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Retraction notice to “Tumor-secreted GRP78 facilitates the migration of macrophages into tumors by promoting cytoskeleton remodeling” [Cellular Signalling volume (60) August 2019, 1–16] 肿瘤分泌的GRP78通过促进细胞骨架重塑促进巨噬细胞向肿瘤迁移》的撤稿通知[《细胞信号》2019年8月卷(60),1-16]。
IF 4.4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-15 DOI: 10.1016/j.cellsig.2024.111460
Xiaoqin La , Lichao Zhang , Yufei Yang , Hanqing Li , Guisheng Song , Zhuoyu Li
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引用次数: 0
Histone methyltransferase WHSC1 cooperate with YBX1 promote glioblastoma progression via regulating PLK1 expression 组蛋白甲基转移酶WHSC1与YBX1合作,通过调节PLK1的表达促进胶质母细胞瘤的进展。
IF 4.4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-13 DOI: 10.1016/j.cellsig.2024.111471
Shuaijun Lu, Zhibo Zheng, Changling Zhu
Wolf-Hirschhorn syndrome candidate gene 1 (WHSC1), a histone methyltransferase, has been implicated in various tumor development processes by regulating target gene expression. However, the role of WHSC1 in glioblastoma remains unexplored. This study investigates the impact of WHSC1 in glioblastoma and its association with prognosis. Our findings reveal that WHSC1 is overexpressed in glioblastoma and correlates with poor patient outcomes. Functional assays demonstrate that the reduction of WHSC1 significantly impairs cell proliferation and tumorigenicity. Mechanistically, WHSC1 modulates PLK1 expression by binding to its promoter region, leading to the activation of the PLK1-AKT pathway, and regulating H3K36 dimethylation levels. Furthermore, YBX1 can cooperate with WHSC1 to activate PLK1 transcription. These results shed light on the potential significance of WHSC1 in glioblastoma and offer a promising avenue for future therapeutic approaches targeting this molecule in glioblastoma treatment.
沃尔夫-赫希霍恩综合征候选基因1(WHSC1)是一种组蛋白甲基转移酶,它通过调节靶基因的表达与多种肿瘤的发生发展过程有关。然而,WHSC1 在胶质母细胞瘤中的作用仍有待探索。本研究探讨了WHSC1在胶质母细胞瘤中的影响及其与预后的关系。我们的研究结果表明,WHSC1在胶质母细胞瘤中过度表达,并与患者的不良预后相关。功能测试表明,减少 WHSC1 会显著影响细胞增殖和致瘤性。从机理上讲,WHSC1 通过与其启动子区域结合来调节 PLK1 的表达,导致 PLK1-AKT 通路的激活,并调节 H3K36 的二甲基化水平。此外,YBX1 还能与 WHSC1 合作激活 PLK1 的转录。这些结果揭示了WHSC1在胶质母细胞瘤中的潜在意义,并为未来针对该分子的胶质母细胞瘤治疗方法提供了一个前景广阔的途径。
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引用次数: 0
Txnip promotes autophagic apoptosis in diabetic cardiomyopathy by upregulating FoxO1 and its acetylation Txnip 通过上调 FoxO1 及其乙酰化促进糖尿病心肌病的自噬性凋亡
IF 4.4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-11 DOI: 10.1016/j.cellsig.2024.111469
Yaoting Zhang, Bing Li, Yu Fu, He Cai, Yang Zheng
Autophagy dysfunction and apoptosis exacerbate the risk of heart failure in patients with diabetic cardiomyopathy (DCM). However, the interactions between autophagy and apoptosis in DCM and their underlying mechanisms remain poorly understood. This study induced type 1 DCM in C57BL/6 mice via streptozotocin injection and exposed H9C2 cells to high glucose to investigate these mechanisms. The study revealed a significant elevation in autophagic vesicles and compromised autophagic flux, accompanied by pronounced myocardial cell apoptosis in the myocardium of diabetic mice. Long-term exposure to high glucose in H9C2 cells led to enhanced autophagosome formation and impaired autophagic flux, while inhibition of autophagy with 3-MA reduced cell apoptosis. Additionally, we observed an increase in Txnip expression in the myocardium of diabetic mice and in high glucose-treated H9C2 cells, which regulates autophagic apoptosis in high glucose-treated H9C2 cells. Furthermore, Txnip regulates autophagic apoptosis through the modulation of forkhead box-1 (FoxO1) expression and acetylation. Prolonged high glucose exposure resulted in increased levels of phosphorylated sirtuin 1 (SIRT1) and reduced SIRT1/FoxO1 interaction, changes that were ameliorated by Txnip knockdown. Txnip overexpression elevated FoxO1 levels, which could be suppressed by NAC and GSH. These findings revealed that Txnip mediates autophagic apoptosis in DCM by upregulating FoxO1 via ROS and enhancing FoxO1 acetylation through the suppression of SIRT1 activity. The discovery of this new mechanism provides new perspectives and potential therapeutic targets for understanding and treating DCM.
