Probiotics have received considerable attention owing to their potential benefits in maintaining intestinal health,modulating immune function,and antioxidant activity.The antioxidant capacity of recently isolated and ...Probiotics have received considerable attention owing to their potential benefits in maintaining intestinal health,modulating immune function,and antioxidant activity.The antioxidant capacity of recently isolated and screened probiotics have not been characterized.Therefore,the present study used Caenorhabditis elegans as a model to investigate the effects of three novel probiotics(Limosiactobacillus reuteri B1-10,Lactobacillus paragasseri B1-26,and Lacticaseibacillus rhamnosus B2-1)and their probiotic complexes,isolated from breast milk,on the ability to delay aging and antioxidant capacity.Probiotics significantly prolonged the lifespan of nematodes by reducing lipofuscin accumulation,and their average lifespan was prolonged by19.40%(B1-10),7.72%(B1-26),19.72%(B2-1)and 20.30%(complex probiotic),respectively.The probiotics reduce nematode fecundity and retard their growth and development,possibly due to dietary restriction.Additionally,the probiotics reduced the accumulation of reactive oxygen species and malondialdehyde content,the reductions were 9.7%-44.5%and 18.69%-46.99%,respectively,and increased the activity of antioxidant enzymes,such as superoxide dismutase,catalase,and glutathione,the increases were 26.22%to 41.72%,30.33%to 83.20%and 77.13%to 171.85%,respectively.The complex probiotic was the most effective in improving the C.elegans resistance to hydrogen peroxide stressors.Furthermore,the probiotics acts on the insulin/insulin-like pathway to regulate the expression of daf-16,which in turn upregulates the expression of sod-3,ctl-1,sod-1,down-regulated the expression of age-1,and promoted the nuclear localization of DAF-16::GFP nematodes to prolong the lifespan and antioxidant capacity of C.elegans.These results provide a new basis and research direction for further analyses of the role of probiotics in maintaining the health,improving stress resistance,and prolonging the lifespan of the host.They also provide potential insights into the development of functional food to facilitate anti-aging management in humans.展开更多
4-Nitrophenol(4-NP),as a toxic and refractory pollutant,has generated significant concern due to its adverse effects.However,the potential toxic effects andmechanism remained unclear.In this study,the reproduction,dev...4-Nitrophenol(4-NP),as a toxic and refractory pollutant,has generated significant concern due to its adverse effects.However,the potential toxic effects andmechanism remained unclear.In this study,the reproduction,development,locomotion and reactive oxygen species(ROS)production of Caenorhabditis elegans were investigated to evaluate the 4-NP toxicity.We used metabolomics to assess the potential damage mechanisms.The role of metabolites in mediating the relationship between 4-NP and phenotypes was examined by correlation and mediation analysis.4-NP(8 ng/L and 8μg/L)caused significant reduction of brood size,ovulation rate,total germ cells numbers,head thrashes and body bends,and an increase in ROS.However,the oosperm numbers in uterus,body length and body width were decreased in 8μg/L.Moreover,36 differential metabolites were enriched in the significant metabolic pathways,including lysine biosynthesis,β-alanine metabolism,tryptophan metabolism,pentose phosphate pathway,pentose and glucuronate interconversions,amino sugar and nucleotide sugar metabolism,starch and sucrose metabolism,galactose metabolism,propanoate metabolism,glycerolipid metabolism,and estrogen signaling pathway.The mechanism of 4-NP toxicity was that oxidative stress caused by the perturbation of amino acid,which had effects on energy metabolism through disturbing carbohydrate and lipid metabolism,and finally affected the estrogen signaling pathway to exert toxic effects.Moreover,correlation and mediation analysis showed glycerol-3P,glucosamine-6P,glucosamine-1P,UDP-galactose,L-aspartic acid,and uracilwere potential markers for the reproduction and glucose-1,6P2 for developmental toxicity.The results provided insight into the pathways involved in the toxic effects caused by 4-NP and developed potential biomarkers to evaluate 4-NP toxicity.展开更多
Nanoplastics are emerging contaminants that may co-exist with organochlorine pesticides and adversely affect invertebrates in the environment.However,the impact of environmental aging on the combined toxicity of nanop...Nanoplastics are emerging contaminants that may co-exist with organochlorine pesticides and adversely affect invertebrates in the environment.However,the impact of environmental aging on the combined toxicity of nanoplastics and organochlorine pesticides remains unclear.This study investigated the effects of aging on the combined toxicity of polystyrene nanoplastics(PS NPs)and chlordane against Caenorhabditis elegans.The results showed that photo-aging altered the physicochemical properties of PS NPs and promoted the combined toxicity of PS NPs and chlordane to nematodes by reducing survival rate,body length and enhancing germline apoptosis.Additionally,combined exposure of nematodes to aged PS NPs and chlordane significantly increased reactive oxygen species production and intestinal permeability,suggesting that aging enhances combined toxicity through oxidative stress and intestinal damage.Moreover,aging increased chlordane contents in nematodes without promoting PS NPs accumulation,potentially leading to increased combined toxicity of PS NPs and chlordane.Notably,aging significantly increased the accumulation of PS NPs in the posterior intestine of the nematode during co-exposure,which may be responsible for the most sensitive and highest degree of change in germline apoptosis.These observations emphasize the significance of accounting for environmental aging as well as the accumulation and distribution of nanoplastics in organisms when assessing the combined effects of nanoplastics and coexisting pollutants.展开更多
A class of persistent organic pollutants,polychlorinated biphenyls(PCBs),are ubiquitous in the environment and human tissues which are continuously and long-term threatened.We aim to investigate the toxic effects and ...A class of persistent organic pollutants,polychlorinated biphenyls(PCBs),are ubiquitous in the environment and human tissues which are continuously and long-term threatened.We aim to investigate the toxic effects and the underlying mechanisms of PCB153 using Caenorhabditis elegans as a model organism.Our findings demonstrated that exposure to an optimized concentration of 2μmol/L PCB153 had adverse effects on C.elegans,led to reduction of lifespan,body length,frequency of body bending,and head wiggling.Additionally,this exposure led to an increase in the accumulation of reactive oxygen species,superoxide dismutase,lipofuscin and fat content within the organism.Furthermore,gene set enrichment analysis and whole transcriptome sequencing revealed,a significant up-regulation of Cytochrome P450(CYP)family genes,which are crucial for the xenobiotics metabolism in C.elegans.Knocking down specific genes within the CYPs family,including cyp-35C1,cyp-35A5,cyp-35A3,cyp-34A1,and cyp-34A10,via RNA interference were able to reverse the shortening of lifespan and fat accumulation induced by PCB153 exposure.Moreover,a comprehensive a competing endogenous RNA network was constructed by integrating qPCR-validated differentially expressed m RNA along with lncRNA,circRNA,and miRNA identified by transcriptomic sequencing.This study emphasizes that PCB153 exposure leads to the physiological impairments,particularly fat accumulation and a shorter lifespan,through the modulation of CYP450 family genes.These findings contribute to our understanding of environmental pollutants and their impact on biological systems and provide valuable information on the toxic effects and potential risks associated with PCB153 exposure.展开更多
