Ginkgolide C inhibits ROS-mediated activation of NLRP3 inflammasome in chondrocytes to ameliorate osteoarthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba, as the most widely available medicinal plant worldwide, has been frequently utilized for treat cardiovascular, cerebrovascular, diabetic and other diseases. Due to its distinct pharmacological effects, it has been broadly applications in pharmaceuticals, health products, dietary supplements, and so on. Ginkgolide C (GC), a prominent extract of Ginkgo biloba, possesses potential in anti-inflammatory and anti-oxidant efficacy. AIMS OF THE STUDY: To determine whether GC mitigated the progressive degeneration of articular cartilage in a Monosodium Iodoacetate (MIA)-induced osteoarthritis (OA) rat model by inhibiting the activation of the NLRP3 inflammasome, and the specific underlying mechanisms. MATERIALS AND METHODS: In vivo, an OA rat model was established by intra-articular injection of MIA. The protective effect of GC (10 mg/kg) on articular cartilage was evaluated. Application of ATDC5 cells to elucidate the mechanism of the protective effect of GC on articular cartilage. Specifically, the expression levels of molecules associated with cartilage ECM degrading enzymes, OS, ERS, and NLRP3 inflammasome activation were analyzed. RESULTS: In vivo, GC ameliorated MIA-induced OA rat joint pain, and exhibited remarkable anti-inflammatory and anti- ECM degradation effects via inhibition of the activation of NLRP3 inflammasome, the release of inflammatory factors, and the expression of matrix-degrading enzymes in cartilage. Mechanically, GC inhibited the activation of NLRP3 inflammasome by restraining ROS-mediated p-IRE1α and activating Nrf2/NQO1 signal path, thereby alleviating OA. The ROS scavenger NAC was as effective as GC in reducing ROS production and inhibiting the activation of NLRP3 inflammasome. CONCLUSIONS: GC have exerted chondroprotective effects by inhibiting the activation of NLRP3 inflammasome.

Integrated 16S and metabolomics revealed the mechanism of drought resistance and nitrogen uptake in rice at the heading stage under different nitrogen levels.

The normal methods of agricultural production worldwide have been strongly affected by the frequent occurrence of drought. Rice rhizosphere microorganisms have been significantly affected by drought stress. To provide a hypothetical basis for improving the drought resistance and N utilization efficiency of rice, the study adopted a barrel planting method at the heading stage, treating rice with no drought or drought stress and three different nitrogen (N) levels. Untargeted metabolomics and 16S rRNA gene sequencing technology were used to study the changes in microorganisms in roots and the differential metabolites (DMs) in rhizosphere soil. The results showed that under the same N application rate, the dry matter mass, N content and N accumulation in rice plants increased to different degrees under drought stress. The root soluble protein, nitrate reductase and soil urease activities were improved over those of the no-drought treatment. Proteobacteria, Bacteroidota, Nitrospirota and Zixibacteria were the dominant flora related to N absorption. A total of 184 DMs (98 upregulated and 86 downregulated) were identified between low N with no drought (LN) and normal N with no drought (NN); 139 DMs (83 upregulated and 56 downregulated) were identified between high N with no drought (HN) and NN; 166 DMs (103 upregulated and 63 downregulated) were identified between low N with drought stress (LND) and normal N with drought stress (NND); and 124 DMs (71 upregulated and 53 downregulated) were identified between high N with drought stress (HND) and NND. Fatty acyl was the metabolite with the highest proportion. KEGG analysis showed that energy metabolism pathways, such as D-alanine metabolism and the phosphotransferase system (PTS), were enriched. We conclude that N-metabolism enzymes with higher activity and higher bacterial diversity have a significant effect on drought tolerance and nitrogen uptake in rice.

Analysis of Related Metabolites Affecting Taste Values in Rice under Different Nitrogen Fertilizer Amounts and Planting Densities.

