scholarly journals Inhibition of Methylglyoxal-Induced AGEs/RAGE Expression Contributes to Dermal Protection by N-Acetyl-L-Cysteine

2017 ◽  
Vol 41 (2) ◽  
pp. 742-754 ◽  
Author(s):  
Chun-tao Yang ◽  
Fu-hui Meng ◽  
Li Chen ◽  
Xiang Li ◽  
Lai-Jian Cen ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Condensation Reaction ◽  
Neutralizing Antibody ◽  
Cellular Adhesion ◽  
Type I ◽  
Hacat Cells ◽  
Protective Effects ◽  
Cellular Viability ◽  
Inflammatory Injury

Background/Aim: Accumulation of advanced glycation end products (AGEs) is a major cause of diabetes mellitus (DM) skin complications. Methylglyoxal (MGO), a reactive dicarbonyl compound, is a crucial intermediate of AGEs generation. N-acetyl-L-cysteine (NAC), an active ingredient of some medicines, can induce endogenous GSH and hydrogen sulfide generation, and set off a condensation reaction with MGO. However, there is rare evidence to show NAC can alleviate DM-induced skin injury through inhibition of AGEs generation or toxicity. The present study aimed to observe the effects of NAC on MGO-induced inflammatory injury and investigate the roles of AGEs and its receptor (RAGE) in NAC’s dermal protection in human HaCaT keratinocytes. Methods: The cells were exposed to MGO to simulate a high MGO status in diabetic blood or tissues. The content of AGEs in serum or cell medium was measured with ELISA. The protective effects of NAC against MGO-induce injury were evaluated by administration before MGO one hour, in virtue of cell viability, mitochondrial membrane potential, inflammation reaction, nuclear factor (NF)-κB activation, matrix metalloproteinase (MMP)-9 expression, as well as cellular behavioral function. Results: We found the AGEs levels of patients with DM were elevated comparing with healthy volunteers. The in vitro AGEs generation was also able to be enhanced by the exposure of HaCaT cells to MGO, which reduced dose-dependently cellular viability, damaged mitochondrial function, triggered secretion of interleukin (IL)-6 and IL-8, activated NF-κB and upregulated MMP-9 expression. Furthermore, the exposure caused cellular adhesion and migration dysfunction, as well as collagen type I inhibition. Importantly, before the exposure to MGO, the preconditioning with NAC significantly attenuated MGO-induced AGEs generation, improved cellular viability and mitochondrial function, partially reversed the overexpression of proinflammatory factors and MMP-9, as well as the activation of NF-κB. Lastly, NAC blocked MGO-induced RAGE upregulation, and inhibition of RAGE with its neutralizing antibody significantly alleviated MGO-induced NF-κB activation, MMP-9 upregulation and inflammatory injury in HaCaT cells. Conclusion: The present work indicates the administration of NAC can prevent MGO-induced dermal inflammatory injury through inhibition of AGEs/RAGE signal, which may provide a basal support for the treatment of diabetic skin complications with NAC-containing medicines in the future.

scholarly journals Effects of a New Bioceramic Material on Human Apical Papilla Cells

2018 ◽  
Vol 9 (4) ◽  
pp. 74 ◽  
Author(s):  
Diana Sequeira ◽  
Catarina Seabra ◽  
Paulo Palma ◽  
Ana Cardoso ◽  
João Peça ◽  
...  
Keyword(s):  
Wound Healing ◽  
Mineral Trioxide Aggregate ◽  
Cellular Adhesion ◽  
Cellular Migration ◽  
Cellular Viability ◽  
Migration Rates ◽  
Apical Papilla ◽  
And Migration ◽  
Proliferation And Migration

