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Experiments were conducted to investigate the potential of the efficient resource utilization of waste cow manure and corn straw in an agricultural ecosystem. In this study, a magnetic cow manure and straw biochar were synthesized by a co-precipitation method, and cadmium (Cd(II)) was removed by adsorption in aqueous solution. Several physicochemical characterization techniques were applied, including SEM, BET, Zeta, FTIR, Raman, XPS, and VSM. The effects of pH value, magnetic biochar content, adsorption kinetics, and isothermal adsorption on the adsorption of Cd(II) were investigated. The physicochemical characterizations revealed that the physical and chemical properties of the magnetic biochar were substantially changed compared to the unmodified biochar. The results showed that the surface of the biochar became rough, the number of oxygen (O)-containing functional groups increased, and the specific surface area increased. The results of the adsorption experiments showed that the adsorption capacity was affected by pH, magnetic biochar addition, Cd(II) concentration, and adsorption time. The adsorption kinetics and isothermal adsorption experiments showed that the Cd(II) adsorption processes of the cow manure and corn straw magnetic biochars were consistent with the Freundlich model and pseudo-second-order kinetic model. The results also showed that the Cd(II) adsorption effect of cow manure magnetic biochar was found to be more effective than that of corn straw magnetic biochar. The optimal conditions for Cd(II) adsorption were 800 â for cow manure magnetic biochar, with a pH value of 5 and 0.14 g biochar addition, and 600 â for straw magnetic biochar with a pH value of 8 and 0.12 g biochar addition. In conclusion, the cow manure magnetic biochar was an effective adsorbent for the absorption of Cd(II) in wastewater.
Subject(s)
Cadmium , Water Pollutants, Chemical , Cadmium/analysis , Adsorption , Manure , Ecosystem , Water Pollutants, Chemical/analysis , Charcoal/chemistry , Magnetic Phenomena , KineticsABSTRACT
Although secretory IgA (SIgA) is the dominant antibody in mucosal secretions, the capacity of the SIgA-antigen complex to prime the activation of dendritic cells (DCs) and T cells in the intestinal epithelium is not well understood. To this end, the SIgA-ETEC F5 immune complexes (ICs) were prepared via Ni-NTA pull-down. After injecting the ICs into the intestines of SPF BALB/c mice, most ICs were observed in the Peyer's patch (PP). We established a microfold (M) cell culture model in vitro for transport experiments and the inhibition test. To evaluate the priming effect of mucosal immunity, we employed the DC2.4 stimulation test, T lymphocyte proliferation assays, and cytokine detection assays. We found that the ICs were taken up via clathrin-dependent endocytosis through M cells. The high expression of costimulatory molecules CD86, CD80, and CD40 indicated that the ICs promoted the differentiation and maturation of DC2.4 cells. The stimulation index (SI) in the complex group was significantly higher than in the control group, suggesting that the ICs stimulated the proliferation of primed T cells. The secretion of some cytokines, namely TNF-α, IFN-γ, IL-2, IL-4, IL-5, and IL-6, in spleen cells from the immunized mice was upregulated. These results indicate that ETEC F5 delivery mediated by SIgA in PPs initiates mucosal immune responses.
ABSTRACT
INTRODUCTION: This study aimed to investigate the height and thickness of alveolar bone by cone-beam computed tomography imaging after orthodontic treatment in the unilateral maxillary anterior region and speculate on reasons for the difference in alveolar bone morphology. METHODS: This study selected 11 patients (3 males and 8 females; mean age, 9.42 ± 1.45 years). Cone-beam computed tomography was performed for these 11 patients before and after treatment using Dolphin Imaging software (Dolphin Imaging and Management Solutions, Chatsworth, Calif). Labial and palatal alveolar bone thickness (BT) at root apices and different levels along the roots and loss of alveolar bone height was measured for each impacted tooth and its contralateral homonymous tooth. RESULTS: After orthodontic therapy, all 3 impacted anterior teeth had different degrees of loss of labial alveolar bone height compared with the normal side (central incisor: -1.5 mm, P <0.005; lateral incisor: -1.06 mm, P <0.01; canine: -0.59 mm, P < 0.01). The lateral incisors also showed palatal alveolar bone height loss compared with the unaffected side (-0.8 mm, P <0.005). Alveolar BT at root apices of impacted canines was 1.14 mm thicker than the normal side (P <0.005). Central and lateral incisors were similar to the normal side. The thickness of the alveolar bone at 8, 10, and 12 mm of the impacted canine position was still larger than that on the healthy side, whereas the difference in average thickness between the healthy and affected side had been significantly reduced compared with pretreatment measurements. CONCLUSIONS: There is satisfactory retention of alveolar bone height in canines after orthodontic treatment; however, alveolar bone loss is slightly worse at central and lateral incisors. Retention of alveolar BT was normal for impacted anterior teeth, whereas excess apical alveolar BT at the canines, although still present, was substantially less significant than had been observed before treatment.
