Extracellular Oxidative Stress Research Articles

Ecotoxicity of as-synthesised copper nanoparticles on soil bacteria.

Release of metallic nanoparticles in soil poses a serious threat to the ecosystem as they can affect the soil properties and impose toxicity on soil microbes that are involved in the biogeochemical cycling. In this work, in vitro ecotoxicity of as‐synthesised copper nanoparticles (CuNPs) on Bacillus subtilis (MTCC No. 441) and Pseudomonas fluorescens (MTCC No. 1749), which are commonly present in soil was investigated. Three sets of colloidal CuNPs with identical physical properties were synthesised by chemical reduction method with per batch yield of 0.2, 0.3 and 0.4 gm. Toxicity of CuNPs against these soil bacteria was investigated by MIC (minimum inhibitory concentration), MBC (minimum bactericidal concentration), cytoplasmic leakage and ROS (reactive oxygen species) assay. MIC of CuNPs were in the range of 35–60 µg/ml and 35–55 µg/ml for B. subtilis and P. fluorescens respectively, while their MBC ranged from 40–70 µg/ml and 40–60 µg/ml respectively. MIC and MBC tests reveal that Gram‐negative P. fluorescens was more sensitive to CuNPs as compared to Gram positive B. subtilis mainly due to the differences in their cell wall structure and composition. CuNPs with smaller hydrodynamic size (11.34 nm) were highly toxic as revealed by MIC, MBC tests, cytoplasmic leakage and ROS assays, which may be due to the higher active surface area of CuNPs and greater membrane penetration. Leakage of cytoplasmic components and generation of extra‐cellular oxidative stress by reactive oxygen species (ROS) causes cell death. The present study realizes in gauging the negative impact of inadvertent release of nanoparticles in the environment, however, in situ experiments to know its overall impact on soil health and soil microflora can help in finding solution to combat ecotoxicity of nanoparticles.

Citrullination of histones decreases extracellular histones-mediated oxidative stress, cell death, and vascular dysfunction in endothelial cells

Citrullination of histones decreases extracellular histones-mediated oxidative stress, cell death, and vascular dysfunction in endothelial cells

Knockdown of plasmacytoma variant translocation 1 (PVT1) inhibits high glucose-induced proliferation and renal fibrosis in HRMCs by regulating miR-23b-3p/early growth response factor 1 (EGR1)

Long noncoding RNAs (lncRNAs) have been reported to play critical role in the development of diabetic nephropathy (DN). However, the effects and mechanism of plasmacytoma variant translocation 1 (PVT1) remain poorly understood. The expression of PVT1, miR-23b-3p, early growth response factor 1 (EGR1), Fibronectin (FN), Collagen IV (Col IV), alpha smooth muscle actin (α-SMA), E-cadherin, and vimentin, transforming growth factor (TGF)-β1 was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed by Cell Counting-8 (CCK-8) assay. Western blot assay was conducted to measure the protein levels of FN, Col IV, E-cadherin, α-SMA, vimentin, TGF-β1, and EGR1. The interaction between miR-23b-3p and PVT1 or EGR1 was predicted by starBase or TargetScan and confirmed by the dual luciferase reporter assay. The oxidative stress factors were analyzed by corresponding kits. We found that the expression of PVT1 and EGR1 was increased and miR-23b-3p was decreased in serum samples of DN patients and HG-induced HRMCs. Knockdown of PVT1 significantly inhibited HG-induced proliferation, extracellular matrix (ECM) accumulation, epithelial-mesenchymal transition (EMT), and oxidative stress in HRMCs, while these effects were abated by inhibiting miR-23b-3p. In addition, EGR1 was confirmed as downstream target of miR-23b-3p and miR-23b-3p could specially bind to PVT1. Besides, downregulation of PVT1 inhibited the progression of DN partially via upregulating miR-23b-3p and downregulating EGR1. In conclusion, our results suggested that PVT1 knockdown suppressed DN progression though functioning as ceRNA of miR-23b-3p to regulate EGR1 expression in vitro, providing potential value for the treatment of DN.

