Size effect in polymeric lattice materials with size-dependent Poisson's ratio caused by Cosserat elasticity.

Polymeric lattice materials with micro/nano-structures are attractive for applications in a wide range of bioengineering systems. Resent experimental results show that elastic constitutive law of polymer materials is in line with the Cosserat elasticity. In this work, a Cosserat continuum spectral element method is employed to explore the size-dependent mechanical performance of polymer polymeric lattice with horseshoe microstructures, efficiently. The mechanical performance predicted by the proposed method agrees very well with the experiment data. Our results demonstrate that size effects are significant in polymeric lattice materials. The size-dependent negative Poisson's ratio is found in the polymeric lattice materials with the same topological structure due to the size effect caused by the Cosserat elasticity of the polymer materials. It could be implied that it is possible to continuously adjust the negative Poisson's ratio of the polymeric lattice material over a wide range by only changing its microstructural size.

Surface property and in vitro toxicity effect of insoluble particles given by protein corona: Implication for PM cytotoxicity assessment.

In vitro toxicological assessment helps explore key fractions of particulate matter (PM) in association with the toxic mechanism. Previous studies mainly discussed the toxicity effects of the water-soluble and organic-soluble fractions of PM. However, the toxicity of insoluble fractions is relatively poorly understood, and the adsorption of proteins is rarely considered. In this work, the formation of protein corona on the surface of insoluble particles during incubation in a culture medium was investigated. It was found that highly abundant proteins in fetal bovine serum were the main components of the protein corona. The adsorbed proteins increased the dispersion stability of insoluble particles. Meanwhile, the leaching concentrations of some metal elements (e.g., Cu, Zn, and Pb) from PM increased in the presence of proteins. The toxicity effects and potential mechanisms of the PM insoluble particle-protein corona complex on macrophage cells RAW264.7 were discussed. The results revealed that the PM insoluble particle-protein corona complex could influence the phagosome pathway in RAW264.7 cells. Thus, it promoted the intracellular reactive oxygen species generation and induced a greater degree of cell differentiation, significantly altering cell morphology. Consequently, this work sheds new light on the combination of insoluble particles and protein corona in terms of PM cytotoxicity assessment.

The role of allogeneic platelet-rich plasma in patients with diabetic foot ulcer: Current perspectives and future challenges.

The frequency of chronic cutaneous wounds are sharply increasing in aging populations. Patients with age-related diseases, such as diabetes, tumors, renal failure and stroke are prone to soft tissue and skin injury, compounded by slowed healing in aging. Imbalance of wound inflammation, loss of growth factor secretion, and impairment of tissue repair abilities are all possible reasons for failed healing. Therefore, it is vital to explore novel approaches to accelerate wound healing. Platelet-rich plasma (PRP) as a cell therapy has been widely applied for tissue repair and regeneration. PRP promotes wound healing by releasing antimicrobial peptides, growth factors and micro-RNAs. Medical evidence indicates that autologous platelet-rich plasma (au-PRP) can promote wound healing effectively, safely and rapidly. However, its clinical application is usually restricted to patients with chronic cutaneous wounds, generally because of other severe complications and poor clinical comorbidities. Allogeneic platelet-rich plasma (al-PRP), with abundant sources, has demonstrated its superiority in the field of chronic wound treatment. Al-PRP could overcome the limitations of au-PRP and has promising prospects in clinical applications. The aim of this review is to summarize the current status and future challenges of al-PRP in chronic cutaneous wound management. We also summarized clinical cases to further describe the application of al-PRP for chronic wounds in clinical practice.

B(C6F5)3-Catalyzed transfer hydrogenation of esters and organic carbonates towards alcohols with ammonia borane.

Herein, we report an efficient metal-free system for the transfer hydrogenation of esters and carbonates by-passing the otherwise ubiquitous formation of transesterification side-products. The Lewis acid B(C6F5)3 is used as catalyst and ammonia borane as hydrogen donor. This methodology shows broad substrate scope and functional group tolerance in excellent yields at very mild conditions.

