International Journal of Nanomedicine
·
2023
·
IF 8
Yihan Wang,Yizhen Wei,Yichun Wu,Yue Zong,Yingying Song,Shengyan Pu,Wenwen Wu,Yun Zhou,Jun Xie,Haitao Yin
Purpose Realgar, as a kind of traditional mineral Chinese medicine, can inhibit multiple solid tumor growth and serve as an adjuvant drug in cancer therapy. However, the extremely low solubility and poor body absorptive capacity limit its application in clinical medicine. To overcome this therapeutic hurdle, realgar can here be fabricated into a nano-realgar hydrogel with enhanced chemotherapy and radiotherapy (RT) ability. Our objective is to evaluate the superior biocompatibility and anti-tumor activity of nano-realgar hydrogel.Methods We have successfully synthesized nano-realgar quantum dots (QDs) coupling with 6-AN molecules (NRA QDs) and further encapsulated with a pH-sensitive dextran hydrogel carrier with hyaluronic acid coating (DEX-HA gel) to promote bioavailability, eventually forming a multifunctional nano-realgar hydrogel (NRA@DH Gel). To better investigate the tumor therapy efficiency of the NRA@DH Gel, we have established the mice in situ bearing GL261 brain glioblastoma as animal models assigned to receive intratumor injection of NRA@DH Gel.Results The designed NRA@DH Gel as an antitumor drug can not only exert the prominent chemotherapy effect but also as a “sustainable reactive oxygen species (ROS) generator” can inhibit in the pentose phosphate pathway (PPP) metabolism and reduce the production of nicotinamide adenine dinucleotide phosphate (NADPH), thereby inhibiting the conversion of glutathione disulfide (GSSG) to glutathione (GSH), reducing GSH concentrations in tumor cells, triggering the accumulation of ROS, and finally enhancing the effectiveness of RT.Conclusion Through the synergistic effect of chemotherapy and RT, NRA@DH Gel effectively inhibited the proliferation and migration of tumor cells, suppressed tumor growth, improved motor coordination, and prolonged survival in tumor-bearing mice. Our work aims to improve the NRA@DH Gel-mediated synergistic chemotherapy and RT will endow a “promising future” for the old drug in clinically comprehensive applications.
研究领域:
药学
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肿瘤学
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纳米技术
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生物医学工程
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
APPLIED AND ENVIRONMENTAL MICROBIOLOGY
·
2024
·Vol. 90
·期 8
·
IF 3.9
Yating Li,Tong Xu,Yanqin Tu,Tong Li,Yifeng Wei,Yan Zhou
Phloroglucinol (1,3,5-trihydroxybenzene) is a key intermediate in the degradation of polyphenols such as flavonoids and hydrolysable tannins and can be used by certain bacteria as a carbon and energy source for growth. The identification of enzymes that participate in the fermentation of phloroglucinol to acetate and butyrate in Clostridia was recently reported. In this study, we present the discovery and characterization of a novel metabolic pathway for phloroglucinol degradation in the bacterium Collinsella sp. zg1085, from marmot respiratory tract. In both the Clostridial and Collinsella pathways, phloroglucinol is first reduced to dihydrophoroglucinol by the NADPH-dependent phloroglucinol reductase (PGR), followed by ring opening to form (S)-3-hydroxy-5-oxohexanoate by a Mn2+-dependent dihydrophloroglucinol cyclohydrolase (DPGC). In the Collinsella pathway, (S)-3-hydroxy-5-oxohexanoate is then cleaved to form malonate semialdehyde and acetone by a newly identified aldolase (HOHA). Finally, a NADP+-dependent malonate-semialdehyde dehydrogenase converts malonate semialdehyde to CO2 and acetyl-CoA, an intermediate in carbon and energy metabolism. Recombinant expression of the Collinsella PGR, DPGC, and HOHA in E. coli enabled the conversion of phloroglucinol into acetone, providing support for the proposed pathway. Experiments with Olsenella profusa, another bacterium containing the gene cluster of interest, show that the PGR, DPGC, HOHA, and MSDH are induced by phloroglucinol. Our findings add to the variety of metabolic pathways for the degradation of phloroglucinol, a widely distributed phenolic compound, in the anaerobic microbiome.
