Effects of herbal dregs supplementation of Salvia miltiorrhiza and Isatidis Radix residues improved production performance and gut microbiota abundance in late-phase laying hens.

The present study was designed to evaluate the effect of a mixture of Chinese medicinal residues (CMRs) consisting of Salvia miltiorrhiza residues (SMR) and Isatidis Radix residues (IRR) on productive performance, egg quality, serum lipid and hormone levels, liver and blood antioxidant capacity, oviduct inflammation levels, and gut microbiota in the late-laying stage. A total of 288 fifty-four-week-old BaShang long-tailed hens were divided into four groups. The feed trial period was 8 weeks. The control group was fed the basic diet as a CCMR group, supplemented with 3, 4, and 6% for the experimental groups LCMR, MCMR, and HCMR. The egg production rate of the MCMR group was 8.1% higher than that of the CCMR group (p < 0.05). Serum triglyceride (TG) levels of hens of the CMR-supplemented group were significantly decreased than those of the CCMR group (p < 0.05). The group supplemented with different levels of CMR had significantly higher serum HDL-C levels compared with the control group (p < 0.05). Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were remarkably increased for the LCMR and MCMR groups and significantly decreased for the HCMR group compared to CCMR (p < 0.05). Serum and liver glutathione peroxidase (GSH-PX) activities were significantly increased, and malondialdehyde (MDA) levels were significantly decreased in the MCMR group compared to the CCMR group (p < 0.05). The expression levels of tubal inflammatory factor markers (IL-4, IL-1ß, TNF-α) in the MCMR and HCMR groups were consistent with the pathological findings of the sections. As for cecal microbiota, supplementation with CMR affected the alpha diversity of the cecum microbiome at the genus level. The Shannon index was significantly higher in the MCMR group than in the CCMR and HCMR groups (p < 0.05). Supplementation with different levels of CMR mainly regulated the ratio of intestinal Firmicutes to Bacteroidetes and the abundance of phyla such as Proteobacteria. In addition, CMR supplementation at different levels in the diet enriched lipid-metabolizing bacteria, such as Bacteroides and Ruminococcus_gnavus_group. Furthermore, according to linear discriminant analysis (LDA) effect size (LEfSe) analysis, the MCMR group showed an increase in the number of short-chain fatty acid-producing bacteria Romboutsia and fiber-degrading specialized bacteria Monoglobus. Therefore, supplementation of appropriate amounts of CMR to the diet of laying hens enhanced reproductive hormone levels, hepatic antioxidant capacity, and lipid metabolism, alleviated the levels of oviductal inflammatory factors, and modulated the abundance structure of bacterial flora to improve the late-laying performance and egg quality. The results of the current study showed that CMR is a beneficial feed supplement for chickens when added in moderation.

Transcriptomics and metabolomics revealed the molecular mechanism of the toxic effect of mancozeb on liver of mice.

Mancozeb (MCZ), a broad-spectrum fungicide, has been widely used in crops (tomatoes and potatoes) in the past few decades, resulting in its bioaccumulation in the food web. However, the mechanism of MCZ on liver injury has not been reported yet. This study combined transcriptomics and metabolomics to explore the potential mechanism of MCZ on liver injury. MCZ group was given 100 mg/kg MCZ every day, and the C group was given 0.2 mL of deionized water every day. One hundred mg/kg MCZ led to unclear hepatocyte structure and hemorrhagic inflammatory cell infiltration. Transcriptomics and metabolomics analyses showed that the MCZ group resulted in 326 differentially expressed genes (DEGs) and 179 differential metabolites. Joint analysis showed that DEGs and differential metabolites were mainly enriched in the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. We found that MCZ could increase the content of reactive oxygen species (ROS) and reduce the activities of superoxide dismutase (SOD) and catalase (CAT). The contents of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) in the liver decreased significantly, and the state of DNA methylation was significantly higher than the control (C) group (p < 0.05). Our results suggest that AMPK and mitogen­activated protein kinase (MAPK) signaling pathways play an important role in MCZ-induced liver injury and are the key mechanisms for understanding the hepatotoxicity of MCZ.