Background: The development of materials with bioregenerative properties is critically important for vital pulp therapies and regenerative endodontic procedures. The aim of this study was to evaluate the cytocompatibility and cytotoxicity of a new endodontic biomaterial, PulpGuard, in comparison with two other biomaterials widely used in endodontic procedures, ProRoot Mineral Trioxide Aggregate (MTA) and Biodentine. Methods: Apical papilla cells (APCs) were isolated from third molars with incomplete rhizogenesis from patients with orthodontic indication for dental extraction. Cultured APCs were incubated for 24, 48, or 72 h with different dilutions of eluates prepared from the three materials. Cellular viability, mobility, and proliferation were assessed in vitro using the Alamar Blue assay and a wound-healing test. The cells were also cultured in direct contact with the surface of each material. These were then analyzed via Scanning Electron Microscopy (SEM), and the surface chemical composition was determined by Energy-Dispersive Spectroscopy (EDS). Results: Cells incubated in the presence of eluates extracted from ProRoot MTA and PulpGuard presented rates of viability comparable to those of control cells; in contrast, undiluted Biodentine eluates induced a significant reduction of cellular viability. The wound-healing assay revealed that eluates from ProRoot MTA and PulpGuard allowed for unhindered cellular migration and proliferation. Cellular adhesion was observed on the surface of all materials tested. Consistent with their disclosed composition, EDS analysis found high relative abundance of calcium in Biodentine and ProRoot MTA and high abundance of silicon in PulpGuard. Significant amounts of zinc and calcium were also present in PulpGuard discs. Concerning solubility, Biodentine and ProRoot MTA presented mild weight loss after eluate extraction, while PulpGuard discs showed significant water uptake. Conclusions: PulpGuard displayed a good in vitro cytocompatibility profile and did not significantly affect the proliferation and migration rates of APCs. Cells cultured in the presence of PulpGuard eluates displayed a similar profile to those cultured with eluates from the widely used endodontic cement ProRoot MTA.

scholarly journals α1-Microglobulin (A1M) Protects Human Proximal Tubule Epithelial Cells from Heme-Induced Damage In Vitro

2020 ◽  
Vol 21 (16) ◽  
pp. 5825 ◽  
Author(s):  
Amanda Kristiansson ◽  
Sara Davidsson ◽  
Maria E. Johansson ◽  
Sarah Piel ◽  
Eskil Elmér ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Proximal Tubule ◽  
Mitochondrial Function ◽  
Radical Scavenging ◽  
Related Factor ◽  
Protective Effects ◽  
Cellular Expression ◽  
Human Proximal Tubule

Oxidative stress is associated with many renal disorders, both acute and chronic, and has also been described to contribute to the disease progression. Therefore, oxidative stress is a potential therapeutic target. The human antioxidant α1-microglobulin (A1M) is a plasma and tissue protein with heme-binding, radical-scavenging and reductase activities. A1M can be internalized by cells, localized to the mitochondria and protect mitochondrial function. Due to its small size, A1M is filtered from the blood into the glomeruli, and taken up by the renal tubular epithelial cells. A1M has previously been described to reduce renal damage in animal models of preeclampsia, radiotherapy and rhabdomyolysis, and is proposed as a pharmacological agent for the treatment of kidney damage. In this paper, we examined the in vitro protective effects of recombinant human A1M (rA1M) in human proximal tubule epithelial cells. Moreover, rA1M was found to protect against heme-induced cell-death both in primary cells (RPTEC) and in a cell-line (HK-2). Expression of stress-related genes was upregulated in both cell cultures in response to heme exposure, as measured by qPCR and confirmed with in situ hybridization in HK-2 cells, whereas co-treatment with rA1M counteracted the upregulation. Mitochondrial respiration, analyzed with the Seahorse extracellular flux analyzer, was compromised following exposure to heme, but preserved by co-treatment with rA1M. Finally, heme addition to RPTE cells induced an upregulation of the endogenous cellular expression of A1M, via activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)-pathway. Overall, data suggest that A1M/rA1M protects against stress-induced damage to tubule epithelial cells that, at least partly, can be attributed to maintaining mitochondrial function.

scholarly journals Estrogen-Receptor-Mediated Protection of Cerebral Endothelial Cell Viability and Mitochondrial Function after Ischemic Insult in vitro

