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Mulberry (Morus alba L.) twigs are a traditional Chinese medicine and edible agricultural by-product. Oxyresveratrol (OXY) is one of the natural resorcinol-type polyphenols obtained from mulberry twigs with anti-melanogenesis effects. This study aimed to investigate the ameliorative effects and mechanisms of OXY on post-inflammatory hyperpigmentation (PIH) in vitro. The results of DPPH radical scavenging and tyrosinase inhibition assays showed that OXY exhibited potent antioxidant and tyrosinase inhibitory activities. In human melanocytes, OXY significantly down-regulated protein expression related to melanin synthesis and transport. A molecular docking study suggested that OXY could inhibit these GTPases (RAB27A, RAC1, and CDC42) activities in melanosome transfer processes. Furthermore, OXY significantly reduced inflammatory factor secretion, promoted human β-defensin production, and up-regulated the expression of barrier proteins in UVB-induced human keratinocytes. This research indicated that the OXY from mulberry twigs has potential applications in ameliorating PIH through its antioxidant, anti-melanogenic, melanosome transport inhibition, anti-inflammatory, and photoprotective properties.

Oxidative stress-induced neuronal damage is the main cause of neurodegenerative diseases, which is characterized by cognitive impairment. We selected a high-content natural alkaloid, trigonelline, from daily vegetables eggplants. The results showed that eggplants were rich in trigonelline. It has antioxidant and anticancer effects, but there is limited research on neurodegenerative diseases. An in vitro neuronal injury model was established using PC12 cells damaged by H2O2 to explore neuroprotective effect of trigonelline. An aging model was established in vivo by injecting D-galactose into mice for 6 weeks. Trigonelline have been found to improve cognitive impairment by improving brain-damage, enhancing antioxidant system activity in mice, regulating the activity of ChAT and AChE to maintain the balance of cholinergic system. The experimental results indicate that trigonelline has good neuroprotective effects, providing a reference for the development of functional foods made from eggplant and trigonelline, as well as prevention and treatment of neurodegenerative diseases.

Objective: Autoimmune hepatitis (AIH) is a chronic immune-mediated inflammatory liver disease. Intestinal flora disturbance in AIH is closely related to TFH/TFR cell imbalances. As a new method of microbial therapy, the role of fecal microbiota transplantation (FMT) in AIH remains elusive. Here, we attempted to verify the functional role and molecular mechanism of FMT in AIH. Methods: An experimental autoimmune hepatitis (EAH) mouse model was established to mimic the characteristics of AIH. H&E staining was used to detect histological features in mouse liver tissues. Serological tests were employed to identify several liver function biomarkers. Flow cytometry was utilized to examine the status of TFH/TFR cell subsets. Western blotting was used to evaluate TLR pathway-associated protein abundance. RT‒qPCR was applied to evaluate Treg cell markers and inflammation marker levels in mouse liver tissues. Results: There was significant liver inflammation and dysregulated TFR/TFH cells with elevated levels of liver inflammation-associated biomarkers in EAH mice. Interestingly, transferring therapeutic FMT into EAH mice dramatically reduced liver injury and improved the imbalance between splenic TFR and TFH cells. FMT treatment also reduced elevated contents of serum alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in EAH mice. Furthermore, therapeutic FMT reversed the increased levels of IL-21 while promoting IL-10 and TGF-β cytokines. Mechanistically, FMT regulated TFH cell response in EAH mice in a TLR4/11/MyD88 pathway-dependent manner. Conclusion: Our findings demonstrated that liver injury and dysregulation between TFR and TFH cells in EAH might be reversed by therapeutic FMT via the TLR4/11-MyD88 signaling pathway.

