The Influence of Removable Complete Denture on Pro-Oxidant Antioxidant Balance and Redox-Sensitive Inflammation Biomarker NF-ĸB in the Oral Cavity: An Interventional Follow-Up Study.

OBJECTIVES: Oxidative stress, an imbalance between the body's natural antioxidant defenses and the production of reactive oxygen species (ROS), can result in serious oral diseases, including oral cancer, periodontal diseases, and oral lichen planus, through the activation of the redox-sensitive transcription factors and inflammation. The purpose of this study was to assess the potential effects of a removable complete denture on the levels of oxidative stress markers, such as lipid peroxidation (MDA), advanced oxidation protein products (AOPP), and catalase, and the quantitative expression of the redox-sensitive transcription factor NF-κB p65 subunit. MATERIALS AND METHODS: This interventional follow-up study enrolled 40 participants of both sexes aged 28-78 years, with a median age of 56 years, where unstimulated saliva was collected before denture placement, immediately after the denture placement, and 24 h, 7 days, and 30 days after the denture placement. The most prominent ROS overproduction was reported on the seventh day (p < 0.05), followed by a significant fall in antioxidative defense. RESULTS: The NF-κB p65 subunit, whose expression pattern was highest in the same time period on the seventh day, serves as a signaling molecule for redox imbalance due to ROS production. Over the next 30 days, its levels remained moderately increased compared to the basal value, which may influence pro-inflammatory pathways and the integrity of oral tissue components. These alterations may be induced by the dentures, which can produce high pressures on the supporting tissues or by the synthetic materials used for producing the dentures. CONCLUSION: Our research may help to clarify the potential pathways by which oxidative stress and redox-sensitive inflammatory mediators, as well as mechanical and chemical irritants, may serve as risk factors for premalignant lesions in the mouth. Further research on this topic is required to understand the molecular mechanisms behind the relationship between inflammation and oral premalignant lesions caused by mechanical and chemical irritation.

Vitamin D in Type 2 Diabetes and Its Correlation With Heat Shock Protein 70, Ferric Reducing Ability of Plasma, Advanced Oxidation Protein Products and Advanced Glycation End Products.

AIM: To investigate the association between vitamin D3 level and oxidative stress biomarkers such as Heat Shock Protein 70 (HSP70), ferric reducing ability of plasma (FRAP), advanced oxidation protein products (AOPP) and advanced glycation end products (AGEs) in patients with Type 2 diabetes. METHOD: In this cross-sectional study, 54 patients including 32 females and 22 males with a mean age of 54.92 ± 11.37 years with T2D attending the diabetes clinic from 2021 to 2022 were included. According to the average level of vitamin D in this population (14.91), they were divided into two groups with vitamin D ≤15 ng/mL and vitamin D >15 ng/mL. Multivariate regression analysis was conducted to evaluate the relationship between vitamin D and AOPP, HSP and FRAP parameters. The correlation between vitamin D and other variables was evaluated via the Pearson correlation test. RESULT: Vitamin D level had a positive relation with FRAP (ß = 0.32, p = 0.017) and HSP (ß = 0.39, p = 0.003), but had a negative relation with AOPP (ß = -0.30, p = 0.02). The level of 2hPP also had a negative relation with the level of vitamin D (ß = -0.33, p = 0.03). There was not any relationship between the level of vitamin D and AGEs or other variables. After adjusting for multiple confounders for the multivariate regression model, HSP remained significant. CONCLUSION: This research indicates the relationship between vitamin D levels and oxidative stress biomarkers in patients with Type 2 diabetes.

Quantification of oxidative stress markers in the blood sera following subacute administration of different oximes in rats.

Oxidative stress status, as a disruption of redox homeostasis, in the blood sera of Wistar rats caused by repeated application of selected acetylcholinesterase reactivators - asoxime, obidoxime, K027, K048, K074, and K075 were evaluated. Throughout this study, each oxime in a dose of 0.1 of LD50/kg im was given 2x/week for 4 weeks. Then, seven days after the last oximes' application, markers of lipid peroxidation (malondialdehyde, MDA), and protein oxidation (advanced oxidation protein products, AOPP), as well as the activity of antioxidant enzymes (catalase, CAT, superoxide dismutase, SOD, reduced glutathione, GSH, and oxidized glutathione, GSSG), were determined. Oxidative stress parameters, MDA and AOPP were significantly highest in the K048-, K074- and K075-treated groups (p < 0.001). The activity of CAT was significantly elevated in the obidoxime-treated group (p < 0.05), while treatment with K027, K048, and K074 induced high elevation in SOD levels (p < 0.01, p < 0.001). Interestingly, the activity of GSH in each oxime-treated group was significantly elevated. Unlike, treatment with obidoxime caused elevation in GSSG levels (p < 0.01). As a continuation of our previously published data, these results assure that applied oximes following subacute treatment ameliorated the oxidative status and further adverse systemic toxic effects in rats.