BACKGROUND Neurodegeneration refers to the progressive loss of neurons,affecting both their structure and function.It is driven by synaptic dysfunction,disruptions in neural networks,and the accumulation of abnormal p...BACKGROUND Neurodegeneration refers to the progressive loss of neurons,affecting both their structure and function.It is driven by synaptic dysfunction,disruptions in neural networks,and the accumulation of abnormal protein variants.Endoplasmic reticulum(ER)stress,caused by the accumulation of misfolded or unfolded protein,is a major contributor to neurodegeneration.Dithiothreitol(DTT)is a widely used redox reagent that disrupts the oxidative protein folding environment,inducing ER stress and leading to the imbalance in protein homeostasis can activate stress response pathway,potentially contributing to neurodegenerative processes.Caenorhabditis elegans(C.elegans)is a widely used model organism for studying neurodegeneration due to its well-mapped nervous system,approximately onethird of neuron cells in their body,complete genome sequenced,and conserved stress response pathway.AIM To study the neurodegeneration in C.elegans caused by DTT-induced ER stress,assessed by behavioral,molecular,and lifespan changes.METHODS C.elegans were cultured on nematode growth medium plates with OP50,and ER stress was induced using DTT.Effects were assessed via behavioral assays such as locomotion,chemotaxis,lifespan assay,and molecular studies.RESULTS DTT exposure led to a significant decline in locomotion and chemotaxis response,indicating neurotoxicity.A reduction in lifespan was observed,suggesting an overall impact on health.Molecular analysis confirmed ER stress activation.DTT-induced ER stress negatively affects C.elegans,leading to behavioral impairments and molecular alterations associated with neurodegeneration.CONCLUSION These findings establish C.elegans as a potential model for studying ER stress-mediated neurotoxicity and its implications in neurodegenerative diseases.展开更多
We examined the possible multiple defects induced by acute and prolonged exposure to high levels of manganese(Mn) solution by monitoring the endpoints of lifespan,development,reproduction,and stress response.Our dat...We examined the possible multiple defects induced by acute and prolonged exposure to high levels of manganese(Mn) solution by monitoring the endpoints of lifespan,development,reproduction,and stress response.Our data suggest that acute exposure(6 h) to Mn did not cause severe defects of life span,development,and reproduction,similarly,no significant defect could be found in animals exposed to a low concentration of Mn(2.5 μmol/L) for 48 h.In contrast,prolonged exposure(48 h) to high Mn concentrations(75 and 200 μmol/L) resulted in significant defects of life span,development,and reproduction,as well as the increase of the percentage of population with hsp-16.2::gfp expression indicating the obvious induction of stress responses in exposed animals.Moreover,prolonged exposure(48 h) to high concentrations(75 and 200 μmol/L) of Mn decreased the expression levels of antioxidant genes of sod-1,sod-2,sod-3,and sod-4 compared to control.Therefore,prolonged exposure to high concentrations of Mn will induce the severe defects of life span,development,and reproduction in nematodes possibly by affecting the stress response and expression of antioxidant genes in Caenorhabditis elegans.展开更多
Sophora moorcroftiana(S. moorcroftiana) is an endemic leguminous dwarf shrub in Tibet, China. Decoctions of the seeds have been used in Chinese folk medicine for dephlogistication, detoxication, and infectious disease...Sophora moorcroftiana(S. moorcroftiana) is an endemic leguminous dwarf shrub in Tibet, China. Decoctions of the seeds have been used in Chinese folk medicine for dephlogistication, detoxication, and infectious diseases. The present study aimed to investigate the constituent and biological effects of polysaccharides from S. moorcroftiana seeds in Caenorhabditis elegans(C. elegans). Polysaccharides from S. moorcroftiana seeds(SMpol) were extracted with 60% ethanol and constituent was analyzed by GC-MS. SMpol was composed of glucose, galactose and inositol in the molar ratio of 35.7 : 1.3 : 17.0. Synchronized worms were treated with SMpol and then lifespan, motility, reproduction, stress resistance and antimicrobial activity were examined. Compared with the control group, the lifespan was increased to the average of 27.3 days and the number of laying eggs showed a 1.3-fold increase in nematodes treated with SMpol(4 mg×mL–1). In SMpol(4 mg×mL–1) treated worms, there was a 1.1-fold increase in 24-h survival of acute heat stress and a 1.6-fold increase in 2-h survival of oxidative stress The colonization of the bacteria in the SMpol treated nematode was significantly lower than that of the untreated group by 68.3%. In vivo studies showed SMpol significantly extended the life span, improved reproduction, increased stress resistance and antimicrobial capacity of C. elegans. In conclusion, those results indicated that the polysaccharides from S. moorcroftiana seeds were involved in a variety of biological activities leading to its modulatory effects on C. elegans which may be developed as a natural supplement agent.展开更多
Aging is the major risk factor for many human diseases and degeneration.Thus,clinically effective medicine could delay the process of aging and aging-related diseases are desperately wanted.In traditional Chinese medi...Aging is the major risk factor for many human diseases and degeneration.Thus,clinically effective medicine could delay the process of aging and aging-related diseases are desperately wanted.In traditional Chinese medicine(TCM),some were claimed to slow down aging.Qingyangshen(Cynanchum otophyllum schneid)is such a TCM.Here,we assayed the longevity effect of compound Otophylloside B(Ot B),a C-21 steroidal glycoside isolated from Qingyangshen,in Caenorhabditis elegans,which is a popular model for aging research.Our results showed that Ot B could modestly extend the lifespan of C.elegans,delay the age-related decline of body movement and improve the stress resistance.Further investigating the molecular mechanism of lifespan extension effect revealed that Ot B could activate the FOXO transcription factor DAF-16.Ot B could not further extend the lifespan of long-lived mutant of insulin/IGF-1-like receptor(daf-2).In addition,Ot B also requires SIR-2.1 and CLK-1 which is an enzyme in ubiquinone synthesis,for lifespan extension.展开更多
Sulfamethoxazole(SMX)is one of the most common detected antibiotics in the environment.In order to study whether SMX can affect behavior and growth and whether these effects could be transferred to the progeny,Caenorh...Sulfamethoxazole(SMX)is one of the most common detected antibiotics in the environment.In order to study whether SMX can affect behavior and growth and whether these effects could be transferred to the progeny,Caenorhabditis elegans was exposed at environmentally relevant concentrations for 24,48,72 and 96 hr,respectively.After exposure,the exposed parent generation(P0)was measured for behavior and growth indicators,which were presented as percentage of controls(POC).Then their corresponding unexposed progeny(F1)was separated and measured for the same indicators.The lowest POC for P0 after 96 hr-exposure at 100 mg/L were 37.8%,12.7%,45.8%and 70.l%for body bending frequency(BBF),reversal movement(RM),Omega turns(OT)and body length(BL),respectively.And F1 suffered defects with the lowest POC as 55.8%,24.1%,48.5%and 60.7%for BBF,RM,OT and BL,respectively.Defects in both P0 and F1 showed a time-and concentration-dependent fashion and behavior indicators showed better sensitivity than growth indicator.The observed effects on F1 demonstrated the transferable properties of SMX.Defects of SMX at environmental concentrations suggested that it is necessary to perform further systematical studies on its ecological risk in actual conditions.展开更多