研究领域:
微生物学
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生物化学
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代谢途径
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酶学
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产品关联
DOI
PubMed
高影响因子
OPTICAL MATERIALS
·
2021
·
IF 3.08
Gengcheng Liao,Hui Qiao,Zongyu Huang,Siwei Luo,Yuan Ji,Yundan Liu,Xiang Qi
Designing a Z-scheme heterojunction is of great significance to achieve high separation of photogenerated carriers and strong photo-redox properties of two semiconductor materials . In photosynthesis, the effects of photocatalytic electrolytes (adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH)) on chemical energy has attracted numerous interests. In this case, developing photocatalytic electrolytes with more active site and efficient charge extraction and separation would be beneficial for superior photocatalytic activity in Z-scheme system. Herein, we synthesized a Black/Red (BP/RP) phosphorus Z-scheme hybrid via a feasible two-steps sonochemical method, and the adding photocatalytic electrolytes ATP and NADPH in KOH solution endow the system with new vitality in photocatalysis . Consequently, photoelectrochemical (PEC) tests demonstrated the as-prepared BP/RP Z-scheme hybrid exhibits enhanced photocurrent of 9 μA/cm 2 at 0.5 V compared to the sole RP, while adding NADPH and ATP, the photocurrent of BP/RP Z-scheme hybrid shows dramatic increment of 30 μA cm −2 at a bias potential of 0.6 V. The improved photocatalytic activity is ascribed to the abundant active sites, higher carrier mobility of the BP/RP Z-scheme system, as well as the efficient photogenerated carrier separation and the prolonged lifetime of photocatalytic electrolytes. This work demonstrated the photocatalytic electrolytes can meet the unity of coordination and efficiency of achieving efficient PEC catalytic in the Z-Scheme system, and provides positive ideas for the possibility and superiority for other 2D materials in the field of ultrafast Photonics , photodetectors , etc.
研究领域:
材料科学
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光化学
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电化学
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光子学
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纳米技术
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产品关联
DOI
高影响因子
ACS Nano
·
2024
·
IF 15.8
Lanlan Fan,Panyu Du,Yaru Li,Xuefei Chen,Fang Liu,Yuning Liu,Alexey M. Petrov,Xin Li,Zheng Wang,Yanjun Zhao
Ferroptotic cancer therapy has been extensively investigated since the genesis of the ferroptosis concept. However, the therapeutic efficacy of ferroptosis induction in heterogeneous and plastic melanoma has been compromised, because the melanocytic and transitory cell subpopulation is resistant to iron-dependent oxidative stress. Here, we report a phenotype-altering liposomal nanomedicine to enable the ferroptosis-resistant subtypes of melanoma cells vulnerable to lipid peroxidation via senescence induction. The strategy involves the ratiometric coencapsulation of a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor (palbociclib) and a ferroptosis inducer (auranofin) within cRGD peptide-modified targeted liposomes. The two drugs showed a synergistic anticancer effect in the model B16F10 melanoma cells, as evidenced by the combination index analysis (<1). The liposomes could efficiently deliver both drugs into B16F10 cells in a targeted manner. Afterward, the liposomes potently induced the intracellular redox imbalance and lipid peroxidation. Palbociclib significantly provoked cell cycle arrest at the G0/G1 phase, which sensitized auranofin-caused ferroptosis through senescence induction. Meanwhile, palbociclib depleted intracellular glutathione (GSH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH), further boosting ferroptosis. The proof-of-concept was also demonstrated in the B16F10 tumor-bearing mice model. The current work offers a promising ferroptosis-targeting strategy for effectively treating heterogeneous melanoma by manipulating the cellular plasticity.