Dual-Responsive and Deep-Penetrating Nanomicelles for Tumor Therapy via Extracellular Matrix Degradation and Oxidative Stress.

Tumor microenvironment (TME), with complex composition, plays a vital role in the occurrence, development, and metastasis of tumors. TME becomes an important obstacle to the accessibility of nanotherapy, thus indicating the need to improve the functional design to overcome this challenge. In this study, we generate an intelligent nano-drug-delivery system (DOX@PssP-Hh NPs) with dual environmental response, which involves heparanase (HPSE) in TME and glutathione (GSH) in tumor cells. The nanosystem consists of a nanoskeleton formed by self-assembly of mPEG-ss-PEI and α-CD (PssP), chemotherapy drug doxorubicin (DOX) for enhancing antitumor efficacy, together with hyaluronidase (HAase), which is designed to degrade extracellular matrix to increase drug penetration, and an outer shell of heparin. Through the process of "responsive disintegration-remodeling tumor microenvironment-enhancing drug penetration-inducing oxidative stress", the semi-rotaxaneself-assembled nanomicelles were constructed to achieve the progressive function. DOX@PssP-Hh NPs with the size of 81.85 ± 1.85 nm exhibited satisfactory cytotoxicity (IC50 = 0.80 ± 0.33 μg/mL). With the disulfide bond-mediated GSH depletion and DOX-mediated reactive oxygen species (ROS) production, treatment with DOX@PssP-Hh NPs prominently reduced glutathione peroxidase 4 (GPX4) level and would lead to enhanced oxidative stresses. Hyaluronic acid (HA), collagen I, and α-smooth muscle actin (α-SMA) were significantly reduced for TME remodulation. Moreover, the antitumor effect in vivo implied that DOX@PssP-Hh NPs could inhibit tumor growth effectively and reduce tumor interstitial fluid pressure (IFP) evidently. In conclusion, DOX@PssP-Hh NPs improved the penetration of drugs and exhibited enhanced antitumor efficacy.

Integrated Transcriptomic and Proteomic Analyses Reveal the Role of NprR in Bacillus anthracis Extracellular Protease Expression Regulation and Oxidative Stress Responses.

NprR is a protein of Bacillus anthracis that exhibits moonlighting functions as either a phosphatase or a neutral protease regulator that belongs to the RNPP family. We previously observed that the extracellular protease activity of an nprR deletion mutant significantly decreased within in vitro cultures. To identify the genes within the regulatory network of nprR that contribute to its protease activity, integrated transcriptomic and proteomic analyses were conducted here by comparing the nprR deletion mutant and parent strains. A total of 366 differentially expressed genes (DEGs) between the strains were observed via RNA-seq analysis. In addition, label-free LC-MS/MS analysis revealed 503 differentially expressed proteins (DEPs) within the intracellular protein fraction and 213 extracellular DEPs with significant expressional differences between the strains. The majority of DEGs and DEPs were involved in environmental information processing and metabolism. Integrated transcriptomic and proteomic analyses indicated that oxidation-reduction-related GO terms for intracellular DEPs and endopeptidase-related GO terms for extracellular DEPs were significantly enriched in the mutant strain. Notably, many genes involved in protease activity were largely downregulated in the nprR deletion mutant cultures. Moreover, western blot analysis revealed that the major extracellular neutral protease Npr599 was barely expressed in the nprR deletion mutant strain. The mutant also exhibited impaired degradation of protective antigen, which is a major B. anthracis toxin component, thereby resulting in higher protein yields. Concomitantly, another global transcriptional regulator, SpxA1, was also dramatically downregulated in the nprR deletion mutant, resulting in higher sensitivity to oxidative and disulfide stress. These data consequently indicate that NprR is a transcriptional regulator that controls genes whose products function as extracellular proteases and also is involved in oxidative stress responses. This study thus contributes to a more comprehensive understanding of the biological function of NprR, and especially in the middle growth stages of B. anthracis.

