International Journal of Biological Sciences
·
2019
·
IF 4.067
Peihai Cao,Yiqun Xia,Wei He,Tingting Zhang,Lin Hong,Peisen Zheng,Xin Shen,Guang Liang,Ri Cui,Peng Zou
Colon cancer is a malignant type of cancer with high prevalence and is one of the primary causes of cancer-related deaths. Oxaliplatin plays a significant role in the treatment of cancer, but the application of oxaliplatin is restricted due to its toxic side effects and drug resistance in clinical practice. Therefore, there is an urgent need for new strategies that can synergize with oxaliplatin for confronting colon cancer. Alantolactone (ALT), a natural sesquiterpene lactone, possesses antitumor properties in a number of cancer cell lines. In the present study, we investigated how ALT acts synergistically with oxaliplatin on human colorectal cancer HCT116 and RKO cells in vitro and in vivo . We observed that ALT strengthened the effect of oxaliplatin-induced growth restrain and apoptosis in HCT116 and RKO cells. It is through a mechanism concerning remarkable accumulation of intracellular reactive oxygen species (ROS) and activation of JNK and p38 MAPK signaling pathways. These changes ultimately induced apoptosis of HCT116 and RKO cells. Pretreatment of cells with the ROS reversal agent NAC significantly blocked the apoptosis induced by the combination treatment, and suppressed expression of JNK and p38 phosphorylation in HCT116 and RKO cells. In the xenograft model, the combination therapy displayed stronger antitumor activity compared with single agents. Immunohistochemistry of subsequent treatment tumors showed a significant decrease in proliferation as compared to either of the treatments alone. These results suggest that the combination treatment with ALT and oxaliplatin may become a potential therapeutic strategy for colon cancer.
研究领域:
肿瘤学
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药理学
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Biomaterials and Tissue Engineering
·
2023
·Vol. 13
·期 11
·1072-1081
·
IF 0.1
Zhou Conglai,Zhao Kaixu,You XiaoLi,Wang Yuanzheng,Chen Long,Sun Li
In recent years, there has been significant development and application of bioactive materials with antioxidant and anti-inflammatory properties in skin regenerative medicine. In this study, we utilized sodium hyaluronate (HA), which has good biological activity and compatibility, as
a carrier for material mixing. Ginger extract (GE), a natural biologically active compound, was combined with N-Acetyl-L-cysteine (NAC) for the treatment of skin wounds. GE was extracted from fresh ginger juice through freeze-drying, which exhibit pharmacological effects such as antioxidant,
anti-inflammatory, and antibacterial properties. Additionally, NAC possesses notable pharmacological activities, particularly as an antioxidant and anti-inflammatory agent. By harnessing the natural advantages of GE in combination with NAC for wound healing, remarkable results were observed
in terms of antioxidant efficacy, anti-inflammatory effects, promotion of granulation tissue and wound repair processes. These outcomes surpassed those achieved by using the individual components alone. These experimental findings underscore the potential of combining plant-based medicines
and chemical drugs. This approach strengthens the synergistic effects of drug efficacy, reduces the use of and side effects associated with chemical drugs, and holds significant research and development potential. Moreover, it promotes the wider adoption and application of traditional Chinese
medicine technology.