Downregulation of miR-485-3p promotes proliferation, migration and invasion in prostate cancer through activation of TGF-ß signaling.

BACKGROUND: Prostate cancer (PC) is the second leading cause of cancer-related death among men worldwide. Downregulation of miR-485-3p has been revealed to participate in the tumorigenesis and progression of many types of cancer. However, the clinical and biological role of miR-485-3p in PC remains largely unknown. METHODS: The expression of miR-485-3p was analyzed in the published databases and detected in our clinical samples and cell lines by RT-qPCR assay. CCK8, transwell invasion and migration, and colony formation assays were performed to investigate the biological function of miR-485-3p. Bioinformatical analysis, RIP, western blotting and luciferase reporter assays were carried out to explore the downstream mechanism of miR-485-3p. RESULTS: The level of miR-485-3p was downregulated in PC tissues, particularly in primary PC tissues with metastasis relative to normal prostate tissues. miR-485-3p downregulation was positively correlated with poor disease-free and overall survival in patients with PC. Functionally, miR-485-3p overexpression dramatically suppressed the proliferation, migration and invasion ability of PC cells in vitro. Mechanistically, miR-485-3p overexpression suppressed the activity of TGF-ß signaling by targeting TGFBR2 to play tumor-suppressive roles in PC progression. CONCLUSION: Our study reports the miR-485-3p/TGFBR2/ TGF-ß signaling axis in tumor development of PC, suggesting miR-485-3p may be a potential target to develop therapeutic strategies against PC.

Fluorescent Hybrid Porous Polymers as Sustainable Heterogeneous Photocatalysts for Cross-Dehydrogenative Coupling Reactions.

A series of hybrid porous polymers (HPPs) based on polyhedral oligomeric silsesquioxane (POSS) were synthesized, characterized, and successfully used as metal-free heterogeneous photocatalysts for cross-dehydrogenative coupling reactions (CDC), for which the aza-Henry coupling of tetrahydroisoquinolines and nitroalkanes was studied as the model reaction. The reactions run smoothly at room temperature under visible (blue) light irradiation using gaseous oxygen as an oxidant under atmospheric pressure. These novel metal-free heterogeneous photocatalysts can be readily recovered and reused without a significant loss of reactivity. Mechanistic investigations revealed the intermediacy of 1O2, obtained from 3O2 sensitization (energy transfer) by the photoexcited catalyst.

Efficient destruction of emerging contaminants in water by UV/S(IV) process with natural reoxygenation: Effect of pH on reactive species.

UV/sulfite systems with oxygen have recently been considered as advanced oxidation processes in view of the participation of oxysulfur radicals. However, the contribution of •OH and the efficiency of destructing emerging contaminants (ECs) in water remain largely unclear. Here, the UV/S(IV) process was applied with natural reoxygenation to degrade two typical ECs, diethyl phthalate (DEP) and bisphenol A (BPA) showing different properties. Solution pH played the key role in determining the reactive species, and both DEP and BPA were more favorably degraded at more alkaline conditions with higher utilization efficiency of SO32-. Specifically, the H•, O2•-, •OH and SO3•- were identified at acidic condition, but the amount of •OH accumulated significantly with the elevation of pH. Competitive quenching experiments showed that eaq- and •OH dominated the degradation of DEP and BPA at alkaline condition, respectively. Besides, DEP showed higher quantum efficiency for the indirect photolysis and mineralization degree than that of BPA at pH 9.2 mainly due to the direct use of the primary photoproduct. The possible transformation mechanisms of S(IV) and mineralization routes of both pollutants were proposed. This study may provide new insights into the mechanisms involved in UV/S(IV) process and a promising alternative for efficient removal of ECs in water.

Transport of environmental natural organic matter coated silver nanoparticle across cell membrane based on membrane etching treatment and inhibitors.

