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Geraniin attenuates isoproterenol-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis. 格拉宁通过抑制炎症、氧化应激和细胞凋亡,减轻异丙肾上腺素诱发的心肌肥大。
IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-22 DOI: 10.4196/kjpp.24.200
Jiaqi Ding, Shenjie Zhang, Qi Li, Boyu Xia, Jingjing Wu, Xu Lu, Chao Huang, Xiaomei Yuan, Qingsheng You

Geraniin, a polyphenol derived from the fruit peel of Nephelium lappaceum L., has been shown to possess anti-inflammatory and antioxidant properties in the cardiovascular system. The present study explored whether geraniin could protect against an isoproterenol (ISO)-induced cardiac hypertrophy model. Mice in the ISO group received an intraperitoneal injection of ISO (5 mg/kg) once daily for 9 days, and the administration group were injected with ISO after 5 days of treatment with geraniin or spironolactone. Potential therapeutic effects and related mechanisms analysed by anatomical coefficients, histopathology, blood biochemical indices, reverse transcription-PCR and immunoblotting. Geraniin decreased the cardiac pathologic remodeling and myocardial fibrosis induced by ISO, as evidenced by the modifications to anatomical coefficients, as well as the reduction in collagen I/III á1mRNA and protein expression and cross-sectional area in hypertrophic cardiac tissue. In addition, geraniin treatment reduced ISO-induced increase in the mRNA and protein expression levels of interleukin (IL)-6, IL-1β and tumor necrosis factor-α, whereas ISO-induced IL-10 showed the opposite behaviour in hypertrophic cardiac tissue. Further analysis showed that geraniin partially reversed the ISO-induced increase in malondialdehyde and nitric oxide, and the ISO-induced decrease in glutathione, superoxide dismutase and glutathione. Furthermore, it suppressed the ISO-induced cellular apoptosis of hypertrophic cardiac tissue, as evidenced by the decrease in Bcell lymphoma-2 (Bcl-2)-associated X/caspase-3/caspase-9 expression, increase in Bcl-2 expression, and decrease in TdT-mediated dUTP nick-end labeling-positive cells. These findings suggest that geraniin can attenuate ISO-induced cardiac hypertrophy by inhibiting inflammation, oxidative stress and cellular apoptosis.

香叶木素是一种多酚类物质,提取自Nephelium lappaceum L.的果皮,已被证明在心血管系统中具有抗炎和抗氧化特性。本研究探讨了龙葵素能否保护异丙肾上腺素(ISO)诱导的心肌肥大模型。ISO 组小鼠腹腔注射 ISO(5 毫克/千克),每天一次,连续 9 天;给药组小鼠在接受格拉宁或螺内酯治疗 5 天后再注射 ISO。通过解剖学系数、组织病理学、血液生化指标、逆转录-PCR和免疫印迹分析了潜在的治疗效果和相关机制。格拉宁能减少 ISO 诱导的心脏病理重塑和心肌纤维化,这体现在解剖学系数的改变、胶原 I/III á1mRNA和蛋白表达的减少以及肥厚型心脏组织横截面积的减少。此外,格拉宁还能降低 ISO 诱导的白细胞介素(IL)-6、IL-1β 和肿瘤坏死因子-α 的 mRNA 和蛋白表达水平,而 ISO 诱导的 IL-10 在肥厚的心脏组织中则表现出相反的行为。进一步的分析表明,格拉宁能部分逆转 ISO 诱导的丙二醛和一氧化氮的增加,以及 ISO 诱导的谷胱甘肽、超氧化物歧化酶和谷胱甘肽的减少。此外,它还抑制了 ISO 诱导的肥厚性心脏组织的细胞凋亡,具体表现为 Bcell 淋巴瘤-2(Bcl-2)相关 X/caspase-3/caspase-9 表达的减少、Bcl-2 表达的增加以及 TdT 介导的 dUTP 缺口标记阳性细胞的减少。这些研究结果表明,龙葵素能通过抑制炎症、氧化应激和细胞凋亡来减轻 ISO 诱导的心肌肥大。
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引用次数: 0
Haloperidol, a typical antipsychotic, inhibits 5-HT3 receptormediated currents in NCB-20 cells: a whole-cell patch-clamp study. 氟哌啶醇(一种典型的抗精神病药)抑制 NCB-20 细胞中的 5-HT3 受体电流:全细胞贴片钳研究。
IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-22 DOI: 10.4196/kjpp.24.320
Yong Soo Park, Gyu Min Kim, Ho Jun Sung, Ju Yeong Yu, Ki-Wug Sung