CYP2E1 mediated advanced oxidation protein products exacerbate acetaminophen induced drug-derived liver injury in vitro and in vivo.

Drug-induced liver injury (DILI) is prevalent in the treatment of chronic kidney disease (CKD). Advanced oxidation protein products (AOPPs) are markers of CKD progression and participate in the occurrence and development of liver diseases. However, the mechanisms underlying the regulation of DILI in CKD have not been established. Herein, we demonstrate the involvement of Cytochrome p450 2E1 (CYP2E1) in DILI induced by AOPPs is exacerbated by exposure to acetaminophen (APAP). We used a adenine-induced CKD model, a model of DILI induced by APAP, and the AOPPs model was generated by intraperitoneal injection. The decline in renal function was associated with a significantly increased concentration of Scr, BUN and AOPPs, and renal tissue fibrosis. The ALT, AST, and AOPPs levels and liver tissue necrosis increased significantly in CKD model group compared with the sodium carboxymethyl cellulose (CMCNa) group. In the AOPPs model, compared to the PBS controls, ALT, AST, and AOPP levels, and liver tissue necrosis increased significantly. In HepG2 or L0-2 cell lines, cell survival was significantly reduced in the AOPP + APAP treatment and CYP2E1 protein expression was increased. FPS-ZM1 or NAC attenuated the hepatocyte toxicity induced by AOPP + APAP and suppression of CYP2E1 expression. AOPPs exacerbated APAP-induced DILI through CYP2E1 signaling pathways. Protein uremic toxins, such as AOPPs, can modify drug toxicity in patients with CKD. This study provides new a rationale to reduce the generation of DILIs in clinical treatment in patients with CKD. AOPPs targeting may present a novel approach to reduce the occurrence of DILI.

Characterization of two novel hydrolases from Sphingopyxis sp. DBS4 for enantioselective degradation of chiral herbicide diclofop-methyl.

Diclofop-methyl, an aryloxyphenoxypropionate (AOPP) herbicide, is a chiral compound with two enantiomers. Microbial detoxification and degradation of various enantiomers is garnering immense research attention. However, enantioselective catabolism of diclofop-methyl has been rarely explored, especially at the molecular level. This study cloned two novel hydrolase genes (dcmA and dcmH) in Sphingopyxis sp. DBS4, and characterized them for diclofop-methyl degradation. DcmA, a member of the amidase superfamily, exhibits 26.1-45.9% identity with functional amidases. Conversely, DcmH corresponded to the DUF3089 domain-containing protein family (a family with unknown function), sharing no significant similarity with other biochemically characterized proteins. DcmA exhibited a broad spectrum of substrates, with preferential hydrolyzation of (R)-(+)-diclofop-methyl, (R)-(+)-quizalofop-ethyl, and (R)-(+)-haloxyfop-methyl. DcmH also preferred (R)-(+)-quizalofop-ethyl and (R)-(+)-haloxyfop-methyl degradation while displaying no apparent enantioselective activity towards diclofop-methyl. Using site-directed mutagenesis and molecular docking, it was determined that Ser175 was the fundamental residue influencing DcmA's activity against the two enantiomers of diclofop-methyl. For the degradation of AOPP herbicides, DcmA is an enantioselective amidase that has never been reported in research. This study provided novel hydrolyzing enzyme resources for the remediation of diclofop-methyl in the environment and deepened the understanding of enantioselective degradation of chiral AOPP herbicides mediated by microbes.

Increased levels of advanced oxidation protein products (AOPPs) were associated with nociceptive behavior and clinical scores in an experimental progressive autoimmune encephalomyelitis model (PMS-EAE).

Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system (CNS) generating neuropathic pain and anxiety. Primary progressive MS (PPMS) is the most disabling clinical form, and the patients present an intense neurodegenerative process. In this context, the advanced oxidation protein products (AOPPs) are oxidized compounds and their accumulation in plasma has been related to clinical disability in MS patients. However, the involvement of AOPPs in neuropathic pain- and anxiety-like symptoms was not previously evaluated. To assess this, female mice C57BL/6J were used to induce progressive experimental autoimmune encephalomyelitis (PMS-EAE). Clinical score, weight, strength of plantar pressure, rotarod test, mechanical allodynia, and cold hypersensitivity were evaluated before induction (baseline) and on days 7th, 10th, and 14th post-immunization. We assessed nest building, open field, and elevated plus-maze tests 13 days post-immunization. Animals were killed at 14 days post-immunization; then, AOPPs levels, NADPH oxidase, and myeloperoxidase (MPO) activity were measured in the prefrontal cortex, hippocampus, and spinal cord samples. The clinical score increased 14th post-immunization without changes in weight and mobility. Reduced paw strength, mechanical allodynia, and cold allodynia increased in the PMS-EAE animals. PMS-EAE mice showed spontaneous nociception and anxiety-like behavior. AOPPs concentration, NADPH oxidase, and MPO activity increase in CNS structures. Multivariate analyses indicated that the rise of AOPPs levels, NADPH oxidase, and MPO activity influenced the clinical score and cold allodynia. Thus, we indicated the association between non-stimuli painful perception, anxiety-like, and CNS oxidative damage in the PMS-EAE model.

Incremental values of AOPP, IL-6, and GDF15 for identifying arteriosclerosis in patients with obstructive sleep apnea.

BACKGROUND: The objective of this study was to determine the independent and incremental values of advanced oxidative protein product (AOPP), interleukin 6 (IL-6), and growth differentiation factor 15 (GDF15) in identifying arteriosclerosis in patients with obstructive sleep apnea (OSA). METHODS: A total of 104 individuals diagnosed with OSA by polysomnography were recruited in our study. Arteriosclerosis was defined by measuring the ultrafast pulse wave velocity of the carotid artery. Peripheral venous blood samples were collected to analyze the levels of AOPP, IL-6, and GDF15 utilizing commercially available enzyme-linked immunosorbent assays. RESULTS: Compared to OSA patients without arteriosclerosis, those with arteriosclerosis exhibited significantly higher levels of AOPP, IL-6, and GDF15. GDF15 remained significantly associated with arteriosclerosis even after accounting for clinical factors such as age, gender, body mass index, systolic blood pressure, fasting blood glucose, smoking, and the apnea-hypoxia index (AHI). GDF15 demonstrated the largest area under the curve (AUC) for identifying arteriosclerosis in OSA patients (AUC, 0.85 [0.77-0.94]). The logistic regression model, combining clinical factors and AHI, was enhanced by the inclusion of AOPP and IL-6 (Chi-square = 25.06), and even further improved when GDF15 was added (Chi-square = 50.74). The integrated discrimination index increased by 0.06 to 0.16 when GDF15 was added to the models including clinical factors, AOPP, and IL-6. CONCLUSIONS: This study verified the independent and incremental value of GDF15 in identifying arteriosclerosis in OSA patients, surpassing clinical risk factors and other serum biomarkers such as AOPP and IL-6.

Advanced oxidation protein products attenuate the autophagy-lysosome pathway in ovarian granulosa cells by modulating the ROS-dependent mTOR-TFEB pathway.

Oxidative stress dysfunction has recently been found to be involved in the pathogenesis of premature ovarian insufficiency (POI). Previously, we found that advanced oxidation protein products (AOPPs) in plasma were elevated in women with POI and had an adverse effect on granulosa cell proliferation. However, the mechanism underlying the effects of AOPPs on autophagy-lysosome pathway regulation in granulosa cells remains unclear. In this study, the effect of AOPPs on autophagy and lysosomal biogenesis and the underlying mechanisms were explored by a series of in vitro experiments in KGN and COV434 cell lines. AOPP-treated rat models were employed to determine the negative effect of AOPPs on the autophagy-lysosome systems in vivo. We found that increased AOPP levels activated the mammalian target of rapamycin (mTOR) pathway, and inhibited the autophagic response and lysosomal biogenesis in KGN and COV434 cells. Furthermore, scavenging of reactive oxygen species (ROS) with N-acetylcysteine and blockade of the mTOR pathway with rapamycin or via starvation alleviated the AOPP-induced inhibitory effects on autophagy and lysosomal biogenesis, suggesting that these effects of AOPPs are ROS-mTOR dependent. The protein expression and nuclear translocation of transcription factor EB (TFEB), the key regulator of lysosomal and autophagic function, were also impaired by the AOPP-activated ROS-mTOR pathway. In addition, TFEB overexpression attenuated the AOPP-induced impairment of autophagic flux and lysosomal biogenesis in KGN and COV434 cells. Chronic AOPP stimulation in vivo also impaired autophagy and lysosomal biogenesis in granulosa cells of rat ovaries. The results highlight that AOPPs lead to impairment of autophagic flux and lysosomal biogenesis via ROS-mTOR-TFEB signaling in granulosa cells and participate in the pathogenesis of POI.

