Oxidative Stress Conditions Research Articles

Effects of Auricularia auricula-judae (Bull.) Quél. polysaccharide acid hydrolysate on glucose metabolism in diabetic mice under oxidative stress

BackgroundOxidative stress can lead to uncontrolled glucose metabolism and, thus, diabetes. Auricularia auricula-judae (Bull.) Quél. polysaccharides possess biological activities, such as antioxidant and hypoglycemic effects, but their mechanism of their acid hydrolysates on oxidative stress-injured glucose metabolism disorders is unclear. PurposeUsing diabetic mice, we investigated the effect of the acid hydrolysate of polysaccharides from Auricularia auricula-judae (Bull.) Quél. on improving diabetes. Study design and MethodsThe structural information of sample polysaccharides was measured by high performance gel permeation chromatography, nuclear magnetic resolution, and high performance liquid chromatography. The diabetic model was established by intraperitoneal injection of streptozotocin. For eight consecutive weeks, the mice were orally administered sample polysaccharides (100, 200, and 300 mg/kg b.w. per day) for intervention. The improvement effect of the samples on diabetes was explored by detecting the changes in biochemical indicators in mice, and the underlying mechanism was studied by transcriptomic and metabolomic analysis. ResultsThe results showed that acid hydrolysate of Auricularia auricula-judae (Bull.) Quél. polysaccharides consisted mainly of mannose, xylose, glucuronic acid, and glucose; its weight-averaged molecular weight was 6.3842 × 104 Dalton, its number average molecular weight was 2.9594 × 104 Dalton; and the molecule contained α-Glc(1→4)-, β-Glc(1→3)-, and β-Man(1→4)-linked glycosidic bonds. A total of 100 mg/kg b.w. per day sample was the best intervention concentration. After eight weeks of intervention, the sample polysaccharides significantly reduced dynamic blood glucose and serum lipids, enhanced antioxidant enzyme activities, promoted glucagon like peptide-1 and insulin secretion, improved insulin sensitivity and alleviated insulin resistance in diabetic mice. Transcriptomic and metabolomic analyses showed that sample polysaccharides was able to ameliorate disorders of glucose metabolism by modulating gene expression such as glucokinase; and modulate the state of oxidative stress in mice in vivo by regulating the glutathione metabolism pathway. ConclusionAcid hydrolysate of Auricularia auricula-judae (Bull.) Quél. polysaccharides improved glucose metabolism disorders by slowing down the oxidative stress injury in mice, thereby alleviating diabetes. This study provided a basis for determining the underlying mechanism of the antidiabetic effect of Auricularia auricula-judae (Bull.) Quél. polysaccharides, which would significantly improve the deep development and application of these materials in diabetes control.

Neuroprotective effects of polyphyllin VI against rotenone-induced toxicity in SH-SY5Y cells

BackgroundA substantial body of evidence is drawing connections between Parkinson's disease (PD) and the phenomena of oxidative stress and mitochondrial dysfunction. Polyphyllin VI (PPVI), an active compound found in Rhizoma Paridis-commonly known as Chonglou (CL) in China, has been identified for its various pharmacological properties, including anti-tumor and anti-inflammatory effects. ObjectiveIn the present study, an in vitro model of PD was established by treating SH-SY5Y cells with rotenone (ROT), to evaluate the potential neuroprotective effects of polyphyllin VI and its underlying mechanism. MethodsSH-SY5Y cells were treated with ROT to establish an in vitro model of PD. The effects of polyphyllin VI on cell viability were assessed using the resazurin assay. Cell morphology was examined using a microscope. The YO-PRO-1/PI was used to detect apoptosis. Mito-Tracker Red CMXRos, Mito-Tracker Green, and JC-1 were used to detect the effects of polyphyllin Ⅵ on mitochondrial viability, morphology, and function. Oxidative stress-related marker detection kits were used to identify the effects of polyphyllin VI on oxidative stress. Western blot analysis was employed to investigate the signaling pathways associated with neuroprotection. ResultsPPVI increased ROT-induced SH-SY5Y cell viability and improved ROT-induced cellular morphological changes. PPVI ameliorated ROT-induced oxidative stress status, and attenuated mitochondrial function and morphological changes. PPVI may exert neuroprotective effects through FOXO3α/CREB1/DJ-1-related signaling pathways. ConclusionThese preliminary findings suggested that PPVI possesses neuroprotective attributes in vitro, and it may be a potential candidate for PD treatment. However, extensive research is necessary to fully understand the mechanisms of PPVI and its effectiveness both in vitro and in vivo.

