Levels Of Oxidative Stress Biomarkers Research Articles

Optimization of Phloretin-loaded Nanospanlastics for Targeting of FAS/SREBP1c/AMPK/ OB-Rb Signaling Pathway in HFD-induced Obesity.

Obese patients are at increased risk for CVD, which is the main cause of premature death and has been a major cause of disability and ill health in recent years. PTN, a natural dihydrochalcone flavonoid, has a variety of pharmacological characteristics. This article aimed to prepare PTN-NSLs to evaluate their anti-obesity activity. Morphology, Particle size, zeta potential, UV-vis, entrapment efficiency, FT-IR spectra, and an in vitro release study of PTN-NSLs were described. PTN-NSLs were also tested for their anti-obesity properties in obese rats. The LD50 of PTN-NSLs was calculated, as was the 1/20 LD50 prepared for the treatment of obese rats. Also, the level of glycemic, oxidative stress and inflammatory biomarkers were estimated in the obese rat's model. The synthesized PTN-NSLs were uniform, spherically shaped, and well dispersed with no aggregation noted, with a size range of 114.06 ± 8.35 nm. The measured zeta potential value of PTN-NSLs was -32.50.8 mv. Also, the UV spectra of PTN and PTN-NSLs have strong absorption at 225 and 285 nm. Also, the LD50 of PTN-NSLs was found to be 2750 mg/kg.b.w. Moreover, administrating obese rats with PTN-NSLs resulted in improved glycemic features as well as GSH, SOD, GPx, GR, IL10, TBARs, and IL-6 levels, as well as attenuated FAS, SREBP1c, AMPK, ACO, CPT1, and OB-Rb gene expression. Administration of PTN-NSLs significantly attenuated the levels of glycemic, oxidative stress, and inflammatory biomarkers. The biochemical and PCR findings are aided by histological investigations. Also, the present findings imply that PTN-NSLs might be a promising pharmacological tool for the treatment of obesity-related diseases.

Ecotoxicological evaluation of chitosan biopolymer films particles in adult zebrafish (Danio rerio): A comparative study with polystyrene microplastics

To mitigate the environmental impact of microplastics (MPs), the scientific community has innovated sustainable and biodegradable polymers as viable alternatives to traditional plastics. Chitosan, the deacetylated form of chitin, stands as one of the most thoroughly investigated biopolymers and has garnered significant interest due to its versatile applications in both medical and cosmetic fields. Nevertheless, there is still a knowledge gap regarding the impact that chitosan biopolymer films (CBPF) may generate in aquatic organisms. In light of the foregoing, this study aimed to assess and compare the potential effects of CBPF on the gastrointestinal tract, gills, brain, and liver of Danio rerio against those induced by MPs. The findings revealed that both CBPF and MPs induced changes in the levels of oxidative stress biomarkers across all organs. However, it is essential to note that our star plots illustrate a tendency for CBPF to activate antioxidant enzymes and for MPs to produce oxidative damage. Regarding gene expression, our findings indicate that MPs led to an up-regulation in the expression of genes associated with apoptotic response (p53, casp3, cas9, bax, and bcl2) in all fish organs. Meanwhile, CBPF produced the same effect in genes related to antioxidant response (nrf1 and nrf2). Overall, our histological observations substantiated these effects, revealing the presence of plastic particles and tissue alterations in the gills and gastrointestinal tract of fish subjected to MPs. From these results, it can be concluded that CBPF does not represent a risk to fish after long exposure.

Biochemical, morphological and molecular assessments of n butanol fraction of Phoenix dactylifera L. following exposure to inorganic mercury on the liver of Wistar rats