Pulsed Hyperoxia Acts on Plasmatic Advanced Glycation End Products and Advanced Oxidation Protein Products and Modulates Mitochondrial Biogenesis in Human Peripheral Blood Mononuclear Cells: A Pilot Study on the "Normobaric Oxygen Paradox".

The "normobaric oxygen paradox" (NOP) describes the response to the return to normoxia after a hyperoxic event, sensed by tissues as an oxygen shortage, up-regulating redox-sensitive transcription factors. We have previously characterized the time trend of oxygen-sensitive transcription factors in human PBMCs, in which the return to normoxia after 30% oxygen is sensed as a hypoxic trigger, characterized by hypoxia-induced factor (HIF-1) activation. On the contrary, 100% and 140% oxygen induce a shift toward an oxidative stress response, characterized by NRF2 and NF-kB activation in the first 24 h post exposure. Herein, we investigate whether this paradigm triggers Advanced Glycation End products (AGEs) and Advanced Oxidation Protein Products (AOPPs) as circulating biomarkers of oxidative stress. Secondly, we studied if mitochondrial biogenesis was involved to link the cellular response to oxidative stress in human PBMCs. Our results show that AGEs and AOPPs increase in a different manner according to oxygen dose. Mitochondrial levels of peroxiredoxin (PRX3) supported the cellular response to oxidative stress and increased at 24 h after mild hyperoxia, MH (30% O2), and high hyperoxia, HH (100% O2), while during very high hyperoxia, VHH (140% O2), the activation was significantly high only at 3 h after oxygen exposure. Mitochondrial biogenesis was activated through nuclear translocation of PGC-1α in all the experimental conditions. However, the consequent release of nuclear Mitochondrial Transcription Factor A (TFAM) was observed only after MH exposure. Conversely, HH and VHH are associated with a progressive loss of NOP response in the ability to induce TFAM expression despite a nuclear translocation of PGC-1α also occurring in these conditions. This study confirms that pulsed high oxygen treatment elicits specific cellular responses, according to its partial pressure and time of administration, and further emphasizes the importance of targeting the use of oxygen to activate specific effects on the whole organism.

Association of Free Radical Product and Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis.

PURPOSE: Polycystic ovary syndrome (PCOS) is an endocrine disorder that primarily affects women of reproductive age. It is recognized as the leading cause of infertility due to anovulation. This research aims to evaluate the diagnostic potential of oxidative stress biomarkers, including advanced oxidation protein products (AOPP), malondialdehyde (MDA), uric acid (UA), and nitric oxide (NO), in identifying PCOS. METHODS: A literature search was conducted in the EMBASE, PubMed, Cochrane Library, and Scopus databases. The standardized mean difference (SMD) and 95% confidence interval (CI) were employed to assess the correlation between free radical product and PCOS. Moreover, the presence of heterogeneity among the studies was assessed utilizing the I2 statistic and Cochran Q test. The methodological rigor of the incorporated studies was assessed through the application of the Newcastle-Ottawa Scale. Furthermore, the presence of publication bias was determined via Begg and Egger tests. RESULTS: This meta-analysis reviewed 38 observational studies, including 17,845 women. The results revealed a significant association between PCOS in women and alterations in free radical levels. The study revealed that the PCOS group had significantly higher levels of AOPP (SMD = 3.193; 95% CI, 2.86 to 3.25), UA (SMD = 0.68; 95% CI, 0.24 to 1.13), and MDA (SMD = 1.16; 95% CI, 0.77 to 1.56) compared to the healthy control group. Furthermore, the analysis found a significantly lower level of NO (SMD = (- 0.59); 95% CI, - 1.15 to - 0.03) in the PCOS patient. CONCLUSION: Screening of specific biomarkers associated with free radical products could provide valuable benefits in the prognosis and diagnosis of PCOS.