2009 ◽  
Vol 30 (3) ◽  
pp. 545-554 ◽  
Author(s):  
Jiabin Guo ◽  
Diana N Krause ◽  
James Horne ◽  
John H Weiss ◽  
Xuejun Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Estrogen Receptor ◽  
Endothelial Cell ◽  
Cell Viability ◽  
Mitochondrial Function ◽  
Protective Effects ◽  
Brain Endothelial Cells ◽  
Ischemic Insult ◽  
Mitochondrial Superoxide

Protective effects of estrogen against experimental stroke and neuronal ischemic insult are well-documented, but it is not known whether estrogen prevents ischemic injury to brain endothelium, a key component of the neurovascular unit. Increasing evidence indicates that estrogen exerts protective effects through mitochondrial mechanisms. We previously found 17β-estradiol (E2) to improve mitochondrial efficiency and reduce mitochondrial superoxide in brain blood vessels and endothelial cells. Thus we hypothesized E2 will preserve mitochondrial function and protect brain endothelial cells against ischemic damage. To test this, an in vitro ischemic model, oxygen-glucose deprivation (OGD)/reperfusion, was applied to immortalized mouse brain endothelial cells (bEnd.3). OGD/reperfusion-induced cell death was prevented by long-term (24, 48 h), but not short-term (0.5, 12 h), pretreatment with 10 nmol/L E2. Protective effects of E2 on endothelial cell viability were mimicked by an estrogen-receptor (ER) agonist selective for ERα (PPT), but not by one selective for ERβ (DPN). In addition, E2 significantly decreased mitochondrial superoxide and preserved mitochondrial membrane potential and ATP levels in early stages of OGD/reperfusion. All of the E2 effects were blocked by the ER antagonist, ICI-182,780. These findings indicate that E2 can preserve endothelial mitochondrial function and provide protection against ischemic injury through ER-mediated mechanisms.

scholarly journals IFN-λ1 Displays Various Levels of Antiviral Activity In Vitro in a Select Panel of RNA Viruses

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1602
Author(s):  
Marina Plotnikova ◽  
Alexey Lozhkov ◽  
Ekaterina Romanovskaya-Romanko ◽  
Irina Baranovskaya ◽  
Mariia Sergeeva ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Rna Viruses ◽  
Antiviral Effect ◽  
Vero Cells ◽  
Genome Replication ◽  
Type I ◽  
Protective Effects ◽  
Cellular Models ◽  
Viral Genome Replication

Type III interferons (lambda IFNs) are a quite new, small family of three closely related cytokines with interferon-like activity. Attention to IFN-λ is mainly focused on direct antiviral activity in which, as with IFN-α, viral genome replication is inhibited without the participation of immune system cells. The heterodimeric receptor for lambda interferons is exposed mainly on epithelial cells, which limits its possible action on other cells, thus reducing the likelihood of developing undesirable side effects compared to type I IFN. In this study, we examined the antiviral potential of exogenous human IFN-λ1 in cellular models of viral infection. To study the protective effects of IFN-λ1, three administration schemes were used: ‘preventive’ (pretreatment); ‘preventive/therapeutic’ (pre/post); and ‘therapeutic’ (post). Three IFN-λ1 concentrations (from 10 to 500 ng/mL) were used. We have shown that human IFN-λ1 restricts SARS-CoV-2 replication in Vero cells with all three treatment schemes. In addition, we have shown a decrease in the viral loads of CHIKV and IVA with the ‘preventive’ and ‘preventive/therapeutic’ regimes. No significant antiviral effect of IFN-λ1 against AdV was detected. Our study highlights the potential for using IFN-λ as a broad-spectrum therapeutic agent against respiratory RNA viruses.

scholarly journals A Mitochondrial Approach to Cardiovascular Risk and Disease

2019 ◽  
Vol 25 (29) ◽  
pp. 3175-3194 ◽  
Author(s):  
Caroline D. Veloso ◽  
Getachew D. Belew ◽  
Luciana L. Ferreira ◽  
Luís F. Grilo ◽  
John G. Jones ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Energy Demand ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Alcoholic Fatty Liver ◽  
Cardiovascular Morbidity And Mortality

