Oncology Letters
·
2018
·Vol. 17
·期 1
·652-659
·
IF 1.664
Hongchao Han,Jie Xu,Weiwei Ji,Lisheng Wang,Aikun Wang
Transmembrane protein with epidermal growth factor (EGF)‑like and two follistatin motifs 2 (TMEFF2) is downregulated in human gastric cancer, and its levels are associated with tumor aggressiveness. Herein, a positive correlation was identified between serum vitamin C levels (µg/ml) and mRNA levels of TMEFF2 in gastric cancer tissue. TMEFF2 silencing promotes cell proliferation in GES‑1 normal human gastric epithelial cells and AGS human gastric adenocarcinoma cells. Notably, vitamin C and AG490 exerted antiproliferative effects on the two cell lines. The present study demonstrated that small interfering (si)‑RNA‑TMEFF2 exerts pro‑proliferative effects on GES‑1 and AGS cells. The results revealed that vitamin C significantly inhibited the growth of GES‑1 and AGS cells by reducing cell viability, decreasing the expression of proliferating cell nuclear antigen (PCNA), and blocking the STAT3 pathway. Moreover, siRNA‑TMEFF2‑induced enhanced cell viability and PCNA expression were significantly reversed by additional vitamin C treatment; notably, markedly enhanced TMEFF2 expression was observed. Upregulated TMEFF2 expression was observed in association with the antiproliferative effect of AG490. In conclusion, serum vitamin C content (µg/ml) was positively correlated with the mRNA levels of TMEFF2 in gastric cancer tissue. Exploring novel drugs that target TMEFF2 is a potential therapeutic strategy for blocking human GC.
研究领域:
肿瘤学
·
分子生物学
·
药理学
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PubMed
高影响因子
Pharmaceuticals
·
2026
·Vol. 19
·期 8
·1165
·
IF 5.7
Yongsheng Huang,Zhengguang Guo,Ludan Chang,Mei Huang,Lin Wang,Rongtao Lai,Chunlin Zhang
Background: P97 regulates diverse cellular processes, including proteostasis, metabolism and pluripotency. Pharmacological inhibitors of P97 protein have shown antitumor activity in various cancers. However, the downstream pathways and effectors remain poorly characterized, limiting clinical translation.Methods: We performed a quantitative proteomic analysis using liquid chromatography–mass spectrometry (LC–MS) to identify differentially expressed proteins (DEPs) (fold change > 1.5,p< 0.05) and pathway alterations in gastric cancer AGS cells following treatment with two distinct P97 inhibitors, Eeyarestatin I (EerI) and NMS873.Results: Proteomic analysis revealed that both inhibitors significantly perturbed multiple signaling pathways. The endoplasmic reticulum (ER) proteostasis network was markedly disrupted, evidenced by activation of the unfolded protein response (UPR) and upregulation of ER-associated degradation (ERAD) components. Pathway enrichment further indicated that cell death processes, particularly ferroptosis, were prominently affected (p< 0.05). Key ferroptosis regulators showed altered expression, which was validated by Western blotting. Functional assays demonstrated that P97 inhibition suppressed cell proliferation and increased the accumulation of ferroptosis-associated lipid hydroperoxides in vitro, suggesting execution of ferroptotic cell death. In vivo, using a xenograft mouse model established by subcutaneous injection of AGS cells into nude mice, P97 inhibition significantly reduced tumor growth, confirming its antitumor efficacy.Conclusions: This integrated proteomic and functional study delineates that pharmacological P97 inhibitors disrupt ER proteostasis and simultaneously trigger ferroptosis in gastric cancer cells. These findings identify ferroptosis as a key downstream mechanism of P97 inhibition and provide molecular mechanisms for developing P97-targeted therapies in gastric cancer.