English

BACKGROUND Kidneys are vital organs for excretory and many other biochemical functions in the human body. Most chronic diseases end up damaging the kidneys, acute to chronic, based on the cause and duration. Chronic kidney disease is a sequence of damages to the renal cells and parenchyma leading to progressive deterioration of kidney function, which eventually develops into terminal stage of chronic kidney failure. Chronic renal failure leads to a pro-oxidant state, which leads to damage to the renal cells and parenchyma and the amount of intracellular oxidative stress or extracellular oxidative stress has a relation to the severity of renal failure either directly or indirectly. The study aimed to find the correlation between high sensitivity c-reactive protein (hs-CRP) to lipid peroxidation product, malondialdehyde (MDA). METHODS This prospective study was designed and conducted from January 2018 to December 2019 in the Department of Biochemistry, Government Medical College, Ananthapuramu. The study comprised a total of 70 subjects in the age group of 35 - 65 years. The subjects of the approved study plan were divided into two groups; 35 subjects were healthy controls (group-1), and 35 subjects were chronic renal failure (CRF) patients. A blood sample was collected in Government General Hospital, Anantapuramu. RESULTS The sample was analysed for estimation of blood urea, plasma glucose, serum creatinine, Malondialdehyde (MDA) and C-reactive protein (CRP). The mean value of blood urea, serum creatinine, serum hs-CRP, serum MDA was higher in CRF (group-2) patients when compared to healthy controls (group-1) (p < 0.0001). We observed a positive correlation between serum MDA and serum creatinine (r = 0.46832), hs-CRP (r = 0.0234). CONCLUSIONS In CRF, oxidative stress is obviously evident, but the inflammation induced oxidative stress which can be corrected if detected early will reduce oxidative damage. Our study shows that there is an elevation in hs-CRP and MDA which confirms the presence of oxidative damage, inflammation and probably inflammation induced oxidative damage. KEYWORDS CRF, Oxidative Stress, MDA, Serum Creatinine, hs-CRP

Neutrophil Extracellular Traps Increase Airway Mucus Viscoelasticity and Slow Mucus Particle Transit.

Mucus obstruction is a key feature of many inflammatory airway diseases. Neutrophil extracellular traps (NETs) are released upon neutrophil stimulation and consist of extracellular chromatin networks studded with cytotoxic proteins. When released in the airways, these NETs can become part of the airway mucus. We hypothesized that the extracellular DNA and/or oxidative stress (e.g., by the release of reactive oxygen species and myeloperoxidase during NETs formation in the airways) would increase mucus viscoelasticity. We collected human airway mucus from endotracheal tubes of healthy patients admitted for elective surgery and coincubated these samples with NETs from phorbol 12-myristate 13-acetate-stimulated neutrophils. Unstimulated neutrophils served as controls, and blocking experiments were performed with dornase alfa for extracellular DNA and the free radical scavenger dimethylthiourea for oxidation. Compared with controls, the coincubation of mucus with NETs resulted in 1) significantly increased mucus viscoelasticity (macrorheology) and 2) significantly decreased mesh pore size of the mucus and decreased movement of muco-inert nanoparticles through the mucus (microrheology), but 3) NETs did not cause visible changes in the microstructure of the mucus by scanning EM. Incubation with either dornase alfa or dimethylthiourea attenuated the observed changes in macrorheology and microrheology. This suggests that the release of NETs may contribute to airway mucus obstruction by increasing mucus viscoelasticity and that this effect is not solely due to the release of DNA but may in part be due to oxidative stress.

Quantitative Proteome of Infant Stenotic Ureters Reveals Extracellular Matrix Organization and Oxidative Stress Dysregulation Underlying Ureteropelvic Junction Obstruction.