Haloperidol is a typical antipsychotic drug effective in alleviating positive symptoms of schizophrenia by blocking dopamine receptor 2 (DR2). However, it is also known to produce neuropsychiatric effects by acting on various targets other than DR. In this study, we investigated effect of haloperidol on function of 5-hydroxytryptamine (5-HT)3 receptor, a ligand-gated ion channel belonging to the serotonin receptor family using the whole-cell voltage clamp technique and NCB20 neuroblastoma cells. When co-applied with 5-HT, haloperidol inhibited 5-HT3 receptormediated currents in a concentration-dependent manner. A reduction in maximal effect (Emax) and an increase in EC50 observed during co-application indicated that haloperidol could act as a non-competitive antagonist of 5-HT3 receptors. Haloperidol inhibited the activation of 5-HT3 receptor, while also accelerating their deactivation and desensitization. The inhibitory effect of haloperidol showed no significant difference between pre- and co-application. Haloperidol did not alter the reversal potential of 5-HT3 receptor currents. Furthermore, haloperidol did not affect recovery from deactivation or desensitization of 5-HT3 receptors. It did not show a use-dependent inhibition either. These findings suggest that haloperidol can exert its inhibitory effect on 5-HT3 receptors by allosterically preventing opening of ion channels. This mechanistic insight enhances our understanding of relationships between 5-HT3 receptors and pharmacological actions of antipsychotics.

氟哌啶醇是一种典型的抗精神病药物,通过阻断多巴胺受体2(DR2)来有效缓解精神分裂症的阳性症状。然而,众所周知,除了多巴胺受体2外,氟哌啶醇还能通过作用于其他靶点产生神经精神作用。在这项研究中,我们使用全细胞电压钳技术和 NCB20 神经母细胞瘤细胞研究了氟哌啶醇对 5- 羟色胺(5-HT)3 受体功能的影响,5-HT3 受体是属于血清素受体家族的配体门控离子通道。当与 5-HT 同时应用时,氟哌啶醇以浓度依赖的方式抑制 5-HT3 受体调节的电流。联合应用时观察到的最大效应(Emax)降低和EC50增加表明氟哌啶醇可以作为5-HT3受体的非竞争性拮抗剂。氟哌啶醇在抑制 5-HT3 受体激活的同时,还能加速其失活和脱敏。氟哌啶醇的抑制作用在使用前和同时使用时没有显著差异。氟哌啶醇不会改变 5-HT3 受体电流的逆转电位。此外,氟哌啶醇不影响 5-HT3 受体失活或脱敏后的恢复。它也没有表现出依赖使用的抑制作用。这些研究结果表明,氟哌啶醇可以通过异位作用阻止离子通道的开放,从而对 5-HT3 受体产生抑制作用。这一机理认识加深了我们对 5-HT3 受体与抗精神病药药理作用之间关系的理解。
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引用次数: 0
Lactobacillus johnsonii JERA01 upregulates the production of Th1 cytokines and modulates dendritic cells-mediated immune response. 约翰逊乳杆菌 JERA01 能上调 Th1 细胞因子的产生并调节树突状细胞介导的免疫反应。
IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-14 DOI: 10.4196/kjpp.24.205
Si-Yeon Kim, Hong-Gu Joo

Lactic acid bacteria are known to have various effects on the immune system. The type and extent of the effect differ, depending on the type of lactic acid bacteria. This study aimed to investigate the effects of Lactobacillus johnsonii bacterin on mouse-derived immune cells. Treating splenocytes with L. johnsonii bacterin slightly increased the metabolic activity. Additionally, the expression of the activation marker CD25 and production of the Th1-type inflammatory cytokine interferon (IFN)- gamma increased. We confirmed that the increase in IFN-gamma production due to L. johnsonii stimulation was mainly due to T and B cells among splenocytes. Treating dendritic cells (DCs) with L. johnsonii bacterin at concentrations of 106 and 107 cfu/ ml significantly increased tumor necrosis factor-alpha, a pro-inflammatory cytokine, and interleukin-12, a cell-mediated immunity cytokine. Additionally, the expression of surface markers increased. Allogeneic mixed lymphocyte reactions showed that L. johnsonii reduced the antigen-presenting ability of DCs. In cocultures of DCs and splenocytes, L. johnsonii decreased cellular metabolic activity and increased cell death. L. johnsonii upregulated the expression of programmed death ligand 1 on DCs. The findings of this study indicate that L. johnsonii bacterin has immunomodulatory and immunostimulatory effects. While L. johnsonii increased the expression of cytokines and surface markers of immune cells, it modulated DC-mediated immune response. Further studies are needed to determine the effects of L. johnsonii bacterin on DCs and related immune cells.