BackgroundMercury chloride (HgCl2) damages tissues it comes in contact with in sufficient concentration. This study evaluated the protective effects of n-butanol fraction of Phoenix dactylifera (BFPD) on mercury-triggered liver toxicity in Wistar rats. 25 male rats were divided into 5 groups of 5 rats each. Group I was administered 2 ml/kg of distilled water; group II was administered 5 mg/kg of HgCl2; group III was administered 500 mg/kg of BFPD + 5 mg/kg of HgCl2; group IV was administered 1000 mg/kg of BFPD + 5 mg/kg of HgCl2, while group V was administered 100 mg/kg of silymarin + 5 mg/kg of HgCl2. orally for 2 weeks. The rats were euthanized and liver tissue blood samples were collected for histological, histochemical, stereological, immunohistochemical, molecular, and biochemical studies.ResultsThe results revealed that HgCl2 induced oxidative stress in the rats evident by histoarchitectural distortions and altered levels of liver enzymes, proteins, and oxidative stress biomarkers when compared to the control. However, BFPD treatment restored these changes. Glutathione peroxidase levels decreased (p < 0.05) in the HgCl2−treated group when compared to the control and BFPD-treated groups. HgCl2 group revealed reduced reactivity with histochemical and immunohistochemical stains (Masson’s Trichrome and B cell Lymphoma 2) when compared to the control, with a significant decrease in quantified liver Bcl-2 stain intensity when compared to the silymarin-treated group. BFPD administration revealed normal staining intensity comparable to the control. HgCl2 administration revealed a remarked decrease in the number of hepatocytes when compared to the control, BFPD, and silymarin groups. BFPD preserved (p < 0.05) the stereological features when compared to the HgCl2-treated group. GPx activity in the liver decreased (p < 0.05) with HgCl2 administration when compared to the control and silymarin-treated groups. BFPD attenuated GPx gene activity to levels similar to the control indicating some level of amelioration against HgCl2-induced toxicity.ConclusionsThe ability of BFPD to mitigate HgCl2 triggered liver alterations could be attributed to the antioxidant property of its flavonoid content. Therefore, BFPD may be a potential candidate for treating and managing liver-induced mercury intoxication.

Toxicity of three microcystin variants on the histology, physiological and metabolism of hepatopancreas and intestinal microbiota of Litopenaeus vannamei

Microcystins (MCs) are prevalent harmful contaminants within shrimp aquaculture systems, exhibiting a diverse array of variants. Gut microbiota can engage in mutual interactions with the host through the gut-liver axis. In this study, the shrimp Litopenaeus vannamei were subjected to three different variants of MCs (LR, YR, RR) at a concentration of 1 μg/L each, and elucidated the alterations in both intestinal microbiota and hepatopancreas physiological homeostasis. The results showed that all three variants of MCs prompted histological alterations in the hepatopancreas, induced elevated levels of oxidative stress biomarkers (H2O2, T-SOD, and CAT), disturbed the transcription levels of immune-related genes (Crus, ALF, and Lys), along with an increase in apoptotic genes (Casp-3 and P53). Furthermore, the metabolic profiles of the hepatopancreas were perturbed, particularly in amino acid metabolism such as “lysine degradation” and “β-alanine metabolism”; the mTOR and FoxO signaling were also influenced, encompassing alterations in the transcription levels of related genes. Additionally, the alterations were observed in the intestinal microbiota's diversity and composition, particularly potential beneficial bacteria (Alloprevotella, Bacteroides, Collinsella, Faecalibacterium, and Prevotellaceae UCG-001), which exhibited a positive correlation with the metabolite berberine. These findings reveal that the three MCs variants can impact the health of the shrimp by interfering with the homeostasis of intestinal microbial and hepatopancreas physiology.

Radioprotective effect of piperine, as a major component of black pepper, against radiation-induced colon injury: biochemical and histological studies.

Patients undergoing radiotherapy are prone to radiation-induced gastrointestinal injury. Piperine is an alkaloid component in black pepper with a unique chemopreventive activity against oxidative stress-related damage in healthy tissues. The purpose of this study was to investigate the effects of piperine on intestinal damage. In this study, mice were divided into eight groups: including the control, piperine (10, 25, and 50 mg/kg), radiation (6 Gy), and piperine+radiation (10, 25 and 50 mg/kg + 6 Gy) groups. The radioprotective effects of piperine were evaluated by biochemical (MDA, GSH, and PC) and histopathological assessments in colon tissues. The 10 mg/kg dose of piperine significantly reduced the levels of oxidative stress biomarkers compared to the group that received only radiation. In addition, pre-treatment with 10 mg/kg piperine diminished the histopathological changes like vascular congestion in the submucosa, while the dose of 50 mg/kg led to the infiltration of inflammatory cells. Based on this study, it is concluded that piperine, at low dose, with its antioxidant properties, could reduce the colon damage caused by radiation.