Toxicity identification evaluation (TIE) can be used to determine the specific toxicant(s) in industrial effluents.In the current study,the authors have attempted to combine the advantages of the model organism,Caenor...Toxicity identification evaluation (TIE) can be used to determine the specific toxicant(s) in industrial effluents.In the current study,the authors have attempted to combine the advantages of the model organism,Caenorhabditis elegans,with the virtues of the TIE technique,to evaluate and identify the toxicity on aging from a paper recycling mill effluent.The results indicate that only the toxicities from mixed cellulose (MC) filtration and EDTA treatment are similar to the baseline aging toxicity,suggesting ...展开更多
Parasite infections of humans and animals remain a major global health problem, with limited choice of drugs being available to the treatment of parasitosis in the clinic. Sophora moorcroftiana(S. moorcroftiana) is a ...Parasite infections of humans and animals remain a major global health problem, with limited choice of drugs being available to the treatment of parasitosis in the clinic. Sophora moorcroftiana(S. moorcroftiana) is a shrub that grows in Tibet Plateau of China. Decoction of the seeds has been used as a traditional Tibetan medicine to treat parasitosis for years. But the anti-parasitic effects of water-soluble fractions in the seeds need further investigation. In the present study, the water-soluble alkaloid fractions(E2) were obtained from S. moorcroftiana seeds by refluxing extraction with 60% ethanol and low polarity fraction(E2-a) and high polarity fraction(E2-b) were subsequently isolated from E2 using column chromatography. As a parasite model, Caenorhabditis elegans(C. elegans) were treated with different fractions and their survivals were recorded. The results showed that that E2-a induced a lower survival rate in C. elegans than E2-b and E2. The protoscoleces of Echinococcus granulosus(E. granulosus) were cultured in the presence of E2-a. Compared with E2-b and E2, protoscoleces exhibited decreased survival rate following E2-a treatment. Furtherly, the effects of E2-a on the behavior, brood size, and lifespan of the worms were investigated. Body bend frequencies of the worms treated with the high concentration of E2-a were reduced by two-thirds compared with the control group(P < 0.01). Compared with non-E2-a-treated group, exposure of nematodes to E2-a led to a decrease in head thrashes and pharyngeal pumps frequency(P < 0.01). E2-a treatment resulted in a significantly lower brood size(P < 0.01). Additional E2-a treatment induced a significantly shortened lifespan, compared with the control(P < 0.05). These findings indicated that water-soluble fraction E2-a from S. moorcroftiana seeds was a potential helminthic agent.展开更多
Among more than 75 variants of microcystin (MC), microcystin-LR (MC-LR) is one of the most common toxins. In this study, the feasibility of using Caenorhabditis elegans to evaluate MC-LR toxicity was studied. C. e...Among more than 75 variants of microcystin (MC), microcystin-LR (MC-LR) is one of the most common toxins. In this study, the feasibility of using Caenorhabditis elegans to evaluate MC-LR toxicity was studied. C. elegans was treated with MC-LR at different concentrations ranging from 0.1 to 80 μg/L. The results showed that MC-LR could reduce lifespan, delay development, lengthen generation time, decrease brood size, suppress locomotion behavior, and decreases hsp-16-2-gfp expression. The endpoints of generation time, brood size, and percentage of the population expressing hsp-16-2-gfp were very sensitive to 1.0μg/L of MC-LR, and would be more useful for the evaluation of MC-LR toxicity. Furthermore, the tissue-specific hsp-16-2-gfp expressions were investigated in MC-LR-exposed animals, and the nervous system and intestine were primarily affected by MC-LR. Therefore, the generation time, brood size, and hsp-16-2-gfp expression in C. elegans can be explored to serve as valuable endpoints for evaluating the potential toxicity from MC-LR exposure.展开更多
Chemotaxis to water-soluble attractants is mainly controlled by ASE sensory neuron whose specification is regulated by che-1 in Caenorhabditis elegans.Our data suggested that exposure to high concentrations of metals,...Chemotaxis to water-soluble attractants is mainly controlled by ASE sensory neuron whose specification is regulated by che-1 in Caenorhabditis elegans.Our data suggested that exposure to high concentrations of metals,such as Pb,Cu,Ag,and Cr,would result in severe defects of chemotaxis to water-soluble attractants of NaCl,cAMP,and biotin.Moreover,the morphology of ASE neuron structures as observed by relative fluorescent intensities and relative size of fluorescent puncta of cell bodies,relative lengths of sensory endings in ASE neurons,and the expression patterns of che-1 were obviously altered in metal exposed animals when they meanwhile exhibited obvious chemotaxis defects to water-soluble attractants.In addition,the dendrite morphology could be noticeably changed in animals exposed to 150μmol/L of Pb,Cu,and Ag.Furthermore,we observed significant decreases of chemotaxis to water-soluble attractants in Pb exposed che-1 mutant at concentrations more than 2.5μmol/L,and in Cu,Ag,and Cr exposed che-1 mutant at concentrations more than 50μmol/L.Therefore,impairment of the ASE neuron structures and functions may largely contribute to the appearance of chemotaxis defects to water-soluble attractants in metal exposed nematodes.展开更多
Whether the multi-biological toxicity from lead exposure could be transferred to progeny has not been clarified. In the present study, we explored the Caenorhabditis elegans to analyze the multiple toxicities from lea...Whether the multi-biological toxicity from lead exposure could be transferred to progeny has not been clarified. In the present study, we explored the Caenorhabditis elegans to analyze the multiple toxicities from lead exposure and their possibly transferable properties. The lead exposure could cause series of severe multi-biological defects with a concentration-dependent manner by affecting the endpoints of life span, development, reproduction and locomotion behaviors in nematodes. Moreover, most of these toxicities could be transferred to progeny from lead exposed animals and some of the defects in progeny appeared even more severe than in their parents, such as the body sizes and mean life spans. We summarized the defects caused by lead exposure into three groups according to their transferable properties or rescue patterns. That is, the defects caused by lead exposure could be largely, or partially, or became even more severe in progeny animals. Therefore, our results suggest that lead exposure can cause severely multi-biological defects, and most of these multiple toxicities can be considered as transferable for exposed animals in C. elegans.展开更多