众所周知,乳酸菌对免疫系统有各种影响。影响的类型和程度因乳酸菌的类型而异。本研究旨在探讨约翰逊乳杆菌细菌素对小鼠衍生免疫细胞的影响。用约翰逊乳杆菌细菌素处理脾细胞可轻微提高代谢活性。此外,活化标记 CD25 的表达和 Th1 型炎症细胞因子干扰素(IFN)- γ 的产生也有所增加。我们证实,由于约翰逊酵母菌的刺激,IFN-γ的产生增加主要是由于脾细胞中的T细胞和B细胞。用浓度为 106 和 107 cfu/ ml 的约翰逊酵母菌菌素处理树突状细胞(DCs)会显著增加肿瘤坏死因子-α(一种促炎细胞因子)和白细胞介素-12(一种细胞介导免疫细胞因子)。此外,表面标志物的表达也有所增加。异体混合淋巴细胞反应表明,约翰逊酵母菌降低了直流细胞的抗原递呈能力。在直流细胞和脾细胞的共培养物中,约翰逊菌降低了细胞的代谢活性,增加了细胞死亡。约翰逊鹅膏菌上调了DC上程序性死亡配体1的表达。本研究结果表明,约翰逊酵母菌素具有免疫调节和免疫刺激作用。约翰逊鹅膏菌增加了细胞因子和免疫细胞表面标志物的表达,调节了直流介导的免疫反应。要确定约翰逊鹅膏菌细菌素对直流电和相关免疫细胞的影响,还需要进一步的研究。
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引用次数: 0
Protective effect of 6'-Sialyllactose on LPS-induced macrophage inflammation via regulating Nrf2-mediated oxidative stress and inflammatory signaling pathways. 6'-Sialyllactose 通过调节 Nrf2 介导的氧化应激和炎症信号通路对 LPS 诱导的巨噬细胞炎症有保护作用
IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-01 DOI: 10.4196/kjpp.2024.28.6.503
Hami Yu, Yujin Jin, Hyesu Jeon, Lila Kim, Kyung-Sun Heo

Macrophages play a central role in cardiovascular diseases, like atherosclerosis, by accumulating in vessel walls and inducing sustained local inflammation marked by the release of chemokines, cytokines, and matrix-degrading enzymes. Recent studies indicate that 6'-sialyllactose (6'-SL) may mitigate inflammation by modulating the immune system. Here, we examined the impact of 6'-SL on lipopolysaccharide (LPS)-induced acute inflammation using RAW 264.7 cells and a mouse model. In vivo, ICR mice received pretreatment with 100 mg/kg 6'-SL for 2 h, followed by intraperitoneal LPS injection (10 mg/kg) for 6 h. In vitro, RAW 264.7 cells were preincubated with 6'-SL before LPS stimulation. Mechanistic insights were gained though Western blotting, qRT-PCR, and immunofluorescence analysis, while reactive oxygen species (ROS) production was assessed via DHE assay. 6'-SL effectively attenuated LPS-induced p38 MAPK and Akt phosphorylation, as well as p65 nuclear translocation. Additionally, 6'-SL inhibited LPS-induced expression of tissue damage marker MMP9, IL-1β, and MCP-1 by modulating NF-κB activation. It also reduced ROS levels, mediated by p38 MAPK and Akt pathways. Moreover, 6'-SL restored LPS-suppressed Nrf2 and HO-1 akin to specific inhibitors SB203580 and LY294002. Consistent with in vitro results, 6'-SL decreased oxidative stress, MMP9, and MCP-1 expression in mouse endothelium following LPS-induced macrophage activation. In summary, our findings suggest that 6'-SL holds promise in mitigating atherosclerosis by dampening LPS-induced acute macrophage inflammation.

