Biochimica et Biophysica Acta-Gene Regulatory Mechanisms
·
2018
·
IF 5.179
Quan Gan,Xinwei Zhang,Daobo Zhang,Liang Shi,Yue Zhou,Tongtong Sun,Song Jiang,Junshan Gao,Yan Meng
Sucrose is the most commonly transported sugar in plants and is easily assimilated by insects to fulfill the requirement of physiological metabolism. BmSuc1 is a novel animal β-fructofuranosidase (β-FFase, EC 3.2.1.26) - encoding gene that was firstly cloned and identified in silkworm , Bombyx mori . BmSUC1 was presumed to play an important role in the silkworm-mulberry enzymatic adaptation system by effectively hydrolyzing sucrose absorbed from mulberry leaves. However, this has not been proved with direct evidence thus far. In this study, we investigated sucrose hydrolysis activity in the larval midgut of B. mori by inhibition tests and found that sucrase activity mainly stemmed from β-FFase, not α-glucosidase. Next, we performed shRNA-mediated transgenic RNAi to analyze the growth characteristics of silkworm larvae and variations in glycometabolism in vivo in transgenic silkworms. The results showed that in the RNAi- BmSuc1 transgenic line, larval development was delayed, and their body size was markedly reduced. Finally, the activity of several disaccharidases alone in the midgut and the sugar distribution, total sugar and glycogen in the midgut, hemolymph and fat body were then determined and compared. Our results demonstrated that silencing BmSuc1 significantly reduced glucose and apparently activated maltase and trehalase in the midgut. Together with a clear decrease in both glycogen and trehalose in the fat body, we conclude that BmSUC1 acts as an essential sucrase by directly modulating the degree of sucrose hydrolysis in the silkworm larval midgut, and insufficient sugar storage in the fat body may be responsible for larval malnutrition and abnormal petite phenotypes.
研究领域:
昆虫学
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分子生物学
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DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Yueyang Guo,Zhuang Hu,Linyue Bai,Yanjun Tang,Jingyi Hu,Qianqian Zhang,Jiali Liu,Siqi Feng
Gastric cancer, a leading cause of cancer-related mortality, has a median survival of just 15 months in advanced stages and currently lacks effective treatment options. Neddylation blockade is a promising therapeutic strategy, yet its clinical application faces challenge with the emergence of drug resistance. Currently, the underlying mechanisms behind the drug resistance are not fully understood. Our study uncovers the link between MLN4924-induced metabolic reprogramming and its antitumor efficacy in gastric cancer cells. We first demonstrated that MLN4924, a neddylation blocker, has multiple effects on gastric cancer cell growth, notably inducing mitochondrial damage. Untargeted metabolomic analysis revealed that MLN4924 enhances glucose utilization in gastric cancer cells in a concentration-dependent manner. Mechanistically, MLN4924 reduces the neddylation of cullin2, thereby inhibiting the degradation of HIF-1α. This leads to the accumulation of HIF-1α, which upregulates GLUT1 levels and facilitates increased glucose uptake. This metabolic adaptation allows gastric cancer cells to maintain their energy supply despite mitochondrial impairment. Based on the increased glucose dependency following neddylation inhibition by MLN4924, we propose a co-targeting strategy with GLUT1 inhibition, which significantly improves therapeutic efficacy in vitro and in vivo models without safety risks. This dual-targeting approach represents a potent new strategy for gastric cancer treatment.
研究领域:
肿瘤学
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代谢组学
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药理学
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DOI
PubMed
高影响因子
Frontiers in Public Health
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2025
·
IF 3.4
Xiaomei Cheng,Haifeng Gao,Qiaojun Li,Naifan Zhang,Ying Lu
Background: Polycyclic aromatic hydrocarbons (PAHs) are a class of large organic compounds that persist in the environment and are classified as an important subset of persistent organic pollutants (POPs). This study aimed to assess PAH exposure in pregnant women and newborns in Haikou City, China, and evaluate their impact on glycolipid metabolism.Methods: A total of 300 pregnant women and their newborns were selected for the study between May 2022 and December 2023. Data on lifestyle and dietary habits were collected, and PAH levels in venous blood and umbilical cord blood were measured using gas chromatography-mass spectrometry. Glycolipid metabolism indicators, including fasting plasma glucose (FPG), triglycerides (TG), total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL), were also measured. Correlation and regression analyses were conducted to explore the relationships between PAH exposure and metabolic indicators.Results: Thirteen PAHs were detected in both maternal and cord blood. The median concentrations of ΣPAHs (the total concentration of the 16 detected PAHs) were 11.211 μg/L in maternal blood and 10.921 μg/L in newborns. Significant correlations were observed between PAH exposure and glycolipid metabolism, with PAH exposure linked to reduced levels of TC and TG. Factors such as proximity to roads, cooking fuel type, and dietary habits influenced PAH levels. Higher education levels were associated with lower PAH concentrations, whereas living near roads and using gas as cooking fuel increased exposure.Conclusion: There is a notable risk of PAH exposure in pregnant women and newborns in Haikou, influenced by environmental and lifestyle factors. PAH exposure during pregnancy may affect glycolipid metabolism in both mothers and newborns, highlighting the need for interventions to reduce exposure.