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高影响因子
PETROLEUM CHEMISTRY
·
2021
·Vol. 61
·期 11
·1305-1318
·
IF 1.029
Zhu Wenxi,Zheng Xiuhua
Abstract Colloidal Gas Aphron (CGA) drilling fluid is one of the most promising
techniques in underbalanced drilling with excellent plugging and reservoir
protection functions. Due to the limitation of poor thermal stability of
commercial foaming agents used in oilfields, the research on high-temperature
resistant CGA drilling fluid is still a challenge. In this study, a
biodegradable glycine foaming agent AGS-12 was synthesized via a one-step
method. The surface activity, foaming performance (25–150°C) of AGS-12 and the
high temperature performance of AGS-12 based CGA drilling fluid (120–150°C) were
studied. All the results provide a basis for the potential application of AGS-12
as an eco-friendly foaming agent in high-temperature CGA drilling fluids: 1) The
product AGS-12 with 87% conversion rate was synthesized successfully by one-step
method, which can be verified by FT-IR. TGA analysis suggested that AGS-12 had
good thermal stability within 315°C. Moreover, AGS-12 is easily biodegradable
and fully meets the first level discharge standard of petrochemical industry
pollutants. 2) AGS-12 can reduce the surface tension of solvent water from 72.38
to 28.44 mN/m. Analysis of fundamental surface activity parameters illustrates
the higher surface activity of AGS-12, compared with a variety of amino acid
surfactants. 3) Waring-Blender test showed that foams generated by 3% AGS-12
always have higher half-life, foam quality and lower drainage speed than the
foaming agents available on market within 150°C. 4) At 120/140/150°C, aphrons
with diameter of 10–150 µm have been successfully generated in CGA drilling
fluid by using AGS-12 as foaming agent. Rheological and filtration tests
suggested that AGS-12 based CGA drilling fluid is a high-performance drilling
fluid with strong shear thinning behavior, high viscosity, and low filtration
invasion.
研究领域:
石油工程
·
环境科学
·
材料化学
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高影响因子
Journal of Environmental Chemical Engineering
·
2026
·Vol. 14
·期 6
·125429
·
IF 7.5
Fu Wei,Quanli Chen,Xilong Liu,Xiaozhuo Li,Chenhui Zhang,Yuyang Zhang,Qian Zhang
8 mg·L⁻¹ SMX is the threshold, beyond which TN removal severely deteriorates (<30%). • Inhibition stems from AMO/NR activity loss, causing gene-function decoupling. • Thauera abnormally surges under SMX stress but fails to execute actual N-removal. • Microbes shift from N-removal to survival defense, enriching sul1/sul2 ARGs. • SMX activates ABC transporters and quorum sensing for resistance and survival. To investigate the microscale inhibition mechanism of sulfamethoxazole (SMX) on nitrogen removal in Aerobic granular sludge–sequencing batch reactor(AGS–SBRs), system responses were evaluated under gradient SMX concentrations (0–20 mg·L⁻¹). Pollutant sensitivity followed TN > NH₄⁺–N > COD, exhibiting distinct disruption thresholds. Specifically, 8 mg·L⁻¹ emerged as a critical threshold for nitrification inhibition, where NH₄⁺-N removal decreased to 89.88%. As stress intensified to 10 mg·L⁻¹ , TN removal severely deteriorated to below 30%, marking the collapse of denitrification. LC-MS and metagenomic analyses revealed that at low concentrations, SMX was detoxified via S-N bond cleavage and hydroxylation, followed by high-mass coupling polymerization and β-oxidation-driven complete mineralization. However, at 8 mg·L⁻¹ , an enzymatic degradation bottleneck emerged. This accumulation of SMX served as the turning point for microbial succession, significantly inhibiting Nitrosomonas while causing an abnormal abundance surge of Thauera . Under this stress, although nitrogen transformation genes remained abundant, AMO and NR enzymatic activities were suppressed by 12.59% and 33.42%, causing severe gene function decoupling. Consequently, the microbial strategy shifted fundamentally from metabolic degradation to survival defense, evidenced by the marked enrichment of sul1 and sul2 resistance genes, alongside Thauera’s peak contributions to ABC transporters and quorum sensing. These findings provide multidimensional insights for threshold regulation in antibiotic-containing wastewater treatment. Download: Download high-res image (243KB) Download: Download full-size image
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高影响因子
iScience
·
2022
·
IF 6.107
Dawei Yang,Jie Yin,Liuqun Shan,Xingling Yi,Wei Zhang,Yongbin Ding
Summary Cancer cells tend to utilize aerobic glycolysis to generate energy and metabolites; the end product of aerobic glycolysis is lactate, which promotes lysine lactylation (Kla). Kla is a newly discovered histone post-translational modification (PTM) that plays important roles in regulating gene expression. However, Kla in non-histone mammalian proteins is unclear. Here, a comprehensive analysis of lactylated proteins in gastric cancer AGS cells was conducted. There were 2375 Kla sites found in 1014 proteins. Interestingly, KEGG pathway analysis showed that these proteins were significantly enriched in spliceosome function. In addition, Kla was more abundant in gastric tumors than in adjacent tissues, and high levels of Kla in gastric tumors were associated with poor prognosis. These results suggest that Kla could be a prognostic marker in gastric cancer. This lysine lactylome analysis in gastric cancer cells, the first of its kind, provides a valuable foundation for further studies of Kla.