Acute poisoning by chlorpyrifos differentially impacts survival and cardiorespiratory function in normotensive and hypertensive rats.

Hypertension is the most important and well-known risk factor for cardiovascular disease (CVD). Recently, acute organophosphate (OP) poisoning has also been pointed as a CVD risk factor. Despite this evidence, no studies have contrasted the acute toxicosis and cardiovascular (CV) effects of OP poisoning under conditions of normotension and hypertension. In this work, adult male normotensive Wistar and Spontaneously Hypertensive rats (SHR) were intraperitoneally injected with saline or chlorpyrifos (CPF), an OP compound, monitored for acute toxicosis signs and 24-h survival. After poisoning, blood pressure, heart rate and ventilation were recorded, the Bezold-Jarisch Reflex (BJR), the Chemoreflex (CR) were chemically activated, as well as the cardiac autonomic tone (AUT) was assessed. Erythrocyte and brainstem acetylcholinesterase and plasmatic butyrylcholinesterase (BuChE) activities were measured as well as lipid peroxidation, advanced oxidation protein products (AOPP), nitrite/nitrate levels, expression of catalase, TNFα and angiotensin-I converting enzyme (ACE-1) within the brainstem. CPF induced a much more pronounced acute toxicosis and 33 % lethality in SHR. CPF poisoning impaired ventilation in SHR, the BJR reflex responses in Wistar rats, and the chemoreflex tachypneic response in both strains. CPF inhibited activity of cholinesterases in both strains, increased AOPP and nitrite/nitrate levels and expression of TNFα and ACE-1 in the brainstem of Wistar rats. Interestingly, SHR presented a reduced intrinsic BuChE activity, an important bioscavenger. Our findings show that, CPF at sublethal doses in normotensive rats lead to lethality and much more pronounced acute toxicity signs in the SHR. We also showed that cardiorespiratory reflexes were differentially impacted after CPF poisoning in both strains and that the cardiorespiratory disfunction seems to be associated with interference in cholinergic transmission, oxidative stress and inflammation. These results points to an increased susceptibility to acute toxicosis in hypertension, which may impose a significant risk to vulnerable populations.

The influence of Klotho protein and prooxidant-antioxidant balance combination on the mortality of HD patients.

PURPOSE: End-stage renal disease patients on chronic hemodialysis (HD) have a shortened life expectancy compared to the general population. The aim of this study was to evaluate a possible link between three new and emerging factors in renal pathophysiology: Klotho protein, telomere length in peripheral blood mononuclear cells (TL) and redox status parameters before HD (bHD) and after HD (aHD), and to test mortality prediction capability of these emerging parameters in a population of HD patients. METHODS: The study included 130 adult patients with average age 66 (54-72), on HD (3 times per week; 4-5 h per session). Klotho level, TL, routine laboratory parameters, dialysis adequacy and redox status parameters: advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), superoxide anion (O2.-), malondialdehyde (MDA), ischemia-modified albumin (IMA), total sulfhydryl group content (SHG), and superoxide dismutase (SOD) were determined. RESULTS: Klotho concentration was significantly higher aHD; 68.2 (22.6-152.9) vs. bHD 64.2 (25.5-119.8) (p = 0.027). The observed increase in TL was not statistically significant. AOPP, PAB, SHG, and SOD activity were significantly increased aHD (p > 0.001). The patients with the highest mortality risk score (MRS) had significantly higher PAB bHD (p = 0.002). Significantly lower O2.- (p < 0.001), SHG content (p = 0.072), and IMA (p = 0.002) aHD were found in patients with the lowest MRS values. Principal component analysis revealed redox balance-Klotho factor as a significant predictor of high mortality risk (p = 0.014). CONCLUSION: Decreased Klotho and TL attrition as well as redox status disturbance could be connected with higher mortality rate in HD patients.

Severity of Mitral Valve Stenosis　- Possible Relationships With Blood Oxidant Markers and Antioxidants.