研究领域:
皮肤再生医学
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药理学
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天然产物研究
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DOI
高影响因子
Environmental Science-Processes & Impacts
·
2023
·Vol. 25
·期 12
·1962-1973
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IF 5.5
Jine Wang,Chen Zhang,Rui Zhao,Pei Wang,Meihua Jin,Jiujun Xu
Marine biofouling is a thorny issue that causes serious economic losses and adverse ecological impacts on marine ecosystems. Effective and promising antifouling strategies such as surface hydration, flow shear force, and lubricant injection have been developed to address this challenge. However, for the complex marine environment, they still appear inadequate. Mussels are a common fouling organism with strong surface adhesion ability. However, when hypoxia and the oxidative cross-linking reaction of 3,4-dihydroxy phenyl-L-alanine (DOPA) in the structure of adhesion proteins are disrupted, their adhesion ability will be greatly reduced. Inspired by this, we developed an effective antifouling strategy based on reactive oxygen species (ROS) scavenging using N-acetylcysteine (NAC) and evaluated its performance. As a ROS scavenger interfered with the oxidative cross-linking reaction of DOPA in an aqueous solution, the adhesion of DOPA was also affected on the surface of NAC functionalized polyvinyl chloride (PVC) (PVC-NAC). In addition, the colonization level of mussels and the adhesion rate of marine bacteria and benthic diatoms on PVC-NAC were low. The antifouling strategy proposed in this paper was eco-friendly and broad-spectrum, and may provide a new idea for solving marine biofouling and reducing the environmental and economic impacts of fouling organisms.
研究领域:
海洋生物学
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材料科学
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环境科学
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产品关联
DOI
PubMed
高影响因子
Antioxidants
·
2024
·Vol. 13
·期 7
·786
·
IF 6
Tiantian Liu,Bin Jiang,Baoqiang Fu,Changyi Shang,Haobin Feng,Tao Chen,Yan Jiang
Previous research has established a correlation between PM2.5 exposure and aging-related cardiovascular diseases, primarily in blood vessels. However, the impact of PM2.5 on cardiomyocyte aging remains unclear. In this study, we observed that extractable organic matter (EOM) from PM2.5 exposure led to cellular senescence in H9c2 cardiomyoblast cells, as characterized by an increase in the percentage of β-galactosidase-positive cells, elevated expression levels of p16 and p21, and enhanced H3K9me3 foci. EOM also induced cell cycle arrest at the G1/S stage, accompanied by downregulation of CDK4 and Cyclin D1. Furthermore, EOM exposure led to a significant elevation in intracellular reactive oxygen species (ROS), mitochondrial ROS, and DNA damage. Supplementation with the antioxidant NAC effectively attenuated EOM-induced cardiac senescence. Our findings also revealed that exposure to EOM activated the aryl hydrocarbon receptor (AhR) signaling pathway, as evidenced by AhR translocation to the nucleus and upregulation of Cyp1a1 and Cyp1b1. Importantly, the AhR antagonist CH223191 effectively mitigated EOM-induced oxidative stress and cellular senescence. In conclusion, our results indicate that PM2.5-induced AhR activation leads to oxidative stress, DNA damage, and cell cycle arrest, leading to cardiac senescence. Targeting the AhR/ROS axis might be a promising therapeutic strategy for combating PM2.5-induced cardiac aging.
研究领域:
心血管疾病
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毒理学
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细胞生物学
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环境健康
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产品关联
DOI
PubMed
高影响因子
Scientific Reports
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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
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药理学
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分子生物学
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癌症治疗
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产品关联
DOI
PubMed
高影响因子
ACS ES&T Engineering
·
2021
·
IF 0
Lichun Li,Xiaoli Wei,Shenglan Zhou,Zhongsheng Jia,Chuanzhao Wang,Houlin Yu,Sen Wu,Ying Li,Wenfeng Han
Hydrochlorofluorocarbon (HCFC) has been widely applied as the third-generation refrigerant globally, however, the global warming potential of such gases is often 100 and 1000 times higher than that of CO2. Dehydrochlorination reaction offers an encouraging strategy to transform the high-global-warming-potential gases of hydrochlorofluorocarbons (HCFCs) to low-global-warming-potential gases of hydrofluoroolefins (HFOs). However, the handling of a large amount of byproduct HCl remains one of the major challenges blocking the industrialization of dehydrochlorination of HCFC-142a for the production of vinylidene fluoride (VDF). A one-pot cascade reaction combining dehydrochlorination of HCFC-142b and hydrochlorination of acetylene was first proposed to spontaneously produce valuable monomers of VDF and vinyl chloride monomer (VCM) while eliminating the tedious HCl treatment step. Both thermodynamic calculations and experimental results validate the feasibility of the cascade reaction. Five different heterogeneous catalysts were screened for the proposed cascade reaction, including monocomponent catalyst BaF2, NAC, bifunctional BaF2/NAC catalyst, and bicomponent BaF2-NAC-S and BaF2-NAC-M catalysts. Among them, the mixed BaF2-NAC-M catalyst demonstrated the best catalytic performance, with BaF2 mainly acting as the dehydrochlorination site and NAC mainly acting as the hydrochlorination site. The corresponding reaction mechanism was also proposed.