Subject(s)
Alveolar Bone Loss , Tooth, Impacted , Male , Female , Humans , Child , Tooth, Impacted/diagnostic imaging , Tooth, Impacted/therapy , Tooth Root , Maxilla/diagnostic imaging , Alveolar Bone Loss/diagnostic imaging , Alveolar Bone Loss/etiology , Palate , Cone-Beam Computed Tomography/methodsABSTRACT
The intestine barrier, the front line of normal body defense, relies on its structural integrity, microbial composition and barrier immunity. The intestinal mucosal surface is continuously exposed to a complex and dynamic community of microorganisms. Although it occupies a relatively small proportion of the intestinal microbiota, Lactobacilli has been discovered to have a significant impact on the intestine tract in previous studies. It is undeniable that some Lactobacillus strains present probiotic properties through maintaining the micro-ecological balance via different mechanisms, such as mucosal barrier function and barrier immunity, to prevent infection and even to solve some neurology issues by microbiota-gut-brain/liver/lung axis communication. Notably, not only living cells but also Lactobacillus derivatives (postbiotics: soluble secreted products and para-probiotics: cell structural components) may exert antipathogenic effects and beneficial functions for the gut mucosal barrier. However, substantial research on specific effects, safety and action mechanisms in vivo should be done. In clinical application of humans and animals, there are still doubts about the precise evaluation of Lactobacilli's safety, therapeutic effect, dosage and other aspects. Therefore, we provide an overview of central issues on the impacts of Lactobacillus casei (L. casei) and their products on the intestinal mucosal barrier and some diseases and highlight the urgent need for further studies.
ABSTRACT
For improved actuation at low voltages of dielectric elastomers, a high dielectric permittivity has been targeted for several years but most successful methods then either increase the stiffness of the elastomer and/or introduce notable losses of both mechanical and dielectric nature. For polydimethylsiloxane (PDMS)-based elastomers, most high-permittivity moieties inhibit the sensitive platinum catalyst used in the addition curing scheme. In contrast to the classical addition curing pathway to prepare PDMS elastomers, here, an alternative strategy is reported to prepare PDMS elastomers via the crosslinking reaction between multifunctional imidazole-grafted PDMS with difunctional bis(1-ethylene-imidazole-3-ium) bromide ionic liquid (bis-IL). The prepared IL-elastomer entails uniformly dispersed IL and presents stable mechanical and dielectric properties due to the covalent nature of the crosslinking as opposed to previously reported physical mixing in of ILs. The relative permittivity was improved up to 200% by including the bis-IL in the elastomer, and Young's modulus was around 0.04 MPa. As a result of the excellent combination of properties, the dielectric actuator developed exhibits an area strain of 20% at 15 V/µm. The novel strategy to prepare PDMS elastomers provides a new paradigm for achieving high-performance dielectric elastomer actuators by a simple methodology.