Ureteropelvic junction obstruction (UPJO) is the most frequent cause of congenital hydronephrosis in child. To better investigate the molecular mechanisms of this pathological process, the stenotic ureter proteome of UPJO in infants is compared with their own normal pre-stenotic segments. Data independent acquisition-based proteomics are performed to compare proteome between pre-stenotic and stenotic ureter from nine UPJO infants. Gene ontology analysis, hierarchical cluster analysis, and network interaction are performed to characterize biological functions of significantly altered proteins. Selected significantly altered proteins are validated by western blot on another three UPJO infants. 15 proteins are up-regulated and 33 proteins are down-regulated during stenotic pathology. Significantly altered proteins are involved in decreased extracellular matrix and cytoskeleton organization, increased regulation of oxidative activity, and altered inflammatory associated exocytosis. Significant expression of biglycan, fibulin-1, myosin-10, cytochrome b5 are validated providing possible mechanism in UPJO which could be associated impaired smooth muscle cell, epithelial integrity, and increased oxidative stress. CONCLUSIONS AND CLINICALRELEVANCE: This study provides molecular evidence of dysregulated extracellular matrix organization, impaired smooth muscle cell, and oxidative stress during UPJO pathology, indicating that biglycan, fibulin-1, myosin-10, cytochrome b5 might reflect the pathology of UPJO.

A Multi-Omics Approach Identifies Key Regulatory Pathways Induced by Long-Term Zinc Supplementation in Human Primary Retinal Pigment Epithelium.

In age-related macular degeneration (AMD), both systemic and local zinc levels decline. Elevation of zinc in clinical studies delayed the progression to end-stage AMD. However, the molecular pathways underpinning this beneficial effect are not yet identified. In this study, we used differentiated primary human fetal retinal pigment epithelium (RPE) cultures and long-term zinc supplementation to carry out a combined transcriptome, proteome and secretome analysis from three genetically different human donors. After combining significant differences, we identified the complex molecular networks using Database for Annotation, Visualization and Integrated Discovery (DAVID) and Ingenuity Pathway Analysis (IPA). The cell cultures from the three donors showed extensive pigmentation, development of microvilli and basal infoldings and responded to zinc supplementation with an increase in transepithelial electrical resistance (TEER) (apical supplementation: 443.2 ± 79.3%, basal supplementation: 424.9 ± 116.8%, compared to control: 317.5 ± 98.2%). Significant changes were observed in the expression of 1044 genes, 151 cellular proteins and 124 secreted proteins. Gene set enrichment analysis revealed changes in specific molecular pathways related to cell adhesion/polarity, extracellular matrix organization, protein processing/transport, and oxidative stress response by zinc and identified a key upstream regulator effect similar to that of TGFB1.

Altered Gene Expression Profiles in the Lungs of Streptozotocin-induced Diabetic Mice.

Diabetes mellitus is a common heterogeneous metabolic disorder, characterized by deposition of extracellular matrix, oxidative stress, and vascular dysfunction, thereby leading to gradual loss of function in multiple organs. However, little attention has been paid to gene expression changes in the lung under hyperglycemic conditions. In this study, we found that diabetes inuced histological changes in the lung of streptozotocin-induced diabetic mice. Global gene expression profiling revealed a set of genes that are up- and down-regulated in the lung of diabetic mice. Among these, expression of Amigo2, Adrb2, and Zbtb16 were confirmed at the transcript level to correlate significantly with hyperglycemia in the lung. We further evaluated the effect of human umbilical cord-derived perivascular stem cells (PVCs) on these gene expression in the lung of diabetic mice. Our results show that administration of PVC-conditioned medium significantly suppressed Amig2, Adrb2, and Zbtb16 upregulation in these mice, suggesting that these genes may be useful indicators of lung injury during hyperglycemia. Furthermore, PVCs offer a promising alternative cell therapy for treating diabetic complications via regulation of gene expression.

Genetic and Epigenetic Mechanisms Underlying Vascular Smooth Muscle Cell Phenotypic Modulation in Abdominal Aortic Aneurysm.

