; 0.05) on d 7 to 18 of the post-challenge period when compared with PC. Furthermore, SYP reduced protein carbonyl (P &amp;lt; 0.05), reduced (P &amp;lt; 0.05) the relative abundance of Erysipelotrichaceae, and had a tendency to increase Leuconostocaceae (P = 0.090), Streptococcaceae (P = 0.068), Corynebacteriaceae (P = 0.085), and had a tendency to reduce (P = 0.077) Ruminococcaceae when compared with PC. Additionally, SYP reduced (P &amp;lt; 0.05) gene expression of toll-like receptor 4 (TLR4) and increased (P &amp;lt; 0.05) gene expression mammalian target of rapamycin (mTOR), when compared with PC. In conclusion, challenge with F18+ E. coli increased fecal score, disrupted the microbiota composition in the jejunal mucosa, and increased gene expression associated with recognition of pathogens, without any impact on inflammation; therefore, negatively affecting growth performance. Saccharomyces yeast postbiotics could reduce the negative effects associated with F18+ E. coli infection by altering microbial diversity and reducing inflammation associated with expression of TLR4, and oxidative stress products, without changes in growth.

Early pyridoxine administration rescues autism-like behavior in the BTBR T+tf/J autistic model

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder characterized by social impairment and repetitive, stereotyped behaviors. An imbalanced oxidative stress status and neuroinflammation are involved in ASD development. In this study, we investigated the effects of pyridoxine, a form of vitamin B6 with potent anti-oxidant and anti-inflammatory features, on autism-like behavior in BTBR T + ltpr3tf/J (BTBR) mice, a model of autism. Mice received pyridoxine from postnatal days 7 to 14. Behavioral tests were conducted on 8-week-old male mice, and the inflammatory status and oxidative stress levels were also assessed in the mouse hippocampus. Postnatal pyridoxine treatment significantly improved social deficits, stereotyped behaviors, and cognitive deficits in BTBR mice. In addition, pyridoxine treatment alleviated neuroinflammation in the hippocampus manifested by reduced Iba1+ microglia and inflammatory factors, such as interleukin-1β (IL-1β), IL-6, TNF-α, and NF-κB. Further, pyridoxine-treated BTBR mice had elevated Nrf2 and HO-1 in the hippocampus. Postnatal pyridoxine administration might improve autistic-like behaviors in BTBR mice via attenuating oxidative stress and neuroinflammation in the hippocampus.

280 Feeding a combination of feed additives before and during farrowing of sows reduces inflammation and oxidative stress and increases blood calcium to support uterine contraction

Abstract Farrowing is associated with inflammation and increasing oxidative stress status. In addition, during farrowing, calcium requirement increases to support uterine contraction. We have previously observed that feeding a combination of feed additives (FA), that contains inulin, Bacillus velezensis, extracts of olive oil and artichoke, and calcitriol, reduced the duration and assistance of farrowing in sows, and the number of stillborn piglets. It was hypothesized that feeding the combination of FA would reduce inflammation and oxidative stress and provide Ca to support uterine contractions during farrowing. A total of 34 sows from d 107 of gestation until 2 d post-farrowing were randomly allotted (balanced by parity 3.8 ± 2.5) to two treatments: without (control -CON) or with the FA combination (FA, Adicare Vita, 200 g/d). At the starting d (D 107 of gestation) and 24 h post-farrowing, blood samples were obtained to analyze for pig major acute-phase protein (Pig-MAP as an inflammation biomarker) and glutathione peroxidase (GPx as an antioxidant biomarker). During farrowing, sows were monitored, and blood samples were collected at 0 h, 2.5 h and 5 h to analyze for ionized Ca (iCa). Data was analyzed using SAS 9.4. Mean values were calculated using LSMeans statement. P-values &amp;lt; 0.05 were considered significant while tendencies were considered at 0.05 ≤ P &amp;lt; 0.10. Pig-MAP and GPx were analyzed using the MIXED procedure and iCa concentrations as repeated measures using the MIXED procedure. Sows fed the FA combination compared with CON sows tended to have decreased post-farrowing Pig-MAP l concentrations (2.52 vs. 4.29 mg/mL, respectively; P = 0.08) and greater GPx concentrations (2,112 vs. 1,588 U/L, respectively; P &amp;lt; 0.01). FA sows had greater (P &amp;lt; 0.05) blood Ca concentrations during farrowing compared with CON sows (0.90, 1.10, and 1.01 vs. 0.85, 0.98, and 0.96 mmol/L at 0, 2.5 and 5h, respectively). To conclude, feeding a combination of FA during the last week of gestation might provide antioxidant effects, reduce inflammation caused by farrowing, and increase blood Ca to favor the uterine contractions.

