Biomolecules
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2019
·Vol. 9
·期 11
·695
·
IF 4.694
Dong-Sheng Wang,Xin-Jun Yu,Xiao-Yu Zhu,Zhao Wang,Hui-Juan Li,Zhi-Peng Wang
In the current study, corn steep liquor (CSL) is evaluated as an ideal raw agro-material for efficient lipid and docosahexaenoic acid DHA production byAurantiochytriumsp. Low CSL level in medium (nitrogen deficiency) stimulated the biosynthesis of lipids and DHA while inhibiting cellular growth. The transcriptomic profiles of theAurantiochytriumsp. cells are analyzed and compared when cultured under high (H group), normal (N group), and low (L group) levels of CSL in the medium. The discriminated transcriptomic profiles from the three groups indicates that changes in CSL level in medium result in a global change in transcriptome ofAurantiochytriumsp. The overall de novo assembly of cDNA sequence data generated 61,163 unigenes, and 18,129 of them were annotated in at least one database. A total of 5105 differently expressed (DE) genes were found in the N group versus the H group, with 2218 downregulated and 2887 upregulated. A total of 3625 DE genes were found in the N group versus the L group, with 1904 downregulated and 1721 upregulated. The analysis and categorization of the DE genes indicates that the regulation mechanism of CSL involved in the perception and transduction of the limited nitrogen signal, the interactions between the transcription factors (TFs) and multiple downstream genes, and the variations in downstream genes and metabolites, in sequence, are illuminated for the first time in the current study.Keywords:Aurantiochytriumsp.;nitrogen-deficiency;RNA-seq;corn steep liquor (CSL);signal transduction;DHA
研究领域:
生物技术
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分子生物学
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DOI
PubMed
高影响因子
Journal of Cancer
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2019
·
IF 3.182
Mingtong Ye,Nengzhi Pang,Ting Wan,Yuanling Huang,Tianyi Wei,Xuye Jiang,Yujia Zhou,Yufeng Huang,Hainan Yang,Zhenfeng Zhang,Lili Yang
Switching aerobic respiration to anaerobic glycolysis of cancer cells plays an important role in development and progression of acquired resistance. Since vitamin C enabled the inhibition of glycolysis of cancer cells, and erlotinib-resistant sub-line of HCC827 (ER6 cells) switched its metabolic features to higher glycolysis for survival, we hypothesize that vitamin C is able to inhibit glycolysis of ER6 cells. In this study, we found that both reduced vitamin C and oxidized vitamin C (DHA) could selectively suppress the viability of ER6 cells. DHA was efficient in inhibiting glycolysis and leading to energy crisis, which could be one mechanism for overcoming drug resistance to erlotinib of ER6 cells. Our data suggest that applying DHA could be a novel treatment strategy for NSCLC with acquired resistance to targeted therapy.
研究领域:
肿瘤学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Honglei Zhang,Yun Lu,Yuanlei Zhang,Jiayu Dong,Su Jiang,Yunping Tang
Objective This study explores the therapeutic effects and mechanisms of DHA-enriched phosphatidylserine (DHA-PS) on liver injury induced by cyclophosphamide (CTX) in mice, focusing on the gut-liver axis. Methods A mouse model was established by administering CTX (80 mg/kg) intraperitoneally for 5 days. DHA-PS (50 or 100 mg/kg) was administered for the next 7 days to assess its reparative impact on liver damage. Results The findings revealed significant improvements in liver biochemical indices, inflammatory markers, and oxidative stress levels in the mice treated with DHA-PS. Through non-targeted metabolomics analysis, DHA-PS mitigated CTX-induced metabolic disruptions by modulating lipid, amino acid, and pyrimidine metabolism. Immunofluorescence analysis further confirmed that DHA-PS reduced the expression of liver-associated inflammatory proteins by inhibiting the TLR4/NF-κB pathway. Additionally, DHA-PS restored the intestinal barrier, evidenced by adjustments in the levels of intestinal lipopolysaccharide (LPS), secretory immunoglobulin A (sIgA), and tight junction proteins (Claudin-1, Occludin, and ZO-1). It also improved gut microbiota balance by enhancing microbial diversity, increasing beneficial bacteria, and altering community structures. Conclusion These results suggest that DHA-PS could be a potential therapeutic agent or functional food for CTX-induced liver injury through its regulation of the gut-liver axis.
