International Heart Journal
·
2024
·
IF 1.2
Xiaoyu Shen,Jiamei Zhang,Zhou Zhou,Ruiqun Yu
Cardiomyocyte lipotoxicity and ferroptosis are the key to the development of diabetic cardiomyopathy (DCM). Perilipin 5 (PLIN5) is perceived as a significant target of DCM. This study aimed to focus on the role and mechanism of PLIN5 on lipotoxicity and ferroptosis in DCM.Following transfection, mouse cardiomyocytes HL-1 were induced by 0.1 mM palmitic acid (PA) to set up lipotoxic cardiomyocyte models. The cell viability and lipid accumulation were evaluated by cell counting kit-8 assay and Oil red O staining, respectively. Ferrous ion (Fe2+), glutathione (GSH), malondialdehyde (MDA), and reactive oxygen species (ROS) levels were determined to verify the effects of PLIN5 or Pirin (PIR) on ferroptosis. Quantitative real-time reverse transcription polymerase chain reaction or Western blot was performed for quantitative analysis.PLIN5 overexpression promoted the viability, GSH level, and expression of GPX4/PIR/intracellular P65, yet suppressed lipid accumulation, level of Fe2+/MDA/ROS, and expression of interleukin (IL) -1β/IL-18/intranuclear P65 in PA-stimulated HL-1 cells. PIR silencing counteracted the roles of PLIN5 overexpression in PA-stimulated HL-1 cells.PLIN5 suppresses lipotoxicity and ferroptosis in cardiomyocyte via modulating PIR/NF-κB axis, hinting its potential as a therapeutic target in DCM.
研究领域:
心脏病学
·
细胞生物学
·
分子生物学
·
糖尿病
·
病理学
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产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH
·
2024
·
IF 2.7
Zhu Wang,Bowen Li,Jingrui Yang,Ying Gao,Liu Gao,Qiang Jia,Li Yu,Yunzhi Ling
The aim of this study was to examine the effects of ML365, a two-pore potassium channel (K2P) inhibitor, on postoperative cognitive impairment (POCD). A mouse model of POCD was constructed by subjecting aged C57BL/6 mice to exploratory laparotomy. Changes in cognitive function were assessed using the Morris water maze test. Western blotting and qPCR were used to detect hippocampal NLRP3, Caspase-1 and IL-1β expression levels on days 3 and 7 post-surgery. Apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) expression level was also assessed by western blotting. Pathological changes and nerve damage in the hippocampal CA1 and CA3 regions were detected by H&E staining, while the concentration of malondialdehyde (MDA) in the plasma was measured. We found that pretreatment with ML365 (administered intraperitoneally at a dose of 10 mg/kg) 30 min prior to exploratory laparotomy effectively ameliorated POCD in mice. ML365 pretreatment also reduced NLRP3, Caspase-1, ASC and IL-1β expression levels in the hippocampus, improved POCD-induced pathological changes in the hippocampal CA1 and CA3 areas of aged mice, and decreased levels of plasma MDA and oxidative stress. Together, our findings indicate that ML365 can alleviate POCD in mice by inhibiting NLRP3 inflammasome activation in the hippocampus.