研究领域:
癌症生物学
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蛋白质组学
·
分子生物学
·
生物化学
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PubMed
高影响因子
JOURNAL OF ENVIRONMENTAL MANAGEMENT
·
2023
·
IF 8.7
Feiyu Zhang,Shuqian Cheng,Jinbo Zhao,Anjie Li
Even after pre-treatment, livestock and poultry wastewater still contain high concentrations of ammonia and residual antibiotics. These could be removed economically using the aerobic granular sludge (AGS) process with zero-valent iron (ZVI). The interaction of antibiotics and nitrogen in this process needs to be clarified and controlled, however, to achieve good removal performance. Otherwise, antibiotics might generate transformation products (TPs) with higher toxicity and lead to the emergence of antibiotic-resistant bacteria carrying antibiotic resistance genes (ARGs), which could cause persistent toxicity and the risk of disease transmission to the ecological environment. This study investigated the impact of ZVI on AGS for nitrogen and sulfamethoxazole (SMX) removal. The results show that AGS could maintain good ammonia removal performance and that the existence of SMX had a negative impact on ammonia oxidation activities. ZVI contributed to an increase in the abundance of nitrite oxidation bacteria, denitrifying bacteria and the functional genes of nitrogen removal. This led to better total nitrogen removal and a decrease in N 2 O emission. Accompanied by biological nitrogen transformation, SMX could be transformed into 14 TPs through five pathways. ZVI has the potential to enhance transformation pathways with TPs of lower ecotoxicity, thereby reducing the acute and chronic toxicity of the effluent. Unfortunately, ZVI might enhance the abundance of sul1 , sul2 , and sul3 in AGS, which increases the risk of sulfonamide antibiotic resistance. In AGS, Opitutaceae , Xanthomonas , Spartobacteria and Mesorhizobium were potential hosts for ARGs. This study provides theoretical references for the interaction of typical antibiotics and nitrogen in the biological treatment process of wastewater and bioremediation of natural water bodies.
研究领域:
环境工程
·
水处理
·
微生物学
·
生物修复
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DOI
PubMed
高影响因子
mBio
·
2026
·
IF 5.4
Luan Luan,Xiuling Song,Yunfei Zeng,Yunyun Xie,Yongxuan Hong,Jiawei Tang,Cong Ma,Bing Gu,Liang Wang
Gastric cancer remains a major global health burden, ranking fifth worldwide in both incidence and mortality. While Helicobacter pylori is a well-established Group I carcinogen, increasing evidence suggests that non-H. pylori bacteria, including Streptococcus anginosus, may also contribute to gastric carcinogenesis. However, their comparative pathogenic roles and interactions remain poorly defined. In this study, public databases showed stage-dependent abundance changes of H. pylori and S. anginosus but no significant correlation during gastric cancer progression. We further quantified both bacteria in gastric fluid samples collected from 500 individuals using a non-invasive gastric string test and in fecal samples from an independent cohort of 500 individuals by qPCR. In the two cohorts, no significant correlations were observed between the two bacterial pathogens, suggesting distinct colonization and pathogenic patterns. To evaluate functional differences, AGS cell co-culture models were established to explore their pro-tumorigenic effects. H. pylori predominantly exerted tumor-promoting effects through bacterial cell-associated mechanisms, whereas S. anginosus exerted stronger pro-tumorigenic effects via its metabolites. In particular, transcriptomic analysis revealed that proliferation-associated genes, including DEK and RTF1, were significantly upregulated by 21.9-fold and 19.2-fold, respectively, in cells treated with Streptococcus anginosus metabolite (SAM). Metabolomic profiling of SAM identified increased levels of spermidine and polyamine-related metabolites. Among these, N-acetylcadaverine, N-acetyltyrosine, N-acetyltryptophan, and urocanic acid were experimentally validated to significantly promote AGS cell proliferation. Collectively, these findings demonstrate that H. pylori and S. anginosus drive gastric tumorigenesis through contact-dependent and metabolite-mediated mechanisms, respectively, highlighting bacterial metabolites as emerging contributors to gastric cancer progression.
