BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Jiani Zhan,Yijia Chen,Yuying Liu,Yunqiu Chen,Zhiyao Li,Xuewen Li,Zhenning He,Fangzhou Meng,Xiaoyang Qian,Lili Yang,Qing Yang
Ferroptosis is a type of cell death marked by iron-dependent lipid peroxide accumulation. Indoleamine 2,3-dioxygenase 1 (IDO1), a key enzyme in the catabolism of tryptophan through kynurenine pathway, participates in the development of multiple tumor types. However, the role of IDO1 in tumor ferroptosis is unclear. In this study, we identified IDO1 as a key regulator of ferroptosis in lung cancer. With Erastin-treated lung cancer cells, we found that IDO1 inhibited ferroptosis, reduced the generation of lipid peroxide and ROS. Mechanistically, IDO1 promoted the expression of nuclear factor erythroid 2-related factor 2 (NRF2) through activating aryl hydrocarbon receptor (AhR) pathway. IDO1 up-regulated the expression of solute carrier family 7 member 11 (SLC7A11) and the activity of pentose phosphate pathway (PPP) via AhR-NRF2 axis, promoted the production of reduced nicotinamide adenine dinucleotide phosphate (NADPH) and glutathione (GSH), thereby inhibiting ferroptosis. Moreover, combined treatment with IDO1 inhibitor and Erastin inhibited tumor growth, down-regulated SLC7A11 expression and PPP activity, promoted tumor ferroptosis in lung cancer-bearing mice. In conclusion, this study revealed the function of IDO1 in lung cancer ferroptosis and provided a new strategy for lung cancer therapy.
研究领域:
肿瘤学
·
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
RENEWABLE ENERGY
·
2022
·
IF 8.634
Lincai Peng,Xin Huangfu,Yao Liu,Huai Liu,Junhua Zhang
The processing of C6 sugars to alkyl levulinate (AL), a versatile biomass-derived building block, can be readily implemented via the straightforward acid-catalyzed reaction in alcohol medium while it remains a challenge to produce AL from C5 sugars in the one-pot procedure over a monolithic catalyst. In this contribution, a budget and multifunctional natural lignocellulose welded Zr–Al bimetallic hybrid (ZrAl@CS-MSA) has been successfully constructed with crude corn stalk as a sustainable support. The becoming Lewis and Brønsted acid sites of ZrAl@CS-MSA catalyst guarantee a high AL yield of 54.3% from xylose via a one-pot process in a renewable n -butanol medium. Experimental findings revealed that the sulfonic group of ZrAl@CS-MSA plays a significant role in the xylose dehydration, furfuryl alcohol etherification and alcoholysis reactions while Zr species is in charge of the transfer hydrogenation of furfural. The Al species enclosed in ZrAl@CS-MSA can regulate its Brønsted and Lewis acidity, accelerating the etherification and alcoholysis reactions as well as alleviating the over hydrogenation of AL. This work opens a green, sustainable and reliable avenue for producing C5 sugar-based AL using natural lignocellulose-related multifunctional catalysts.
研究领域:
催化化学
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生物质能
·
绿色化学
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产品关联
DOI
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2025
·
IF 4.2
Qiuxia Yu,Wenwen Tan,Xingdong Ma,Lieqiang Xu,Guoshu Lin,Juanjuan Cheng,Qingfeng Xie,Yuhong Liu,Yucui Li,Yanfang Xian,Zhixiu Lin,Jiannan Chen,Ziren Su,Xiaobo Yang,Jianhui Xie
Fructose is a nutrient used widely and indiscriminately as a sweetener in various types of foods and beverages. Accumulating evidence suggests that dietary fructose has a close relationship with metabolic diseases like hyperuricemia (HUA). However, the role and metabolic fate of fructose intake remain elusively obscure. The present work made a pioneering endeavor to unravel the potential mechanistic link between prolonged fructose overconsumption and the incidence of HUA. High-fructose (30%) free drinking was provided to rats for 17 weeks. Results indicated that long-term high-fructose intake remarkably increased the levels of uric acid, creatinine, and urea. Besides, mild renal alteration induced by high fructose was observed in the hyperuricemic rats. Instead of activating ketohexokinase, high-fructose intake activated the pentose phosphate pathway (PPP) to produce abundant ribose 5-phosphate and phosphoribosyl pyrophosphate. The de novo purine biosynthesis (DNPB) was activated to produce purines and accelerate the purine cycle. High-fructose intake significantly enhanced the expression of core enzymes of DNPB and changed the purinosome formation and forming areas. Furthermore, up-regulation of xanthine oxidase (XOD) promoted the purine metabolism, resulting in increased levels of inosine monophosphate, inosine, hypoxanthine, and xanthine. Besides, the targeted metabolome analysis also showed that fructose metabolism triggered bioenergetic alteration with the consumption of ATP and a surge in NAD + and NADH. Hence, chronic ingestion of high-fructose contributed to HUA, which was intimately associated with activation of original biosynthetic and metabolic pathways of endogenous purine simultaneously mediated by PPP, DNPB, and XOD and accompanied by bioenergetic alteration.
