Role of ER Stress in Xenobiotic-Induced Liver Diseases and Hepatotoxicity.

The liver is a highly metabolic organ and plays a crucial role in the transportation, storage, and/or detoxication of xenobiotics. Liver damage induced by xenobiotics (e.g., heavy metal, endocrine disrupting chemicals, Chinese herbal medicine, or nanoparticles) has become a pivotal reason for liver diseases, leading to great clinical challenge and much attention for the past decades. Given that endoplasmic reticulum (ER) is the prominent organelle involved in hepatic metabolism, ER dysfunction, namely, ER stress, is clearly observed in various liver diseases. In response to ER stress, a conserved adaptive signaling pathway known as unfolded protein response (UPR) is activated to restore ER homeostasis. However, the prolonged ER stress with UPR eventually leads to the death of hepatocytes, which is a pathogenic event in many hepatic diseases. Therefore, analyzing the perturbation in the activation or inhibition of ER stress and the UPR signaling pathway is likely an effective marker for investigating the molecular mechanisms behind the toxic effects of xenobiotics on the liver. We review the role of ER stress in hepatic diseases and xenobiotic-induced hepatotoxicity, which not only provides a theoretical basis for further understanding the pathogenesis of liver diseases and the mechanisms of hepatotoxicity induced by xenobiotics but also presents a potential target for the prevention and treatment of xenobiotic-related liver diseases.

Epigallocatechin-3-gallate: A phytochemical as a promising drug candidate for the treatment of Parkinson's disease.

Epigallocatechin 3-gallate (EGCG), an abundant polyphenolic component derived from green tea extract, possesses versatile bioactivities that can combat many diseases. During the last decade, EGCG was shown to be effective in experimental models of Parkinson's disease (PD). Several experimental studies have suggested that it has pleiotropic neuroprotective effects, which has enhanced the appeal of EGCG as a therapeutic strategy in PD. In this review, we compiled recent updates and knowledge of the molecular mechanisms underlying the neuroprotective effects of EGCG in PD. We focused on the effects of EGCG on apoptosis, oxidative stress, inflammation, ferroptosis, modulation of dopamine production, and the aggregation of α-synuclein. The review highlights the pharmacological features of EGCG and its therapeutic implications in PD. Taken together, the accumulated data indicate that EGCG is a promising neuroprotective compound for the treatment of PD.

Antibacterial phenylspirodrimanes from the marine-derived fungus Stachybotrys sp. SCSIO 40434.

Five new phenylspirodrimanes, stachybomycins A - E (1-5), together with four known compounds (6-9), were isolated from the marine-derived fungus Stachybotrys sp. SCSIO 40434. Their structures were elucidated by comprehensive spectroscopic analyses of NMR and HRESIMS. The absolute configuration of 1 was confirmed by single crystal X-ray diffraction analysis. Compounds 5 and 7 showed moderate antibacterial activities against Micrococcus luteus, Staphylococcus aureus and methicillin resistant Staphylococcus aureus with minimal inhibition concentration (MIC) values of 8, 16 and 16 µg mL-1, respectively.

Transcriptome analysis reveals the potential mechanism of dietary carotenoids improving antioxidative capability and immunity of juvenile Chinese mitten crabs Eriocheir sinensis.

