Journal of Fungi
·
2023
·Vol. 9
·期 8
·863
·
IF 4.7
Yinggu Wu,Xinyu Li,Li Dong,Tong Liu,Zhengbin Tang,Runmao Lin,Justice Norvienyeku,Mengyu Xing
The litchi downy blight disease of litchi caused byPeronophythora litchiiaccounts for severe losses in the field and during storage. While ample quantitative studies have shown that 6-pentyl-2H-pyran-2-one (6PP) possesses antifungal activities against multiple plant pathogenic fungi, the regulatory mechanisms of 6PP-mediated inhibition of fungal pathogenesis and growth are still unknown. Here, we investigated the potential molecular targets of 6PP in the phytopathogenic oomycetesP. litchiithrough integrated deployment of RNA-sequencing, functional genetics, and biochemical techniques to investigate the regulatory effects of 6PP againstP. litchii. Previously we demonstrated that 6PP exerted significant oomyticidal activities. Also, comparative transcriptomic evaluation ofP. litchiistrains treated with 6PP Revealed significant up-regulations in the expression profile of TOR pathway-related genes, includingPlCytochrome Cand the transcription factorsPlYY1. We also noticed that 6PP treatment down-regulated putative negative regulatory genes of the TOR pathway, includingPlSpm1andPlrhoH12inP. litchii. Protein-ligand binding analyses revealed stable affinities between PlYY1, PlCytochrome C, PlSpm1, PlrhoH12 proteins, and the 6PP ligand. Phenotypic characterization ofPlYY1targeted gene deletion strains generated in this study using CRISPR/Cas9 and homologous recombination strategies significantly reduced the vegetative growth, sporangium, encystment, zoospore release, and pathogenicity ofP. litchii. These findings suggest that 6PP-mediated activation ofPlYY1expression positively regulates TOR-related responses and significantly influences vegetative growth and the virulence ofP. litchii. The current investigations revealed novel targets for 6PP and underscored the potential of deploying 6PP in developing management strategies for controlling the litchi downy blight pathogen.Keywords:P. litchii;6-pentyl-2H-pyran-2-one (6PP);TOR pathway;CRISPR/Cas 9;PlYY1
研究领域:
植物病理学
·
分子生物学
·
真菌学
✓ 已验证
DOI
PubMed
高影响因子
FISH PHYSIOLOGY AND BIOCHEMISTRY
·
2019
·Vol. 45
·期 2
·539-549
·
IF 1.729
Chen Jiaojiao,Zhang Dianfu,Tan Qingsong,Liu Mengmei,Hu Pengcheng
Dietary arginine (Arg) could improve the intestinal structure and absorption of grass carp ( Ctenopharyngodon idellus ); however, the mechanism of Arg on intestinal morphology improvement was unclear. The present study aimed to explain the possible mechanism of the positive effect of Arg on intestinal epithelial cells of grass carp. An in vitro study was conducted through a primary culture model to assess the growth, cell viability, mRNA expressions of TOR signal pathway, and tight junction proteins of enterocytes after culture in the medium with 6 levels of Arg (0, 0.1, 0.2, 0.5, 1.0, and 2.0 mmol/L). The results showed that 0.5 mmol/L Arg improved the cell number and decreased the lactate dehydrogenase and creatine kinase activities in culture medium ( P < 0.05). The alkaline phosphatase activity in cell lysis buffer was depressed by 1 and 2 mmol/L Arg ( P < 0.05). The nitric oxide (NO) content showed an increasing trend with the Arg content ( P < 0.05), whereas the NO synthase activity showed an opposite trend to NO. TOR expression was higher in 0.2 and 0.5 mmol/L groups, whereas S6K1 expression in 1.0 mmol/L and 2.0 mmol/L groups were lower ( P < 0.05). The mRNA expressions of occludin, claudin 3, and claudin c in 0.5 mmol/L group were the highest, while ZO-1 and claudin b expressions were higher in 0.2 and 0.5 mmol/L groups ( P < 0.05). This study indicated that Arg enhanced the growth and integrity of intestinal epithelial cells of grass carp through upregulation of mRNA expression of TOR signal pathway and tight junction proteins at an optimal Arg content of 0.2–0.5 mmol/L.