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PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-15
·
IF 3.8
Wang Yan,Wang Shasha,Ma Chenchen,Qi Weiwei,Lv Jing,Zhang Mengqi,Wang Shibo,Wang Rui,Lu Yangyang,Qiu Wensheng
Gastric cancer (GC) is the most common malignant tumor of the gastrointestinal tract and currently has a poor clinical outcome. Turmeric’s rhizome contains a polyphenolic component called curcumin (Cur), which has been demonstrated to inhibit a variety of tumor cells, such as pancreatic, colon, lung and gastric cancers. However, it remains to be elucidated how Cur functions in GC and what molecular processes underlie it. Here, Cur showed a stronger inhibitory effect on GC cells AGS and HGC27. In addition, Cur’s inhibition of GC cells growth was accompanied by increased ROS production, triggering of the Keap1-Nrf2 signaling pathway, and increased transcription of its downstream antioxidant genes HO-1, GCLM, and NQO1. However, when a ROS scavenger NAC was used, the inhibitory effect of Cur on GC cells was reversed. Nuclear factor erythroid 2-related factor 2 (Nrf2) is overexpressed or activated in cancers to shield cancer cells from oxidative damage by responding to oxidative stress (OS). Cur has been found to act as an activator of Nrf2. Notably, compared with Nrf2 knockdown and Cur alone, the combination of the two dramatically increased Cur-induced ROS overaccumulation and inhibition of GC cells proliferation, migration, and invasive abilities. Consistent with in vitro experiments, Cur combined with Nrf2 knockdown significantly inhibited tumor growth in nude mice transplanted with AGS cells. Therefore, we concluded that Nrf2 depletion enhanced Cur therapy effect in GC by inducing the excessive accumulation of ROS, indicating that this is a promising treatment strategy.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症治疗
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PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2025
·
IF 2.5
Xiao-Jian Li,Xinli Lu,Yunxia Wang,Zhanquan Zhang,Yongfa Zhang
This study successfully developed a highly sensitive electrochemiluminescence (ECL) sensor based on the ECL resonance energy transfer mechanism for detecting the key biomarker of acute myocardial infarction, heart–type fatty acid binding protein (h–FABP). Through the meticulous design of the Ag/Cu2O/Ti3C2 ternary nanocomposite material, this material demonstrated significant catalase–like catalytic activity, enabling the efficient decomposition of H2O2 to generate more superoxide radicals (O₂•⁻), thereby significantly enhancing the ECL signal of the luminol–H2O2 system. Notably, AgS quantum dots (AgS QDs), due to broad–spectrum ultraviolet absorption overlapping with the ECL emission spectrum of luminol, triggered an efficient energy resonance transfer effect, resulting in the decrease of ECL intensity. NH2–MIL–101(Fe) was utilized to couple with AgS QDs (AgS QDs@NH2–MIL–101(Fe)), which can further enhance the quenching efficiency. Based on this signal–off strategy, an ultrasensitive detection platform for h–FABP was successfully constructed. Experimental results indicated that the immunosensor exhibited an excellent response relationship within a wide linear range from 1.00 fg mL–1 to 100 ng mL–1, and a low detection limit reached 0.36 fg mL–1 (S/N = 3). This study provides an innovative methodological approach for ultra–trace detection of myocardial injury markers and demonstrates significant application potential in early clinical diagnosis.