巨噬细胞在动脉粥样硬化等心血管疾病中发挥着核心作用,它们聚集在血管壁上,通过释放趋化因子、细胞因子和基质降解酶诱发持续的局部炎症。最近的研究表明,6'-水苏糖(6'-SL)可通过调节免疫系统来缓解炎症。在这里,我们使用 RAW 264.7 细胞和小鼠模型研究了 6'-SL 对脂多糖(LPS)诱导的急性炎症的影响。在体内,ICR 小鼠接受 100 毫克/千克 6'-SL 预处理 2 小时,然后腹腔注射 LPS(10 毫克/千克)6 小时。在体外,RAW 264.7 细胞在 LPS 刺激前与 6'-SL 预孵育。通过 Western 印迹分析、qRT-PCR 和免疫荧光分析,对机理进行了深入了解,同时通过 DHE 分析评估了活性氧(ROS)的产生。6'-SL 有效地减轻了 LPS 诱导的 p38 MAPK 和 Akt 磷酸化以及 p65 核转运。此外,6'-SL 通过调节 NF-κB 的活化,抑制了 LPS 诱导的组织损伤标志物 MMP9、IL-1β 和 MCP-1 的表达。它还通过 p38 MAPK 和 Akt 途径降低了 ROS 水平。此外,与特异性抑制剂 SB203580 和 LY294002 相似,6'-SL 能恢复 LPS 抑制的 Nrf2 和 HO-1。与体外实验结果一致,6'-SL 在 LPS 诱导的巨噬细胞活化后可降低小鼠内皮的氧化应激、MMP9 和 MCP-1 的表达。总之,我们的研究结果表明,6'-SL 有望通过抑制 LPS 诱导的急性巨噬细胞炎症来缓解动脉粥样硬化。
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引用次数: 0
Norepinephrine triggers glutamatergic long-term potentiation in hypothalamic paraventricular nucleus magnocellular neuroendocrine cells through postsynaptic β1-AR/PKA signaling pathway in vitro in rats. 去甲肾上腺素通过突触后β1-AR/PKA 信号通路触发体外大鼠下丘脑室旁核大细胞神经内分泌细胞的谷氨酸能长期延时。
IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-01 DOI: 10.4196/kjpp.2024.28.6.569
Jing-Ri Jin, Zhao-Yi Zhang, Chun-Ping Chu, Yu-Zi Li, De-Lai Qiu

Norepinephrine (NE) modulates synaptic transmission and long-term plasticity through distinct subtype adrenergic receptor (AR)-mediated-intracellular signaling cascades. However, the role of NE modulates glutamatergic long-term potentiation (LTP) in the hypothalamic paraventricular nucleus (PVN) magnocellular neuroendocrine cells (MNCs) is unclear. We here investigate the effect of NE on high frequency stimulation (HFS)-induced glutamatergic LTP in rat hypothalamic PVN MNCs in vitro, by whole-cell patch-clamp recording, biocytin staining and pharmacological methods. Delivery of HFS induced glutamatergic LTP with a decrease in N2/N1 ratio in the PVN MNCs, which was enhanced by application of NE (100 nM). HFS-induced LTP was abolished by the blockade of N-methyl-D-aspartate receptors (NMDAR) with D-APV, but it was rescued by the application of NE. NE failed to rescue HFS-induced LTP of MNCs in the presence of a selective β1-AR antagonist, CGP 20712. However, application of β1-AR agonist, dobutamine HCl rescued HFS-induced LTP of MNCs in the absence of NMDAR activity. In the absence of NMDAR activity, NE failed to rescue HFS-induced MNC LTP when protein kinase A (PKA) was inhibited by extracellular applying KT5720 or intracellular administration of PKI. These results indicate that NE activates β1-AR and triggers HFS to induce a novel glutamatergic LTP of hypothalamic PVN NMCs via the postsynaptic PKA signaling pathway in vitro in rats.

