CHEMICAL & PHARMACEUTICAL BULLETIN
·
2014
·Vol. 62
·期 6
·505-507
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IF 1.375
Meiling Zhang,Mingjie Deng,Jianshe Ma,Xianqin Wang
Hydrogen sulfide (H2S) is the second leading cause of toxin-related deaths in the operational site. Its main target organs of toxic effects are the central nervous system and respiratory system. In this study, we developed a serum metabonomic method, based on gas chromatography-mass spectrometry (GC/MS), to evaluate the effect of acute poisoning by hydrogen sulfide on rats. Pattern recognition analysis, including both principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA), revealed that acute hydrogen sulfide poisoning induced metabolic perturbations. Compared to the control group, the level of urea, glucose, glyceryl stearate in rat serum of the poisoning group increased after two hours, and the level of glucose, docosahexaenoic acid, glyceryl stearate and arachidonic acid in rat serum of the poisoning group increased after 48 h, while the l-valine, galactose, l-tyrosine levels decreased. Our results indicate that metabonomic methods based on GC/MS may be useful to elucidate acute hydrogen sulfide poisoning through the exploration of biomarkers.
研究领域:
毒理学
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分析化学
·
医学
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Zhen Guo,Renlu Han,Yun Gao,Jie Fu,Zekai Zhuang,Yafei Hou,Jiancheng Yu,Keqi Tang
Abnormal metabolic symbiosis is one of the most typical features of tumors that distinguishes them from normal tissues. Disrupting tumor metabolic symbiosis has been recognized a promising tumor therapeutic approach. However, a single pathway intervention strategy greatly impedes its treatment efficiency. Herein, α-cyano-4-hydroxycinnamic acid (CHCA) and elesclomol (ES) co-loaded Cu 7 S 4 nanoplatform (named as CCE) is developed to synchronously intervene tricarboxylic acid (TCA) cycle and lactic acid metabolism through self-enhanced cuproptosis and acidosis for tumor metabolic symbiosis destruction. CCE could be triggered by up-regulated glutathione (GSH) in cancer cells to release ES, CHCA, Cu ions, and S 2− ions. On the one hand, ES significantly improves the influx efficiency of Cu ions to mitochondria where cuproptosis is initiated and TCA cycle is attacked. Meanwhile, the H 2 S produced by the binding of S 2− to H + in acidic tumor cells could induce mitochondrial damage and inhibit Cu ions efflux by depriving energy supply. Moreover, the GSH consumption reduces its chelation with Cu ions. Collectively, the increased intracellular Cu ions level significantly boosts cuproptosis mediated proteotoxicity of TCA cycle, thus aggravating TCA cycle injury. On the other hand, CHCA down-regulates the expression of monocarboxylate transporters 4 (MCT4) and inhibits lactic acid transport between tumor cells, causing the tumor cytoplasm acidification. Interestingly, H 2 S accelerates lactate production by promoting the glucose uptake to further potent the lactate metabolic disorder. In vitro and in vivo experiments confirm anti-tumor efficacy and biosafety of CCE. This study further enriches tumor therapeutic strategy.
研究领域:
肿瘤生物学
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代谢调控
·
生物化学
✓ 已验证
产品关联
DOI
高影响因子
Journal of Forensic and Legal Medicine
·
2015
·
IF 0.76
Mingjie Deng,Meiling Zhang,Xueli Huang,Jianshe Ma,Lufeng Hu,Guanyang Lin,Xianqin Wang
Hydrogen sulfide poisoning is a common occupational hazard, whose mortality and incidence rates are first and second, respectively, among occupational poisoning incidents in China. The main target organs of its toxicity are in the central nervous system and respiratory system. However, there are currently no specific direct tests that can be used to diagnose poisoned patients. In this study, we developed a serum metabonomic method using orthogonal partial least squares-discriminate analysis (OPLS-DA), based on gas chromatography–mass spectrometry (GC/MS) to evaluate the effect of chronic poisoning by hydrogen sulfide in rats. The OPLS-DA data demonstrated that the model group (n = 60) differed significantly from the control group (n = 30), suggesting that the metabolic profiles of the two groups are markedly different. Alterations in the levels of some metabolites such as citrate, galactose , lactate, mannose , inositol , urea, phosphate, alanine and valine were detected by OPLS-DA analysis. We observed changes in metabolic pathways including lipid metabolism , energy metabolism and amino metabolism in the model group. Our results indicate that GC/MS-based metabonomic methods may provide novel detection means for chronic hydrogen sulfide poisoning.
