Local chicken breeds exhibit abundant TCR-V segments but similar repertoire diversity.

The thymus-derived lymphocytes of jawed vertebrates have four T-cell receptor (TCR) chains that play a significant role in immunity. As chickens have commercial value, their immune systems require a great deal of attention. Local chicken breeds are an essential part of poultry genetic resources in China. Here, we used high-throughput sequencing to analyze the TCRα and TCRß repertoires and their relative expression levels in the native chicken breeds Baier Buff, Longyou Partridge, Xiaoshan, and Xianju. We found that TCR Vα and TCR Vß were expressed and included 17, 19, 17, and six segments of the Vα2, Vα3, Vß1, and Vß2 subgroups, respectively. V-J pairing was biased; Jα11 was utilized by nearly all Vα segments and was the most commonly used. Breed-specific V segments and V-J pairings were detected as well. The results of the principal coordinate analysis (PCoA) as well as the V-J pairing and CDR3 diversity analyses suggested that the four local chicken breeds did not significantly differ in terms of TCR diversity. Hence, they expressed not significant differentiation, and they are rich genetic resources for the development and utilization of immune-related poultry breeding.

Effects of Helicobacter pylori and Moluodan on the Wnt/ß-catenin signaling pathway in mice with precancerous gastric cancer lesions.

BACKGROUND: Helicobacter pylori (H. pylori) is the primary risk factor for gastric cancer (GC), the Wnt/ß-Catenin signaling pathway is closely linked to tumourigenesis. GC has a high mortality rate and treatment cost, and there are no drugs to prevent the progression of gastric precancerous lesions to GC. Therefore, it is necessary to find a novel drug that is inexpensive and preventive to against GC. AIM: To explore the effects of H. pylori and Moluodan on the Wnt/ß-Catenin signaling pathway and precancerous lesions of GC (PLGC). METHODS: Mice were divided into the control, N-methyl-N-nitrosourea (MNU), H. pylori + MNU, and Moluodan groups. We first created an H. pylori infection model in the H. pylori + MNU and Moluodan groups. A PLGC model was created in the remaining three groups except for the control group. Moluodan was fed to mice in the Moloudan group ad libitum. The general condition of mice were observed during the whole experiment period. Gastric tissues of mice were grossly and microscopically examined. Through quantitative real-time PCR (qRT-PCR) and Western blotting analysis, the expression of relevant genes were detected. RESULTS: Mice in the H. pylori + MNU group showed the worst performance in general condition, gastric tissue visual and microscopic observation, followed by the MNU group, Moluodan group and the control group. QRT-PCR and Western blotting analysis were used to detect the expression of relevant genes, the results showed that the H. pylori + MNU group had the highest expression, followed by the MNU group, Moluodan group and the control group. CONCLUSION: H. pylori can activate the Wnt/ß-catenin signaling pathway, thereby facilitating the development and progression of PLGC. Moluodan suppressed the activation of the Wnt/ß-catenin signaling pathway, thereby decreasing the progression of PLGC.

Copy number and selection of MHC genes in ruminants are related to habitat, average life span and diet.

The ruminants, as the main group of livestock, have been extensively studied in terms of their physiology, endocrinology, biochemistry, genetics, and nutrition. Despite the wide geographic distribution and habitat diversity of animals in this group, their ecology and evolution remain poorly understood. In this study, we analyzed the gene copy number, selection, and ecological and evolutionary processes that have affected the evolution of major histocompatibility complex (MHC) genes across ruminant lineages based on available genomic data. The 51 species analyzed represented all six families of ruminants. Our finding indicated that the architecture of the MHC region is conserved in ruminants, but with variable copy numbers of MHC-I, MHC-IIA, and MHC-IIB genes. No lineage-specific gene duplication was observed in the MHC genes. The phylogenetic generalized least squares regression (PGLS) model revealed association between ecological and biological factors (habitat and lifespan) and gene duplication in DQA and DQB, but not in DRB. The selection pressure of DQA and DQB were related with lifespan, diet, and the ratio of genetic repeat elements. These results suggest that the MHC evolution in ruminants, including copy number and selection, has been influenced by genetic repeat elements, pathogen exposure risk, and intrinsic cost of possessing multiple MHC genes.

Macroevolution of avian T cell receptor C segments using genomic data.