Adjuvant Effects of Lavandula angustifolia Oil in Experimental Carrageenan-Induced Thrombosis

Antinociceptive, sedative, anti-inflammatory, and antioxidant effects of lavender oil (LO) have been documented. The aim of our study was to evaluate the adjuvant effects of pretreatment with LO compared to standard treatment (low molecular weight heparin) in thrombosis. We evaluated the effects of two doses of LO in addition to nadroparin calcium (NC) on experimentally induced thrombosis in rats. The groups were as follows: the control (C) group received intraperitoneal (i.p.) saline and vehicle (DMSO), the thrombosis (T) group received saline plus vehicle pretreatment, nadroparin calcium (NC) was administrated subcutaneously (s.c.), TNCL1 and TNCL2 received pretreatment with LO (TNCL1—100 mg/kg body weight (b.w.) i.p. and TNCL2—200 mg/kg b.w. i.p. and NC s.c.). Thrombosis was successfully obtained in all groups, except the C group. Statistically significant differences between groups (p-values &lt; 0.001) were found for the levels of oxidative stress biomarkers (malondialdehyde, nitric oxide, and total oxidative stress) and antioxidant parameters (total antioxidant capacity and thiols), TNF-α, MCP-1, and RANTES. Dose-dependent effects are seen on the biomarkers under evaluation, with higher LO doses producing the best outcomes. When compared to the group receiving standard treatment (NC alone), the LO pretreatment led to an increase in antioxidant levels (p-values &lt; 0.001) and a decrease in oxidative stress and pro-inflammatory levels (p-values &lt; 0.001). Lavender oil associated with NC treatment alleviates the inflammatory components of experimental carrageenan-induced thrombosis in rats by decreasing oxidative stress and inflammatory cytokines and improving antioxidant activity.

The Role of Salivary Biomarkers in Monitoring Oral Health in Patients with Implants and Periodontitis

Oxidative stress, a physiological process that can damage cells, is known to affect various aspects of oral health. Oxidative stress can influence dental implant longevity and health. Assessing biomarkers of oxidative stress in saliva is beneficial for diagnosing and tracking the progression of oral diseases. A study is made of salivary oxidative stress in patients with dental implants with or without periodontitis. The study consisted of the following groups: Group1 (healthy without dental implants); Group 2 (subjects undergoing periodontal maintenance without dental implants); Group 3 (healthy patients with implants older than six months); and Group 4 (patients undergoing periodontal maintenance with implants older than six months). A complete examination of the oral cavity was made in each patient and a questionnaire was used to assess habits of hygiene, quality of life, and information about the implants. The following parameters were recorded in unstimulated whole saliva: ferric reducing antioxidant power (FRAP), Trolox equivalent antioxidant capacity (TEAC), cupric reducing antioxidant capacity (CUPRAC), advanced oxidation protein products (AOPP), and total proteins (TP). A total of 160 patients were studied, with 40 patients per group. The mean oxidative stress biomarker values obtained in the patients without implants and with implants were FRAP 0.590 ± 0.514 and 0.588 ± 0.334 mmol/L (p = 0.974); TEAC 0.320 ± 0.223 and 0.315 ± 0.172 mmol/L (p = 0.879); CUPRAC 0.286 ± 0.216 and 0.288 ± 0.151 mmol/L (p = 0.956); AOPP 456.04 ± 789.75 and 430.65 ± 752.05 µmol/L (p = 0.838); and TP 73.90 ± 50.83 and 70.36 ± 56.93 mg/dL (p = 0.684), respectively. No substantial variations were noted in the salivary oxidative stress biomarker levels between patients with controlled periodontal disease and/or dental implants compared to healthy individuals.

Anti-radiation effect of MRN-100: a hydro-ferrate fluid, in vivo.

Ionizing radiation (IR) severely harms many organs, especially the hematopoietic tissue, mandating the development of protective nutraceuticals. MRN-100, a hydro-ferrate fluid, has been shown to protect γ-radiated fish against hematopoietic tissue damage and lethality. The current study aimed to examine MRN-100's protective effect against irradiated mice and explore the mechanisms underlying its effect. Mice received a single acute, sub-lethal, 5Gy, whole body dose of X-ray IR. MRN-100 treatment was administered daily for 2-weeks pre-irradiation until 1-week post-irradiation. Spleen and blood were analysed for oxidative stress, hematological, histological and biochemical parameters. Radiation exposure markedly decreased complete blood count (CBC) parameters including hemoglobin, hematocrit, red blood cells, platelets, white blood cells and lymphocytes, and significantly increased neutrophils. In contrast, MRN-100 supplementation to irradiated mice ameliorated all CBC parameters and protected against DNA damage in both splenic cells and serum. It also had an antioxidant effect, increasing the levels of glutathione, superoxide dismutase, catalase and total antioxidant capacity, which were otherwise decreased by irradiation. MRN-100 intake reduced the oxidative stress biomarker levels of nitric oxide, protein carbonyl, malondialdehyde, reactive oxygen species and 8-hydroxydeoxyguanosine, a marker specific to DNA damage. Furthermore, MRN-100 enhanced serum iron and reversed the radiation-induced elevations of liver enzymes. Finally, MRN-100 protected splenic tissue from irradiation as observed by histology. We conclude that MRN-100 consumption may protect against oxidative stress generated by radiation exposure, suggesting that it may be employed as an adjuvant treatment to prevent radiation's severe damage to important organs.