研究领域:
环境科学
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医学
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公共卫生
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DOI
PubMed
高影响因子
POSTHARVEST BIOLOGY AND TECHNOLOGY
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2021
·
IF 5.537
Xinguang Fan,Zhilei Du,Xinzhi Cui,Wenju Ji,Jiteng Ma,Xiulian Li,Xiaomei Wang,Handong Zhao,Bangdi Liu,Fengjun Guo,Hansheng Gong
Apricot is highly susceptible to chilling injury during low temperature storage, while methyl salicylate (MeSA) can alleviate chilling injury and enhance the postharvest quality of fruit. The apricots were preharvest sprayed twice with 0.05 mmol L −1 , 0.1 mmol L −1 and 0.2 mmol L −1 of MeSA solution, and then were harvested and stored at 2 °C (humidity of 70 %). After cold storage for every 4 d, apricots were transferred to 20 °C for 2 d to determine the fruit quality. Our results indicated that 0.2 mmol L −1 MeSA treatment exhibited the best efficacy. Preharvest MeSA treatment could reduce decay rate and chilling injury (CI) index, and maintain firmness, soluble solid content (SSC), organic acids and antioxidant capacities at a relative higher level. Preharvest MeSA treatment inhibited the increase of electrolyte leakage, malondialdehyde (MDA) and H 2 O 2 content in apricot. The chilling temperature of 2 °C could lead to the degradation of sucrose to fructose and glucose in apricot. At the same time, preharvest MeSA treatment effectively alleviated CI symptoms of apricot by reducing the degradation rate. The enhanced chilling tolerance of apricot treated with MeSA could be affected by the increased sucrose content, which was regulated by the higher activities of sucrose phosphate synthase (SPS) and sucrose synthase-synthesis (SS-S), and the lower activities of acid invertase (AI), neutral invertase (NI) and sucrose synthase-cleavage (SS-C). We proposed that preharvest MeSA treatment could enhance the chilling tolerance by regulating sugar metabolism and further improve the postharvest quality of apricot during low temperature storage.
研究领域:
园艺学
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植物生理学
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DOI
高影响因子
Marine Drugs
·
2023
·Vol. 21
·期 10
·518
·
IF 5.4
Qianxia Lin,Yueping Guo,Jie Li,Shuqi He,Yan Chen,Huoxi Jin
Oxidative stress and abnormal glucose metabolism are the important physiological mechanisms in the occurrence and development of diabetes. Antioxidant peptides have been reported to attenuate diabetes complications by regulating levels of oxidative stress, but few studies have focused on peptides from marine bone collagen. In this study, we prepared the peptides with a molecular weight of less than 1 kD (HNCP) by enzymolysis and ultrafiltration derived fromHarpadon nehereusbone collagen. Furthermore, the effects of HNCP on blood glucose, blood lipid, liver structure and function, oxidative stress, and glucose metabolism were studied using HE staining, kit detection, and Western blotting experiment in streptozocin-induced type 1 diabetes mice. After the 240 mg/kg HNCP treatment, the levels of blood glucose, triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) in streptozotocin-induced diabetes mice decreased by 32.8%, 42.2%, and 43.2%, respectively, while the levels of serum insulin and hepatic glycogen increased by 142.0% and 96.4%, respectively. The antioxidant enzymes levels and liver function in the diabetic mice were markedly improved after HNCP intervention. In addition, the levels of nuclear factor E2-related factor 2 (Nrf2), glucokinase (GK), and phosphorylation of glycogen synthase kinase-3 (p-GSK3β) in the liver were markedly up-regulated after HNCP treatment, but the glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase1 (PEPCK1) were down-regulated. In conclusion, HNCP could attenuate oxidative stress, reduce blood glucose, and improve glycolipid metabolism in streptozocin-induced type 1 diabetes mice.Keywords:diabetes;collagen peptides;Nrf2;glucose metabolism;oxidative stress
研究领域:
药理学
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生物化学
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糖尿病研究
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DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
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2024
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IF 5.6
Yina Jia,Jianrong Tang,Yunfu Dang,Yizhou Yang,Shan He,Yue Jiang,Yong Wang,Juntao Feng,Zhiqing Ma,Xili Liu,He Yan