研究领域:
神经科学
·
药理学
·
外科手术
·
炎症
·
认知障碍
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产品关联
DOI
PubMed
高影响因子
CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
·
2021
·Vol. 99
·期 12
·
IF 2.273
Weimin Xu,Peng Wang,Dalong Wang,Ke Liu,Shuaishuai Zhang,Wei Zhao,Guoqing Liu
The aim of the present study was to investigate the protective effect of S-ketamine (S-KET) against carbon tetrachloride (CCl4) – induced liver damage and oxidative stress, as well as to elucidate the related underlying mechanisms. Blood was collected to measure biochemical parameters (alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total bilirubin (TB) and γ-glutamyltransferase (γ-GT)) and the liver was harvested for histopathological analysis of enzymes related to the antioxidant response (malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-PX)). Liver cell apoptosis was evaluated using the TUNEL assay. In addition, the expression levels of apoptosis-related proteins and the nuclear factor erythroid 2–related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway were detected by Western blot analysis to explore potential mechanisms. S-KET protected the liver from CCl4-induced damage. The changes to the liver biochemical parameters (increased ALT, AST, ALP, TB, and γ-GT) and oxidative stress-related indicators (increased MDA; depleted SOD, GSH, and GSH-PX) induced by CCl4 were inhibited by S-KET. S-Ket also inhibited CCl4-induced cell apoptosis, the changes in expression of related proteins, and blocked CCl4-induced liver injury and oxidative stress via activation of the Nrf2/HO-1 signaling pathway. S-KET effectively protected the liver by inhibition of CCl4-induced damage via upregulation the Nrf2/HO-1 signaling pathway.
研究领域:
药理学
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肝病学
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分子生物学
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毒理学
✓ 已验证
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2018
·
IF 5.158
Zheng-Nan Cai,Wan Li,Shomaila Mehmood,Wen-Juan Pan,Ya Wang,Fan-Ju Meng,Xiao-Fang Wang,Yong-Ming Lu,Yan Chen
This study aimed to investigate the structural features, in vitro and in vivo antioxidant activities of a heteropolysaccharide from the fruiting bodies of Morchella esculenta (FMP-1). FMP-1 had an average molecular weight of 4.7 × 10 3 Da and consisted of mannose, glucose and galactose. By methylation and NMR analysis, the backbone of FMP-1 was deduced to be made up of 1,4-linked Glc p and 1,6-linked Gal p . Hydroxyl, DPPH and superoxide radicals could be efficiently scavenged by FMP-1, with IC 50 values of 74.26, 119.32 and 161.49 μg/mL, respectively. Furthermore, FMP-1 could significantly protect zebrafish embryos against AAPH-induced oxidative damage. Decrease in malformations and mortalities was observed along with the reduction of ROS production, NO production and cell death. The protective effects were by decreasing MDA content and increasing SOD, CAT and GSH-Px levels. The current work provided a good suggestion of the potential utilization of FMP-1 as an attractive natural antioxidant.
研究领域:
药理学
·
生物化学
·
真菌学
·
毒理学
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产品关联
DOI
PubMed
高影响因子
Aging-US
·
2019
·
IF 5.515
Jin-Lan Huang,Chao Yu,Min Su,Si-Man Yang,Fan Zhang,Yuan-Yuan Chen,Jin-Yuan Liu,Yi-Fan Jiang,Zhen-Guo Zhong,Deng-Pan Wu
Oxidative stress plays a vital role in the initiation and progression of age-related neurodegenerative diseases. Ameliorating oxidative damage is therefore considered as a beneficial strategy for the treatment of age-related neurodegenerative disorders. Probucol (Prob), a lipid-lowering prototype agent, was reported to treat cardiovascular diseases, chronic kidney disease and diabetes mellitus. However, whether Prob has an effect on age-related neurodegenerative diseases remains unknown. In the study, it was found that Prob ameliorated D-galactose (D-gal) induced cognitive deficits and neuronal loss in the hippocampal CA1 region. Moreover, Prob alleviated ROS and MDA levels by elevating SOD, GSH-PX and HO-1 mRNA and protein expressions, and improving plasmic and cerebral SOD and GSH-PX activities in D-gal treated mice. Furthermore, Prob promoted the dissociation of Keap1/Nrf2 complex leading to the accumulation of Nrf2 in nucleus, implying that the improved anti-oxidant property of Prob is mediated by Keap1/Nrf2 pathway. The study firstly demonstrates the favorable effects of Prob against cognitive impairments in a senescent mouse model, rendering this compound a promising agent for the treatment or prevention of age-related neurodegenerative disease.
