Levels Of Oxidative Stress Markers Research Articles

Pharmacological Activities and Molecular Mechanisms of Sinapic Acid in Neurological Disorders.

Sinapic acid (SA) is a phenylpropanoid derivative found in various natural sources that exhibits remarkable versatile properties, including antioxidant, anti-inflammatory, and metal-chelating capabilities, establishing itself as a promising candidate for the prevention and treatment of conditions affecting the central nervous system, such as Alzheimer's disease (AD), Parkinson's disease (PD), ischemic stroke, and other neurological disorders. These effects also include neuroprotection in epilepsy models, as evidenced by a reduction in seizure-like behavior, cell death in specific hippocampal regions, and lowered neuroinflammatory markers. In AD, SA treatment enhances memory, reverses cognitive deficits, and attenuates astrocyte activation. SA also has positive effects on cognition by improving memory and lowering oxidative stress. This is shown by lower levels of oxidative stress markers, higher levels of antioxidant enzyme activity, and better memory retention. Additionally, in ischemic stroke and PD models, SA provides microglial protection and exerts anti-inflammatory effects. This review emphasizes SA's multifaceted neuroprotective properties and its potential role in the prevention and treatment of various brain disorders. Despite the need for further research to fully understand its mechanisms of action and clinical applicability, SA stands out as a valuable bioactive compound in the ongoing quest to combat neurodegenerative diseases and enhance the quality of life for affected individuals.

The association of umbilical cord blood oxidative stress with maternal iron deficiency anemia: A tertiary center experience.

To compare the levels of oxidative stress markers in the umbilical cord blood between pregnant women diagnosed with iron deficiency anemia (IDA) and low-risk controls. The sample consisted of 131 patients, including 55 pregnant women with IDA and 76 controls with similar demographic characteristics. Participants were selected from patients delivered at ≥37 weeks. We compared the two groups in terms of the native thiol, total thiol, disulfide, and ischemia-modified albumin (IMA) levels measured in pregnant women's umbilical cord venous blood. The native thiol and total thiol values were statistically significantly lower in the anemia group, and the disulfide and IMA values were statistically significantly higher in the IDA group (P < 0.001). Perinatal outcomes were similar between the groups. In the present study, pregnant women with IDA had lower native and total thiol values and higher disulfide and IMA values in umbilical cord blood. Iron deficiency anemia in pregnancy may be a potential cause of increased oxidative stress.

Measurement of Serum Ceruloplasmin, Lipid Hydroperoxide Level and Prolidase Activity in Children with Primary Headache

Introduction Primary headache is a significant health problem in children as it remarkably negatively affects the child and his/her family. Migraine and tension-type headaches constitute the majority of primary headaches in childhood. Studies regarding adult migraine patients suggest that oxidative stress has a significant role in the pathogenesis. This study aimed to investigate the relationship between primary headache in chidhood and the levels of oxidative stress markers. Materials and methods Pediatric patients diagnosed with primary headache and healthy controls in the pediatric age range were recruited. Data regarding age, gender, height, weight, and body mass index (BMI) were recorded. The levels of ceruloplasmin, lipid hydroperoxide, and prolidase activity were measured in plasma using the ELISA method. Statistical analyses were conducted using the SPSS 11.5 statistical program. A p-value of less than 0.05 was considered significant. Results The study included 76 patients with primary headache and 61 healthy controls. The mean ages of the patients and healthy controls were 14.4±3.2 and 13.6±2.9 years. The patient and control groups were similar in terms of gender distribution (p=0.948), age (p=0.079), and BMI (p=0.196). Migraine accounted for 35.5% (n=27), while tension-type headache accounted for 64.5% (n=49) of the patients. Serum ceruloplasmin (p=0.033), lipid hydroperoxide (p&lt;0.001), and prolidase (p=0.010) levels were higher in patients compared to the control group. Lipid hydroperoxide (p=0.021) and prolidase (p=0.013) levels were higher in migraine patients than in tension-type headache patients, while ceruloplasmin levels were similar between patients with different headache types (p=0.581). Conclusion In this study, oxidative stress markers were shown to be increased in pediatric patients with primary headache. These findings support the hypothesis that patients with primary headaches are exposed to oxidative stress. Future studies may elucidate the role of oxidative stress in the etiopathogenesis of childhood migraine and other headache types.

