Objective This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans(C.elegans).Methods In this study,the fermented barley protein LFBEP-C1 was prepared and test...Objective This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans(C.elegans).Methods In this study,the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C.elegans.The worms were fed Escherichia coli OP50(E.coli OP50),glucose,and different concentrations of LFBEP-C1.Body size,lifespan,movement,triglyceride content,and gene expression were analyzed.The results were analyzed using ANOVA and Tukey's multiple comparison test.Results Compared with the model group,the head-swing frequency of C.elegans in the group of LFBEP-C1 at 20μg/mL increased by 33.88%,and the body-bending frequency increased by 27.09%.This indicated that LFBEP-C1 improved the locomotive ability of C.elegans.The average lifespan of C.elegans reached 13.55 days,and the body length and width of the C.elegans decreased after LFBEP-C1 intake.Additionally,LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels.The expression levels of sbp-1,daf-2,and mdt-15 significantly decreased,while those of daf-16,tph-1,mod-1,and ser-4 significantly increased after LFBEP-C1 intake.Changes in these genes explain the signaling pathways that regulate lipid metabolism.Conclusion LFBEP-C1 significantly reduced lipid deposition in C.elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development,lifespan,and exercise behavior of C.elegans.In addition,LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein,insulin,and 5-hydroxytryptamine signaling pathways.展开更多
Objective:To explore the anti-aging effects of chlorogenic acid(CGA)and the underlying mechanisms based on a Caenorhabditis elegans(C.elegans)model.Methods:The anti-agingactivityofCGAwasstudied basedon thebodylength,e...Objective:To explore the anti-aging effects of chlorogenic acid(CGA)and the underlying mechanisms based on a Caenorhabditis elegans(C.elegans)model.Methods:The anti-agingactivityofCGAwasstudied basedon thebodylength,exercisebehavior,lipofuscin content,antioxidative stress ability,swallowing frequency,body-bending frequency,and head-swinging ability of C.elegans.Through DAF-16 nuclear translocation and SOD-3-GFP fluorescence experiments,the effects of CGA on ROS levels,antioxidant enzyme activities,MDA content,mutant-strain lifespan,and anti-aging molecular signaling pathways were explored,as well as the underlying mechanisms.Results:CGA improved multiple indices of the nematode:body length was increased(all P<0.001),head-swing frequency and body-bending frequency were increased(all P<0.05),nematode longevity was prolonged(P=0.0021),lipofuscin deposition in nematodes was slowed down(all P<0.001),the chemotaxis index was improved(P=0.0012),ROS levels were reduced(all P<.001),and SOD activity and MDA content were reduced(SOD:P=0.0017 between the low-concentration group and the control group,P<.001 between the high-concentration and medium-concentration groups and the control group;MDA:P=0.0135 between the low-concentration group and the control group,and P<0.001 between the high-concentration and medium-concentration groups and the control group).In addition,CGA also activated the DAF-16 transcription factor,promoted DAF-16 nuclear translocation under oxidative stress conditions(both P<0.001 between the high-concentration and medium-concentration groups and the control group),and increased SOD-3 gene expression in nematodes(all P<0.001).Conclusion:CGA plays an anti-aging role in C.elegans.The underlying mechanisms include activation of the insulin/IGF-1 signaling pathway and enhancement of DAF-16 activity.This study lays a foundation for further research into the anti-aging effects of CGA.展开更多
