JOURNAL OF CELL BIOLOGY
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2024
·Vol. 224
·期 1
·e202403198
·
IF 7.4
Liu Xiaofan,Chang Zhi,Sun Pingping,Cao Beibei,Wang Yuzhi,Fang Jie,Pei Yechun,Chen Baohui,Zou Wei
Maximizing cell survival under stress requires rapid and transient adjustments of RNA and protein synthesis. However, capturing these dynamic changes at both single-cell level and across an organism has been challenging. Here, we developed a system named MONITTR (MS2-embedded mCherry-based monitoring of transcription) for real-time simultaneous measurement of nascent transcripts and endogenous protein levels in C. elegans. Utilizing this system, we monitored the transcriptional bursting of fasting-induced genes and found that the epidermis responds to fasting by modulating the proportion of actively transcribing nuclei and transcriptional kinetics of individual alleles. Additionally, our findings revealed the essential roles of the transcription factors NHR-49 and HLH-30 in governing the transcriptional kinetics of fasting-induced genes under fasting. Furthermore, we tracked transcriptional dynamics during heat-shock response and ER unfolded protein response and observed rapid changes in the level of nascent transcripts under stress conditions. Collectively, our study provides a foundation for quantitatively investigating how animals spatiotemporally modulate transcription in various physiological and pathological conditions.
研究领域:
分子生物学
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遗传学
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DOI
高影响因子
Nature Communications
·
2023
·Vol. 14
·期 1
·1-19
·
IF 16.6
Zhan Xu,Chen Chao,Niu Longgang,Du Xinran,Lei Ying,Dan Rui,Wang Zhao-Wen,Liu Ping
Locomotor activities can enhance learning, but the underlying circuit and synaptic mechanisms are largely unknown. Here we show that locomotion facilitates aversive olfactory learning in C. elegans by activating mechanoreceptors in motor neurons, and transmitting the proprioceptive information thus generated to locomotion interneurons through antidromic-rectifying gap junctions. The proprioceptive information serves to regulate experience-dependent activities and functional coupling of interneurons that process olfactory sensory information to produce the learning behavior. Genetic destruction of either the mechanoreceptors in motor neurons, the rectifying gap junctions between the motor neurons and locomotion interneurons, or specific inhibitory synapses among the interneurons impairs the aversive olfactory learning. We have thus uncovered an unexpected role of proprioception in a specific learning behavior as well as the circuit, synaptic, and gene bases for this function.
研究领域:
神经科学
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分子生物学
·
行为生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Aging Neuroscience
·
2024
·
IF 4.1
Xue Weikang,Lei Ziyi,Liu Bin,Guo Hanxin,Yan Weiyi,Jin Youngnam N.,Yu Yanxun V.
Neurodegenerative diseases such as Alzheimer's disease and polyglutamine diseases are characterized by abnormal accumulation of misfolded proteins, leading to neuronal dysfunction and subsequent neuron death. However, there is a lack of studies that integrate molecular, morphological, and functional analyses in neurodegenerative models to fully characterize these time-dependent processes. In this study, we used C. elegans models expressing Aβ1-42 and polyglutamine to investigate early neuronal pathogenic features in olfactory neurons. Both models demonstrated significant reductions in odor sensitivity in AWB and AWC chemosensory neurons as early as day 1 of adulthood, while AWA chemosensory neurons showed no such decline, suggesting cell-type-specific early neuronal dysfunction. At the molecular level, Aβ1-42 or Q40 expression caused age-dependent protein aggregation and morphological changes in neurons. By day 6, both models displayed prominent protein aggregates in neuronal cell bodies and neurites. Notably, AWB neurons in both models showed significantly shortened cilia and increased instances of enlarged cilia as early as day 1 of adulthood. Furthermore, AWC neurons expressing Aβ1-42 displayed calcium signaling defects, with significantly reduced responses to odor stimuli on day 1, further supporting early behavioral dysfunction. In contrast, AWA neuron did not exhibit reduced calcium responses, consistent with the absence of detectable decreases in olfactory sensitivity in these neurons. These findings suggest that decreased calcium signaling and dysfunction in specific sensory neuron subtypes are early indicators of neurodegeneration in C. elegans, occurring prior to the formation of visible protein aggregates. We found that the ER unfolded protein response (UPR) is significantly activated in worms expressing Aβ1-42. Activation of the AMPK pathway alleviates olfactory defects and reduces fibrillar Aβ in these worms. This study underscores the use of C. elegans olfactory neurons as a model to elucidate mechanisms of proteostasis in neurodegenerative diseases and highlights the importance of integrated approaches.