The aim of this study was to explore the differences in metabolites related to rice quality formation under different nitrogen (N) fertilizers and planting densities. In this study, Yangnongxiang 28 was used as the experimental material with the following conditions: high nitrogen and low density (HNLD; high nitrogen: 360 kg·hm-2, low density: the row spacing of rice plants was 16 cm × 30 cm), medium nitrogen and medium density (MNMD; medium nitrogen: 270 kg·hm-2, medium density: the row spacing of rice plants was 13 cm × 30 cm), and low nitrogen and high density (LNHD; low nitrogen: 270 kg·hm-2, high density: the row spacing of rice plants was 10 cm × 30 cm). The rice quality indexes, including the processing quality, amylose content, and taste value, were compared under different treatments, and we analyzed their relationship with the metabolites. The results show that the milled rice rate of HNLD was 13.85% and was 1.89% higher than that of LNHD and MNMD, respectively. The head milled rice rate of HNLD was 32.45% and 6.39% higher than that of LNHD and MNMD, respectively. The milled rice rate and head milled rice rate of HNLD and MNMD were significantly higher than those of LNHD. This study identified 22 differential metabolites (DMs) in HNLD and LNHD, 38 DMs in HNLD and MNMD, and 23 DMs in LNHD and MNMD. Most of the identified differential metabolites were lipid metabolites, which were mainly enriched in the lipid metabolic pathways and amino acid metabolic pathways. The correlation analysis showed that the lipid metabolite physapubescin was significantly negatively correlated with the taste value. The lipid metabolites 2-undecen-1-ol, lucidenic acid F, and 8-deoxy-11,13-dihydroxygrosheimin were significantly positively correlated with the taste value. Lipids may be important substances that lead to differences in taste under different nitrogen fertilizer and density treatments.

Can ensemble machine learning be used to predict the groundwater level dynamics of farmland under future climate: a 10-year study on Huaibei Plain.

Accurate and simple prediction of farmland groundwater level (GWL) is an important aspect of agricultural water management. A farmland GWL prediction model, GWPRE, was developed that integrates four machine learning (ML) models (support vector machine regression, random forest, multiple perceptions, and the stacking ensemble model) with weather forecasts. Based on the GWL and meteorological data of five monitoring wells (N1, N2, N3, N4, and N5) in Huaibei plain from 2010 to 2020, the feasibility of predicting GWL by meteorological factors and ML algorithm was tested. In addition, the stacking ensemble model and future meteorological data after Bayesian model averaging were introduced for the first time to predict GWL under future climate conditions. The results showed that GWL showed an increasing trend in the past decade, but it will decrease in the future. The performance of the stacking ensemble model was better than that of any single ML model, with RMSE reduced by 4.26 ~ 96.97% and the running time reduced by 49.25 ~ 99.40%. GWL was most sensitive to rainfall, and the sensitivity index ranged from 0.2547 to 0.4039. The fluctuation range of GWL of N1, N2, and N3 was 1.5 ~ 2.5 m in the next decade. Due to the possible high rainfall, the GWL decreased in 2024 under RCP 2.6 and 2026 under RCP 8.5. It is worth noting that although the stacking ensemble model can improve the accuracy, it is not always the best among ML models in terms of portability. Nevertheless, the stacking ensemble model was recommended for GWL prediction under climate change.

Dihydromyricetin alleviates Escherichia coli lipopolysaccharide-induced hepatic injury in chickens by inhibiting the NLRP3 inflammasome.