Brozopine ameliorates cognitive impairment via upregulating Nrf2, antioxidation and anti-inflammation activities.

Oxidative stress and inflammation are crucial factors contributing to the occurrence and development of vascular dementia (VD). In a previous study, we demonstrated that brozopine (BZP) is an anti-ischemic drug. In this study, a model of VD in rats with modified permanent bilateral common carotid artery occlusion (2-VO) was established in vivo, a model of cellular excitotoxicity/oxidative stress was established via L-glutamate-induced PC12 cell injury, a model of neuroinflammation was established in LPS-induced BV2 cells in vitro, and the ameliorative effect of BZP on cognitive impairment was assessed. BZP treatment improved memory deficit in VD rats through inhibiting Ca2+overload and the levels of oxidative stress, ferroptosis, and inflammatory markers (IL-1β, IL-6, and COX-2) in different brain regions. Additionally, we found that the levels of inflammatory markers in the plasma were also reduced in the VD rats. BZP was further found to have antioxidative stress, antiferroptosis (ferroptosis markers: GPX4, P53, and ACSL4), and antineuroinflammatory effects in PC12 and BV2 cells. Its mechanisms of action were found to be related to the activation of the Nrf2/TLR4/NF-κB pathway; the protective effect of BZP was partially inhibited after using Nrf2-specific inhibitors. Thus, BZP has therapeutic properties for the potential mitigation of cognitive impairment.

Alleviative effect of scopolamine‑induced memory deficit via enhancing antioxidant and cholinergic function in rats by pinostrobin from Boesenbergia rotunda (L.).

Pinostrobin, a key bioactive compound found in the medicinal plant Boesenbergia rotunda (L.), has been noted for its beneficial biological properties including antioxidant, anti-inflammation, anti-cancer and anti-amnesia activities. In view of this, the present study purposed to evaluate the neuroprotective potential of pinostrobin in reversing scopolamine-induced cognitive impairment involving oxidative stress and cholinergic function in rats. A total of 30 male Wistar rats were randomly divided into five groups (n=6): Group 1 received vehicle as a control, group 2 received vehicle + scopolamine (3 mg/kg, i.p.), group 3 received pinostrobin (20 mg/kg, p.o.) + scopolamine, group 4 received pinostrobin (40 mg/kg, p.o.) + scopolamine and group 5 received donepezil (5 mg/kg, p.o.) + scopolamine. Treatments were administered orally to the rats for 14 days. During the final 7 days of treatment, a daily injection of scopolamine was administered. Scopolamine impaired learning and memory performance, as measured by the novel object recognition test and the Y-maze test. Additionally, oxidative stress marker levels, acetylcholinesterase (AChE) activity, choline acetyltransferase (ChAT) and glutamate receptor 1 (GluR1) expression were determined. Consequently, the findings demonstrated that the administration of pinostrobin (20 and 40 mg/kg) markedly improved cognitive function as indicated by an increase in recognition index and by spontaneous alternation behaviour. Pinostrobin also modulated the levels of oxidative stress by causing a decrease in malondialdehyde levels accompanied by increases in superoxide dismutase and glutathione activities. Similarly, pinostrobin markedly enhanced cholinergic function by decreasing AChE activity and promoting ChAT immunoreactivity in the hippocampus. Additionally, the reduction in GluR1 expression due to scopolamine was diminished by treatment with pinostrobin. The findings indicated that pinostrobin exhibited a significant restoration of scopolamine-induced memory impairment by regulating oxidative stress and cholinergic system function. Thus, pinostrobin could serve as a potential therapeutic agent for the management of neurodegenerative diseases such as Alzheimer's disease.