研究领域:
毒理学
·
分析化学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomed Research International
·
2015
·
IF 1.579
Mingjie Deng,Meiling Zhang,Fa Sun,Jianshe Ma,Lufeng Hu,Xuezhi Yang,Guanyang Lin,Xianqin Wang
Gas chromatography-mass spectrometry (GS-MS) in combination with multivariate statistical analysis was applied to explore the metabolic variability in urine of chronically hydrogen sulfide- (H2S-) poisoned rats relative to control ones. The changes in endogenous metabolites were studied by partial least squares-discriminate analysis (PLS-DA) and independent-samples t-test. The metabolic patterns of H2S-poisoned group are separated from the control, suggesting that the metabolic profiles of H2S-poisoned rats were markedly different from the controls. Moreover, compared to the control group, the level of alanine, d-ribose, tetradecanoic acid, L-aspartic acid, pentanedioic acid, cholesterol, acetate, and oleic acid in rat urine of the poisoning group decreased, while the level of glycine, d-mannose, arabinofuranose, and propanoic acid increased. These metabolites are related to amino acid metabolism as well as energy and lipid metabolism in vivo. Studying metabolomics using GC-MS allows for a comprehensive overview of the metabolism of the living body. This technique can be employed to decipher the mechanism of chronic H2S poisoning, thus promoting the use of metabolomics in clinical toxicology.
研究领域:
毒理学
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代谢组学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ARCHIVES OF MEDICAL RESEARCH
·
2020
·
IF 2.093
Li-li Deng
Object Astragaloside IV (AS IV) has antioxidative and anti-apoptotic properties, however, its effects on juvenile mice with diabetic ketoacidosis (DKA) have not been determined. This study aims to explore the effect and mechanism of Astragaloside IV (AS-IV) on juvenile mice with DKA. Methods DKA model was established through intraperitoneal injection of streptozotocin (STZ) and alloxan (ALX). DKA mice were divided into Control group, DKA group, DKA+AS-IV group, DKA+AS-IV+SP600125 group, DKA+AS-IV+Anisomycin group, DKA+AS-IV+GV248 group and DKA+AS-IV+GV248-Nrf2 group. To verify the implication of JNK signal pathway, JNK inhibitor SP600125 and activator Anisomycin were injected. The effects of AS-IV on antioxidant capacity and pathologies of pancreatic tissues in DKA juvenile mice were assessed. The expression of JNK/Nrf2 signal pathway was measured by Western blot. Results DKA juvenile mouse models were successfully established, evidenced by elevated blood glucose and blood ketone, suppressed insulin and pH value, and notable injuries in pancreatic tissues. Gavage of AS-IV can enhance antioxidant capacity of pancreatic tissue and ameliorate injuries in pancreatic tissues. AS-IV increased insulin level, in addition to suppressing blood glucose in DKA juvenile mice. In pancreatic tissues of DKA juvenile mice, protein level of p-JNK/JNK in pancreatic tissue and Nrf2 in the nuclei were increased after administration of AS-IV. Inhibition on JNK/Nrf2 signal pathway would impair the favorable effect of AS-IV on DKA juvenile mice, while antioxidant capacity, insulin level and blood glucose were improved in DKA juvenile mice injected an activator of JNK/Nrf2 pathway. Conclusion Collectively, AS-IV can enhance the antioxidant capacity of DKA juvenile mice to decrease blood glucose and to increase serum insulin secretion. The mechanism of action may be realized through the JNK/Nrf2 pathway.