研究领域:
神经科学
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分子生物学
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神经退行性疾病
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模式生物
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DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Lin An,Shuhao Wang,Bingyu Liao,Jin Liu,Xiaoyan Jin,Yuyang Cai,Zibo Li,Yue Li,Junfeng Ma,Junbai Li
Self-assembled dipeptide hydrogel provides three-dimensional networks through noncovalent interactions for the embedment and the release of multiple biocomponents as well as for the growth of live cells. Here we demonstrate that Caenorhabditis elegans ( C. elegans ) as model organisms can be immobilized with significant vital signs in N -fluorenylmethoxycarbonyl diphenylalanine (Fmoc-FF) dipeptide hydrogel. With the controllability of dipeptide, assembly conditions for immobilization, growth and imaging of C. elegans were optimized. Compared with conventional anesthesia method, dipeptide hydrogel minimized unintended interferences for long-termed imaging. Particularly, nanofiber-based hydrogel can be diluted in solution as nanofiber dispersions alongside the release of C. elegans . By further analyzing the physiological phenotypes including basic growth, movement and reproduction once released from hydrogel, we confirmed the practicality and biocompatibility of Fmoc-FF hydrogel especially towards repeated immobilization and release of small-scaled living organisms, further broadening the scope of dipeptide hydrogel usage.
研究领域:
细胞生物学
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材料科学
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生物医学工程
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DOI
PubMed
高影响因子
Journal of Functional Foods
·
2025
·
IF 4
Yehua Huang,Bingbing Song,Zhuo Wang,Kit Leong Cheong,Rui Li,Qiaoli Zhao,Jing Chen,Saiyi Zhong
Sulfated glycosaminoglycan from swim bladder (SBG) is a marine-derived bioactive polysaccharide structurally similar to chondroitin sulfate A. This study investigates the potential of SBG in mitigating hyperlipidemia linked to lipid metabolism disorders. The results indicate that SBG significantly mitigates glucose-induced metabolic disturbances in C. elegans , including reduced fertility, shortened lifespan, elevated ROS levels, lipofuscin accumulation, and impaired antioxidant responses. Notably, at 1 mg/mL, SBG reduced triglyceride and free fatty acid levels by 56.76 % and 26.64 %, respectively ( P < 0.05), as confirmed by Oil Red O staining. At the molecular level, SBG downregulated the expression of lipid metabolism genes, such as daf-2 , mdt-15 , sbp-1 , and acs-2 . Additionally, SBG upregulated the expression of nhr-49 and daf-16 , which enhanced Δ9-desaturase activity and promoted the synthesis of monounsaturated fatty acids. The deletion of nhr-49 further confirmed that SBG regulates Δ9-desaturase through NHR-49 activation, thereby improving lipid accumulation and preserving metabolic homeostasis.
