CHEMBIOCHEM
·
2025
·Vol. 26
·期 20
·e202500271
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IF 2.8
Yanan Wei,Yanying Sun,Xinyue Zhou,Doyoun Kim,Jihyeon Lee,Jeong Kyu Bang,Woo Jae Kim
Antimicrobial peptides (AMPs) represent a promising alternative to conventional antibiotics in combating multidrug-resistant pathogens, yet their clinical translation is hindered by proteolytic instability, cytotoxicity, and poor bioavailability. Herein, it is demonstrated that glycosylphosphatidylinositol-mediated membrane tethering of honeybee defensin1 (Def1) in Drosophila melanogaster enhances its antimicrobial efficacy by 100-fold compared to secreted or untethered forms, while preserving physiological and behavioral integrity under baseline conditions. Using a genetically engineered Drosophila model, three Def1 variants are expressed: native (Def1), secreted (s-Def1), and membrane-tethered (t-Def1). Flies expressing t-Def1 exhibit superior bacterial clearance of Pseudomonas aeruginosa and show improved survival postinfection, with no adverse effects on locomotion, courtship, or sleep architecture. However, under stress paradigms—including sleep deprivation and dextran sulfate sodium (DSS)-induced gut injury—t-Def1 exacerbates intestinal barrier dysfunction, as evidenced by elevated Smurf phenotype incidence, highlighting a trade-off between antimicrobial potency and epithelial vulnerability. This work establishes Drosophila as a powerful platform for dissecting AMP mechanisms and engineering spatially targeted therapies, offering translational insights for pollinator health and human infectious disease management. These results advocate for iterative refinement of membrane-anchoring strategies to balance therapeutic efficacy with host safety, advancing the development of next-generation AMPs with minimized off-target effects. Graphical Confocal images showing bacterial proliferation in the Drosophila gut reveal antimicrobial activity of t-Def1(tethered defensin1) against Pseudomonas aeruginosa.
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SCIENCE OF THE TOTAL ENVIRONMENT
·
2023
·
IF 9.8
Xing Zhang,Yuanyuan Song,Jie Wang,Chunyan Wu,Hanhui Xiang,Jiawei Hu,Hongyang Gong,Mingkuan Sun
Titanium dioxide nanoparticles (TiO 2 NPs) are widely used in several consumer products. However, because of their neurotoxic nature, exposure to TiO 2 NPs could impair locomotor behavior. Whether the impairment in locomotor behavior caused by TiO 2 NPs exposure is sustained and the effects is gender-specific has remained elusive, warranting further studies to elucidate the underlying mechanisms. Thus, we established a Drosophila model to study the effects of chronic TiO 2 NPs exposure on the locomotor behavior of Drosophila in different generations and explore the underlying mechanisms. Chronic TiO 2 NPs exposure caused accumulation of Ti in the body and affected the life history traits of Drosophila . Furthermore, chronic exposure to TiO 2 NPs decreased the total crawling distance of larvae and the total movement distance of adult males in the F3 generation, indicating the damage caused to the locomotor behavior of Drosophila . Impaired neuromuscular junction (NMJ) morphology was observed, manifested by the reduced number of boutons, size of boutons, and branch length of NMJ. In addition, several differentially expressed genes (DEGs) related to NMJ development were selected by RNA sequencing and their expression was confirmed by quantitative real-time-polymerase chain reaction (qRT-PCR). Compared with the control group, the gene expression of Cyp6a17, frac , and kek2 in the TiO 2 NPs exposure group decreased, whereas that of Gba1a , Hll and List was elevated. These findings indicated that chronic TiO 2 NPs exposure damage the morphology of NMJ by altering the expression of genes related to NMJ development, consequently causing locomotor behavior deficits in Drosophila .
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BIOGERONTOLOGY
·
2024
·
IF 4.4
Yuan Qianhua,Luo Mengliu,Xie Yutong,Song Wanhan,Wang Ya,Deng Dazhang,Chen Shuyan,Guo Honghui
Aging entails the progressive decline in the body’s self-regulation and functionality over time. Notably, obesity and aging exhibit parallel phenotypes, with obesity further accelerating the aging process across multiple dimensions and diminishing lifespan. In this study, we explored the impact of trans fatty acid (TFA) consumption on the overall health and lifespan of male Drosophila melanogaster under an isocaloric high-sugar and high-fat diet. Our results indicate that TFA intake results in a shortened lifespan, elevated body weight, and increased triglyceride levels in flies fed a high-sugar and high-fat diet with equivalent caloric intake. Additionally, TFA exposure induces oxidative stress, locomotor deficits, and damage to the intestinal barrier in flies. Collectively, chronic TFA consumption expedites the aging process and reduces the lifespan of male Drosophila melanogaster . These results contribute supplementary evidence regarding the adverse health effects associated with TFAs. Graphical Abstract Trans fatty acid intake results in a shortened lifespan, elevated body weight, and increased triglyceride levels in male Drosophila melanogaster fed a high-sugar and high-fat diet with equivalent caloric intake. Additionally, Trans fatty acid exposure induces oxidative stress, locomotor deficits, and damage to the intestinal barrier in flies.