Dihydromyricetin (DHM), a flavonoid in vine tea, has many pharmacological activities, including anti-inflammatory and antibacterial effects. Lipopolysaccharide is the key inducer of inflammation in avian pathogenic Escherichia coli (E. coli) infection; however, the effect of DHM on E. coli lipopolysaccharide-induced hepatic injury remains unknown. The present study aimed to explore the role of the NLRP3 inflammasome in hepatic injury and the possible protective mechanisms of DHM against hepatic injury in chickens. The results showed that when chickens were administered lipopolysaccharide, liver damage was observed, accompanied by increased levels of serum transaminases and direct bilirubin. Additionally, hepatic expression levels of NLRP3 and caspase-1 p20, the subunit of caspase-1 that is cleaved after NLRP3 activation, significantly increased in liver injury. We found that treatment with MCC950, a specific NLRP3 inhibitor, significantly decreased serum transaminase activities, direct bilirubin content, and hepatic NLRP3 and caspase-1 p20 expression levels. DHM significantly reduced serum transaminase activities and direct bilirubin content and ameliorated histopathological and ultrastructural changes in the liver. DHM decreased hepatic levels of H2O2 and malondialdehyde and increased the activities of superoxide dismutase and glutathione peroxidase. Furthermore, DHM significantly decreased the expression levels of NLRP3, pro-caspase-1 and caspase-1 p20. Moreover, DHM reduced serum lactate dehydrogenase, IL-1ß and IL-18 levels and repressed hepatic IL-1ß, IL-18 and gasdermin A expression. The results demonstrated that the NLRP3 inflammasome was involved in the mechanism of lipopolysaccharide-induced hepatic injury. Furthermore, DHM could inhibit NLRP3 inflammasome activation and subsequent pyroptosis, eventually ameliorating E. coli lipopolysaccharide-induced liver injury.

Exploration of water-nitrogen coupling effects in paddy field based on ORYZA (v3) model.

BACKGROUND: Nitrogen and water are two major factors in rice production. Due to the lack of ample evidence and much uncertainty in field experiments, the coupling effects of water and nitrogen in paddy fields have remained debatable over recent years. RESULTS: A fine-calibrated ORYZA (v3) model was applied to simulate rice growth and development under different nitrogen (N) rates and irrigation regimes for a double rice-cropping system in South China. We designed a numerical experiment of 504 treatments, consisting of seven nitrogen rates (0-300 kg ha-1 ), eight irrigation thresholds (30-100%, presented as the percentage of saturated soil water content) and nine irrigation quotas (20-100 mm), and each treatment was simulated for 30 years. Yield varied greatly with different water-nitrogen conditions, particularly in the scenario of frequently alternate wetting and drying irrigation and low-N rates. The coupling effects had a negligible influence on water input and water loss, which were found to be sensitive only to the irrigation regime and rainfall distribution. Based on the results, the N fertilizer for early rice growing in the wet season is suggested as 150-200 kg ha-1 , and 200-250 kg ha-1 for late rice growing in the dry season. The irrigating threshold and irrigation quota for early rice are suggested as lower than 70% and 30-40 mm, respectively, and, for late rice, 70-80% and 40-60 mm. CONCLUSION: Remarkable water-nitrogen coupling effects were found in the paddy field, and integrative water-nitrogen management strategies were suggested for both early rice and late rice in South China. © 2021 Society of Chemical Industry.

Drug-induced liver injury: Oltipraz and C2-ceramide intervene HNF-1α/GSTA1 expression via JNK signaling pathway.

Drug-induced liver injury (DILI) is a serious and frequently occurring issue in drug development. The c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in many diseases; hepatocyte nuclear factor-1α (HNF-1α) and glutathione S-transferase A1 (GSTA1) are important in regulating liver-specific genes expressions and affecting drug metabolism. Oltipraz is used to treat liver cirrhosis by improving liver function, and C2-ceramide is a pro-apoptotic lipid that regulates multiple signaling pathways. In this study, we investigated the function of the JNK signaling pathway with HNF-1α and GSTA1 in a cellular model of DILI and whether oltipraz and C2-ceramide exert effects via the JNK pathway. The results showed that inhibiting JNK could ameliorate APAP-induced hepatocyte injury, reduced oxidative stress, suppressed JNK and c-Jun activation, and hepatocyte apoptosis. Meanwhile, the mRNA and protein expressions of HNF-1α and GSTA1 were increased significantly compared to control conditions. The effect of oltipraz (8 µmol/L) was similar to a JNK inhibitor and significantly increased HNF-1α/GSTA1 expression, but oltipraz combined with JNK inhibitor did not show a synergistic effect. Although C2-ceramide (8 µmol/L) aggravated hepatocyte injury and apoptosis, exacerbated oxidative stress, increased phosphorylation of JNK and c-Jun, and markedly decreased HNF-1α/GSTA1 expression, C2-ceramide combined with JNK inhibitor could partially alleviate these alterations. These results demonstrated that the JNK signaling pathway with HNF-1α/GSTA1 are involved in the process of DILI. Inhibiting JNK up-regulated HNF-1α and GSTA1 expressions which could attenuate hepatocyte injury. Oltipraz and C2-ceramide might affect the expression of HNF-1α/GSTA1 though JNK signaling.