Ionizing radiation can cause changes in nervous system function.However,the underlying mechanism remains unclear.In this study,Coenorhabditis elegans(C.elegans)was irradiated with 75 Gy of ^(60)Co whole-body γ radiat...Ionizing radiation can cause changes in nervous system function.However,the underlying mechanism remains unclear.In this study,Coenorhabditis elegans(C.elegans)was irradiated with 75 Gy of ^(60)Co whole-body γ radiation.Behavioral indicators(head thrashes,touch avoidance,and foraging),and the development of dopaminergic neurons related to behavioral function,were evaluated to assess the effects of ionizing radiation on nervous system function in C.elegans.Various behaviors were impaired after whole-body irradiation and degeneration of dopamine neurons was observed.This suggests that 75 Gy of γ radiation is sufficient to induce nervous system dysfunction.The genes nhr-76 and crm-1,which are reported to be related to nervous system function in human and mouse,were screened by transcriptome sequencing and bioinformatics analysis after irradiation or sham irradiation.The expression levels of these two genes were increased after radiation.Next,RNAi technology was used to inhibit the expression of crm-1,a gene whose homologs are associated with motor neuron development in other species.Downregulation of crm-1 expression effectively alleviated the deleterious effects of ionizing radiation on head thrashes and touch avoidance.It was also found that the expression level of crm-1 was regulated by the nuclear receptor gene nhr-76.The results of this study suggest that knocking down the expression level of nhr-76 can reduce the expression level of crm-1,while down-regulating the expression level of crm-1 can alleviate behavioral disorders induced by ionizing radiation.Therefore,inhibition of crm-1 may be of interest as a potential therapeutic target for ionizing radiation-induced neurological dysfunction.展开更多
As an irreplaceable dietary constituent,lipids play a vital important role in health,but their effects on aging process and longevity are still not well known yet.In this paper,the metabolic profiling and gene express...As an irreplaceable dietary constituent,lipids play a vital important role in health,but their effects on aging process and longevity are still not well known yet.In this paper,the metabolic profiling and gene expression levels of Caenorhabditis elegans were investigated to explore the effects of different edible oils on senescence and lifespan.The results showed that teaseed oil(TO)could prolong the life expectancy and slow down the aging process of C.elegans.Compared to the control group,the intake of lard oil(LO)and TO increased the expression levels of genes related to inhibition of protein aggregation(akt-1,daf-16,hsf-1,hsp-16.2)and lipid metabolism(daf-7,daf-1,mdt-15,lipl-4,fat-5,fat-6,fat-7),with a more significant alteration in TO group.Metabolomics revealed that palm oil can upregulated plenty of fatty acids(palmitic acid,stearic acid,tetracosanoic acid),together with some amino acids(tryptophan,L-aspartate,L-valine)and carbohydrate(D-glucose),while the trend was opposite in TO group.Besides,moderate-to-strong correlations were found between differential metabolites and changed genes.In general,this paper claimed that TO could prolong lifespan and slow down aging process via regulating the lipids,amino acids and carbohydrates metabolism.展开更多
People continue to recognize the important role of Chinese medicine in the treatment of diseases,and there is an urgent need to clarify the mechanism of Chinese medicine.Because of the multi-target and multi-component...People continue to recognize the important role of Chinese medicine in the treatment of diseases,and there is an urgent need to clarify the mechanism of Chinese medicine.Because of the multi-target and multi-component characteristics of traditional Chinese medicine,it is difficult to elaborate from a single perspective.As a high-quality animal model,Caenorhabditis elegans with the characteristics of small size and fast reproduction,has been widely used in traditional Chinese medicine activity experiments.In this article,Caenorhabditis elegans,as model organisms used to screen the active components of traditional Chinese medicine were reviewed.展开更多
Due to the large number of ionic liquids （ILs） and their potential environmental risk, assessing the toxicity of ILs by ecotoxicological experiment only is insufficient. Quantitative structure- activity relationship...Due to the large number of ionic liquids （ILs） and their potential environmental risk, assessing the toxicity of ILs by ecotoxicological experiment only is insufficient. Quantitative structure- activity relationship （QSAR） has been proven to be a quick and effective method to estimate the viscosity, melting points, and even toxicity of ILs. In this work, the LC50 values of 30 imidazolium-based ILs were determined with Caenorhabditis elegans as a model animal. Four suitable molecular descriptors were selected on the basis of genetic function approximation algorithm to construct a QSAR model with an R^2 value of 0.938. The predicted lgLC50 in this work are in agreement with the experimental values, indicating that the model has good stability and predictive ability. Our study provides a valuable model to predict the potential toxicity of ILs with different sub-structures to the environment and human health.展开更多