Environmental natural organic matters (NOMs) have great effects on the physicochemical properties of engineering nanoparticles, which may impact the transport of nanoparticles across plasma membrane and the cytotoxicity. Therefore, the kinetics, uptake pathway and mass of transporting into A549 cell membrane of silver nanoparticles (AgNPs) coated with citric acid (CA), tartaric acid (TA) and fulvic acid (FA) were investigated, respectively. CA, FA and TA enhanced the colloidal stability of AgNPs in culture medium and have greatly changed the surface plasmon resonance spectrum of AgNPs due to the absorption of CA, FA and TA on surface of AgNPs. Internalizing model showed that velocity of CA-, TA- and FA-nAg transporting into A549 cell were 5.82-, 1.69- and 0.29-fold higher than those of the control group, respectively. Intracellular mass of Ag was dependent on mass of AgNPs delivered to cell from suspension, which obeyed Logistic model and was affected by NOMs that CA- and TA-nAg showed a large promotion on intracellular mass of Ag. The lipid raft/caveolae-mediated endocytosis (LME) of A549 cell uptake of AgNPs were susceptible to CA, TA and FA that uptake of CA-, TA- and FA-nAg showed lower degree of dependent on LME than that of the control (uncoated AgNPs). Actin-involved uptake pathway and macropinocytosis would have less contribution to uptake of FA-nAg. Overall, transmembrane transport of NOMs-coated AgNPs differs greatly from that of the pristine AgNPs.

Composite ammonium glycyrrhizin has hepatoprotective effects in chicken hepatocytes with lipopolysaccharide/enrofloxacin-induced injury.

Composite ammonium glycyrrhizin (CAG) has anti-inflammatory activity. Lipopolysaccharide (LPS) and enrofloxacin (ENR) induce liver damage; however, the mechanism underlying LPS/ENR-induced hepatic injury remains to be elucidated. In the present study, the mechanism of LPS/ENR-induced liver injury was investigated in vitro and the protective effects of CAG were also evaluated. Primary chicken hepatocytes were isolated and a model of LPS/ENR-induced hepatocyte injury was established. mRNA and protein expression levels were evaluated by reverse transcription-quantitative polymerase chain reaction and western blot, respectively. LPS/ENR exposure significantly increased supernatant aspartate aminotransferase (AST) and alanine aminotransferase (ALT). In the LPS/ENR-treated group, glutathione (GSH) and the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) activities were significantly increased. Flow cytometry results revealed that the apoptotic rate significantly increased in the LPS/ENR-treated group compared with the control, while treatment with CAG given 24 h prior to LPS/ENR caused a significant decrease in the apoptotic rate compared with the model group. Furthermore, CAG treatment reversed LPS/ENR-associated alterations in the mRNA and protein expression of Caspase-3, apoptosis regulator Bcl-2 (Bcl-2) and Bcl-2 associated X-protein. The mitochondrial membrane potential significantly decreased and the mitochondrial microstructure was notably altered following exposure to LPS/ENR compared with the control. In conclusion, these results suggested that LPS/ENR-treated hepatocytes were damaged via apoptotic signaling pathways and CAG prevented LPS/ENR-induced hepatocyte injury.

Comparison of Allogeneic Platelet-rich Plasma With Autologous Platelet-rich Plasma for the Treatment of Diabetic Lower Extremity Ulcers.

REGISTRATION NUMBER OF CLINICAL TRIALS: ChiCTR1900021317.

Two Pathogenic Gene Mutations Identified Associating with Congenital Cataract and Iris Coloboma Respectively in a Chinese Family.