Hematologic and biochemical reference intervals for 1-month-old specific-pathogen-free Landrace pigs.

BACKGROUND: Hematologic and biochemical reference intervals (RIs) provide valuable data for the nutritional status and clinical diagnosis of animals. However, the specific hematologic and biochemical RIs for specific-pathogen-free (SPF) Landrace pigs has not been determined. OBJECTIVE: The present study was designed to establish the hematologic and biochemical RIs for SPF 1-month-old Landrace pigs. METHODS: Blood samples were collected from the jugular vein of 105 SPF 1-month-old Landrace pigs (50 males and 55 females), and complete blood counts and biochemical examinations were performed. The mean, RI, and 90% confidence interval were calculated for each variable, and gender differences were analyzed. RESULTS: Reference intervals for SPF 1-month-old Landrace pigs were generated. The results revealed that there was generally no significant difference between male and female hematologic and serum biochemical variables (P > .05). However, a significant difference was noted in serum triglyceride concentrations between male and female pigs (P < .05). CONCLUSIONS: This study provides hematologic and biochemical RIs for SPF 1-month-old Landrace pigs and provides basic data for the research and application of SPF Landrace pigs as a laboratory animal.

Dihydromyricetin attenuates Escherichia coli lipopolysaccharide-induced ileum injury in chickens by inhibiting NLRP3 inflammasome and TLR4/NF-κB signalling pathway.

Lipopolysaccharide (LPS) as a major component of Escherichia coli cell wall can cause inflammation and cell death. Dihydromyricetin (ampelopsin, DHM) is a natural flavonoid compound with anti-inflammatory, anti-oxidant and anti-bacterial effects. The preventive effects of DHM against ileum injury remain unclear. Here, we explored the protective role of DHM against LPS-induced ileum injury in chickens. In this study, DHM significantly attenuated LPS-induced alteration in diamine oxidase, malondialdehyde, reduced glutathione, glutathione peroxidase and superoxide dismutase levels in chicken plasma and ileum. Histology evaluation showed that the structure of blood vessels in ileum was seriously fragmented and presence of necrotic tissue in the lumen in the LPS group. Scanning electron microscopic observation revealed that the surface of the villi was rough and uneven, the structure was chaotic, and the normal finger shape was lost in the LPS group. In contrast, 0.05% and 0.1% DHM treatment partially alleviated the abnormal morphology. Additionally, DHM maintained the barrier function by restoring the protein expression of occludin, claudin-1 and zonula occludens protein-1. DHM inhibited apoptosis through the reduction of the expression of bax and caspase-3 and restored the expression of bcl-2. Importantly, DHM could reduce ileum NLR family pyrin domain-containing 3 (NLRP3), caspase-1, interleukin (IL)-1ß and IL-18 expression to protect tissues from pyroptosis and inhibited toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signalling pathway. In summary, DHM attenuated the ileum mucosal damage, oxidative stress and apoptosis, maintained barrier function, inhibited NLRP3 inflammasome and TLR4/NF-κB signalling pathway activation triggered by Escherichia coli LPS.

JNK Signaling Pathway Mediates Acetaminophen-Induced Hepatotoxicity Accompanied by Changes of Glutathione S-Transferase A1 Content and Expression.

