本研究旨在探讨肝复胶囊(Gan Fu capsule, GFC)对TGF-1诱导HSC-T6细胞增殖的影响及作用机制。试验采用制备空白血清和GFC含药血清,体外培养HSC-T6细胞24 h后,CCK8法筛选最佳给药血清浓度,采用不同浓度TGF-1诱导HSC-T6细胞,CCK8法筛选最...本研究旨在探讨肝复胶囊(Gan Fu capsule, GFC)对TGF-1诱导HSC-T6细胞增殖的影响及作用机制。试验采用制备空白血清和GFC含药血清,体外培养HSC-T6细胞24 h后,CCK8法筛选最佳给药血清浓度,采用不同浓度TGF-1诱导HSC-T6细胞,CCK8法筛选最佳造模浓度,将细胞分为空白组(CON)、模型组(MOD)、肝复胶囊低剂量组(GFC-L)、肝复胶囊中剂量组(GFC-M)、肝复胶囊高剂量组(GFC-H),采用细胞增殖检测(CCK8)法检测各组细胞增殖情况,酶联免疫吸附试验(ELISA)检测IL-6、IL-1 、TNF-含量,蛋白免疫印记试验(Western blot)检测各细胞中核苷酸结合寡聚化结构域样受体蛋白3(Nod-like receptor protein 3,NLRP3)、凋亡相关斑点样蛋白(Apoptosis associated speck-like protein containing a caspase activating recruitment domain, ASC)、半胱氨酸蛋白酶-1(Cysteinyl aspartate specific proteinase-1,Caspase-1)及-平滑肌动蛋白(Alpha-smooth muscle actin,-SMA)的表达。结果表明,与CON组相比,GFC能抑制HSC-T6细胞的增殖能力,减少HSC分泌IL-6、IL-1 、TNF-含量,降低HSC中NLRP3、ASC、Caspase-1及-SMA的表达量。GFC可能通过调节NLRP3/ASC/Caspase-1信号通路和减少-SMA蛋白表达,从而抑制HSC-T6增殖,起到抗肝纤维化的作用。展开更多
铁是几乎所有生物系统中必不可少的金属。然而,细胞内的铁含量需要严格调节,因为过量的铁会随着ROS的产生而产生破坏性影响,铁死亡是一种新型的由铁依赖性脂质过氧化作用引起的氧化调节细胞死亡。铁死亡涉及遗传、代谢和蛋白质的调节、...铁是几乎所有生物系统中必不可少的金属。然而,细胞内的铁含量需要严格调节,因为过量的铁会随着ROS的产生而产生破坏性影响,铁死亡是一种新型的由铁依赖性脂质过氧化作用引起的氧化调节细胞死亡。铁死亡涉及遗传、代谢和蛋白质的调节、触发和执行机制,在很大程度上与其他形式的受调节细胞死亡不重叠。脂质代谢对于肿瘤的增殖以及侵袭、转染都具有很重要的作用,例如细胞膜层面的高水平膜脂质与肿瘤细胞抵御活性氧(ROS)的损伤密切相关,由于高饱和度的膜脂对于氧化反应的刺激不敏感这为肿瘤细胞无形中提供了保护作用。目前主流的肿瘤化疗采用诱导凋亡的方式杀死或抑制肿瘤细胞。然而,越来越明显地是,肿瘤细胞可能对这些依赖凋亡的抗肿瘤方式表现出内在或获得性抵抗,从而大大增加了治疗失败和治疗后复发的风险。对于肿瘤而言,越来越多研究表明,在肿瘤组织中,铁死亡被显著抑制,导致了肿瘤不受控制地转移以及侵袭,这也为调节靶向肿瘤细胞的死亡对于肿瘤的免疫治疗提供了一种新的治疗方式以及为其他以异常细胞增生的疾病提供新的治疗思路。有趣的是,治疗耐药的癌细胞,特别是那些间充质状态和易于转移的癌细胞,非常容易发生铁死亡。目前许多研究证实:铁死亡与肿瘤存在密切的联系,并且涉及一系列机制,并且铁死亡还可以根除一些凋亡不敏感的肿瘤细胞,激活铁死亡途径可能是克服传统癌症治疗耐药机制的潜在策略。故此铁死亡的相关研究进展对于肿瘤的治疗而言具有重要的意义。Iron is an essential metal in almost all biological systems. However, the intracellular iron content needs to be strictly regulated because excessive iron can have destructive effects along with the generation of reactive oxygen species (ROS). Ferroptosis is a novel type of oxidative regulated cell death caused by iron-dependent lipid peroxidation. Ferroptosis involves the regulatory, triggering and execution mechanisms of genetics, metabolism and proteins, and largely does not overlap with other forms of regulated cell death. Lipid metabolism plays a very important role in the proliferation. High levels of membrane lipids at the cellular membrane level are highly correlated with the ability of tumor cells to avoid damage from reactive oxygen species (ROS). Because membrane lipids with high saturation are insensitive to the stimuli of oxidation reactions, they provide an invisible protective effect for tumor cells. Currently, the mainstream tumor chemotherapy uses the method of inducing apoptosis to kill or inhibit tumor cells. However, it is becoming increasingly evident that tumor cells may exhibit intrinsic or acquired resistance to these apoptosis-dependent anti-tumor approaches, which greatly increases the risk of treatment failure and recurrence after treatment. For tumors, more and more studies have shown that in tumor tissues, ferroptosis