The nematode Caenorhabditis elegans is an attractive model organism to study the behavioral plasticity for its simple system and ability to respond to diverse environmental stimuli, such as touch, smell, taste and tem...The nematode Caenorhabditis elegans is an attractive model organism to study the behavioral plasticity for its simple system and ability to respond to diverse environmental stimuli, such as touch, smell, taste and temperature. Learning in C. elegans encompasses both non-associative learning and associative learning. Till now, themotaxis and chemotaxis are two major paradigms for associative learning and there are at least 6 forms of chemotaxis-mediated associative learning. Three research systems have also been explored to study the mechanism of learning choice in worms. This review will discuss the forms, research models, genetic and molecular regulation of learning and learning choice in C. elegans.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
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
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
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
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
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 150 μmol/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 2.5 μmol/L, and in Cu, Ag, and Cr exposed che-1 mutant at concentrations more than 50 μmol/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
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
Apart from the liver disruption, embryotoxicity and genotoxicity, microcystin （MC）-LR also could cause neurotoxicity. Nematode Caenorhabditis elegans was explored as a model to study the neurotoxicity. In the presen...Apart from the liver disruption, embryotoxicity and genotoxicity, microcystin （MC）-LR also could cause neurotoxicity. Nematode Caenorhabditis elegans was explored as a model to study the neurotoxicity. In the present study, we provided evidence to indicate the neurotoxicity on chemotaxis to NaCl and diacetyl, and thermotaxis from MC-LR exposure to C. elegans. As a result, higher concentrations of MC-LR caused significantly severe defects of chemotaxis to NaCl and diacetyl, and thermotaxis. The neurotoxicity on chemotaxis to NaCl and diacetyl, and thermotaxis from MC-LR exposure might be largely mediated by the damage on the corresponding sensory neurons （ASE, AWA, and AFD） and interneuron AIY. The expression levels ofche-1 and odr-7 were significantly decreased （P 〈 0.01） in animals exposed to MC-LR at concentrations lower than 10 μg/L, whereas the expression levels of ttx-1 and ttx-3 could be significantly （P 〈 0.01） lowered in animals even exposed to 1 μg/L of MC-LR. Moreover, both the chemotaxis to NaCl and diacetyl and the thermotaxis were more significantly reduced in MC-LR exposed mutants of che-1（p674）, odr-7（ky4）, ttx-1（p767）, and ttx-3（ks5） than those in exposed wild-type N2 animals at the same concentrations.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
Objective To investigate the toxic effect of sodium fluoride（NaF） on the nematode Caenorhabditis elegans（C.elegans）.Methods Adult C.elegans were exposed to different concentrations of NaF（0.038 mmol/L,0.38 mmol/L...Objective To investigate the toxic effect of sodium fluoride（NaF） on the nematode Caenorhabditis elegans（C.elegans）.Methods Adult C.elegans were exposed to different concentrations of NaF（0.038 mmol/L,0.38 mmol/L,and 3.8 mmol/L） for 24 h.To assess the physiological effects of NaF,the brood size,life span,head thrashes,and body bend frequency were examined.Reactive oxygen species（ROS） and cell apoptosis were detected as parameters of biochemical response.The gene expressions were determined by real‐time polymerase chain reaction（PCR） to assess the molecular‐level response.Results At the physiological level,the brood size of C.elegans exposed to 0.038 mmol/L,0.38 mmol/L,and 3.8 mmol/L concentrations of NaF were reduced by 6%,26%,and 28% respectively