Acetaminophen (APAP) is an analgesic-antipyretic drug and widely used in clinics. Its overdose may cause serious liver damage. Here, we examined the mechanistic role of c-Jun N-terminal kinase (JNK) signaling pathway in liver injury induced by different doses of APAP. Male mice were treated with APAP (150 and 175 mg·kg-1), and meanwhile JNK inhibitor SP600125 was used to interfere APAP-induced liver damage. The results showed that JNK signaling pathway was activated by APAP in a dose-dependent manner. C-Jun N-terminal kinase inhibitor decreased JNK and c-Jun activation significantly (P < 0.01) at 175 mg·kg-1 APAP dose, and phosphorylation levels of upstream proteins of JNK were also decreased markedly (P < 0.05). In addition, serum aminotransferases activities and hepatic oxidative stress increased in a dose-dependent manner with APAP treatment, but the levels of aminotransferases and oxidative stress decreased in mice treated with JNK inhibitor, which implied that JNK inhibition ameliorated APAP-induced liver damage. It was observed that apoptosis was increased in APAP-induced liver injury, and SP600125 can attenuate apoptosis through the inhibition of JNK phosphorylation. Meanwhile, glutathione S-transferases A1 (GSTA1) content in serum was enhanced, while GSTA1 content and expression in liver reduced significantly with administration of APAP (150 and 175 mg·kg-1). After inhibiting JNK, GSTA1 content in serum decreased significantly (P < 0.01); meanwhile, GSTA1 content and expression in liver enhanced. These findings suggested that JNK signaling pathway mediated APAP-induced hepatic injury, which was accompanied by varying GSTA1 content and expression in liver and serum.

Comparison of hematologic and biochemical reference values in specific-pathogen-free 1-month-old Yorkshire pigs and Yorkshire-Landrace crossbred pigs.

Analysis of hematologic and biochemical values in pigs is an important basis for biomedical research and veterinary clinical diagnosis. Reference values for specific-pathogen-free (SPF) 1-month-old Yorkshire (Y) pigs and Yorkshire-Landrace crossbred (YL) pigs are limited. The present research aimed to describe and compare the reference values for hematologic and biochemical parameters in such pigs. Blood samples were obtained from 90 Y pigs (52 males and 38 females) and 88 YL pigs (55 males and 33 females), all 1 month old and bred in an SPF environment. Among the 16 hematologic and 15 serum biochemical parameters tested, no significant differences between the Y and YL pigs were found except in the concentration of triglyceride (P < 0.05), and heterosis was not observed. Thus, the values determined in this study can be used as basic reference values for 1-month-old Y and YL pigs and will contribute to the use of SPF pigs in biomedical research.

L'analyse des valeurs hématologiques et biochimiques chez les porcs est une base importante pour la recherche biomédicale et le diagnostic clinique vétérinaire. Des valeurs de référence pour des porcs exempts d'agents pathogènes spécifiques (SPF) âgés de 1 mois de race Yorkshire (Y) ou Yorkshire­Landrace croisée (YL) sont limitées. La présente étude visait à décrire et comparer les valeurs de référence pour des paramètres hématologiques et biochimiques chez ces porcs. Des échantillons sanguins furent obtenus de 90 porcs Y (52 mâles et 38 femelles) et 88 porcs YL (55 mâles et 33 femelles), tous âgés de 1 mois et élevés dans un environnement SPF. Parmi les 16 paramètres hématologiques et les 15 paramètres biochimiques sériques testés, aucune différence significative ne fut trouvée entre les porcs Y et YL sauf pour la concentration de triglycérides (P < 0,05), et aucune hétérosis ne fut observée. Ainsi, les valeurs déterminées dans la présente étude peuvent être utilisées comme valeurs de référence de base pour des porcs Y et YL âgés de 1 mois et vont contribuer à l'utilisation de porcs SPF en recherche biomédicale.(Traduit par Docteur Serge Messier).

Acetaminophen-induced hepatocyte injury: C2-ceramide and oltipraz intervention, hepatocyte nuclear factor 1 and glutathione S-transferase A1 changes.