Arsenic and chromium induced hepatotoxicity in zebrafish (Danio rerio) at environmentally relevant concentrations: Mixture effects and involvement of Nrf2-Keap1-ARE pathway

Arsenic (As) and chromium (Cr), two well-known cytotoxic and carcinogenic metals are reported to coexist in industrial effluents and groundwater. Their individual toxicities have been thoroughly studied but the combined effects, especially the mechanism of toxicity and cellular stress response remain unclear. Considering co-exposure as a more realistic scenario, current study compared the individual and mixture effects of As and Cr in the liver of zebrafish (Danio rerio). Fish were exposed to environmentally relevant concentrations of As and Cr for 15, 30 and 60 days. ROS generation, biochemical stress parameters like lipid peroxidation, reduced glutathione content, catalase activity and histological alterations were studied. Results showed increase in ROS production, MDA content and GSH level; and vicissitude in catalase activity as well as altered histoarchitecture, indicating oxidative stress conditions after individual and combined exposure of As and Cr which were additive in nature. This study also included the expression of Nrf2, the key regulator of antioxidant stress responses and its nuclear translocation. Related antioxidant and xenobiotic metabolizing enzyme genes like keap1, nqo1, ho1, mnsod and cyp1a were also studied. Overall results indicated increased nrf2, nqo1, ho1, mnsod expression at all time points and increased cyp1a expression after 60 days exposure. Emphasizing on the Nrf2-Keap1 pathway, this study exhibited additive or sometimes synergistic effects of As and Cr in zebrafish liver.

Antioxidant and Neuroproliferative Effects of THL-3-PTD5 Peptide Derived from Hydramacin-1 Antimicrobial Peptide

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by reduced dopamine levels in the brain, affecting over 6 million people worldwide. While current treatments for patients primarily focus on symptom relief, there is a necessity for the development of novel therapeutic agents due to the presence of side effects and declining effectiveness. Functional peptides, known for their high selectivity, specificity, and diverse bioactivities, have shown the potential to develop therapeutic candidates for neurodegenerative diseases. Notably, the macin family of proteins exhibits potent antimicrobial activity and nerve repair effects. In this study, we investigated the antioxidant activity and neuroproliferative effects of a series of truncated peptides (THL, THL-1, THL-2, and THL-3) derived from the C-terminal sequence of hydramacin-1. Results showed that THL-3 exhibited the strongest antioxidant activity (EC50 of 22.5 μM) in ABTS-radical scavenging assays, with amino acid residues Cys5, Pro6, Leu7, Lys9, and Lys10 playing critical roles in its activity. Upon conjugation with the cell-penetrating PTD5 peptide to form THL-3-PTD5, it exhibited a significant dose-dependent neuroproliferative effect, increasing the viability of SH-SY5Y cells by 118% at 100 μM. However, it did not exhibit neuroprotective effects under in vitro conditions of oxidative stress induced by an exogenous oxidizing agent. This study suggests that THL-3-PTD5 may serve as a potential candidate for developing therapeutic agents against neurodegenerative diseases.

Function of Burkholderia pseudomallei RpoS and RpoN2 in bacterial invasion, intracellular survival, and multinucleated giant cell formation in mouse macrophage cell line.