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INTRODUCTION: There are several cannabidiol (CBD) transdermal patches available on the market. However, none are FDA-approved. Furthermore, not much evidence has been published about CBD release and skin permeation from such patches, so the effectiveness and reliability remain unclear. OBJECTIVES: We aimed to develop a method to determine the in vitro release and skin permeation of CBD from transdermal patches using Franz cell diffusion in combination with quantitative 1 H-NMR (qNMR). MATERIALS AND METHODS: The study was conducted on CBD patches with known CBD content and six different commercially available or market-ready CBD patches using a Franz cell with a Strat-M™ membrane and with samples taken directly from the transdermal patch for qNMR analysis. RESULTS: The use of qNMR yielded an average recovery of 100% ± 7% when samples with known CBD content were tested. Results from the testing of six commercially available patches indicated that five out of six patches did not contain the CBD amount stated by the manufacturer according to a ± 10% variance margin, of which four patches were under-labeled and one was over-labeled. The release rate of patches was determined, and significant differences between the patches were shown. Maximum release of CBD was calculated to occur after 39 to 70 h. CONCLUSION: The established method was proven to be a reliable means of determining the quantity and release of CBD from transdermal patches and can be used to verify CBD content and release rate in transdermal patches.
Subject(s)
Cannabidiol , Transdermal Patch , Skin Absorption , Cannabidiol/metabolism , Reproducibility of Results , Skin/metabolismABSTRACT
BACKGROUND: Bovine parainfluenza virus type 3 (BPIV3) infection often causes respiratory tissue damage and immunosuppression and further results in bovine respiratory disease complex (BRDC), one of the major diseases in dairy cattle, caused huge economical losses every year. However, the pathogenetic and immunoregulatory mechanisms involved in the process of BPIV3 infection remain unknown. However, the pathogenetic and immunoregulatory mechanisms involved in the process of BPIV3 infection remain unknown. Proteomics is a powerful tool for high-throughput identification of proteins, which has been widely used to understand how viruses interact with host cells. METHODS: In the present study, we report a proteomic analysis to investigate the whole cellular protein alterations of MDBK cells infected with BPIV3. To investigate the infection process of BPIV3 and the immune response mechanism of MDBK cells, isobaric tags for relative and absolute quantitation analysis (iTRAQ) and Q-Exactive mass spectrometry-based proteomics were performed. The differentially expressed proteins (DEPs) involved in the BPIV3 invasion process in MDBK cells were identified, annotated, and quantitated. RESULTS: A total of 116 proteins, which included 74 upregulated proteins and 42 downregulated proteins, were identified as DEPs between the BPIV3-infected and the mock-infected groups. These DEPs included corresponding proteins related to inflammatory response, immune response, and lipid metabolism. These results might provide some insights for understanding the pathogenesis of BPIV3. Fluorescent quantitative PCR and western blotting analysis showed results consistent with those of iTRAQ identification. Interestingly, the upregulated protein MKK3 was associated with the p38 MAPK signaling pathway. CONCLUSIONS: The results of proteomics analysis indicated BPIV3 infection could activate the p38 MAPK pathway to promote virus replication.
Subject(s)
Parainfluenza Virus 3, Human , Proteomics , Animals , Cattle , Parainfluenza Virus 3, Bovine/physiology , Virus Replication/physiology , p38 Mitogen-Activated Protein KinasesABSTRACT
In the last 20 years, accumulating evidence indicates that the gut microbiota contribute to the development, maturation, and regulation of the host immune system and mediate host anti-pathogen defenses. Lactobacillus casei (L.casei) is a normal flora of the gastrointestinal tract in mammals and, as a great mucosal delivery vehicle, has wide use in bioengineering. However, the diarrhea prevention role of commensal intestinal microbiota interfered by the recombinant L.casei (rL.casei) in newborn piglets is not well understood. In our study, newborn piglets orally fed with the rL.casei surface displayed the fimbrial protein K88 of enterotoxigenic Escherichia coli (ETEC) and their feces were collected for a period of time after feeding. The next-generation sequencing of these fecal samples showed that the relative abundance of L.casei was significantly increased. The oral administration of rL.casei altered the intestinal microbial community as evidenced by altered microbial diversity and microbial taxonomic composition. Remarkably, the functional enhancing of the intestinal bacterial community by rL.casei was positively correlated with membrane transport, replication, and repair (p < 0.05). The specific antibody detection indicates that high levels of anti-K88 secretory immunoglobulin A (sIgA) were induced in fecal samples and systemic immunoglobulin G was produced in serum. The diarrhea rate in piglets caused by ETEC K88 was decreased by about 24%. Thus, the oral administration of rL.casei not only activated the mucosal and humoral immune responses in vivo but also contributed to shape the intestinal probiotics in newborn piglets and to significantly reduce the diarrhea rates of newborn piglets.