Lansiumamide B (LB) is a cinnamamide alkaloid isolated from Clausena lansium seeds. The compound is the main antifungal ingredient found in C. lansium . In this paper, the antifungal activity of LB against 10 plant pathogenic fungi was evaluated and found that it was the most effective to Rhizoctonia solani (EC 50 = 2.99 μg/mL). The compound also exhibits certain protective (53.06%) and curative (71.01%) activities against R. solani at 800 μg/mL. The mechanism of action of LB was further elucidated through physiological and biochemical experiments, mycelial morphology and ultrastructure observations, and transcriptomics studies with R. solani as the experimental strain. SEM and TEM observation showed that it caused abnormal mycelium growth, extravasation of contents and cell wall degradation. Physiological and biochemical tests showed that LB treatment had no significant effect on the cellular respiration of mycelium , but it could increase the membrane permeability , cause the leakage of intracellular electrolyte, reduce the content of extracellular polysaccharide and chitin in cell wall and increased the contents of intracellular reducing sugar. The results of transcriptome sequencing analysis showed that LB had significant effects on polysaccharide and oligosaccharide related metabolic pathways, such as starch and sucrose metabolic pathways, galactose metabolic pathways, and amino sugar metabolic pathways. Furthermore, LB treatment increased the specific enzyme activity of α-1, 4-glucanase, α-1,6-glucanase, cellulase and maltase of R. solani in vivo . Comprehensive analysis of the above experimental results shows that LB induces and regulates the degradation of polysaccharides and oligosaccharides of R. solani at the transcriptional level, thereby destroying the cell wall structure and ultimately leading to the death of fungi.
研究领域:
植物化学
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真菌学
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分子生物学
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DOI
高影响因子
FEBS LETTERS
·
2018
·Vol. 593
·期 2
·175-186
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IF 2.999
Shengnan Yang,Yuan Zhang,Fukui Shen,Xiaoyao Ma,Man Zhang,Yuanyuan Hou,Gang Bai
Baicalin is one of the main flavonoids of the dried root of Scutellaria baicalensis Georgi and is reported to exert beneficial effects on the regulation of glucose/lipid metabolism. However, understanding its specific target and unique mechanism for improving glucose utilization is a challenge. In this paper, target fishing with a baicalin probe reveals that baicalin interacts with AKT. An immunofluorescence assay further demonstrates the colocalization of baicalin with AKT in the cytoplasm. A competitive test and virtual docking show that baicalin might bind to the pleckstrin homology domain of AKT. This specific binding hampers AKT membrane translocation, activates the phosphorylation of AKT on Ser473, induces the downstream glycogen synthase kinase 3β activation, and affects glycogen synthesis.
研究领域:
药理学
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分子生物学
·
代谢
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2024
·
IF 8.2
Chanlin Fang,Yundong Yu,Shanshan Di,Xinquan Wang,Yuanxiang Jin
The tire antioxidant 6PPD has garnered extensive attention due to its widespread presence in the environment and the harmful effects of its transformation products on aquatic organisms. 6PPD has been detected in airborne dust, and it can enter mammals through inhalation exposure. While the toxic effects of 6PPD exposure have been reported in mammals, its effects on hepatic metabolism still remain poorly understood. Here, we collected the serum and liver samples at 1, 6, and 72 h following a single oral exposure of 100 mg/kg body weight (bw) 6PPD, respectively. We also investigated changes in serum and hepatic physiological indicators and metabolites, correspondingly. Results indicated that single time oral exposure a high dose of 6PPD did not significantly affect the physiological indexes of rats within a short time frame. However, untargeted metabolomics analysis of the metabolites in the liver at 1, 6, and 72 h revealed that the number of differential expression metabolites gradually increased over time and the most affected substances were lipids and lipid-like molecules. Interestingly, the KEGG pathway enrichment analysis indicated that 6PPD disrupted the riboflavin metabolism, leading to a significant decrease in FMN levels at all time points. In addition, the hepatic glucose metabolism was significantly affected at 6 and 72 h after oral administration. Taken together, short-term exposure to 6PPD disturbed lipid and riboflavin metabolism and gradually affected glucose metabolism in the liver of rats. These findings revealed the impacts of 6PPD on the hepatic metabolism in animals, and also offered some important insights into its toxicology and health risk.