Sediment is the ultimate sink of environmental pollutants.A total of 128 surface sediment sampleswere collected from8 rivers and 3 reservoirs in Maoming City,Guangdong Province.This study assessed the content and dist...Sediment is the ultimate sink of environmental pollutants.A total of 128 surface sediment sampleswere collected from8 rivers and 3 reservoirs in Maoming City,Guangdong Province.This study assessed the content and distribution of brominated flame retardants in sediments.The acute toxicity effects of tetrabromobisphenol A(TBBPA)and hexabromocyclododecane(HBCDs)in sediments were evaluated using Caenorhabditis elegans as model organisms.The concentration of TBBPA in sediments ranged from not detected(ND)to 12.59μg/kg andwas mainly distributed in the central area,whichwas affected by the emission of TBBPA from residential and factory.The concentration of HBCDs ranged from ND to 6.31μg/kg,and the diastereoisomer distribution was consistent,showing a trend close to the South China Sea.The composition pattern of HBCDs in the surface sediments from rivers were 41.73%-62.33%,7.89%-25.54%,and 18.76%-40.65%forα-,β-,andγ-HBCD,respectively,and in the sediments from reservoirs were 26.15%-45.52%,7.44%-19.23%,and 47.04%-61.89%forα-,β-,andγ-HBCD,respectively.When the sum of concentrations of TBBPA and HBCD in sediments were above high levels,reactive oxygen species in nematodes significantly increased,resulting in an oxidative stress response.Intestinal permeabilitywas also enhanced,causing intestinal damage.In addition,in terms of this study,TBBPA had a greater impact on biotoxicity compared to HBCDs,and more attention should be paid to the toxic effects of the river ecosystem organisms in Maoming City,Guangdong Province.This study can complement the pollution database in the study area and provide basic data for pollution control.展开更多
Here we investigated the possible roles of oxidative stress in the formation of decreased thermotaxis to cultivation temperature in lead(Pb)-exposed nematodes Caenorhabditis elagans.Exposure to Pb at the examined conc...Here we investigated the possible roles of oxidative stress in the formation of decreased thermotaxis to cultivation temperature in lead(Pb)-exposed nematodes Caenorhabditis elagans.Exposure to Pb at the examined concentrations decreased thermotaxis behaviors,and induced severe deficits in the structural properties of AFD sensory neurons.Meanwhile,Pb exposure caused the induction of severe oxidative damage,reactive oxygen species(ROS)production,and mitochondrial dysfunction in young adults.Moreover,pre-treatment with the antioxidants dimethyl sulfoxide(DMSO),ascorbate and N-acetyl-L-cysteine(NAC),used to inhibit both the ROS elevation and the mitochondrial dysfunction caused by Pb exposure,at the L2-1arval stage prevented the induction of oxidative damage and the formation of severe deficits in thermotaxis and structural properties of AFD sensory neurons in Pb-exposed young adults.Therefore,the formation of oxidative stress caused by Pb exposure may be due to both the induction of ROS elevation and damage to mitochondrial function,and oxidative stress may play a key role in inducing the neurotoxic effects on the structures and function of AFD sensory neurons in Pb-exposed nematodes.展开更多
Alzheimer’s disease(AD)is a major public health concern worldwide and the few drugs currently available only treat the symptoms.Hence,there is a strong need to find more effective anti-AD agents.Cynanchum otophyllum ...Alzheimer’s disease(AD)is a major public health concern worldwide and the few drugs currently available only treat the symptoms.Hence,there is a strong need to find more effective anti-AD agents.Cynanchum otophyllum is a traditional Chinese medicine for treating epilepsy,and otophylloside B(Ot B),isolated from C.otophyllum,is the essential active component.Having previously identified anti-aging effects of Ot B,we evaluated Ot B for AD prevention in C.elegant models of AD and found that Ot B extended lifespan,increased heat stress-resistance,delayed body paralysis,and increased the chemotaxis response.Collectively,these results indicated thatOt B protects against Aβtoxicity.Further mechanistic studies revealed that Ot B decreased Aβdeposition by decreasing the expression of Aβat the mRNA level.Genetic analyses showed that Ot B mediated its effects by increasing the activity of heat shock transcription factor(HSF)by upregulating the expression of hsf-1 and its target genes,hsp-12.6,hsp-16.2 and hsp-70.Ot B also increased the expression of sod-3 by partially activating DAF-16,while SKN-1 was not essential in Ot B-mediated protection against Aβtoxicity.展开更多
In this study,we aimed to evaluate the toxic effects,changes in life span,and expression of various metabolismrelated genes in Caenorhabditis elegans,using RNA interference(RNAi)and mutant strains,after 3-bromopyruvat...In this study,we aimed to evaluate the toxic effects,changes in life span,and expression of various metabolismrelated genes in Caenorhabditis elegans,using RNA interference(RNAi)and mutant strains,after 3-bromopyruvate(3-BrPA)treatment.C.elegans was treated with various concentrations of 3-BrPA on nematode growth medium(NGM)plates,and their survival was monitored every 24 h.The expression of genes related to metabolism was measured by the real-time fluorescent quantitative polymerase chain reaction(qPCR).Nematode survival in the presence of 3-BrPA was also studied after silencing three hexokinase(HK)genes.The average life span of C.elegans cultured on NGM with 3-BrPA was shortened to 5.7 d compared with 7.7 d in the control group.hxk-1,hxk-2,and hxk-3 were overexpressed after the treatment with 3-BrPA.After successfully interfering hxk-1,hxk-2,and hxk-3,the 50%lethal concentration(LC50)of all mutant nematodes decreased with 3-BrPA treatment for 24 h compared with that of the control.All the cyp35 genes tested were overexpressed,except cyp-35B3.The induction of cyp-35A1 expression was most obvious.The LC50 values of the mutant strains cyp-35A1,cyp-35A2,cyp-35A4,cyp-35B3,and cyp-35C1 were lower than that of the control.Thus,the toxicity of 3-BrPA is closely related to its effect on hexokinase metabolism in nematodes,and the cyp-35 family plays a key role in the metabolism of 3-BrPA.展开更多
Objective To evaluate whether the thermotaxis tracking model is suitable for assessing long-term memory (LTM) in the nematode Caenorhabditis elegans. Methods Animals were trained at 20℃ overnight in presence of foo...Objective To evaluate whether the thermotaxis tracking model is suitable for assessing long-term memory (LTM) in the nematode Caenorhabditis elegans. Methods Animals were trained at 20℃ overnight in presence of food. The percentage of animals performing isothermal tracking (IT) behavior was measured at different time intervals after the training. Results The percentage of animals performing IT behavior, the numbers of body bends inside and outside the training temperature, and the expression patterns of AFD and AIY neurons were similar to those in control animals at 36 and 48 h after training; whereas when extending to 60, 72, and 84 h, locomotory behavior defects were observed in the assayed animals, suggesting that this thermal tracking model is feasible for analyzing LTM at 36 and 48 h after training. Moreover, the percent-age of animals performing IT behavior was reduced at 18, 36, and 48 h after training in neuronal calcium sensor-1 gene (nsc-1) mutant animals compared with that in wild-type N2 animals. In addition, exposure to plumbum (Pb) significantly repressed the LTM at 18, 36, and 48 h after training in both wild-type N2 and ncs-1 mutant animals. Conclusion The thermotaxis tracking model is suitable for evaluating the LTM regulated by NCS-1, and can be employed for elucidating regulatory functions of specific genes or effects of stimuli on memory in C. elegans.展开更多
基金supported by National Natural Science Foundation of China(32072191)Special Funds for Guiding Local Scientific and Technological Development by the Central Government(Guike ZY22096025)+1 种基金Beijing Science and Technology Plan(Z221100006422012)Beijing Innovation Team of Livestock Industry Technology System(BAIC05)。