去甲肾上腺素(NE)通过不同亚型肾上腺素能受体(AR)介导的细胞内信号级联调节突触传递和长期可塑性。然而,NE 在下丘脑室旁核(PVN)大细胞神经内分泌细胞(MNCs)中调节谷氨酸能长期延时(LTP)的作用尚不清楚。我们在此通过全细胞膜片钳记录、生物细胞素染色和药理学方法,研究 NE 对高频刺激(HFS)诱导的大鼠下丘脑室旁核 MNCs 谷氨酸能 LTP 的体外影响。HFS诱导的谷氨酸能LTP与PVN MNCs中N2/N1比值的降低有关,而NE(100 nM)的应用增强了这种LTP。用D-APV阻断N-甲基-D-天冬氨酸受体(NMDAR)后,HFS诱导的LTP被取消,但应用NE后LTP被挽救。在选择性β1-AR拮抗剂 CGP 20712 的存在下,NE 无法挽救 HFS 诱导的 MNCs LTP。然而,在没有 NMDAR 活性的情况下,应用 β1-AR 激动剂盐酸多巴酚丁胺可挽救 HFS 诱导的 MNCs LTP。在没有 NMDAR 活性的情况下,当蛋白激酶 A(PKA)被细胞外应用 KT5720 或细胞内应用 PKI 抑制时,NE 无法挽救 HFS 诱导的 MNC LTP。这些结果表明,NE 可激活 β1-AR 并触发 HFS,通过突触后 PKA 信号通路诱导体外大鼠下丘脑 PVN NMC 的新型谷氨酸能 LTP。
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引用次数: 0
Salidroside attenuates sepsis-induced acute lung injury by inhibiting ferroptosis-dependent pathway. 水杨甙通过抑制铁蛋白依赖性途径减轻败血症诱发的急性肺损伤
IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-01 DOI: 10.4196/kjpp.2024.28.6.549
Lingling Zhen, Mingtong Hou, Shengbao Wang

Sepsis triggers a systemic inflammatory response that can lead to acute lung injury (ALI). Salidroside (SAL) has many pharmacological activities such as antiinflammatory and anti-oxidation. The objective of the study was to explore the mechanism of SAL on ALI caused by sepsis. A model of ALI in septic mice was established by cecal ligation and puncture. Following SAL treatment, the effect of SAL on the ferroptosis pathway in mice was analyzed. The pathological damage of lung tissue, the levels of inflammatory factors and apoptosis in bronchoalveolar lavage fluid (BALF) of mice were evaluated, and the changes of gene expression level and metabolite content abundance were explored by combining transcriptomics and metabolomics analysis. The effect of SAL on ferroptosis in mice with lung injury was observed by intraperitoneal injection of ferroptosis activator Erastin or ferroptosis inhibitor Ferrostatin-1 to promote or inhibit ferroptosis in mice. SAL significantly alleviated the pathological damage of lung tissue, decreased the number of TUNEL positive cells and the levels of TNF-α, IL-1β, IL-6 in BALF, and increased the level of IL- 10 in lung injury mice. Moreover, the Fe2+ content and malondialdehyde decreased significantly, the reactive oxygen species and glutathione content increased significantly, and the arachidonic acid metabolites 20-hydroxyeicosatetraenoic acid (20- HETE), (5Z, 8Z, 10E, 14Z)-12-Oxoeicosa-5,8,10,14-tetraenoic acid (12-OxOETE), (5Z, 8Z, 10E, 14Z)-(12S)-12-Hydroxyeicosa-5,8,10,14-tetraenoic acid (12(S)-HETE), (5Z, 8Z, 14Z)-11,12-Dihydroxyeicosa-5,8,14-trienoic acid (11,12-DHET), (5Z, 11Z, 14Z)-8,9- Dihydroxyeicosa-5,11,14-trienoic acid, Leukotriene B4, Leukotriene D4 were significantly up-regulated after SAL treatment. Salidroside alleviates ALI caused by sepsis by inhibiting ferroptosis.