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Food Bioscience
·
2024
·
IF 4.8
Li Jin,Xinyu Zheng,Chenxi Yu,Ping Li,Guiran Xiao
Metastasis is one of the most important factors related to malignant tumor development and therapeutic failure. Phytic acid (PA), a poly-phosphorylated inositol derivative in plant seeds and grains, has been shown to have antitumoral activity. However, the effect of PA on tumor metastasis and the underlying mechanisms remain uncharacterized. In the current study, we aimed to identify the effect of PA on tumor metastasis by employing a Drosophila model of malignant tumor Raf GOF Scrib −/− . We observed that PA supplementation in food inhibited the invasion and migration of tumors. Further studies indicated that PA drives Yki phosphorylation and inactivation through Lats kinase, which subsequently results in decreased expression of the JAK/STAT pathway ligands unpaired cytokines (Upds). Moreover, the reduced JAK/STAT pathway inhibits the recruitment and proliferation of hemocytes. To summarize, these findings provide valuable pathological and mechanistic insights into the potential application of PA for functional food or natural medicine development.
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Autophagy
·
2026
·
IF 18.6
Zhengran Li,Huiqing Zhao,Danjie Zhang,Jing Wei,Xiyue Tao Liu,Ruiyan Kong,Xuejing Ren,Hang Zhao,Xiaomin Fang,Jingyan Fu,Zhouhua Li
The self-renewal and differentiation of stem cells are tightly controlled to maintain tissue homeostasis. Failure in stem cell maintenance results in stem cell depletion and precocious aging. However, how stem cells are maintained still remains not fully understood. Here, through a large-scale RNAi screen for maintenance and proliferation of adult Drosophila intestinal stem cells (ISCs), we identify several subunits of V-ATPase including Vha68-2/ATP6V1A, required for ISC proliferation, differentiation and tissue regeneration. Inactivation of Vha68-2 results in accumulation of plasma membrane (PM)-derived structures in autophagosomes and lysosomes through Atg16 and Rab5. Furthermore, Vha68-2-defective ISCs undergo direct differentiation due to ectopic Notch activation. Mechanistically, Vha68-2 facilitates Notch receptor internalization and subsequent degradation in autolysosomes to quench ectopic Notch activation, thereby maintaining ISC fate. Truncated Notch product devoid of its extracellular domain is accumulated in autolysosomes upon Vha68-2 deficiency. The Notch products accumulated in autolysosomes still require further cleavage to drive ISC differentiation. The functions of Vha68-2 in macroautophagy/autophagy and ISC maintenance are evolutionarily conserved. Our results provide new insights into the underlying mechanism of how autophagy is involved in stem cell maintenance under physiological conditions.Abbreviations: aph-1: anterior pharynx defective 1; ATP6V1A: ATPase H+ transporting V1 subunit A; CASM: conjugation of ATG8s to single membranes; EB: enteroblast; EC: absorptive enterocyte; ER: endoplasmic reticulum; ISC: intestinal stem cell; kuz: kuzbanian; LTDR: LysoTracker Deep Red; LTR: LysoTracker Red; MARCM: mosaic analysis with a repressible cell marker; NECD: Notch extracellular domain; NICD: Notch intracellular domain; PM: plasma membrane; PAS: phagophore assembly site; SNARE: soluble N-ethylmaleimide-sensitive factor-attachment protein receptor; TEM: transmission electron microscopy; TM: tunicamycin.