摘要Probiotics have received considerable attention owing to their potential benefits in maintaining intestinal health,modulating immune function,and antioxidant activity.The antioxidant capacity of recently isolated and screened probiotics have not been characterized.Therefore,the present study used Caenorhabditis elegans as a model to investigate the effects of three novel probiotics(Limosiactobacillus reuteri B1-10,Lactobacillus paragasseri B1-26,and Lacticaseibacillus rhamnosus B2-1)and their probiotic complexes,isolated from breast milk,on the ability to delay aging and antioxidant capacity.Probiotics significantly prolonged the lifespan of nematodes by reducing lipofuscin accumulation,and their average lifespan was prolonged by19.40%(B1-10),7.72%(B1-26),19.72%(B2-1)and 20.30%(complex probiotic),respectively.The probiotics reduce nematode fecundity and retard their growth and development,possibly due to dietary restriction.Additionally,the probiotics reduced the accumulation of reactive oxygen species and malondialdehyde content,the reductions were 9.7%-44.5%and 18.69%-46.99%,respectively,and increased the activity of antioxidant enzymes,such as superoxide dismutase,catalase,and glutathione,the increases were 26.22%to 41.72%,30.33%to 83.20%and 77.13%to 171.85%,respectively.The complex probiotic was the most effective in improving the C.elegans resistance to hydrogen peroxide stressors.Furthermore,the probiotics acts on the insulin/insulin-like pathway to regulate the expression of daf-16,which in turn upregulates the expression of sod-3,ctl-1,sod-1,down-regulated the expression of age-1,and promoted the nuclear localization of DAF-16::GFP nematodes to prolong the lifespan and antioxidant capacity of C.elegans.These results provide a new basis and research direction for further analyses of the role of probiotics in maintaining the health,improving stress resistance,and prolonging the lifespan of the host.They also provide potential insights into the development of functional food to facilitate anti-aging management in humans.
基金supported by the National Natural Science Foundation of China(Nos.82173479 and 81872579)Jiangsu Provincial Maternal and Child Health Scientific Research Project(No.F201907).
摘要4-Nitrophenol(4-NP),as a toxic and refractory pollutant,has generated significant concern due to its adverse effects.However,the potential toxic effects andmechanism remained unclear.In this study,the reproduction,development,locomotion and reactive oxygen species(ROS)production of Caenorhabditis elegans were investigated to evaluate the 4-NP toxicity.We used metabolomics to assess the potential damage mechanisms.The role of metabolites in mediating the relationship between 4-NP and phenotypes was examined by correlation and mediation analysis.4-NP(8 ng/L and 8μg/L)caused significant reduction of brood size,ovulation rate,total germ cells numbers,head thrashes and body bends,and an increase in ROS.However,the oosperm numbers in uterus,body length and body width were decreased in 8μg/L.Moreover,36 differential metabolites were enriched in the significant metabolic pathways,including lysine biosynthesis,β-alanine metabolism,tryptophan metabolism,pentose phosphate pathway,pentose and glucuronate interconversions,amino sugar and nucleotide sugar metabolism,starch and sucrose metabolism,galactose metabolism,propanoate metabolism,glycerolipid metabolism,and estrogen signaling pathway.The mechanism of 4-NP toxicity was that oxidative stress caused by the perturbation of amino acid,which had effects on energy metabolism through disturbing carbohydrate and lipid metabolism,and finally affected the estrogen signaling pathway to exert toxic effects.Moreover,correlation and mediation analysis showed glycerol-3P,glucosamine-6P,glucosamine-1P,UDP-galactose,L-aspartic acid,and uracilwere potential markers for the reproduction and glucose-1,6P2 for developmental toxicity.The results provided insight into the pathways involved in the toxic effects caused by 4-NP and developed potential biomarkers to evaluate 4-NP toxicity.
基金supported by the National Key Research and Development Program of China(No.2020YFC1808204)the National Natural Science Foundation of China(Nos.22206001 and U22A20406)the Scientific Research Foundation of Education Department of Anhui Province of China(No.KJ2021A0074).
摘要Nanoplastics are emerging contaminants that may co-exist with organochlorine pesticides and adversely affect invertebrates in the environment.However,the impact of environmental aging on the combined toxicity of nanoplastics and organochlorine pesticides remains unclear.This study investigated the effects of aging on the combined toxicity of polystyrene nanoplastics(PS NPs)and chlordane against Caenorhabditis elegans.The results showed that photo-aging altered the physicochemical properties of PS NPs and promoted the combined toxicity of PS NPs and chlordane to nematodes by reducing survival rate,body length and enhancing germline apoptosis.Additionally,combined exposure of nematodes to aged PS NPs and chlordane significantly increased reactive oxygen species production and intestinal permeability,suggesting that aging enhances combined toxicity through oxidative stress and intestinal damage.Moreover,aging increased chlordane contents in nematodes without promoting PS NPs accumulation,potentially leading to increased combined toxicity of PS NPs and chlordane.Notably,aging significantly increased the accumulation of PS NPs in the posterior intestine of the nematode during co-exposure,which may be responsible for the most sensitive and highest degree of change in germline apoptosis.These observations emphasize the significance of accounting for environmental aging as well as the accumulation and distribution of nanoplastics in organisms when assessing the combined effects of nanoplastics and coexisting pollutants.
基金supported by the National Natural Science Foundation of China(No.81872584)the Natural Science Foundation of Shenzhen(No.JCYJ20210324093211030)+1 种基金Henan Province’s Key R&D and Promotion Projects(No.252102310075)the Interdisciplinary Research for Firstclass Discipline Construction Project of Henan University(No.2019YLXKJC04)。
摘要A class of persistent organic pollutants,polychlorinated biphenyls(PCBs),are ubiquitous in the environment and human tissues which are continuously and long-term threatened.We aim to investigate the toxic effects and the underlying mechanisms of PCB153 using Caenorhabditis elegans as a model organism.Our findings demonstrated that exposure to an optimized concentration of 2μmol/L PCB153 had adverse effects on C.elegans,led to reduction of lifespan,body length,frequency of body bending,and head wiggling.Additionally,this exposure led to an increase in the accumulation of reactive oxygen species,superoxide dismutase,lipofuscin and fat content within the organism.Furthermore,gene set enrichment analysis and whole transcriptome sequencing revealed,a significant up-regulation of Cytochrome P450(CYP)family genes,which are crucial for the xenobiotics metabolism in C.elegans.Knocking down specific genes within the CYPs family,including cyp-35C1,cyp-35A5,cyp-35A3,cyp-34A1,and cyp-34A10,via RNA interference were able to reverse the shortening of lifespan and fat accumulation induced by PCB153 exposure.Moreover,a comprehensive a competing endogenous RNA network was constructed by integrating qPCR-validated differentially expressed m RNA along with lncRNA,circRNA,and miRNA identified by transcriptomic sequencing.This study emphasizes that PCB153 exposure leads to the physiological impairments,particularly fat accumulation and a shorter lifespan,through the modulation of CYP450 family genes.These findings contribute to our understanding of environmental pollutants and their impact on biological systems and provide valuable information on the toxic effects and potential risks associated with PCB153 exposure.