败血症会引发全身炎症反应,导致急性肺损伤(ALI)。皂苷(SAL)具有抗炎和抗氧化等多种药理活性。本研究的目的是探索水杨甙对脓毒症引起的急性肺损伤(ALI)的作用机制。研究人员通过盲肠结扎和穿刺建立了败血症小鼠 ALI 模型。在 SAL 治疗后,分析了 SAL 对小鼠铁蛋白沉积途径的影响。通过转录组学和代谢组学分析,评估了小鼠肺组织的病理损伤、支气管肺泡灌洗液(BALF)中炎症因子和细胞凋亡的水平,并探讨了基因表达水平和代谢物含量丰度的变化。通过腹腔注射铁蛋白激活剂Erastin或铁蛋白抑制剂Ferrostatin-1来促进或抑制小鼠的铁蛋白沉积,观察了SAL对肺损伤小鼠铁蛋白沉积的影响。SAL 能明显减轻肺损伤小鼠肺组织的病理损伤,减少 TUNEL 阳性细胞的数量,降低 BALF 中 TNF-α、IL-1β、IL-6 的水平,提高 IL- 10 的水平。此外,Fe2+ 含量和丙二醛含量显著下降,活性氧和谷胱甘肽含量显著增加,花生四烯酸代谢物 20-hydroxyeicosatetraenoic acid(20-HETE)、(5Z, 8Z, 10E, 14Z)-12-Oxoeicosa-5,8,10,14-tetraenoic acid(12-OxOETE)、(5Z,8Z,10E,14Z)-(12S)-12-羟基-5,8,10,14-四烯酸(12(S)-HETE)、(5Z,8Z,14Z)-11,12-二羟基-5,8,14-三烯酸(11、12-DHET)、(5Z, 11Z, 14Z)-8,9- 二羟基二十二碳-5,11,14-三烯酸、白三烯 B4、白三烯 D4 在 SAL 处理后显著上调。皂苷能通过抑制铁变态反应减轻败血症引起的急性呼吸道感染。
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引用次数: 0
Precision proteomics with TurboID: mapping the suborganelle landscape. 利用 TurboID 进行精准蛋白质组学研究:绘制亚细胞器图谱。
IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-01 DOI: 10.4196/kjpp.2024.28.6.495
Han Byeol Kim, Kwang-Eun Kim

Recent research underscores the pivotal role of cellular organelles, such as mitochondria, the endoplasmic reticulum, and lysosomes, in maintaining cellular homeostasis. Their dynamic interactions are critical for metabolic regulation and stress response. Analysis of organelle proteomes offers valuable insights into their functions in both physiology and disease. Traditional proteomic approaches to studying isolated organelles are now complemented by innovative methodologies focusing on inter-organelle interactions. This review examines the integration of advanced proximity labeling technologies, including TurboID and split-TurboID, which address the inherent limitations of traditional techniques and enable precision proteomics of suborganelle compartments and inter-organellar contact sites. These innovations have led to discoveries regarding organelle interconnections, revealing mechanisms underlying metabolic processes such as cholesterol metabolism, glucose metabolism, and lysosomal repair. In addition to highlighting the advancements in TurboID applications, this review delineates the evolving trends in organelle research, underscoring the transformative potential of these techniques to significantly enhance organelle-specific proteomic investigations.

最新研究强调了线粒体、内质网和溶酶体等细胞器在维持细胞平衡方面的关键作用。它们之间的动态相互作用对于新陈代谢调节和应激反应至关重要。细胞器蛋白质组的分析为了解它们在生理和疾病中的功能提供了宝贵的信息。研究分离细胞器的传统蛋白质组学方法现在得到了侧重于细胞器间相互作用的创新方法的补充。本综述探讨了先进的近距离标记技术(包括 TurboID 和 split-TurboID)的整合,这些技术解决了传统技术的固有局限性,实现了亚细胞器区室和细胞器间接触点的精确蛋白质组学研究。这些创新发现了细胞器之间的相互联系,揭示了胆固醇代谢、葡萄糖代谢和溶酶体修复等代谢过程的内在机制。本综述除了重点介绍 TurboID 的应用进展外,还描述了细胞器研究的演变趋势,强调了这些技术在显著增强细胞器特异性蛋白质组学研究方面的变革潜力。
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引用次数: 0
Chemopreventive potential of goniothalamin in diethylnitrosamine-induced hepatocellular carcinoma through the suppression of P13K/AKT signalling pathway. 通过抑制P13K/AKT信号通路,补骨脂素对二乙亚硝胺诱导的肝细胞癌具有化学预防潜力
IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-01 DOI: 10.4196/kjpp.2024.28.6.539
Jie Li, Dong Zhan, Cui Chen, Rongfu Li, Fang-Qing Zhu