Carotenoids are known to be involved in the regulation of the antioxidative capability, immune response and stress resistance in crustacean species; however, very limited information is available on their underlying molecular mechanisms. This study performed transcriptome sequencing of hemolymph and hepatopancreas of juvenile Chinese mitten crabs (Eriocheir sinensis) that fed with three diets, i.e. diet A containing 90 mg kg-1 dry weight of astaxanthin, diet B containing 200 mg kg-1 dry weight of ß-carotene and control diet without supplementation of dietary carotenoids. The results showed that there were 2955 and 497 differentially expressed genes (DEGs) in the hemolymph between the astaxanthin treatment and control groups, and between the ß-carotene treatment and control groups, respectively. Moreover, compared with the control group, 833 and 1886 DEGs were obtained in the hepatopancreas of the astaxanthin treatment and the ß-carotene treatment groups, respectively. The DEGs in the three groups were enriched in 255 specific KEGG metabolic pathways according to KEGG enrichment analysis. Through this study, a series of key genes involved in Nrf2 signalling, ROS production, intracellular antioxidant enzymes and chaperones were significantly affected by dietary carotenoids. Dietary carotenoids also significantly altered the expression levels of immune-related molecules associated with signal transduction, prophenoloxidase cascade, apoptosis, pattern recognition proteins/receptors and antimicrobial peptides. In conclusion, this transcriptomic study provides valuable information for understanding the molecular mechanism and potential pathway of dietary carotenoids improved the antioxidative capability and immunity of juvenile E. sinensis.

Micro-algal astaxanthin could improve the antioxidant capability, immunity and ammonia resistance of juvenile Chinese mitten crab, Eriocheir sinensis.

Green alga Haematococcus pluvialis is an important source of natural astaxanthin (Ast), which have been shown to be beneficial for the color formulation, survival, antioxidation, immunity and stress resistance of many crustacean. This study was conducted to investigate the effects of dietary supplementation of H. pluvialis meal on growth, antioxidant status, ammonia resistance, color parameters, and carotenoids composition of juvenile Chinese mitten crab Eriocheir sinensis. Five diets were formulated to contain 0, 30, 60, 90 and 120 mg/kg dry diets of natural Ast (defined as Diet 1-5) using H. pluvialis meal as astaxanthin source. The results showed that: (1) Although all treatments with Ast supplementation had the relatively higher growth performance and survival than the control (Diet 1 treatment), no significant differences were found on growth performance, feed conversion ratio and hepatosomatic index among all treatments. (2) The highest total antioxidant capacity (T-AOC) in hepatopancreas and hemolymph were observed in Diet 4 and 3 treatments respectively, while the lowest malondialdehyde (MDA) contents in hepatopancreas and hemolymph were also found in these two treatments. Furthermore, the significantly positive relationships were detected on acid phosphatase (ACP) activities and dietary Ast contents for hepatopancreas and hemolymph. (3) Diet 3 treatment had the highest mRNA levels of EsLecA, EsTrx, and EsPrx6 in hepatopancreas, while both Diet 3 and 4 treatments reached the peaks for mRNA expression levels of EsMyd88 and EsHc, respectively. (4) The stress test with ammonia-N indicated Diet 1 treatment had the highest mortality among all treatments, and the lowest mortality was found on Diet 3 treatment during the stress test. (5) Dietary Ast significantly improved the redness (a*) of carapace and hepatopancreas, which were consistent with the Ast contents in these tissues from the different treatments. Ast concentrations in carapace reached the plateau for Diet 3 treatment while hepatopancreatic Ast concentration kept increasing with elevating dietary Ast contents. In conclusion, natural astaxanthin could enhance the antioxidative capability, non-specific immunity, tissue Ast contents and stress resistance to ammonia-N, and these results suggested the optimal diet micro-algal astaxanthin was around 60 mg/kg for juvenile E. sinensis.

Increased pollen source area does not always enhance the risk of pollen dispersal and gene flow in Oryza sativa L.

Pollen dispersal is one of the main ways of gene flow. In the past years, rice pollen dispersal and gene flow have been well studies. However, there is much dispute whether the risk of pollen dispersal and gene flow continuously increases with the source area. A Lagrangian stochastic model was used to simulate the pollen depositions at different distances from different pollen source areas. The field experiments showed a good fit in the pollen depositions. The larger the source area, the more the pollen grains were deposited at each distance, with the pollen dispersal distance increasing accordingly. However, this effect gradually leveled off as the source area increased. In the large-area of pollen source, we found a significantly higher saturation point for the amount of pollen deposition. Once the source area exceeded 1000 × 1000 m2, the pollen deposition no longer increased, even if the source area continued to increase, indicating the "critical source area" of rice pollen dispersal. However, a 100 × 100 m2 critical source area for conventional rice and hybrid rice was sufficient, while the critical source area for the sterile line was about 230 × 230 m2.