All jawed vertebrates have four T cell receptor (TCR) chains expressed by thymus-derived lymphocytes that play a significant role in animal immune defense. However, avian TCR studies have been limited to a few species, although their co-functional major histocompatibility complexes (MHCs) have been studied for decades, showing various copy numbers and polymorphisms. Here, using public genome data, we characterized the copy numbers, the phylogenic relationship and selection of T cell receptor complex (TCR-C) segments, and the genomic organization of TCR loci across birds. Various numbers of C segments were found in the TCRα/TCRδ, TCRß, and TCRγ loci, and phylogenetic analysis reflected both ancient gene duplication events (two Cß segments and Cδ segments divergent into CδI and CδII) and contemporary evolution (lineage-specific and species-specific characteristics). Most passerines lack CδII segments and a second TRD locus, except Meliphagidae and Maluridae. A relatively stable structure was verified in four TCR loci of birds, except for the arrangement of V segment groups. In this study, we explored the phylogenetic relationships of TCR-C segments across avians for the first time. We inferred gene duplication and loss events during the evolution process. The finding of diverse TCR germline repertoires provides a better understanding of the immune systems of birds.

Study on the mechanism of Huangqin Decoction on rats with ulcerative colitis of damp-heat type base on mtDNA, TLR4, p-PI3K, p-Akt protein expression and microbiota.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin decoction (HQD), composed of Scutellaria(Huangqin), Peony(Shaoyao), Liquorice(Gancao) and Jujube(Dazao), is a traditional Chinese medicine prescription, originated from treatise on Febrile Diseases, has the functions of clearing heat, stopping benefits and relieving pain. It is the original prescription for treating heat and relieving dysentery, and is commonly used in clinic for diarrhea and other diseases. In ulcerative colitis, damp-heat syndrome is the most common. However, its mechanism of action is not completely clear. AIMS OF THE REVIEW: The purpose of the research is to investigate the protective effect of HQD on ulcerative colitis rats and the regulation effect of mitochondrial DNA, TLR4, p-Akt, p-PI3K protein and microbiota. MATERIALS AND METHODS: The effects of HQD anti-UC were investigated by fluorescence quantitative PCR, cytokine level and histopathological analysis in DSS-induced ulcerative colitis (UC) rats. The content of mtDNA in colon epithelial cells of rats in each group was detected by fluorescence quantitative PCR, p-PI3K, p-Akt and TLR4 protein expressions in colon tissues of rats in each group were detected by Western blotting. IL-6, IL-17 and IL-23 inflammatory factors were detected by ELISA. The effect of HQD on intestinal microbiota of rats with ulcerative colitis was studied by high-throughput sequencing technology, and the correlation between mtDNA level and inflammatory factors as well as protein expression in colonic epithelium of rats with ulcerative colitis was analyzed by SPSS23.0. RESULTS: HQD significantly alleviated UC symptoms by improving the mucosal intestinal epithelial cell structure, mental state, hair gloss, fecal occult blood, lamina propria intestinal glands and inflammatory cell infiltration. And HQD reduced the pro-inflammatory cytokines in the colonic epithelium of UC rats Production of IL-6, IL-17 and IL-23. The HE stained section of colon tissue showed a complete intestinal epithelial mucosal layer structure. The structure of epithelial cells was more normal and abundant. There were more goblet cells in lamina propria adenoma, which improved the infiltration of inflammatory cells. HQD significantly inhibited the mtDNA content in rat colonic epithelial tissue, and significantly inhibited the expression of TLR4, p-PI3K and p-Akt inflammatory signaling pathways. The results of the microbiota experiment showed that the abundance of HQD in the phylum Firmicutes increased, and the number of Bacteroides phylum decreased (p < 0.05). At the genus level, HQD significantly increased Lactobacillus and Firmicutes Bacteroides, while Treponema and Bacteroides were significantly reduced (p < 0.05). CONCLUSION: HQD has a certain protective effect on rats with damp heat ulcerative colitis. Its mechanism may be related to regulating the expression of p-PI3K, p-Akt and TLR4 proteins, mitochondrial DNA as well as microbiota.

Reconstructing Macroevolutionary Patterns in Avian MHC Architecture With Genomic Data.