研究领域:
药理学
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内分泌学
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分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2024
·
IF 9.4
Yajing Chi,Chaoqi Song,Qian Jia,Ruili Zhang,Fang Sun,Zheng Li,Yuanyuan Jia,Xian An,Zhongliang Wang,Jianxiong Li
Background: Chemodynamic therapy (CDT) has become increasingly important as a tumor treatment strategy, which relies on intracellular acid and hydrogen peroxide to kill tumor cells by generating hydroxyl radicals (·OH) through Fenton/Fenton-like reactions. However, the weakly alkaline intracellular environment considerably caused by the efflux of lactate and H + from glioblastoma cells is not conducive to CDT performance. Intracellular acidification induced by inhibiting the transmembrane monocarboxylate transporter 4 (MCT4) can enhance the therapeutic efficacy of CDT. Existing approaches suffer from insufficient MCT4 inhibition, involve complex drug synthesis, and have many unsatisfactory side effects. Methods: In this study, we constructed an anti-tumor nanoparticle formed by self-assembly driven by the coordination interaction of Fe 3+ and α-cyano-4-hydroxycinnamate (CHC) to avoid safety issues posed by excessive modification. Fe-CHC nanoparticles were designed to decrease intracellular pH through inhibition of MCT4, which transports lactate/H + to the extracellular space. The resulting intracellular accumulation of lactate and H + led to fatal acidosis and promoted ·OH generated by Fenton/Fenton-like reactions with the presence of the Fe 3+ , thus enhancing CDT-induced tumor cell death. Results: In vitro and in vivo results revealed that Fe-CHC exerted a significant synergistic anti-tumor effect by re-establishing acidosis and enhancing CDT in glioblastoma. Furthermore, the decreased H + outside the cells caused by the inhibition of lactate/H + efflux hindered extracellular matrix degradation, thereby inhibiting tumor metastasis. Conclusion: Fe-CHC is an effective anti-cancer agent against glioblastoma. This study provides valuable insights for developing acid-modulating anti-tumor nanoparticles, as well as enriching and optimizing the application of CDT in tumor therapy. Statement of Significance Our study pioneers the Fe-CHC nanoparticle, a metal-coordination polymer that targets MCT4 in glioblastoma cells to restore intracellular acidity and synergize with Fe 3+ to boost chemodynamic therapy (CDT). Unlike other studies, Fe 3+ and CHC work together to maximize the therapeutic potential and safety of Fe-CHC with minimal complexity. This innovative approach not only increased the production of reactive oxygen species within tumor cells, but also hindered tumor metastasis. Our work has important scientific implications for tumor microenvironment regulation and the application of CDT, and will provide a promising pathway for the treatment of aggressive cancers and attract a wide audience through its scientific implications.
研究领域:
肿瘤学
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纳米医学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 25
·13801-13810
·
IF 6.895
Xia Meng,Yurui Xu,Qiangbing Lu,Lei Sun,Xueying An,Jikang Zhang,Jianmei Chen,Ya Gao,Yu Zhang,Xinghai Ning
Lactic acidosis is one of the key characteristics of the tumor microenvironment (TME), and plays a critical role in therapy resistance, making it an attractive target for enhancing anticancer treatment. However, no effective systems exhibit the ability to selectively neutralize tumor lactic acidosis in a controlled manner. Here, we have developed novel ultrasound-responsive alkaline nanorobots (AN-DSP), composed of PLGA nanoparticles containing doxorubicin (DOX), sodium carbonate (Na2CO3) and perfluorocarbon (PFC), for recovering from lactic acidosis-mediated drug resistance. AN-DSP exhibit sensitive response to ultrasound stimulation, and rapidly release Na2CO3 to neutralize lactic acidosis, consequently enhancing DOX susceptibility in vitro and in vivo. Particularly, our nanorobots autonomously accumulate in tumors by an enhanced permeability and retention effect, and can specifically disrupt the tumor acidic microenvironment in response to external ultrasonic powering, resulting in the inhibition of tumor growth with minimal adverse effects. Therefore, AN-DSP represent a promising approach for selectively overcoming tumor lactic acidosis induced therapeutic resistance.