Hesperidin neuroprotective effects against carbon monoxide-induced toxicity in male rats.

Carbon monoxide (CO) is produced via incomplete combustion of fossil fuels and it may cause long-term neurological sequel upon exposure. Hesperidin (HES), a flavanone glycoside found in citrus plants, exerts diverse beneficial health effects. The present study mechanistically examined the neuroprotective effects of HES in CO-poisoned rats. Thirty male Wistar rats (five groups of six animals) were exposed to 3000 ppm CO for 1 h. Immediately after the exposure and on the next 4 consecutive days (totally five doses), rats intraperitoneally received either normal saline (the control group) or different doses of HES (25, 50, and 100 mg/kg). A sham group that was not exposed to CO was also considered. After evaluation of spatial learning and memory using a Morris water maze (MWM), animals were sacrificed and oxidative stress status in blood samples, and Akt, Bax, Bcl2, and brain-derived neurotrophic factor (BDNF) expression in brain samples were assessed. Western blot analysis indicated increased Akt but decreased Bax/Bcl2 levels in the HES 100 mg/kg, and induced BDNF levels in all HES-treated groups. MWM results showed that HES significantly decreased memory loss. The current findings indicate that HES could alleviate neurological impairments induced by CO in rats.

The effects of oxidative stress and intracellular calcium on mitochondrial permeability transition pore formation in equine spermatozoa

AbstractThe in vitro storage of stallion spermatozoa for use in artificial insemination leads to oxidative stress and imbalances in calcium homeostasis that trigger the formation of the mitochondrial permeability transition pore (mPTP), resulting in premature cell death. However, little is understood about the dynamics and the role of mPTP formation in mammalian spermatozoa. Here, we identify an important role for mPTP in stallion sperm Ca2+ homeostasis. We show that stallion spermatozoa do not exhibit “classical” features of mPTP; specifically, they are resistant to cyclosporin A‐mediated inhibition of mPTP formation, and they do not require exogenous Ca2+ to form the mPTP. However, chelation of endogenous Ca2+ prevented mPTP formation, indicating a role for intracellular Ca2+ in this process. Furthermore, our findings suggest that this cell type can mobilize intracellular Ca2+ stores to form the mPTP in response to low Ca2+ environments and that under oxidative stress conditions, mPTP formation preceded a measurable increase in intracellular Ca2+, and vice versa. Contrary to previous work that identified mitochondrial membrane potential (MMP) as a proxy for mPTP formation, here we show that a loss of MMP can occur independently of mPTP formation, and thus MMP is not an appropriate proxy for the detection of mPTP formation. In conclusion, the mPTP plays a crucial role in maintaining Ca2+ and reactive oxygen species homeostasis in stallion spermatozoa, serving as an important regulatory mechanism for normal sperm function, thereby contraindicating the in vitro pharmacological inhibition of mPTP formation to enhance sperm longevity.

Role of Antioxidant Vitamins in Oral Submucous Fibrosis: A Narrative Review.