Melioidosis, a human infectious disease with a high mortality rate in many tropical countries, is caused by the pathogen Burkholderia pseudomallei (B. pseudomallei). The function of the B. pseudomallei sigma S (RpoS) transcription factor in survival during the stationary growth phase and conditions of oxidative stress is well documented. Besides the rpoS, bioinformatics analysis of B. pseudomallei genome showed the existence of two rpoN genes, named rpoN1 and rpoN2. In this study, by using the mouse macrophage cell line RAW264.7 as a model of infection, the involvement of B. pseudomallei RpoS and RpoN2 in the invasion, intracellular survival leading to the reduction in multinucleated giant cell (MNGC) formation of RAW264.7 cell line were illustrated. We have demonstrated that the MNGC formation of RAW264.7 cell was dependent on a certain number of intracellular bacteria (at least 5 × 104). In addition, the same MNGC formation (15%) observed in RAW264.7 cells infected with either B. pseudomallei wild type with multiplicity of infection (MOI) 2 or RpoN2 mutant (∆rpoN2) with MOI 10 or RpoS mutant (∆rpoS) with MOI 100. The role of B. pseudomallei RpoS and RpoN2 in the regulation of type III secretion system on bipB-bipC gene expression was also illustrated in this study.

The neuroprotective potential of curcumin on T. Spiralis infected mice

BackgroundTrichinella spiralis can affect the brain by inducing inflammatory and vascular changes. Drug management with the antiparasitic drug albendazole can be enhanced by natural compounds such as curcumin. The potential benefit of curcumin as an adjuvant to albendazole in the management of cerebral affection during experimental T. spiralis infection was evaluated. Animals received either curcumin 150 mg/Kg, albendazole 50 mg/Kg or a combination of both drugs. Animal groups receiving treatment were compared with infected and non-infected control groups. Blood levels of reduced glutathione (GSH) and dopamine were measured, and brain tissue expression of cyclooxygenase-2 enzyme (COX-2) and CD34 was assessed by immunohistochemistry.ResultsT. spiralis infection resulted in a state of oxidative stress, which was improved by albendazole and curcumin. Also, both drugs restored the peripheral dopamine level, which was decreased in infected non-treated mice. Curcumin was also found to be efficient in improving brain pathology and reducing local COX-2 and CD 34 expression.ConclusionsInflammatory and pathological changes during neurotrichinosis can be improved by the addition of curcumin to conventional anti-parasitic drugs.

Shengjihuayu formula ameliorates the oxidative injury in human keratinocytes via blocking JNK/c-Jun/MMPs signaling pathway

Ethnopharmacological relevanceThe reactive oxygen species (ROS) surge in the chronic wound tissue of diabetic ulcers (DUs) aggravates the inflammatory response. The oxidative stress state during inflammation will exacerbate inflammation and cause tissue damage, resulting in prolonged wound healing. Shengjihuayu Formula (SJHYF) is a renowned Chinese medicine prescription for treating chronic wounds in diabetic ulcers. Growing clinical evidence has demonstrated that SJHYF exhibits superior therapeutic efficacy and has a favorable safety profile. However, the underlying mechanisms by which SJHYF ameliorates oxidative damage under pathological conditions of DUs remain unclear. ObjectiveTo investigate the cytoprotective properties of SJHYF on hydrogen peroxide (H2O2)-induced cell damage in human HaCaT keratinocytes and to explore its potential targets and molecular pathways in treating DUs using RNA-seq. MethodsHaCaT cells were incubated with H2O2 for 24 h to construct an oxidative stress cell model. Cell viability and proliferation were measured using the MTT and EdU assays, respectively. Cell migration was assessed using the scratch assay, and the fluorescence intensity of ROS was measured using the DCFH-DA probe. The chemical components of SJHYF were analyzed by UPLC-Q-TOF/MS, while the therapeutic effects of SJHYF on H2O2-induced HaCaT cells were analyzed using RNA-Seq. The potential target genes were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). At the same time, the pathway phenotype expression of SJHYF on the protection of H2O2-induced HaCaT cells was explored using Western Blot. ResultsThe application of SJHY at a concentration of 0.25 mg/mL promoted cell proliferation, cell migration, and reduced ROS production. In addition, SJHYF was detected to have a total of 93 active compounds, including key components such as Galloyl-beta-D-glucose, Danshensu, Procyanidin B2, Catechin, and Alkannin. The RNA-seq analysis identified several core targets namely KRT17, TGM1, JUNB, PRDX5, TXNIP, PRDX1, HSP90AA1, HSP90AB1, HSPA8, and TNF-α. Western blot revealed the presence of the JNK/c-Jun/MMPs pathway and its related transcription factors. ConclusionSJHYF displays significant protective effects on H2O2-induced oxidative cell damage in HaCaT cells via blocking the JNK/c-Jun/MMPs pathway.