is significantly inhibited, leading to uncontrolled metastasis and invasion of tumors. This also provides a new treatment approach for tumor immunotherapy by regulating the death of targeted tumor cells, and offers new treatment ideas for other diseases characterized by abnormal cell proliferation. Interestingly, cancer cells resistant to treatment, especially those in a mesenchymal state and prone to metastasis, are highly susceptible to ferroptosis. Currently, many studies have confirmed that there is a close relationship between ferroptosis and tumors, involving a series of mechanisms. Moreover, ferroptosis can also eradicate some tumor cells that are insensitive to apoptosis. Activating the ferroptosis pathway may be a potential strategy to overcome the resistance mechanisms of traditional cancer treatments. Therefore, the relevant research progress of ferroptosis is of great significance for the treatment of tumors.展开更多
建筑科学领域高质量科技期刊分级目录期刊High-quality Sci-Tech Journal of Building Science,certificated by CAST and ASC中国科技核心期刊Source Journal for Chinese Scientific and Technical Papers and Citations,certificated...建筑科学领域高质量科技期刊分级目录期刊High-quality Sci-Tech Journal of Building Science,certificated by CAST and ASC中国科技核心期刊Source Journal for Chinese Scientific and Technical Papers and Citations,certificated by ISTIC RCCSE中国核心学术期刊China Core Academic Journal of RCCSE《建筑节能(中英文)》杂志,是由中国建筑东北设计研究院有限公司主管,中国建筑东北设计研究院有限公司、中国建筑节能协会主办的国家级建筑节能专业技术期刊。展开更多
The Antarctic Slope Current(ASC)links the processes occurring in the coast area with the global ocean by modulating the flow across the continental slope,which influences global overturning circulation and the mass ba...The Antarctic Slope Current(ASC)links the processes occurring in the coast area with the global ocean by modulating the flow across the continental slope,which influences global overturning circulation and the mass balance of the Antarctic ice shelves.This paper aims to explore the effects of wind and buoyancy fluxes on the long-term changes in the ASC using observation and reanalysis datasets.From 1993 to 2022,the ASC accelerated in all seasons,particularly in austral autumn,and was accompanied with the advancement of the strong flow.The positive buoyancy flux anomaly generates a low-density anomaly,which is accumulated by the prevailing surface easterly,maintaining a sharp density front along the continental slope.The heat flux intensifies the positive trend of buoyancy flux in summer and autumn,increasing the input of the lighter density anomaly into the ocean and advancing the strong flow of ASC.Compared with the annual mean,the additional acceleration of the ASC in autumn is mainly due to the contribution of the barotropic component,which could be explained by the local momentum input from the weakly enhanced local surface wind.The acceleration of the ASC is primarily driven by the positive trend of the buoyancy flux,while the influence of the wind on its seasonal variability becomes more significant due to the contribution of the local surface wind in autumn.展开更多