Effects of coenzyme Q10 supplementation on oxidative stress biomarkers following reperfusion in STEMI patients undergoing primary percutaneous coronary intervention.

It is well-established that oxidative stress is deeply involved in myocardial ischemia-reperfusion injury. Considering the potent antioxidant properties of coenzyme Q10 (CoQ10), we aimed to assess whether CoQ10 supplementation could exert beneficial effects on plasma levels of oxidative stress biomarkers in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPIC). Seventy patients with the first attack of STEMI, eligible for PPCI were randomly assigned to receive either standard treatments plus CoQ10 (400 mg before PPCI and 200 mg twice daily for three days after PPCI) or standard treatments plus placebo. Plasma levels of oxidative stress biomarkers, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured at 6, 24, and 72 hours after completion of PPCI. The changes in plasma levels of the studied biomarkers at 6 and 24 hours after PPCI were similar in the both groups (P values>0.05). This is while at 72 hours, the CoQ10- treated group exhibited significantly higher plasma levels of SOD (P value<0.001), CAT (P value=0.001), and TAC (P value<0.001), along with a lower plasma level of MDA (P value=0.002) compared to the placebo-treated group. The plasma activity of GPX showed no significant difference between the groups at all the study time points (P values>0.05). This study showed that CoQ10 has the potential to modulate the balance between antioxidant and oxidant biomarkers after reperfusion therapy. Our results suggest that CoQ10, through its antioxidant capacity, may help reduce the reperfusion injury in ischemic myocardium.

N-Acetylcysteine Ameliorates 5-Fluorouracil‐Induced Ovarian Injury in Rats

Objective: Although 5-fluorouracil (5-FU) is one of the most commonly used chemotherapeutics worldwide, it has been shown that 5-FU administration can cause reproductive toxicity in recent years. N-acetylcysteine (NAC) is the precursor of glutathione, the most important endogenous antioxidant molecule and is known for its effective antioxidant and anti-inflammatory properties. Although NAC is one of the most studied antioxidant molecules, its curative effect against ovarian damage caused by 5-FU has not been demonstrated to date. It was therefore aimed to investigate whether NAC is therapeutic against 5-FU-induced ovotoxicity in this study for the first time.&#x0D; Methods: Rats were first exposed to a single dose of 5-FU (100 mg/kg) and then treated with NAC (10 and 20 mg/kg) for three days. The oxidative stress, inflammation and apoptosis markers in ovarian tissues were also determined using spectrophotometric methods. Ovarian tissues were also evaluated histologically.&#x0D; Results: It was revealed that the levels of oxidative stress, inflammation and apoptosis biomarkers in ovarian tissue increased by 5-FU administration (p

Combined exposure of MAHs and PAHs enhanced amino acid and lipid metabolism disruption in epithelium leading asthma risk

Monoaromatic hydrocarbons (MAHs) and polycyclic aromatic hydrocarbons (PAHs) are ubiquitous air pollutants from industry, with multiple adverse effects on respiratory system. However, the underlying mechanisms of their mixture to induce asthma is still unclear. Here, we examined mixture of 8 MAHs, mixture of 16 PAHs and a total mixture (MIX) on human bronchial epithelial (16-HBE) cells. Exposure to MIX resulted in increased expressions of asthma alarm cytokines (TSLP, IL-25 and IL-33), indicating potential asthma risk. Exposure to MIX led to significant upregulation of transcriptional level of oxidative stress and inflammation biomarkers through aryl hydrocarbon receptor activation, including SOD-2, NQO-1, IL-1β, IL-6 and IL-8 with 3.1, 19.9, 3.5, 23.4, 18.7, 28.1-fold change, indicated asthma related epithelial cell lesions. A total of 25, 49 and 59 differential metabolites were identified in cells response to MAH, PAH and MIX exposure, respectively, and enrichment analysis demonstrated MIX exposure disturbing alanine, aspartate and glutamate metabolism, glutathione metabolism, methionine metabolism and sphingolipid metabolism, involved in antioxidative defense and inflammation response. Combined exposure of MAHs and PAHs may result in increased toxic risks, and provide evidence to asthma onset and deterioration.