研究领域:
化学工程
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催化
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环境化学
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绿色化学
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产品关联
DOI
MECHANISMS OF AGEING AND DEVELOPMENT
·
2024
·
IF 5.3
Qingqiu Chen,Rong Hu,Hongmei Qiu,Shan Li,Peng Xiang,Yining Lu,Xianmin Wang,Tongchuan Wang,Lan Zhou,Wanping Zhang,E Wen,Limei Ma,Chao Yu
Endothelial cell senescence characterized by reactive oxygen species (ROS) accumulation and chronic inflammation is widely recognized as a key contributor to atherosclerosis (AS). Regulated in development and DNA damage response 1 (REDD1), a conserved stress-response protein that regulates ROS production, is involved in the pathogenesis of various age-related diseases. However, the role of REDD1 in endothelial cell senescence is still unclear. Here, we screened REDD1 as a differentially expressed senescence-related gene in the AS progression using bioinformatics methods, and validated the upregulation of REDD1 expression in AS plaques, senescent endothelial cells, and aging aorta by constructing AS mice, D-galactose (DG)-induced senescent endothelial cells and DG-induced accelerated aging mice, respectively. siRNA against REDD1 could improve DG-induced premature senescence of endothelial cells and inhibit ROS accumulation, similar to antioxidant N-Acetylcysteine (NAC) treatment. Meanwhile, NAC reduced the upregulation of REDD1 induced by DG, supporting the positive feedback loop between REDD1 and ROS contributes to endothelial cell senescence. Mechanistically, the regulatory effect of REDD1 on ROS might be related to the TXNIP-REDD1 interaction in DG-induced endothelial cell senescence. Collectively, experiments above provide evidence that REDD1 participates in endothelial cell senescence through repressing TXNIP-mediated oxidative stress, which may be involved in the progression of atherosclerosis.
研究领域:
心血管生物学
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分子生物学
·
细胞衰老
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衰老研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Xiaoxiao Xu,Chuang Ma,Hang Wu,Yuanqiao Ma,Zejin Liu,Peijie Zhong,Chaolei Jin,Wenjuan Ning,Xiao Wu,Yijie Zhang,Jichang Han,Junpeng Wang
Fructose is a commonly used food additive and has many adverse effects on human health, but it is unclear whether fructose impacts pulmonary fibrosis. TGF-β1, a potent fibrotic inducer, is produced as latent complexes by various cells, including alveolar epithelial cells, macrophages, and fibroblasts, and must be activated by many factors such as reactive oxygen species (ROS). This study explored the impact of fructose on pulmonary fibrotic phenotype and epithelial-mesenchymal transition (EMT) using lung epithelial cells (A549 or BEAS-2B) and the underlying mechanisms. Fructose promoted the cell viability of lung epithelial cells, while N-Acetyl-l-cysteine (NAC) inhibited such. Co-treatment of fructose and latent TGF-β1 could induce the fibrosis phenotype and the epithelial-mesenchymal transition (EMT)-related protein expression, increasing lung epithelial cell migration and invasion. Mechanism analysis shows that fructose dose-dependently promoted the production of total and mitochondrial ROS in A549 cells, while NAC eliminated this promotion. Notably, post-administration with NAC or SB431542 (a potent TGF-β type I receptor inhibitor) inhibited fibrosis phenotype and EMT process of lung epithelial cells co-treated with fructose and latent TGF-β1. Finally, the fibrosis phenotype and EMT-related protein expression of lung epithelial cells were mediated by the ROS-activated latent TGF-β1/Smad3 signal. This study revealed that high fructose promoted the fibrotic phenotype of human lung epithelial cells by up-regulating oxidative stress, which enabled the latent form of TGF-β1 into activated TGF-β1, which provides help and reference for the diet adjustment of healthy people and patients with fibrosis.