Raddeanin A Induces Apoptosis and Cycle Arrest in Human HCT116 Cells through PI3K/AKT Pathway Regulation In Vitro and In Vivo.

This study aimed to investigate the in vitro and in vivo effects of Raddeanin A on apoptosis and the cell cycle in the human colorectal cell line, HCT116, and to explore the possible underlying mechanisms of action. We found the growth inhibition rate gradually increased as the drug concentration increased via the 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, which indicated that Raddeanin A significantly inhibited the growth of HCT116 cells. Flow cytometry (FCM) showed that Raddeanin A concentration-dependently induced apoptosis in HCT116 cells. In addition, the percentage of cells in the G0/G1 phase was noticeably increased, which indicated that Raddeanin A blocked cell cycle progression in HCT116 cells and caused arrest in the G0/G1 phase. Moreover, the expression of proteins involved in the PI3K/AKT signaling pathway (e.g., p-PI3K and p-AKT) was decreased. The results showed that in vivo revealed that Raddeanin A significantly inhibited tumor growth in an HCT116-xenografted mouse model; apoptotic cells were also detected in the tumor tissue. The expression of the tissue proteins cyclinD1, cyclinE, p-PI3K, and p-AKT was decreased. The above results show that the Raddeanin A exerted a strong antitumor effect in the human colorectal cell line HCT116 both in vitro and in vivo. This effect may be caused by the induction of apoptosis and cycle arrest achieved through PI3K/AKT signaling pathway regulation.

Reevaluation of the post-marketing safety of Xuebijing injection based on real-world and evidence-based evaluations.

AIMS: To determine the causes of adverse reactions associated with Xuebijing injection and provide medical evidence for its safe and rational post-marketing use in clinical practice. MATERIALS AND METHODS: We used prospective nested case-control and prescription sequence analysis designs. Using data from the Hospital Information System, patients exhibiting trigger signals after receiving Xuebijing injection were classified as suspected allergic patients. Logistic regression analysis was performed on the risk factors associated with Xuebijing-induced allergic reactions. Randomized controlled and cohort studies on adverse drug reactions to Xuebijing injection were screened from databases and the results were subjected to meta-analysis. RESULTS: The overall incidence of allergic reactions or anaphylaxis tended to increase with dosage and patient's age. Moreover, compared with Xuebijing alone, co-administration of Xuebijing with other drugs or agents (including Ringer's sodium acetate solution, reduced glutathione, aspirin-DL-lysine, and torasemide) increased the risk of adverse reactions. The use of glucose as a vehicle also provoked a greater incidence of allergic reactions than that by the use of 0.9% w/v sodium chloride as a vehicle. Adverse reactions occurred more frequently in patients receiving indicated dosages than in those receiving off-label dosages. CONCLUSIONS: Adverse reactions to Xuebijing injections were correlated with vehicle type, dosage, age, and drug combination. There was no clear association between patient's condition at admission and suspected adverse reactions to Xuebijing injection. Factors influencing the adverse reactions to Xuebijing injection must be fully considered in clinical practice.

Reevaluation of the post-marketing safety of Shuxuening injection based on real-world and evidence-based evaluations.