摘要BACKGROUND Neurodegeneration refers to the progressive loss of neurons,affecting both their structure and function.It is driven by synaptic dysfunction,disruptions in neural networks,and the accumulation of abnormal protein variants.Endoplasmic reticulum(ER)stress,caused by the accumulation of misfolded or unfolded protein,is a major contributor to neurodegeneration.Dithiothreitol(DTT)is a widely used redox reagent that disrupts the oxidative protein folding environment,inducing ER stress and leading to the imbalance in protein homeostasis can activate stress response pathway,potentially contributing to neurodegenerative processes.Caenorhabditis elegans(C.elegans)is a widely used model organism for studying neurodegeneration due to its well-mapped nervous system,approximately onethird of neuron cells in their body,complete genome sequenced,and conserved stress response pathway.AIM To study the neurodegeneration in C.elegans caused by DTT-induced ER stress,assessed by behavioral,molecular,and lifespan changes.METHODS C.elegans were cultured on nematode growth medium plates with OP50,and ER stress was induced using DTT.Effects were assessed via behavioral assays such as locomotion,chemotaxis,lifespan assay,and molecular studies.RESULTS DTT exposure led to a significant decline in locomotion and chemotaxis response,indicating neurotoxicity.A reduction in lifespan was observed,suggesting an overall impact on health.Molecular analysis confirmed ER stress activation.DTT-induced ER stress negatively affects C.elegans,leading to behavioral impairments and molecular alterations associated with neurodegeneration.CONCLUSION These findings establish C.elegans as a potential model for studying ER stress-mediated neurotoxicity and its implications in neurodegenerative diseases.
基金supported by the National Natural Science Foundation of China (No. 30771113, 30870810)the Program for New Century Excellent Talents in University
摘要We examined the possible multiple defects induced by acute and prolonged exposure to high levels of manganese(Mn) solution by monitoring the endpoints of lifespan,development,reproduction,and stress response.Our data suggest that acute exposure(6 h) to Mn did not cause severe defects of life span,development,and reproduction,similarly,no significant defect could be found in animals exposed to a low concentration of Mn(2.5 μmol/L) for 48 h.In contrast,prolonged exposure(48 h) to high Mn concentrations(75 and 200 μmol/L) resulted in significant defects of life span,development,and reproduction,as well as the increase of the percentage of population with hsp-16.2::gfp expression indicating the obvious induction of stress responses in exposed animals.Moreover,prolonged exposure(48 h) to high concentrations(75 and 200 μmol/L) of Mn decreased the expression levels of antioxidant genes of sod-1,sod-2,sod-3,and sod-4 compared to control.Therefore,prolonged exposure to high concentrations of Mn will induce the severe defects of life span,development,and reproduction in nematodes possibly by affecting the stress response and expression of antioxidant genes in Caenorhabditis elegans.
基金supported by the National Science Foundation of China(No.31360604)
摘要Sophora moorcroftiana(S. moorcroftiana) is an endemic leguminous dwarf shrub in Tibet, China. Decoctions of the seeds have been used in Chinese folk medicine for dephlogistication, detoxication, and infectious diseases. The present study aimed to investigate the constituent and biological effects of polysaccharides from S. moorcroftiana seeds in Caenorhabditis elegans(C. elegans). Polysaccharides from S. moorcroftiana seeds(SMpol) were extracted with 60% ethanol and constituent was analyzed by GC-MS. SMpol was composed of glucose, galactose and inositol in the molar ratio of 35.7 : 1.3 : 17.0. Synchronized worms were treated with SMpol and then lifespan, motility, reproduction, stress resistance and antimicrobial activity were examined. Compared with the control group, the lifespan was increased to the average of 27.3 days and the number of laying eggs showed a 1.3-fold increase in nematodes treated with SMpol(4 mg×mL–1). In SMpol(4 mg×mL–1) treated worms, there was a 1.1-fold increase in 24-h survival of acute heat stress and a 1.6-fold increase in 2-h survival of oxidative stress The colonization of the bacteria in the SMpol treated nematode was significantly lower than that of the untreated group by 68.3%. In vivo studies showed SMpol significantly extended the life span, improved reproduction, increased stress resistance and antimicrobial capacity of C. elegans. In conclusion, those results indicated that the polysaccharides from S. moorcroftiana seeds were involved in a variety of biological activities leading to its modulatory effects on C. elegans which may be developed as a natural supplement agent.
基金the Yunnan provincial government(20080A007)the 100 Talents Program of the Chinese Academy of Sciences,the State Key Laboratory of Phytochemistry and Plant Resources in West China,Kunming Institute of Botany(P2008-ZZ21 and T2009-KF05)。
摘要Aging is the major risk factor for many human diseases and degeneration.Thus,clinically effective medicine could delay the process of aging and aging-related diseases are desperately wanted.In traditional Chinese medicine(TCM),some were claimed to slow down aging.Qingyangshen(Cynanchum otophyllum schneid)is such a TCM.Here,we assayed the longevity effect of compound Otophylloside B(Ot B),a C-21 steroidal glycoside isolated from Qingyangshen,in Caenorhabditis elegans,which is a popular model for aging research.Our results showed that Ot B could modestly extend the lifespan of C.elegans,delay the age-related decline of body movement and improve the stress resistance.Further investigating the molecular mechanism of lifespan extension effect revealed that Ot B could activate the FOXO transcription factor DAF-16.Ot B could not further extend the lifespan of long-lived mutant of insulin/IGF-1-like receptor(daf-2).In addition,Ot B also requires SIR-2.1 and CLK-1 which is an enzyme in ubiquinone synthesis,for lifespan extension.
基金supported by the Key Project of Shanghai Natural Science Foundation(No.08JC1418900)the National Natural Science Foundation of China(No.20777055)the National Major Science and Technology Project:Water Pollution Control and Management(No.2008ZX07421-001)
摘要Sulfamethoxazole(SMX)is one of the most common detected antibiotics in the environment.In order to study whether SMX can affect behavior and growth and whether these effects could be transferred to the progeny,Caenorhabditis elegans was exposed at environmentally relevant concentrations for 24,48,72 and 96 hr,respectively.After exposure,the exposed parent generation(P0)was measured for behavior and growth indicators,which were presented as percentage of controls(POC).Then their corresponding unexposed progeny(F1)was separated and measured for the same indicators.The lowest POC for P0 after 96 hr-exposure at 100 mg/L were 37.8%,12.7%,45.8%and 70.l%for body bending frequency(BBF),reversal movement(RM),Omega turns(OT)and body length(BL),respectively.And F1 suffered defects with the lowest POC as 55.8%,24.1%,48.5%and 60.7%for BBF,RM,OT and BL,respectively.Defects in both P0 and F1 showed a time-and concentration-dependent fashion and behavior indicators showed better sensitivity than growth indicator.The observed effects on F1 demonstrated the transferable properties of SMX.Defects of SMX at environmental concentrations suggested that it is necessary to perform further systematical studies on its ecological risk in actual conditions.