文摘目的 探讨miR-383在单钠尿酸盐(monosodium urate, MSU)诱导的非感染性类病原炎症反应中的调控作用,重点评估其在NLRP3炎性体活性调节及炎症自限性维持中的分子机制,为DAMPs介导的无菌性炎症调控提供理论基础。方法 构建miR-383基因敲除(miR-383-/-)及野生型(WT)小鼠的急性痛风性关节炎模型,分别于MSU注射后0、6、12、24、48 h测定足掌厚度。建立腹腔炎症模型并于刺激后6 h和12 h收集腹腔灌洗液,采用流式细胞术分析Ly6G+CD11b+中性粒细胞与F4/80+CD11b+巨噬细胞构成比,ELISA检测IL-1β与IL-6水平。另分离骨髓源性巨噬细胞(BMDMs),于MSU刺激(100μg/mL)后0、4、8 h收集RNA,利用RT-qPCR检测NLRP3、ASC、caspase-1与IL-1β mRNA表达水平。结果 miR-383-/-小鼠在MSU注射后6 h、12 h、24 h的足掌厚度较WT组显著增高(2.81±0.17 mm vs. 2.37±0.14 mm, 3.08±0.21 mm vs. 2.52±0.19 mm, 2.67±0.15 mm vs. 2.29±0.12 mm,均P<0.01)。12 h时腹腔中Ly6G+CD11b+中性粒细胞比例升高至72.34%±4.26%,显著高于WT组的60.91%±3.74%(P<0.01),F4/80+CD11b+巨噬细胞占比亦显著上升(18.46%±2.81%vs. 12.73%±2.57%,P<0.01)。ELISA结果显示miR-383-/-组IL-1β和IL-6峰值分别达641.5±43.6 pg/mL和984.2±51.8 pg/mL,均显著高于WT组(分别为438.7±39.4 pg/mL和732.4±44.9 pg/mL,均P<0.01)。BMDMs中,miR-383-/-组在刺激4 h时ASC mRNA表达为WT组的2.91倍(P<0.01),caspase-1和IL-1β表达分别升高至2.26倍(P<0.01)与3.42倍(P<0.01),NLRP3表达差异无统计学意义(P=0.117)。结论 miR-383通过负向调控ASC表达,从而限制NLRP3炎性体的激活及促炎因子的过度释放。其缺失导致炎症表型加重、免疫细胞过度募集及IL-1β、IL-6水平显著升高,提示miR-383在DAMPs介导的无菌性炎症应答中发挥关键负调控功能。miR-383-ASC信号轴的识别不仅丰富了炎性小体调控网络,也为痛风等炎症性疾病的分子干预提供潜在靶点。
文摘铁是几乎所有生物系统中必不可少的金属。然而,细胞内的铁含量需要严格调节,因为过量的铁会随着ROS的产生而产生破坏性影响,铁死亡是一种新型的由铁依赖性脂质过氧化作用引起的氧化调节细胞死亡。铁死亡涉及遗传、代谢和蛋白质的调节、触发和执行机制,在很大程度上与其他形式的受调节细胞死亡不重叠。脂质代谢对于肿瘤的增殖以及侵袭、转染都具有很重要的作用,例如细胞膜层面的高水平膜脂质与肿瘤细胞抵御活性氧(ROS)的损伤密切相关,由于高饱和度的膜脂对于氧化反应的刺激不敏感这为肿瘤细胞无形中提供了保护作用。目前主流的肿瘤化疗采用诱导凋亡的方式杀死或抑制肿瘤细胞。然而,越来越明显地是,肿瘤细胞可能对这些依赖凋亡的抗肿瘤方式表现出内在或获得性抵抗,从而大大增加了治疗失败和治疗后复发的风险。对于肿瘤而言,越来越多研究表明,在肿瘤组织中,铁死亡被显著抑制,导致了肿瘤不受控制地转移以及侵袭,这也为调节靶向肿瘤细胞的死亡对于肿瘤的免疫治疗提供了一种新的治疗方式以及为其他以异常细胞增生的疾病提供新的治疗思路。有趣的是,治疗耐药的癌细胞,特别是那些间充质状态和易于转移的癌细胞,非常容易发生铁死亡。目前许多研究证实:铁死亡与肿瘤存在密切的联系,并且涉及一系列机制,并且铁死亡还可以根除一些凋亡不敏感的肿瘤细胞,激活铁死亡途径可能是克服传统癌症治疗耐药机制的潜在策略。故此铁死亡的相关研究进展对于肿瘤的治疗而言具有重要的意义。Iron is an essential metal in almost all biological systems. However, the intracellular iron content needs to be strictly regulated because excessive iron can have destructive effects along with the generation of reactive oxygen species (ROS). Ferroptosis is a novel type of oxidative regulated cell death caused by iron-dependent lipid peroxidation. Ferroptosis involves the regulatory, triggering and execution mechanisms of genetics, metabolism and proteins, and largely does not overlap with other forms of regulated cell death. Lipid metabolism plays a very important role in the proliferation. High levels of membrane lipids at the cellular membrane level are highly correlated with the ability of tumor cells to avoid damage from reactive oxygen species (ROS). Because membrane lipids with high saturation are insensitive to the stimuli of oxidation reactions, they provide an invisible protective effect for tumor cells. Currently, the mainstream tumor chemotherapy uses the method of inducing apoptosis to kill or inhibit tumor cells. However, it is becoming increasingly evident that tumor cells may exhibit intrinsic or acquired resistance to