Abdominal aortic aneurysm (AAA) refers to the localized dilatation of the infra-renal aorta, in which the diameter exceeds 3.0 cm. Loss of vascular smooth muscle cells, degradation of the extracellular matrix (ECM), vascular inflammation, and oxidative stress are hallmarks of AAA pathogenesis and contribute to the progressive thinning of the media and adventitia of the aortic wall. With increasing AAA diameter, and left untreated, aortic rupture ensues with high mortality. Collective evidence of recent genetic and epigenetic studies has shown that phenotypic modulation of smooth muscle cells (SMCs) towards dedifferentiation and proliferative state, which associate with the ECM remodeling of the vascular wall and accompanied with increased cell senescence and inflammation, is seen in in vitro and in vivo models of the disease. This review critically analyses existing publications on the genetic and epigenetic mechanisms implicated in the complex role of SMCs within the aortic wall in AAA formation and reflects the importance of SMCs plasticity in AAA formation. Although evidence from the wide variety of mouse models is convincing, how this knowledge is applied to human biology needs to be addressed urgently leveraging modern in vitro and in vivo experimental technology.

Enhancement of cell growth by uncoupling extracellular electron uptake and oxidative stress production in sediment sulfate-reducing bacteria

Microbial extracellular electron uptake (EEU) from solid electron donors has critical implications for microbial energy acquisition in energy-limited environments as well as electrochemical microbial technologies. Although EEU supplies sufficient energy to support cellular growth, additional soluble electron donors are required for most microbes to grow on electrode surfaces. Here, we demonstrated that the minimization of exogenous and endogenous oxidative stress greatly enhanced the growth rate of the sediment EEU-capable sulfate-reducing bacterium Desulfovibrio ferrophilus IS5 on an electrode without the addition of a soluble electron donor. Single-cell activity analysis by nanoscale secondary ion mass spectrometry showed that the metabolic activity of IS5 cells on the electrode was significantly enhanced following incubation in an H-type reactor, which was configured to reduce the exposure of cells to the potential oxidative stress source of the Pt counter electrode (CE). Additionally, the highest metabolic activity was observed at an electrode potential of −0.4 V (versus the standard hydrogen electrode), where electron uptake rate was not at peak. Compared to a single-chamber reactor, incubation in an H-type reactor at −0.4 V shortened the cell doubling time by 50-fold, which resulted in sufficient anabolism for cell replication (15N/Ntotal > 50%). The production of strongly oxidizing species at the CE was confirmed by X-ray photoelectron spectroscopy and inductively coupled plasma mass spectrometry analyses. Transcriptome analysis revealed overexpression of antioxidative genes in cells incubated at a potential with higher current production. These results suggested that higher levels of endogenous oxidative species were produced by a more reduced electron-transport chain from trace amounts of oxygen in the reactor, thereby lowering cell activity. In conclusion, EEU may enable sediment microbes to undergo enhanced cell growth and to find niches on minerals under anaerobic energy-limited conditions, where oxidative stress is much less likely to be present.

Semicarbazide-sensitive amine oxidase inhibition ameliorates albuminuria and glomerulosclerosis but does not improve tubulointerstitial fibrosis in diabetic nephropathy.

Semicarbazide-sensitive amine oxidase (SSAO) is an enzyme with a unique dual function in controlling inflammation as well as reactive oxygen species (ROS) generation. We have demonstrated benefit of SSAO inhibition in acute kidney fibrosis. However the function of SSAO in chronic kidney disease (CKD) and diabetic kidney disease (DKD) is yet to be determined. We aimed to assess the effectiveness of a SSAO inhibitor (SSAOi; PXS-4728A) as an antifibrotic agent using a diabetic model of CKD. Diabetic mice were treated with SSAOi for 24 weeks and outcomes compared with untreated diabetic mice and telmisartan treated animals as a standard of care comparator. Extracellular matrix markers, fibronectin and oxidative stress, were downregulated in diabetic mice treated with SSAOi compared with untreated diabetic mice. Expression of the pan-leukocyte marker CD45 was also supressed by SSAOi. SSAO inhibition in diabetic mice resulted in a significant reduction in glomerulosclerosis and associated albuminuria compared to untreated diabetic mice. However, the effect of SSAO inhibition was less obvious in the tubulointerstitial compartment than in the glomeruli. Therefore, SSAO may be a potential target for diabetic glomerulosclerosis.

EMT and EndMT: Emerging Roles in Age-Related Macular Degeneration.