Liver cancer is the most lethal form of cancer and carries a high risk of death around the world. Goniothalamin (GTN) is a styryl-lactone that possesses antiproliferative and apoptotic activity. The molecular action of GTN is not yet fully evaluated. Thus, our research has been intended to assess the chemopreventive and apoptotic activities of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) in rats. Rats were separated into 4 groups: control, DEN only, DEN + GTN (30 mg/kg bw), and GTN (30 mg/kg bw) alone. We evaluated body weight, liver weight, tumor incidence, hepatic toxic markers, antioxidants, inflammatory cytokines, histopathology, immunohistochemistry, and Western blot studies. DEN lessened body weight, antioxidants, and apoptosis, whereas it elevated tumor incidence, toxic markers, cytokines, and Bcl-2 expression. GTN treatment maintains body weight, liver weight, and antioxidant levels, and it also prevents tumor incidence, oxidative stress, toxic markers, pro-inflammatory cytokines, and histological changes. It triggers apoptosis by constraining Bcl-2 and elevating caspase-3 levels. GTN also attenuated the P13K/ AKT signaling which enhanced apoptosis. These findings revealed that GTN subdues the P13K/AKT pathway and has auspicious chemopreventive and apoptotic actions in DEN-induced HCC. Therefore, GTN would be suggested as a new medicine in natural remedies for liver cancer.

肝癌是最致命的癌症,在全世界都有很高的死亡风险。Goniothalamin(GTN)是一种苯乙烯内酯,具有抗增殖和细胞凋亡活性。GTN 的分子作用尚未得到充分评估。因此,我们的研究旨在评估二乙基亚硝胺(DEN)诱导的大鼠肝细胞癌(HCC)的化学预防和细胞凋亡活性。大鼠被分为 4 组:对照组、仅 DEN 组、DEN + GTN(30 毫克/千克体重)组和仅 GTN(30 毫克/千克体重)组。我们对大鼠的体重、肝脏重量、肿瘤发病率、肝脏毒性标记物、抗氧化剂、炎症细胞因子、组织病理学、免疫组化和 Western 印迹进行了评估。DEN降低了体重、抗氧化剂和细胞凋亡,而提高了肿瘤发病率、毒性标志物、细胞因子和Bcl-2的表达。GTN 治疗可维持体重、肝脏重量和抗氧化剂水平,还能防止肿瘤发生、氧化应激、毒性标志物、促炎细胞因子和组织学变化。它通过抑制 Bcl-2 和提高 caspase-3 水平来触发细胞凋亡。GTN 还能减弱 P13K/ AKT 信号传导,从而增强细胞凋亡。这些研究结果表明,GTN 可抑制 P13K/AKT 通路,对 DEN 诱导的 HCC 具有良好的化学预防和细胞凋亡作用。因此,GTN可作为肝癌自然疗法的一种新药。
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引用次数: 0
Exercise improves muscle mitochondrial dysfunction-associated lipid profile under circadian rhythm disturbance. 在昼夜节律紊乱的情况下,运动可改善肌肉线粒体功能障碍相关的血脂状况。
IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-01 DOI: 10.4196/kjpp.2024.28.6.515
Yu Gu, Dong-Hun Seong, Wenduo Liu, Zilin Wang, Yong Whi Jeong, Jae-Cheol Kim, Dae Ryong Kang, Rose Ji Eun Lee, Jin-Ho Koh, Sang Hyun Kim

We investigated whether endurance exercise training (EXT) ameliorates circadian rhythm (CR)-induced risk factors by improving skeletal muscle (SKM) mitochondrial biogenesis, reducing oxidative stress, and modulating apoptotic protein expression. We distinguished between regular and shift workers using the National Health and Nutrition Examination Survey (NHANES) and investigated the health problems caused by shift work (CR disturbance) and the potential therapeutic effects of exercise. In our animal study, 36 rats underwent 12 weeks of CR disturbance, divided into regular and irregular CR groups. These groups were further split into EXT (n = 12) and sedentary (n = 12) for an additional 8 weeks. We analyzed SKM tissue to understand the molecular changes induced by CR and EXT. NHANES data were analyzed using SAS 9.4 and Prism 8 software, while experimental animal data were analyzed using Prism 8 software. The statistical procedures used in each experiment are indicated in the figure legends. Our studies showed that CR disturbance increases dyslipidemia, alters circadian clock proteins (BMAL1, PER2), raises apoptotic protein levels, and reduces mitochondrial biogenesis in SKM. EXT improved LDL-C and HDLC levels without affecting muscle BMAL1 expression. It also enhanced mitochondrial biogenesis (AMPK, PGC-1α, Tfam, NADH-UO, COX-I), antioxidant levels (Catalase, SOD1, SOD2), and apoptotic protein (p53, Bax/Bcl2) expression or activity in SKM. We demonstrated that shift work-induced CR disturbance leads to dyslipidemia, diminished mitochondrial biogenesis, and reduced antioxidant capacity in SKM. However, EXT can counteract dyslipidemia under CR disturbance, potentially lowering the risk of cardiovascular disorders.