基金the National Natural Science Foundation of China (No.30771113)the Southeast University Foundation for Excellent Young Scholars (No.4023001013)
摘要Toxicity identification evaluation (TIE) can be used to determine the specific toxicant(s) in industrial effluents.In the current study,the authors have attempted to combine the advantages of the model organism,Caenorhabditis elegans,with the virtues of the TIE technique,to evaluate and identify the toxicity on aging from a paper recycling mill effluent.The results indicate that only the toxicities from mixed cellulose (MC) filtration and EDTA treatment are similar to the baseline aging toxicity,suggesting ...
基金supported by the National Natural Science Foundation of China(No.31360604)Lanzhou University Innovation and Entrepreneurship Fund for College Students(No.2015073001362)
摘要Parasite infections of humans and animals remain a major global health problem, with limited choice of drugs being available to the treatment of parasitosis in the clinic. Sophora moorcroftiana(S. moorcroftiana) is a shrub that grows in Tibet Plateau of China. Decoction of the seeds has been used as a traditional Tibetan medicine to treat parasitosis for years. But the anti-parasitic effects of water-soluble fractions in the seeds need further investigation. In the present study, the water-soluble alkaloid fractions(E2) were obtained from S. moorcroftiana seeds by refluxing extraction with 60% ethanol and low polarity fraction(E2-a) and high polarity fraction(E2-b) were subsequently isolated from E2 using column chromatography. As a parasite model, Caenorhabditis elegans(C. elegans) were treated with different fractions and their survivals were recorded. The results showed that that E2-a induced a lower survival rate in C. elegans than E2-b and E2. The protoscoleces of Echinococcus granulosus(E. granulosus) were cultured in the presence of E2-a. Compared with E2-b and E2, protoscoleces exhibited decreased survival rate following E2-a treatment. Furtherly, the effects of E2-a on the behavior, brood size, and lifespan of the worms were investigated. Body bend frequencies of the worms treated with the high concentration of E2-a were reduced by two-thirds compared with the control group(P < 0.01). Compared with non-E2-a-treated group, exposure of nematodes to E2-a led to a decrease in head thrashes and pharyngeal pumps frequency(P < 0.01). E2-a treatment resulted in a significantly lower brood size(P < 0.01). Additional E2-a treatment induced a significantly shortened lifespan, compared with the control(P < 0.05). These findings indicated that water-soluble fraction E2-a from S. moorcroftiana seeds was a potential helminthic agent.
基金supported by the National Natural Sci-ence Foundation of China (No. 30771113, 30870810)the Doctoral Program of Higher Education of China (No.20050286035)+1 种基金the Jiangsu 333 Project Foundation (No.07056)the Natural Science Foundation of Jiangsu Province (No. BK2006107, BK2008320)
摘要Among more than 75 variants of microcystin (MC), microcystin-LR (MC-LR) is one of the most common toxins. In this study, the feasibility of using Caenorhabditis elegans to evaluate MC-LR toxicity was studied. C. elegans was treated with MC-LR at different concentrations ranging from 0.1 to 80 μg/L. The results showed that MC-LR could reduce lifespan, delay development, lengthen generation time, decrease brood size, suppress locomotion behavior, and decreases hsp-16-2-gfp expression. The endpoints of generation time, brood size, and percentage of the population expressing hsp-16-2-gfp were very sensitive to 1.0μg/L of MC-LR, and would be more useful for the evaluation of MC-LR toxicity. Furthermore, the tissue-specific hsp-16-2-gfp expressions were investigated in MC-LR-exposed animals, and the nervous system and intestine were primarily affected by MC-LR. Therefore, the generation time, brood size, and hsp-16-2-gfp expression in C. elegans can be explored to serve as valuable endpoints for evaluating the potential toxicity from MC-LR exposure.
基金supported by the National Natural Science Foundation of China(No.30771113,30870810)the Program for New Century Excellent Talents in Universityprovided by the Caenorhabdits Genetics Center(funded by the NIH National Center for Research Resource,USA).
摘要Chemotaxis to water-soluble attractants is mainly controlled by ASE sensory neuron whose specification is regulated by che-1 in Caenorhabditis elegans.Our data suggested that exposure to high concentrations of metals,such as Pb,Cu,Ag,and Cr,would result in severe defects of chemotaxis to water-soluble attractants of NaCl,cAMP,and biotin.Moreover,the morphology of ASE neuron structures as observed by relative fluorescent intensities and relative size of fluorescent puncta of cell bodies,relative lengths of sensory endings in ASE neurons,and the expression patterns of che-1 were obviously altered in metal exposed animals when they meanwhile exhibited obvious chemotaxis defects to water-soluble attractants.In addition,the dendrite morphology could be noticeably changed in animals exposed to 150μmol/L of Pb,Cu,and Ag.Furthermore,we observed significant decreases of chemotaxis to water-soluble attractants in Pb exposed che-1 mutant at concentrations more than 2.5μmol/L,and in Cu,Ag,and Cr exposed che-1 mutant at concentrations more than 50μmol/L.Therefore,impairment of the ASE neuron structures and functions may largely contribute to the appearance of chemotaxis defects to water-soluble attractants in metal exposed nematodes.
基金Project supported by the Southeast University Foundation for Excellent Young Scholars(No.4023001013)
摘要Whether the multi-biological toxicity from lead exposure could be transferred to progeny has not been clarified. In the present study, we explored the Caenorhabditis elegans to analyze the multiple toxicities from lead exposure and their possibly transferable properties. The lead exposure could cause series of severe multi-biological defects with a concentration-dependent manner by affecting the endpoints of life span, development, reproduction and locomotion behaviors in nematodes. Moreover, most of these toxicities could be transferred to progeny from lead exposed animals and some of the defects in progeny appeared even more severe than in their parents, such as the body sizes and mean life spans. We summarized the defects caused by lead exposure into three groups according to their transferable properties or rescue patterns. That is, the defects caused by lead exposure could be largely, or partially, or became even more severe in progeny animals. Therefore, our results suggest that lead exposure can cause severely multi-biological defects, and most of these multiple toxicities can be considered as transferable for exposed animals in C. elegans.
基金supported by the National Key Research and Development Program of China(Nos.2022YFC3902102 and 2019YFC1803403)the Key Programof National Natural Science Foundation of China(No.41931298).
