应对可转移多黏菌素耐药性--饲料添加剂来源的白屈菜红碱具有双重效应

The emergence and spread of the mobile colistin-resistance gene,mcr-1,and its variants pose achallenge to the use of colistin,a last-resort antibiotic used to treat severe infections caused by extensively drug-resistant(XDR)Gram-negative pathogens.Antibiotic adjuvants are a promising strategy to enhance the efficacy of colistin against colistin-resistant pathogens;however,few studies have considered the effects of adjuvants on limiting resistance-gene transmission.We found that chelerythrine(4 mg·L^(-1))derived from Macleaya cordata extract,which is used as an animal feed additive,reduced the minimal inhibitory concentration(MIC)of colistin against an mcr-1 positive Escherichia coli(E.coli)strain by 16-fold(from 2.000 to 0.125 mg·L^(-1)).eliminated approximately 10^(4) colony-forming units(CFUs)of an mcr-1-carrying strain in a murine intestinal infection model,and inhibited the conjugation of an mcr-1-bearing plasmid in vitro(by>100-fold)and in a mouse model(by up to 5-fold).A detailed analysis revealed that chelery-thrine binds to phospholipids on bacterial membranes and increases cytoplasmic membrane fluidity,thereby impairing respiration,disrupting proton motive force(PMF),generating reactive oxygen species(ROS),and decreasing intracellular adenosine triphosphate(ATP)levels,which subsequently downregu-lates mcr-1 and conjugation-associated genes.These dual effects of chelerythrine can expand the use of antibiotic adjuvants and may provide a new strategy for circumventing mobile colistin resistance.

Molecular mechanisms of aflatoxin neurotoxicity and potential neuroprotective agents

Aflatoxins(AFTs)represent one of the most notorious classes of deadly mycotoxins produced by certain fungi that are found on agricultural crops.Aflatoxins are highly toxic to mammals and are known to cause a series of detrimental effects,including neuro-,hepato-,nephron-,and immuno-toxicity.In this original review we summarize the mechanisms of aflatoxin-induced neurotoxicity and the clinical potential of novel neuroprotective agents.Aflatoxin B1(AFB1)is the most toxic congener among the 21 identified AFTs.Recent studies have shown that food borne exposure to AFB1 and/or its metabolites often leads to fatal neurotoxicity in animals and humans.Animal studies indicated that AFB1 exposure could induce abnormal behavioral changes,including anxiety,lethargy disorders,depression-like behavior,cognitive,learning and memory defects,and decreased feeding behavior.Mechanistically,AFB1 exposure has been associated with lipid peroxidation,ablation of non-enzymatic and enzymatic antioxidant defense systems and decreased neurotransmitter levels.AFB1 exposure has also been shown to induce DNA damage,apoptosis,pyroptosis,and mitochondrial dysfunction in the brain tissue.Several signaling pathways,including gasdermin D,toll like receptor 2(TLR2),TLR4,Akt,NF-κB,ERK/MAPK,protein kinase C(PKC),and mitochondrial apoptotic pathways have been shown to participate in AFB1-induced neuronal or astrocyte cell death.Targeting these pathways by small molecules(e.g.,quercetin,curcumin,and gallic acid,and dimethyl fumarate),Chinese herbal extracts(e.g.,Artichoke leaf extract,Chelidonium majus ethanolic extract,pumpkin extract,and Crocus sativus L.tea),and probiotic supplements could effectively improve AFB1-induced neurobehavioral abnormalities and neurotoxicity.To date,the precise molecular mechanisms of AFB1-induced neurotoxicity and potential neuroprotective agents remain unclear.In the present review,the clinical manifestations,molecular mechanisms,and potential neuroprotective agents of AFB1-induced neurotoxicity are summarized in the broadest overview.It is most hopeful that this broad reaching review provides valuable insights and stimulates broader discussion to develop the effective neuroprotective agents against aflatoxins.

Morphological Characteristics of the Dorsal Skin of Two Hynobiids and Their Adaptive Role in Aquatic and Terrestrial Habitats

The morphological characteristics of the dorsal skin of trunk in two species of hynobiid salamanders, Batrachuperus pinchonii and Hynobius chinensis were examined by light microscopy. The basic structures of the skin in the two species are similar and consist of two layers： epidermis and dermis. The epidermis consists of stratum corneum, stratum intermedium and stratum germinativum, while the dermis is composed of a stratum spongiosum and stratum compactum. However, some species-specific variation has been identified （e.g., the distribution of capillary vessels and gland cells, and the thickness of skin）. H. chinensis is a terrestrial species and only lives in water during breeding period, but B. pinchonii is aquatic and remains aquatic throughout its lifetime. The differences in the distribution of capillary vessels and gland cells are related to their different habitats, and show a morphological adaptation.

Osthole ameliorates myonecrosis caused by Clostridium perfringens type A infection in mice

This study aimed to investigate the protective effect of the nature product osthole(OST)against Clostridium perfrin-gens type A infection-caused myonecrosis in a mouse model.Male mice were divided into(1)control,(2)infected,(3)OST50 and(4)OST100 treatment groups.In the infected groups,mice were intramuscularly injected with 1×10^(8) CFU of C.perfringens per day for 6 days.Mice in the OST50 and OST100 groups were administrated intraperitoneally with OST at the doses of 50 or 100 mg/kg per day post C.perfringens infection.Our results showed that C.perfringens infection caused marked necrosis and inflammatory cell infiltration in the muscle tissues of mice.Mice in the OST50 and OST100 treatment groups displayed significantly attenuated C.perfringens infection-induced lipid peroxida-tion,oxidative stress,and apoptosis in their muscle tissue.Furthermore,OST treatment significantly downregulated the expressions of NF-κB,IL-1β,and TNF-αmRNA and protein levels,while concomitantly upregulating the expressions of Nrf2 and HO-1 mRNA and protein.OST treatments also inhibited the expression of phosphorylation(p)-p38,p-mTOR,and p-Erk1/2 proteins,and upregulated LC3II and Beclin1 proteins.In summary,our results reveal that OST therapy confers a protective effect against C.perfringens infection-induced oxidative stress and inflammation in muscle tissue,via activation of Nrf2/HO-1 and autophagy pathways and inhibition of p38,Erk1/2 and NF-κB pathways.