Molecular and immunological studies on Theileria equi and its vector in Egypt

Equine piroplasmosis is not fully understood regarding pathogenicity, prophylaxis, host immune response expression, and specific vectors. Accurately identifying the parasite vector is crucial for developing an effective control plan for a particular infection. This study focused on morphologically identifying two Hyalomma species (H. anatolicum and H. marginatum) and one Rhipicephalus annulatus (R. annulatus) at the species level. The identification process was followed by phylogenetic analysis using the neighbor-joining method based on the cytochrome oxidase subunit 1 (COXI) gene as a specific vector for Theileria equi (T. equi) in horses. T. equi was diagnosed morphologically and molecularly from infected blood samples and crushed tick species using conventional PCR. Subsequently, phylogenetic analysis based on the amplification of the 18 S rRNA gene was conducted. The obtained sequence data were evaluated and registered in GenBank under accession numbers OR064161, OR067911, OR187727, and OR068139, representing the three tick species and the isolated T. equi, respectively. The study demonstrated that T. equi infection leads to immune system suppression by significantly increasing the levels of oxidative stress markers (CAT, GPx, MDA, and SOD) (P ≤ 0.0001), with this elevation being directly proportional to parasitemia levels in infected blood cells. Furthermore, a correlation was observed between parasitemia levels and the expression of immune response infection genes (IFN-gamma, TGF-β1, and IL-1β cytokines) in infected horses compared to non-infected equine. Common macroscopic symptoms indicating T. equi infection in horses include intermittent fever, enlarged lymph nodes (LN), and tick infestation.

Neurobehavioral, neurotransmitter and redox modifications in Nauphoeta cinerea under mixed heavy metal (silver and mercury) exposure

Heavy metals are encountered in nature, and are used in several human endeavors, including in dental fillings. It is well known that the safety of metals depends on their chemical form, as well as the dose and route through which biological systems are exposed to them. Here, we used the Nauphoeta cinerea model to examine the mechanism by which salts of the heavy metals used in dental fillings – silver and mercury – exert their neurotoxicity. Nymphs exposed to heavy metals presented with reduced motor and exploratory abilities as they spent more time immobile, especially in the periphery of a novel object, and covered less distance compared with control nymphs. Exposure to AgNO3 and HgCl2 also exacerbated levels of oxidative stress markers (MDA & ROS) and the neurotransmitter regulators – AChE and MAO, while reducing antioxidant activity markers, both in biochemical (thiol & GST) and RT-qPCR (TRX, GST, SOD, Catalase) examinations, in neural tissues of the cockroach. The observed disruptions in neurolocomotor control, synaptic transmission and redox balance explain how heavy metal salts may predispose organisms to neurological disorders.

Glucose-6-Phosphate Dehydrogenase Levels and Oxidative Stress Markers Among Cancer Patients in Jos, Nigeria

Glucose-6-phosphate dehydrogenase (G6PD) is a sensitive cytosolic antioxidant enzyme that could be associated with carcinogenesis. Hence, its plasma levels are a good indicator to monitor cancer-induced cellular stress. This study aimed to determine the correlation between Glucose-6-phosphate dehydrogenase and oxidative stress markers among cancer patients in Jos, Nigeria. This case-control study involved 100 subjects (60 cancer patients and 40 healthy control subjects). Their blood samples were collected to measure the levels of G6PD and oxidative stress markers (malondialdehyde, total plasma peroxide, total antioxidant potential, and oxidative stress indices). Twenty-four (40.0%) of the cancer patients were G6PD deficient. Of this, 13 (54.2%) were females G6PD. Of the G6PD deficient cancer patients, 11(45.8%) were male, conversely, 16 (44.4%) of the cancer subjects who had normal G6PD were males. Of the cancer patients, 26.7%; 13.3%, 11.7 % and 10% had prostate, breast cancer, chronic lymphocytic leukemia (CLL), and hepatocellular carcinoma (HCC), respectively were the most frequent. There was no significant association between G6PD deficiency and cancer (&amp;lt;I&amp;gt;X&amp;lt;sup&amp;gt;2&amp;lt;/sup&amp;gt;&amp;lt;/I&amp;gt;=0.025, &amp;lt;i&amp;gt;p&amp;lt;/i&amp;gt;=0.804). Among G6PD deficiency cancer patients, the oxidative stress markers were significantly (&amp;lt;i&amp;gt;p&amp;lt;&amp;lt;/i&amp;gt;0.05) higher compared to the control group. These findings showed that relatively more of the cancer patients had normal G6PD status even in increased cellular oxidative stress which could be due to host genetic factors. This suggests the need for further experiments on molecular characterization of mechanisms responsible for the findings.

Comparison of the effects of axillary brachial plexus block, inhalation anesthesia, and total intravenous anesthesia on tourniquet-induced ischemia-reperfusion injury in upper extremity surgery.