ROS Scavenging Effect of Selected Isoflavones in Provoked Oxidative Stress Conditions in Human Skin Fibroblasts and Keratinocytes.

Isoflavones, belonging to polyphenolic compounds, show structural similarity to natural estrogens, and in this context, they have been extensively studied. Some of them are also applied as cosmetic additives; however, little is known regarding their effects on skin cells. In this investigation, common isoflavones, including genistein, daidzein, glycitein, formononetin, and biochanin A, as well as coumestrol, were evaluated for antioxidant activity and their impact on human skin fibroblasts and keratinocytes. Antioxidant effects were assessed using DPPH, ABTS, and FRAP tests, and the ability to scavenge reactive oxygen species (ROS) was tested in cells with H2O2-provoked oxidative stress. The impact on the activity of antioxidant enzymes (SOD, CAT, GSH) and lipid peroxidation (MDA) was also explored. As shown by Alamar Blue and neutral red uptake assays, the compounds were not toxic within the tested concentration range, and formononetin and coumestrol even demonstrated a stimulatory effect on cells. Coumestrol and biochanin A demonstrated significant antioxidative potential, leading to a significant decrease in ROS in the cells stimulated by H2O2. Furthermore, they influenced enzyme activity, preventing depletion during induced oxidative stress, and also reduced MDA levels, demonstrating protection against lipid peroxidation. In turn, genistein, daidzein, and glycitein exhibited low antioxidant capacity.

Oxidative Stress and Acrosomal Status of Human Spermatozoa Subjected to Hydrophobic Carbon Soot Treatments.

The fourth industrial revolution extensively reshapes the reality we are living in by blurring the boundaries of physical, digital and biological worlds. A good example is the previously unthinkable incursion of nanoscale waste materials, such as soot, into the technologies for assisted reproduction. Although the rapeseed oil soot may efficiently enhance the progressive motility of human spermatozoa, it is yet unknown whether this material induces undesirable oxidative stress and premature acrosome reaction, endangering the sperm-oocyte fusion and blastocyst formation. In an attempt to clarify this issue, we reveal that the three-hour incubation of human semen mixed with three main types of soot does not cause oxidative stress and spontaneous acrosome reaction of the sperm. These unique findings are attributed to synchronous elimination and stabilization of the oxidants via hydrogen bonding to the acidic groups of the soot (i.e., C=O and/or C-O-C) and electron donation by its basic chemical sites (i.e., C-OH and/or COOH). Moreover, the soot nanoparticles are electrostatically attracted by discrete positively charged areas on the sperm head, increasing its negative charge and in some cases interfering the acrosome reaction. Such novel mechanistic insights emphasize the credibility of rapeseed oil soot to confidently shift from the purely diagnostic and therapeutic phases in reproductive medicine to research dealing with the effect of carbon nanomaterials on the embryo development and implantation.

Relative quantitation of chiral thiol compounds labeled based on isotope novel mass spectrometry probes: Monitoring of the dynamic changes of chiral thiol compounds in human urine during normal, exercise, and rest recovery states