Acetaminophen (APAP) is an antipyretic and analgesic, which is commonly associated with drug-induced hepatic injury. C2-ceramide plays a key role in mediating cell life activities, and oltipraz was extensively studied as a cancer chemopreventive agent. Glutathione S-transferase A1 (GSTA1) acts as a vital liver detoxification enzyme. Hepatocyte nuclear factor 1 (HNF-1) regulates various cellular signaling pathways. In this study, we investigated the effects of C2-ceramide and oltipraz on APAP-induced hepatocyte injury and the changes of HNF-1 and GSTA1. Results showed that C2-ceramide (6 µmol/L) exacerbated APAP-induced hepatocyte injury and caused a significant decrease (P < .01) in HNF-1 and GSTA1 expressions. Meanwhile, GSTA1 content in supernatant was significantly increased (P < .01). In contrast, oltipraz (8 µmol/L) reduced the injury and significantly elevated (P < .01) HNF-1 and GSTA1 expressions while GSTA1 content in supernatant was significantly decreased (P < .01). In conclusion, these findings revealed that C2-ceramide inhibited HNF-1 and GSTA1 expression and exacerbated hepatocyte injury, while oltipraz treatment results in the reduction of hepatocyte injury, and promoted HNF-1 and GSTA1 expression. Additionally, the changes in HNF-1 and GSTA1 were related to APAP-induced hepatocyte injury. These results were useful to investigate the mechanism of an antipyretic and analgesic drug combination.

Acetaminophen-induced reduction in glutathione-S-transferase A1 in hepatocytes: A role for hepatic nuclear factor 1α and its response element.

The role of hepatic nuclear factor 1α (HNF-1α) and its response element in the expression of glutathione S-transferase A1 (GSTA1) was investigated in hepatocytes cells injury induced by acetaminophen (APAP). Treatment of hepatocytes with C2-ceramide exacerbated cells injury with GSTA1 mRNA level reducing. Contrastingly, administration of oltipraz alleviated cells damage with GSTA1 mRNA level elevating relative to hepatotoxicity induced by APAP. Western blot analysis showed that C2-ceramide decreased the translocation of HNF-1α and expression of GSTA1 protein, while oltipraz increased nuclear HNF-1α level and transactivation of GSTA1. The role of HNF-1α on GSTA1 expression was confirmed by transfection experiment and dual-luciferase reporter assay system. In the cells transfected with pGSTA1-1298-LUC vector in which HNF-1 response element (HRE) was contained, the luciferase activity decreased with reduction of nuclear HNF-1α and increased with elevation of nuclear HNF-1α. However, the luciferase activity had no change with the variation of nuclear HNF-1α when the cells transfected with the plasmid of pGSTA1-ΔHNF1-LUC in which the HRE was mutated. In conclusion, HNF-1α could affect the transcription of GSTA1 and HNF-1 response element in the GSTA1 promoter region, which is functionally active for the GSTA1 transcription.

Improved test to determine design parameters for optimization of free surface flow constructed wetlands.

Orthogonal tests were performed to assess the effect of design parameters on hydraulic and treatment performances of constructed wetlands. The results showed that water depth, layout of in- and outlet, flow rate, and aspect ratio mainly affected hydraulic performance, and water depth, plant spacing, and layout of in- and outlet mainly affected treatment performance. Optimal integrated performance was achieved with combination of 20-30 cm water depth, five evenly distributed inlets and one middle outlet, a flow rate of 0.4-0.55 m3/h, 20-cm plant spacing, a 1.125:1 aspect ratio, and planted with Scripus tabernaemontani. The average treatment performances of 27.2%, 16.3%, and 30.7% removal rates were received for total nitrogen, total phosphorus, and total suspended solid, respectively. The design parameters that significantly influenced hydraulic performance did not significantly influence treatment performance. Various hydraulic and purification indicators displayed extremely significant correlations. There was a significant correlation between hydraulic performance and mass removal capacity.

Combination of berberine and ciprofloxacin reduces multi-resistant Salmonella strain biofilm formation by depressing mRNA expressions of luxS, rpoE, and ompR.