研究领域:
药理学
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肝病学
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胃肠病学
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免疫学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2024
·
IF 6.6
Kang Dong,Xin Wang,Ze-jia Zhou,Xin-ru Zheng,Zhuang-peng Chang,Rui Zhao,Jun-jin Liu,Rui-gang Hou,Xiao Zhang,Yun-yun Shao
Introduction Ulcerative colitis (UC) is a chronic intestinal disease characterized by spleen-lung qi deficiency and dampness-pathogenic obstruction. Although there are various treatment options available, patients frequently encounter significant drug-related side effects. Previous studies have shown the potential of Codonopsis Radix polysaccharides A (CPA) in treating UC, but their limited bioavailability has restricted their clinical use. Therefore, the objective of this study was to develop a novel formulation that can address the aforementioned limitations and assess its potential advantages.Methods and Results We synthesized a negatively charged amphipathic prodrug called CPA-SA-DHA (CSD), which consists of CPA as the hydrophilic component, and succinic anhydride and docosahexaenoic acid as the hydrophobic segments. The CSD nanoparticles obtained had a particle size of 180.0 ± 3.2 nm, a negative zeta potential of −29.8 ± 5.3 mV, and a uniform shape with a PDI index of 0.230 ± 0.003. The interaction between positive and negative charges significantly increased the retention time of CSD nanoparticles in the colonic microenvironment. Furthermore, CSD nanoparticles demonstrated enhanced bioavailability in UC mice compared to CPA. Additionally, we observed that CSD nanoparticles exhibited therapeutic effects on DSS-induced UC mice by regulating the diversity and abundance of gut microbiota. This effect may be mediated by the inhibition of pro-inflammatory signaling pathways TLR4/NF-κB.Conclusion These findings confirm the potential of CSD nanoparticles as a promising treatment option for UC.
研究领域:
药学
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胃肠病学
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纳米技术
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免疫学
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产品关联
DOI
PubMed
高影响因子
BIORESOURCE TECHNOLOGY
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2023
·
IF 11.4
Zi-Xu Zhang,Lu-Wei Xu,Ying-Shuang Xu,Jin Li,Wang Ma,Xiao-Man Sun,He Huang
Schizochytrium sp., a microalga with high lipid content, holds the potential for co-producing docosahexaenoic acid (DHA) and carotenoids. In this study, the ability of Schizochytrium sp. to naturally produce carotenoids was systematically explored. Further, by enhancing the precursor supply of geranylgeranyl diphosphate, regulating carbon source through sugar limitation fermentation and employing a combination of response surface methodology and artificial neural networks to precisely optimize nitrogen sources, a new record of 43-fold increase in β-carotene titer was achieved in the 5L bioreactor (653.2 mg/L) . Meanwhile, a high DHA content was maintained (13.4 g/L). Furthermore, the use of corn stover hydrolysate has effectively lowered the production costs of carotenoid and DHA while sustaining elevated production levels (with total carotenoid titer and DHA titer reached 502.0 mg/L and 13.2 g/L, respectively). This study offers an efficient and cost-effective method for the co-production of carotenoid and DHA in Schizochytrium sp. .
研究领域:
生物工程
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发酵工程
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遗传工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2019
·
IF 3.571
Xin-Jun Yu,Hong Chen,Chang-Yi Huang,Xiao-Yu Zhu,Zhi-Peng Wang,Dong-Sheng Wang,Xiao-Yan Liu,Jie Sun,Jian-Yong Zheng,Hui-Juan Li,Zhao Wang
The phytohormone 6-benzylaminopurine (6-BAP) significantly improves lipid synthesis of oleaginous microorganisms with the great potential applied in lipid production. In the current study, the lipid and DHA productions in oleaginous Aurantiochytrium sp. were found to be improved by 48.7% and 55.3%, respectively, induced by 6-BAP treatments. Then, using high-throughput RNA-seq technology, the overall de novo assembly of the cDNA sequence data generated 53871 unigenes, and 15902 of these were annotated in at least one database. The comparative transcriptomic profiles of cells with and without 6-BAP treatments revealed that a total of 717 were differently expressed genes (DE), with 472 upregulated and 245 downregulated. Further annotation and categorization indicated that some DE genes were involved in pathways crucial to lipid and DHA productions, such as fatty acid synthesis, central carbon metabolism, transcriptional factor, signal transduction, and mevalonate pathway. A regulation mode of 6-BAP, in turn, perception and transduction of 6-BAP signal, transcription factor, expression regulations of the downstream genes, and metabolic changes, respectively, was put forward for the first time in the present study. This research illuminates the transcriptomic mechanism of phytohormone stimulation of lipid and DHA production in an oleaginous microorganism and provides the potential targets modified using genetic engineering for improving lipid and DHA productivity.