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CHEMISTRY & BIOLOGY
·
2015
·Vol. 22
·期 11
·1461-1469
·
IF 6.645
Shan Feng,Yuling Chen,Fan Yang,Lei Zhang,Yiyi Gong,Gulishana Adilijiang,Yan Gao,Haiteng Deng
Protein glutathionylation is an important post-translational modification that regulates many cellular processes, including energy metabolism, signal transduction, and protein homeostasis. Global profiling of glutathionylated proteins (denoted as glutathionylome) is crucial for understanding redox-regulated signal transduction. Here, we developed a novel method based on click reaction and proteomics to enrich and identify the glutathionylated peptides in Escherichia coli and Drosophila lysates, in which 937 and 1,930 potential glutathionylated peptides were identified, respectively. Bioinformatics analysis showed that the cysteine residue next to negatively charged amino acid residues has a higher frequency of glutathionylation. Importantly, we found that most proteins associated with metabolic pathways were glutathionylated and that the glutathionylation sites of metabolic enzymes were highly conserved among different species. Our results indicate that the glutathione analog is a useful tool to characterize protein glutathionylation, and glutathionylation of metabolic enzymes, which play important roles in regulating cellular metabolism, is conserved.
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FOOD AND CHEMICAL TOXICOLOGY
·
2021
·
IF 6.025
Yin Li,Dongyi Hu,Jianlian Huang,Shaoyun Wang
With the aging problems increasing, the discovery of anti-aging compounds has become a popular research direction. Accumulation of free radicals and the consequent oxidative stress are the chief culprit of aging. Given this, cultured crocodile meat peptides-Maillard reaction product (CMP-MRP) with remarkable antioxidant activity was obtained via Maillard reaction of cultured crocodile meat hydrolysates and xylose . The antioxidant activity in vitro and anti-aging activity in vivo of CMP-MRP were investigated. Results indicated that the lifespan and the athletic ability of Drosophila were significantly improved after the administration of CMP-MRP in natural aging, H 2 O 2 - and paraquat-induced models. Furthermore, the antioxidant enzyme activities of Drosophila treated with CMP-MRP were enhanced while the levels of malondialdehyde (MDA) and protein carbonyl (PCO) were reduced in three Drosophila models. With the supplement of 5 mg/mL CMP-MRP in natural aging Drosophila model, the maximum lifespan increased from 61 days to 73 days, athletic ability raised by 95.45%, MDA and PCO reduced by 52.72% and 47.43%, respectively. Taken together, CMP-MRP exhibited outstanding antioxidant and anti-aging capacities in Drosophila models, suggesting that CMP-MRP possesses great potential in the health food and biomedicine fields as a food-derived anti-aging agent.
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CELL PROLIFERATION
·
2023
·
IF 8.5
Juanyu Zhou,Li He,Mengyou Liu,Xiaoxin Guo,Gang Du,La Yan,Zehong Zhang,Zhendong Zhong,Haiyang Chen
Sleep is essential for maintaining health. Indeed, sleep loss is closely associated with multiple health problems, including gastrointestinal disorders. However, it is not yet clear whether sleep loss affects the function of intestinal stem cells (ISCs). Mechanical sleep deprivation and sss mutant flies were used to generate the sleep loss model. qRT-PCR was used to measure the relative mRNA expression. Gene knock-in flies were used to observe protein localization and expression patterns. Immunofluorescence staining was used to determine the intestinal phenotype. The shift in gut microbiota was observed using 16S rRNA sequencing and analysis. Sleep loss caused by mechanical sleep deprivation and sss mutants disturbs ISC proliferation and intestinal epithelial repair through the brain–gut axis. In addition, disruption of SSS causes gut microbiota dysbiosis in Drosophila . As regards the mechanism, gut microbiota and the GABA signalling pathway both partially played a role in the sss regulation of ISC proliferation and gut function. The research shows that sleep loss disturbed ISC proliferation, gut microbiota, and gut function. Therefore, our results offer a stem cell perspective on brain–gut communication, with details on the effect of the environment on ISCs.
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Bioactive Carbohydrates and Dietary Fibre
·
2025
·
IF 3.6
Dima Atehli,Tianyu Qi,Rui Liu,Wan Wang,Qiaomei Zhu,Yuanlin Sun,Qingbin Guo,Ji Kang
Both arabinoxylan (AX) and catechin (CA) have shown promising therapeutic potential for inflammatory bowel disease (IBD). However, the efficacy of their covalent (S, CP) and non-covalent (PM) complexes against IBD remains largely unexplored. This study evaluated the therapeutic effects of AX, CA, and their respective complexes in a Drosophila melanogaster model of dextran sodium sulfate (DSS)-induced colitis. Results demonstrated that covalent AX-CA complexes generated by ultrasonic treatment provided the greatest therapeutic benefits, followed by those produced using cold plasma treatment. These complexes significantly improved survival rates, restored locomotor activity, enhanced metabolic rate, improved intestinal barrier function, markedly reduced the expression of genes associated with JAK/STAT signaling pathway, and concurrently upregulated the expression of genes within the Nrf2/Keap1 pathway.