研究领域:
营养学
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代谢生物学
·
医学
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产品关联
DOI
PubMed
高影响因子
METABOLIC ENGINEERING
·
2024
·
IF 6.8
Yajing Zhang,Tao Sun,Linqi Liu,Xupeng Cao,Weiwen Zhang,Wangyin Wang,Can Li
Microbial CO 2 fixation into lactic acid (LA) is an important approach for low-carbon biomanufacturing. Engineering microbes to utilize CO 2 and sugar as co-substrates can create efficient pathways through input of moderate reducing power to drive CO 2 fixation into product. However, to achieve complete conservation of organic carbon, how to engineer the CO 2 -fixing modules compatible with native central metabolism and merge the processes for improving bioproduction of LA is a big challenge. In this study, we designed and constructed a solar formic acid/pentose (SFAP) pathway in Escherichia coli , which enabled CO 2 fixation merging into sugar catabolism to produce LA. In the SFAP pathway, adequate reducing equivalents from formate oxidation drive glucose metabolism shifting from glycolysis to the pentose phosphate pathway. The Rubisco-based CO 2 fixation and sequential reduction of C3 intermediates are conducted to produce LA stoichiometrically. CO 2 fixation theoretically can bring a 20% increase of LA production compared with sole glucose feedstock. This SFAP pathway in the integration of photoelectrochemical cell and an engineered Escherichia coli opens an efficient way for fixing CO 2 into value-added bioproducts.
研究领域:
合成生物学
·
微生物学
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产品关联
DOI
PubMed
高影响因子
ChemistrySelect
·
2024
·Vol. 9
·期 11
·e202400114
·
IF 1.9
Jin Liang,Xiaoxin Wang,Dongsheng Yu,XiTao Luo,Xiangfeng Liang,Zhongliang Su,Qinghui Shou
Graphical Self-supported osmotic membranes were prepared by blending PIM-1-mPEG, which was obtained by modifying PIM-1 with polyethylene glycol monomethyl ether (mPEG), and hydrophilic Tröger's base polymer (DMBP-TB). The membranes utilized microporous molecular sieves and the differences in solute-membrane interactions to achieve high pentose/hexose selectivity in aqueous solutions. Monosaccharides are vital building blocks in bioengineering applications; however, their extraction from intricate mixtures is challenging and uses substantial amounts of energy. Polymers of intrinsic microporosity (PIMs) offer an innovative avenue for separating monosaccharides. We modified PIM-1membranes to improve the glucose/xylose separation by incorporating polyethylene glycol monomethyl ether (mPEG). The optimal mPEG (molecular weight: 1000 Da; mass fraction: 2.5 %; solvent: methanol) delivered a xylose separation coefficient of 2.62. With the hybrid membrane of PIM-1-mPEG (50 w.t.%) and hydrophilic Tröger's base polymerer (DMBP-TB, 50 w.t.%), the separation factor for xylose/glucose in an aqueous solution was 2.51 for single-stage running and 11.32 after five-stage running. There are large fractions of micropores for PIM-1-mPEG, and there is difference on solute-membrane interactions for pentose/hexose, which are regarded to be the main driving force for the high pentose/hexose selectivity in methanol. The blending of PIM-1-mPEG and DMBP-TB, integrates the microporosity and hydrophilicity, finally endues the high pentose/hexose selectivity in aqueous solution. These microporous membranes are promising materials for efficiently separating monosaccharides and jnl> small organic molecules while minimizing energy consumption. We established a solid foundation for further exploring microporous membranes for various applications, notably in bioengineering.