研究领域:
癌症治疗
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药学
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纳米技术
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肿瘤学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Food Bioscience
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2024
·
IF 4.8
Chao Wang,Wang Ma,Luwei Xu,Zhiyun Wei,Ke Tang,Jingwen Zhou,Jian Chen
Flavonoids, including dihydroflavonols and anthocyanins, are phenolic compounds with significant biological activity, playing a crucial role in the sensory characteristics and health benefits of wine. In this study, we selected the naringenin-producing strain HB52 （ Saccharomyces cerevisiae ） as the starting strain and introduced synthetic pathways for dihydroflavonols and anthocyanins, achieving de novo synthesis of various flavonoid compounds. To further optimize flavonoid production, we employed several strategies, including overexpressing 5-enolpyruvylshikimate 3-phosphate synthase to enhance metabolic flux, integrating NADPH regeneration genes, and using citric acid/isocitric acid transporter genes to increase the levels of cofactors. Additionally, organelle engineering was utilized to strengthen the β-oxidation pathway, thereby elevating the levels of precursors such as acetyl-coenzyme A (CoA) and malonyl-CoA. Engineered strains significantly improved their ability to synthesize various flavonoids directly from glucose. In the final engineered strains, the production levels of NAR, DHQ, and DHM in the dihydroflavonol-engineered strains reached 379.2 mg/L, 231.3 mg/L, and 284.8 mg/L, respectively. The anthocyanin-engineered strains achieved the highest yield of anthocyanin synthesized from glucose in S. cerevisiae , reaching 45.7 mg/L (33.4 mg/L for C3G and 12.3 mg/L for D3G). This study highlights the potential of metabolic and organelle engineering in S. cerevisiae to increase flavonoid production, offering new prospects for enhancing sensory quality and health benefits in the wine industry.
研究领域:
代谢工程
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细胞生物学
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生物技术
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生物化学
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葡萄酒科学
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产品关联
DOI
高影响因子
BIOMATERIALS
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2024
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IF 12.8
Jiajia Luo,Yaqi Shang,Ning Zhao,Xiaoying Lv,Zheng Wang,Xin Li,Xuan Meng,Yanjun Zhao
ABSTRACT Ferroptosis has been recognized as a promising therapeutic strategy for cancer due to its unique mechanism of action. However, the upregulation of stearoyl-CoA desaturase 1 (SCD1) in ovarian cancer leads to resistance to ferroptotic therapy. Zinc ion (Zn 2+ ) serves as the cofactor of SCD1. It was hypothesized that selective deprivation of Zn 2+ from SCD1 could sensitize ferroptotic ovarian cancer therapy. Here, we report a hypoxia-responsive polymer micelle for enhanced ferroptosis of ovarian cancer cells. An SCD1 inhibitor, PluriSIn 1 (Plu), and a ferroptosis inducer, Auranofin (Aur), were co-encapsulated in nitroimidazole-bearing micelles. Under the hypoxic tumor microenvironment, the conversion of nitroimidazole to aminoimidazole triggered the cargo release and induced the depletion of antioxidant molecules (e.g., glutathione, thioredoxin, and NADPH). Meanwhile, because of the strong coordination between aminoimidazole and Zn 2+ compared to that of histidine and Zn 2+ , such conversion can deprive the metal cofactor of SCD1, hence sensitizing the action of Plu and Aur. The proof-of-concept was demonstrated in cell and animal models with minimal systemic toxicity. The current work integrates ferroptosis induction with SCD1 inhibition in a hypoxia-responsive vehicle, offering a promising strategy for addressing the ferroptosis resistance and opening novel avenues for managing difficult-to-treat ovarian cancer.
研究领域:
癌症生物学
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药学
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材料科学
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治疗学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Microbiology
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2021
·
IF 5.64
Li Jingxin,Zhang Yuxiao,Wang Xing,Walk Seth T.,Wang Gejiao
Antimony (Sb)-resistant bacteria have potential applications in the remediation of Sb-contaminated sites. However, the effect of Sb(III) exposure on whole-cell metabolic change has not been studied. Herein, we combined untargeted metabolomics with a previous proteomics dataset and confirmatory gene transcription analysis to identify metabolic responses to Sb(III) exposure in Agrobacterium tumefaciens GW4. Dynamic changes in metabolism between control and Sb(III)-exposed groups were clearly shown. KEGG pathway analysis suggested that with Sb(III) exposure: (1) the branching pathway of gluconeogenesis is down-regulated, resulting in the up-regulation of pentose phosphate pathway to provide precursors of anabolism and NADPH; (2) glycerophospholipid and arachidonic acid metabolisms are down-regulated, resulting in more acetyl-CoA entry into the TCA cycle and increased capacity to produce energy and macromolecular synthesis; (3) nucleotide and fatty acid synthesis pathways are all increased perhaps to protect cells from DNA and lipid peroxidation; (4) nicotinate metabolism increases which likely leads to increased production of co-enzymes (e.g., NAD+ and NADP+) for the maintenance of cellular redox and Sb(III) oxidation. Expectedly, the total NADP+/NADPH content, total glutathione, and reduced glutathione contents were all increased after Sb(III) exposure in strain GW4, which contribute to maintaining the reduced state of the cytoplasm. Our results provide novel information regarding global bacterial responses to Sb(III) exposure from a single gene level to the entire metabolome and provide specific hypotheses regarding the metabolic change to be addressed in future research.