The Major Histocompatibility Complex (MHC) is a hyper-polymorphic genomic region, which forms a part of the vertebrate adaptive immune system and is crucial for intra- and extra-cellular pathogen recognition (MHC-I and MHC-IIA/B, respectively). Although recent advancements in high-throughput sequencing methods sparked research on the MHC in non-model species, the evolutionary history of MHC gene structure is still poorly understood in birds. Here, to explore macroevolutionary patterns in the avian MHC architecture, we retrieved contigs with antigen-presenting MHC and MHC-related genes from available genomes based on third-generation sequencing. We identified: 1) an ancestral avian MHC architecture with compact size and tight linkage between MHC-I, MHC-IIA/IIB and MHC-related genes; 2) three major patterns of MHC-IIA/IIB unit organization in different avian lineages; and 3) lineage-specific gene translocation events (e.g., separation of the antigen-processing TAP genes from the MHC-I region in passerines), and 4) the presence of a single MHC-IIA gene copy in most taxa, showing evidence of strong purifying selection (low dN/dS ratio and low number of positively selected sites). Our study reveals long-term macroevolutionary patterns in the avian MHC architecture and provides the first evidence of important transitions in the genomic arrangement of the MHC region over the last 100 million years of bird evolution.

Association between polymorphisms of collagen genes and susceptibility to intervertebral disc degeneration: a meta-analysis.

BACKGROUND: Collagens are important structural components of intervertebral disc. A number of studies have been performed for association between polymorphisms of collagen genes and risk of intervertebral disc degeneration (IVDD) but yielded inconsistent results. Here, we performed a meta-analysis to investigate the association of collagen IX alpha 2 (COL9A2) Trp2, collagen IX alpha 3 (COL9A3) Trp3, collagen I alpha 1 (COL1A1) Sp1 and collagen XI alpha 1 (COL11A1) C4603T polymorphisms with susceptibility to IVDD. METHOD: Eligible studies were retrieved by searching MEDLINE, EMBASE, Web of Science prior to 31 March, 2021. Odds ratio (OR) and corresponding 95% confidence interval (CI) were calculated for association strength. RESULTS: A total of 28 eligible studies (31 datasets comprising 5497 cases and 5335 controls) were included. COL9A2 Trp2 carriers had an increased risk of IVDD than non-carriers in overall population (OR = 1.43, 95% CI 0.99-2.06, P = 0.058), which did not reach statistical significance. However, Trp2 carriers had 2.62-fold (95% CI 1.15-6.01, P = 0.022) risk than non-carriers in Caucasians. COL9A3 Trp3 was not associated with IVDD risk (OR = 1.28, 95% CI 0.81-2.02, P = 0.299). T allele and TT genotype of COL1A1 Sp1 (+ 1245G > T) were correlated with increased risk of IVDD. Significant associations were found between COL11A1 C4603T and IVDD risk under allelic (OR = 1.33, 95% CI 1.20-1.48), dominant (OR = 1.45, 95% CI 1.26-1.67), recessive (OR = 1.55, 95% CI 1.21-1.98) and homozygote model (OR = 1.81, 95% CI 1.40-2.34). CONCLUSIONS: COL1A1 Sp1 and COL11A1 C4603T polymorphism are associated with IVDD risk while the predictive roles of collagen IX gene Trp2/3 need verification in more large-scale studies.

Trends and correlation between antibacterial consumption and carbapenem resistance in gram-negative bacteria in a tertiary hospital in China from 2012 to 2019.

BACKGROUND: To investigate the trends and correlation between antibacterial consumption and carbapenem resistance in Gram-negative bacteria from 2012 to 2019 in a tertiary-care teaching hospital in southern China. METHODS: This retrospective study included data from hospital-wide inpatients collected between January 2012 and December 2019. Data on antibacterial consumption were expressed as defined daily doses (DDDs)/1000 patient-days. Antibacterials were classified according to the Anatomical Therapeutic Chemical (ATC) classification system. The trends in antimicrobial usage and resistance were analyzed by linear regression, while Pearson correlation analysis was used for assessing correlations. RESULTS: An increasing trend in the annual consumption of tetracyclines, ß-lactam/ß-lactamase inhibitor (BL/BLI) combinations, and carbapenems was observed (P < 0.05). Carbapenem resistance in Acinetobacter baumannii (A. baumannii) significantly increased (P < 0.05) from 18% in 2012 to 60% in 2019. Moreover, significant positive correlations were found between resistance to carbapenems in A. baumannii (P < 0.05) and Escherichia coli (E. coli; P < 0.05) and consumption of carbapenems, while the resistance rate of A. baumannii to carbapenems was positively correlated with cephalosporin/ß-lactamase inhibitor (C/BLI) combinations (P < 0.01) and tetracyclines usage (P < 0.05). We also found that use of quinolones was positively correlated with the resistance rate of Burkholderia cepacia (B. cepacia) to carbapenems (P < 0.05), and increasing uses of carbapenems (P < 0.01) and penicillin/ß-Lactamase inhibitor (P/BLI) combinations (P < 0.01) were significantly correlated with reduced resistance of Enterobacter cloacae (E. cloacae) to carbapenems. CONCLUSION: These results revealed significant correlations between consumption of antibiotics and carbapenem resistance rates in Gram-negative bacteria. Implementing proper management strategies and reducing the unreasonable use of antibacterial drugs may be an effective measure to reduce the spread of carbapenem-resistant Gram-negative bacteria (CRGN), which should be confirmed by further studies.