Subject(s)
Enterotoxigenic Escherichia coli , Escherichia coli Infections , Gastrointestinal Microbiome , Lacticaseibacillus casei , Animals , Animals, Newborn , Diarrhea/microbiology , Diarrhea/prevention & control , Diarrhea/veterinary , Escherichia coli Infections/prevention & control , Escherichia coli Infections/veterinary , Mammals , SwineABSTRACT
Low-energy (80-300 keV) electron beam accelerators are gaining in importance in the radiation processing industry due to their ease of use and wide range of applications (e.g. product surface sterilizations or polymer curing and cross-linking). Due to their very low penetration depth (tens to hundreds of microns), currently used film dosimeters exhibit dose gradients over their thickness and do not resolve the dose response in the first microns of the irradiated material. Hence, the surface dose, defined as the dose in the first micron Dµ, cannot be measured directly. This study presents a polymer material as a dosimeter candidate for high-dose low-energy electron beam irradiations. The readout of the dose-dependent fluorescence intensity, originating from a pararosaniline dye reaction when irradiated, is measured using fluorescence microscopy. So far, no in-depth characterization of the material has been performed, leaving the stability and fluorescence properties of the material not fully optimized. We describe the improvements in polymer composition and the fabrication method, and characterize the material properties in terms of the thermal stability, glass transition temperature, refractive index, hardness, rheological behavior, and water affinity. All of these create a complex set of requirements a polymer needs to fulfill to become an effective dosimeter when measuring using confocal microscopy. The fluorescence readout procedure will be addressed in further studies.
ABSTRACT
Interpenetrating polymer networks (IPNs) represent an interesting approach for tuning the properties of silicone elastomers due to the possible synergism that may occur between the networks. A new approach is presented, which consists of mixing two silicone-based networks with different crosslinking pathways; the first network being cured by condensation route and the second network by UV curing. The networks were mixed in different ratios and the resulted samples yield good mechanical properties (improved elongations, up to 720%, and Young's modulus, 1 MPa), thermal properties (one glass transition temperature, ~-123 °C), good dielectric strength (~50 V/µm), and toughness (63 kJ/m3).
ABSTRACT
Developing highly sensitive flexible pressure sensors has become crucially urgent due to the increased societal demand for wearable electronic devices capable of monitoring various human motions. The sensitivity of such sensors has been shown to be significantly enhanced by increasing the relative dielectric permittivity of the dielectric layers used in device construction via compositing with immiscible ionic conductors. Unfortunately, however, the elastomers employed for this purpose possess inhomogeneous morphologies, and thus suffer from poor long-term durability and unstable electrical response. In this study, we developed a novel, flexible, and highly sensitive pressure sensor using an elastomeric dielectric layer with particularly high permittivity and homogeneity due to the addition of synthesized ionic liquid-grafted silicone oil (denoted LMS-EIL). LMS-EIL possesses both a very high relative dielectric permittivity (9.6 × 105 at 10-1 Hz) and excellent compatibility with silicone elastomers due to the covalently connected structure of conductive ionic liquid (IL) and chloropropyl silicone oil. A silicone elastomer with a relative permittivity of 22 at 10-1 Hz, Young's modulus of 0.78 MPa, and excellent homogeneity was prepared by incorporating 10 phr (parts per hundreds rubber) of LMS-EIL into an elastomer matrix. The sensitivity of the pressure sensor produced using this optimized silicone elastomer was 0.51 kPa-1, which is 100 times higher than that of the pristine elastomer. In addition, a high durability illustrated by 100 loading-unloading cycles and a rapid response and recovery time of approximately 60 ms were achieved. The excellent performance of this novel pressure sensor suggests significant potential for use in human interfaces, soft robotics, and electronic skin applications.