Epithelial–mesenchymal transition (EMT) and endothelial–mesenchymal transition (EndMT) are physiological processes required for normal embryogenesis. However, these processes can be hijacked in pathological conditions to facilitate tissue fibrosis and cancer metastasis. In the eye, EMT and EndMT play key roles in the pathogenesis of subretinal fibrosis, the end-stage of age-related macular degeneration (AMD) that leads to profound and permanent vision loss. Predominant in subretinal fibrotic lesions are matrix-producing mesenchymal cells believed to originate from the retinal pigment epithelium (RPE) and/or choroidal endothelial cells (CECs) through EMT and EndMT, respectively. Recent evidence suggests that EMT of RPE may also be implicated during the early stages of AMD. Transforming growth factor-beta (TGFβ) is a key cytokine orchestrating both EMT and EndMT. Investigations in the molecular mechanisms underpinning EMT and EndMT in AMD have implicated a myriad of contributing factors including signaling pathways, extracellular matrix remodelling, oxidative stress, inflammation, autophagy, metabolism and mitochondrial dysfunction. Questions arise as to differences in the mesenchymal cells derived from these two processes and their distinct mechanistic contributions to the pathogenesis of AMD. Detailed discussion on the AMD microenvironment highlights the synergistic interactions between RPE and CECs that may augment the EMT and EndMT processes in vivo. Understanding the differential regulatory networks of EMT and EndMT and their contributions to both the dry and wet forms of AMD can aid the development of therapeutic strategies targeting both RPE and CECs to potentially reverse the aberrant cellular transdifferentiation processes, regenerate the retina and thus restore vision.

Attenuation of Oxidative Stress Contributes to Sex Differences in Renal Function between Adult Dahl S Rats

Hypertension is a major contributor to morbidity and mortality worldwide. In the United States, age‐matched prevalence of hypertension from 2015–2016 was 45.4%. Sex differences in hypertension are well established. Before 45 years of age, more men have hypertension than women, whereas after 65 years of age, more women have hypertension than men. However, many studies in hypertension show results only in male animals. This study uses male and female Dahl SS/jr rats to test the hypothesis that the ability to attenuate levels of oxidative stress in the kidney contributes to sex differences in renal injury and function. Male and female Dahl S rats were mated non‐consanguineously and offspring were weaned at four weeks of age. All animals in all studies were on a 0.3% NaCl diet, and measurements were made in offspring at three and six months of age. Systolic BP (n=6–10/group, tail cuff) at three and six months did not differ between sexes, although male animals did exhibit a significant increase over this period (3 months; male: 159±9 mmHg; female: 165±3 mmHg, p=0.6; 6 months; male: 180±4 mmHg; female: 173±12 mmHg, p=0.5). Urine was collected (n=7–20/group) for measurement of urinary protein (Bradford assay), nephrin, and kidney injury marker‐1 (KIM‐1). Females exhibited reduced renal injury at both three and six months of age as indicated by a significant reduction in both proteinuria (3 months, male: 102±8 mg/day; female: 55±5 mg/day, p<0.0001; 6 months, male: 238±25 mg/day; female: 44±7 mg/day, p=0.0001) and KIM‐1 (3 months, male: 24±2 ng/day; female: 18±2 ng/day, p=0.03; 6 months, male: 26±2 ng/day; female: 14±2 ng/day, p=0.001). Nephrin excretion was significantly lower in females at three months (Male: 107±13 ng/day; female: 59±6 ng/day, p=0.006), but this difference did not appear at six months of age (Male: 249±53 ng/day; female: 231±57 ng/day, p=0.8), suggesting that glomerular injury progressed in both sexes by this time. Targeted RNA sequencing was performed on RNA isolated from kidney using a custom renal injury/inflammation gene panel (n=32 genes), including Sod1, 2, and 3 genes. Females exhibited higher levels of the extracellular isoform Sod3 at three (male: 0.35±0.03 normalized CPM; female: 1.44±0.2, p=0.002) and six months (male: 0.41±0.05; female: 1.29±0.11, p=0.003). However, no significant differences were seen in expression of Sod1 or Sod2. Urinary TBARS was quantified as a measure of lipid peroxidation and was significantly lower in females at three months (Male: 65±3 μM/day; female: 44±4 μM/day, p=0.009), but a difference was not present at six months (Male: 91±16 μM/day; female: 77±12 μM/day, p=0.5). These data support the hypothesis that the ability to attenuate levels of extracellular oxidative stress in the kidney contributes to sex differences in renal injury and function.Support or Funding InformationThis research was supported by the National Institutes of Health under award numbers R01HL134711 (J.M. Sasser), F30DK118864 (H.R. Turbeville), and R01HL137673 (M.R. Garrett).