Therapeutic effect of Schisandrin A on avian colibacillosis through gut-liver axis.

This study evaluated the therapeutic efficacy of Schisandrin A on systemic colibacillosis of chickens. One hundred and eighty, 1-day-old Hailan Brown chickens were divided into 6 groups of 30 chickens each and assigned to the following treatments: 1) uninfected/untreated control; 2) infected Escherichia coli; 3) infected-plus low dose of Schisandrin A therapy (50 mg/kg); 4) infected-plus medium dose of Schisandrin A therapy (100 mg/kg); 5) infected-plus high dose of Schisandrin A therapy (200 mg/kg) and 6) infected-plus antimicrobial therapy (florfenicol). Each group of chickens was placed in cages with a photoperiod of 12 h of light and 12 h of dark. Feed and water for all groups were provided ad libitum for the duration of the study. On d 14, all the chickens except the uninfected control group were intraperitoneally inoculated with a fresh culture of E. coli containing 1 × 108 CFU/mL. The parameters measured included: average daily weight gain (ADG), percent survivability, liver index, serum activity of enzymes (ALT and AST), hepatic and intestinal concentrations of TNF-α, IL-1ß, IL-6, IL-8, and LPS, expression of tight junction proteins (occludin, ZO-1, and claudin-1), relative abundance of bacterial species and histopathological changes in hepatic and intestinal tissue. The results showed that the medium and high doses of Schisandrin A ameliorated the detrimental effects of colibacillosis on weight gain. Regarding organ indexes, E. coli infection induced a significant increase in liver index, all the doses of Schisandrin A produced a significant reduction of liver index in comparison to the E. coli infected control. Serum activity of ALT and AST enzymes significantly increased due to E. coli infection, with the exception of the low dose of Schisandrin A for AST enzyme activity, all the Schisandrin A treatments significantly lowered enzyme activity in comparison to the E. coli infected control. Regarding concentrations of inflammatory markers in hepatic and intestinal, E. coli infection caused a significant increase in TNF-α, IL-1ß, IL-6, and IL-8, except the lowest dose of Schisandrin A for IL-1ß, the rest of the doses tested were able to significantly reduced the concentrations of inflammatory markers. Concentrations of LPS in hepatic and intestinal tissues were significantly increased by E. coli infection, all doses of Schisandrin A significantly reduced the concentration of LPS in hepatic and intestinal tissue. E. coli infection significantly reduced the expression of 2 tight junction proteins (ZO-1 and Claudin-1), the higher doses of Schisandrin A were effective in significantly increasing the expression of these tight junction proteins when compared with the E. coli infected control. Taken together, these results show that Schisandrin A has potential as an alternative therapy for the treatment of colibacillosis in chickens.

Maternal exposure to perfluorooctanoic acid (PFOA) causes liver toxicity through PPAR-α pathway and lowered histone acetylation in female offspring mice.

The study was conducted to investigate the liver toxicity in female offspring mice induced by maternal exposure to perfluorooctanoic acid (PFOA). Fifty pregnant Kunming mice were randomly divided into 5 groups with 10 of each, which were treated with 0.2 mL PFOA solution dissolved with deionized water at 0, 1, 2.5, 5, and 10 mg/kg BW, respectively, from the pregnancy day (PND) 0 to day 17. Female offspring mice were sacrificed to collect serum and liver at postpartum day 21. The results showed that PFOA significantly reduced the body weight at weaning and the survival rate of the female offspring mice (P < 0.01) increased the liver index of the pups (P < 0.01). Meanwhile, PFOA also caused hepatic bleeding, local necrosis, and enlargement of hepatocytes and vacuolization. The levels of serum AST, ALT, SOD, and CAT in PFOA treatment group were upregulated significantly (P < 0.01). The expressions of Acot1, Acox1, and Acsl1 genes were increased significantly (P < 0.01). The expression of PPAR-α gene was decreased significantly (P < 0.01). There was no significant difference in the expression of Cpt1a gene among the 5 groups. HAT activity was reduced significantly and HDAC activity was increased significantly. The expression of anti-acetyl-histone H3 and acetyl-histone H4 was reduced significantly. Thus, our findings indicate that exposure to PFOA during pregnancy affects the growth and development of the pups and causes liver damage, disrupting the secretion of enzymes involved in fatty acid oxidation induced by PPAR-α, leading to liver oxidative stress and a decrease in the degree of histone acetylation. Elevated HDAC may aggravate downstream fatty acid metabolism disorders through PPAR-α.