ABSTRACT
Lactobacillus casei (L. casei), a normal resident of the gastrointestinal tract of mammals, has been extensively studied over the past few decades for its probiotic properties in clinical and animal models. Some studies have shown that some bacterium of Lactobacillus stimulate the production of antimicrobial peptides in intestinal cells to clear enteric pathogens, however, which antimicrobial peptides are produced by L. casei stimulation and its function are still not completely understood. In this study, we investigated the changes of antimicrobial peptides' expression after intragastric administration of L. casei to mice. The bioinformatics analysis revealed there were nine genes strongly associated with up-regulated DEGs. But, of these, only the antimicrobial peptide mReg3a gene was continuously up-regulated, which was also confirmed by qRT-PCR. We found out the mReg3a expressed in engineering E.coli promoted cell proliferation and wound healing proved by CCK-8 assay and wound healing assay. Moreover, the tight junction proteins ZO-1 and E-cadherin in mReg3a treatment group were significantly higher than that in the control group under the final concentration of 0.2 mg/ml both in Porcine intestinal epithelial cells (IPEC-J2) and Mouse intestinal epithelial cells (IEC-6) (p < 0.05). Surprisingly, the recombinant mReg3a not only inhibited Enterotoxigenic Escherichia coli (ETEC), but also reduced the copy number of the piglet diarrheal viruses, porcine epidemic diarrhea virus (PEDV), porcine transmissible gastroenteritis virus (TGEV), and porcine rotavirus (PoRV), indicating the antimicrobial peptides mReg3a may be feed additives to resist the potential of the intestinal bacterial and viral diarrhea disease.
ABSTRACT
Fatty liver is a common metabolic disorder afflicting dairy cows during the periparturient period and is closely associated with endoplasmic reticulum (ER) stress. The onset of ER stress in humans and mice alters hepatic lipid metabolism, but it is unknown if such event contributes to fatty liver in dairy cows soon after parturition. ORAI calcium release-activated calcium modulator 1 (ORAI1) is a key component of the store-operated Ca2+ entry mechanism regulating cellular Ca2+ balance. The purpose of this study was to investigate the role of ORAI1 on hepatic lipidosis via ER stress in dairy cows. Liver tissue biopsies were collected from Holstein cows diagnosed as healthy (n = 6) or with hepatic lipidosis (n = 6). Protein and mRNA abundance of ER stress-related targets, lipogenic targets, or the transcription regulator SREBP1 and ORAI1 were greater in cows with lipidosis. In vitro, hepatocytes were isolated from four healthy female calves and used for culture with a 1.2 mM mixture of fatty acids (oleic, linoleic, palmitic, stearic, and palmitoleic acid) for various times (0, 3, 6, 9, or 12 h). As incubation time progressed, increases in concentration of Ca2+ and abundance of protein kinase RNA-like ER kinase (PERK), inositol-requiring protein 1α (IRE1α), and activating transcription factor-6 (ATF6) protein in response to exogenous fatty acids underscored a mechanistic link among Ca2+, fatty acids, and ER stress. In a subsequent study, hepatocytes were transfected with small interfering RNA (siORAI1) or the ORAI1 inhibitor BTP2 for 48 h or 2 h followed by a challenge with the 1.2 mM mixture of fatty acids for 6 h. Compared with control group, silencing or inhibition of ORAI1 led to decreased abundance of fatty acid synthesis (FASN, SREBP1, and ACACA) and ER stress-related proteins in bovine hepatocytes. Overall, data suggested that NEFA through ORAI1 regulate intracellular Ca2+ signaling, induce ER stress, and lead to lipidosis in isolated hepatocytes.