Antioxidant Graphene Oxide Nanoribbon as a Novel Whitening Agent Inhibits Microphthalmia-Associated Transcription Factor-Related Melanogenesis Mechanism.

In the melanin synthesis process, oxidative reactions play an essential role, and it is a good strategy to inhibit melanin production by reducing oxidative stress. Fullerene and its derivatives, or the complexes, were considered as strong free-radical scavengers, and we further applied multilayered sp2 nanocarbons to discover melanin synthesis inhibitory mechanisms. In the present study, we used novel nanomaterials, such as multiwalled carbon nanotubes (MWCNTs), short-type MWCNTs, graphene oxide nanoribbons (GONRs), and short-type GONRs, as anti-oxidative agents to regulate melanin production. The results showed that GONRs had better anti-oxidative capabilities in intracellular and extracellular oxidative stress analysis platforms than others. We proposed that GONRs have oxygen-containing functional groups. In the 2′,7′-dichlorodihydrofluorescein diacetate assay, we found out GONR could chelate metal ions to scavenge reactive oxygen species. In the molecular insight view, we observed that these nanomaterials downregulated the melanin synthesis by decreasing microphthalmia-associated transcription factor-related gene expressions, and there were similar consequences in protein expressions. To sum up, GONRs is a potential agent as a novel antioxidant and skin-whitening cosmetology material.

Ampelopsin inhibits high glucose-induced extracellular matrix accumulation and oxidative stress in mesangial cells through activating the Nrf2/HO-1 pathway.

Oxidative stress plays an important role in diabetic nephropathy (DN), which is a diabetic complication. Ampelopsin (AMP) is a natural flavonoid that has been found to possess antidiabetic and antioxidative activities. However, the effect of AMP on DN remains unclear. In this study, we aimed to evaluate the protective effect of AMP on glomerular mesangial cells (MCs) exposed to high glucose (HG). We found that AMP improved HG-caused cell viability reduction in MCs. AMP significantly suppressed the intracellular ROS production and expression levels of ROS producing enzymes NADPH oxidase 2 (NOX2) and NOX4. Increased of NOX activity in HG-stimulated MCs was suppressed by AMP. Pretreatment with AMP inhibited extracellular matrix (ECM) accumulation in HG-stimulated MCs with decreased expression levels of fibronectin (FN) and collagen type IV (Col IV). Furthermore, AMP elevated the expression levels of nuclear Nrf2 and heme oxygenase-1 (HO-1), as well as increased the mRNA levels of Nrf2-driven genes NAD(P)H dehydrogenase quinone-1 (NQO-1) and HO-1 in HG-treated MCs. Knockdown of Nrf2 reversed the protective effects of AMP against HG-induced oxidative stress and EMC accumulation in MCs. In conclusion, these findings indicated that AMP protected MCs from HG-induced oxidative damage and ECM accumulation, which might be mediated by Nrf2/HO-1 pathway.

Protective effects of lycopene on hippocampal neurotoxicity and memory impairment induced by bisphenol A in rats.