研究领域:
分析化学
·
生物传感器
·
纳米技术
·
生物化学
·
临床诊断
·
心血管研究
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高影响因子
Environmental Science-Nano
·
2018
·Vol. 5
·期 12
·2936-2944
·
IF 6.087
Xiaoying Zheng,Dan Lu,Yuan Zhang,Wei Chen,Mengqi Jin,Xiaoyao Shao,Mengmeng Yang
The increasing use of cerium dioxide nanoparticles (CeO2 NPs) has raised concerns about their potential environmental toxicity. Denitrifying phosphorus removal-aerobic granular sludge (DPR-AGS) is a distinct form of microbial aggregates. In this study, the phosphorus removal efficiencies, the metabolic intermediates of polyhydroxyalkanoates (PHA) and glycogen, the enzyme activities of exophosphatase (PPX) and polyphosphate kinase (PPK), and the microbial community of DPR-AGS under long-term exposure to CeO2 NPs (0 (the control), 1, and 10 mg L−1) in anaerobic/oxic/anoxic (A/O/A) sequencing batch reactors (SBRs) were investigated. The results showed that chronic toxicity caused by 10 mg L−1 CeO2 NPs resulted in increased reactive oxygen species (ROS) production and lactate dehydrogenase (LDH) release, which reached 176.32% and 237.35%, respectively, when compared with the control (100%). High-throughput sequencing showed that denitrifying-phosphorus-accumulating organisms (DPAOs) were more sensitive to CeO2 NPs than phosphorus-accumulating organisms (PAOs), which was in accordance with phosphorus transformations during one cycle. However, the abundance of Dechloromonas and Defluviicoccus increased from 4.68% and 3.08% (R0) to 9.95% and 7.06% (R10), respectively, indicating that the tolerance of glycogen-accumulating organisms to CeO2 NPs was stronger than that of PAOs, which was consistent with the transformation of the metabolic pathway from polyphosphate accumulation (PAM) to glycogen accumulation (GAM).
研究领域:
环境科学
·
微生物学
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高影响因子
Cell and Bioscience
·
2023
·Vol. 13
·期 1
·1-10
·
IF 7.5
Yu Yu,Wang Miao,Li Xiao-Wei,Mao Jie,Zhu Ying-Jie,Wang Na,Yin Le-Hua,Guo Zeng-Lin,Cai Hong,Li Tao,Liang Ting-Ting,Cui Jiuwei,Zhou Tao
Background Cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is critical for cytosolic DNA-sensing and the subsequent immune responses. The inappropriate activation of this pathway leads to DNA-induced autoimmune response. Understanding the precise regulation of cGAS-STING pathway is important for developing therapeutics to treat several autoimmune diseases caused by self-DNA.Results We report that Meloxicam (MXC) inhibits intracellular DNA-, but not RNA-induced immune responses. We find that MXC inhibits the phosphorylation of STING by examining in different cells with various DNA stimulations. We further find that MXC significantly dampens the expression levels of interferon-stimulated genes (ISGs) by using DNA 3’ repair exonuclease 1 (TREX1)-deficient cell, an experimental model for self-DNA-induced autoimmune disease. Importantly, we demonstrate that MXC could promote the survival in Trex1–/– mouse model for Aicardi-Goutières syndrome (AGS).Conclusion sOur study identified a non-steroidal anti-inflammatory drug, MXC, that exhibits potential effect in treating the autoimmunity caused by self-DNA.
研究领域:
免疫学
·
药理学
·
自身免疫疾病
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·Vol. 33
·期 19
·2213465
·
IF 19
Huiyi Liang,Yibo Du,Lixin Liu,Junqiu Liu,Yongming Chen
Excessive self-DNAs recognized by intracellular DNA sensors can initiate innate immunity to express disordered TNF-α or type I IFN resulting in several autoimmune diseases. Cationic polymers have been profoundly proved to alleviate the inflammatory symptoms by removing the debris of cell-free DNA (cfDNA). However, clinical applications of cationic materials have been impeded by concerns of their toxicity and the fate of cfDNA in polymer-cfDNA complex. Herein, it is showed that PEGylated polyimidazoles as a biomimetic DNase potently alleviate pathologic symptoms of self-DNA-associated rheumatoid arthritis (RA) rats and Trex1 (DNase III) deficient Aicardi-Goutiéres syndrome (AGS) mice. The mechanism studies demonstrate that the polyimidazole efficiently attacks the phosphodiester linkages of NAs and cleavages them into small pieces. As imidazole unit is a much weaker organic base that occurs in natural proteins, the polyimidazoles are less toxic to cells and tissues, as manifested by the IC50 values larger than 1000 µg mL −1 . This work suggests that synthetic tailored DNase can be a new and safe therapeutic agent to treat chronic autoimmune and refractory inflammatory diseases by degradation of excessive nucleic acids.
研究领域:
免疫学
·
生物医学工程
·
分子生物学
·
药理学
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DOI
高影响因子
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