these apoptosis-dependent anti-tumor approaches, which greatly increases the risk of treatment failure and recurrence after treatment. For tumors, more and more studies have shown that in tumor tissues, ferroptosis is significantly inhibited, leading to uncontrolled metastasis and invasion of tumors. This also provides a new treatment approach for tumor immunotherapy by regulating the death of targeted tumor cells, and offers new treatment ideas for other diseases characterized by abnormal cell proliferation. Interestingly, cancer cells resistant to treatment, especially those in a mesenchymal state and prone to metastasis, are highly susceptible to ferroptosis. Currently, many studies have confirmed that there is a close relationship between ferroptosis and tumors, involving a series of mechanisms. Moreover, ferroptosis can also eradicate some tumor cells that are insensitive to apoptosis. Activating the ferroptosis pathway may be a potential strategy to overcome the resistance mechanisms of traditional cancer treatments. Therefore, the relevant research progress of ferroptosis is of great significance for the treatment of tumors.
文摘建筑科学领域高质量科技期刊分级目录期刊High-quality Sci-Tech Journal of Building Science,certificated by CAST and ASC中国科技核心期刊Source Journal for Chinese Scientific and Technical Papers and Citations,certificated by ISTIC RCCSE中国核心学术期刊China Core Academic Journal of RCCSE《建筑节能(中英文)》杂志,是由中国建筑东北设计研究院有限公司主管,中国建筑东北设计研究院有限公司、中国建筑节能协会主办的国家级建筑节能专业技术期刊。
基金The National Natural Science Foundation of China under contract Nos 42376256,42230405,and 41576020.
文摘The Antarctic Slope Current(ASC)links the processes occurring in the coast area with the global ocean by modulating the flow across the continental slope,which influences global overturning circulation and the mass balance of the Antarctic ice shelves.This paper aims to explore the effects of wind and buoyancy fluxes on the long-term changes in the ASC using observation and reanalysis datasets.From 1993 to 2022,the ASC accelerated in all seasons,particularly in austral autumn,and was accompanied with the advancement of the strong flow.The positive buoyancy flux anomaly generates a low-density anomaly,which is accumulated by the prevailing surface easterly,maintaining a sharp density front along the continental slope.The heat flux intensifies the positive trend of buoyancy flux in summer and autumn,increasing the input of the lighter density anomaly into the ocean and advancing the strong flow of ASC.Compared with the annual mean,the additional acceleration of the ASC in autumn is mainly due to the contribution of the barotropic component,which could be explained by the local momentum input from the weakly enhanced local surface wind.The acceleration of the ASC is primarily driven by the positive trend of the buoyancy flux,while the influence of the wind on its seasonal variability becomes more significant due to the contribution of the local surface wind in autumn.