研究领域:
微生物学
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分子生物学
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生物技术
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转录组学
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DOI
PubMed
高影响因子
ACS Food Science & Technology
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2024
·
IF 2.6
Yiting Zhu,Yinghui Feng,Jiawei Wang,Zhaoting Yuan,Yulu Miao,Tingwei Miao,Bei Gao,Lujia Zhang
The synthesis of long-chain n-3 polyunsaturated fatty acid (n-3 PUFA) triacylglycerols (TAGs) via lipase-catalyzed esterification is crucial for optimal human nutrition. However, existing lipases lack selectivity for long-chain n-3 PUFAs, hindering the efficient synthesis of highly polyunsaturated TAGs. By two-dimensional NMR and quantum chemical calculations, polyunsaturated DHA was found to have a unique curved conformation. We rationally designed the lipase MAS1 from marine Streptomyces sp. Strain W007 was based on the bent conformation of DHA, using virtual saturation mutagenesis and binding free energy calculations. Consequently, D150V with more hydrogen bonds and a lower binding free energy to DHA (−28.3820 kcal/mol) was obtained. The esterification selectivity of D150V to DHA was 2.18-fold that of the wild type, whereas its selectivity to behenic acid exhibited minimal improvement. Collectively, our findings present a significant advancement in lipase design for selective long-chain n-3 PUFA esterification, thereby opening avenues for lipase modification and industrial applications.
研究领域:
生物化学
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酶工程
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营养科学
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产品关联
DOI
高影响因子
Molecular Catalysis
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2020
·
IF 3.687
Jia-Qin Wu,Ding-Lin Wang,Xiao-Mei Xu,Neng-Bing Long,Rui-Feng Zhang
Novel nano-composites were prepared by coating epoxy resin-based cationic polymer in nano-thickness via in-situ curing on the wall of macroporous SiO 2 with pore size of 0.5∼1 μm. By changing the thickness of polymer coating the porosity and specific surface area varied in range of 90.4∼83.9 % and 115∼74 m 2 /g, respectively. Through electrostatic adsorption phospholipase A 1 (PLA 1 ) was efficiently immobilized on the nano-composited support, the loading amount of PLA 1 on the nano-composited support reached to a maximum of 138.6 mg/g support , the specific activity of the immobilized PLA 1 reached as high as 21,300 U/g protein . The immobilized PLA 1 was applied for the highly efficient synthesis of DHA/EPA-rich phosphatidylcholine . The incorporation of DHA/EPA reached as high as 74.8 % and the yield of phosphatidylcholine (PC) was 83.1 % within 20 h at 60 °C using PC/ethyl esters mass ratio of 1:6. After 12 cycling reuses the immobilized PLA 1 still retained 57.8 % of the incorporation of DHA/EPA.
研究领域:
生物化学
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食品科学
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酶工程
✓ 已验证
产品关联
DOI
高影响因子
Heliyon
·
2024
·
IF 3.4
Jing Tian,Yun Lu,Qiao-ling Zhao,Qiu-yan Pu,Su Jiang,Yun-ping Tang
To investigate the alleviating effect and mechanism of the docosahexaenoic acid-enriched phosphatidylserine (DHA-PS) on bisphenol A (BPA)-induced liver injury in mice, the murine liver injury model was established by gavage of BPA (5 mg/kg) or co-administration of BPA and DHA-PS (50 mg/kg or 100 mg/kg) for 6 weeks. The results showed that after administration of 100 mg/kg DHA-PS, the liver index, serum levels of AST, ALT, TC, TG, NEFA, and LDL-C in mice were significantly decreased, while HDL-C was significantly increased. The LPS, IL-6, IL-1β, TNF-α, and MDA levels in liver tissues were effectively down-regulated, and IL-10, SOD, GSH-Px, and CAT levels were effectively up-regulated. The H&E and Oil Red O staining results showed that liver damage was notably repaired and lipid deposition was notably reduced after DHA-PS administration. Furthermore, metabolomics and immunohistochemical studies revealed that DHA-PS mainly regulates glycerophospholipid metabolism and the SIRT1-AMPK pathway to improve metabolic disorders of the liver caused by BPA. Therefore, DHA-PS could potentially alleviate BPA-induced murine liver injury through suppressing inflammation and oxidative stress, and modulating lipid metabolism disorders.