Subject(s)
Fatty Liver , Rodent Diseases , Animals , Calcium/metabolism , Cattle , Endoribonucleases , Fatty Liver/veterinary , Female , Liver/metabolism , Mice , ORAI1 Protein , Protein Serine-Threonine KinasesABSTRACT
Development of a flexible pressure sensor is crucial for the future improvement of the wearable electronic devices designed to detect dynamic human motion. In this study, a novel pressure sensor with remarkably improved force sensing characteristics is obtained through combined usage of polydimethylsiloxane (PDMS) and ionic liquid (IL). Keratin is dispersed homogeneously in the PDMS matrix to serve as a reinforcing filler. High conductivity IL is employed as sensitivity-enhancing constituent in the elastomer, and the effect of the amount of IL on elastomers' pressure-sensing performance is investigated. The elastomer with 70 parts per hundred rubber (phr) IL shows excellent pressure-sensing performance. This novel pressure sensor demonstrates high linear sensitivity (0.037 kPa-1 ) in the large pressure region of 0-10 kPa. Response and recovery times are 8 and 11 ms, respectively, which are much shorter than previously reported. Moreover, the pressure sensor could distinguish different pressures via stable sensing signals in the pressure range of 0 to 50 kPa. The excellent performance of the novel pressure sensor has application potential in various fields, such as health monitoring and soft robotics.
Subject(s)
Ionic Liquids , Wearable Electronic Devices , Elastomers , Humans , Keratins , Silicone ElastomersABSTRACT
The store-operated Ca2+ entry (SOCE) moiety ORAI calcium release-activated calcium modulator 1 (ORAI1) located in the endoplasmic reticulum (ER) participates in key cellular functions such as protein folding, transport, and secretion, and lipid metabolism. We used an in vitro approach to test whether exogenous fatty acids alter ORAI1 signaling and to explore potential consequences on mitochondrial dysfunction and ER stress. First, hepatocytes isolated from 4 healthy female calves (1 d old, 40-50 kg) were challenged with a 1.2 mM mixture of oleic, linoleic, palmitic, stearic, and palmitoleic acids for 0.5, 1, 3, 6, 9, and 12 h to measure oxidative stress [intracellular reduced glutathione (GSH), superoxide dismutase (SOD), malondialdehyde (MDA), and hydrogen peroxide] and ER stress (protein abundance of PERK, IRE, ATF6, and GRP78). Concentrations of GSH and SOD decreased at 0.5 h, and MDA and hydrogen peroxide increased at 1 h; ER stress proteins increased at 6 h. To determine whether ER stress was caused by oxidative stress, primary calf hepatocytes were treated with the same 1.2 mM fatty acid mix or the reactive oxygen species (ROS) inhibitor N-acetylcysteine (NAC) for 6 h. We found that NAC prevented an increase in ER stress protein abundance. Next, the role of ORAI1 on ER stress was measured by transfecting hepatocytes with small interfering (si)ORAI1 or the ORAI1 inhibitor BTP2, followed by a challenge with 1.2 mM fatty acids for 3 h. Without inhibiting ORAI1, exogenous fatty acids upregulated ORAI1 mRNA and protein abundance, oxidative stress, ER stress proteins, and protein abundance of marker indicators of an opened mitochondrial permeability transition pore (mPTP). Inhibition with BPT2 or silencing via siORAI1 abrogated oxidative stress, including increased GSH concentration and SOD activity, decreased MDA, hydrogen peroxide, and ROS concentration; ER stress protein abundance was downregulated, and mitochondrial function was restored. Last, changes in markers of mPTP opening were evaluated by culturing hepatocytes for 6 h with the sarcoendoplasmic Ca2+ ATPase inhibitor thapsigargin or the calcium ionophore ionomycin. We detected an increase in VDAC1, CLPP, and CypD protein abundance, all of which indicated opening of the mPTP. Overall, data from these in vitro studies suggest that ORAI1 mediates ER stress induced by high concentrations of fatty acids, in part through alleviating mitochondrial dysfunction caused by oxidative stress.