研究领域:
生物化学
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分子生物学
·
营养学
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产品关联
DOI
高影响因子
Food & Function
·
2025
·
IF 5.4
Qi Gu,Litao Wang,Mingyue Xu,Wan-Mei Zhou,Guosheng Liu,Haiting Tian,Thomas Efferth,Chenlu Wang,Yujie Fu
Phloretin is a natural dihydrochalcone with a variety of biological activities. Its potential in modulating lipid metabolism in vitro and in vivo with HepG2 and C. elegans was investigated in this study. Phloretin significantly diminished lipid accumulation and ROS levels, mitigated the degree of lipid peroxidation, and ameliorated mitochondrial dysfunction in HepG2 cells. The expression levels of lipid synthesis genes (SREBP and FASN) were downregulated, while PI3K-AKT related genes (AKT, FOXO, MTOR) were upregulated. Furthermore, phloretin significantly alleviated the detrimental effects of lipid accumulation on growth indices and locomotor ability in C. elegans. It also reduced lipofuscin, ROS level as well as glucose and triglyceride contents, significantly affected amino acid and lipid metabolism pathways based on metabolomics profiles and analysis. Gene expression levels of sbp-1, mdt-15, fat-5, fat-6, and fat-7 were markedly down-regulated following treatment with phloretin, while daf-16, age-1 and skn-1were significantly up-regulated. Tests with mutant C. elegans strains of daf-16, age-1, sbp-1 and nhr-49 further confirmed that the phloretin-induced decrease in lipid accumulation was attributed to the inhibition of lipid biosynthesis pathway by IIS and sbp-1/SREBP. Our study indicated that phloretin exerted hypolipidemic effects in vitro and in vivo, providing a basic foundation for considering phloretin as a phytochemical candidate for regulating lipid metabolism and preventing hyperlipidemia.
研究领域:
代谢生物学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2024
·
IF 4
Yinyin Gao,Cheng Li,Junfei Li,Mengyao Duan,Xuan Li,Lina Zhao,Ying Wu,Shaobin Gu
Introduction: Hyperuricemia (HUA) refers to the presence of excess uric acid (UA) in the blood, which increases the risk of chronic kidney disease and gout. Probiotics have the potential to alleviate HUA.Methods: This study established a hyperuricemia model using Caenorhabditis elegans (C. elegans), and studied the anti-hyperuricemia activity and potential mechanisms of Weizmannella coagulans BC99 (W. coagulans) at different concentrations (107 CFU/mL BC99, 108 CFU/mL BC99). Subsequently, we utilized UPLC-Q-TOF/MS to investigate the impact of BC99 on endogenous metabolites in C. elegans and identified pathways and biomarkers through differential metabolomics analysis.Results: The results of this study showed that BC99 treatment significantly reduced the expression of P151.2 and T22F3.3 (p < 0.05), reduced the levels of UA and xanthine oxidase (XOD) in nematodes (p < 0.05), while extending their lifespan and movement ability (p < 0.05). Mechanistically, BC99 activates the transcription factors DAF-16 and SKN-1, thereby inducing the expression of stress response genes, enhancing the activity of antioxidant enzymes and tolerance to heat stress in the body, and reducing the production of ROS (p < 0.001). This effect was most significant in the H-BC99 group. Furthermore, non-targeted metabolomics indicated that BC99 predominantly regulated pathways associated with amino acid metabolism (Carnosine), glycerophospholipid metabolism, and purine metabolism.Discussion: These results underscore BC99 as an effective and economical adjunct therapeutic agent for hyperuricemia, providing a scientific basis for further development and application.