Monitoring changes in the content of chiral thiol compounds in the human body is crucial for the early diagnosis of oxidative stress-related diseases and the exploration of their pathogenesis. To address this, we synthesized a novel isotope mass spectrometry (MS) probe, denoted as (R)-(5-(3-isothiocyanato (13C) pyrrolidin-1-yl)-5-oxopentyl) triphenylphosphonium (N13CS-OTPP), with triphenylphosphine as its parent structure. In this study, we established a new ultra-high-performance liquid chromatography high-resolution mass spectrometry (UHPLCHRMS) relative quantitative method to monitor chiral thiol compounds in human urine under varying oxidative stress conditions. This method relies on the ratio of 12C/13C isotope-labeled peak areas. To assess the chiral separation efficiency of N13CS-OTPP, we employed three types of thiol compounds (D/L-GSH, D/L-Cys, and D/L-Hcy) and observed separation degrees (Rs) ranging from 1.82 to 1.89. We further validated the accuracy and feasibility of our relative quantitative methods using D/L-Cys-as a model compound. N12C/13CS-OTPP-Cys-exhibited excellent linearity (R2 = 0.9993–0.9994) across different molar ratios (D/L-Cys = 10:1, 4:1, 2:1, 1:1, 1:2, 1:4, 1:10) and achieved a low limit of detection (LOD) of 2.5 fmol. Additionally, we monitored the dynamic changes in urine D/L-Cys-and D/L-Hcy ratios in 12 healthy volunteers (six males and six females) under various oxidative stress states. We generated fitting curves and investigated the trends in chiral thiol compounds in vivo. This study introduces a novel method for the relative quantitative monitoring of chiral thiol compounds in different oxidative stress states within the human body. It also presents a new strategy for understanding the pathogenesis of related diseases resulting from the abnormal metabolism of thiol compounds.

An Overview of Therapeutic Targeting of Nrf2 Signaling Pathway in Rheumatoid Arthritis.

Rheumatoid arthritis (RA), an autoimmune condition that has a significant inflammatory component and is exacerbated by dysregulated redox-dependent signaling pathways. In RA, the corelationship between oxidative stress and inflammation appears to be regulated by the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Furthermore, it has been shown that transcriptional pathways involving Nrf2 and NFκB significantly interact under conditions of oxidative stress and inflammation. Because pathologic cells in RA have a higher chance of surviving, Nrf2's influence on concomitant pathologic mechanisms in the disease is explained by its interaction with key redox-sensitive inflammatory pathways. The current review not only updates knowledge about Nrf2's function in RA but also highlights the complex interactions between Nrf2 and other redox-sensitive transcription factors, which are essential to the self-sustaining inflammatory processes that define RA. This paper also reviews the candidates for treating RA through Nrf2 activation. Finally, future directions for pharmacologic Nrf2 activation in RA are suggested.

Alginate oligosaccharides exert protective effects on hydrogen peroxide-induced senescence in H9C2 cardiomyocytes by regulating the redox state of cells.

Aging is a known independent risk factor for several cardiovascular diseases. Here, we evaluated potential effects and possible mechanisms through which alginate oligosaccharides (AOS) affect hydrogen peroxide (H2O2)-induced senescence in H9C2 cardiomyocytes. A series of AOS molecules, including oligoM, oligoG, M-5, and G-5, were investigated. AOS significantly decreased SA-β-gal and DAPI-stained positive cells, downregulated p53 and p21 (aging-related markers) expression, and eventually protected H9C2 cells from H2O2-induced senescence. AOS decreased reactive oxygen species and malondialdehyde production, recovered mitochondrial function, and alleviated the oxidative stress state by regulating PGC-1α and NADPH oxidase subunit expression. Furthermore, AOS treatment restored the expression of antioxidant enzymes in senescent H9C2 cells. Thus, our results show in vitro evidence that AOS alleviate senescence in H9C2 cells by regulating the redox state; thus, AOS may be an effective therapeutic agent that could protect against cardiomyocyte senescence.

Anti-Apoptotic and Anti-Inflammatory Properties of Grapefruit IntegroPectin on Human Microglial HMC3 Cell Line.

In this study, we investigated the beneficial effects of grapefruit IntegroPectin, derived from industrial waste grapefruit peels via hydrodynamic cavitation, on microglia cells exposed to oxidative stress conditions. Grapefruit IntegroPectin fully counteracted cell death and the apoptotic process induced by cell exposure to tert-butyl hydroperoxide (TBH), a powerful hydroperoxide. The protective effects of the grapefruit IntegroPectin were accompanied with a decrease in the amount of ROS, and were strictly dependent on the activation of the phosphoinositide 3-kinase (PI3K)/Akt cascade. Finally, IntegroPectin treatment inhibited the neuroinflammatory response and the basal microglia activation by down-regulating the PI3K- nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)- inducible nitric oxide synthase (iNOS) cascade. These data strongly support further investigations aimed at exploring IntegroPectin's therapeutic role in in vivo models of neurodegenerative disorders, characterized by a combination of chronic neurodegeneration, oxidative stress and neuroinflammation.