研究领域:
神经科学
·
药理学
·
衰老研究
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DOI
PubMed
高影响因子
CHEMBIOCHEM
·
2018
·Vol. 19
·期 10
·1060-1065
·
IF 2.774
Xueyu Zhao,Gaochao Lv,Ying Peng,Qingzhu Liu,Xi Li,Shanshan Wang,Ke Li,Ling Qiu,Jianguo Lin
Graphical Active duty : An activatable fluorescent probe consisting of a peptide, Arg-Val-Arg-Arg (RVRR), and an aminoluciferin fluorophore is designed and prepared for the responsive and activatable detection of furin activity in living cells. This probe is shown to have “off–on” florescence properties, and in the presence of furin in vitro, its fluorescence intensity is increased by a factor of ≈3.58. Furin, a protein convertase, plays a crucial role in the progression of tumors. In this work, a new fluorescent probe consisting of a peptide, Arg-Val-Arg-Arg (RVRR), and an aminoluciferin fluorophore was designed and prepared for the responsive and activatable detection of furin activity in vitro and in living cells. We demonstrated that this probe could be responsive toward furin with an “off–on” florescence signal and generated an approximately 3.58-fold enhancement in the fluorescence intensity in vitro. Fluorescence imaging in MDA-MB-468 and LoVo cells showed that the probe could be cleaved by overexpressed furin with fluorescence turn-on in MDA-MB-468 cells, and this probe was also found to be capable of discriminating between furin-overexpressing and furin-deficient cell lines. Our research indicates that this probe has great potential for the detection of furin activity in living cells.
研究领域:
生物化学
·
分子生物学
·
癌症研究
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
BIOLOGICAL TRACE ELEMENT RESEARCH
·
2017
·Vol. 181
·期 1
·62-70
·
IF 2.399
Zhang Hui,Chang Zhenyu,Mehmood Khalid,Abbas Rao Zahid,Nabi Fazul,Rehman Mujeeb Ur,Wu Xiaoxing,Tian Xinxin,Yuan Xiaodan,Li Zhaoyang,Zhou Donghai
Nano-sized copper particles are widely used in various chemical, physical, and biological fields. However, earlier studies have shown that nano copper particles (40–100 μg/mL) can induce cell toxicity and apoptosis. Therefore, this study was conducted to investigate the role of nano copper in mitochondrion-mediated apoptosis in PK-15 cells. The cells were treated with different doses of nano copper (20, 40, 60, and 80 μg/mL) to determine the effects of apoptosis using acridine orange/ethidium bromide (AO/EB) fluorescence staining and a flow cytometry assay. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the PK-15 cells were examined using commercially available kits. Moreover, the mRNA levels of the Bax, Bid, Caspase-3, and CYCS genes were assessed by real-time PCR. The results revealed that nano copper exposure induced apoptosis and changed the mitochondrial membrane potential. In addition, nano copper significantly altered the levels of the Bax, Bid, Caspase-3, and CYCS genes at a concentration of 40 μg/mL. To summarize, nano copper significantly ( P < 0.05) decreased the level of SOD and increased the level of MDA in PK-15 cells. Altogether, these results suggest that nano copper can play an important role in inducing the apoptotic pathway in PK-15 cells, which may be the mechanism by which nano copper induces nephrotoxicity.