Bacterial biofilms have been demonstrated to be closely related to clinical infections and contribute to drug resistance. Berberine, which is the main component of Coptis chinensis, has been reported to have efficient antibacterial activity. This study aimed to investigate the potential effect of a combination of berberine with ciprofloxacin (CIP) to inhibit Salmonella biofilm formation and its effect on expressions of related genes (rpoE, luxS, and ompR). The fractional inhibitory concentration (FIC) index of the combination of berberine with CIP is 0.75 showing a synergistic antibacterial effect. The biofilm's adhesion rate and growth curve showed that the multi-resistant Salmonella strain had the potential to form a biofilm relative to that of strain CVCC528, and the antibiofilm effects were in a dose-dependent manner. Biofilm microstructures were rarely observed at 1/2 × MIC/FIC concentrations (MIC, minimal inhibition concentration), and the combination had a stronger antibiofilm effect than each of the antimicrobial agents used alone at 1/4 × FIC concentration. LuxS, rpoE, and ompR mRNA expressions were significantly repressed (p ＜ 0.01) at 1/2 × MIC/FIC concentrations, and the berberine and CIP combination repressed mRNA expressions more strongly at the 1/4 × FIC concentration. The results indicate that the combination of berberine and CIP has a synergistic effect and is effective in inhibiting Salmonella biofilm formation via repression of luxS, rpoE, and ompR mRNA expressions.

Effects of C2-Ceramide and Oltipraz on Hepatocyte Nuclear Factor-1 and Glutathione S-Transferase A1 in Acetaminophen-Mediated Acute Mice Liver Injury.

In this study, acetaminophen (APAP)-induced acute liver injury mice model was used to investigate the effects of C2-ceramide and oltipraz on hepatocyte nuclear factor 1 (HNF-1) and glutathione S-transferase A1 (GSTA1). Notably, C2-ceramide caused alteration in mice serum transaminases and liver tissue indexes, and aggravated hepatic injury, while oltipraz alleviated hepatic injury. By screening, the optimal concentrations of C2-ceramide and oltipraz were confirmed to be 120 and 150 µmol/L, respectively. In histopathology, karyolysis and more necrotic cells and bleeding spots were appeared on administration of C2-ceramide, but only a small amount of inflammatory cells infiltration was seen after oltipraz treatment. In addition, RT-PCR and western blot results revealed that the mRNA and protein expression levels of HNF-1 and GSTA1 in liver were significantly decreased (p < 0.01) with the administration of 120 µmol/L C2-ceramide. Meanwhile, GSTA1 content in serum increased up to 1.27-fold. In contrast, 150 µmol/L oltipraz incorporation to APAP model mice resulted in obvious elevation (p < 0.01) in the mRNA and protein expression levels of HNF-1 and GSTA1 in liver, and serum GSTA1 content decreased up to 0.77-fold. In conclusion, C2-ceramide could down-regulate the expression of HNF-1 and GSTA1 which exacerbated hepatic injury, while oltipraz could up-regulate the expression of HNF-1 and GSTA1 which mitigated hepatic injury.

Evaluation of hepatoprotective activity of Syringa oblata leaves ethanol extract with the indicator of glutathione S-transferase A1

Abstract The leaves of Syringa oblata Lindl., Oleaceae, had been extensively used as a folk medicine to treat various infections, heal inflammations, icteric hepatitis and acute mastitis. The study was designed to evaluate the hepatoprotective activity of S. oblata leaves ethanol extract against CCl4-induced hepatotoxicity in primary hepatocytes and mice with the indicator of glutathione S-transferase alpha 1. The hepatoprotective effects of S. oblata leaves ethanol extract were evaluated on the basis of liver histopathology and biochemical parameters as well as hepatic oxidative stress markers. The results showed that CCl4 negatively modulated biochemical parameters and liver antioxidant activities. However, the use of S. oblata leaves ethanol extract restored altered-serum biochemical parameters and liver antioxidant activities in a dose-dependent manner. Importantly, the trends in S-transferase alpha 1 were similar to alanine aminotransferase and aspartate aminotransferase level, and S-transferase alpha 1 was suggested to be a marker for the evaluation of hepatoprotective activity of S. oblata leaves ethanol extract. Histopathological examination showed that CCl4 causes significant hepatic injury relative to control group. The above findings suggested that S. oblata leaves ethanol extract has hepatoprotective effects against CCl4-induced hepatic injury and S-transferase alpha 1 may be an indicator to evaluate the protective effects of S. oblata leaves ethanol extract.

Study of stiffness and bearing capacity degradation of reinforced concrete beams under constant-amplitude fatigue.