GPER activation attenuates cardiac dysfunction by upregulating the SIRT1/3-AMPK-UCP2 pathway in postmenopausal diabetic rats.

Postmenopausal diabetic women are at higher risk to develop cardiovascular diseases (CVD) compared with nondiabetic women. Alterations in cardiac cellular metabolism caused by changes in sirtuins are one of the main causes of CVD in postmenopausal diabetic women. Several studies have demonstrated the beneficial actions of the G protein-coupled estrogen receptor (GPER) in postmenopausal diabetic CVD. However, the molecular mechanisms by which GPER has a cardioprotective effect are still not well understood. In this study, we used an ovariectomized (OVX) type-two diabetic (T2D) rat model induced by high-fat diet/streptozotocin to investigate the effect of G-1 (GPER-agonist) on sirtuins, and their downstream pathways involved in regulation of cardiac metabolism and function. Animals were divided into five groups: Sham-Control, T2D, OVX+T2D, OVX+T2D+Vehicle, and OVX+T2D+G-1. G-1 was administrated for six weeks. At the end, hemodynamic factors were measured, and protein levels of sirtuins, AMP-activated protein kinase (AMPK), and uncoupling protein 2 (UCP2) were determined by Western blot analysis. In addition, cardiac levels of oxidative stress biomarkers were measured. The findings showed that T2D led to left ventricular dysfunction and signs of oxidative stress in the myocardium, which were accompanied by decreased protein levels of Sirt1/2/3/6, p-AMPK, and UCP2 in the heart. Moreover, the induction of the menopausal state exacerbated these changes. In contrast, treatment with G-1 ameliorated the hemodynamic changes associated with ovariectomy by increasing Sirt1/3, p-AMPK, UCP2, and improving oxidative status. The results provide evidence of the cardioprotective effects of GPER operating through Sirt1/3, p-AMPK, and UCP2, thereby improving cardiac function. Our results suggest that increasing Sirt1/3 levels may offer new therapeutic approaches for postmenopausal diabetic CVD.

Effects of topical ketorolac tromethamine on tear parameters, meibography, goblet cell density, and conjunctival oxidative stress in healthy dogs.

The objective of the study was to evaluate whether a twice-daily instillation of 0.45% preservative-free ketorolac tromethamine (FKT) or 0.4% benzalkonium chloride-preserved ketorolac tromethamine (BACKT), every 12 h for 30 days may affect tear film parameters and the meibography in healthy dogs. Additionally, we assessed whether the same treatments irritated the ocular surface, affected goblet cell density (GCD), and the levels of oxidative stress biomarkers (OSB) in the conjunctiva of the same dogs. Experimental and masked comparison study. In 11 healthy dogs baseline values of the lipid layer thickness, tear meniscus height, non-invasive tear breakup time (NI-TFBT), and the meibomian gland (MG) loss were assessed by OSAvet®. For each dog, one eye received 40 μL of BACKT, while the other received 40 μL FKT, every 12 h for 30 consecutive days. Tear parameters and meibography were repeated 15, 30, and 60 days post-treatments. Conjunctival hyperemia and blepharospasm were monitored at the same time points. At baseline and Day 30, a conjunctival biopsy was collected for GCD and OSB determination. Conjunctival hyperemia and blepharospasm were not observed. At Day 15, the MG loss increased only in FKT-treated eyes (p < .001). On Day 30, both treatment groups showed increased MG loss, shortened NI-TFBT, and reduced GCD and catalase (p < .05). At Day 30, BACKT-treated eyes showed lower levels of superoxide dismutase (SOD) (p = .006) and higher levels of malondialdehyde (MDA) (p = .02). Differences between treatments were not observed for any parameter at any time point (p > .05). 60 days after treatment, OSAvet® parameters tended to return to values assessed at baseline; however, significant differences remained for MG loss (p < .05). Twice-daily instillation of KT, containing or not BAC, for 30 consecutive days shortened NI-TFBT, decreased GCD, and increased the MG loss in healthy dogs. KT should be used with caution when prescribed for long periods, particularly in patients with tear film abnormalities. However, future controlled studies using KT, BAC, and other topical NSAIDs are indicated to further support this finding.