研究领域:
肿瘤学
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纳米医学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
INORGANIC CHEMISTRY
·
2024
·
IF 4.3
Yanqi Li,Han Li,Bingbing Sun,Jie Zheng,Tian Xu,Yuan Liu,Xiaorong Zhu,Shiqi Zhang,Sisi Liu,Ming Ge,Xiaolei Yuan
As a critical component for the oxygen reduction reaction (ORR), platinum (Pt) catalysts exhibit promising catalytic performance in High-temperature-proton exchange membrane fuel cells (HT-PEMFCs). Despite their success, HT-PEMFCs primarily utilize phosphoric acid-doped polybenzimidazole (PA–PBI) as the proton exchange membrane, and the phosphoric acid within the PBI matrix tends to leach onto the Pt-based layers, easily causing toxicity. Herein, we first propose UiO-66@Pt3Co1-T composites with precisely engineered interfacial structures. The UiO-66@Pt3Co1-T exhibits an octahedral porous framework with uniform structural dimensions and even distribution of surface nanoparticles, which demonstrate superior ORR performance compared to commercial Pt/C. The unique structure and morphology of the composites also exhibit a favorable half-wave potential in different concentrations of phosphoric acid electrolyte, regulated by the phosphoric acid adsorption site and intensity.This finding suggests that the incorporation of Co could effectively modulate the Pt d-band center, thereby enhancing the ORR performance. Furthermore, the selective adsorption of phosphoric acid by ZrO2 enables precise control over the phosphoric acid distribution. Notably, the retention of the octahedral framework post high-temperature treatment facilitates the establishment of dual transport pathways for gases and protons, leading to a stable and efficient triple-phase boundary.
研究领域:
材料科学
·
化学工程
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能源科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Mengyao Mu,Mengmeng Zhang,Jie Liu,Ke Ren,Hui Liu,Lixian Yip,Kai Guo,Feifei Teng,Jian Dong,Xueli Xu,David Tai Leong,Xiao Sun
Traditional antitumor strategies often require sufficient time to assess the effectiveness according to changes in tumor structure. Once ineffective, patients may miss the critical window for pursuing alternative treatment options. Herein, a manganese sulfide nanoplatform loaded with proton pump inhibitor (PPI) is developed. This nanoplatform is designed for visualizing tumor acidosis degree by magnetic resonance imaging (MRI), achieving real-time therapeutic efficacy precognition. The nanoplatform releases PPI, H 2 S, and Mn 2+ within the acidic lysosome of tumor cells. PPI inhibits V-ATPase expression, leading to an increase in intracellular H + levels. H 2 S accelerates glucose consumption of tumor cells, producing more lactic acid and further inducing tumor acidosis. Tumor acidosis in turn accelerates the nanoplatform's degradation, achieving higher tumor MRI. As the tumor acidosis degree correlates positively with tumor regression, real-time visualization of acidosis degree effectively predicts future therapeutics. Interestingly, tumor acidosis achieves efficient tumor metastasis suppression rather than increases it. Overall, this work presents a nanoplatform capable of visualizing tumor acidosis in real-time and precisely predicting future therapeutics.