Nitric oxide-releasing multifunctional catechol-modified chitosan/oxidized dextran hydrogel with antibacterial, antioxidant, and pro-angiogenic properties for MRSA-infected diabetic wound healing

The study presents a multifunctional catechol-modified chitosan (Chi-Ca)/oxidized dextran (Dex-CHO) hydrogel (CDP-PB) that possesses antibacterial, antioxidant, and pro-angiogenic properties, aimed at improving the healing of diabetic wounds. The achievement of the as-prepared CDP-PB hydrogel with superb antibacterial property (99.9 %) can be realized through the synergistic effect of phenylboronic acid-modified polyethyleneimine (PEI-PBA) and photothermal therapy (PTT) of polydopamine nanoparticles loaded with the nitric oxide (NO) donor BNN6 (PDA@BNN6). Notably, CDP-PB hydrogel achieves ∼3.6 log10 CFU/mL MRSA of inactivation efficiency under 808 nm NIR laser irradiation. In order to mitigate oxidative stress, the Chi-Ca was synthesized and afterward subjected to a reaction with Dex-CHO via a Schiff-base reaction. The catechol-containing hydrogel demonstrated its effectiveness in scavenging DPPH, •OH, and ABTS radicals (> 85 %). In addition, the cellular experiment illustrates the increased migration and proliferation of cells by the treatment of CDP-PB hydrogel in the presence of oxidative stress conditions. Moreover, the findings from the animal model experiments provide evidence that the CDP-PB hydrogel exhibited efficacy in the eradication of wound infection, facilitation of angiogenesis, stimulation of granulation, and augmentation of collagen deposition. These results indicate the potential of the CDP-PB hydrogel for use in clinical applications.

Understanding fenpropathrin-induced pulmonary toxicity: What apoptosis, inflammation, and pyreptosis reveal analyzing cross-links at the molecular, immunohistochemical, and immunofluorescent levels

Fenpropathrin (FN), a pyrethroid has been linked to potential pulmonary toxic effects to humans via incident direct or indirect ingestion. Thus, we aimed to the investigate the underlying mechanisms of lung toxicity upon exposure to FN in the rat model, besides studying whether curcumin (CCM) and curcumin-loaded chitosan nanoformulation (CCM-Chs) can mitigate FN-induced lung damage. Six distinct groups, namely, control, CCM, CCM-Chs, FN, and CCM + FN, CCM-Chs + FN were assigned separately. The inflammatory, apoptotic, and oxidative stress states, histological, immunohistochemical, and immunofluorescence examination of different markers within the pulmonary tissue were applied. The results revealed that the FN-induced tissue damage might be caused by the oxidative stress induction and depressed antioxidant glutathione system in the lungs of rats. Furthermore, FN upregulated the expression of genes related to inflammation, and pyroptosis, and elevated the immunoreactivity of Caspase-3, tumor necrosis factor-α, vimentin, and 4-Hydroxynonenal in pulmonary tissues of FN-exposed rats compared to the control. CCM and CCM-Chs mitigated the FN-induced disturbances, while remarkably, CCM-Chs showed better potency than CCM in mitigating the FN-induced toxicity. In conclusion, this study shows the prominent preventive ability of CCM-Chs more than CCM in combatting the pulmonary toxicity induced by FN. This may be beneficial in developing therapeutic and preventive strategies against FN-induced pulmonary toxicity.