in comparison with the control group.The maximum life spans of C.elegans exposed to 0.038 mmol/L,0.38 mmol/L,and 3.8 mmol/L concentrations of NaF were reduced by 3 days and 5 days,respectively.Head thrashes and body bend frequency both decreased with increasing concentrations of NaF.At the biochemical level,the production of ROS and the incidence of cell apoptosis increased with increasing concentrations of NaF（P0.05）.At the molecular level,different concentrations of NaF exposure raised the expression of stress‐related genes,such as hsp16.1,sod‐3,ctl‐2,dhs‐28,gst‐1,and cep‐1.Conclusion NaF exposure could induce multiple biological toxicities to C.elegans in a concentration‐dependent manner.These toxicities may be relevant to the oxidative stress induced by increased ROS production and accumulation in C.elegans.展开更多
Naphthalene is a common environmental contaminant substance. The toxic effects of naphthalene on Caenorhabditis elegans were investigated at the molecular, biochemical and physiological levels. To assess the molecular...Naphthalene is a common environmental contaminant substance. The toxic effects of naphthalene on Caenorhabditis elegans were investigated at the molecular, biochemical and physiological levels. To assess the molecular-level effect, stress-related gene expression was investigated such as those of hsp-16.1, sod-3, ctl-2, cep-1, cyp35a2, ugt-44, gst-1 and dhs-28. Cell apoptosis was assessed at the biochemical level. Life span, locomotion behaviors and brood size were investigated at the physiological level. The results indicate that naphthalene exposure could not only induce the expression of stress-related genes such as hsp16.1, sod-3, ctl-2 and cep-1 but also reduce the life span of Caenorhabditis elegans. At the same time, naphthalene exposure could result in cell apoptosis and interfere in the locomotion behaviors of Caenorhabditis elegans. These data suggest that naphthalene has multiple toxicity on Caenorhabditis elegans.展开更多
Model invertebrate organism Caenorhabditis elegans has become an ideal model to unravel the complex processes of memory. C. elegans has three simple forms of memory： memory for thermosensation, memory for chemosensat...Model invertebrate organism Caenorhabditis elegans has become an ideal model to unravel the complex processes of memory. C. elegans has three simple forms of memory： memory for thermosensation, memory for chemosensation, and memory for mechanosensation. In the form of memory for mechanosensation, short-term memory, intermediate-term memory, and long-term memory have been extensively studied. The short-term memory and intermediate-term memory may occur in the presynaptic sensory neurons, whereas the long-term memory may occur in the postsynaptic interneurons. This review will discuss the recent progress on genetic and molecular regulation of memory in C. elegans.展开更多
Genomic DNAs of metallothionein Ⅰ and Ⅱ in Caenorhabditis elegans (CeMT-Ⅰand CeMT-Ⅱ) were isolated by YAC library/polytene filter hybridization followed by subcloning of corresponding cosmid clones. Both genes are...Genomic DNAs of metallothionein Ⅰ and Ⅱ in Caenorhabditis elegans (CeMT-Ⅰand CeMT-Ⅱ) were isolated by YAC library/polytene filter hybridization followed by subcloning of corresponding cosmid clones. Both genes are mapped at chromosome V. Although the similarities of 5'-flanking regions and coding regions have shown only 55-58%, the introns are split at the same position in both genes, indicating that these two genes are originally from the same gene. While several metal responsive elements are conserved among eukaryotes, only one metal responsive element was found in the promoter region in CeMT-Ⅱ and not in CeMT-Ⅰ. Indced, neither of 5'-flanking regions of CeMT-Ⅰ nor CeMT-Ⅱ connected to chloramphenicol acetyltransferase reporter gene is responsive to heavy metals in mammalian culture cells by transient transfection analysis. These results would suggest that the metal regulatory factors in C.elegans might be different from those conserved in invertebrates and vertebrates, although the MTs in C elegans revealed the similarities to mammalian MTs in several points展开更多
基金supported by the priority academic program development of Jiangsu Higher education institutionsthe National Natural Science Foundation of China [31801538, 32072200]China Postdoctoral Science Foundation[2019M651747].