Emerging role of vitamin D3 in alleviating intestinal structure injury caused by Aeromonas hydrophila in grass carp (Ctenopharyngodon idella)

Bacterial pathogens destroy the structural integrity of functional organs in fish, leading to severe challenges in the aquaculture industry. Vitamin D3 (VD3) prevents bacterial infections and strengthens immune system function via vitamin D receptor (VDR). However, the correlation between VD3/VDR and the structural integrity of functional organs remains unclarified. This study aimed to investigate the influence of VD3 supplementation on histological characteristics, apoptosis, and tight junction characteristics in fish intestine during pathogen infection. A total of 540 healthy grass carp (257.24 ± 0.63 g) were fed different levels of VD3 (15.2, 364.3, 782.5, 1,167.9, 1,573.8, and 1,980.1 IU/kg) for 70 d. Subsequently, fish were challenged with Aeromonas hydrophila, a pathogen that causes intestinal inflammation. Our present study demonstrated that optimal supplementation with VD3 (1) alleviated intestinal structural damage, and inhibited oxidative damage by reducing levels of oxidative stress biomarkers; (2) attenuated excessive apoptosis-related death receptor and mitochondrial pathway processes in relation to p38 mitogen-activated protein kinase signaling (P < 0.05); (3) enhanced tight junction protein expression by inhibiting myosin light chain kinase signaling (P < 0.05); and (4) elevated VDR isoform expression in fish intestine (P < 0.05). Overall, the results demonstrated that VD3 alleviates oxidative injury, apoptosis, and the destruction of tight junction protein under pathogenic infection, thereby strengthening pathogen defenses in the intestine. This finding supports the rationale for VD3 intervention as an essential practice in sustainable aquaculture.

Carbon Dioxide (CO2) Dietary Emissions Are Related to Oxidative and Inflammatory Status in Adult Population.

Carbon dioxide (CO2) is a primary greenhouse gas (GHG) causing global temperature to rise. Unsustainable diets induce an increment in the risk of obesity and noncommunicable diseases but also contribute to the global GSG burden. To assess whether CO2 dietary emissions influence the inflammatory and oxidative status of subjects with metabolic syndrome (MetS). As part of the PREDIMED-Plus study, 100 adults (55-75 years old) from the Balearic Islands, Spain, were recruited and classified according to their dietary CO2 emissions. Anthropometric parameters were determined, fasting blood samples were collected and plasma, neutrophils, and peripheral blood mononuclear cells (PBMCs) were obtained. Dietary inflammatory index (DII), adherence to a Mediterranean diet (ADM), fatty liver index (FLI), and estimated glomerular filtration (eGFR) were calculated. Clinical biochemical parameters, blood count, and oxidative stress and inflammatory biomarker levels were also determined. DII was higher in participants with high dietary CO2 emissions. Adherence to the MedDiet was inversely associated with CO2 emissions. Malondialdehyde (MDA) levels were higher in urine and plasma samples from subjects with high dietary CO2 emissions. Reactive oxygen species (ROS) production by PBMCs was greater in participants with high CO2 emissions. Interleukin-15, resistin, and leptin plasma levels were increased in participants with high dietary CO2 emissions. Dietary CO2 emissions influence oxidative status and inflammation in relation to the increased prooxidative and proinflammatory status in PBMCs and plasma. These biomarkers were useful for monitoring diet sustainability and health.

The Effect of Hippo Pathway Inhibitor Xmu‐mp‐1 on Cognitive Impairment in a Rat Model of Alzheimer’s Disease: Protection against Oxidative Stress, Tau Hyperphosphorylation, and Neurodegeneration