AIM: To evaluate the factors influencing suspected hypersensitivity and adverse systemic reactions after Shuxuening injection and to provide innovative ideas and methods for the reevaluation of post-marketing safety of Shuxuening. METHODS: This study used a prospective, nested case-control study design, combined with a prescription sequence analysis design method. It classified patients who exhibited trigger signals after administration of Shuxuening injection as suspected allergic patients and made comparisons with patients who did not report adverse effects to calculate the correlation between relevant risk factors and suspected allergic reactions. Randomized controlled studies and cohort studies of the adverse drug reaction (ADR) of Shuxuening were performed using a computer database. Data retrieval was carried out by the foundation governing the individual database. Meta-analysis was performed by using R3.2.3 software to evaluate the ADRs of Shuxuening. RESULTS: The results of real-world study showed that administration of Shuxuening in combination with potassium aspartate and magnesium, atorvastatin calcium, Shengmai injection, pantoprazole sodium, or high-dose medication was a risk factor for suspected allergic reactions. Meta-analysis showed that the incidence of adverse events was 5.84% (95% CI 0.0499; 0.0674), and serious adverse reaction rate was 4.36% (95% CI 0.0188; 0.0760) when Shuxuening was used in combination with these drugs. The incidence of allergic reaction was also influenced by the vehicle, duration of treatment, single dose, and indicated vs off-label use. CONCLUSION: Risk factors for adverse reaction following the use of Shuxuening injection in patients are associated with a single dose, vehicle, type of disease, and combination with potassium aspartate, atorvastatin calcium, Shengmai injection, injection with pantoprazole sodium, and other drugs. Physicians should be careful to follow guidelines when administering this drug. We further propose that the unique methodology used in this study may be useful for reevaluation of the safety of other traditional Chinese medicines.

Protective effect and mechanism of ginsenoside Rg1 on carbon tetrachloride­induced acute liver injury.

Liver injury is a common pathological state in various types of liver disease; severe or persistent liver damage is the basis of hepatic failure. Ginsenoside Rg1 (Rg1), one of the primary active ingredients of ginseng, has been reported to reduce concanalin A­induced hepatitis and protect against lipopolysaccharide­ and galactosamine­induced liver injury. However, the underlying protective mechanism of Rg1 in acute liver injury remains unclear. In the present study, a carbon tetrachloride (CCl4)­induced acute liver injury model was established, and the protective effect of Rg1 on CCl4­induced acute liver injury was demonstrated in cell culture and animal experimental systems. Further investigation of the mechanisms demonstrated that pretreatment with Rg1 reduced elevated levels of alanine aminotransferase and aspartate aminotransferase, enhanced the antioxidant activity of superoxide dismutase (SOD) and decreased malondialdehyde (MDA) content. Experiments in vitro demonstrated that Rg1 decreased p65 expression and inhibited nuclear factor (NF)­κB activity. In addition to the effect of Rg1, an NF­κB inhibitor promoted cell survival, enhanced SOD activity and reduced MDA level. It was observed through in vivo experiments that pretreatment with Rg1 inhibited NF­κB expression and activity in Kupffer cells and reduced the serum levels of tumor necrosis factor­α and interleukin­6. In conclusion, the results of the present study indicated that pretreatment with Rg1 may rescue CCl4­induced acute liver injury in vivo and in vitro through inhibition of NF­κB activity, to restore the anti­oxidative defense system and down­regulate pro­inflammatory signaling pathways. The present observations provide a theoretical foundation for the clinical application of Rg1 therapy in acute liver injury.

Effect of folic acid supplementation on cancer risk among adults with hypertension in China: A randomized clinical trial.