文摘Objective This study aimed to investigate the lipid-lowering activity of LFBEP-C1 in high glucose-fed Caenorhabditis elegans(C.elegans).Methods In this study,the fermented barley protein LFBEP-C1 was prepared and tested for its potential anti-obesity effects on C.elegans.The worms were fed Escherichia coli OP50(E.coli OP50),glucose,and different concentrations of LFBEP-C1.Body size,lifespan,movement,triglyceride content,and gene expression were analyzed.The results were analyzed using ANOVA and Tukey's multiple comparison test.Results Compared with the model group,the head-swing frequency of C.elegans in the group of LFBEP-C1 at 20μg/mL increased by 33.88%,and the body-bending frequency increased by 27.09%.This indicated that LFBEP-C1 improved the locomotive ability of C.elegans.The average lifespan of C.elegans reached 13.55 days,and the body length and width of the C.elegans decreased after LFBEP-C1 intake.Additionally,LFBEP-C1 reduced the content of lipid accumulation and triglyceride levels.The expression levels of sbp-1,daf-2,and mdt-15 significantly decreased,while those of daf-16,tph-1,mod-1,and ser-4 significantly increased after LFBEP-C1 intake.Changes in these genes explain the signaling pathways that regulate lipid metabolism.Conclusion LFBEP-C1 significantly reduced lipid deposition in C.elegans fed a high-glucose diet and alleviated the adverse effects of a high-glucose diet on the development,lifespan,and exercise behavior of C.elegans.In addition,LFBEP-C1 regulated lipid metabolism mainly by mediating the expression of genes in the sterol regulatory element-binding protein,insulin,and 5-hydroxytryptamine signaling pathways.
基金This study was supported by the Key Research Project Fund of Beijing University of Chinese Medicine(2021JYB2002001)the National Natural Science Foundation of Tibetan medicine Collabo-rative Innovation(82130113).
文摘Objective:To explore the anti-aging effects of chlorogenic acid(CGA)and the underlying mechanisms based on a Caenorhabditis elegans(C.elegans)model.Methods:The anti-agingactivityofCGAwasstudied basedon thebodylength,exercisebehavior,lipofuscin content,antioxidative stress ability,swallowing frequency,body-bending frequency,and head-swinging ability of C.elegans.Through DAF-16 nuclear translocation and SOD-3-GFP fluorescence experiments,the effects of CGA on ROS levels,antioxidant enzyme activities,MDA content,mutant-strain lifespan,and anti-aging molecular signaling pathways were explored,as well as the underlying mechanisms.Results:CGA improved multiple indices of the nematode:body length was increased(all P<0.001),head-swing frequency and body-bending frequency were increased(all P<0.05),nematode longevity was prolonged(P=0.0021),lipofuscin deposition in nematodes was slowed down(all P<0.001),the chemotaxis index was improved(P=0.0012),ROS levels were reduced(all P<.001),and SOD activity and MDA content were reduced(SOD:P=0.0017 between the low-concentration group and the control group,P<.001 between the high-concentration and medium-concentration groups and the control group;MDA:P=0.0135 between the low-concentration group and the control group,and P<0.001 between the high-concentration and medium-concentration groups and the control group).In addition,CGA also activated the DAF-16 transcription factor,promoted DAF-16 nuclear translocation under oxidative stress conditions(both P<0.001 between the high-concentration and medium-concentration groups and the control group),and increased SOD-3 gene expression in nematodes(all P<0.001).Conclusion:CGA plays an anti-aging role in C.elegans.The underlying mechanisms include activation of the insulin/IGF-1 signaling pathway and enhancement of DAF-16 activity.This study lays a foundation for further research into the anti-aging effects of CGA.