PURPOSE: To screen out pathogenic genes in a Chinese family with congenital cataract and iris coloboma. Material and Methods. A three-generation family with congenital cataract and iris coloboma from a Han ethnicity was recruited. DNA was extracted from peripheral blood samples collected from all individuals in the family. Whole exon sequencing was employed for screening the disease-causing gene mutations in the proband, and Sanger sequencing was used for other members of the family and a control group of 500 healthy individuals. Bioinformatics analysis and three-dimensional structure predictions were used to predict the impact of amino acid changes on protein structure and function. RESULTS: The candidate genes of cataract and iris coloboma were successfully screened out. A heterozygote mutation, CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation. CONCLUSIONS: We report a novel mutation, WFS1 p.C505S, and a known mutation, CRYGD p.P24T, that cosegregate with iris coloboma and congenital cataract, respectively, in a Chinese family. This is the first time the association of WFS1 p.C505S with iris coloboma has been demonstrated, although CRYGD p.P24T has been widely reported as being associated with congenital cataract, especially in the Eastern Asian population. These findings may have future therapeutic benefit for the diagnosis of iris coloboma and congenital cataract. The results may also be relevant in further studies aiming to investigate the molecular pathogenesis of iris coloboma and congenital cataract.WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation, WFS1 c.1514G>C (p.C505S), which had not been reported previously, cosegregated with congenital iris coloboma. Bioinformatic analyses and three-dimensional structure prediction proved that the three-dimensional structures of CRYGD c.70C>A (p.P24T), was identified as cosegregating with congenital cataracts, while another heterozygous mutation.

Cytotoxicity and toxicoproteomic analyses of human lung epithelial cells exposed to extracts of atmospheric particulate matters on PTFE filters using acetone and water.

Differences of cytotoxicity associated with exposure to different extracts of atmospheric particulate matters (PMs) are still not well characterized by in vitro toxicoproteomics. In this study, in vitro cytotoxicity assays and toxicoproteomic analyses were carried out to investigate toxic effects of PM collected using polytetrafluoroethylene (PTFE) filters extracted with acetone for PM2.1 and water for PM2.1 and PM10 on A549 human lung epithelial cells. The cytotoxicity assays based on cell viability, cell apoptosis and reactive oxygen species generation indicated that PM2.1 extracted with acetone had the highest toxicity. iTRAQ labeling and LC-MS/MS analyses indicated that the number of differentially expressed proteins in A549 cells affected by PM2.1 extracted with acetone was noticeably higher than that of the other two groups. Hierarchical cluster analyses showed that the influences of the extracts of PM2.1 and PM10 using water on the proteome of A549 cells were similar, whereas significantly different from the effect of PM2.1 extracted with acetone. Pathways analyses indicated that PM2.1 extracted with acetone influenced the expression of proteins involved in 14 pathways including glycolysis/gluconeogenesis, pentose phosphate pathway, proteasome, etc. PM2.1 extracted with water affected the expression of proteins involved in 3 pathways including non-homologous end-joining, ribosome and endocytosis. However, PM10 extracted with water affected the expression of proteins involved in only spliceosome pathway. The extracts of PM using different extractants to detach PM from PTFE filters influenced the cytotoxic effects of PM and the proteome of A549 cells. Therefore, extractants should be assessed carefully before the investigations on cytotoxicity to improve the compatibility of experimental results among research teams.

Farnesoid X Receptor (FXR) Aggravates Amyloid-ß-Triggered Apoptosis by Modulating the cAMP-Response Element-Binding Protein (CREB)/Brain-Derived Neurotrophic Factor (BDNF) Pathway In Vitro.