研究领域:
微生物学
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环境科学
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分子生物学
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代谢组学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2021
·
IF 5.875
Congjun Xu,Haolan Yang,Zhanghong Xiao,Tao Zhang,Zilin Guan,Jie Chen,Hualu Lai,Xiaoyu Xu,Yanjuan Huang,Zeqian Huang,Chunshun Zhao
The pentose phosphate pathway (PPP) plays a critical role by providing ribulose-5-phosphate (Ru5P) and NADPH for nucleotide synthesis and reduction energy, respectively. Accordingly, blocking the PPP process may be an effective strategy for enhancing oxidation therapy and inhibiting cell replication. Here, we designed a novel reduction-responsive PEGylated prodrug and constructed nanoparticles [email protected] to simultaneously deliver a PPP blocker, dehydroepiandrosterone (DHEA), and chemotherapeutic camptothecin (CPT) to integrate amplification of oxidation therapy and enhance cell replication inhibition. Following cellular uptake, DHEA and CPT were released from [email protected] in the presence of high glutathione (GSH) levels. As expected, DHEA-mediated reduction level decreases and CPT-induced oxidation level increases synergistically, breaking the redox balance to aggravate cancer oxidative stress. In addition, suppressing nucleotide synthesis by DHEA through the reduction of Ru5P and blocking DNA replication by CPT further motivates a synergistic inhibition effect on tumor cell proliferation . The results showed that [email protected] featuring multimodal treatment has satisfactory antitumor activity both in vitro and in vivo . This study provides a new tumor treatment strategy, which combines the amplification of oxidative stress and enhancement of inhibition of cell proliferation based on inhibition of the PPP process.
研究领域:
药理学
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肿瘤学
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纳米技术
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生物化学
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治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2020
·
IF 4.679
Di Wu,Shuangqiu Li,Peixuan Li,Aimin Jiang,Ziyi Liu,Yong Zhang,Jingjing Wang,Zhengtao Yang,Zhengkai Wei
Diacetoxyscirpenol (DAS) is one kind of type A trichothecene mycotoxin which produced by Fusarium species which contaminates agricultural crops and food . DAS attracts particular attention because of the strong toxicity. Heterophil extracellular traps (HETs) is a defense mechanism in the chicken innate immune. In this study, we firstly examine the effects and molecular mechanisms of DAS on HETs release, and then investigate the immune toxicity of DAS-induced HETs on chicken liver. HETs structures were observed by immunofluorescence staining and mechanisms were investigated by fluorescence microplate and Western blot . The results showed DAS triggered HETs formation which consists of chromatin decorated with citrullinated histone 3 (citH3) and elastase . Glycolysis was confirmed to be involved in this process and the inhibitors of NADPH oxidase , ERK 1/2 , p38 MAPK-signaling pathways and glycolysis significantly decreased HETs formation. Moreover, investigation in vivo showed DAS significantly increased HETs formation in serum and DNase I (a standard degradative agent of HETs) significantly decreased the ALT and AST levels and ameliorated DAS-caused inflammatory cell infiltration of liver. In conclusion, this study proves that DAS-induced HETs formation plays an immune toxicity role in chicken liver injury and these results provide a new therapeutic target for DAS-induced liver injury in chickens.