BACKGROUND: This study examined whether the severity of mitral valve stenosis (MVS) is associated with oxidative stress (OS) markers in the blood, and other hematological and clinicodemographic parameters.Methods and Results: This prospective study was conducted between March and May 2022. Seventy-five patients with newly diagnosed MVS (25 mild, 25 moderate, 25 severe) were included. Mild, moderate, and severe MVS was defined as MV area >2, 1.5-2, and <1.5 cm2, respectively. Various OS markers and laboratory parameters were determined in venous blood samples. For predictive analyses, 2 different analyses were performed to detect patients with severe MVS and those with moderate or severe (moderate/severe) MVS. Age (P=0.388) and sex (P=0.372) distribution were similar in the 3 groups. Multiple logistic regression analysis revealed that a high white blood cell (WBC) count (P=0.023) and high malondialdehyde (P=0.010), superoxide dismutase (SOD; P=0.008), and advanced oxidation protein products (AOPP; P=0.007) levels were independently associated with severe MVS. A low platelet count (P=0.030) and high malondialdehyde (P=0.018), SOD (P=0.008), and AOPP (P=0.001) levels were independently associated with having moderate/severe MVS. The best discriminatory factors for severe MVS were SOD (cut-off >315.5 ng/mL) and glutathione (cut-off >4.7 µmol/L). CONCLUSIONS: MVS severity seems to be affected by oxidant markers (malondialdehyde and AOPP), antioxidant enzymes (SOD), and inflammation-related cells (WBC and platelets). Future studies are needed to examine these relationships in larger populations.

Oxidative Stress Induced by Chemotherapy: Evaluation of Glutathione and Its Related Antioxidant Enzyme Dynamics in Patients with Colorectal Cancer.

One of the mechanisms of chemotherapy is to increase the oxidative stress of cancer cells, leading to their apoptosis. Glutathione (GSH) and its related antioxidant enzymes might be stimulated to cope with increased oxidative stress during chemotherapy. Here, we studied the fluctuation in oxidative stress and GSH-related antioxidant capacities before tumor resection, after tumor resection, and after resection either with or without chemotherapy in patients with colorectal cancer (CRC). This was a cross-sectional and follow-up design. We followed patients before having tumor resection (pre-resection), one month after tumor resection (post-resection), and after the first scheduled chemotherapy (post-chemo). If patients were required to receive chemotherapy after tumor resection, they were assigned to the chemotherapy group. Eligible patients were scheduled to undergo six to twelve cycles of chemotherapy at 2-week intervals and received single, double, or triple chemotherapeutic drugs as required. Those patients who did not require chemotherapy were assigned to the non-chemotherapy group. Indicators of oxidative stress and GSH-related antioxidant capacities were determined at the above three time points. We found in 48 patients of the chemotherapy group and in 43 patients of the non-chemotherapy group different fluctuations in levels of oxidative stress indicators and GSH-related antioxidant capacities starting from pre-resection, post-resection through the post-chemo period. Both groups showed significantly or slightly increased levels of advanced oxidation protein products (AOPP), GSH, and its related enzymes in tumor tissues compared to adjacent normal tissues. Patients in the chemotherapy group had significantly lower plasma levels of GSH and glutathione disulfide (GSSG), but had significantly higher plasma glutathione peroxidase and glutathione reductase activities than patients in the non-chemotherapy group post-chemo. Plasma levels of malondialdehyde and AOPP were positively or negatively associated with GSH and GSSG levels post-chemo after adjustment for age, sex, and histological grading in patients receiving chemotherapy. These significant associations were, however, not seen in patients without chemotherapy. Patients with CRC may require higher GSH demands to cope with a greater oxidative stress resulting from chemotherapy.

Plasma levels of soluble RAGE, AGEs and AOPPs at the early stage of amyotrophic lateral sclerosis: A preliminary study.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disorder with largely unknown pathogenesis and no effective cure. It is believed that several, not mutually exclusive mechanisms contribute to the pathogenesis and progression of this disease, including, among others, elevated oxidative stress, excitotoxicity, increased neuroinflammation, and protein aggregation. Receptor for advanced glycation end products (RAGE) is a part of immunoglobulin superfamily; it is believed to participate in ALS pathogenesis. OBJECTIVES: Our previous studies on ALS demonstrated that RAGE is likely one of the key players in ALS, acting on its own and in tandem with its oxidative stress and pro-inflammatory ligands, such as advanced glycation end products (AGEs) or advanced oxidation protein products (AOPPs). In this study, based on our previous results, we aimed to establish blood levels of soluble RAGE, AGE and AOPP in ALS patients. MATERIAL AND METHODS: Forty-six coded and anonymized surplus plasma samples from ALS patients and non-neurological control were used in the study. The plasma levels of RAGE, AGE and AOPP were measured using enzyme-linked immunosorbent assay (ELISA) commercially available kits. Statistical evaluation of data was performed using one-way non-parametric analysis of variance (ANOVA) with Kruskal-Wallis post hoc test. RESULTS: Our results revealed a decline in soluble RAGE level, concurrent with an increase in the levels of AGEs and AOPPs in blood samples from ALS patients, signifying a loss of neuroprotective form of RAGE and a simultaneous increase in AGE and AOPP production and uptake at the early stage of the disease. CONCLUSIONS: The results obtained from our study indicate that further longitudinal study of RAGE, AGE and AOPP levels would be beneficial, outlining the dynamics between RAGE and its ligand levels as the disease progresses, and making them valuable diagnostic tools and potential therapeutic targets.