Mitigating alcohol-induced neurohepatotoxicity in male albino rats with avocado and mustard

Alcohol abuse is dangerous to one’s health and contributes to disorders such as neurotoxicity and hepatotoxicity worldwide. Twenty-five male albino rats, each weighing 200 ± 10 g, were divided into five groups. For 4 weeks, rats in the control group were given only a regular chow diet and ad libitum. Rats in the alcohol group received an oral gavage of alcohol at a dose of 40 mg/kg body weight each day. Rats in the alcohol and avocado extract group received oral gavage doses of 250 mg/kg b. wt./day of avocado extract and 40 mg/kg b. wt. of alcohol. Rats in the alcohol and mustard seed extract group received oral gavage doses of 250 mg/kg/day of mustard seed extract and 40 mg/kg/day of alcohol, respectively. Rats were given alcohol and a mixture of avocado and mustard seed extract at a dose of 250 mg/kg body weight each day by oral gavage for 4 weeks. Our results showed increased levels of hydrogen peroxide (H2O2) and lipid peroxidation in the liver and brain tissues, decreased glutathione content, glutathione peroxidase, superoxide dismutase, catalase, and glutathione-S-transferase. In rats consumed excessive alcohol, there was an increase in the activity of the tumor marker α-l-fucosidase in sera. Additionally, the liver and brain tissues of the alcoholic group showed decreased cytochrome c oxidase activity. Furthermore, changes in the expression levels of the genes for brain α-secretase and liver alcohol dehydrogenase (ADH) were observed. The administration of extracts from avocado and mustard seeds improved the state of oxidative stress and restored antioxidant enzyme activity. The expression levels of brain α-secretase and liver ADH genes were almost fully recovered at the molecular level.

Duodenal-jejunal bypass improves hypothalamic oxidative stress and inflammation in diabetic rats via glucagon-like peptide 1-mediated Nrf2/HO-1 signaling.

Type 2 diabetes mellitus (T2DM) is often accompanied by impaired glucose utilization in the brain, leading to oxidative stress, neuronal cell injury and infla-mmation. Previous studies have shown that duodenal jejunal bypass (DJB) surgery significantly improves brain glucose metabolism in T2DM rats, the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain unclear. To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats. A T2DM rat model was induced via a high-glucose and high-fat diet, combined with a low-dose streptozotocin injection. T2DM rats were divided into DJB operation and Sham operation groups. DJB surgical intervention was carried out on T2DM rats. The differential expression of hypothalamic proteins was analyzed using quantitative proteomics analysis. Proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry, quantitative real-time PCR, Western blotting, and immunofluorescence. Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress, inflammation, and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery, compared to the T2DM-Sham groups of rats. Oxidative stress-related proteins (glucagon-like peptide 1 receptor, Nrf2, and HO-1) were significantly increased (P < 0.05) in the hypothalamus of rats with T2DM after DJB surgery. DJB surgery significantly reduced (P < 0.05) hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin (IL)-1β and IL-6. DJB surgery significantly reduced (P < 0.05) the expression of factors related to neuronal injury (glial fibrillary acidic protein and Caspase-3) in the hypothalamus of T2DM rats and upregulated (P < 0.05) the expression of neuroprotective factors (C-fos, Ki67, Bcl-2, and BDNF), thereby reducing hypothalamic injury in T2DM rats. DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the glucagon-like peptide 1 receptor-mediated Nrf2/HO-1 signaling pathway.

Comparing the effect of intravenous versus intracranial grafting of mesenchymal stem cells against parkinsonism in a rat model: Behavioral, biochemical, pathological and immunohistochemical studies.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases worldwide. Currently applied therapeutic protocols are limited to improve the motor functions of patients. Therefore, seeking alternative regimes with better therapeutic impact is crucial. This study aims to validate the therapeutic impact of mesenchymal stem cell injection using two delivery methods, intracranial administration and intravenous administration, on rotenone (ROT)-induced PD model in rats. Our work included behavioral, biochemical, histological, and molecular investigations. Open field test (OFT) and rotarod tests were applied. Important oxidative stress, antioxidant and proinflammatory markers were monitored. Substantia Nigra and Striatum tissues were examined histologically and the molecular expression of DOPA decarboxylase, Tyrosine hydroxylase, and α-synuclein in neurons in these tissues were investigated. Our results showed that MSC grafting improved motor and memory impairments and oxidative stress status that were observed after ROT administration. Additionally, BM-MSCs application restored SOD and CAT activities and the levels of DA, L-Dopa, IL6, IL1β, and TNFα. Moreover, MSC grafting overwhelmed the pathological changes induced by ROT and normalized the expression of Tyrosine hydroxylase, DOPA decarboxylase, and α-synuclein towards the control values in the Nigral and Striatal tissues of male rats. Conclusively, both administration routes improved motor function, protection of the nigrostriatal system, and improved striatal dopamine release. The observed beneficial effect of applying MSCs suggests potential benefits in clinical applications. No significant differences in the outcomes of the treatment would favor a certain way of MSC application over the other. However, the intravenous delivery method seems to be safer and more feasible compared to the intrastriatal method.