AbstractBackgroundAlzheimer’s Disease (AD), the most common form of dementia, is a growing global health concern with unmet clinical therapeutics. AD can be attributed to amyloid beta aggregation and tau hyperphosphorylation‐induced oxidative stress and neurodegeneration in the brain. Previous studies have implicated a hyper‐activated Hippo signaling pathway with neuronal loss in neurodegenerative disorders, including AD. However, it is still unknown if suppressing the Hippo pathway can rescue neuronal death in AD.MethodIn this study, we investigated the cognitive impairment ameliorative effect of the novel Hippo signaling inhibitor, Xmu‐mp‐1, in a rat model of AD. Adult male Wistar rats were stereotaxically injected with a well‐known AD inducer Streptozotocin (STZ), to mimic AD‐like features. A pharmacological antagonist of Hippo signaling component MST1 called Xmu‐mp‐1 was administered intraperitoneally at a dose of 0.5mg/kg body weight for 14 days. Then the effect of Xmu‐mp‐1 on cognitive impairment was assessed using the Morris water maze test and novel object recognition test. Further, we did biochemical and histopathological studies to explore the effect of Xmu‐mp‐1 on several AD‐associated pathophysiological changes, including oxidative stress, tau hyperphosphorylation, and neurodegeneration.ResultXmu‐mp‐1 significantly improved the cognitive impairment of the AD rats in the Morris water maze test and the novel object recognition test (n = 7). Biochemical analysis of the brain hippocampal and cortical tissues revealed that Xmu‐mp‐1 also ameliorated the AD‐associated oxidative stress burden as the levels of anti‐oxidants (SOD, Catalase, GSH) significantly increased and the levels of oxidative stress biomarkers (protein carbonyl and lipid peroxidation) significantly reduced after Xmu‐mp‐1 treatment in the AD rats (n = 6). Moreover, the level of tau phosphorylation, a prime characteristic of AD, was also reduced following Xmu‐mp‐1 treatment (n = 3). Finally, neuronal death was also found to be rescued after Xmu‐mp‐1 treatment in AD rats (n = 3).ConclusionXmu‐mp‐1 exhibits a neuroprotective role against AD as it improves the cognitive impairment induced by STZ. Further mechanistic investigations into the neuroprotective role of Xmu‐mp‐1 revealed that Xmu‐mp‐1 provides protection from oxidative stress, tau hyperphosphorylation, and aberrant neurodegeneration under an AD background. Future studies can explore the therapeutic potential of Hippo signaling inhibition against AD in more detail.

Association between biomarkers of redox status and cytokines with different patterns of habitual physical activity in eutrophic and overweight/obese preschoolers: multivariate analysis of a cross-sectional study

BackgroundAlthough it is well known that obesity is frequently associated with reduced levels of habitual physical activity (HPA), which contributes to determining severe oxidative stress and inflammatory state, this association is however unknown in preschoolers so far. This study aimed to investigate the association between biomarkers of redox status and cytokines with different patterns of HPA according to the adiposity of preschoolers.MethodsA cross-sectional study was conducted in 50 preschoolers (25 overweight/obese, OW/OB and 25 eutrophic, EU), matched for age, sex, economic level, and maternal education. Total antioxidant capacity (TAC), superoxide dismutase (SOD) and catalase (CAT) activities, substances reactive to thiobarbituric acid (TBARS), soluble tumor necrosis factor receptors (sTNFRs), and leptin levels were evaluated. HPA levels were evaluated by accelerometry (ActiGraph GT9X accelerometer). Correlation, multiple linear regression, and partial least squares regression analysis were used to determine the association between redox status biomarkers and cytokines with different patterns of HPA (HPA level, bouts of moderate to vigorous physical activity [MVPA], and multivariate pattern of HPA) in EU and OW/OB preschoolers.ResultsOW/OB preschoolers had lower CAT activity, higher levels of TAC, TBARS, and cytokines, and similar levels of HPA to EU preschoolers. In EU preschoolers, SOD activity exhibited a stronger negative association with moderate intensity ranges of HPA (R2 = 0.18), and negative correlation with sTNFRs (r = -0.40 to -0.46). TBARS had a stronger positive association with ranges of light intensity in the multivariate pattern of HPA (R2 = 0.10). In OW/OB preschoolers, the HPA multivariate associative pattern was predominantly from vigorous intensity ranges. Thus, SOD activity had a positive association with the multivariate pattern of HPA (R2 = 0.38) and MVPA bouts (β [95% CI] = 0.457 [0.0026. 0.0576]). TAC had a negative association with the multivariate pattern of HPA (R2 = 0.38) and MVPA bouts (β [95% CI] = -0.718 [-0.0025. -0.0003]). Additionally, leptin levels were lower in OW/OB preschoolers engaged in vigorous physical activity (VPA) (8000–9999 counts/min) for longer periods of time.ConclusionThe results of this study indicate that OW/OB preschoolers have higher levels of oxidative stress biomarkers and pro-inflammatory cytokines compared to EU preschoolers. Moreover, VPA may exert antioxidative and anti-inflammatory effects in OW/OB preschoolers.

Oxybutynin ameliorates LPS-induced inflammatory response in human bladder epithelial cells.