Bisphenol A (BPA) is used to produce polycarbonate plastic and epoxy resins which are used in many consumer products. Most people encounter BPA in their daily routines. However, it has been heavily reported that BPA has a neurotoxic effect. The present study aimed to investigate the effect of lycopene on cognitive deficits induced by a high dose of BPA focusing on mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, oxidative stress, apoptosis, and memory retrieval in adult male rats. Therefore, 72 rats were divided into four groups: control group, BPA group (50 mg/kg body weight (bw)) 3 days a week for 42 days, lycopene group (10 mg/kg bw) daily for 42 days, and lycopene + BPA group. Concurrent treatment of lycopene with BPA improved the learning and cognition memory in Morris water maze and novel object recognition tests along with an increase in acetylcholine esterase activity as well as inhibition of oxidative stress by restoring reduced glutathione and suppressing malondialdehyde hippocampal level to their normal levels. Mechanistically, lycopene upregulated the protein expression of tyrosine receptor kinase B, which resulted in an upsurge in its downstream cascades MAPK/ERK1/2/cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway in the hippocampus of BPA-intoxicated rats. Furthermore, concurrent treatment of lycopene with BPA prevented apoptosis by marked decrease in Bcl-2 associated X protein (Bax) gene expression and caspase 3 activity while restoring B-cell leukemia/lymphoma-2 (Bcl-2) gene expression. In conclusion, the present study provided evidence that lycopene exerted a neuroprotective effect against BPA intoxication in hippocampi of rats via its antioxidant properties, activation of MAPK/ERK pathway, and inhibiting a neuronal apoptosis which reflected on improving the learning and cognition memory.

Multifactor dimensionality reduction reveals a strong gene-gene interaction between STC1 and COL11A1 genes as a possible risk factor of knee osteoarthritis.

Articular cartilage is an avascular tissue with a structure that allows it to support and cushion the overload of the surfaces in contact. It maintains its metabolic functions due to the contribution of different signaling pathways. However, several factors play a role in its deterioration, allowing to the development of osteoarthritis (OA), and one of the major factors is genetic. Our goal was to identify gene-gene interactions (epistasis) between five signaling pathways involved in the articular cartilage metabolism as possible indicators of OA risk. We applied the Multifactor-Dimensionality Reduction (MDR) method to identify and characterize the epistasis between 115 SNPs located in 73 genes related to HIF-1α, Wnt/β-catenin, cartilage extracellular matrix metabolism, oxidative stress, and uric acid transporters. Ninety three patients diagnosed with primary knee OA and 150 healthy controls were included in the study. Genotyping was performed with the OpenArray system, the statistical analysis was carried out with the STATA software v14, and epistasis was analyzed with the MDR software v3.0.2. The MDR analysis revealed that the best interaction model was between polymorphisms rs17786744 of the STC1 gene and rs2615977 of the COL11A1 gene, with an entropy value of 4.44%, CVC 8/10, OR 5.60, 95% CI 3.27-9.59, p < 0.0001. Under this interaction model, we identified high and low risk genotypes involved in OA development. Our results suggest complex interactions between STC1 and COL11A1 genes that might have an impact on genetic susceptibility to develop OA. Further studies are required to confirm it.

Impact of polystyrene nanoparticles on marine diatom Skeletonema marinoi chain assemblages and consequences on their ecological role in marine ecosystems

Marine diatoms have been identified among the most abundant taxa of microorganisms associated with plastic waste collected at sea. However, the impact of nano-sized plastic fragments (nanoplastics) at single cell and population level is almost unknown. We exposed the marine diatom Skeletonema marinoi to model polystyrene nanoparticles with carboxylic acid groups (PS–COOH NPs, 90 nm) for 15 days (1, 10, 50 μg/mL). Growth, reactive oxygen species (ROS) production, and nano-bio-interactions were investigated. No effect on diatom growth was observed, however Dynamic light scattering (DLS) demonstrated the formation of large PS aggregates which were localized at the diatoms’ fultoportula process (FPP), as shown by TEM images. Increase production of ROS and reduction in chain length were also observed upon PS NPs exposure (p < 0.005). The observed PS-diatom interaction could have serious consequences on diatoms ecological role on the biogeochemical cycle of carbon, by impairing the formation of fast-sinking aggregates responsible for atmospheric carbon fixation and sequestration in the ocean sea floor.S. marinoi exposure to PS NPs caused an increase of intracellular and extracellular oxidative stress, the reduction of diatom’s chain length and the adhesion of PS NPs onto the algal surface.