ABSTRACT: It has been reported that dietary administration of Bacillus subtilis KC1 is effective in alleviating lung injury induced by Mycoplasma gallisepticum (MG) infection in chickens. However, the underlying molecular mechanism of B. subtilis KC1 against MG infection is still unclear. The purpose of this study was to determine whether B. subtilis KC1 could alleviate MG infection-induced lung injury in chickens by regulating their gut microbiota. The results of this study indicate that B. subtilis KC1 supplementation has the potential to alleviate MG infection-induced lung injury as reflected by reduced MG colonization, reduced pathologic changes, and decreased production of pro-inflammatory cytokines. In addition, B. subtilis KC1 supplementation was partially effective in alleviating the gut microbiota disorder caused by MG infection. Importantly, B. subtilis KC1 enriched the beneficial Bifidobacterium animalis in gut and thus reversed indole metabolic dysfunction caused by MG infection. B. subtilis KC1 supplementation increased levels of indole, which enhanced aryl hydrocarbon receptor activation, improving barrier function and alleviating lung inflammation caused by MG. Overall, this study indicates that B. subtilis KC1 has a “gut-lung axis” mechanism that can reduce the severity of MG infection by enriching intestinal B. animalis and regulating indole metabolism.

ABSTRACT: Mycoplasma gallisepticum (MG) is dependent on its host for many nutrients due to the loss of many important metabolic pathways. Ceramide is a sphingolipid that regulates multiple cellular processes in eukaryotic cell. Several studies highlighted the crucial role of ceramide on the pathogenesis of various pathogens. This study aimed to determine whether ceramide plays a crucial role in the pathogenesis of MG. Based on an MG infection model in DF-1 cells, the results revealed that MG infection induced ceramide accumulation in DF-1 cells. Inhibiting the de novo synthesis of ceramide significantly inhibited MG proliferation and inflammatory injury caused by MG in DF-1 cells. Meanwhile, MG infection led to endoplasmic reticulum stress, and pharmacologic inhibition of endoplasmic reticulum stress prevented ceramide accumulation and MG proliferation in DF-1 cells, alleviating the inflammatory injury caused by MG. In addition, MG infection significantly promoted expression level of stromal interaction molecule 1 (STIM1), thus induced calcium overload and oxidative stress. Furthermore, inhibition of STIM1 expression partially restored calcium homeostasis and mitigated oxidative stress, thus alleviated endoplasmic reticulum stress. Importantly, the inflammatory injury caused by MG were partially ameliorated by baicalin treatment (20 µg/mL) through downregulating STIM1 expression. In summary, these results suggests that ceramide accumulation through the de novo pathway plays an important role to promote MG proliferation and baicalin can alleviate MG infection induced inflammatory injury via regulating STIM1-related oxidative stress, endoplasmic reticulum stress and ceramide accumulation in DF-1 cells.

Objectives: To investigate acute toxicity of Bajitian (Morinda officinalis) in zebrafish embryos. Methods: Zebrafish embryos at 48-h post fertilization (hpf) were exposed to Bajitian ethanol extract for 72 h. The causative action of a delay in yolk sac absorption by Bajitian was investigated by RT-PCR analysis of lipid metabolism-related microsomal triglyceride transfer protein (MTP), apolipoprotein C-II (ApoC2) and lipogenesis-related liver x receptor (LXR) genes. The effect of Bajitian eliciting an inflammatory response was studied by exposing 72 hpf myeloperoxidase (MPO): GFP transgenic zebrafish embryos to Bajitian extract for 4 h. Assessment was done by TUNEL, caspase-3/7, and RT-PCR analysis of the apoptosis related pathway B-cell lymphoma 2 associated X protein (Bax), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) genes, neutrophil development-related stem cell leukaemia (SCL) and transcription factor PU.1 genes, to reveal the causative action of Bajitian reducing neutrophils. Results: RT-PCR analysis found that Bajitian extract had no effect on the expression of MTP or ApoC2 genes, but upregulated LXR gene, which might explain the delay in yolk sac absorption. Analysis of the inflammatory response showed that compared with negative controls, Bajitian extract significantly (P