研究领域:
毒理学
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肝病学
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代谢组学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomass Conversion and Biorefinery
·
2022
·Vol. 13
·期 18
·16807-16818
·
IF 4.05
Wang Qing,Jin Wenbiao,Han Wei,Song Kang,Chen Yidi,Chen Chuan,Jiang Guangming,Zhou Xu
In order to achieve strain improvement and reduction of fermentation medium cost, atmospheric and room temperature plasma (ARTP) mutagenesis and microbial microdroplet culture (MMC) high-throughput screening were used to obtain high-yield Aurantiochytrium sp. strain. Meanwhile, low-cost food waste liquid was added into culture medium to reduce cost. The results showed that the optimal treatment time of ARTP mutagenesis for Aurantiochytrium sp. was 25 s, and 20 mutant strains were screened out by MMC to investigate their performance. The most significant increase in DHA yield was mutant Aurantiochytrium sp. MA20, whose biomass, lipid, and DHA yield were 29.0 ± 0.24, 15.8 ± 0.11, and 9.22 ± 0.37 g/L and 5.77, 16.9, and 83.2% higher than those of original strain, respectively. Compared with the original strain, the DHA proportion in total fatty acids of Aurantiochytrium sp. MA20 increased from 37.2 to 58.3%, while the DHA proportion in biomass increased from 18.4 to 31.7%. The genetic stability for Aurantiochytrium sp. MA20 showed that the yield of biomass, lipid, and DHA of the 50th generation were 29.1 ± 0.13, 16.2 ± 0.31, and 9.47 ± 0.26 g/L, respectively, which was no significant difference between original strain, indicating that the mutant MA20 could be inherited stably. Using food waste liquid to replace 100% yeast extract and 50% sea water of the fermentation medium, the DHA yield reached 9.54 g/L, which was equivalent to that of traditional medium, while the cost of medium was reduced by 45% that achieved the recycle of food waste resource. Graphical abstract
研究领域:
微生物学
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生物技术
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环境科学
✓ 已验证
DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2024
·
IF 4
Hua Fang,Xiumei Wang,Mengyu Li,Mengxian Huang,Yiping Zhang,Taige Zhao,Cuiling Sun,Min Xu,Wenhui Jin,Weizhu Chen,Meijuan Fang
In this study, twenty-five novel carboxylic acid DHA-alkanolamine derivatives were synthesized by the reaction of cis -docosa-4,7,10,13,16,19-hexaenoic acid-alkanolamine (DHA-AA) with various carboxylic acids, including Naproxen (S1), Ibuprofen (S2), Ferulic acid (S3), Mefenamic acid (S4), and Aspirin (S5). Their molecular structures were characterized using 1 H/ 13 C NMR and HRMS techniques. To evaluate the anti-inflammatory activities of synthesized compounds, RAW264.7 macrophage cells pretreated with or without these compounds, were stimulated by LPS, and the levels of pro-inflammatory cytokines (NO, TNF-α, IL-1β, and IL-6) were then measured by ELISA, qPCR, and Western Blot. The cell-based assays showed that compound 11 had marked anti-inflammatory activity. In addition, the molecular docking study and SPR assay demonstrated that compound 11 exhibited good Nur77-binding affinity (K D = 3.61 × 10 −6 M). Moreover, compound 11 was found to inhibit NF-κB activation in a Nur77-dependent manner. Notably, compound 11 could attenuate LPS-induced inflammation in the mouse acute lung injury (ALI) model. In conclusion, these derivatives are potential Nur77-targeting anti-inflammatory agents against versatile inflammatory and autoimmune disorders.
研究领域:
药理学
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炎症研究
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药物化学
✓ 已验证
DOI
高影响因子
Marine Drugs
·
2023
·Vol. 21
·期 1
·39
·
IF 5.4
Hong-Yu Zou,Hui-Juan Zhang,Ying-Cai Zhao,Xiao-Yue Li,Yu-Ming Wang,Tian-Tian Zhang,Chang-Hu Xue
It has been reported that dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) exert therapeutic potential for the preservation of functional β-cell mass. However, the effect of dietary n-3 PUFA deficiency on pancreatic injury and whether the supplementation of n-3 PUFA could prevent the development of pancreatic injury are still not clear. In the present study, an n-3 PUFA deficiency mouse model was established by feeding them with n-3 PUFA deficiency diets for 30 days. Results showed that n-3 PUFA deficiency aggravated streptozotocin (STZ)-induced pancreas injury by reducing the insulin level by 18.21% and the HOMA β-cell indices by 31.13% and the area of islet by 52.58% compared with the STZ group. Moreover, pre-intervention with DHA and EPA for 15 days could alleviate STZ-induced pancreas damage by increasing the insulin level by 55.26% and 44.33%, the HOMA β-cell indices by 118.81% and 157.26% and reversed the area of islet by 196.75% and 205.57% compared to the n-3 Def group, and the effects were significant compared to γ-linolenic acid (GLA) and alpha-linolenic acid (ALA) treatment. The possible underlying mechanisms indicated that EPA and DHA significantly reduced the ration of n-6 PUFA to n-3 PUFA and then inhibited oxidative stress, inflammation and islet β-cell apoptosis levels in pancreas tissue. The results might provide insights into the prevention and alleviation of pancreas injury by dietary intervention with PUFAs and provide a theoretical basis for their application in functional foods.Keywords:streptozotocin;polyunsaturated fatty acid;pancreas injury;oxidative stress;inflammation;apoptosis;mouse
研究领域:
营养学
·
内分泌学
·
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）