BACKGROUND Alzheimer's disease (AD), which results in cognitive deficits, usually occurs in older people and is mainly caused by amyloid beta (Aß) deposits and neurofibrillary tangles. The bile acid receptor, farnesoid X receptor (FXR), has been extensively studied in cardiovascular diseases and digestive diseases. However, the role of FXR in AD is not yet understood. The purpose of the present study was to investigate the mechanism of FXR function in AD. MATERIAL AND METHODS Lentivirus infection, flow cytometry, real-time PCR, and western blotting were used to detect the gain or loss of FXR in cell apoptosis induced by Aß. Co-immunoprecipitation was used to analyze the molecular partners involved in Aß-induced apoptosis. RESULTS We found that the mRNA and protein expression of FXR was enhanced in Ab-triggered neuronal apoptosis in differentiated SH-SY5Y cells and in mouse hippocampal neurons. Overexpression of FXR aggravated Aß-triggered neuronal apoptosis in differentiated SH-SY5Y cells, and this effect was further increased by treatment with the FXR agonist 6ECDCA. Molecular mechanism analysis by co-immunoprecipitation and immunoblotting revealed that FXR interacted with the cAMP-response element-binding protein (CREB), leading to decreased CREB and brain-derived neurotrophic factor (BDNF) protein levels. Low expression of FXR mostly reversed the Aß-triggered neuronal apoptosis effect and prevented the reduction in CREB and BDNF. CONCLUSIONS These data suggest that FXR regulates Aß-induced neuronal apoptosis, which may be dependent on the CREB/BDNF signaling pathway in vitro.

Response of the environmental thermal neutron flux to earthquakes.

Some new results were obtained by the array of EN-detectors (Electron and Neutron detectors) developed in the frame of the PRISMA (PRImary Spectrum Measurement Array) project for Extensive Air Showers detection. Our EN-detectors running both on the Earth surface and underground are continuously measuring the environmental thermal neutron flux. Neutrons are partially produced by radioactive gas radon and its daughter decays through (α,n)-reactions in soil close to the detectors. Then neutrons thermalize in media and, being in equilibrium with it, they are sensitive to many geo-dynamic phenomena including earthquakes. In this work the EN-detectors were measuring the variations of an environmental neutron flux in Tibet (30.11 N, 90.53 E, 4300 m a.s.l) at a distance of ∼600 km from the collision zone of the Asian-Indian plates subduction zone (Nepal region). We have observed some anomalies in the dynamics of the neutron flux around the time of the catastrophic earthquakes of magnitude M = 7.8 happened in Gorkha (Nepal) on 25.04.2015 followed by a series of aftershocks of M > 6. The use of nuclear physics methods can provide novel results in geophysics and this work demonstrates the sensitivity of the environmental thermal neutron flux to changes in tense-deformed crust conditions caused by earthquakes with epicentral distances greater than 500 km.

Promoting Fe3+/Fe2+ cycling under visible light by synergistic interactions between P25 and small amount of Fenton reagents.

Merits of adding P25 to homogeneous photo-Fenton-like process (ph-F) were evaluated under visible light using Bisphenol A (BPA) as a model pollutant. Interactions between P25 and Fe3+/H2O2 were emphasized. Results show that adsorption of Fe(III) on P25 produced redshift of light absorption, and interactions between P25 and H2O2 promoted photoelectron generation, effectively introducing visible light into ph-F. The visible-light-driven ph-F demonstrated adequate performance at high Fe3+/H2O2 dosage, while P25 addition showed significant acceleration of BPA degradation with saving amount of Fe3+/H2O2. The mechanism was confirmed to be enhanced Fe3+/Fe2+ cycling by photo-electrons, particularly pronounced at low [Fe(III)]. Additionally, H2O2 was utilized more efficiently in P25-ph-F than that in ph-F by diminishing the radical scavenging role of H2O2 at lower [Fe(III)]. Kinetics and ESR analysis supported this mechanism. Compared to ph-F, the P25-ph-F process also demonstrated stronger potentials in degrading BPA at high concentrations and better mineralization capability with reduced Fe3+/H2O2 reagents. The sustainability of P25-ph-F was also examined in regard to its advantage under sunlight and the strong recyclable and reusable capability. BPA decomposition was dominated by •OH attack at both the aromatic ring and the connecting carbon, and P25-ph-F was more competent in transforming the primary intermediates than ph-F.

Impaired Cognitive Function and Altered Hippocampal Synaptic Plasticity in Mice Lacking Dermatan Sulfotransferase Chst14/D4st1.

Chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycans (PGs) are major extracellular matrix (ECM) components of the central nervous system (CNS). A large body of evidence has shown that CSPGs/DSPGs play critical roles in neuronal growth, axon guidance, and plasticity in the developing and mature CNS. It has been proposed that these PGs exert their function through specific interaction of CS/DS chains with its binding partners in a manner that depends on the sulfation patterns of CS/DS. It has been reported that dermatan 4-O-sulfotransferase-1 (Chst14/D4st1) specific for DS, but not chondroitin 4-O-sulfotransferase-1 (Chst11/C4st1) specific for CS, regulates proliferation and neurogenesis of neural stem cells (NSCs), indicating that CS and DS play distinct roles in the self-renewal and differentiation of NSCs. However, it remains unknown whether specific sulfation profiles of DS has any effect on CNS plasticity. In the present study, Chst14/D4st1-deficient (Chst14 -/-) mice was employed to investigate the involvement of DS in synaptic plasticity. First, behavior study using Morris Water Maze (MWM) showed that the spatial learning and memory of Chst14 -/- mice was impaired when compared to their wild type (WT) littermates. Corroborating the behavior result, long-term potentiation (LTP) at the hippocampal CA3-CA1 connection was reduced in Chst14 -/- mice compared to the WT mice. Finally, the protein levels of N-Methyl-D-aspartate (NMDA) receptor, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, postsynaptic density 95 (PSD95), growth associated protein 43 (GAP-43), synaptophysin (SYN) and N-ethylmaleimide sensitive factor (NSF) which are important in synaptic plasticity were examined and Chst14/D4st1 deficiency was shown to significantly reduce the expression of these proteins in the hippocampus. Further studies revealed that Akt/mammalian target rapamycin (mTOR) pathway proteins, including protein kinase B (p-Akt), p-mTOR and p-S6, were significantly lower in Chst14 -/- mice, which might contribute to the decreased protein expression. Together, this study reveals that specific sulfation of DS is critical in synaptic plasticity of the hippocampus and learning and memory, which might be associated with the changes in the expression of glutamate receptors and other synaptic proteins though Akt/mTOR pathway.

Extremely Low-Cost and Green Cellulose Passivating Perovskites for Stable and High-Performance Solar Cells.

The fast evolution of metal halide perovskite solar cells has opened a new chapter in the field of renewable energy. High-quality perovskite films as the active layers are essential for both high efficiency and long-term stability. Here, the perovskite films with enlarged crystal grain size and decreased defect density are fabricated by introducing the extremely low-cost and green polymer, ethyl cellulose (EC), into the perovskite layer. The addition of EC triggers hydrogen bonding interactions between EC and the perovskite, passivating the charge defect traps at the grain boundaries. The long chain of EC further acts as a scaffold for the perovskite structure, eliminating the annealing-induced lattice strain during the film fabrication process. The resulting devices with the EC additive exhibit a remarkably enhanced average power conversion efficiency from 17.11 to 19.27% and an improvement of all device parameters. The hysteresis index is found to decrease by three times from 0.081 to 0.027, which is attributed to suppressed ion migration and surface charge trapping. In addition, the defect passivation by EC significantly improves the environmental stability of the perovskite films, yielding devices that retain 80% of their initial efficiency after 30 days in ambient air at 45% relative humidity, whereas the pristine devices without EC fully degrade. This work provides a low-cost and green avenue for passivating defects that improves both the efficiency and operational stability of perovskite solar cells.

Organocatalytic decarboxylative alkylation of N-hydroxy-phthalimide esters enabled by pyridine-boryl radicals.

The decarboxylative alkylation of N-hydroxyphthalimide (NHPI) based reactive esters with olefins has been achieved via an organocatalytic strategy. Control experiments and density functional theory calculations suggest that these reactions involve a boryl-radical mediated decarboxylation pathway, which is different from the single electron transfer involved in decarboxylative alkylation reactions reported previously. This metal-free decarboxylative alkylation reaction features good functional compatibility, and broad substrate scope illustrated by the transformations of both the alkyl and aryl carboxylic acid derivatives.