ZIF-mediated N-doped hollow porous carbon as a high performance adsorbent for tetracycline removal from water with wide pH range.

The N-doped porous carbon (NPC) and N-doped hollow porous carbons (NHPC-1 and NHPC-2) were fabricated using ZIF-8 and its composites (resorcinol and formaldehyde coated ZIF-8, ZIF-8@RF and tannic acid coated ZIF-8, ZIF-8@TA) as precursors via high-temperature pyrolysis and their applications for removing tetracycline (TC) from water were investigated. The various technologies, including SEM, TEM, FT-IR, Raman, N2 adsorption-desorption, XRD and XPS were used to characterize the morphology, textual property, phase and microstructure of three porous carbon materials. The adsorption isotherms and kinetics of TC on three porous carbon materials were fitted well with Langmuir model and pseudo-2nd order model, respectively. In terms of the Langmuir model, the maximum TC adsorption capacities on the NPC, NHPC-1 and NHPC-2 were 180.2, 284.9 and 518.1 mg g-1 at 25 °C, respectively. The excellent performance of NHPC-2 for TC removal is mainly attributed to the suitable pore size distribution and pore volume, high nitrogen contents and large amounts of defects. High TC adsorption was achieved in 3-10 pH range and hardly affected by humic acid. TC adsorption on NHPC-2 is spontaneous and endothermic process. The NHPC-2 kept excellent TC adsorption capacity even after eight cycles, showing its good repeatability. Our result indicates that the MOF-mediated N-doped hollow porous carbon is promising for the TC removal from aqueous media.

High oxidase-mimic activity of Fe nanoparticles embedded in an N-rich porous carbon and their application for sensing of dopamine.

The N-doped porous carbon (NC) has been regarded as one of the promising support materials for nanoparticles (NPs) catalyst due to its inherent virtues such as porosity, large surface areas, and heteroatom incorporation. In this work, Fe/NC-800 hybrid was facilely prepared by uniform dispersion of in situ formed FeNPs onto NC-800 from carbonization of ZIF-8 at 800 °C for the first time. The optimized Fe/NC-800 catalyst was characterized by TEM, XPS and XRD. Compared with sole FeNPs and NC-800, the Fe/NC-800 catalyst exhibited an enhanced oxidase-like activity that could oxidize the colorless 3,3',5,5'-tetramethylbenzidine (TMB) to the heavy blue without extra oxidants such as H2O2. The possible reason for the enhanced oxidase-like activity of the Fe/NC-800 was discussed on the basis of the experiments of radical scavengers, indicating the importance of superoxide (O2•-) and singlet (1O2) in colorimetric reaction between TMB and Fe/NC-800 hybrid. Furthermore, the oxidase-like activity of Fe/NC-800 was significantly inhibited by dopamine (DA), leading to blue color fading. On this basis, a sensitive and selective colorimetric sensor was fabricated for the quantitative analysis of DA with a linear range of 0.01-40 µM and a low detection limit of 10 nM. The proposed colorimetric method was successfully applied to determine DA in human serum and injection samples, suggesting a promising application in biological analysis.

Gypsophila elegans isoorientin-2″-O-α-l-arabinopyranosyl ameliorates porcine serum-induced immune liver fibrosis by inhibiting NF-κB signaling pathway and suppressing HSC activation.

The present study was to investigate the inhibitory effect of Gypsophila elegans isoorientin-2″-O-α-l-arabinopyranosyl (GEI) on hepatic stellate cells (HSCs), to reveal the underlying mechanism of GEI against hepatic fibrosis. Our study showed that GEI significantly alleviated liver injury induced by porcine serum (PS) in rats; it notably alleviated collagen accumulation as evidenced by a significant decrease in the levels of collagen biomarkers including hyaluronic acid, laminin, hydroxyproline and procollagen III N-terminal peptide. Moreover, GEI treatment markedly decreased the secretion of inflammatory cytokines by inhibiting the NF-κB pathway and significantly inhibited the generation of excessive extracellular matrix (ECM) components by restoring the balance between matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases (TIMPs). Additionally, the cell experiments in vitro showed that GEI strongly inhibited HSC proliferation, migration and clonogenicity and markedly induced HSC apoptosis. Moreover, GEI caused cell cycle arrest at G2 phase. In conclusion, our study demonstrates that GEI significantly alleviates PS-induced hepatic fibrosis by inhibiting the NF-κB pathway, restoring the balance between MMPs and TIMPs, and suppressing HSC activation.