Oral submucous fibrosis (OSMF) has a high rate of malignant transformation and is an insidious chronic inflammatory disease. Though this disorder seems to be multifactorial in origin, betel quid chewing appears to be the main etiologic factor. Various treatment strategies have been attempted but none proven to cure the disorder because of its multimodal pathogenesis. Reactive oxygen species (ROS) appear to have a role in cancer formation. As OSMF is an oral premalignant disorder and found to be associated with carcinogens like areca nut and tobacco, it is believed to have some relationship with ROS. Tissue damage due to ROS along with other mechanisms may result in the complex pathophysiology of OSMF. The antioxidant system in the body helps to prevent damage caused by highly reactive ROS and helps in the repair of tissues. To study the levels of oxidative stress and antioxidant vitamins in OSMF condition, the present review was done. We carried out a thorough literature search to identify original reports and studies determining the status of oxidative stress and antioxidant vitamins in OSMF condition using several databases including Google Scholar, PubMed, and Scopus. Our review observed that the oxidative stress increased in the condition of OSMF as shown by an increase in malonaldehyde (MDA) and a decrease in antioxidant vitamins like vitamin A, vitamin C, and vitamin E. Also, after the intake of antioxidant vitamins, there was symptomatic improvement in OSMF patients. With the help of identifying oxidative stress and antioxidant status, we can assess the clinical stage of OSMF and can develop a comprehensive treatment plan.

Salicylic Acid and Calcium Chloride Seed Priming: A Prominent Frontier in Inducing Mineral Nutrition Balance and Antioxidant System Capacity to Enhance the Tolerance of Barley Plants to Salinity.

The current investigation aims to underline the impact of salicylic acid or calcium chloride seed pre-treatments on mineral status and oxidative stress markers, namely levels of electrolyte leakage (EL) and lipid peroxidation levels, measured as thiobarbituric reactive substances (TBARS), and the activity of some antioxidant enzymes in roots and leaves of plants in two barley species grown under various salt treatments. Overall, our results revealed that salinity inhibits essential nutrient absorption such as iron, calcium, magnesium and potassium and stimulates the absorption of sodium. Also, this environmental constraint induced oxidative stress in plants in comparison with the control conditions. This state of oxidative stress is reflected by an increase in TBARS content as well as the stimulation of EL values. In addition, salinity induced disturbances in the activity of antioxidant enzymes, which were mainly dependent on the applied salt concentration and the species. In addition, Hordeum marinum maintained high antioxidant enzyme activity and low levels of oxidative stress parameters, which reinforces its salt-tolerant character. Importantly, salicylic acid or calcium chloride seed priming alleviated the mineral imbalance and the oxidative damage induced by salinity. Moreover, seed priming improves iron, calcium magnesium and potassium content and limitsthe accumulation of sodium. Also, both treatments not only decrease TBARS levels and limit EL, but they also stimulate the antioxidant enzyme activities in the leaves and roots of the stressed plants as compared with stressed plants grown from non-primed seeds. Interestingly, the beneficial effects of the mentioned treatments were more notable on Hordeum vulgare species.

Analysis of thioredoxin 1 levels in a mouse model of unilateral renal ischemia-reperfusion injury

Kidney disease, acute and chronic, is associated with high morbidity and mortality. Currently, a major obstacle in the field of nephrology is the lack of novel and more sensitive biomarkers that would allow an early diagnose and a proper monitoring of disease progression. Oxidative stress and the increased production of reactive oxygen species (ROS) have been implicated in the pathophysiology of a variety of renal diseases. Proteins of the thioredoxin (Trx) family, among others thioredoxins (Trxs) and glutaredoxins (Grxs), represent one of the most important protective systems in the defense against ROS as well as in the repair of their intracellular effects. Thioredoxin 1 (Trx1) is a cytosolic redox protein that catalyzes the reduction of protein disulfides using the thiol groups of two cysteine residues on its CGPC active site. Trx1 is abundantly expressed in different segments of the nephron and has been shown to be released from cells under conditions of oxidative stress in vitro and in vivo. We hypothesized that renal IRI induces the release of Trx1 from cells into extracellular fluids such as serum and tubular fluid/urine and that Trx1 increase may correlate with the degree of damage in the kidney. We established an effective mouse model of unilateral renal ischemia-reperfusion injury (IRI) and studied Trx1 levels in the serum, urine, as well as in various nephron segments of mice following IRI or sham surgery. We compared different reperfusion times (4h, 8h, 16h, 24h, 48h, 96h, and 168h) to track Trx1 levels fluctuation over time. Serum levels of Trx1 increased 4h after renal IRI, while other markers such as blood urea nitrogen and creatinine remained low. Serum Trx1 showed a positive correlation with tubular injury score helping predict intrarenal damage over time. Additionally, immunohistochemistry studies revealed an increase in Trx1 signals in the proximal tubules and collecting ducts as well as a strong nuclear localization in the same nephron segments that became more intense by 96h, a time point characterized by an intense mitotic activity in the tubules. Between 16 and 24h, Trx1 appeared in the lumen of proximal tubules, however urinary levels of Trx1 did not significantly increase. Based on these findings we conclude that serum Trx1 may represent a novel biomarker for assessing renal damage. In addition to this, we hypothesize that intrarenal changes in Trx1 expression and localization might be related to the activation of regeneration mechanisms in the renal tubular epithelium. Further studies are needed to understand the role of Trx1 in the regeneration process after renal IRI. This work was funded by the Center of Integrative Mammalian Research of Ross University School of Veterinary Medicine and by a Startup funding from Long Island University. 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.