Protective effects of compound ammonium glycyrrhizin, L­arginine, silymarin and glucurolactone against liver damage induced by ochratoxin A in primary chicken hepatocytes.

Ochratoxin A (OTA) is a mycotoxin that is produced by fungi in improperly stored food and animal feed. It exhibits nephrotoxic, hepatotoxic, embryotoxic, teratogenic, neurotoxic, immunotoxic and carcinogenic effects in laboratory and farm animals. In the present study, the hepatotoxicity of OPA was investigated in chicken primary hepatocytes. On this basis, the cytoprotective effects of compound ammonium glycyrrhizin (CAG), L­arginine (L­Arg), silymarin (Sil) and glucurolactone (GA) were investigated in vitro. Hepatocytes were treated with OTA, which resulted in a significant decrease in cell viability and increases in serum aspartate transaminase and alanine transaminase activities, as determined by an MTT assay and commercial kits, respectively. Furthermore, following OTA treatment, the levels of hepatic antioxidants, such as superoxide dismutase and glutathione, were decreased, and the lipid peroxidation product malondialdehyde was increased, compared with the control group. However, pretreatment with CAG, L­Arg, Sil and GA significantly ameliorated these alterations and Sil exerted the optimum hepatoprotective effect. The apoptotic rates were measured by flow cytometry and the results revealed that OTA increased cell apoptosis. The four types of hepatoprotective compounds employed in the present study decreased the apoptosis rate and significantly reversed OTA­induced increases in the mRNA expression levels of caspase­3, which was determined by reverse transcription­quantitative polymerase chain reaction. Furthermore, B­cell lymphoma­2 (Bcl­2) mRNA expression was increased in OTA­treated cells when pretreated with CAG, L­Arg, Sil and GA. However, no alterations in the mRNA expression of Bcl­2­associated X were observed in the L­Arg and GA groups, compared with the OTA­only group. These results indicate that OTA may exhibit hepatotoxicity in chickens and that CAG, L­Arg, Sil and GA may protect the liver against this via anti­oxidative and antiapoptosis mechanisms. In addition, CAG and GA are likely to mediate their effects through the mitochondrion­dependent apoptosis pathway; however, the exact hepatoprotective mechanism of L­Arg and GA require further investigation. Therefore, CAG, L­Arg, Sil and GA are potential candidates for the prevention and treatment of chicken liver injury.

Ammonium glycyrrhizin counteracts liver injury caused by lipopolysaccharide/amoxicillin-clavulanate potassium.

We treated isolated chicken primary hepatocytes with lipopolysaccharide/amoxicillin clavulanate potassium (LPS/AC) to model liver injury and investigate its underlying mechanisms. We also used this model to assess the cytoprotective effects of compound ammonium glycyrrhizin (CAG) in vitro. LPS/AC-induced injury decreased cell viability and increased the activity of serum aspartate transaminase and alanine transaminase. Levels of superoxide dismutase, glutathione, and glutathione peroxidase were lower than control, while levels of the oxidative product malondialdehyde and reactive oxygen species were higher. Treatment with CAG for 24 h ameliorated these changes. Caspase-3 activity assays and flow cytometry revealed increased apoptosis in the model group. However, apoptosis decreased after CAG treatment, as confirmed by Hoechst 33342 staining. We also observed changes in mitochondrial ultrastructure. Real-time PCR and western blot analyses showed that CAG treatment downregulated LPS/AC-induced RNA expression of caspase-3, caspase-9, bax, cytochrome c, and fas, and upregulated the expression of bcl-2. Mitochondrial cytochrome c was released into the cytosol and the inner mitochondrial membrane potential (ΔΨm) was decreased. Our results highlight CAG as a potential therapeutic agent to counteract LPS/AC-induced liver injury.