Post-ischemia reperfusion can lead to oxidative stress and an increase in oxidative markers. Employing preventive strategies and antioxidant agents may help mitigate ischemia-reperfusion injury (IRI). The use of a tourniquet in extremity surgery has been associated with IRI. This study aims to investigate the impact of three different approaches- brachial plexus block, total intravenous anesthesia (TIVA), and inhalation anesthesia-on IRI during upper extremity surgery using a tourniquet. Patients aged 18 to 45 with American Society of Anesthesiologists (ASA) I-II scores were randomly assigned to one of three groups: Group A received an axillary block with bupivacaine; Group I underwent inhalation anesthesia with sevoflurane; and Group T received TIVA with propofol and remifentanil infusion. Blood samples were collected to measure glucose, lactate, total anti-oxidant status (TAS), total oxidant status (TOS), and ischemia-modified albumin (IMA) levels at various time points: before anesthesia (t1), 1 minute before tourniquet release (t2), 20 minutes after tourniquet release (t3), and 4 hours after tourniquet release (t4). In Group I, lactate levels at t3, and glucose levels at t2 and t3, were higher compared to the other groups. Group A exhibited lower IMA levels at t2, t3, and t4 than the other groups. Additionally, Group I had lower IMA levels at t2, t3, and t4 compared to Group T. TAS levels were higher in Group I at t2, t3, and t4 compared to the other groups. TOS levels at t2 and t3 were lower in Group A than in Group I. Axillary anesthesia results in a sympathetic block, promoting better perfusion of the upper extremity. This study demonstrated lower levels of oxidative stress markers with axillary plexus block. Therefore, these results suggest that the axillary block has the potential to mitigate IRI.

MK2 inhibitor PF-3644022 shows protective effect in mouse microglial N9 cell line induced with cigarette smoke extract.

Neuroinflammation is suggested as one of the potential links between CS-induced neuronal dysfunction. Cigarette smoke (CS) is one of the significant contributors of neuroinflammation, consequently leading to cognitive impairment and neurodegeneration. Microglia are the key resident macrophage cells in the brain with cell surface TLR4 receptor for responding to various stress signals. The CS constituents promote inflammation and oxidative stress in microglia leading to cytotoxicity through the TLR4-MK2 axis. However, the role of MK2 kinase in CS-induced microglial inflammation is not yet clearly understood. Therefore, we have used an MK2 inhibitor, PF-3644022 to study modulation of CS-extract induced oxidative and inflammatory signaling in a mouse microglial cell line, Furthermore, we also evaluated the enzymatic activity of acetylcholinesterase (AChE) on a direct exposure of enzyme with CS. CS exposure led to microglial cytotoxicity and enhanced the level of oxidative stress and proinflammatory cytokine release by microglial cells. The microglial cells pretreated with MK2 inhibitor, PF-3644022 significantly reduced the levels of oxidative stress markers, proinflammatory markers, and improved the level of antioxidant proteins in these cells. In addition, direct exposure of CS showed reduction in the enzymatic activity of AChE.

Interference with Histone Deacetylase 4 Regulates c-Jun N-terminal Kinase/Activating Protein-1 Signaling to Ameliorate Sepsis-induced Alveolar Epithelial Cell Injury.

Sepsis is a syndrome of systemic inflammatory response resulting from infection, which can lead to severe lung injury. Histone deacetylase 4 (HDAC4) is a key protein known to regulate a wide range of cellular processes. This study was designed to investigate the role of HDAC4 in lipopolysaccharide (LPS)-induced alveolar epithelial cell injury as well as to disclose its potential molecular mechanisms. The alveolar epithelial cell injury model was established by inducing A549 cells with LPS. A549 cell viability was detected by cell counting kit-8 assay and the transfection efficiency of small interfering RNA targeting HDAC4 was appraised utilizing Western blot. The levels of inflammatory cytokines and oxidative stress markers were detected using corresponding assay kits. Dichloro-dihydro-fluorescein diacetate assay was used for the measurement of reactive oxygen species (ROS) content. Flow cytometry, 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-benzimidazolyl-carbocyanine iodide-1 staining, adenosine triphosphate (ATP) assay kits, and MitoSOX Red assay kits were employed to estimate cell apoptosis, mitochondrial membrane potential, ATP level, and mitochondrial ROS level, respectively. The oxygen consumption rate of A549 cells was evaluated with XF96 extracellular flux analyzer. Western blot was applied for the evaluation of HDAC4, apoptosis- and c-Jun N-terminal kinase (JNK)/activating protein-1 (AP-1) signaling pathway-related proteins. HDAC4 expression was found to be increased in LPS-induced A549 cells and HDAC4 silence inhibited inflammatory damage, repressed oxidative stress, alleviated cell apoptosis, improved mitochondrial function, and blocked JNK/AP-1 signaling in A549 cells stimulated by LPS, which were all reversed by JNK activator anisomycin. Collectively, the interference with HDAC4 could ameliorate LPS-induced alveolar epithelial cell injury, and such protective effect may be potentially mediated through the JNK/AP-1 signaling pathway.