研究领域:
医学
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分子生物学
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营养学
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产品关联
DOI
PubMed
高影响因子
GeroScience
·
2024
·
IF 5.3
Zhou Yiming,Chen Lijuan,Wang Meijing,Yang Yang,Hu Bin,Li Guolin,Wei Fang
Paroxetine, a selective serotonin reuptake inhibitor, is widely used in the clinical treatment of depression. While several antidepressants show promise as geroprotectors, the role of paroxetine in aging remains unclear. In this study, we evaluated the lifespan extension effect of paroxetine in Caenorhabditis elegans ( C. elegans ) and elucidated the underlying mechanisms. The results showed that paroxetine can prolong lifespan concomitant extension of healthspan as indicated by increasing mobility and reducing lipofuscin accumulation, as well as confer protection to nematodes against different abiotic stresses. Paroxetine upregulated ser-7 expression and downregulated dop-4 expression. dop-4 RNA interference (RNAi) mimicked the beneficial effect of paroxetine on lifespan. Conversely, ser-7 RNAi abolished paroxetine-induced lifespan extension and the expression changes of dop-4 and genes related to insulin/insulin-like growth factor 1 signaling (IIS). Moreover, paroxetine exhibited a comparable lifespan extension effect to that observed in daf-2 or age-1 mutants; however, this effect was abolished in daf-16 mutant. Taken together, these results suggest that paroxetine promotes health and longevity in C. elegans through the ser-7 - dop-4 -IIS pathway, underscoring its potential as a geroprotector.
研究领域:
生物学
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老年医学
·
神经科学
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产品关联
DOI
PubMed
高影响因子
FREE RADICAL BIOLOGY AND MEDICINE
·
2024
·
IF 7.1
Lu-Yao Zheng,Yan-Xin Da,Xiu Luo,Xiao Zhang,Zhi-Jie Sun,De-Li Dong
Sorafenib is a targeted anticancer drug in clinic. Low-dose sorafenib has been reported to activate AMPK through inducing mitochondrial uncoupling without detectable toxicities. AMPK activation has been the approach for extending lifespan, therefore, we investigated the effect of sorafenib on lifespan and physical activity of C. elegans and the underlying mechanisms. In the present study, we found that the effect of sorafenib on C. elegans lifespan was typically hermetic. Sorafenib treatment at higher concentrations (100 μM) was toxic but at lower concentrations (1, 2.5, 5 μM) was beneficial to C. elegans . Sorafenib (1 μM) treatment for whole-life period extended C. elegans lifespan and improved C. elegans physical activity as manifested by increasing pharyngeal pumping and body movement, preserving intestinal barrier integrity, muscle fibers organization and mitochondrial morphology. In addition, sorafenib (1 μM) treatment enhanced C. elegans stress resistance. Sorafenib activated AMPK through inducing mitochondrial uncoupling in C. elegans . Sorafenib treatment activated DAF-16, SKN-1, and increased SOD-3, HSP-16.2, GST-4 expression in C. elegans . Sorafenib treatment induced AMPK-dependent autophagy in C. elegans . We conclude that low-dose sorafenib protects C. elegans against aging through activating AMPK/DAF-16 dependent anti-oxidant pathways and stimulating autophagy responses. Low-dose sorafenib could be a strategy for treating aging and aging-related diseases.
研究领域:
药理学
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老年学
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分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
Autophagy
·
2022
·
IF 13.391
Rong Fu,Xiaowan Jiang,Yuyan Yang,Chunxia Wang,Yun Zhang,Yi Zhu,Huimin Zhang
A variety of disturbances such as starvation, organelle damage, heat stress, hypoxia and pathogen infection can influence the autophagic process. However, how the macroautophagy/autophagy machinery is regulated intrinsically by structural damage of the cell remains largely unknown. In this work, we utilized the C. elegans epidermis as the model to address this question. Our results showed that structural damage by mechanical wounding exerted proximal inhibitory effect and distant promotional effect on autophagy within the same epidermal cell. By disrupting individual mechanical supporting structures, we found that only damage of the basal extracellular matrix or the underlying muscle cells activated a distinct autophagic response in the