For a reinforced concrete beam subjected to fatigue loads, the structural stiffness and bearing capacity will gradually undergo irreversible degeneration, leading to damage. Moreover, there is an inherent relationship between the stiffness and bearing capacity degradation and fatigue damage. In this study, a series of fatigue tests are performed to examine the degradation law of the stiffness and bearing capacity. The results pertaining to the stiffness show that the stiffness degradation of a reinforced concrete beam exhibits a very clear monotonic decreasing "S" curve, i.e., the stiffness of the beam decreases significantly at the start of the fatigue loading, it undergoes a linear decline phase in the middle for a long loading period, and before the failure, the bearing capacity decreases drastically again. The relationship between the residual stiffness and residual bearing capacity is determined based on the assumption that the residual stiffness and residual bearing capacity depend on the same damage state, and then, the bearing capacity degradation model of the reinforced concrete beam is established based on the fatigue stiffness. Through the established model and under the premise of the known residual stiffness degradation law, the degradation law of the bearing capacity is determined by using at least one residual bearing capacity test data, for which the parameters of the stiffness degradation function are considered as material constants. The results of the bearing capacity show that the bearing capacity degradation of the reinforced concrete beam also exhibits a very clear monotonic decreasing "S" curve, which is consistent with the stiffness degradation process and in good agreement with the experiment. In this study, the stiffness and bearing capacity degradation expressions are used to quantitatively describe their occurrence in reinforced concrete beams. In particular, the expression of the bearing capacity degradation can mitigate numerous destructive tests and save cost. The stiffness and bearing capacity degradation expressions for a reinforced concrete beam can be used to predict the deformation and bearing capacity of a structure during the service process and determine the structural fatigue damage and degree of degradation.

Expression of glutathione S-transferase A1, a phase II drug-metabolizing enzyme in acute hepatic injury on mice.

In the present study, three models of acute liver injury in mice were induced via the administration of CCl4 (35 mg/kg, 24 h), acetyl-para-aminophenol (APAP; 200 mg/kg, 12 h) and ethanol (14 ml/kg, 8 h) to study the effect of glutathione S-transferase A1 (GSTA1) on acute liver injury. The serum levels of alanine transaminase, aspartate transaminase and liver homogenate indicators (superoxide dismutase, glutathione and glutathione peroxidase) were significantly lower in model groups compared with the control group (P<0.01), whereas the liver homogenate indicator malondialdehyde was significantly increased (P<0.01). The expression of GSTA1 in liver was significantly decreased in the model groups compared with the control group (P<0.01). GSTA1 protein content was 3.8, 1.3 and 2.6 times lower in the CCl4, APAP and ethanol model groups, respectively. Furthermore, GSTA1 mRNA expression levels decreased by 4.9, 2.1 and 3.7 times in the CCl4, APAP and ethanol model groups, respectively. Among the three models, the injury induced by CCl4 was the most marked, followed by ethanol and finally APAP. These results suggest that GSTA1 may be released by the liver and serve as an antioxidant in the prevention of liver damage.

A novel prognostic index for oral squamous cell carcinoma patients with surgically treated.

This study aims to develop an applicable prognostic index with conventional factors for predicting outcome of patients with oral squamous cell carcinoma (OSCC). We performed a prospective study in a large cohort of 892 OSCC patients in Fujian, China. All patients were randomly divided into a discovery group and validation group. A prognostic index was developed based on ß value of each significant variable obtained from the multivariate Cox regression model. The results from discovery and validation set demonstrated thatthe model-4(included clinical stage, tumor differentiation, ill-fitting denture, oral hygiene and cigarette smoking) was the optimal model. The optimal cutoff points of prognostic index (1.88 and 2.80) were determined by X-tile program which categorized all subjects into low, middle and high risk subsets. Patients in high risk group were at the greatest risk of death compared with those in low risk group (HR: 6.02; 95%CI: 4.33-8.38). Moreover, there was a significant tendency of the worse overall survival with the higher prognostic index (Ptrend <0.001). The discriminatory capacity of prognostic index was 0.661(95%CI: 0.621-0.701). This study developed and validated a prognostic index that is an economical and useful tool for predicting the clinical outcomes of OSCC patients in Southeast China. Future randomized trials with larger cohort are required to confirm our results.