研究领域:
水产养殖
·
分子生物学
·
营养学
✓ 已验证
DOI
PubMed
高影响因子
FISH PHYSIOLOGY AND BIOCHEMISTRY
·
2020
·Vol. 46
·期 6
·2085-2099
·
IF 2.249
Rong Hua,Lin Fan,Zhang Yunlong,Bi Baoliang,Dou Tengfei,Wu Xiangwei,Aweya Jude Juventus,Wen Xiaobo
Commonly used aquatic feed naturally contains low-level or no hydroxyproline (Hyp). This study was conducted to evaluate the effects of dietary Hyp inclusion on growth performance, body composition, amino acid profiles, blood biochemistry, and the expression of target of rapamycin (TOR) pathway-related genes in juvenile Nibea diacanthus . Fish with similar size (initial body weight, 133.00 ± 2.14 g) were fed six isonitrogenous and isolipidic practical diets supplemented with graded levels of Hyp (0, 5, 10, 15, 20, and 25 g kg −1 of dry matter) for 8 weeks. The results indicated that growth performance and feed utilization were improved with increased levels of dietary Hyp ( P < 0.05), and the optimum amount of dietary Hyp estimated from SGR as 16.6 g kg −1 . The crude protein of whole body and swim bladder and the amino acid composition of muscle and swim bladder were significantly ( P < 0.05) affected by the addition of dietary Hyp, which reflects the important role of feed composition in animal body composition. In addition, the expression levels of mammalian target of rapamycin (TOR) and ribosomal protein S6 kinase1 (S6K1) genes in the liver, muscle, and swim bladder increased with increasing Hyp content of diets, while the mRNA expression level of eukaryotic translation initiation factor 4E-binding protein (4E-BP) gene in these tissues decreased. These results indicated that Hyp improved fish growth and the ability to synthesize proteins, most likely through the TOR pathway. It is suggested that dietary Hyp supplementation is particularly necessary for application in aquatic feed.
研究领域:
水产养殖
·
分子生物学
·
营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BREAST CANCER RESEARCH
·
2025
·Vol. 27
·期 1
·217
·
IF 5.6
Wang Ding,Luo Shulei,Yu Rongji,Wen Doudou,Jiang Hao,Xu Keli,Di Xiaotang,Zhang Shubing
Background Triple negative breast cancer (TNBC), characterized by its aggressive clinical behavior and propensity for distant metastasis, presents critical challenges in therapeutic management. Emerging evidence implicates lipid metabolic reprogramming as a key facilitator of tumor progression and metastatic dissemination. However, the precise molecular mechanisms underlying lipid metabolic dysregulation in TNBC metastasis remain poorly characterized. Our work systematically elucidates the mechanistic role of ALDH3A2 in orchestrating lipid metabolic adaptations that drive breast cancer metastasis. Methods Transcriptomic analysis of clinical datasets identified metastasis-related metabolic regulators. Cellular migration/invasion assays and murine metastasis models were utilized to assess metastatic effects of ALDH3A2. Lipidomic profiling coupled with pathway analysis characterized metabolic alterations. Mechanistic studies integrated western blot analysis with lipid droplet quantification. Computational approaches including structure-based virtual screening and molecular docking simulations were employed for inhibitor discovery. Results ALDH3A2 was significantly upregulated in TNBC clinical specimens and showed significant association with adverse clinical outcomes. Functional validation confirmed that ALDH3A2 potentiates TNBC cell migration/invasion through epithelial-mesenchymal transition (EMT) activation. Metabolic profiling revealed ALDH3A2-driven lipid accumulation, evidenced by increased lipid droplet formation and elevated triglyceride levels. Specifically, arachidonic acid (AA) enrichment was observed in ALDH3A2-overexpressing cells, corresponding to enhanced glycerophospholipid metabolism. Mechanistic studies demonstrated that ALDH3A2-mediated AMP/ATP imbalance suppresses AMPK phosphorylation while activating mTOR/SREBP1 signaling. mTOR inhibition effectively attenuated ALDH3A2-induced lipid metabolic alterations. Importantly, oxaliplatin was identified as a potential therapeutic agent targeting ALDH3A2-mediated AA metabolism to suppress metastasis. Conclusions Our work establishes ALDH3A2 as a pivotal regulator of lipid metabolic reprogramming in TNBC metastasis, providing mechanistic insights into AA-mediated tumor progression. These findings position ALDH3A2 as a promising therapeutic target and prognostic biomarker for TNBC management.