Raf Kinase Inhibitory Protein Down-Expression Exacerbates Hepatic Fibrosis In Vivo and In Vitro.

BACKGROUND/AIMS: Raf kinase inhibitory protein (RKIP) is closely associated with numerous tumors and participates in their development through regulating the growth, apoptosis, invasion and metastasis of tumor cells. However, the role of RKIP in chronic liver injury and particularly in liver fibrosis is still unclear. METHODS: In the present study, hepatic fibrosis was induced by porcine serum (PS) in rats and primary hepatic stellate cells (HSCs) were isolated from rat livers. Moreover, locostatin was used to interfere with RKIP expression. RESULTS: RKIP expression was significantly inhibited by locostatin in both liver tissues of rats and primary HSCs. Down-regulating RKIP expression resulted in serious liver injury, extensive accumulation of collagen, and significant increase in the levels of ALT, AST and TNF-α during liver fibrosis in rats. Moreover, down-regulating RKIP significantly promoted HSCs proliferation and colony formation in vitro. Reduced RKIP significantly increased the production of collagen and the level of α-SMA as well as the expression of MMP-1 and MMP-2 in both liver tissues and primary HSCs. Furthermore, down-regulating RKIP promoted the activation of the ERK and TLR4 signaling pathways. CONCLUSION: Our findings clearly indicate an inverse correlation between RKIP level and the degree of the liver injury and fibrosis. The decrease in RKIP expression may exacerbate chronic liver injury and liver fibrosis.

Loss of Raf kinase inhibitor protein is associated with malignant progression in hepatic fibrosis.

Raf kinase inhibitory protein (RKIP), besides regulating important intracellular signaling cascades, was described to be associated with progression, metastasis and prognosis in several human neoplasms. But its role in hepatic fibrogenesis remains unclear. In the present study, we found that the absence of RKIP expression significantly enhanced the proliferation of HSC-T6 cells. Reduced RKIP expression promoted the activation of HSCs and the accumulation of collagen, as evidenced by the increases in the levels of collagen I and α-smooth muscle actin. Moreover, down-regulating RKIP expression led to severe histopathological changes and collagen accumulation in hepatic tissues of rats with liver fibrosis. Furthermore, the absence of RKIP promoted the activation of ERK/MAPK pathway in vitro and in vivo. Our findings clearly demonstrate an inverse correlation between RKIP level and the degree of the liver injury and fibrosis. Loss of RKIP may be associated with malignant progression in hepatic fibrosis.

Pratensein ameliorates ß-amyloid-induced cognitive impairment in rats via reducing oxidative damage and restoring synapse and BDNF levels.

This study was designed to investigate the protective effect of pratensein against cognitive impairment induced by amyloid beta (1-42) (Aß1-42) in rats. Aß1-42 peptide was injected bilaterally in the hippocampus of rat. Next, pratensein was administered orally for 3 weeks. Our findings demonstrated that treatment with pratensein ameliorated learning and memory deficits in Aß1-42 rat model of AD. Pratensein treatment significantly attenuated neuronal degeneration and apoptosis in hippocampus. Moreover, the over-expression in IL-1ß and TNF-α as well as the extensive astrogliosis and microgliosis in hippocampus induced by Aß1-42 were significantly reduced following administration of pratensein. Concomitantly, pratensein treatment significantly suppressed the activation of NF-κB in hippocampus. In addition, pratensein was able to increase the levels of synaptophysin and brain-derived neurotrophic factor (BDNF). These results indicate that pratensein could significantly ameliorate Aß1-42-induced spatial learning and memory impairment through reducing neuroinflammation via inhibition of glial activation and NF-κB activation, and restoring synapse and BDNF levels, suggesting that administration of pratensein could likely provide a therapeutic approach for AD.

The protective effects of Acanthus ilicifolius alkaloid A and its derivatives on pro- and anti-inflammatory cytokines in rats with hepatic fibrosis.