Hazards of bisphenol A -- blocks RNA splicing leading to abnormal testicular development in offspring male mice.

This study was conducted to investigate the effects of maternal exposure to BPA on testicular development in offspring males. Pregnant Kunming mice were randomly divided into 7 groups with 20 mice in each group. Group A was the control group and the mice were given distilled water orally. Mice in groups B, C, D, E, F, G received BPA orally at a dose of 0.05 mg/kg/d, 0.5 mg/kg/d, 5 mg/kg/d, 10 mg/kg/d, 20 mg/kg/d, 50 mg/kg/d, respectively. F0 mice were exposed to BPA for 40 days from gestation day 0 to lactation day 21. F1 male mice were sacrificed at weaning (postnatal day 21). Histological observations revealed architectural damages in testis in BPA exposed groups. The testicular organ index increased significantly when the BPA oral exposure dose was above 20 mg/kg/d (P < 0.05). BPA contents in serum of F1 male mice increased significantly when BPA was above 5 mg/kg/d (P < 0.05), while the contents significant increased in maternal serum when BPA was higher than 0.5 mg/kg/d. The damage of cell nuclear DNA of testis was significantly aggravated when BPA was above 5 mg/kg/d. The expression of AR in the testis was significantly increased when BPA was above 20 mg/kg/d (P < 0.05). Transcriptome sequencing showed that the Snrnp 40 which encoding U5 snRNA subunit was significantly up-regulated in spliceosome pathway, and the Hnrnpu which encoding splicing universal protein component was significantly down-regulated. The blockage of spliceosome might be one of the reasons why BPA affects testicular development.

Lycopene reduces in utero bisphenol A exposure-induced mortality, benefits hormones, and development of reproductive organs in offspring mice.

This study was conducted to investigate the protective effect of lycopene on reproductive toxicity induced by in utero exposure to bisphenol A (BPA) in offspring mice. Pregnant mice in the BPA model group were given orally 500 mg/kg/day BPA from pregnant day (PD)8 to PD14. Mice of lycopene group were gavaged with 20 mg/kg/day lycopene from PD1 to PD7 and then given 500 mg/kg/day BPA from PD8 to PD14. Results showed that lycopene reduced the elevated mortality in offspring mice of the mother exposed to BPA. BPA lowered the levels of testosterone, luteinizing hormone, and follicle-stimulating hormone while lycopene treatment increased the levels significantly. BPA elevated estradiol while lycopene lowered estradiol in the offspring. BPA caused testicular damage as shown by less Leydig cells and ovarian injury as shown by less corpus granules in adult offspring, while lycopene decreased the damages. Maternal exposure to BPA increased Bax and decreased Bcl-2 in testicular and ovary tissues in the offspring mice. Lycopene decreased Bax in testis and ovary and increased Bcl-2 in ovary tissues in the offspring mice. These findings suggest lycopene has protective effects on in utero BPA exposure-induced reproductive toxicity in offspring mice.

Effects of Radix scutellariae and Rhizoma atractylodis on LPS-induced abortion and the uterine IL-10 contents in mice.

In the present study, lipopolysaccharide (LPS) was injected i.v. via the tail vein (0.1 microg per mouse) to induce abortion (embryo resorption) in Kunming mice. The interleukin 10 (IL-10) contents in the uterus were assayed by ELISA. The results revealed that the IL-10 level was significantly decreased in the LPS-induced abortion group of mice compared to the controls. Use of Pentoxifylline (PXF), or a combination of Radix scutellariae and Rhizoma atractylodis reversed the LPS effects: bringing down the fetal resorption rate, and increasing the IL-10 level significantly. The study indicates that the anti-abortive effects of PXF and the combination of Radix scutellariae and Rhizoma atractylodis are closely related to up-regulation of the Th2 cytokine IL-10 at the maternal fetal interface.