ABSTRACT: Aflatoxin B1 (AFB1) is one of the most toxic mycotoxins. It has been reported that dietary exposure to AFB1 is related to the low growth performance, immunosuppression, and high susceptibility to infectious diseases of chickens. The aim of the present study was to evaluate the protective effects of Lactobacillus salivarius on broiler chickens challenged with AFB1. First, AFB1 degradation ability of Lactobacillus salivarius was measured by a high-performance liquid chromatography (HPLC) method. Then, the Arbor Acres broiler chickens were randomly assigned to experimental groups. The effects of Lactobacillus salivarius supplementation on the growth performance, liver function, and meat quality were measured, and immune response was also determined after vaccination with attenuated infectious bursal disease virus (IBDV) vaccine of broilers challenged with AFB1. Besides, resistance to Salmonella Pullorum infection along with AFB1 exposure was determined in broilers. The results showed that Lactobacillus salivarius could effectively degrade AFB1. Lactobacillus salivarius supplementation improved growth performance, liver function, and meat quality of broilers challenged with AFB1. In addition, Lactobacillus salivarius supplementation resulted in enhanced specific antibody and IFN-γ production, and lymphocyte proliferation in broilers challenged with AFB1 after IBDV vaccine immunization. Furthermore, Lactobacillus salivarius supplementation enhanced Salmonella Pullorum infection resistance in broilers challenged with AFB1. Our results revealed a tremendous potential of Lactobacillus salivarius as feed additive to degrading AFB1 and increasing broilers production performance in poultry production.

ABSTRACT: The purpose of the present study was to evaluate the probiotic properties of Bacillus subtilis KC1 as a feed additive in the poultry feed. Effects of the Bacillus subtilis supplementation on growth performance, heat-stress tolerance, resistance to Mycoplasma gallisepticum (MG) and Salmonella Pullorum challenge of broilers were determined. The protective effects of the Bacillus subtilis on liver function and immune response of broilers challenged with Aflatoxin B1 (AFB1) were also scrutinized. The results showed that the Bacillus subtilis supplementation could improve growth performance, increased body weight, relative weight of the immune organ and dressing percentage, and decrease feed conversion ratio. In addition, the Bacillus subtilis supplementation alleviated adverse effects caused by heat stress, MG, and Salmonella Pullorum challenge. Furthermore, the Bacillus subtilis supplementation resulted in improved liver function and enhanced immune response of broilers challenged with AFB1. In conclusion, these results suggested a tremendous potential of Bacillus subtilis KC1 as a feed additive in the poultry feed.

Cannabidiol (CBD) extracts have gained attention for their therapeutic efficacy. The present study used a zebrafish embryo caudal fin amputation model and found 1.25 mg/L crude CBD extract accelerated caudal fin regeneration and reduced apoptosis after amputation, while not altering mitotic regenerating cells. The purity of the CBD extract was 55.5 ± 0.37%. Pure CBD promoted fin regeneration and inhibited neutrophil accumulation in a dose-dependent manner, while these effects were not seen in a high concentration of CBD (2.5 mg/L), possibly due to the toxicity of the high dose. An equivalent amount of pure CBD (0.625 to 1.25 mg/L) enhanced regeneration and reduced apoptosis similarly to crude CBD extract (1.25 mg/L). Additionally, CBD reduced the gene expression level of cxcl8, tnf-a, and il-1β, and protein expression level of IL-1β, Caspase 3, and PARP, but not Bcl-2 or Bax. These results suggest that CBD exerts its effect on wound pro-regeneration in part by modulating the inflammatory response and the IL-1β/Caspase 3/PARP signal pathway.

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are genetically, pathologically and clinically-related progressive neurodegenerative diseases. Thus far, several SQSTM1 variations have been identified in patients with ALS and FTD. However, it remains unclear how SQSTM1 variations lead to neurodegeneration. To address this issue, we investigated the effects of ectopic expression of SQSTM1 variants, which were originally identified in Japanese and Chinese sporadic ALS patients, on the cellular viability, their intracellular distributions and the autophagic activity in cultured cells. Expression of SQSTM1 variants in PC12 cells exerted no observable effects on viabilities under both normal and oxidative-stressed conditions. Further, although expression of SQSTM1 variants in PC12 cells and Sqstm1-deficient mouse embryonic fibroblasts resulted in the formation of numerous granular SQSTM1-positive structures, called SQSTM1-bodies, their intracellular distributions were indistinguishable from those of wild-type SQSTM1. Nonetheless, quantitative colocalization analysis of SQSTM1-bodies with MAP1LC3 demonstrated that among ALS-linked SQSTM1 variants, L341V variant showed the significantly lower level of colocalization. However, there were no consistent effects on the autophagic activities among the variants examined. These results suggest that although some ALS-linked SQSTM1 variations have a discernible effect on the intracellular distribution of SQSTM1-bodies, the impacts of other variations on the cellular homeostasis are rather limited at least under transiently-expressed conditions.