This study was designed to investigate the protective effects of Acanthus ilicifolius alkaloid A [4-hydroxy-2-benzoxazolone (HBOA)] and its acetylated derivatives including 4-acetoxy-2-benzoxazolone (TC-2) and 3-acetyl-4-acetoxy-2-benzoxazolone (TC-3) on carbon tetrachloride (CCl4 )-induced liver fibrosis in rats. Sprague-Dawley rats were given CCl4 twice per week for 8 weeks to induce liver fibrosis. Then, they were treated with HBOA, TC-2, and TC-3 daily for 4 weeks, respectively. The serum indicators including total protein (TP), albumin (Alb), globulin, hyaluronic acid (HA), and laminin (LN) were measured by commercial kits. The messenger ribonucleic acid expression of adiponectin, peroxisome proliferator-activated receptor-γ (PPAR-γ), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-ß1 (TGF-ß1 ) and Toll-like receptor 4 (TLR4 ) was determined by reverse-transcriptase -PCR. The proteins of adiponectin, TGF-ß1 , α-smooth muscle actin (α-SMA), and TLR4 were also detected by the immunohistochemical assay. The results showed that HBOA, TC-2, and TC-3 significantly attenuated the fibrotic degree induced by CCl4 as evidenced by higher levels of TP, Alb, adiponectin, and PPAR-γ, which in turn decreased the proliferation of hepatic stellate cells. Moreover, those drugs markedly decreased the levels of HA, LN, TNF-α, IL-6, TGF-ß1 , α-SMA, and TLR4 . Our study indicates that HBOA, TC-2, and TC-3 have beneficial effects against liver fibrosis, and the mechanisms may be related to the inhibition of inflammatory response.

Protective effect of madecassoside against cognitive impairment induced by D-galactose in mice.

This study was designed to investigate the protective effect of madecassoside from Hydrocotyle sibthorpioides against cognitive impairment induced by D-galactose (D-gal) in mice. The result revealed that treatment with madecassoside significantly reversed D-gal-induced learning and memory impairments, as measured by the Morris water-maze test. Studies on the potential mechanisms of this action showed that madecassoside significantly reduced oxidative stress and suppress inflammatory responses via blocking NF-κB and ERK/p38 MAPK pathways. Moreover, madecassoside markedly attenuated the content and deposition of ß-amyloid peptide by inducing a decrease in the expression of amyloid protein precursor, ß-site amyloid cleaving enzyme-1 and cathepsin B and an increase in the levels of neprilysin and insulin-degrading enzyme. Madecassoside significantly increased the expression of synapse plasticity-related proteins in the hippocampus, such as postsynaptic density 95, long-term potentiation, N-methyl-D-aspartic acid receptors, Ca(2+)/calmodulin-dependent protein kinase II, NMDA receptor subunit 1, protein kinase C, protein kinase A, cAMP-response element binding protein, and brain-derived neurotrophic factor. In addition, madecassoside significantly increased the levels of acetylcholine but decreased cholinesterase activity. In conclusion, the protective effect of madecassoside against d-gal-induced cognitive impairment was mainly due to its ability to reduce oxidative damage, improve synaptic plasticity and restore cholinergic function. These findings suggest that madecassoside can be considered as a potential agent for preventing cognitive impairment.

Protective effect of genistein on lipopolysaccharide/D-galactosamine- induced hepatic failure in mice.

This study examined the effect of genistein from Hydrocotyle sibthorpioides on lipopolysaccharide (LPS)/D-galactosamine (D-GalN)-induced acute hepatic failure. Compared to the model control, genistein treatment significantly protected against LPS/D-GalN-induced liver injury, as evidenced by the decrease in serum alanine and aspartate aminotransferases activities and the attenuation of histopathological changes. Furthermore, genistein alleviated the pro-inflammatory cytokines including tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO)/inducible nitric oxide synthase (iNOS) by inhibiting nuclear factor-κB (NF- κB) activity. Genistein attenuated the elevated level of caspases-3, while augmented the expression of Bcl-2. In addition, LPS/D-GalN induced significant increase of heme oxygenase (HO), carbon monoxide and bilirubin levels and these alterations were augmented by genistein treatment. In conclusion, the protective effect of genistein on LPS/D-GalN-induced liver damage was mainly due to its ability to block NF-κB signaling pathway for anti-inflammation response, attenuate hepatocellular apoptosis and increase HO level. These findings suggest that genistein can be considered as a potential agent for preventing acute hepatic failure.