基金supported by the National Natural Science Foundation of China,Nos.82003391(to NC),U1867204(to YT)the Natural Science Research Projects of Colleges and Universities in Jiangsu Province,No.20KJB310007(to NC).
文摘Ionizing radiation can cause changes in nervous system function.However,the underlying mechanism remains unclear.In this study,Coenorhabditis elegans(C.elegans)was irradiated with 75 Gy of ^(60)Co whole-body γ radiation.Behavioral indicators(head thrashes,touch avoidance,and foraging),and the development of dopaminergic neurons related to behavioral function,were evaluated to assess the effects of ionizing radiation on nervous system function in C.elegans.Various behaviors were impaired after whole-body irradiation and degeneration of dopamine neurons was observed.This suggests that 75 Gy of γ radiation is sufficient to induce nervous system dysfunction.The genes nhr-76 and crm-1,which are reported to be related to nervous system function in human and mouse,were screened by transcriptome sequencing and bioinformatics analysis after irradiation or sham irradiation.The expression levels of these two genes were increased after radiation.Next,RNAi technology was used to inhibit the expression of crm-1,a gene whose homologs are associated with motor neuron development in other species.Downregulation of crm-1 expression effectively alleviated the deleterious effects of ionizing radiation on head thrashes and touch avoidance.It was also found that the expression level of crm-1 was regulated by the nuclear receptor gene nhr-76.The results of this study suggest that knocking down the expression level of nhr-76 can reduce the expression level of crm-1,while down-regulating the expression level of crm-1 can alleviate behavioral disorders induced by ionizing radiation.Therefore,inhibition of crm-1 may be of interest as a potential therapeutic target for ionizing radiation-induced neurological dysfunction.
基金supported by National Key R&D Program of China(2019YFC1606205)Natural Science Foundation of China(32172136)Jiangsu distinguished professor project and Talent plan of Taihu Lake.
文摘As an irreplaceable dietary constituent,lipids play a vital important role in health,but their effects on aging process and longevity are still not well known yet.In this paper,the metabolic profiling and gene expression levels of Caenorhabditis elegans were investigated to explore the effects of different edible oils on senescence and lifespan.The results showed that teaseed oil(TO)could prolong the life expectancy and slow down the aging process of C.elegans.Compared to the control group,the intake of lard oil(LO)and TO increased the expression levels of genes related to inhibition of protein aggregation(akt-1,daf-16,hsf-1,hsp-16.2)and lipid metabolism(daf-7,daf-1,mdt-15,lipl-4,fat-5,fat-6,fat-7),with a more significant alteration in TO group.Metabolomics revealed that palm oil can upregulated plenty of fatty acids(palmitic acid,stearic acid,tetracosanoic acid),together with some amino acids(tryptophan,L-aspartate,L-valine)and carbohydrate(D-glucose),while the trend was opposite in TO group.Besides,moderate-to-strong correlations were found between differential metabolites and changed genes.In general,this paper claimed that TO could prolong lifespan and slow down aging process via regulating the lipids,amino acids and carbohydrates metabolism.
基金This work was financially supported by Scientific Research Fund Project of Education Department of Liaoning Province(LJKZ0960)Science Foundation of Shenyang Pharmaceutical University(GGJJ2021105).
文摘People continue to recognize the important role of Chinese medicine in the treatment of diseases,and there is an urgent need to clarify the mechanism of Chinese medicine.Because of the multi-target and multi-component characteristics of traditional Chinese medicine,it is difficult to elaborate from a single perspective.As a high-quality animal model,Caenorhabditis elegans with the characteristics of small size and fast reproduction,has been widely used in traditional Chinese medicine activity experiments.In this article,Caenorhabditis elegans,as model organisms used to screen the active components of traditional Chinese medicine were reviewed.
基金This work was supported by the National Natural Science Foundation of China （No.21477121）, and the Fundamental Research Funds for the Central Universities for the support of this work. The numerical calculations were performed on the super computing system in the Supercomputing Center at the University of Science and Technology of China.