CGAs-Rich Conilon Coffee Consumption Improves Cognition and Reduces Oxidative Stress in Elderly with Alzheimer's Disease: A Pilot Study.

BACKGROUND: The consumption of coffee has been associated with beneficial effects when it comes to Alzheimer's disease (AD). However, to the best of our knowledge, there are no studies on Conilon coffee consumption in elderly people with AD. OBJECTIVE: Evaluate the effects of Conilon coffee consumption in elderly with AD. METHODS: The study was carried out with 9 participants who consumed a minimum of 2 cups (200 mL cup) of Conilon coffee per day for 90 days. Cognitive assessment was done before (T0) and after 90 days (T90). Blood analysis was conducted at T0 and T90, as well as the assessment of advanced oxidation protein products (AOPP) and thiobarbituric acid reactive species (TBARS). The levels of chlorogenic acids and caffeine in the coffee beverage were quantified by liquid chromatography. RESULTS: During the treatment, the participants consumed at least 550 mg and 540 mg of CGAs and caffeine, respectively. A significant improvement in cognition between T0 and T90 was observed as per MMSE, CTP, and clock drawing tests. Furthermore, there was a significant reduction in AOPP (37%) and TBARS (60%), indicating a reduction in oxidative stress. The consumption of the coffee did not significantly alter any blood parameter, which confirms the safety of the coffee treatment during the 90 days. CONCLUSIONS: Our study demonstrated for the first time that regular consumption of coffee with high amounts of CGAs and caffeine improves cognitive functions and reduces oxidative stress, without altering blood parameters that indicate possible signs of toxicity in classical target organs.

Serum oxidant-antioxidant status and butyrylcholinesterase activity in dogs with idiopathic epilepsy - A pilot study.

Oxidative stress plays an important role in pathogenesis of idiopathic epilepsy (IE). Although IE is the most common neurological condition, oxidant-antioxidant status in epileptic dogs is still unknown. The aim of this study is to evaluate the serum oxidant-antioxidant status in dogs with newly diagnosed IE. The status in 15 dogs with IE and 15 healthy dogs is estimated through spectrophotometric determination of two oxidant markers: advanced oxidation protein products-albumin index (AOPP) and thiobarbituric acid reactive substances (TBARS); and three antioxidant markers: total thiols (R-SH) level, glutathione (GSH) level, and paraoxonase-1 (PON-1) activity. Also, butyrylcholinesterase (BChE) activity is assessed in both groups of dogs. Higher AOPP is observed in the dogs with newly diagnosed IE, while TBARS level shows no difference when compared to the healthy dogs. In contrast, lower levels of antioxidants (R-SH, GSH, and PON-1) and BChE activity are found in the dogs with IE. No significant differences are observed in the oxidant and antioxidant markers and BChE activity across the investigated IE cases with focal and generalized seizures. Our findings provide evidence that dogs with IE are characterized by an impaired serum oxidant-antioxidant balance and lower BChE activity, which may contribute to a better understanding of IE pathogenesis.

Antioxidant effect of omega-3 fatty acids on exercise-induced oxidative stress in rats.