研究领域:
肿瘤学
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医学影像学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
·
IF 10.8
Yuqing Tong,Meng Gu,Xingyu Luo,Haifeng Qi,Wei Jiang,Yu Deng,Lulu Wei,Jun Liu,Yin Ding,Jianfeng Cai,Yong Hu
Tumor extracellular acidity and chemoresistance are regarded as the main obstacles to achieving optimal chemotherapeutic efficacy in tumor therapy. Herein, a new kind of acid-cascade P-S-Z nanoparticles (NPs) is developed to relieve extracellular acidosis and enhance chemotherapy without causing drug resistance. The P-S-Z NPs selectively accumulate in tumors and then regulate the release of S-Z NPs containing syrosingopine (Syr) and acid-activated prodrug ZMC1-Pt depending on the extracellular acidity. Benefiting from their small size and positive surface charge, S-Z NPs are easily internalized by tumor cells in deep tumor tissue, facilitating the release of Syr to inhibit lactic acid excretion and ultimately enhance cell acidosis. The prolonged intracellular acidosis not only inhibits tumor cell proliferation , but also continuously triggers the activation of ZMC1-Pt prodrug, a platinum-based chemotherapeutic drug that effectively eliminates cancer cells and restores wild-type p53 function to prevent tumor chemoresistance. As a proof of concept, this is a promising strategy to transfer the adverse effect of intracellular acidosis to facilitate chemotherapy. This well-designed delivery system effectively kills tumor cells without causing significant tumor drug resistance, thus opening a new window to treat cancer.
研究领域:
肿瘤学
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药剂学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2020
·Vol. 10
·期 1
·1-9
·
IF 3.998
Zhang Youyou,Yu Yalei,Zhang Jie,Guan Chuhuai,Liu Liang,Ren Liang
Postmortem diagnosis of cantharidin-induced myocardial injury and postmortem interval estimation (PMI) are the challenges in forensic science. Cardiac biomarkers play an important role in the prediction and diagnosis of myocardial injury and can be used to determine the PMI. Based on the evidence, we aimed to explore the biomarkers which may be used for the postmortem diagnosis of cantharidin-induced myocardial injury and PMI estimation using the study of the proteins expression of TN-T, VEGF and HIF-1α by ELISA. Results of this study suggested that postmortem pathological changes were difficult to identify due to the autolysis of myocardium 72 h after death in cantharidin poisoning group. The plasma levels of TN-T and HIF-1α/TN-T are cardiac biomarkers with higher diagnostic accuracy for postmortem diagnosis of cantharidin-induced myocardial injury, VEGF/HIF-1α promises to be a biomarker for PMI estimation. Further studies are needed to verify these biomarkers, based on population, for being a useful tool in postmortem diagnosis of cantharidin-induced myocardial injury and PMI estimation.
研究领域:
法医学
·
病理学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2019
·Vol. 30
·期 6
·1908365
·
IF 15.621
Xiaoyan Chen,Huilin Zhang,Meng Zhang,Peiran Zhao,Ruixue Song,Teng Gong,Yanyan Liu,Xinhong He,Kuaile Zhao,Wenbo Bu
Chemodynamic therapy (CDT) by introducing the Fenton-/Fenton-like reaction in an acidic and H 2 O 2 environment for toxic hydroxyl radical (•OH) generation, is a newly developed tumor-selective therapeutic. However, tumor acidosis, characterized by extracellular acidity (pH e ≈ 6.5) and intracellular alkalinity (pH i ≈ 7.2), undoubtedly confers a large chemical barrier for effective implementation of intracellular CDT and thus limits its functional activity and therapeutic efficacy. Here, the unique amorphous iron nanoparticles (AFeNPs) loaded with carbonic anhydrase IX inhibitor (CAI) are constructed to re-establish tumor acidosis with decreased pH i and increased pH e via inhibiting the over-expressed CA IX in cancer cells by CAI for self-enhanced CDT. The suppression of CA IX leads to H + accumulation in cells that could accelerate the AFeNPs-based Fenton reaction to drastically exacerbate oxidative stress in cells and subsequently induce cell death; meanwhile, the inhibition of H + formation outside cells efficiently represses the potential of tumor invasion and metastasis owing to the insufficient acidic ions for degradation of tumor extracellular matrix. Re-established tumor acidosis not only assists in the optimization of CDT, but also presents an opportunity for the development of new antitumor methods that are more tumor-acidity specific.
研究领域:
纳米医学
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癌症治疗
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生物化学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）