文摘Due to the large number of ionic liquids （ILs） and their potential environmental risk, assessing the toxicity of ILs by ecotoxicological experiment only is insufficient. Quantitative structure- activity relationship （QSAR） has been proven to be a quick and effective method to estimate the viscosity, melting points, and even toxicity of ILs. In this work, the LC50 values of 30 imidazolium-based ILs were determined with Caenorhabditis elegans as a model animal. Four suitable molecular descriptors were selected on the basis of genetic function approximation algorithm to construct a QSAR model with an R^2 value of 0.938. The predicted lgLC50 in this work are in agreement with the experimental values, indicating that the model has good stability and predictive ability. Our study provides a valuable model to predict the potential toxicity of ILs with different sub-structures to the environment and human health.
文摘The nematode Caenorhabditis elegans is an attractive model organism to study the behavioral plasticity for its simple system and ability to respond to diverse environmental stimuli, such as touch, smell, taste and temperature. Learning in C. elegans encompasses both non-associative learning and associative learning. Till now, themotaxis and chemotaxis are two major paradigms for associative learning and there are at least 6 forms of chemotaxis-mediated associative learning. Three research systems have also been explored to study the mechanism of learning choice in worms. This review will discuss the forms, research models, genetic and molecular regulation of learning and learning choice in C. elegans.
基金Project supported by the Southeast University Foundation for Excellent Young Scholars(No.4023001013)
文摘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 Natural Science Foundation of China (No. 30771113, 30870810)the Program for New Century Excellent Talents in University
文摘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the National Natural Science Foundation of China (No.30771113)the Southeast University Foundation for Excellent Young Scholars (No.4023001013)
文摘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 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)
文摘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)。
文摘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 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).
文摘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 150 μmol/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 2.5 μmol/L, and in Cu, Ag, and Cr exposed che-1 mutant at concentrations more than 50 μmol/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.
文摘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.
基金supported by the National Natural Sci- ence Foundation of China (No. 30771113, 30870810)and the Program for New Century Excellent Talents in Universityprovided by the Caenorhabditis Genetics Center (funded by the NIH, National Center for Foundation from Research Resource)
文摘Apart from the liver disruption, embryotoxicity and genotoxicity, microcystin （MC）-LR also could cause neurotoxicity. Nematode Caenorhabditis elegans was explored as a model to study the neurotoxicity. In the present study, we provided evidence to indicate the neurotoxicity on chemotaxis to NaCl and diacetyl, and thermotaxis from MC-LR exposure to C. elegans. As a result, higher concentrations of MC-LR caused significantly severe defects of chemotaxis to NaCl and diacetyl, and thermotaxis. The neurotoxicity on chemotaxis to NaCl and diacetyl, and thermotaxis from MC-LR exposure might be largely mediated by the damage on the corresponding sensory neurons （ASE, AWA, and AFD） and interneuron AIY. The expression levels ofche-1 and odr-7 were significantly decreased （P 〈 0.01） in animals exposed to MC-LR at concentrations lower than 10 μg/L, whereas the expression levels of ttx-1 and ttx-3 could be significantly （P 〈 0.01） lowered in animals even exposed to 1 μg/L of MC-LR. Moreover, both the chemotaxis to NaCl and diacetyl and the thermotaxis were more significantly reduced in MC-LR exposed mutants of che-1（p674）, odr-7（ky4）, ttx-1（p767）, and ttx-3（ks5） than those in exposed wild-type N2 animals at the same concentrations.
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).