Quercetin Ameliorates Zinc Oxide Nanoparticles-induced Impaired Testicular Functions by Regulating Inflammation, Oxidative, and Hormonal Status

Objective: Zinc oxide nanoparticles (ZnO NPs) have various applications, but concerns about their potential adverse effects on human health, particularly the male reproductive system, have led to toxicity. This study investigates the effects of quercetin, a natural compound with anti-oxidative and anti-inflammatory properties, on ZnO NP-induced testicular toxicity in male Swiss mice. Method: In this study, 25 male mice were randomly allocated into 5 groups, each consisting of 5 mice (n=5). The groups were labelled as Control, Corn Oil, Quercetin, ZnO NPs, and ZnO NPs + Quercetin. The dosages administered were 100mg/kg for ZnO NPs and 20mg/kg for quercetin, relative to the weight of the animals. The treatments were conducted for 7 days following a two-week acclimatization period. Results: Zinc oxide nanoparticles (ZnO NPs) were found to increase testicular TNF-α, indicating inflammation at the testes which may have resulted in a significant decrease in testosterone. Malondialdehyde (MDA), an oxidative stress marker was also found to be increased at the level of the testes, in the ZnO NPs group when compared to the control group. Treatment with quercetin, however, was able to reduce the levels of inflammatory and oxidative stress markers at the testes, and restore testosterone to control levels, demonstrating its potential ameliorative effects on testicular toxicity via anti-inflammatory and anti-oxidative properties. Conclusion: The findings from this study indicated that Quercetin is a potential therapeutic agent against inflammation and oxidative stress in ZnO NPs-induced testicular toxicity.

Acupoint catgut embedding attenuates oxidative stress and cognitive impairment in chronic cerebral ischemia by inhibiting the Ang II/AT1R/NOX axis.

Chronic cerebral ischemia (CCI) is a common neurological disorder, characterized by progressive cognitive impairment. Acupoint catgut embedding (ACE) represents a modern acupuncture form that has shown neuroprotective effects; nevertheless, its effects on CCI and the mechanisms remain largely unknown. Here, we aimed to explore the therapeutic action of ACE in CCI-induced cognitive impairment and its mechanisms. The cognitive function of CCI rats was determined using Morris water maze test, and histopathological changes in the brain were assessed through hematoxylin-eosin (HE) staining. To further explore the molecular mechanisms, the expression levels of oxidative stress markers and the Ang II/AT1R/NOX axis-associated molecules in the hippocampus were evaluated using enzyme-linked immunosorbent assay (ELISA), western blotting, and immunohistochemistry. Here, we observed that ACE treatment alleviated cognitive dysfunction and histopathological injury in CCI rats. Intriguingly, candesartan (an AT1R blocker) enhanced the beneficial effects of ACE on ameliorating cognitive impairment in CCI rats. Mechanistically, ACE treatment blocked the Ang II/AT1R/NOX pathway and subsequently suppressed oxidative stress, thus mitigating cognitive impairment in CCI. Our findings first reveal that ACE treatment could suppress cognitive impairment in CCI, which might be partly due to the suppression of Ang II/AT1R/NOX axis.

Thrombomodulin Improves Cognitive Deficits in Heat-Stressed Mice.