Background: Cardiovascular diseases (CVDs) are a leading risk factor for mortality worldwide and the number of CVDs victims is predicted to rise through 2030. While several external parameters (genetic, behavioral, environmental and physiological) contribute to cardiovascular morbidity and mortality; intrinsic metabolic and functional determinants such as insulin resistance, hyperglycemia, inflammation, high blood pressure and dyslipidemia are considered to be dominant factors. Methods: Pubmed searches were performed using different keywords related with mitochondria and cardiovascular disease and risk. In vitro, animal and human results were extracted from the hits obtained. Results: High cardiac energy demand is sustained by mitochondrial ATP production, and abnormal mitochondrial function has been associated with several lifestyle- and aging-related pathologies in the developed world such as diabetes, non-alcoholic fatty liver disease (NAFLD) and kidney diseases, that in turn can lead to cardiac injury. In order to delay cardiac mitochondrial dysfunction in the context of cardiovascular risk, regular physical activity has been shown to improve mitochondrial parameters and myocardial tolerance to ischemia-reperfusion (IR). Furthermore, pharmacological interventions can prevent the risk of CVDs. Therapeutic agents that can target mitochondria, decreasing ROS production and improve its function have been intensively researched. One example is the mitochondria-targeted antioxidant MitoQ10, which already showed beneficial effects in hypertensive rat models. Carvedilol or antidiabetic drugs also showed protective effects by preventing cardiac mitochondrial oxidative damage. Conclusion: This review highlights the role of mitochondrial dysfunction in CVDs, also show-casing several approaches that act by improving mitochondrial function in the heart, contributing to decrease some of the risk factors associated with CVDs.

scholarly journals Chitin Nanofibril Application in Tympanic Membrane Scaffolds to Modulate Inflammatory and Immune Response

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1440
Author(s):  
Serena Danti ◽  
Shivesh Anand ◽  
Bahareh Azimi ◽  
Mario Milazzo ◽  
Alessandra Fusco ◽  
...  
Keyword(s):  
Tympanic Membrane ◽  
Weight Ratio ◽  
Human Mesenchymal Stem Cells ◽  
Cell Types ◽  
Collagen Type I ◽  
In Vitro Tests ◽  
Type I ◽  
Hacat Cells ◽  
Polybutylene Terephthalate

Chitin nanofibrils (CNs) are an emerging bio-based nanomaterial. Due to nanometric size and high crystallinity, CNs lose the allergenic features of chitin and interestingly acquire anti-inflammatory activity. Here we investigate the possible advantageous use of CNs in tympanic membrane (TM) scaffolds, as they are usually implanted inside highly inflamed tissue environment due to underlying infectious pathologies. In this study, the applications of CNs in TM scaffolds were twofold. A nanocomposite was used, consisting of poly (ethylene oxide terephthalate)/(polybutylene terephthalate) (PEOT/PBT) copolymer loaded with CN/polyethylene glycol (PEG) pre-composite at 50/50 (w/w %) weight ratio, and electrospun into fiber scaffolds, which were coated by CNs from crustacean or fungal sources via electrospray. The degradation behavior of the scaffolds was investigated during 4 months at 37 °C in an otitis-simulating fluid. In vitro tests were performed using cell types to mimic the eardrum, i.e., human mesenchymal stem cells (hMSCs) for connective, and human dermal keratinocytes (HaCaT cells) for epithelial tissues. HMSCs were able to colonize the scaffolds and produce collagen type I. The inflammatory response of HaCaT cells in contact with the CN-coated scaffolds was investigated, revealing a marked downregulation of the pro-inflammatory cytokines. CN-coated PEOT/PBT/(CN/PEG 50:50) scaffolds showed a significant indirect antimicrobial activity.