Subject(s)
Calcium/metabolism , Endoplasmic Reticulum Stress , Fatty Acids/adverse effects , ORAI1 Protein/metabolism , Signal Transduction , Animals , Cattle , Endoplasmic Reticulum/metabolism , Female , Hepatocytes/metabolism , Lactation , Lipid Metabolism , Liver/metabolism , Mitochondria/metabolism , ORAI1 Protein/genetics , Oxidative Stress , Reactive Oxygen Species/metabolismABSTRACT
The aim of the present study was to verify the pro-apoptotic anticancer potential of several 5,8-dimethoxy-1,4-phthoquinone (DMNQ) derivatives in Ras-mediated tumorigenesis. MTT assays were used to detect cellular viability and flow cytometry was performed to assess intracellular reactive oxygen species (ROS) levels and apoptosis. The expression levels of proteins were detected via western blotting. Among the 12 newly synthesized DMNQ derivatives, 2-benzylthio-5,8-dimethoxynaphthalene-1,4-dione (BZNQ; component #1) significantly reduced cell viability both in mouse NIH3T3 embryonic fibroblasts cells (NC) and H-RasG12V transfected mouse NIH3T3 embryonic fibroblasts cells (NR). Moreover, BZNQ resulted in increased cytotoxic sensitivity in Ras-mutant transfected cells. Furthermore, the reactive oxygen species (ROS) levels in H-RasG12V transfected HepG2 liver cancer cells (HR) were significantly higher compared with the levels in HepG2 liver cancer cells (HC) following BZNQ treatment, which further resulted in increased cellular apoptosis. Eliminating cellular ROS using an ROS scavenger N-acetyl-L-cysteine markedly reversed BZNQ-induced cellular ROS accumulation and cell apoptosis in HC and HR cells. Western blotting results revealed that BZNQ significantly downregulated H-Ras protein expression and inhibited the Ras-mediated downstream signaling pathways such as protein kinase B, extracellular signal-related kinase and glycogen synthase kinase phosphorylation and ß-catenin protein expression. These results indicated that the novel DMNQ derivative BZNQ may be a therapeutic drug for Ras-mediated liver tumorigenesis. The results of the current study suggest that BZNQ exerts its effect by downregulating H-Ras protein expression and Ras-mediated signaling pathways.
ABSTRACT
Dielectric elastomer transducers can be applied in many different applications, but their current use is limited by either their electrical breakdown strength or by electromechanical instabilities in the case of soft elastomers. The breakdown process is never a single, simple process but rather-most likely-an ensemble of thermoelectric processes taking place in both elastomer and electrode materials, coupled with mechanical and potentially also chemical degradation. In this work, by using a high-speed camera, we follow silicone-based dielectric elastomers undergoing a ramp-up in voltage close to electrical breakdown strength, with differently constructed elastomers and electrodes. As such, we present experimental insights into the electromechanical processes immediately before the dielectric breakdown of elastomers and identify three different actuation mechanisms taking place prior to electrical breakdown, denoted prebreakdown actuation in the following. The prebreakdown actuation mechanisms observed herein include film thinning and stretching, as well as the formation of bubble- and ring-shaped structures from the elastomer surface, respectively. We furthermore present a theoretical explanation for the observed actuation mechanisms.
ABSTRACT
Keratinocyte hyperproliferation is an essential link in skin cancer pathogenesis. Peroxiredoxin I (Prx I) is known to regulate cancer cell proliferation, differentiation, and apoptosis, but its role in skin cancer remains unclear. This study aimed to elucidate the role and mechanism of Prx I in skin cancer pathogenesis. Dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA) were used to create a skin tumor model of the initiation/promotion stage of cancer. The role of Prx I in H2O2-induced keratinocyte apoptosis was also investigated. After DMBA/TPA treatment, Prx I deficiency was significantly associated with less skin tumors, lower Bcl-2 expression, and higher p-p38 and cleaved caspase-3 expressions in Prx I knockout tumors than in wild-type controls. H2O2 stimulation caused more cellular apoptosis in Prx I knockdown HaCaT cells than in normal HaCaT cells. The signaling study revealed that Bcl-2, p-p38, and cleaved caspase-3 expressions were consistent with the results in the tumors. In conclusion, the deletion of Prx I triggered the DMBA/TPA-induced skin tumor formation in vivo and in vitro by regulating the reactive oxygen species (ROS)-p38 mitogen-activated protein kinase (MAPK) pathway. These findings provide a theoretical basis for treating skin cancer.