Thrombomodulin (TM) exerts anticoagulant and anti-inflammatory effects to improve the survival of patients with septic shock. Heat stroke resembles septic shock in many aspects. We tested whether TM would improve cognitive deficits and related causative factors in heat-stressed (HS) mice. Adult male mice were exposed to HS (33°C for 2 hours daily for 7 consecutive days) to induce cognitive deficits. Recombinant human soluble TM (1mg/kg, i.p.) was administered immediately after the first HS trial and then once daily for 7 consecutive days. We performed the Y-maze, novel objective recognition, and passive avoidance tests to evaluate cognitive function. Plasma levels of lipopolysaccharide (LPS), high-mobility group box 1 (HMGB1), coagulation parameters, and both plasma and tissue levels of inflammatory and oxidative stress markers were biochemically measured. The duodenum and hippocampus sections were immunohistochemically stained. The intestinal and blood-brain barrier permeability were determined. Compared with controls, HS mice treated with TM had lesser extents of cognitive deficits, exacerbated stress reactions, gut barrier disruption, endotoxemia, blood-brain barrier disruption, and inflammatory, oxidative, and coagulatory injury to heart, duodenum, and hippocampal tissues, and increased plasma HMGB1. In addition to reducing cognitive deficits, TM therapy alleviated all the abovementioned complications in heat-stressed mice. The findings suggest that HS can lead to exacerbated stress reactions, endotoxemia, gut barrier disruption, blood-brain barrier disruption, hippocampal inflammation, coagulopathy, and oxidative stress, which may act as causative factors for cognitive deficits. TM, an anti-inflammatory, antioxidant, and anti-coagulatory agent, inhibited heat stress-induced cognitive deficits in mice.

Study of the neuroprotective properties of metformin in rats with type 2 diabetes mellitus and brain injury induced by intracerebral hemorrhage

The aim of this study was to study the effect of metformin (Met) on the formation of the conditional passive avoidance skills, markers of neurogenesis and oxidative stress in the brain of rats with acute intracerebral hemorrhage (ICH) in the setting of streptozotocin-nicotinamide-induced diabetes. Type 2 diabetes mellitus (T2DM) was induced in rats via the intraperitoneal injection of streptozotocin (STZ) and nicotinamide (NA), ICH – by microinjection of bacterial collagenase into the striatum. Rats were randomly divided into four groups: 1 – intact animals (n=8), 2 – T2DM (n=9); 3 – T2DM+ICH (n=7); 4 – T2DM+ICH+Met (n=7). The passive avoidance test was used to evaluate behavioural activity. Advanced oxidation protein products (AOPP) and lactate were measured by spectrophotometry, advanced glycation end products (AGEs) by quantitative fluorescence, level of 8-hydroxy-2-deoxyguanosine (8-OHdG) was assessed by enzyme-linked immunosorbent assay (ELISA). Histopathological examination was performed using general histological staining techniques and immunohistochemical methods for assessment of expression of endothelial NO-synthase (eNOS), Growth Associated Protein 43 (GAP43), Hypoxia-inducible factor 1-alpha (HIF-1α), neural cadherine (N-cadherine) and vascular endothelial cadherine (VE-cadherine). In this study, metformin had nootropic (anti-amnestic) activity and decreased oxidative stress markers (AGEs, AOPPs and 8-OHdG) levels by 29.1% (p&lt;0.001), 24.9% (p&lt;0.015) and 29.3% (p&lt;0.05) respectively, which indicates its positive impact on the course of free radical oxidation reactions intensified by both diabetes and intracerebral hemorrhage. The study provides additional information on neuroprotective properties of metformin and the emphasizes possibility of using metformin in diabetic patients at risk of hemorrhagic stroke. Considering the increase in VE-cadherin expression by the drug, it is possible to predict its positive effect on the function of blood-brain barrier. This study may serve as a reference for the feasibility of studying the clinical efficacy of metformin under these conditions.