The relationship of folic acid supplementation with the risk of cancer remains inconclusive. We aimed to evaluate the effects of folic acid supplementation on cancer incidence among adults with hypertension without history of stroke or myocardial infarction (MI) in the China Stroke Primary Prevention Trial (CSPPT). A total of 20,702 hypertensive adults without history of stroke or MI, stratified by MTHFR C677T genotypes(CC, CT and TT), were randomly assigned to receive double-blind daily treatment with a single pill containing 10 mg enalapril and 0.8 mg folic acid(n = 10,348) or a pill containing 10 mg enalapril alone(n = 10,354). During a median treatment duration of 4.5 years, cancer occurred in 116 participants(1.12%) in the enalapril-folic acid group versus 116 participants(1.12%) in the enalapril group (HR, 1.00; 95%CI, 0.77-1.29). There was also no significant difference in the HRs for specific types of cancer(esophageal, gastric, breast, lung, colorectal, head and neck, liver and gynecologic cancer or lymphoma) or cancer mortality(HR, 1.05; 95%CI, 0.69-1.58). For participants not receiving folic acid treatment (enalapril only group), MTHFR 677 TT genotype was an independent predictor of total cancer risk compared to CC genotype (HR, 1.86; 95%CI, 1.07-3.22). Consistently, a beneficial effect was observed in participants with MTHFR TT genotype and low folate levels (<9.0 ng/mL; HR, 0.47; 95%CI, 0.24-0.94). There is no evidence that 0.8 mg daily folic acid supplementation can increase the risk of cancer incidence among adults with hypertension without history of stroke or MI in China. Our data suggest a protective effect in participants with MTHFR TT genotype and low folate levels.

Immuno-enhancement of Taishan Pinus massoniana pollen polysaccharides on recombinant Bordetella avium ompA expressed in Pichia pastoris.

Bordetellosis, caused by Bordetella avium, continues to be an economic problem in the poultry industry of China. Vaccines with good protective ability are lacking. Thus, developing a novel vaccine against the B. avium infection is crucial. Here, we constructed a recombinant Pichia pastoris transformant capable of expressing the outer membrane protein A (ompA) of B. avium to prepare the recombinant ompA subunit vaccine and then evaluated its immune effects. To further investigate the immunomodulation effects of Taishan Pinus massoniana pollen polysaccharides (TPPPS) on this subunit vaccine, three concentrations (20, 40, and 60 mg/mL) of TPPPS were used as the adjuvants of the ompA subunit vaccine respectively. The conventional Freund's incomplete adjuvant served as the control of TPPPS. Chickens in different groups were separately vaccinated with these vaccines thrice. During the monitoring period, serum antibody titers, concentrations of serum IL-4, percentages of CD4(+) and CD8(+) T-lymphocytes in the peripheral blood, lymphocyte transformation rate, and protection rate were detected. Results showed that the pure ompA vaccine induced the production of anti-ompA antibody, the secretion of IL-4, the increase of CD4(+) T-lymphocytes counts and lymphocyte transformation rate in the peripheral blood. Moreover, the pure ompA vaccine provided a protection rate of 71.67% after the B. avium challenge. Notably, TPPPS adjuvant vaccines induced higher levels of immune responses than the pure ompA vaccine, and 60 mg/mL TPPPS adjuvant vaccine showed optimal immune effects and had a 91.67% protection rate. Our findings indicated that this recombinant B. avium ompA subunit vaccine combined with TPPPS had high immunostimulatory potential. Results provided a new perspective for B. avium subunit vaccine research.

[Meta-analysis on incidence of adverse drug reaction induced by Shuanghuanglian injection].