Discovering the Potential Value of Coenzyme Q10 as an Adjuvant Treatment in Patients With Depression.

Depressive disorder or mental cold is the most common mental disorder, and depression exists all over the world and in all countries and cultures. The results of several studies have shown that using compounds with antioxidant properties has been fruitful in patients with depression. Coenzyme Q10 (CoQ10) is a fat-soluble antioxidant and exerts its antioxidant effect by directly neutralizing free radicals or reducing tocopherol and preventing the inhibition of mitochondrial activity because of oxidative stress. This study aimed to investigate the effects of oral CoQ10 in patients with depression as an adjunctive treatment. Sixty-nine patients with moderate and severe depression were randomly divided into 2 CoQ10 groups (36) and placebo (33). The first group of patients received CoQ10 supplements at a dose of 200 mg daily for 8 weeks along with standard interventions and treatments for depression, and the second group received standard treatments for depression along with a placebo. The change in the score of Montgomery-Åsberg Depression Rating Scale depression scale was evaluated 4 and 8 weeks after the intervention. Also, at baseline and 8 weeks later at the end of the study, serum levels of total antioxidant capacity, total thiol groups, nitric oxide, malondialdehyde, and interleukin 6 were assessed. The changes in the depression score at the end of the study showed that, in the group receiving the CoQ10 supplement after 8 weeks, there was a reduction in depression symptoms, which was statistically significant compared with before the start of the study Meanwhile, no significant changes were observed in the patients of the placebo group in terms of symptom reduction. Compared with baseline and the placebo condition, serum levels of nitric oxide and total thiol groups significantly decreased and increased, respectively. Also, no statistically significant changes were observed for interleukin 6, malondialdehyde, and total antioxidant capacity. A dose of 200 mg of CoQ10 supplement daily for 8 weeks can reduce depression and fatigue, as well as improve the quality of life of patients with depression. In addition, CoQ10 can significantly improve inflammation and oxidative stress status in patients with depression.

Circular RNA KIAA0564 Serves as a Competitive Endogenous RNA for MicroRNA-424-5p, Mediating the Expression of Lysine Demethylase 4a, Thereby Facilitating Intervertebral Disc Degeneration.

A growing body of research has confirmed the involvement of circular RNAs (circRNAs) in the regulation of intervertebral disc degeneration (IDD) progression. However, the underlying molecular networks remain largely elusive. This study aimed to explore whether a novel circRNA, named circKIAA0564, affects nucleus pulposus (NP) cell injury and to elucidate its molecular mechanism. Both in vivo and in vitro IDD models were established, and the expression patterns of circKIAA0564/miR-424-5p/lysine demethylase 4a (KDM4A) were evaluated through quantitative reverse transcription PCR and Western blot analysis. Actinomycin D, RNase R, and Northern blotting were utilized to assess the circular structure of circKIAA0564. The Cell Counting Kit-8, flow cytometry, enzyme-linked immunosorbent assay, commercial assay kits, Western blotting, and reactive oxygen species (ROS) probes were employed to assess the inflammatory and oxidative stress status in NP cells and tissues. Hematoxylin and eosin and TUNEL staining were used to evaluate pathological damage in mouse NP tissues. RNA immunoprecipitation and dual-luciferase reporter assays were conducted to assess the direct targeting relationships among circKIAA0564, miR-424-5p, and KDM4A. CircKIAA0564 was found to be abnormally overexpressed in IDD, functioning as a novel circRNA. Knockdown of circKIAA0564 ameliorated interleukin-1 beta (IL-1β)-induced inflammation and oxidative stress in NP cells. The therapeutic effect of circKIAA0564 knockdown on NP cells was reversed by the silencing of miR-424-5p. Overexpression of circKIAA0564 exacerbated IL-1β-induced NP cell injury, a process that was reversed by knockdown of KDM4A. CircKIAA0564 activated the toll-like receptor 4 (TLR4)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)/NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) signaling pathway by regulating the miR-424-5p/KDM4A axis. CircKIAA0564 exacerbates IL-1β-induced inflammation and oxidative stress in NP cells by competitively binding miR-424-5p, thereby mediating KDM4A and activating the TLR4/NF-κB/NLRP3 signaling pathway. These findings provide robust data support for targeted therapy of IDD and the development of future pharmaceuticals.