The Correlation of Oxidative Stress Markers and Biochemical Cardiac Enzymes in Iraqi Patients Diagnosed with Acute Myocardial Infraction

A myocardial infarction (MI), is the irreversible death (necrosis) of heart muscle commonly known as a heart attack. Acute myocardial infarction (AMI) occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. MI is associated with an intelligible imbalance in oxidative stress. After myocardial injury, many cardiac biomarkers become detectable in venous circulation such as cardiac enzymes. The study's main goals were to evaluate the clinical significant change in cardiac enzymes and investigate the positive and negative correlation with some serum oxidative stress markers total oxidative state (TOS), free amine and total antioxidant capacity (TAC) in patient and control groups. This study contained 120 subjects who were divided evenly into patients and control groups for the period between July and September 2022. The serum levels of oxidative stress markers were measured manually using spectrophotometer (model, Cecil, CE10N / England). The activity of cardiac enzymes and lipid profile were also determined by using Spectrophotometric kits supplied from Biolabo, France. The study showed that TOS had a significantly positive correlation with CK (r = 0.269*, p= 0.038) and ALT (r = 0.259*, p= 0.046), also for free amine, TnI (r = 0.287*, p= 0.026). Moreover, cardiac Troponin had highly positive correlation with oxidants and enzymes of the cardiomyocyte.

Mitochondrial biogenesis disorder and oxidative damage promote refractory apical periodontitis in rat and human.

To elucidate whether mitochondrial biogenesis disorder and damage from oxidative stress promote refractory apical periodontitis (RAP) in rat and human. Twenty Enterococcus faecalis-induced RAPs were established in the maxillary first molars of male Wistar rats. Concurrently, 12 periapical lesion specimens from patients presenting with RAP were obtained by apicoectomy. Radiographic examination and histologic analysis were conducted to evaluate periapical bone tissue destruction and morphological changes. The expression of key regulators of mitochondrial biogenesis, PGC-1α and Nrf2, were detected by immunohistochemistry and double immunofluorescence staining, Western blot and real-time PCR were also assayed. Mitochondrial ROS (mtROS) was identified by MitoSOX staining. Mitochondrial function was detected by the quantification of ATP production, mitochondrial DNA (mtDNA) copy number and activities of mitochondrial respiratory chain complexes. Furthermore, mitochondrial oxidative stress was evaluated by the determination of 3-nitrotyrosine (3-NT), 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-deoxyguanosine (8-OHdG) expression levels, as well as malondialdehyde (MDA) expression and antioxidant capacity. Student's t-test was performed to determine significance between the groups; p < .05 was considered significant. In the maxilla, significantly more bone resorption, greater number of periapical apoptotic cells and Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells were observed in the RAP group compared with the control group (p < .01). PGC-1α and Nrf2 were significantly reduced in rat and human RAP lesions compared to the control group (p < .01) at both the mRNA and protein levels. Double immunofluorescence analysis of PGC-1α or Nrf2 with TOMM20 also indicated that mitochondrial biogenesis was impaired in RAP group (p < .01). Additionally, mitochondrial dysfunction was observed in RAP group, as reflected by increased mtROS, decreased ATP production, reduced mtDNA copy number and complexes of the mitochondrial respiratory chain. Finally, the expression levels of mitochondrial oxidative stress markers, 3-NT, 4-HNE and 8-OHdG, were significantly increased in the RAP group (p < .01). Consistent with this, systemic oxidative damage was also present in the progression of RAP, including increased MDA expression and decreased antioxidant activity (p < .01). Mitochondrial biogenesis disorder and damage from oxidative stress contribute to the development of RAP.

MiR-141-3p attenuates inflammation and oxidative stress-induced pulmonary fibrosis in ARDS via the Keap1/Nrf2/ARE signaling pathway.

The present research aimed to investigate the effects and mechanisms of microRNA (miR)-141-3p on pulmonary fibrosis of acute respiratory distress syndrome (ARDS). A rat ARDS model was established by the intratracheal drip of 10mg/kg lipopolysaccharide (LPS). miR-141-3p and Kelch-like ECH-associated protein 1 (Keap1) expression was detected using RT-qPCR assay. Inflammatory factors in bronchoalveolar lavage fluid (BALF) and lung tissues were measured with enzyme-linked immunosorbent assay (ELISA). Lung fibrosis was evaluated using Masson's trichrome staining and hydroxyproline assay kits. Tissue oxidative stress marker levels were assessed by a commercial kit. Protein variations in the EMT pathway and Keap1/nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway were investigated by Western blot analysis. Targeting relationship verified by dual-luciferase reporter assay. The expression of miR-141-3p was significantly upregulatedin LPS-induced ARDS rats, while Keap1 was downregulated. Overexpression of miR-141-3p decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, superoxide dismutase (SOD), and glutathione (GSH) while elevating malondialdehyde (MDA) expressionin LPS-induced ARDS rats. Elevation of miR-141-3p reduced fibrosis scores, enhanced E-cadherin protein expression, and decreased vimentin and α-SMA protein expressionin LPS-induced ARDS rats. This elevation of miR-141-3p also upregulated Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxido-reductase-1 (NQO1) proteinslevels. Moreover, Keap1 overexpression reversed the inhibitory effects of miR-141-3p on LPS-triggered inflammation, oxidative stress, and fibrosis. miR-141-3p may attenuate inflammation and oxidative stress-induced pulmonary fibrosis in ARDS via the Keap1/Nrf2/ARE signaling pathway. Our study provides new ideas for the treatment of ARDS.