研究领域:
肿瘤学
·
癌症生物学
·
分子生物学
·
代谢学
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信号转导
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Autophagy
·
2018
·
IF 11.1
Lun Zhao,Li Deng,Qing Zhang,Xue Jing,Meng Ma,Bin Yi,Jing Wen,Chaozhi Ma,Jinxing Tu,Tingdong Fu,Jinxiong Shen
Sulfonylurea (SU) herbicides inhibit branched-chain amino acid (BCAA) biosynthesis by targeting acetolactate synthase. Plants have evolved target-site resistance and metabolic tolerance to SU herbicides; the GCN2 (general control non-repressible 2) pathway is also involved in SU tolerance. Here, we report a novel SU tolerance mechanism, autophagy, which we call ‘homeostatic tolerance,’ is involved in amino acid signaling in Arabidopsis. The activation and reversion of autophagy and GCN2 by the SU herbicide tribenuron-methyl (TM) and exogenous BCAA, respectively, confirmed that TM-induced BCAA starvation is responsible for the activation of autophagy and GCN2. Genetic and biochemical analyses revealed a lower proportion of free BCAA and more sensitive phenotypes in atg5, atg7, and gcn2 single mutants than in wild-type seedlings after TM treatment; the lowest proportion of free BCAA and the most sensitive phenotypes were found in atg5 gcn2 and atg7 gcn2 double mutants. Immunoblotting and microscopy revealed that TM-induced activation of autophagy and GCN2 signaling do not depend on the presence of each other, and these 2 pathways may serve as mutually compensatory mechanisms against TM. TM inhibited the TOR (target of rapamycin), and activated autophagy in an estradiol-induced TOR RNAi line, suggesting that TM-induced BCAA starvation activates autophagy, probably via TOR inactivation. Autophagy and GCN2 were also activated, and independently contributed to TM tolerance in plants conferring metabolic tolerance. Together, these data suggest that autophagy is a proteolytic process for amino acid recycling and contributes to GCN2-independent SU tolerance, probably by its ability to replenish fresh BCAA.
研究领域:
植物生物学
·
分子生物学
·
植物病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
·
2021
·Vol. 45
·期 4
·e13602
·
IF 2.72
Yang Yue,Mengting Wang,Zhangping Feng,Yanyun Zhu,Jianchu Chen
Rice protein hydrolysates (RPH) prepared by enzymatic hydrolysis have plenty of bioactive functions. Herein, we investigated the antiaging effect of RPH on Drosophila melanogaster (fruit fly) and its mechanisms. According to the results, fruit flies reared on 0.2% and 3.2% RP-supplement diet prolonged their average lifespan, 50% survival days, and the maximum lifespan, together with increasing superoxide dismutase, manganese superoxide dismutase, and catalase activity compared to those reared on basal diet. Further studies showed the lifespan extending effect of RPH was regulated by the cooperation with the intrinsic stress protection system (Nrf2/Keap1), age-related signaling pathway (TOR, S6K) and the expression of longevity genes (methuselah). In conclusion, the lifespan extending effect of RPH makes it possible to be applied in food and healthcare industry. Practical applications In previous studies, rice protein hydrolysates (RPH) have been found to have strong antioxidant properties. But so far, most researches focused on the preparation, identification and in vitro antioxidant experiments of RPH, and there is still a lack of researches on its effect on the antioxidant system of fruit flies and the antiaging of fruit flies. This report showed that RPH enhanced the antioxidant system and prolonged the lifespan of Drosophila, which might help us rationally use rice peptides in functional foods.
研究领域:
衰老研究
·
营养科学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Pharmaceuticals
·
2026
·Vol. 19
·期 6
·819
·
IF 5.7
Xue Jiang,Jicheng Yang,Ying Zhang,Yusheng Zhang,Qingqing Li,Shaoqi Song,Zhen Ouyang,Hongjun Yang,Xianyu Li,Luqi Huang
Background:Neuroinflammation and gut–brain axis (GBX) dysregulation are key pathological drivers of stress-related neuropsychiatric disorders. Zhi-Zi-Chi Decoction (ZZCD), a classic Traditional Chinese Medicine (TCM) formula, has been clinically used to alleviate mental disturbances via the TCM principle of “clearing heat and relieving restlessness.” Still, its modern neuroprotective mechanisms, especially its links to gut microbiota and central signaling pathways, remain incompletely elucidated.Purpose:This study aimed to systematically investigate the therapeutic effects of ZZCD on chronic restraint stress (CRS)-induced neurodysfunction in mice and clarify its mechanisms from the perspectives of TCM theory, material basis, gut microbiota–metabolite axis, and central signaling pathways.Method:CRS mice were treated with ZZCD or protocatechuic acid. Behavioral tests evaluated depression- and anxiety-like behaviors. UHPLC-Q-TOF/MS identified ZZCD’s chemical constituents; 16S rRNA sequencing and untargeted metabolomics analyzed gut microbiota and metabolite changes. Western blot, immunofluorescence, and proteomics examined neuroinflammation, microglial polarization, and signaling pathway activity (PI3K/Akt/mTOR, AMPK).Results:ZZCD reversed CRS-induced depression- and anxiety-like behaviors and suppressed neuroinflammation. Mechanistically, UHPLC-Q-TOF/MS identified 424 ZZCD constituents, with prenol lipids, organooxygen compounds, and flavonoids as the most abundant. ZZCD reversed CRS-induced imbalance in gut microbiota, reducing pro-inflammatory Prevotella and enriching beneficial Lactobacillus, and mediated the enrichment of the prebiotic metabolite PCA in colonic and serum samples, which crossed the blood–brain barrier (BBB) to exert neuroprotection. Additionally, ZZCD and PCA normalized the PI3K/Akt/mTOR pathway and activated AMPK, promoting M2 microglial polarization and restoring synaptic plasticity.Conclusions:ZZCD exerts antidepressant effects by a gut-microbiota-dependent modulation of PCA-PI3K/Akt/mTOR and AMPK dual axes that converts microglia from M1 to M2, providing ethnopharmacological evidence and a mechanistic rationale for its clinical application in major depressive disorder.