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NEUROPHARMACOLOGY
·
2019
·
IF 4.367
Chunting Zhang,Weiwei Liang,Hongyong Wang,Yueqing Yang,Tianhang Wang,Shuyu Wang,Xudong Wang,Ying Wang,Honglin Feng
Oxidative stress plays a critical role in mutant copper/zinc superoxide dismutase 1 ( SOD1 )-linked amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease characterized by selective loss of motor neurons . Thus, an anti-oxidative stress remedy might be a promising means for the treatment of ALS. The aim of the present study is to investigate the neuroprotective effects of γ-oryzanol (Orz) and elucidate its relevant molecular mechanisms in mutant hSOD1 -linked Drosophila and cell models of ALS. Orz treatment provided neuroprotection in flies with expression of hSOD1-G85R in motor neurons, as demonstrated by the prolonged survival, improvement of motor deficits, reduced oxidative damage and regulated redox homeostasis when compared with those in controls. Moreover, Orz significantly decreased neuronal apoptosis and upregulated the nuclear factor erythroid 2-related factor 2 (Nrf2)/glutamate-cysteine ligase catalytic subunit (GCLC) antioxidant pathway via activating Akt in hSOD1-G93A -expressing NSC-34 cells. In addition, our results showed that both in vivo and in vitro , Akt served as an upstream regulator of signal transducers and activators of transcription (Stat) 3 stimulated by Orz, which further increased the level of another anti-oxidative stress factor heat-shock protein 70 (HSP70). Altogether, these findings provide evidence that Orz has potential neuroprotective effects that may be beneficial in the treatment of ALS disease with SOD1 mutations.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.7
Yanju Li,Yonghong Bai,Rong Hu,Yan Fan,Junjie Ying,Qin Chi,Yongfang He,Muling He,Kezhan Han,Huijun Hu,Syed Muhammad Zaka,Jun Huang,Yan Li
Drosophila melanogaster Meigen has become a major threat to fruit crops. Decayed banana, bayberry, blueberry, and strawberry strongly attracted D. melanogaster after 60 days, with banana highest (69.17%). Thirteen compounds from the fruits (GC–MS analyzed) were tested for attraction to the adults; five (ethyl linoleate, γ-decalactone, n-decanoic acid, tetradecanoic acid, and ethyl palmitate) were active attractants. Ethyl linoleate reached an attraction rate of 54.43% at doses of 0.01 mg. The combination of ethyl linoleate + γ-decalactone exhibited the highest attraction rates, reaching 25.40% at 0.01 mg and 26.06% at 0.005 mg. Rotten fruits elicited strong electrophysiological (EAG) responses, unlike single/combined compounds. Highest values were: rotten banana 26.39/24.78, ethyl linoleate 1.79/1.30, ethyl linoleate + γ-decalactone 2.29/1.35 (♀/♂). Docking showed ethyl linoleate bound three Odorant-Binding Protein (OBPs) most strongly, while Lush had the strongest overall affinity. This work identifies the attractants in rotten fruits and provides a basis for designing new insect attractants.
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COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
·
2020
·
IF 2.897
Qing Zhang,Li-Chong Hao,Yu Hong
Diisononyl phthalate (DINP) as a phthalate plasticizer is widely used in daily life and production, which shows endocrine disruption effects and has several adverse effects on the normal physiological function. Here, the effects of DINP (0.1%, 0.2%, 0.5%, and 1.0%) (v/v) on the fertility, lifespan, climbing behavior, anti-starvation ability of Drosophila melanogaster and the potential modes of action were investigated. The results showed that DINP impaired fertility in a dose-dependent manner and smaller ovarian volume, lower hatching rate, and fewer offspring was observed at higher concentrations. The effect of DINP on the lifespan showed gender-specific, and mortality was increased after exposure above 0.2% DINP. The climbing ability increased at 0.1% DINP compared with the vehicle group, while it manifested a dose-dependent decrease at higher concentrations. The anti-starvation ability exhibited hormesis after short-term culture and reduced as culture time extending. By measuring the redox status (catalase (CAT) and reactive oxygen species (ROS)) of adult flies after two exposure methods, it was found that DINP induced redox instability, which may explain the above effects at the molecular level. This study provides data to support a comprehensive analysis of DINP potential toxicity and to guide its rational use and management better.
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