研究领域:
肺科学
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细胞生物学
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分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2023
·
IF 4.1
Aixuan Wang,Qiang Zhao,Minglu Liu,Yang Wang,Guode Zhao,Weiwei Li,Ying Peng,Jiang Zheng
Tolterodine (TOL) is an antimuscarinic drug used for the treatment of patients with overactive bladder presenting urinary frequency, urgency, and urge incontinence. During the clinical use of TOL, adverse events such as liver injury took place. The present study aimed at the investigation of the metabolic activation of TOL possibly associated with its hepatotoxicity. One GSH conjugate, two NAC conjugates, and two cysteine conjugates were found in both mouse and human liver microsomal incubations supplemented with TOL, GSH/NAC/cysteine, and NADPH. The detected conjugates suggest the production of a quinone methide intermediate. The same GSH conjugate was also observed in mouse primary hepatocytes and in the bile of rats receiving TOL. One of the urinary NAC conjugates was observed in rats administered TOL. One of the cysteine conjugates was found in a digestion mixture containing hepatic proteins from animals administered TOL. The observed protein modification was dose-dependent. CYP3A primarily catalyzes the metabolic activation of TOL. Ketoconazole (KTC) pretreatment reduced the generation of the GSH conjugate in mouse liver and cultured primary hepatocytes after TOL treatment. In addition, KTC reduced the susceptibility of primary hepatocytes to TOL cytotoxicity. The quinone methide metabolite may be involved in TOL-induced hepatotoxicity and cytotoxicity.
研究领域:
药理学
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毒理学
·
药物代谢
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产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2023
·
IF 4.3
Kaixuan Li,Guode Zhao,Lan Yang,Xingyu Gao,Yudi Jia,Yang Wang,Xiaohong Zhang,Weiwei Li,Ying Peng,Jiang Zheng
4-Methylquinoline (4-MQ) is a quinoline derivative widely present in groundwater and soil and has been reported to be genotoxic. The mechanisms of the toxic action remain unknown. This study aimed to elucidate the metabolic activation of 4-MQ and to determine the possible role of reactive metabolites in 4-MQ-induced liver injury in rats. In the present study, a hydroxylation metabolite (M1), a GSH conjugate (M2) and an NAC conjugate (M3) derived from 4-MQ were detected in vitro and in vivo . The structures of the two conjugates were verified by chemical synthesis, mass spectrometry, and nuclear magnetic resonance. CYP3A4 was found to dominate the hydroxylation of 4-MQ. Sulfotransferases also participated in the metabolic activation of 4-MQ. Pretreatment of primary hepatocytes with ketoconazole (KTC) or 2,6-dichloro-4-nitrophenol (DCNP) not only reduced the production of GSH conjugate M2 but also decreased the susceptibility of hepatocytes to the cytotoxicity of 4-MQ. Urinary NAC conjugate M3 was found in rats given 4-MQ, and M3 may be a potential biomarker for 4-MQ exposure.