Subject(s)
Apoptosis/genetics , Keratinocytes/metabolism , Peroxiredoxins/genetics , Reactive Oxygen Species/metabolism , Skin Neoplasms/genetics , p38 Mitogen-Activated Protein Kinases/metabolism , Animals , Apoptosis/drug effects , Cell Line , HEK293 Cells , Humans , Hydrogen Peroxide/pharmacology , Keratinocytes/cytology , Keratinocytes/drug effects , Mice, 129 Strain , Mice, Knockout , Oxidants/pharmacology , Peroxiredoxins/deficiency , RNA Interference , Signal Transduction , Skin Neoplasms/metabolism , Skin Neoplasms/pathologyABSTRACT
BACKGROUND: Peroxiredoxin II (PRDX2) performs unique roles in cells. It can reduce peroxides through cysteine residues, and helps prevent the effects of oxidative stress on cells. It is closely related to the occurrence and development of various diseases, especially alcoholic liver injury and even liver cancer. The metabolism of alcohol in hepatocytes leads to the increase in the levels of reactive oxygen species (ROS), oxidative stress, injury, and apoptosis. Therefore, this study focused on the investigating the protection conferred by PRDX2 against alcohol-induced apoptosis of hepatocytes. MATERIALS AND METHODS: PRDX2 inhibition of alcohol-induced apoptosis in L02 hepatocytes was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, fluorescence microscopy, flow cytometry, western blotting and hematoxylin and eosin staining. RESULTS: The results showed that the levels of reactive oxygen species, protein kinase B, ß-catenin, B-cell lymphoma-2 (BCL2), BCL-XL, BCL2-associated X, cleaved caspase-3, and cleaved poly (ADP-ribose) polymerase in PRDX2-silenced cells were increased significantly after the treatment of cells with ethanol. Similar results were obtained in an in vivo Prdx2-knockout mouse model of alcoholic liver injury. Therefore, PRDX2 may regulate the phosphorylation of the AKT signal protein by eliminating reactive oxygen species from cells, and it inhibits the downstream mitochondria-dependent apoptosis pathway, and, thereby, the apoptosis of cells. CONCLUSION: Thus, PRDX2 may be a potential molecular target for the prevention and treatment of alcoholic liver injury.
Subject(s)
Ethanol/adverse effects , Hepatocytes/cytology , Peroxiredoxins/genetics , Signal Transduction , Apoptosis , Cell Line , Gene Expression Regulation/drug effects , Gene Silencing , Hepatocytes/drug effects , Hepatocytes/metabolism , Humans , Phosphorylation/drug effects , Poly(ADP-ribose) Polymerases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , beta Catenin/metabolismABSTRACT
Objective To investigate cerebral autoregulation(CA)in patients with severe unilateral carotid artery stenosis by near infrared spectroscopy. Methods Thirty patients who underwent general anesthesia in our hospital from January 2015 to February 2017 were enrolled in this study.The stenosis group included 15 patients with severe unilateral internal carotid artery stenosis,and the control group included 15 patients without carotid artery stenosis.Both groups were matched in sex and age.Cerebral tissue oxygenation index(TOI)and mean arterial pressure were recorded continuously under stable general anesthesia.The Pearson correlation coefficient(r)was calculated to judge the CA status. Results TOI was not significantly different between the stenosis side and the non-stenosis side in the stenosis group(66.52±6.50 vs. 65.23±4.50;t=0.93, P=0.368)or between the stenosis side in the stenosis group and the stenosis side in the control group(66.52±6.50 vs. 64.22±3.87;t=1.18, P=0.248).The r values of stenosis side and non-stenosis side in the stenosis group were 0.36±0.12 and 0.17±0.11,respectively,and the r values of the stenosis side in the stenosis group and the stenosis side of the control group were 0.36±0.12 and 0.13±0.08,respectively.In the stenosis group,5 patients had transient ischemic attack and 2 patients had a history of stroke within 3 months before operation.When an r value of 0.342 was used as the judgment point of CA abnormality,the sensitivity and specificity were 0.625 and 0.909,respectively. Conclusion Within the range of normal blood pressure fluctuation,cerebral blood flow is linked to blood pressure at the stenosis side in patients with severe unilateral carotid artery stenosis.