scholarly journals Lipin1 Is Involved in the Pathogenesis of Diabetic Encephalopathy through the PKD/Limk/Cofilin Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Min Xie ◽  
Meijian Wang ◽  
Wei Liu ◽  
Min Xu ◽  
Pan Shang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Rat Model ◽  
Type I Diabetes ◽  
Type I ◽  
Protective Effects ◽  
Diabetic Encephalopathy ◽  
Neuroprotective Effects ◽  
Lim Kinase ◽  
Ca1 Region

Diabetic encephalopathy is a type of central diabetic neuropathy resulting from diabetes mainly manifested as cognitive impairments. However, its underlying pathogenesis and effective treatment strategies remain unclear. In the present study, we investigated the effect of Lipin1, a phosphatidic acid phosphatase enzyme, on the pathogenesis of diabetic encephalopathy. We found that in vitro, Lipin1 exerts protective effects on high glucose-induced reductions of PC12 cell viability, while in vivo, Lipin1 is downregulated within the CA1 hippocampal region in a type I diabetes rat model. Increased levels of Lipin1 within the CA1 region are accompanied with protective effects including amelioration of dendritic spine and synaptic deficiencies, phosphorylation of the synaptic plasticity-related proteins, LIM kinase 1 (p-limk1) and cofilin, as well as increases in the synthesis of diacylglycerol (DAG), and the expression of phosphorylated protein kinase D (p-PKD). These effects are associated with the rescue of cognitive disorders as shown in this rat model of diabetes. In contrast, knockdown of Lipin1 within the CA1 region enhanced neuronal abnormalities and the genesis of cognitive impairment in rats. These results suggest that Lipin1 may exert neuroprotective effects involving the PKD/Limk/Cofilin signaling pathway and may serve as a potential therapeutic target for diabetic encephalopathy.

scholarly journals Type I interferons protect mice against enterovirus 71 infection

2005 ◽  
Vol 86 (12) ◽  
pp. 3263-3269 ◽  
Author(s):  
Ming-Liang Liu ◽  
Yi-Ping Lee ◽  
Ya-Fang Wang ◽  
Huan-Yao Lei ◽  
Ching-Chuan Liu ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Enterovirus 71 ◽  
Neutralizing Antibody ◽  
Oral Route ◽  
Type I Interferons ◽  
Ev71 Infection ◽  
Type I ◽  
Type I Ifns ◽  
Protection Against Infection

In this study, the contribution of type I interferons (IFNs) to protection against infection with enterovirus 71 (EV71) was investigated using a murine model where the virus was administrated to neonatal Institute of Cancer Research (ICR) mice by either the intraperitoneal (i.p.) or the oral route. In i.p. inoculated mice, post-infection treatment of dexamethasone (5 mg kg−1 at 2 or 3 days after infection) exacerbated clinical symptoms and increased the tissue viral titre. In contrast, polyriboinosinic : polyribocytidylic acid [poly(I : C); 10 or 100 μg per mouse at 12 h before infection], a potent IFN inducer, improved the survival rate and decreased the tissue viral titres after EV71 challenge, which correlated with an increase in serum IFN-α concentration, the percentage of dendritic cells, their expression of major histocompatibility complex class II molecule and IFN-α in spleen. Treatment with a neutralizing antibody for type I IFNs (104 neutralizing units per mouse, 6 h before and 12 h after infection) resulted in frequent deaths and higher tissue viral load in infected mice compared with control mice. In contrast, an early administration of recombinant mouse IFN-αA (104 U per mouse for 3 days starting at 0, 1 or 3 days after infection) protected the mice against EV71 infection. In vitro analysis of virus-induced death in three human cell lines showed that human type I IFNs exerted a direct protective effect on EV71. It was concluded that type I IFNs play an important role in controlling EV71 infection and replication.

scholarly journals Anti-Photoaging Effect of Plant Extract Fermented with Lactobacillus buchneri on CCD-986sk Fibroblasts and HaCaT Keratinocytes