Background: On September 22, 2013, two patients from Sichuan Province, China presented with symptoms of food-borne botulism, a rare but fatal illness caused by the consumption of foods containing Clostridium botulinum neurotoxins. Methods: Investigators reviewed the medical charts and food consumption histories, and interviewed patients and family members. Food samples and clinical specimens were tested for botulinum toxin and neurotoxin-producing Clostridium species by standard methods. Results: The first two index cases presented with cranial neuropathies and flaccid paralysis, and required mechanical ventilation. There were 12 confirmed outbreak-associated cases. Botulinum toxin type A was identified in the smoked ribs, and all of the patients had consumed the smoked ribs from the same local restaurant. The smoked ribs contained no added salt, sugar, or preservative. Botulinum toxin production likely resulted from the cold-smoking preparation method and inappropriate refrigeration. Conclusions: Smoked ribs produced by a local restaurant, contaminated with type A botulism, was the contributor to this outbreak. The supervision of food safety should be strengthened to prevent future outbreaks in China.

Generally, the principle of linear superposition is not applicable in nonlinear systems. The results of our researches prove that for some certain types of decomposed solutions of (2+1)-dimensional Caudrey–Dodd–Gibbon–Kotera–Sawada(CDGKS) equation, the linear superposition principle holds. First, beginning with the potential (2+1)-dimensional CDGKS equation, six sets of decomposition equations are formulated by the formally variable separation approach. On the basis of these decompositions, the linear superposition solutions are then discussed. More specifically, the combination of two periodic wave solutions, soliton and periodic wave interaction solution and the multi-soliton solution are obtained.

Using the Hirota’s bilinear method combined with the velocity resonance mechanism, the two-soliton molecule, the three-soliton molecule and the four-soliton molecule for the third-fifth-order Lax’s KdV equation, the third-fifth-seventh-order Lax’s KdV equation and the third-fifth-seventh-ninth-order Lax’s KdV equation are obtained respectively. To show the dynamical properties of these soliton molecules, their three dimensional profiles and the density plots with particular choices of the involved free parameters are well displayed. More generally, by summarizing the three expressions for soliton molecules, the general formula of N-soliton molecule for combined (2N+1)th-order Lax’s KdV equation are well given.

Bt crops that are transgenic crops engineered to produce Bt toxins which occur naturally with Bacillus thuringiensis (Bt) have been widely planted and its environmental risk assessment has been heavily debated. The effects of Bt crops on soil microbial communities are possible through changing the quantity and quality of C inputs and potential toxic activity of Bt protein on soil organisms. To date, the direct effects of Bt protein on soil microorganisms is unclear. Here we added Cry1Ac, one of the most commonly used Bt protein in Bt crops, to the soil and monitored changes in soil bacterial, fungal and archaeal diversities and community structures using ribosomal DNA-fingerprinting method, as well as their population sizes by real-time PCR over a 100-day period. Despite the fact that variations were observed in the indices of evenness, diversity and population sizes of bacteria, fungi and archaea with different Cry1Ac addition rates up to 100ngg -1 soil, the indices of soil microbial diversities and evennesses did not significantly shift with Cry1Ac protein addition, nor did population sizes change over time. The diversities of the dominant bacteria, fungi and archaea were not significantly changed, given Cry1Ac protein addition rates over a period of 100 days. These results suggested that Bt protein derived by cultivations of transgenic Bt crops is unlikely to cause transient or even persisting significant changes in soil microorganisms in field., (Copyright © 2017 Elsevier Inc. All rights reserved.)