研究领域:
毒理学
·
药理学
·
环境科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2021
·Vol. 25
·期 11
·4962-4973
·
IF 5.31
Mingyu He,Gege Yan,Yang Wang,Rui Gong,Hong Lei,Shuting Yu,Xiaoqi He,Guanghui Li,Weijie Du,Tianshuai Ma,Manqi Gao,Meixi Yu,Shenzhen Liu,Zihang Xu,Elina Idiiatullina,Naufal Zagidullin,Valentin Pavlov,Benzhi Cai,Ye Yuan,Lei Yang
Osteosarcoma (OS) is the most common primary malignant bone tumour in adolescence. Lately, light-emitting diodes (LED)-based therapy has emerged as a new promising approach for several diseases. However, it remains unknown in human OS. Here, we found that the blue LED irradiation significantly suppressed the proliferation, migration and invasion of human OS cells, while we observed blue LED irradiation increased ROS production through increased NADPH oxidase enzymes NOX2 and NOX4, as well as decreased Catalase (CAT) expression levels. Furthermore, we revealed blue LED irradiation-induced autophagy characterized by alterations in autophagy protein markers including Beclin-1, LC3-II/LC3-I and P62. Moreover, we demonstrated an enhanced autophagic flux. The blockage of autophagy displayed a remarkable attenuation of anti-tumour activities of blue LED irradiation. Next, ROS scavenger N-acetyl-L-cysteine (NAC) and NOX inhibitor diphenyleneiodonium (DPI) blocked suppression of OS cell growth, indicating that ROS accumulation might play an essential role in blue LED-induced autophagic OS cell death. Additionally, we observed blue LED irradiation decreased EGFR activation (phosphorylation), which in turn led to Beclin-1 release and subsequent autophagy activation in OS cells. Analysis of EGFR colocalization with Beclin-1 and EGFR-immunoprecipitation (IP) assay further revealed the decreased interaction of EGFR and Beclin-1 upon blue LED irradiation in OS cells. In addition, Beclin-1 down-regulation abolished the effects of blue LED irradiation on OS cells. Collectively, we concluded that blue LED irradiation exhibited anti-tumour effects on OS by triggering ROS and EGFR/Beclin-1-mediated autophagy signalling pathway, representing a potential approach for human OS treatment.
研究领域:
肿瘤学
·
细胞生物学
·
分子生物学
·
光生物学
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产品关联
DOI
PubMed
高影响因子
NEW PHYTOLOGIST
·
2024
·
IF 8.3
Honglian Gu,Jiaxing Li,Dahe Qiao,Mei Li,Yingjie Yao,Hui Xie,Ke-lin Huang,Shengrui Liu,De-Yu Xie,Chaoling Wei,Junyan Zhu
Summary Numerous herbivore-induced plant volatiles (HIPVs) play important roles in plant defense. In tea plants ( Camellia sinensis ), (Z)-3-hexenyl acetate (3-HAC) has been characterized as associated with resistance to herbivores. To date, how tea plants biosynthesize and regulate 3-HAC to resist herbivores remain unclear. Based on transcriptomes assembled from Ectropis obliqua- fed leaves, a cDNA encoding BAHD acyltransferase, namely CsCHAT1 , was highly induced in leaves fed with E. obliqua . Enzymatic assays showed that CsCHAT1 converted (Z)-3-hexenol into 3-HAC. Further suppression of CsCHAT1 expression reduced the accumulation of 3-HAC and lowered the resistance of tea plants to E. obliqua , while 3-HAC replenishment rescued the reduced resistance of CsCHAT1 -silenced tea plants against E. obliqua . Two transcription factors (TFs), CsNAC30 and CsTCP11 , were co-expressed with CsCHAT1 . An integrative approach of biochemistry, DNA–protein interaction, gene silencing, and metabolic profiling revealed that the two TFs positively regulated the expression of CsCHAT1 . The suppression of either one decreased the production of 3-HAC and eliminated the resistance of tea plants to E. obliqua . Notably, the suppression of either one considerably impaired JA-induced 3-HAC biosynthesis in tea plant. The proposed pathway can be targeted for innovative agro-biotechnologies protecting tea plants from damage by E. obliqua .
研究领域:
植物学
·
分子生物学
·
农业科学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）