To conducted a systematic review on the safety of Shuanghuanglian injection in clinical use. In this paper, data from Pubmed, Embase, the Cochrane Library, CNKI, VIP and WanFang Data were retrieved. After extracting information and evaluating research methodological quality according to inclusion and exclusion criteria, Meta-analysis was conducted by using R3.2.3 software. A total of 56 individual studies were included, in which 585 cases showed adverse reactions in a total of 11 001 patients with Shuanghuanglian injections. Meta-analysis showed that the total incidence of adverse reactions was 6.5% (95%CI 0.051 to 0.082). Subgroup analysis showed that the incidence of adverse reactions was 4.8% (95%CI (0.032 to 0.067) and 8.1% (95%CI 0.054 to 0.112) respectively in children and adults; 7.2% (95%CI 0.049 to 0.095) and 6.6% (95%CI 0.036 to 0.104) respectively in 5%-10% glucose injection and 0.9% sodium chloride injection; 6.3% (95%CI 0.047 to 0.082) and 7.0% (95%CI 0.044 to 0.099) respectively in powder injection and liquid injection; 5.8% (95%CI 0.043 to 0.075) and 8.9% (95%CI 0.049 to 0.140) respectively in cases with duration of ≤7 d and >7 d; 4.2%(95%CI 0.027 to 0.059) and 8.4% (95%CI 0.059 to 0.113) respectively in single use and combined medication. Three most frequent types of adverse reaction symptoms reported were in skin and mucosa, digestive system, and body temperature center, with an incidence of 4% (95%CI 0.03 to 0.04), 3% (95%CI 0.02 to 0.03), and 1% (95%CI 0.00 to 0.01), respectively. The systemic evaluation demonstrated that the occurrence of adverse reaction of Shuanghuanglian injection was related to age, menstruum, duration of medication and combined medication. Incidence of adverse reactions differed considerably among different damage types. From the study demonstrated above, this paper concludes that we should follow the principles of evidence-based medication of traditional Chinese medicine; use Shuanghuanglian injection singly instead of combination with other drugs in clinical use; use Shuanghuanglian injection strictly in accordance to instructions, especially for children and the elderly, whose weight should be calculated and considered in medication; intensively monitor the drug adverse reaction after use; assess the risks of adverse effects for long-term usage, and take corresponding safety measures to ensure safety.

Immunological and protective effects of Bordetella bronchiseptica subunit vaccines based on the recombinant N-terminal domain of dermonecrotic toxin.

Dermonecrotic toxin (DNT) produced by Bordetella bronchiseptica (B. bronchiseptica) can cause clinical turbinate atrophy in swine and induce dermonecrotic lesions in model mice. We know that the N-terminal of DNT molecule contains the receptor-binding domain, which facilitates binding to the target cells. However, we do not know whether this domain has sufficient immunogenicity to resist B. bronchiseptica damage and thereby to develop a subunit vaccine for the swine industry. In this study, we prokaryotically expressed the recombinant N-terminal of DNT from B. bronchiseptica (named DNT-N) and prepared it for the subunit vaccine to evaluate its immunogenicity. Taishan Pinus massoniana pollen polysaccharide (TPPPS), a known immunomodulator, was used as the adjuvant to examine its immune-conditioning effects. At 49 d after inoculation, 10 mice from each group were challenged with B. bronchiseptica, and another 10 mice were intradermally challenged with native DNT, to examine the protection imparted by the vaccines. The immune parameters (T-lymphocyte counts, cytokine secretions, serum antibody titers, and survival rates) and skin lesions were determined. The results showed that pure DNT-N vaccine significantly induced immune responses and had limited ability to resist the B. bronchiseptica and DNT challenge, whereas the mice administered with TPPPS or Freund's incomplete adjuvant vaccine could induce higher levels of the above immune parameters. Remarkably, the DNT-N vaccine combined with TPPPS adjuvant protected the mice effectively to prevent B. bronchiseptica infection. Our findings indicated that DNT-N has potential for development as an effective subunit vaccine to counteract the damage of B. bronchiseptica infection, especially when used conjointly with TPPPS.

[Predictive analysis on Shenmai injection-induced adverse reactions with Logistic model and ROC curve].