2020 ◽  
Vol 11 (1) ◽  
pp. 3 ◽  
Author(s):  
Yun-Mi Kang ◽  
Chul-Hee Hong ◽  
Sa-Haeng Kang ◽  
Dong-Seok Seo ◽  
Seong-Oh Kim ◽  
...  
Keyword(s):  
In Vitro Model ◽  
Type I Collagen ◽  
Dermal Fibroblasts ◽  
Epidermal Keratinocytes ◽  
Type I ◽  
Mrna Levels ◽  
Protective Effects ◽  
Lactobacillus Buchneri ◽  
Vitro Model

Ultraviolet (UV) exposure triggers the abnormal production of reactive oxygen (ROS) species and the expression of matrix metalloproteinases (MMPs) that are responsible for photoaging. Probiotics are widely used in healthcare and for immune enhancement. One probiotic, Lactobacillus buchneri is found in Kimchi. This study was aimed at assessing the anti-photoaging effect of plant extracts fermented with L. buchneri (PELB) to develop functional cosmetics. We investigated the anti-photoaging effect of PELB in a UVB-induced photoaging in vitro model and selected effective extracts using the elastase inhibition assay, ELISA for Type I procollagen and collagenase-1, and quantitative real time PCR. Normal human dermal fibroblasts and epidermal keratinocytes were pre-treated with PELB and exposed to UVB. We found that PELB decreased elastase activity and increased type I collagen expression in a UVB-induced photoaging in vitro model. In addition, PELB greatly reduced collagenase activity and MMP mRNA levels in a UVB-induced photoaging in vitro model. Furthermore, PELB promoted the expression of moisture factor and anti-oxidant enzymes in a UVB-induced photoaging in vitro model. These results indicated that the PELB could be potential candidates for the protective effects against UVB-induced photoaging. Overall, these results suggest that PELB might be useful natural components of cosmetic products.

scholarly journals L-Carnitine has a liver-protective effect through inhibition of inducible nitric oxide synthase induction in primary cultured rat hepatocytes

2018 ◽  
Vol 8 (3) ◽  
pp. 212 ◽  
Author(s):  
Yusuke Nakamura ◽  
Hiroya Iida ◽  
Richi Nakatake ◽  
Tatsuma Sakaguchi ◽  
Masaki Kaibori ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Liver Injury ◽  
Inducible Nitric Oxide Synthase ◽  
Inos Mrna ◽  
Type I ◽  
Protective Effects ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Background: L-Carnitine has protective effects on various injured organs. However, it has not been reported whether L-carnitine influences the induction of inducible nitric oxide synthase (iNOS) expression during inflammation. Nitric oxide (NO) produced by iNOS is an inflammatory indicator in organs which become inflamed, including the liver.Objective: This study aimed to examine whether L-carnitine influences the induction of iNOS gene expression in inflammatory cytokine-stimulated hepatocytes and the mechanisms involved in the action. Methods: L-Carnitine was added into the primary cultures of rat hepatocytes stimulated by interleukin-1β (an in vitro liver injury model). The production of NO and induction of iNOS and its signaling pathway were analyzed.Results: Transfection experiments with iNOS promoter-luciferase constructs revealed how L-carnitine inhibited iNOS mRNA synthesis activity and reduced its stability. In support of this observation, L-carnitine reduced iNOS mRNA and iNOS protein expression levels, resulting in reduced NO production. L-Carnitine blocked two essential pathways for iNOS induction: IκB kinase (IκB degradation/NF-κB activation) and phosphatidylinositol 3-kinase/Akt (type I IL-1 receptor upregulation).Conclusions: L-Carnitine inhibited the induction of inflammatory mediator iNOS, partially through inhibition of NF-κB activation, which demonstrated L-carnitine has protective effects in an in vitro liver injury model. L-Carnitine may have therapeutic potential for organ injuries, including the liver.Keywords: L-carnitine, hepatic encephalopathy, inducible nitric oxide synthase, liver injury, primary cultured hepatocytes, nuclear factor-κB, type I interleukin-1 receptor 

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