研究领域:
毒理学
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环境科学
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代谢组学
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DOI
PubMed
高影响因子
PLoS One
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2014
·Vol. 9
·期 4
·e92962
·
IF 3.534
Yunhai Dai,Xiaopeng Xiong,Gang Huang,Jianjun Liu,Shile Sheng,Hongjian Wang,Wenxin Qin
A unique bioenergetic feature of cancer, aerobic glycolysis is considered an attractive therapeutic target for cancer therapy. Recently, dichloroacetate (DCA), a small-molecule metabolic modulator, was shown to reverse the glycolytic phenotype, induce reactive oxygen species (ROS) generation, and trigger apoptosis in various tumor cells. In this work, the capacity of DCA to enhance Adriamycin (ADM) efficacy in hepatoma cells by modulating glucose metabolism and redox status was evaluated. Two human hepatoma (HCC-LM 3 and SMMC-7721) and a normal liver (LO 2 ) cell lines were treated with DCA or ADM alone, or in combination. Exposure of hepatoma cells to DCA/ADM combination resulted in significantly decreased cell viability and increased percentage of apoptotic cells as well as intracellular ROS levels, in comparison with treatment with DCA or ADM alone. However, simultaneous treatment with the thiol antioxidant N-acetylcysteine (NAC, 10 mmol/L) reduced the elevated ROS levels and protected hepatoma cells from the cytotoxic effects of DCA/ADM combination. L-buthionine-[S,R]-sulfoximine, an inhibitor of glutathione synthesis, enhanced hepatoma cell sensitivity to DCA/ADM combination. Interestingly, treatment with DCA/ADM combination did not significantly increase cytotoxicity in normal hepatocytes in comparison with the drugs administered individually. Finally, DCA reduced tumor growth and enhanced ADM efficacy on HCC-LM 3 hepatoma in mice. Overall, our data suggest that DCA enhances ADM cytotoxicity in hepatoma cells by increasing intracellular ROS levels and provide a strong biochemical rationale for the use of DCA in combination with ADM for treatment of hepatoma.
研究领域:
肿瘤学
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生物化学
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药理学
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产品关联
DOI
PubMed
高影响因子
POSTHARVEST BIOLOGY AND TECHNOLOGY
·
2021
·
IF 5.537
Xiaoya Tao,Qiong Wu,Jiayin Li,Luyun Cai,Linchun Mao,Zisheng Luo,Li Li,Tiejin Ying
Sucrose metabolism is a fundamental process during tomato ripening. Studies have shown the role of the phytohormone methyl jasmonate (MeJA) in tomato fruit ripening. However, the role of MeJA in regulating sucrose metabolism in tomato is still unclear. In this study, mature green cherry tomato fruit were infiltrated with MeJA (0.5 mM) or sterile deionized water (control). The changes in color, firmness, and ethylene production in fruit, the contents of sucrose, glucose and fructose, and the enzymatic activities and the expression levels of key genes associated with sucrose metabolism were determined periodically during a storage period of 16 d. MeJA-treated fruit showed a significant acceleration in ripening, with higher a* value and ethylene production and lower firmness. MeJA treatment enhanced sucrose phosphate synthase (SPS) activity, whereas it inhibited acid invertase (AI) and neutral invertase (NI) activities. These changes in enzyme activities together resulted in a significantly higher sucrose content and lower glucose and fructose contents. Furthermore, exogenous MeJA upregulated the gene expression levels of sucrose-phosphate synthase1–4 ( SPS1 - 4 ) and sucrose-phosphate phosphatase2 ( SPP2 ), which were associated with sucrose biosynthesis, and downregulated those related to sucrose degradation, except for sucrose synthase2 ( SUS2 ) and SUS3 . The findings indicated that exogenous MeJA might alter sucrose metabolism during tomato ripening by regulating the enzymatic activities and gene expression levels. This research provides valuable information to elucidate the mechanisms via which MeJA regulates tomato sucrose metabolism.