研究领域:
生物工程
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材料科学
·
分离技术
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产品关联
DOI
高影响因子
JOURNAL OF BIOSCIENCE AND BIOENGINEERING
·
2022
·
IF 3.185
Lin Yuan,Yan-Li Qin,Zhi-Cheng Zou,Bright Appiah,Hao Huang,Zhong-Hua Yang,Can Qun
The intracellular NAD(P)H insufficiency is the key factor which limits the reduced product (such as chiral alcohols) synthesis by whole cell biocatalysis or microbial cell factory. In this paper, we reported a novel solution to increase NADPH supply through strengthening the pentose phosphate pathway (PPP) flux with overexpression of extra zwf (gene for glucose 6-phosphatedehydrogenase) and glk (gene for glucokinase) by recombinant Escherichia coli BL21(DE3)/pETDuet-1- glk - zwf and pET28a- bccr containing a carbonyl reductase gene bccr . The amount of intracellular NADPH was significantly increased from 150.3 μmol/L to 681.8 μmol/L after strengthening the PPP flux, which was 4.5-fold to that of the control. It was applied to improve the asymmetric reduction of 4-chloroacetoacetate to ethyl S -4-chloro-3-hydroxybutylate catalyzed by the Bc CR, which increased the reaction yield 2.8-fold to the control. This strategy provides a new way to increase NADPH supply in E. coli cell factories.
研究领域:
生物化学
·
生物技术
·
代谢工程
✓ 已验证
DOI
PubMed
高影响因子
Fermentation-Basel
·
2023
·Vol. 9
·期 4
·398
·
IF 3.7
Hongyu Zhang,Deguang Zhang,Ran Liu,Tingting Lou,Ruyue Tan,Suying Wang
The special structure of pentostatin causes it to possess a wide spectrum of biological and pharmacological properties, and it has been extensively employed to treat malignant tumors and is the first-line treatment for hairy cell leukemia. Pentostatin is mainly distributed in several actinomycetes and fungi species. However, its low titer in microbes is not able to meet medical needs. Here, we report a strain improvement strategy based on combined atmospheric and room-temperature plasma (ARTP) mutagenesis and ribosome engineering screening, as well as fermentation optimization, for enhanced pentostatin production. The original strain,Actinomadurasp. ATCC 39365, was treated with ARTP and screened by ribosome engineering to obtain one stable pentostatin high-yield mutantActinomadurasp. S-15, which produced 86.35 mg/L pentostatin, representing a 33.79% increase compared toActinomadurasp. ATCC 39365. qRT-PCR analysis revealed that pentostatin biosynthesis-related gene expression was significantly upregulated inActinomadurasp. S-15. Then, to further enhance pentostatin production, the fermentation medium was optimized in flask culture and the pentostatin production ofActinomadurasp. S-15 reached 152.06 mg/L, which is the highest pentostatin production reported so far. These results demonstrate the effectiveness of combined ARTP mutation, ribosome engineering screening, and medium optimization for the enhancement of pentostatin production, and provide a methodology enabling the sustainable production of pentostatin on an industrial scale.Keywords:Actinomadurasp.;pentostatin;atmospheric and room temperature plasma;ribosome engineering
研究领域:
微生物学
·
生物技术
·
药理学
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产品关联
DOI
高影响因子
INORGANIC CHEMISTRY
·
2022
·
IF 5.436
Yanhong Zhu,Zhongkui Li,Xue Zhong,Xuan Wu,Yongqiu Lu,Maroof Ahmad Khan,Hui Li
The knowledge of accurate geometrical parameters from X-ray diffraction studies in the solid state of metal nucleotide is very important for understanding the relationship between structures and properties, including biochemical processes and even enzyme–metal–substrate interactions. The research is also very necessary to precisely and controllably design the functional materials. Here, seven types of coordination polymers of inosine 5′-diphosphate nucleotide (IDP) with transition metals, {[Zn(HIDP)(azpy)(H2O)2]·4H2O}n (1), {[Cd2(IDP)2(bpda)2]·[Cd(H2O)6]·11H2O}n (2), {[Cd3(IDP)2(4,4′-bipy)2(H2O)3]·6H2O}n (3), {[Cd2(IDP)2(bpe)2(H2O)2]·(H2bpe)·26H2O}n (4), {[Cu3(IDP)2(azpy)2(H2O)5]·5H2O}n (5), {[Cu3(IDP)2(bpe)2(H2O)5]·9H2O}n (6), and {[Co(HIDP)(azpy)(H2O)2]·7H2O}n (7) [4,4′-bipy = 4,4′-bipyridine, azpy = 4,4′-azopyridine, bpe = 1,2-bis(4-pyridyl)ethene, and bpda = 1,4-bis(4-pyridyl)-2,3-diaza-1,3-butadiene], were designed, synthesized, and firmly characterized using single-crystal X-ray diffraction. The coordination patterns of the diphosphate group of IDP in these complexes were studied by crystallographic analysis, namely, open, close, and open–close hybrid types. We have investigated the diverse coordination patterns of the diphosphate group and its spatial relationship relative to the pentose ring on the basis of two conformational parameters, the pseudorotation phase angle and the degree of puckering. Crystallographic studies clearly reveal the correlation between the backbone torsion angle (ω′ and φ) of the sugar–diphosphate and the conformational preference of the pentose ring, i.e., the signs of the backbone torsion angles ω′ and φ are both plus (+) or minus (−), the conformation of the pentose ring is envelope form (E), while when one of the two signs is plus (+) and the other is minus (−), the pentose ring is in the twist form (T). This is the first time elucidation of the coordination pattern of diphosphate relative to the conformation of the pentose ring in nucleotide metal complexes, which are different from the other inorganic or organic diphosphate compounds. The chirality of these coordination polymers was examined by combining solid-state circular dichroism spectroscopy measurements with the explanation of their crystal structures. The results presented in this paper are very important for understanding their nucleotide coordination chemistry, their supramolecular chemistry, and even their biochemistry.