Examining the Impact of Environmental and Genetic Factors that Influence Sarcospan Expression in the Heart

Objective: Susceptibility to cardiac injury can be hereditary and the most common causes include genetic variations in proteins regulating lipid metabolism, arterial hypertension, diabetes, body-mass index as well as environmental causes such as smoking. Sarcospan (SSPN) is an integral member of the dystrophin-glycoprotein complex (DGC) and has an important role in stabilizing the muscle membrane of striated muscle. Genetic variants in the SSPN gene have been linked with increased cardiovascular disease risk and studies are ongoing to identify underlying mechanisms. Our studies using perfused mouse hearts subjected to acute ischemia/reperfusion injury indicate that SSPN deletion increases infarct size and arrhythmia risk (Hwang et al, IJMS, 2023). In addition, adult SSPN−/− cardiomyocytes were found to have decreased antioxidative capacity and heightened susceptibility to oxidative stress. Therefore, we hypothesize that genetic factors that decrease cardiac SSPN expression will increase cardiac susceptibility of mice exposed to conditions of prolonged oxidative stress. In this study we examine the role of SSPN to heart injury caused by chronic oxidative stress mediated by cigarette smoke (CS). Methods: To assess the impact of chronic oxidative stress conditions on SSPN expression in the heart 2 month-old WT C57BL/6J mice were exposed to 4 months CS. We found that SSPN expression was significantly reduced the CS exposed hearts. Since CS increases oxidative damage and deteriorates antioxidant defenses of the heart and vascular system, we examined the combined impact of SSPN deficiency and chronic oxidative stress. To address this, 7-month-old WT and SSPN−/− male and female mice were exposed to CS for 4 months. The mice were assessed after CS for body composition (EchoMRI), glucose tolerance testing and echocardiography. Tissue histology, immunoblotting of oxidative and inflammatory stress markers, serum inflammatory markers were assessed. Lung fibroblasts were isolated from the smoked and non-smoked groups to evaluate inflammatory, fibrotic, and oxidative stress pathway activation to respective stimuli. Results: Preliminary findings indicate that after CS SSPN−/− hearts exhibit larger areas of myocardial damage than WT mice. Surprisingly, after CS the SSPN−/− mice showed better glucose tolerance than WT mice and no significant changes in body mass. Minor decrements were found in the cardiac function of the CSE mice. Exposure of lung fibroblasts obtained from non-smoked SSPN−/− mice to innate immune ligands revealed activation of specific pro-inflammatory pathways.Conclusions: SSPN-deficiency increases susceptibility to cardiac injury in mice subjected to CS exposure, likely through crosstalk mechanisms that exist between oxidative and inflammatory pathways that SSPN appears to influence. Funding Sources: Florida Department of Health, James and Esther King #21K12. 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.