To study relevant risk factors of Shenmai injection induced adverse reactions by using Logistic model and ROC curve, and made the prediction for the occurrence of relevant adverse reactions/events. Case data of patients treated with Shenmai injection were collected by using the prospective, multi-center, large-sample, nested-case control method, in order to analyze the risk factors of Shenmai injection-induced adverse reactions/events, establish the logistic model and draw the receiver operating characteristic (ROC) curve for risk factors. During the study, 7632 patients (including 3 477 males and 4 155 females) were included, and eight of them suffered adverse reactions/events. Based on a multi-factor Logistic model analysis, the age (> or = 50 years) (OR = 5.061, 95% CI: 2.197-7.924; P = 0.001), the total number of medication days (OR = -1.020, 95% CI: -l.652 - 0.388; P = 0.002) and the single dose (OR = 0.245, 95% CI: 0.127-0.364; P = 0.000) were significant independent risk factors for Shenmai injection-induced adverse reactions/events. According to the results, ROC curves were drawn with age (> or = 50 years), the total number of days of inedication and single dose; The area under ROC curves the joint predictor (0.9753, 95% CI: 0.9443-1.000, P < 0.005) was larger than that of the other three single indexes, with a higher risk prediction value. The independent risk factors for Shenmai injection-induced adverse reactions/events included the age (> or = 50 years), the total number of days of medication and single dose. In clinical practice, the age (> or = 50 years), the total number of days of medication and the medication dose can be substituted in the joint predictor calculation formula (P = 1 / [1 + e(-(-21.58 + 5.061 x Xage - 1.020 x Xd + 0.245 x X(mL)] to predict the potential adverse reactions of patients and adjust the dosage regimen.

In vitro Antifungal Activity and Mechanism of Action of Tea Polyphenols and Tea Saponin against Rhizopus stolonifer.

The in vitro antifungal activities and mechanism of action of tea polyphenols (TP), tea saponin (TS) and their combination were evaluated against Rhizopus stolonifer. The results showed that both TP and TS inhibited the mycelial growth in a dose-dependent manner, and their combination at the ratio of 7:3 exhibited synergistic antifungal interaction. We also observed that the treatment of TP or TS significantly induced the production of H2O2 and resulted in membrane lipid peroxidation, thus leading to an increase in cell membrane permeability and the leakage of K(+), soluble protein and soluble sugar. Moreover, combining them for treatment increased the induction of H2O2 production and oxidative damage. Scanning electron microscopic observations also showed the damage to the hyphal cell structure. It was concluded that TP, TS and their combination inhibit the growth of R. stolonifer through the induction of H2O2 production, leading to cell membrane oxidative damage and intracellular constituent leakage. These findings suggest that TP and TS can potentially be used as an alternative to control postharvest fruit diseases caused by R. stolonifer.

Co-adjuvant effects of plant polysaccharide and propolis on chickens inoculated with Bordetella avium inactivated vaccine.

Taishan Pinus massoniana pollen polysaccharide (TPPPS), propolis (PP) and aloe polysaccharide (AP), used as adjuvants, have been proven to possess immunity-enhancing functions. However, their collaborative immunomodulatory effects are largely unknown. To determine which combination can induce the best effects, the three adjuvants were separately or conjointly added into Bordetella avium inactivated vaccines to investigate their co-adjuvant effects on vaccinated chickens. We found that, among all six adjuvant-treated vaccine inoculated groups (TPPPS, PP, AP, TPPPS-PP, PP-AP and TPPPS-AP), the chickens inoculated with TPPPS, PP or TPPPS-PP adjuvant vaccines showed significantly higher levels of antibody titre, cytokine, lymphocyte transformation and peripheral blood T-lymphocyte count than those of non-adjuvant vaccine inoculated groups (P < 0.05), indicating the good immune-enhancing effects of TPPPS and PP. The TPPPS-PP group showed the highest levels of antibody titres and interleukin-2 (IL-2) at 14-28 days post the first inoculation (dpi), lymphocyte transformation rates (LTRs) at 14-35 dpi, CD4(+) T-lymphocyte counts at 14-42 dpi, and CD8(+) T-lymphocyte counts at 28 dpi. The results revealed that B. avium inactivated vaccine used conjointly with TPPPS and PP induced the strongest humoral and cellular immune responses. Thus, there was a synergistic effect between TPPPS and PP on enhancing immunity, which suggests that they can be used as a novel adjuvant formulation for the development of poultry vaccines.

Antifungal activity and mechanism of tea polyphenols against Rhizopus stolonifer.