摘要Sediment is the ultimate sink of environmental pollutants.A total of 128 surface sediment sampleswere collected from8 rivers and 3 reservoirs in Maoming City,Guangdong Province.This study assessed the content and distribution of brominated flame retardants in sediments.The acute toxicity effects of tetrabromobisphenol A(TBBPA)and hexabromocyclododecane(HBCDs)in sediments were evaluated using Caenorhabditis elegans as model organisms.The concentration of TBBPA in sediments ranged from not detected(ND)to 12.59μg/kg andwas mainly distributed in the central area,whichwas affected by the emission of TBBPA from residential and factory.The concentration of HBCDs ranged from ND to 6.31μg/kg,and the diastereoisomer distribution was consistent,showing a trend close to the South China Sea.The composition pattern of HBCDs in the surface sediments from rivers were 41.73%-62.33%,7.89%-25.54%,and 18.76%-40.65%forα-,β-,andγ-HBCD,respectively,and in the sediments from reservoirs were 26.15%-45.52%,7.44%-19.23%,and 47.04%-61.89%forα-,β-,andγ-HBCD,respectively.When the sum of concentrations of TBBPA and HBCD in sediments were above high levels,reactive oxygen species in nematodes significantly increased,resulting in an oxidative stress response.Intestinal permeabilitywas also enhanced,causing intestinal damage.In addition,in terms of this study,TBBPA had a greater impact on biotoxicity compared to HBCDs,and more attention should be paid to the toxic effects of the river ecosystem organisms in Maoming City,Guangdong Province.This study can complement the pollution database in the study area and provide basic data for pollution control.
基金supported by the National Basic Research Program(973)of China(No.2011CB933404)the National Natural Science Foundation of China(No.30870810,81172698)Some strains used were provided by Caenorhabditis Genetics Center(funded by the NIH National Center for Research Resource,USA)
摘要Here we investigated the possible roles of oxidative stress in the formation of decreased thermotaxis to cultivation temperature in lead(Pb)-exposed nematodes Caenorhabditis elagans.Exposure to Pb at the examined concentrations decreased thermotaxis behaviors,and induced severe deficits in the structural properties of AFD sensory neurons.Meanwhile,Pb exposure caused the induction of severe oxidative damage,reactive oxygen species(ROS)production,and mitochondrial dysfunction in young adults.Moreover,pre-treatment with the antioxidants dimethyl sulfoxide(DMSO),ascorbate and N-acetyl-L-cysteine(NAC),used to inhibit both the ROS elevation and the mitochondrial dysfunction caused by Pb exposure,at the L2-1arval stage prevented the induction of oxidative damage and the formation of severe deficits in thermotaxis and structural properties of AFD sensory neurons in Pb-exposed young adults.Therefore,the formation of oxidative stress caused by Pb exposure may be due to both the induction of ROS elevation and damage to mitochondrial function,and oxidative stress may play a key role in inducing the neurotoxic effects on the structures and function of AFD sensory neurons in Pb-exposed nematodes.
基金supported by the Natural Science Foundation of China(81671405,81370453)Natural Science Foundation of Yunnan province(2013FA045,2015FB172)Open Funds of Guangdong Key Laboratory of Marine Materia Mcdica(LMM2016-1).
摘要Alzheimer’s disease(AD)is a major public health concern worldwide and the few drugs currently available only treat the symptoms.Hence,there is a strong need to find more effective anti-AD agents.Cynanchum otophyllum is a traditional Chinese medicine for treating epilepsy,and otophylloside B(Ot B),isolated from C.otophyllum,is the essential active component.Having previously identified anti-aging effects of Ot B,we evaluated Ot B for AD prevention in C.elegant models of AD and found that Ot B extended lifespan,increased heat stress-resistance,delayed body paralysis,and increased the chemotaxis response.Collectively,these results indicated thatOt B protects against Aβtoxicity.Further mechanistic studies revealed that Ot B decreased Aβdeposition by decreasing the expression of Aβat the mRNA level.Genetic analyses showed that Ot B mediated its effects by increasing the activity of heat shock transcription factor(HSF)by upregulating the expression of hsf-1 and its target genes,hsp-12.6,hsp-16.2 and hsp-70.Ot B also increased the expression of sod-3 by partially activating DAF-16,while SKN-1 was not essential in Ot B-mediated protection against Aβtoxicity.
基金Project supported by the National Natural Science Foundation of China(Nos.31172174 and 81460677)the Fundamental Research Funds for the Central Universities of China(No.31920170039)the Natural Science Found of Gansu Province(No.18JR3RA283),China
摘要In this study,we aimed to evaluate the toxic effects,changes in life span,and expression of various metabolismrelated genes in Caenorhabditis elegans,using RNA interference(RNAi)and mutant strains,after 3-bromopyruvate(3-BrPA)treatment.C.elegans was treated with various concentrations of 3-BrPA on nematode growth medium(NGM)plates,and their survival was monitored every 24 h.The expression of genes related to metabolism was measured by the real-time fluorescent quantitative polymerase chain reaction(qPCR).Nematode survival in the presence of 3-BrPA was also studied after silencing three hexokinase(HK)genes.The average life span of C.elegans cultured on NGM with 3-BrPA was shortened to 5.7 d compared with 7.7 d in the control group.hxk-1,hxk-2,and hxk-3 were overexpressed after the treatment with 3-BrPA.After successfully interfering hxk-1,hxk-2,and hxk-3,the 50%lethal concentration(LC50)of all mutant nematodes decreased with 3-BrPA treatment for 24 h compared with that of the control.All the cyp35 genes tested were overexpressed,except cyp-35B3.The induction of cyp-35A1 expression was most obvious.The LC50 values of the mutant strains cyp-35A1,cyp-35A2,cyp-35A4,cyp-35B3,and cyp-35C1 were lower than that of the control.Thus,the toxicity of 3-BrPA is closely related to its effect on hexokinase metabolism in nematodes,and the cyp-35 family plays a key role in the metabolism of 3-BrPA.
摘要Objective To evaluate whether the thermotaxis tracking model is suitable for assessing long-term memory (LTM) in the nematode Caenorhabditis elegans. Methods Animals were trained at 20℃ overnight in presence of food. The percentage of animals performing isothermal tracking (IT) behavior was measured at different time intervals after the training. Results The percentage of animals performing IT behavior, the numbers of body bends inside and outside the training temperature, and the expression patterns of AFD and AIY neurons were similar to those in control animals at 36 and 48 h after training; whereas when extending to 60, 72, and 84 h, locomotory behavior defects were observed in the assayed animals, suggesting that this thermal tracking model is feasible for analyzing LTM at 36 and 48 h after training. Moreover, the percent-age of animals performing IT behavior was reduced at 18, 36, and 48 h after training in neuronal calcium sensor-1 gene (nsc-1) mutant animals compared with that in wild-type N2 animals. In addition, exposure to plumbum (Pb) significantly repressed the LTM at 18, 36, and 48 h after training in both wild-type N2 and ncs-1 mutant animals. Conclusion The thermotaxis tracking model is suitable for evaluating the LTM regulated by NCS-1, and can be employed for elucidating regulatory functions of specific genes or effects of stimuli on memory in C. elegans.