研究领域:
生物化学
·
配位化学
·
材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2025
·
IF 8
Li Liu,Tianhong Liu,Yuanhui Zhao,Mingyong Zeng,Xinxing Xu
The study investigates the impacts of indigenous bacterial strains inoculation specifically L. pentosus , on the flavor characteristics, microbial composition, and metabolite profiles of fermented oyster hydrolysates. This research aimed to elucidate potential mechanisms underlying the reduction of off-flavors in fermented hydrolysates. A total of 46 and 57 volatile compounds were detected by GC–MS and GC-IMS in hydrolysates inoculated with different core microbes, respectively. The 9 key volatile compounds detected by GC–MS analysis. ( E , E )-2,4-heptadienal, heptanal, octanal, pentanal, and ( E )-2-octenal reduced the off-flavor of the fermented oyster hydrolysate. Meanwhile 1-octen-3-ol, 3-octanone, 4-octanone, and ( E , Z )-2,6-nonadienal enhanced the direct contribution of desirable flavors. Variation in 16 amino acids, 10 organic acids and 3 nucleotides were monitored to further understand the metabolic changes affecting flavor quality. Moreover, pyruvate decarboxylase [EC 4.1.1.1], phosphomannanase [EC 3.2.1.109], lipoyl-CoA synthetase [EC 6.3.2.4], and arginine kinase [EC 2.7.3.3] were the main microbiologically active enzymes. An increase in the content of aromatic compounds and a decrease in the content of C6-C9 unsaturated aldehydes through Lys, Phe, Asp, Glu, phosphoenolpyruvate, oleic acid, and linoleic acid metabolism pathways improved the flavor of oyster hydrolysates fermented by L. pentosus . This research provides a theoretical basis for leveraging autochthonous microbial fermentation to systematically improve flavor characteristics in fermented products.
研究领域:
食品科学
·
微生物学
·
代谢组学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF DAIRY SCIENCE
·
2021
·
IF 4.034
Y. Ma,C. Wang,M. Elmhadi,H. Zhang,Y. Han,B. Shen,B.L. He,X.Y. Liu,H.R. Wang
ABSTRACT Data indicate that dietary thiamine supplementation can partly alleviate rumen epithelium inflammation and barrier function in goats fed a high-concentrate diet. The current work aimed to explore whether thiamine promotes rumen epithelium development by regulating carbohydrate metabolism during a long period of feeding high levels of concentrate. For the experiment, 24 female Boer goats (35.62 ± 2.4 kg of body weight) in parity 1 or 2 were allocated to 3 groups (8 goats per replicate) receiving a low-concentrate diet (concentrate:forage 30:70), a high-concentrate diet (HC; concentrate:forage 70:30), or a high-concentrate diet (concentrate:forage 70:30) supplemented with 200 mg of thiamine/kg of dry matter intake (HCT; concentrate:forage 70:30). On the last day of 12 wk, rumen fluid and blood samples were collected to measure ruminal parameters, endotoxin lipopolysaccharide, and blood inflammatory cytokines. Goats were slaughtered to collect ruminal tissue to determine differential metabolites, enzyme activities, and gene expression. Liquid chromatography–tandem mass spectrometry analysis revealed that the HCT group had significantly increased concentrations of d -glucose 6-phosphate, d -fructose 6-phosphate, glyceraldehyde 3-phosphate, thiamine pyrophosphate, oxaloacetate, acetyl-CoA, succinyl-CoA, sedoheptulose 7-phosphate, ribose 5-phosphate, and NADPH compared with the HC group. The pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase enzyme activities in the rumen epithelium of the HCT group were higher than those in the HC group. The plasma total antioxidant capacity values for the HCT group were greater than those for the HC group. The rumen epithelium ATP content in the HCT group was higher than that in the HC group. Compared with the HCT group, the HC group had a lower mRNA abundance of CCND1, CCNA2, CDK2, CDK4, CDK6, BCL2, PI3K , and AKT1 . Taken together, the results suggest that dietary thiamine supplementation could ameliorate disorders in the tricarboxylic acid cycle and the pentose phosphate pathway induced by a long-term high-concentrate diet and could promote rumen epithelial growth.