OBJECTIVE: To investigate the antifungal activity and possible mechanism of tea polyphenols (TPs) against Rhizopus stolonifer, the agent of rotting in nectarines and peaches. RESULTS: TP inhibited both mycelial growth and spore germination in vitro in a dose-dependent manner, and the morphological changes of the treated hyphae with TP, such as irregularly swollen, increased branching, wrinkled, entwining, collapse and breakage, and of the treated spores, such as swelling of germ tube tips, exfoliation of the surface layer and disorganization of cell organelles, were observed using optical microscopy, scanning electron microscopy and transmission electron microscopy. TP also significantly decreased rhizopus rot on inoculated nectarines and induced the activities of phenylalanine ammonia lyase, polyphenol oxidase, peroxidase, chitinase, and ß-1,3-glucanase. CONCLUSION: The mechanism of action might be attributed to direct damage of the mycelium and spore and indirect induction of defensive enzyme activities. TP has the potential to be developed as an alternative to control post-harvest disease of fruit caused by R. stolonifer.

Establishment and optimization of a regionally applicable maize gene-flow model.

Because of the rapid development of transgenic maize, the potential effect of transgene flow on seed purity has become a major concern in public and scientific communities. Setting a proper isolation distance in field experiments and seed production is a possible solution to meet seed-quality standards and ensure adventitious contamination of products is below a specific threshold. By using a Gaussian plume model as basis and data recorded by meteorological stations as input, we have established a simple regionally applicable maize gene-flow model for prediction of the maximum threshold distances (MTD) at which gene-flow frequency is equal to or lower than a threshold value of 1 or 0.1 % (MTD1%, MTD0.1%). After optimization of the model variables, simulated outcrossing rate was a good fit to data obtained from field experiments (y = 1.156x, R (2) = 0.8913, n = 30, P < P 0.01). In the process of model calibration, it was found that only 15.82 % of the total amount of the pollen released by each plant participated in the dispersal process. The variable "a" for genetic pollen competitiveness between donor and recipient was introduced into our model, for the "Zinuo18" and "Su608" used, "a" was 17.47. Finally, the model was successfully used in the spring maize-growing region of Northeast China. The range of MTD1% and MTD0.1% in this region varied from 10 m to 49 m and from 17 m to 125 m, respectively.

Paeonol, the main active principles of Paeonia moutan, ameliorates alcoholic steatohepatitis in mice.

AIM OF STUDY: Paeonol, a major phenolic component of Moutan Cortex, is traditionally used as a Chinese herbal medicine in various diseases including hepatitis. Evidence shows that paeonol has anti-inflammatory, anti-tumor, and anti-atherosclerosis effects. However, the effect of paeonol on alcoholic liver injury remains obscure. The present investigation was designed to determine the effects of paeonol on alcohol-induced hepatic injury in mice. MATERIALS AND METHODS: The degree of alcoholic liver injury was evaluated biochemically by measuring serum markers and pathological examination. Real-time PCR and ELISA methods were used to check the expression of cytokines. Western blotting was used to check CYP 450 expression. RESULTS: Treatment with paeonol significantly attenuated the level of serum aminotransferase, reduced the severe extent of hepatic cell damage, steatosis, and the infiltration of inflammatory cells in a model of alcoholic liver injury (P<0.05). Interestingly, paeonol markedly decreased hepatic mRNA expression of lipogenic genes (P<0.05) while had no effect on protein expression of hepatic CYP2E1. Furthermore, paeonol significantly decreased serum and tissue inflammatory cytokine levels, tissue lipid peroxidation, neutrophil infiltration and inhibited the apoptosis of hepatocytes (P<0.05). Kupffer cells isolated from ethanol-fed mice produced high amounts of tumor necrosis factor alpha, whereas Kupffer cells from paeonol treatment ethanol-fed mice produced less tumor necrosis factor alpha (P<0.05). CONCLUSIONS: These findings suggest that paeonol may represent a novel, protective strategy against alcoholic liver injury by attenuating hepatic steatosis, inflammatory response and apoptosis.