OBJECTIVE: The aim of this study is to examine the effects of omega-3 supplementation on Catalase (CAT) activity, Malondialdehyde (MDA), advanced oxidation protein products (AOPP) and reduced glutathione (GSH) levels in long-term aerobic exercises in rats. MATERIALS AND METHODS: 28 male Wistar albino rats (8 weeks old, 220-350 g body weight) were included in the study. The rats were given treadmill exercise for 20 minutes at an average speed of 15 cm/s, 5 days a week, for 8 weeks. The experiment was terminated at the end of the eighth week. Blood samples were taken. CAT, MDA, AOPP and GSH analyses were performed. SPSS v. 21 package program was used in the analysis of the data. The distribution of the data was examined with the normality homogeneity test, and it was determined that it was a normal distribution. As a result, the One-Way ANOVA test, one of the parametric tests, was used. Tukey test was used to determine the difference between groups. Significance levels were evaluated as (p < 0.05). RESULTS: Statistical analysis showed a statistically significant difference between groups in CAT, MDA and GSH levels (p < 0.05), while there were no differences between the groups in AOPP levels (p > 0.05). CONCLUSIONS: In the conclusion of the study, it was determined that omega-3 supplementation caused a decrease in MDA level, an increase in CAT activity and GSH level in rats exposed to chronic long-term exercise. Thus, it can be said that omega-3 supplementation in chronic long-term exercise will provide antioxidant protection against potential oxidative damage.

The effect of aerobic exercise on oxidative stress in patients with chronic kidney disease: a systematic review and meta-analysis with trial sequential analysis.

PURPOSE: The purpose of this study was to investigate how aerobic exercise affects oxidative stress (OS) in patients with chronic kidney disease (CKD). METHODS: Retrieval dates range from the date the database was established to 19 July 2023, without languages being restricted. A meta-analysis and sensitivity analysis were conducted using RevMan 5.3 and Stata 16.0. RESULTS: The meta-analysis showed that, compared to usual activity or no exercise, aerobic exercise significantly reduced the oxidative markers malondialdehyde (MDA) (mean differences (MD) - 0.96 (95% CI -1.33, - 0.59); p < 0.00001), advanced oxidation protein product (AOPP) (MD - 3.49 (95% CI - 5.05, - 1.93); p < 0.00001), F2-isoprostanes (F2-iso) (MD - 11.02 (95% CI - 17.79, - 4.25); p = 0.001). Aerobic exercise also increased the antioxidant marker superoxide dismutase (SOD) in CKD patients (standardized mean differences (SMD) 1.30 (95% CI 0.56, 2.04); p = 0.0005). Subgroup analysis showed a significant increase in glutathione peroxidase (GPX) in patients aged ≥60 years (SMD 2.11 (95% CI 1.69, 2.54); p < 0.00001). The change in total antioxidant capacity (TAC) after aerobic exercise was insignificant in patients with CKD. The trial sequential analysis supported aerobic exercise's effectiveness in improving MDA, SOD, AOPP, and F2-iso in patients with CKD. CONCLUSION: The results of this review suggest that aerobic exercise improves OS indicators (MDA, SOD, AOPP, and F2-iso) in CKD patients compared to conventional treatment or no exercise and that the effects on GPX and TAC indicators need further confirmation. For better validation of benefits and exploration of the best aerobic exercise regimen to improve OS status with CKD, further studies with high methodological quality and large sample sizes are needed.

Human protozoa infection and dysplasia in ulcerative colitis: a neglected aspect in a prominent disease.

The chance of getting colorectal cancer (CRC) is higher in people with chronic ulcerative colitis (UC). The impact of parasitic infections on UC is underappreciated. The purpose of this study was to look into the effect of intestinal protozoal infections on the dysplastic changes generated by UC. The research included 152 adult patients with histologically confirmed UC and 152 healthy controls. Fecal samples were examined for the presence of parasites and fecal calprotectin (FC). The enzyme-linked immunosorbent assay measured serum anti-p53 antibodies (p53Abs) and metallothioneins (MTs). The advanced oxidation protein products (AOPPs) and reduced glutathione (GSH) levels were measured by a spectrophotometric method in all subjects. Serum C-reactive protein (CRP) and IL-6 were also measured. In addition, histopathological and immunohistochemical investigations of intestinal tissue were done. Our results exhibited significant increases in FC and CRP, IL-6, AOPPs, MTs, and p53Abs in ulcerative colitis patients with parasitic infections compared to those without parasites. In contrast, GSH levels showed a significant decrease in the same group compared with other groups. Histopathological and immunohistochemical assessments of intestinal tissue signified severe inflammation and strong expression of PD-L1 in patients with parasitic infections compared to others without parasitic infections. Our research indicated a greater frequency of intestinal protozoa in UC patients with elevated inflammatory and dysplastic biomarker levels. This suggests that these parasites may be involved in the etiology of chronic UC and the associated carcinogenetic process. This is the first report of a link between parasitic infections and dysplastic alterations in UC patients.