研究领域:
细胞生物学
·
毒理学
·
分子生物学
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2023
·Vol. 11
·期 25
·5856-5869
·
IF 7
Fei Zhou,Yang Yang,Yuying Liu,Haotian Deng,Jianhua Rong,Jianhao Zhao
Intracellular calcium ions (Ca2+) influence the proliferation–apoptosis balance, and lactic acidosis is an innate feature of a malignant tumor. In this study, a calcium hydroxide/oleic acid/phospholipid nanoparticle [CUR–Ca(OH)2-OA/PL NP] with lipase/pH dual responsive delivery of Ca2+ and curcumin (CUR) was developed for inducing cancer cell apoptosis by a combination of intracellular calcium overload and lactic acidosis elimination. The nanoparticle showed a core–shell structure with some good performance, including an adequate nano-size, negative charge, good blood circulation stability, and non-hemolysis. MDA-MB-231 breast cancer cells exhibited a higher lipase activity than A549 human lung adenocarcinoma cells and L929 mouse fibroblasts by fluorescence analysis. CUR–Ca(OH)2-OA/PL NPs were highly internalized by MDA-MB-231 cells, intracellularly released CUR and Ca2+, triggered the activation of caspase 3 and caspase 9, and caused apoptosis by intracellular calcium overload via a mitochondrial-mediated pathway. Lactic acid of 20 mM inhibited the apoptosis of MDA-MB-231 cells depending on the glucose insufficiency level, but this inhibition could be eliminated by CUR–Ca(OH)2-OA/PL NPs, leading to nearly complete apoptosis. Herein, CUR–Ca(OH)2-OA/PL NPs are a potential killer of cancer cells with high lipase activity by a combination of intracellular calcium overload and lactic acidosis elimination.
研究领域:
纳米技术
·
癌症生物学
·
药学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
PESTICIDE BIOCHEMISTRY AND PHYSIOLOGY
·
2023
·
IF 4.7
Enzhuang Pan,Huizhen Chen,Xinyu Wu,Nana He,Jiajie Gan,Huimiao Feng,Yong Sun,Jingquan Dong
Avermectin pollution is an important problem that cannot be ignored in aquatic system in recent years. It has brought great trouble to freshwater aquaculture, especially fishery aquaculture. Plant-derived quercetin has anti-inflammatory and antioxidant properties and is widely used as a dietary additive, but its protective effect on immune damage induced by avermectin in freshwater carp remains unclear. This study evaluated the role of dietary additive quercetin supplementation in chronic avermectin exposure of carp spleen. Sixty carp were divided into 4 groups ( n = 15/ group), including control group, avermectin treatment group, quercetin treatment group, quercetin and avermectin co-treatment group. Carp were exposed to a 1/10 96 h LC 50 dose of avermectin for 30 d and fed a carp diet containing 400 mg/kg quercetin twice a day (3% body weigh/ carp). The results showed that chronic avermectin exposure caused the loose parenchymal structure of carp spleen tissue and the increase of inflammatory cells, accompanied by increased transcription levels of pro-inflammatory il-1β , il-6 , tnf-α and decreased levels of anti-inflammatory factors il-10 and tgf-β1 , ROS accumulation in spleen tissue. MDA content increased and T-AOC, CAT and GSH levels decreased. Quercetin down-regulates the NF-κB pathway by inhibiting the expression of iNOS and activating p38 MAPK, blocking the transcription of inflammatory factors, and alleviating the inflammation of carp spleen caused by chronic avermectin exposure. In addition, quercetin inhibits the over-activation of Nrf2/Keap-1 signaling axis, blocks ROS accumulation, and restores the spleen REDOX homeostasis. In conclusion, quercetin, as a dietary additive for carp feed, can effectively improve the immune damage caused by avermectin pollution in aquatic environment, resist spleen inflammation and oxidative stress, and provide a theoretical basis for clinical development of freshwater carp feed.