Effect of oxidative stress induced by 2,3,7,8- tetrachlorodibenzo-p-dioxin on DNA damage

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a highly toxic persistent organic pollutant (POP) that can induce DNA damage within cells. Although oxidative stress is one of the primary mechanisms causing DNA damage, its role in the process of TCDD-induced DNA damage remains unclear. In this study, the TCDD-induced production of reactive oxygen species (ROS) and the occurrence of DNA damage at the AP site were monitored simultaneously. Further investigation revealed that TCDD impaired the activities of superoxide dismutase (SOD) and catalase (CAT), compromising the cellular antioxidant defense system. Consequently, this led to an increase in the production of O2.− and NO, thus inducing DNA damage at the AP site under oxidative stress. Our findings were further substantiated by the upregulation of key genes in the base excision repair (BER) pathway and the absence of DNA AP site damage after inhibiting O2.− and NO. In addition, transcriptome sequencing revealed that TCDD induces DNA damage by upregulating genes associated with oxidative stress in the mitogen-activated protein kinase (MAPK), cyclic adenosine monophosphate (cAMP), and breast cancer pathways. This study provides important insights into the toxicity mechanisms of TCDD.

Insights about the deleterious impact of a carbamate pesticide on some metabolic immune and antioxidant functions and a focus on the protective ability of a Saharan shrub and its anti-edematous property

Abstract In the Algerian desert, individuals often enjoy a soothing cup of herbal tea made from Ephedra alata Decne before bedtime; this aids in their relaxation. Our previous and earlier investigations demonstrated the richness of the shrub in terms of polyphenols and flavonoids and their effective medicinal properties. In the light of that fact, our interest has been aroused to check for other types of metabolites and for the protective ability of the shrub crude extract (SCE) regarding chemically induced edema and subacute toxicity (following a formalin-induced paw edema model and using a carbamate pesticide “pirimicarb” as a toxic agent, in Wistar male rats, respectively). Evidently, the SCE was used as a preventive agent. Swelling of formalin-injected foot was measured, and the anti-edematous ability was expressed as a percent of paw edema. At the end of induced subacute toxicity procedure, many investigations were carried, namely, checking for biochemical several parameters (hepatic, renal), hematological parameters, oxidative stress status (OSS), and histological examining of liver, spleen, and kidney tissues. The results revealed a remarkable anti-edematous effect. Furthermore, the association of the SCE effect has clearly minimized the OSS, the tissue aberrations, and the disturbance of the other metabolic parameters, along with a reduced immunodepression that was provoked under the effect of pirimicarb. In conclusion, pirimicarb has an important deleterious impact on metabolic and immune functions, and the studied shrub has exhibited an amazing protective potential against chemically induced inflammation and toxicity.

Excessive intragastric alcohol administration exacerbates hepatic encephalopathy and provokes neuronal cell death in male rats with chronic liver disease.

Hepatic encephalopathy (HE) is defined as decline in neurological function during chronic liver disease (CLD). Alcohol is a major etiological factor in the pathogenesis of fibrosis/cirrhosis and has also been documented to directly impact the brain. However, the role of alcohol in the development of HE in CLD remains unclear. Here, we investigated the impact of excessive alcohol administration on neurological deterioration in rats with CLD. Starting day 7 post-BDL surgery, rats were administered alcohol twice daily (51% v/v ethanol, 3 g/kg, via gavage) for 4 weeks. Motor coordination was assessed weekly using rotarod and anxiety-like behavior was evaluated with open field and elevated plus maze at 5 weeks. Upon sacrifice, brains were collected for western blot and immunohistochemical analyses to investigate neuronal integrity and oxidative stress status. Alcohol worsened motor coordination performance and increased anxiety-like behavior in BDL rats. Impairments were associated with decreased neuronal markers of NeuN and SMI311, increased apoptotic markers of cleaved/pro-caspase-3 and Bax/Bcl2, increased necroptosis markers of pRIP3 and pMLKL, decreased total antioxidant capacity (TAC), and increased 4-hydroxynonenal (4-HNE)modified proteins in the cerebellum of BDL-alcohol rats when compared to respective controls. Immunofluorescence confirmed the colocalization of cleaved caspase-3 and pMLKL in the granular neurons of the cerebellum of BDL-alcohol rats. Excessive alcohol consumption exacerbates HE which leads to associated apoptotic and necroptotic neuronal loss in the cerebellum of BDL-alcohol rats. Additionally, higher levels of 4-HNE and decreased TAC in the cerebellum of BDL-alcohol rats suggest oxidative stress is the triggering factor of apoptotic and necroptotic neuronal loss/injury.