我们研究了耐力运动训练(EXT)是否能通过改善骨骼肌(SKM)线粒体生物生成、减少氧化应激和调节凋亡蛋白表达来改善昼夜节律(CR)诱发的风险因素。我们利用美国国家健康与营养调查(NHANES)区分了普通工人和轮班工人,并调查了轮班工作(昼夜节律紊乱)导致的健康问题以及运动的潜在治疗效果。在我们的动物研究中,36 只大鼠接受了为期 12 周的 CR 干扰,分为定期 CR 组和不定期 CR 组。这些组又分为EXT组(n = 12)和静坐组(n = 12),共8周。我们对 SKM 组织进行了分析,以了解 CR 和 EXT 引起的分子变化。NHANES 数据使用 SAS 9.4 和 Prism 8 软件进行分析,实验动物数据使用 Prism 8 软件进行分析。每个实验所使用的统计程序均在图例中标明。我们的研究表明,CR 干扰会增加 SKM 的血脂异常、改变昼夜节律钟蛋白(BMAL1、PER2)、提高凋亡蛋白水平并减少线粒体的生物生成。EXT 可改善低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDLC)水平,但不影响肌肉中 BMAL1 的表达。它还增强了 SKM 的线粒体生物生成(AMPK、PGC-1α、Tfam、NADH-UO、COX-I)、抗氧化水平(过氧化氢酶、SOD1、SOD2)和凋亡蛋白(p53、Bax/Bcl2)的表达或活性。我们证明,轮班工作引起的 CR 干扰会导致 SKM 中的血脂异常、线粒体生物生成减弱和抗氧化能力降低。然而,EXT 可以抵消 CR 干扰下的血脂异常,从而降低心血管疾病的风险。
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引用次数: 0
Predicting antioxidant activity of compounds based on chemical structure using machine learning methods. 利用机器学习方法根据化学结构预测化合物的抗氧化活性。
IF 1.6 4区 医学 Q3 PHARMACOLOGY & PHARMACY Pub Date : 2024-11-01 DOI: 10.4196/kjpp.2024.28.6.527
Jinwoo Jung, Jeon-Ok Moon, Song Ih Ahn, Haeseung Lee

Oxidative stress is a well-established risk factor for numerous chronic diseases, emphasizing the need for efficient identification of potent antioxidants. Conventional methods for assessing antioxidant properties are often time-consuming and resource-intensive, typically relying on laborious biochemical assays. In this study, we investigated the applicability of machine learning (ML) algorithms for predicting the antioxidant activity of compounds based solely on their molecular structure. We evaluated the performance of five ML algorithms, Support Vector Machine (SVM), Logistic Regression (LR), XGBoost, Random Forest (RF), and Deep Neural Network (DNN), using a dataset of over 1,900 compounds with experimentally determined antioxidant activity. Both RF and SVM achieved the best overall performance, exhibiting high accuracy (> 0.9) and effectively distinguishing active and inactive compounds with high structural similarity. External validation using natural product data from the BATMAN database confirmed the generalizability of the RF and SVM models. Our results suggest that ML models serve as powerful tools to expedite the discovery of novel antioxidant candidates, potentially streamlining the development of future therapeutic interventions.

氧化应激是众多慢性疾病的既定风险因素,因此需要有效地识别强效抗氧化剂。评估抗氧化剂特性的传统方法往往耗费时间和资源,通常依赖于费力的生化试验。在本研究中,我们研究了机器学习(ML)算法在仅根据化合物分子结构预测其抗氧化活性方面的适用性。我们使用由 1900 多种经实验确定具有抗氧化活性的化合物组成的数据集,评估了支持向量机(SVM)、逻辑回归(LR)、XGBoost、随机森林(RF)和深度神经网络(DNN)这五种 ML 算法的性能。RF 和 SVM 的总体性能最佳,表现出较高的准确性(> 0.9),并能有效区分结构相似度较高的活性和非活性化合物。利用 BATMAN 数据库中的天然产品数据进行的外部验证证实了 RF 和 SVM 模型的通用性。我们的研究结果表明,ML 模型是加快发现新型抗氧化候选化合物的有力工具,有可能简化未来治疗干预措施的开发。
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引用次数: 0
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Korean Journal of Physiology & Pharmacology
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