研究领域:
水产养殖
·
免疫学
·
毒理学
·
药理学
·
生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2022
·
IF 5.714
Shu-ping Yang,Qing Su,Ya-ru Zhang,Yun Sun,Yu-rong Chai
As the main lymphoid organ, the thymus degenerates with age. The loss of thymic epithelial cells is mainly related to thymus degeneration and reduced T cells development. As an insulin sensitizer, metformin is a first-line drug for the treatment of diabetes and has been shown to prolong the lifespan of mice, but the mechanism is still unclear. In this study, we explored the therapeutic effect of metformin on thymus degeneration in the accelerated aging mice, which was established by intraperitoneal injection D-galactose (120 mg/kg/day) for eight weeks. Metformin was intragastrically given with 100 or 300 mg/kg body weight per day, respectively, for six weeks. Histological examination showed that metformin administration could alleviate thymus atrophy caused by D-galactose. In addition, metformin therapy increased mitochondrial membrane potential, with a reduction in mitochondrial reactive oxygen species, MDA and SOD levels, and restored mitochondrial balance through enhanced expression of dynamin-related protein 1 (Drp1). Furthermore, metformin altered T lymphocyte subsets and cellular senescent cells; the expression of FoxN1, Aire and Sox2 of thymic epithelial cells also increased. Thus, metformin presented a positive effect on thymic degeneration through improving mitochondrial function. Taken together, these findings revealed an unexpected complexity in the anti-aging of this widely used drug.
研究领域:
药理学
·
免疫学
·
老年学
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ANALYST
·
2019
·Vol. 144
·期 15
·4575-4581
·
IF 4.019
Bo Yin,Sha Sha Li,Shao Hua Lu,Jia Ying Mi,Hong Lin Zhai
Although a large number of fluorescent probes have been developed, the simultaneous quantitative analysis of intracellular thiols is still difficult due to the spectral overlap and the complexity of the intracellular environment. In this study, a multi-signal fluorescent probe was employed for the simultaneous quantification of intracellular glutathione (GSH), cysteine (Cys) and homocysteine (Hcy). As the feature variables of the target components, the Tchebichef image moments (TMs) calculated from the grayscale images of the 3D fluorescence spectra were used to establish the quantitative linear models by stepwise regression. The intra-day and inter-day precisions of the proposed method were less than 5.6% and 8.7%, respectively. The recoveries ranged from 97.0% to 105.9%. In addition, the proposed approach was applied to the simultaneous quantitative determination of Cys, GSH and Hcy in the MCF-10A cell (a type of normal cell) and MDA-MB-231 cancer cell. The obtained results indicated that the concentrations of the three thiols in the cancer cell were higher than those in the normal cell. This study not only provides an effective approach for the quantification of multi-target bio-molecules in complicated intracellular environments, but also further extends the applications of multi-signal fluorescent probes, which will promote the design of new multi-signal fluorescent probes.
研究领域:
分析化学
·
生物化学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TOXICOLOGY
·
2022
·
IF 4.571
Yuan Jiang,Lin Qin,Anjing Lu,Juan Chen,Jianmei Wang,Qianru Zhang,Yanliu Lu,Qihai Gong,Jianmei Gao,Hong Ma,Daopeng Tan,Yuqi He
Strychnine is one of the main bioactive and toxic constituents of Semen Strychni. In the present study, the neurotoxic effects of strychnine, and the role of individual differences in metabolism on susceptibility to neurotoxicity of strychnine were investigated. The acute toxicity was observed by a single dose of strychnine (2.92 mg/kg, i.g.) in rats, the epileptic stages of rats were scored according to Racine’s scale. The neurotoxicity of strychnine was evaluated by the levels of ROS , MDA , SOD and GSH in hippocampus, striatum, and cortex tissues measurements and histopathological analysis. The concentrations of strychnine in the plasma, hippocampus, striatum, and cortex tissues were determined using high performance liquid chromatography tandem mass spectrometry (LC-MS/MS). The expressions of the cytochrome P450 , which is the most critical protein family involved in drugs metabolism, were detected by proteomics . The mechanism of susceptibility to neurotoxicity of strychnine was elucidated by correlation analysis among above indicators. The results indicated that striatum and cortex were the main toxic targets of strychnine, and the CYP3A1 might be a susceptible biomarker to neurotoxicity of strychnine. These results provide valuable insights into the neurotoxic susceptibility of strychnine that will aid in the rational clinical use of strychnine (possibly including Semen Strychni).
研究领域:
药理学
·
毒理学
·
神经科学
·
蛋白质组学
✓ 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）