Method validation and characterization of stress degradation products of azelastine hydrochloride using LC-UV/PDA and LC-Q/TOF-MS studies.

Azelastine HCl is a second-generation H1 -receptor antagonist approved by the US Food and Drug Administration (US FDA) for treating seasonal allergic rhinitis and non-allergic vasomotor rhinitis. This study encompasses the validation of a liquid chromatography-ultra violet photo diode array (LC-UV/PDA) method for the drug and its extension to liquid chromatography/quadrupole time-of-flightmassspectrometry (LC-Q/TOF-MS) studies for identification and characterization of various stress degradation products of the drug. Stress degradation of azelastine HCl was undertaken under the International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) prescribed conditions of hydrolytic, photolytic, oxidative, and thermal stress. The degraded drug solutions were analyzed using Ultra Performance Liquid Chromatography (UPLC) employing a C18 (100 × 4.6mm; 2.6μ, Kinetex) column by isocratic elution. Detection wavelength was 241 nm. The degradation products were identified and characterized using UPLC-MS/TOF studies, and an attempt was made to isolate one of the degradation products by solvent extraction. The drug was found to significantly degrade under acidic/alkaline/neutral photolytic, oxidative, and alkaline hydrolytic conditions. Six degradation products (I-VI) were identified through LC-Q/TOF-MS studies that were adequately resolved from the drug with the developed UPLC method. All degradation products (I-VI) were ionized in the total ion chromatogram (TIC) in the LC-MS studies, and these were identified and characterized, and the degradation pathway of the drug was postulated. One of the oxidation products isolated from the degraded drug solution was characterized through differential scanning calorimetry, Fourier-transform infrared spectroscopy, and nuclear magnetic resonance spectral data. Six degradation products generated from stress degradation studies on azelastine HCl were adequately resolved through LC-UV/PDA studies followed by method validation. These were successfully identified and characterized through LC-Q/TOF-MS studies, and the degradation pathways for the generation of these products from the drug have been postulated.

Apakah Kadar Asam Urat Menyebabkan Berkembangnya Prehipertensi Menjadi Hipertensi?

Hypertension is a health problem that continues to increase in prevalence. Several studies showed that hypertension is related to conditions of oxidative stress which can be caused by increased levels of uric acid in the blood. The aim of this study was to analyze the role of uric acid levels in the development of blood pressure from prehypertension to hypertension. This study is a literature review of the results from cohort studies related to the relationship between serum uric acid levels on the development of prehypertension to hypertension.This study was based on the results of the identification from articles in the Google Scholar with the search keywords “Uric acid serum predict prehypertension to hypertension cohort” with inclusion criteria such as full text in PDF format, english, and span of the last ten years (2013-2023). There were 3 international journal articles which showed that increased uric acid levels could affect the development of prehypertension blood pressure into hypertension. Blood pressure belonging to prehypertension with hyperuricemia had a greater incidence of hypertension than the group without hyperuricemia (P&lt;0,001). Prehypertension accompanied by hyperuricemia had a 2 times greater risk of developing hypertension within 2 years (OR, 2.02; P&lt;0,05). Increased uric acid levels that occured over time also predicted the development of the prehypertensive blood pressure category to become hypertension independently (OR, 1.41 ; P&lt;0,0001). Based on the results of the literature review, it was concluded that high serum uric acid levels or hyperuricemia is a risk factor for the development of prehypertension to hypertension.