自噬功能障碍和细胞凋亡会加剧糖尿病心肌病(DCM)患者心力衰竭的风险。然而,人们对自噬和细胞凋亡在 DCM 中的相互作用及其内在机制仍知之甚少。本研究通过注射链脲佐菌素诱导 C57BL/6 小鼠发生 1 型 DCM,并将 H9C2 细胞暴露于高糖环境中,以研究这些机制。研究发现,糖尿病小鼠心肌中的自噬小泡明显增多,自噬通量受到影响,同时伴有明显的心肌细胞凋亡。在 H9C2 细胞中长期暴露于高葡萄糖会导致自噬体形成增强和自噬通量受损,而用 3-MA 抑制自噬会减少细胞凋亡。此外,我们观察到 Txnip 在糖尿病小鼠心肌和高糖处理的 H9C2 细胞中的表达增加,它能调节高糖处理的 H9C2 细胞的自噬凋亡。此外,Txnip 还通过调节叉头盒-1(FoxO1)的表达和乙酰化来调节自噬性凋亡。长期暴露于高葡萄糖会导致磷酸化sirtuin 1(SIRT1)水平升高和SIRT1/FoxO1相互作用减弱,而敲除Txnip后这些变化会得到改善。Txnip 过表达会使 FoxO1 水平升高,而 NAC 和 GSH 可抑制 FoxO1 水平的升高。这些发现揭示了 Txnip 通过 ROS 上调 FoxO1,并通过抑制 SIRT1 的活性增强 FoxO1 乙酰化,从而介导 DCM 的自噬性凋亡。这一新机制的发现为了解和治疗 DCM 提供了新的视角和潜在的治疗靶点。
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引用次数: 0
PRKAA2-mediated mitophagy regulates oxygen consumption in yak renal tubular epithelial cells under chronic hypoxia PRKAA2- 介导的有丝分裂调节慢性缺氧条件下牦牛肾小管上皮细胞的耗氧量
IF 4.4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-11 DOI: 10.1016/j.cellsig.2024.111450
Xuefeng Bai , Hongqin Lu , Yan Cui , Sijiu Yu , Rui Ma , Shanshan Yang , Junfeng He
Hypoxic environments are significant factors in the induction of various kidney diseases and are closely associated with high oxygen consumption in the kidneys. Yaks live at high altitude for a long time, exhibit a unique ability to regulate kidney oxygen consumption, protecting them from hypoxia-induced damage. However, the mechanisms underlying the regulation of oxygen consumption in yak kidneys under hypoxic conditions remain unclear. To explore this hypoxia adaptation mechanism in yak kidneys, this study analyzed the oxygen consumption rate (OCR) of renal tubular epithelial cells (RTECs) under hypoxia. We found that the OCR and apoptosis rates of RTECs under chronic hypoxia (> 24 h) were lower than those under acute hypoxia (≤ 24 h). However, when oxygen consumption was promoted under chronic hypoxia, the apoptosis rate increased, indicating that reducing the cellular OCR is crucial for maintaining RTECs activity under hypoxia. High-throughput sequencing results showed that the mitophagy pathway is likely a key mechanism for inhibiting OCR of yak RTECs, with protein kinase AMP-activated catalytic subunit alpha 2 (PRKAA2) playing a significant role in this process. Further studies demonstrated that chronic hypoxia activates the mitophagy pathway, which inhibits oxidative phosphorylation (OXPHOS) while increasing glycolytic flux in yak RTECs. Conversely, when the mitophagy pathway was inhibited, there was an increase in the activity of OXPHOS enzymes and OCR. To further explore the role of PRKAA2 in the mitophagy pathway, we inhibited PRKAA2 expression under chronic hypoxia. Results showed that the downregulation of PRKAA2 decreased the expression of mitophagy-related proteins, such as p-FUNDC1/FUNDC1, LC3-II/LC3-I, BNIP3 and ULK1 while upregulating P62 expression. Additionally, there was an increase in the enzyme activities of Complex II, Complex IV, PDH, and SDH, which further promoted oxygen consumption in RTECs. These findings suggest that PRKAA2 mediated mitophagy under chronic hypoxia is crucial mechanism for reducing oxygen consumption in yak RTECs.