epidermis. On the contrary, structural disruption of the epidermal cells at the apical side inhibited autophagy activation caused by different stress factors. Mechanistic studies showed that the basal promotional effect of structural damage on epidermal autophagy was mediated by a mechanotransduction pathway going through the basal hemidesmosome receptor and LET-363/MTOR, while the apical inhibitory effect was mostly carried out by activation of calcium signaling. Elevated autophagy in the epidermis played a detrimental rather than a beneficial role on cell survival against structural damage. The results obtained from these studies will not only help us better understand the pathogenesis of structural damage- and autophagy-related diseases, but also provide insight into more generic rules of autophagy regulation by the structural and mechanical properties of cells across species.Abbreviations : ATG: autophagy related; BLI-1: BLIstered cuticle 1; CeHDs: C. elegans hemidesmosomes; COL-19: COLlagen 19; DPY-7: DumPY 7; ECM: extracellular matrix; EPG-5: ectopic PGL granules 5; GFP: green fluorescent protein; GIT-1: GIT1 (mammalian G protein-coupled receptor kinase InTeractor 1) homolog; GTL-2: Gon-Two Like 2 (TRP subfamily); HIS-58, HIStone 58; IFB-1: Intermediate Filament, B 1; LET: LEThal; LGG-1: LC3, GABARAP and GATE-16 family 1; MTOR: mechanistic target of rapamycin; MTORC1: MTOR complex 1; MUP-4: MUscle Positioning 4; NLP-29: Neuropeptide-Like Protein 29; PAT: Paralyzed Arrest at Two-fold; PIX-1: PIX (PAK (p21-activated kinase) Interacting eXchange factor) homolog 1; RFP: red fluorescent protein; RNAi: RNA interference; SQST-1: SeQueSTosome related 1; UNC: UNCoordinated; UV: ultraviolet; VAB-10: variable ABnormal morphology 10; WT: wild type.
研究领域:
细胞生物学
·
分子生物学
·
发育生物学
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DOI
PubMed
高影响因子
MECHANISMS OF AGEING AND DEVELOPMENT
·
2023
·
IF 5.3
Shuzhen Yu,Yating Shao,Qineng Qiu,Yu Cheng,Renkun Qing,Cai-Feng Wang,Su Chen,Chen Xu
Methods allowing light energy to be modulated in a controllable fashion are potentially important for finding the correlation between light-related environmental factors and aging-related lifespan. Here, we report photo- and thermo-regulation based on photonic crystals (PCs) for extended longevity of C. elegans . We show that PCs can function as a regulator of visible spectrum to tune photonic energy received by C.elegans . We provide direct evidence that lifespan depends on photonic energy, and the use of PCs reflecting blue light (440–537 nm) gives 8.3 % increasement in lifespan. We demonstrate that the exposure to modulated light alleviates photo-oxidative stress and unfolded-protein response. We realize reflective passive cooling temperature using PCs, and favorable low temperature could be created for worms to extend lifespan. This work offers a new path based on PCs to resist negative effects light and temperature for longevity, provides an available platform for studying the role of light in aging.
研究领域:
生物学
·
老年学
·
光学
✓ 已验证
DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
·
2019
·
IF 1.984
Ling Zhou,Pan-Pan Huang,Lin-Lin Chen,Ping Wang
The deposition of amyloid beta (Aβ) is the main hallmark of Alzheimer’s disease (AD) and there is no effective drug to cure the progressive cognitive loss or memory deficits caused by the aggregative toxicity of Aβ protein. Oxidative stress has been hypothesized to play a role in progressive neurodegenerative diseases like AD. Panax notoginseng saponin (PNS) from the rhizome of “pseudo-ginseng” exhibits potent antioxidant effects on aging process in neuron cells and animals. By using C. elegans as an ideal model organism, the present study shows that PNS (0.5–4 mg/mL) can significantly inhibit AD-like symptoms of worm paralysis and enhance resistance to oxidative stress induced by paraquat and aging conditions. Additionally, PNS extends lifespan and maintains healthspan of C. elegans by improving the swimming prowess and fertility at old age. It markedly activates the expression of SKN-1 mRNA, which further supports SKN-1 signaling pathway which is involved in the therapeutic effect of PNS on AD C. elegans. Our results provide direct evidence on PNS for treating AD on gene level and theoretical foundation for reshaping medicinal products of PNS in the future.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）