Betulin protects against isoproterenol-induced myocardial injury by inhibiting NF-κB signaling and attenuating cardiac inflammation and oxidative stress in rats

Objective: To investigate the cardioprotective potential of betulin in isoproterenol (ISO)-induced myocardial injury in rats. Methods: Wistar rats were divided into five groups (n=10): normal, ISO, nebivolol 5 mg/kg, and betulin (20 &amp; 40 mg/kg). Nebivolol and betulin were administered orally for 29 days. ISO (85 mg/kg) was administered subcutaneously on day 27 and day 28 to induce myocardial injury. On day 29, blood was collected for determination of cardiac markers, and hemodynamic parameters were investigated. The levels of oxidative stress markers and the gene expressions of apoptotic markers and inflammatory mediators were evaluated. Moreover, 2,3,5-triphenyltetrazolium chloride staining and histopathological analysis were also performed. Results: Betulin reduced the size of myocardial infarction, decreased elevated levels of cardiac enzymes, and maintained hemodynamic functions. It also inhibited ISO-induced upregulation of Bax, caspase-3, NF-κB, and 1L-6, enhanced endogenous antioxidant enzymes, and reduced lipid peroxidation. Additionally, pretreatment with betulin alleviated myocardial ischemic damage, as reflected by reduced myonecrosis, edema, and inflammatory changes. Conclusions: Betulin exhibits strong cardioprotective activity against ISO-induced myocardial injury by anti-inflammatory, anti-apoptotic, and antioxidant activities.

STAT3-induced upregulation of lncRNA TTN-AS1 aggravates podocyte injury in diabetic nephropathy by promoting oxidative stress.

Diabetic nephropathy (DN) is the most common microvascular complication of diabetes mellitus (DM), being the second cause of end-stage renal disease globally. Podocyte injury is closely associated with DN developmen. Our study aimed to investigate the role of long non-coding RNA (lncRNA) TTN-AS1 in DN-associated podocyte injury. The mouse podocyte cell line (MPC5) and human primary podocytes were stimulated by high glucose (HG; 30nM glucose) to establish the cellular model of DN. Before HG stimulation, both podocytes were transfected with sh-TTN-AS1#1/2 or pcDNA3.1/STAT3 to evaluate the influence of TTN-AS1 knockdown or STAT3 overexpression on HG-induced podocyte injury. TTN-AS1 and STAT3 expression in both podocytes was examined by RT-qPCR. Cell viability and death were assessed by CCK-8 and LDH release assay. ELISA was adopted for testing IL-6 and TNF-α contents in cell supernatants. The levels of oxidative stress markers (ROS, MDA, SOD, and GSH) in cell supernatants were determined by commercial kits. Western blotting was used for measuring the expression of fibrosis markers (fibronectin and α-SMA and podocyte function markers (podocin and nephrin) in podocytes. HG stimulation led to decreased cell viability, increased cell death, fibrosis, inflammation, cell dysfunction and oxidative stress in podocytes. However, knockdown of TTN-AS1 ameliorated HG-induced podocyte injury. Mechanically, the transcription factor STAT3 interacted with TTN-AS1 promoter and upregulated TTN-AS1 expression. STAT3 overexpression offset the protective effect of TTN-AS1 silencing on HG-induced podocyte damage. Overall, STAT3-mediated upregulation of lncRNA TTN-AS1 could exacerbate podocyte injury in DN through suppressing inflammation and oxidative stress.