✓ 已验证
DOI
高影响因子
FISH & SHELLFISH IMMUNOLOGY
·
2023
·
IF 4.7
Xinyu Wu,Yue Xin,Yeyun Ma,Kaixin Ping,Qiulu Li,Ying Sun,Zunhan Hu,Jingquan Dong
Abamectin (ABM) abuse contaminated aquatic environment and posed a potential threat to fish health as well as public safety. Silybin (SIL), a flavonoid , has been widely used as a novel feed additive to promote fish health. This research was to explore the potential antagonistic mechanism between ABM and SIL on brain and liver toxicity was investigated in common carp . Sixty carp were divided into four groups at random: the Control group, the SIL group, the ABM group, and ABM + SIL group. This experiment lasted for 30 d. According to behavioral observation, the detection of levels of acetylcholinesterase (AchE), iron, and mRNA expression levels of blood-brain barrier (BBB) related tight junction proteins (ZO-1, Claudin7, Occludin , MMP2 , MMP9 , and MMP13) in brain tissues, it was found that SIL relieved neurobehavioral disorders caused by ABM-induced BBB destruction in carp. H&E staining showed SIL mitigated nerve injury and liver injury caused by ABM. Oil Red O staining and liver-related parameters showed that SIL alleviated hepatotoxicity and lipid metabolism disorder caused by ABM exposure. Furthermore, this work also explored the specific molecular mechanism of SIL in liver protection and neuroprotection. It was shown that SIL lowered ROS levels in liver and brain tissues via the GSK-3β/TSC2/TOR pathway. Simultaneously, SIL inhibited NF-κB signaling pathway and played an anti-inflammatory role. In conclusion, we believed that SIL supplementation has a protective effect on the brain and liver by regulating oxidative stress and inflammation.
研究领域:
水生毒理学
·
药理学
·
分子生物学
·
兽医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2023
·Vol. 14
·期 4
·2149-2161
·
IF 6.1
Ai-Wen Kang,Chi Sun,Hai-Tao Li,Kun Zhong,Xu-Hui Zeng,Zhi-Feng Gu,Bing-Qian Li,Xiao-Ning Zhang,Jian-Lin Gao,Tian-Xing Chen
Lifespan longevity has attracted increasing attention with societal development. To counter the effects of aging on longevity, we focused on the natural chemicals of plants. In this study, we investigated the effects of puerarin supplementation on the lifespan of Drosophila melanogaster. Puerarin supplementation significantly extended the lifespan of D. melanogaster at 60 μM and 120 μM by upregulating proteasome subunit beta 5 (prosbeta5) and sirtuin-1 (Sirt1). However, puerarin-induced longevity of male flies (F0 generation) may not be passed on to descendants. Additionally, a puerarin diet for 10 and 25 days did not influence the body weight and food intake of male Canton-S flies. Puerarin significantly improved the climbing ability, starvation resistance, and oxidation resistance of male flies by upregulating the expression of Shaker, catalase (CAT), superoxide dismutase 1 (SOD1), and Methuselah, and downregulating poly [ADP-ribose] polymerase (PARP-1) and major heat shock 70 kDa protein Aa (HSP70). Moreover, 120 μM puerarin supplementation for 25 days significantly increased adenosine 5′ triphosphate (ATP) content by increasing adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) levels. Additionally, the puerarin diet for 25 days suppressed male fecundity in male flies by decreasing the levels of Bam and Punt. Mechanistically, puerarin enhanced lysosome-involved autophagy by promoting the expression of lysosome markers [β-galactosidase and lysosomal associated membrane protein 1 (LAMP1)], and elevating the levels of autophagy-related genes, including autophagy-associated gene 1 (ATG1), ATG5, and ATG8b. However, puerarin decreased the phosphorylation of the target of rapamycin (TOR) protein. In conclusion, puerarin is a promising compound for improving the longevity of D. melanogaster by activating autophagy.
研究领域:
衰老研究
·
药理学
·
分子生物学
·
遗传学
✓ 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）