文摘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supported by Jilin Provincial Science and Technology Development Project in China,20100407
文摘Objective To investigate the toxic effect of sodium fluoride（NaF） on the nematode Caenorhabditis elegans（C.elegans）.Methods Adult C.elegans were exposed to different concentrations of NaF（0.038 mmol/L,0.38 mmol/L,and 3.8 mmol/L） for 24 h.To assess the physiological effects of NaF,the brood size,life span,head thrashes,and body bend frequency were examined.Reactive oxygen species（ROS） and cell apoptosis were detected as parameters of biochemical response.The gene expressions were determined by real‐time polymerase chain reaction（PCR） to assess the molecular‐level response.Results At the physiological level,the brood size of C.elegans exposed to 0.038 mmol/L,0.38 mmol/L,and 3.8 mmol/L concentrations of NaF were reduced by 6%,26%,and 28% respectively in comparison with the control group.The maximum life spans of C.elegans exposed to 0.038 mmol/L,0.38 mmol/L,and 3.8 mmol/L concentrations of NaF were reduced by 3 days and 5 days,respectively.Head thrashes and body bend frequency both decreased with increasing concentrations of NaF.At the biochemical level,the production of ROS and the incidence of cell apoptosis increased with increasing concentrations of NaF（P0.05）.At the molecular level,different concentrations of NaF exposure raised the expression of stress‐related genes,such as hsp16.1,sod‐3,ctl‐2,dhs‐28,gst‐1,and cep‐1.Conclusion NaF exposure could induce multiple biological toxicities to C.elegans in a concentration‐dependent manner.These toxicities may be relevant to the oxidative stress induced by increased ROS production and accumulation in C.elegans.
基金Supported by the National Natural Science Foundation of China(No.20877017)the National High Technology Research and Development Program of China (No.2007AA03Z314)
文摘Naphthalene is a common environmental contaminant substance. The toxic effects of naphthalene on Caenorhabditis elegans were investigated at the molecular, biochemical and physiological levels. To assess the molecular-level effect, stress-related gene expression was investigated such as those of hsp-16.1, sod-3, ctl-2, cep-1, cyp35a2, ugt-44, gst-1 and dhs-28. Cell apoptosis was assessed at the biochemical level. Life span, locomotion behaviors and brood size were investigated at the physiological level. The results indicate that naphthalene exposure could not only induce the expression of stress-related genes such as hsp16.1, sod-3, ctl-2 and cep-1 but also reduce the life span of Caenorhabditis elegans. At the same time, naphthalene exposure could result in cell apoptosis and interfere in the locomotion behaviors of Caenorhabditis elegans. These data suggest that naphthalene has multiple toxicity on Caenorhabditis elegans.
文摘Model invertebrate organism Caenorhabditis elegans has become an ideal model to unravel the complex processes of memory. C. elegans has three simple forms of memory： memory for thermosensation, memory for chemosensation, and memory for mechanosensation. In the form of memory for mechanosensation, short-term memory, intermediate-term memory, and long-term memory have been extensively studied. The short-term memory and intermediate-term memory may occur in the presynaptic sensory neurons, whereas the long-term memory may occur in the postsynaptic interneurons. This review will discuss the recent progress on genetic and molecular regulation of memory in C. elegans.
文摘Genomic DNAs of metallothionein Ⅰ and Ⅱ in Caenorhabditis elegans (CeMT-Ⅰand CeMT-Ⅱ) were isolated by YAC library/polytene filter hybridization followed by subcloning of corresponding cosmid clones. Both genes are mapped at chromosome V. Although the similarities of 5'-flanking regions and coding regions have shown only 55-58%, the introns are split at the same position in both genes, indicating that these two genes are originally from the same gene. While several metal responsive elements are conserved among eukaryotes, only one metal responsive element was found in the promoter region in CeMT-Ⅱ and not in CeMT-Ⅰ. Indced, neither of 5'-flanking regions of CeMT-Ⅰ nor CeMT-Ⅱ connected to chloramphenicol acetyltransferase reporter gene is responsive to heavy metals in mammalian culture cells by transient transfection analysis. These results would suggest that the metal regulatory factors in C.elegans might be different from those conserved in invertebrates and vertebrates, although the MTs in C elegans revealed the similarities to mammalian MTs in several points