研究领域:
动物营养学
·
代谢生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2022
·
IF 3.318
Yuting Wang,Xin Sun,Jingwen Qiu,An Zhou,Pengbo Xu,Yarong Liu,Hongfei Wu
Atherosclerosis (AS) is a metabolic disorder commonly correlated with a high-fat diet (HFD). There are many endogenous metabolic changes associated with AS development. Gualou-Xiebai (GLXB) is a traditional Chinese medicine herb pair that has been used to treat AS. However, the mechanism of GLXB herb pair on the process of AS is still essentially unknown. In this study, aortic histopathological examination and biochemical analyses were used to validate the anti-atherosclerotic effects of GLXB herb pair on ApoE -/- mice during the disease course of AS. The mechanism of GLXB herb pair were performed by metabolomics approach based on ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). As a result, GLXB herb pair has protective effects on AS lesion development and improves blood lipid levels in ApoE -/- mice. A total of 34, 39, and 49 metabolites were found to be profoundly altered in the 9-week, 14-week, and 19-week model groups compared with the corresponding control groups. Among them, 16, 18, and 18 metabolites showed a trend toward normal levels after pharmacological intervention. Metabolic pathway analysis found that GLXB herb pair mainly affects glycerophospholipid metabolism, pentose and glucuronate interconversions in 9 weeks; linoleic acid metabolism, cysteine and methionine metabolism, and arachidonic acid metabolism in 14 weeks; arachidonic acid metabolism and pentose and glucuronate interconversions in 19 weeks. The results demonstrated that GLXB herb pair mainly played a therapeutic role by regulating glycerophospholipid metabolism and pentose and glucuronate interconversions in the whole process of AS.
研究领域:
药理学
·
代谢组学
·
心血管疾病
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产品关联
DOI
PubMed
高影响因子
PLoS One
·
2017
·Vol. 12
·期 3
·e0173712
·
IF 2.806
Xianzhi Qu,Jiyao Sheng,Luyan Shen,Jing Su,Yunjie Xu,Qi Xie,Yao Wu,Xuewen Zhang,Liankun Sun
The tumor cells have some metabolic characteristics of the original tissues, and the metabolism of the tumor cells is closely related to autophagy. However, the mechanism of autophagy and metabolism in chemotherapeutic drug resistance is still poorly understood. In this study, we investigated the role and mechanism of autophagy and glucose metabolism in chemotherapeutic drug resistance by using cholangiocarcinoma QBC939 cells with primary cisplatin resistance and hepatocellular carcinoma HepG2 cells. We found that QBC939 cells with cisplatin resistance had a higher capacity for glucose uptake, consumption, and lactic acid generation, and higher activity of the pentose phosphate pathway compared with HepG2 cells, and the activity of PPP was further increased after cisplatin treatment in QBC939 cells. It is suggested that there are some differences in the metabolism of glucose in hepatocellular carcinoma and cholangiocarcinoma cells, and the activation of PPP pathway may be related to the drug resistance. Through the detection of autophagy substrates p62 and LC3, found that QBC939 cells have a higher flow of autophagy, autophagy inhibitor chloroquine can significantly increase the sensitivity of cisplatin in cholangiocarcinoma cells compared with hepatocellular carcinoma HepG2 cells. The mechanism may be related to the inhibition of QBC939 cells with higher activity of the PPP, the key enzyme G6PDH, which reduces the antioxidant capacity of cells and increases intracellular ROS, especially mitochondrial ROS. Therefore, we hypothesized that autophagy and the oxidative stress resistance mediated by glucose metabolism may be one of the causes of cisplatin resistance in cholangiocarcinoma cells. It is suggested that according to the metabolism characteristics of tumor cells, inhibition of autophagy lysosome pathway with chloroquine may be a new route for therapeutic agents against cholangiocarcinoma.
研究领域:
肿瘤学
·
细胞生物学
·
药理学
✓ 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）