研究领域:
兽医学
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免疫学
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毒理学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
PLoS One
·
2014
·Vol. 9
·期 4
·e93815
·
IF 3.534
Haishan Qi,Shanshan Li,Sumin Zhao,Di Huang,Menglei Xia,Jianping Wen
To rationally guide the improvement of isobutanol production, metabolic network and metabolic profiling analysis were performed to provide global and profound insights into cell metabolism of isobutanol-producing Bacillus subtilis . The metabolic flux distribution of strains with different isobutanol production capacity (BSUL03, BSUL04 and BSUL05) drops a hint of the importance of NADPH on isobutanol biosynthesis. Therefore, the redox pathways were redesigned in this study. To increase NADPH concentration, glucose-6-phosphate isomerase was inactivated (BSUL06) and glucose-6-phosphate dehydrogenase was overexpressed (BSUL07) successively. As expected, NADPH pool size in BSUL07 was 4.4-fold higher than that in parental strain BSUL05. However, cell growth, isobutanol yield and production were decreased by 46%, 22%, and 80%, respectively. Metabolic profiling analysis suggested that the severely imbalanced redox status might be the primary reason. To solve this problem, gene udhA of Escherichia coli encoding transhydrogenase was further overexpressed (BSUL08), which not only well balanced the cellular ratio of NAD(P)H/NAD(P) + , but also increased NADH and ATP concentration. In addition, a straightforward engineering approach for improving NADPH concentrations was employed in BSUL05 by overexpressing exogenous gene pntAB and obtained BSUL09. The performance for isobutanol production by BSUL09 was poorer than BSUL08 but better than other engineered strains. Furthermore, in fed-batch fermentation the isobutanol production and yield of BSUL08 increased by 11% and 19%, up to the value of 6.12 g/L and 0.37 C-mol isobutanol/C-mol glucose (63% of the theoretical value), respectively, compared with parental strain BSUL05. These results demonstrated that model-driven complemented with metabolic profiling analysis could serve as a useful approach in the strain improvement for higher bio-productivity in further application.
研究领域:
代谢工程
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生物技术
·
微生物学
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系统生物学
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产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2024
·Vol. 15
·期 1
·1-14
·
IF 14.7
Wei Xinlei,Yang Xue,Hu Congcong,Li Qiangzi,Liu Qianqian,Wu Yue,Xie Leipeng,Ning Xiao,Li Fei,Cai Tao,Zhu Zhiguang,Zhang Yi-Heng P. Job,Zhang Yanfei,Chen Xuejun,You Chun
In vitro biotransformation (ivBT) facilitated by in vitro synthetic enzymatic biosystems (ivSEBs) has emerged as a highly promising biosynthetic platform. Several ivSEBs have been constructed to produce poly-3-hydroxybutyrate (PHB) via acetyl-coenzyme A (acetyl-CoA). However, some systems are hindered by their reliance on costly ATP, limiting their practicality. This study presents the design of an ATP-free ivSEB for one-pot PHB biosynthesis via acetyl-CoA utilizing starch-derived maltodextrin as the sole substrate. Stoichiometric analysis indicates this ivSEB can self-maintain NADP + /NADPH balance and achieve a theoretical molar yield of 133.3%. Leveraging simple one-pot reactions, our ivSEBs achieved a near-theoretical molar yield of 125.5%, the highest PHB titer (208.3 mM, approximately 17.9 g/L) and the fastest PHB production rate (9.4 mM/h, approximately 0.8 g/L/h) among all the reported ivSEBs to date, and demonstrated easy scalability. This study unveils the promising potential of ivBT for the industrial-scale production of PHB and other acetyl-CoA-derived chemicals from starch.
研究领域:
生物技术
·
生物化学
·
合成生物学
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代谢工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF HAZARDOUS MATERIALS
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2024
·
IF 12.2
He Zhu,Chentao Ding,Yunbing Tang,Jingyi Zheng,Shaowei Wang,Zhongyao Ji,Yang Zhu,Ren-shan Ge,Huitao Li
Parabens are preservatives used in personal care products, cosmetics, and pharmaceuticals. Steroid 5α-reductase 1 (SRD5A1) catalyzes the conversion of testosterone to dihydrotestosterone and is present in the brain, contributing to neurosteroid production. This study aimed to assess the effects of nine paraben preservatives on SRD5A1 in human SF126 glioblastoma cell and rat brain microsomes, particularly focusing on dihydrotestosterone production in SF126 cells. The results showed that methyl, ethyl, propyl, butyl, hexyl, heptyl, nonyl, phenyl, and benzyl paraben inhibited human SRD5A1, with nonylparaben having the strongest effect (7.59 μM). Additionally, kinetic analysis indicated that parabens acted as mixed/noncompetitive inhibitors, leading to a significant decrease in dihydrotestosterone production in SF126 cells. While rat SRD5A1 exhibited lower sensitivity to parabens, docking analysis revealed that parabens bind to the NADPH-binding site of both human and rat SRD5A1. In conclusion, these results highlight the inhibitory effects of paraben preservatives on SRD5A1 and elucidate their binding mechanisms, underscoring their role in hormone production.
研究领域:
药理学
·
毒理学
·
生物化学
·
分子生物学
·
神经科学
✓ 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）