Urinary tract infection (UTI) mainly results from bacterial infections in the urinary tract and markedly impacts the normal lives of millions of patients worldwide. The infection and damage to urethral epithelial cells is the first and key step of UTI development and is a critical target for treating clinical UTI. Oxybutynin, an agent for treating urinary incontinence, is recently claimed with protective effects on bladder ultrastructure. Our study will assess the impact of Oxybutynin on inflammation in lipopolysaccharide (LPS)-stimulated bladder epithelial cells. Bladder epithelial T24 cells were treated with 1 μg/mL LPS with or without 10 and 20 μM Oxybutynin for 24 h. Increased levels of oxidative stress (OS) biomarkers, such as reactive oxygen species, 8-hydroxy-2'-deoxyguanosine, malondialdehyde, as well as upregulated inducible nitric oxide synthase and promoted release of nitric oxide, were observed in LPS-managed T24 cells, all of which were signally suppressed by Oxybutynin. Furthermore, severe inflammatory responses, including enhanced release of cytokines, upregulated matrix metallopeptidase-2 (MMP-2) and MMP-9, and raised monocyte chemoattractant protein-1 level, were found in LPS-challenged T24 cells, which were markedly reversed by Oxybutynin. Moreover, the activated toll-1ike receptor 4/nuclear factor-κB pathway observed in LPS-managed T24 cells was repressed by Oxybutynin. Collectively, Oxybutynin mitigated LPS-induced inflammatory response in human bladder epithelial cells.

The Potential Benefic Effect of Nicotinamide Riboside in Treating a Murine Model of Monoiodoacetate-Induced Knee Osteoarthritis.

Knee osteoarthritis (KOA), one of the most common orthopedic disorders concerning the adult population worldwide, is a condition characterized by progressive destruction of the articular cartilage and the presence of an inflammatory process. The aim of our study was to assess whether nicotinamide riboside (NR), a popular anti-aging supplement, can reduce the rate of cartilage destruction and alleviate the inflammatory response compared to the commonly prescribed collagen supplement in a murine monoiodoacetate (MIA)-induced KOA model. Twenty Wistar rats were randomly assigned to 4 groups: sham (S), MIA and NR, MIA and hydrolyzed collagen (HC), and MIA. At the end of the experiment, the right knees and blood samples were collected for histological assessment and biochemical evaluation of nitric oxide, malondialdehyde, total antioxidant capacity, reduced glutathione, glutathione peroxidase, superoxide dismutase, catalase, myeloperoxidase, and tumoral necrosis factor-alpha (TNF-α). The study determined that the treatment with NR in a similar dose with HC decreased blood/serum levels of oxidative stress biomarkers and the histological lesions in almost the same manner. The present findings suggest that NR may exhibit chondroprotective and anti-inflammatory effects in MIA-induced KOA in rats.

Meta-Analysis of Assessment of Total Oxidative Stress and Total Antioxidant Capacity in Patients with Periodontitis.

Periodontitis is intricately linked to oxidative stress-antioxidant (redox) imbalance. The antioxidant system scavenges the oxygen free radicals in biological fluids in patients with periodontitis. However, little is still known about the free radicals mediated oxidative stress and reductive ability of the antioxidant system. Thus, the present meta-analysis aims to quantitatively review the literature that assessed the oxidative stress marker total oxidative stress (TOS) and total antioxidant capacity (TAC) in various biological fluids of patients with periodontitis. Methodology. Electronic databases were searched for studies that assessed TOS and TAC levels in various biological samples of patients with periodontitis. From the 1,812 articles identified, 1,754 were excluded based on title and abstract screening due to irrelevance to the topic of interest. A full-text assessment of the remaining 58 articles led to the selection of 42 articles that satisfied the inclusion criteria. Of these, only 24 studies had consistent data for quantitative analysis. The periodontitis group displayed significantly elevated TOS levels (p < 0.05) in serum, gingival crevicular fluid (GCF), and saliva samples in the studies evaluated. In contrast, the periodontitis group exhibited significantly attenuated TAC levels (p < 0.01) compared to healthy controls in plasma, serum, and GCF samples of the studies evaluated, which was insignificant in salivary samples (p=0.433). At the same time, the periodontitis group displayed insignificantly elevated TAC levels after periodontal therapy (p=0.130). The present meta-analysis showed significantly higher TOS and lower TAC in periodontitis, reflecting the elevated oxidative stress level than the control group. Clinical Relevance. Scientific rationale for the study: The imbalance between oxidants and antioxidants (oxidative stress (OS)) plays a critical role in the onset and progression of periodontitis; the assessment of the relationship between OS-related biomarkers in regional samples and systemic samples of patients with periodontitis helps us to evaluate the periodontal disease progression. The OS biomarker levels can be used to assess periodontal disease and therapeutic efficacy.