研究领域:
植物学
·
分子生物学
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产品关联
DOI
高影响因子
MOLECULAR PSYCHIATRY
·
2025
·
IF 10.1
Qin Qian,Li Mengyue,Fan Linlin,Zeng Xin,Zheng Danyang,Wang Han,Jiang Yutong,Ma Xinrui,Xing Lei,Wu Lijie,Liang Shuang
Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder. The microglia activation is a hallmark of ASD, which involves increased glycolysis. Elevated glycolysis regardless of oxygen availability, known as “Warburg effect”, is crucial to pathogenesis in neuropsychiatric disorders. Psychiatric risk gene MIR137 plays an important role in neurogenesis and neuronal maturation, but the impact on neuroinflammation and glucose metabolism remains obscure. Extracellular vesicles (EVs) can delivery miR-137 crossing the blood-brain barrier. Meanwhile, EVs can help miR-137 avoid being rapidly degraded by endogenous nucleases. Here, after first detecting miR-137 decreased both in the peripheral blood of individuals with ASD and the serum and cerebellum of BTBR mice, we demonstrated that microglia activation, the level of lactate and key enzymes (HK2, PKM2 and LDHA) involved in glycolysis were increased significantly in BTBR mice. Of particular note, EVs engineered by rabies virus glycoprotein (RVG) could promote the miR-137 (RVG-miR137-EVs) targeted to the brain accurately, and alleviated autism-like behaviors. Pro-inflammatory activation of BTBR mice was considerably inhibited by RVG-miR137-EVs via tail vein administration, accompanied by decreased lactate production. Mechanically, these effects were attributed to TLR4 , the key target gene, which was regulated by miR-137. The TLR4/NF-κB pathway was inhibited, subsequently reducing HIF-1α and repressing the transcription of HK2, PKM2 and LDHA involved in glycolysis. Pharmacological inhibition of glycolysis and TLR4 attenuated microglial activation and lactate production, ultimately improved autism-like behaviors of BTBR mice. In conclusion, our results indicated that miR-137 could alleviate autism-like behaviors by HIF-1α-mediated adaptive metabolic changes in glycolysis and neuroinflammation.
研究领域:
神经科学
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分子生物学
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医学
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DOI
PubMed
高影响因子
JOURNAL OF FISH BIOLOGY
·
2024
·
IF 1.7
Leya Qu,Liping Yang,Yiran Wang,Shaoyang Zhi,Mengjuan Zhao,Jinrui Xiong,Xiao Yan,Chaobin Qin,Guoxing Nie
Isthmin-1 (Ism1) plays roles in glucose uptake in mammals as an adipokine. To investigate its role in the glucose metabolism of common carp ( Cyprinus carpio. L), the Ism1 sequence was cloned, and its expression and distribution in tissues were detected. In addition, we prepared and purified the recombinant Ism1 protein using the E. coli expression system and assessed changes in the expression of key genes related to glucose metabolism through both in vivo injection experiments and primary hepatocyte experiments in vitro. The results revealed that the open reading frame of Ism1 was 1377 bp long, encoding 458 amino acids. Similarity analysis indicated that Ism1 exhibited a close evolutionary relationship with goldfish ( Carassius auratus ), sharing 98.35% amino acid similarity. Ism1 was expressed in all tissues of common carp, with the highest level observed in the heart, followed by the gill, head kidney, and hepatopancreas. Distinct patterns of Ism1 expression were identified during the oral glucose tolerance test and long-term high-carbohydrate and high-fat diet feeding experiments. In vivo studies demonstrated that the serum glucose concentration was reduced on treatment with Ism1, accompanied by a significant upregulation of mRNA levels for gk , hk , and pfk genes in hepatopancreas; conversely pepck and g6pase mRNA levels were significantly downregulated in the hepatopancreas under these conditions as well. Furthermore, our primary hepatocyte experiment confirmed that Ism1 could inhibit pepck and g6pase mRNA expression, while promoting gk , hk , and pfk mRNA expression levels. In conclusion, Ism1, in common carp, could participate in the glucose metabolism, which provides essential information for future studies on the function of Ism1.
研究领域:
分子生物学
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生理学
·
水产养殖
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DOI
PubMed
高影响因子
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