缺氧环境是诱发各种肾脏疾病的重要因素,与肾脏的高耗氧量密切相关。牦牛长期生活在高海拔地区,具有独特的调节肾脏耗氧量的能力,可保护肾脏免受缺氧引起的损伤。然而,缺氧条件下牦牛肾脏耗氧量的调节机制仍不清楚。为了探索牦牛肾脏的这种缺氧适应机制,本研究分析了缺氧条件下肾小管上皮细胞(RTECs)的耗氧量(OCR)。我们发现,慢性缺氧(24小时)条件下肾小管上皮细胞的耗氧率和凋亡率均低于急性缺氧(≤24小时)条件下的耗氧率和凋亡率。然而,在慢性缺氧条件下,当促进氧消耗时,细胞凋亡率增加,这表明降低细胞OCR对维持RTECs在缺氧条件下的活性至关重要。高通量测序结果显示,有丝分裂途径可能是抑制牦牛RTECs OCR的关键机制,而蛋白激酶AMP激活催化亚基α2(PRKAA2)在这一过程中发挥着重要作用。进一步的研究表明,慢性缺氧会激活有丝分裂途径,从而抑制氧化磷酸化(OXPHOS),同时增加牦牛RTEC的糖酵解通量。相反,当抑制有丝分裂途径时,OXPHOS 酶和 OCR 的活性会增加。为了进一步探讨PRKAA2在有丝分裂途径中的作用,我们在慢性缺氧条件下抑制了PRKAA2的表达。结果显示,下调PRKAA2会降低有丝分裂相关蛋白的表达,如p-FUNDC1/FUNDC1、LC3-II/LC3-I、BNIP3和ULK1,同时上调P62的表达。此外,复合体 II、复合体 IV、PDH 和 SDH 的酶活性也有所增加,这进一步促进了 RTECs 的耗氧量。这些发现表明,PRKAA2在慢性缺氧条件下介导的有丝分裂是降低牦牛RTEC耗氧量的关键机制。
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引用次数: 0
Enriched environment enhances angiogenesis in ischemic stroke through SDF-1/CXCR4/AKT/mTOR pathway 富集环境通过 SDF-1/CXCR4/AKT/mTOR 通路促进缺血性中风的血管生成
IF 4.4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-11 DOI: 10.1016/j.cellsig.2024.111464
Yonggang Zhang , Sheng Qiu , Yi Pang , Zhongzhou Su , Lifang Zheng , Binghao Wang , Hongbo Zhang , Pingping Niu , Shehong Zhang , Yuntao Li
Environmental-gene interactions significantly influence various bodily functions. Enriched environment (EE), a non-pharmacological treatment method, enhances angiogenesis in ischemic stroke (IS). However, underlying the role of EE in angiogenesis in aged mice post-IS remain unclear. This study aimed to determine the potential mechanism by which EE mediates angiogenesis in 12-month-old IS mice and oxygen-glucose deprivation/reperfusion (OGD/R)-induced bEnd.3 cells. In vivo, EE treatment alleviated the neurological deficits, enhanced angiogenesis, upregulated SDF-1, VEGFA, and the AKT/mTOR pathway. In addition, exogenous SDF-1 treatment had a protective effect similar to that of EE treatment in aged mice with IS. However, SDF-1 neutralizing antibody, AMD3100 (CXCR4 inhibitor), ARQ092 (AKT inhibitor), and rapamycin (mTOR inhibitor) treatment blocked the neuroprotective effect of EE treatment and inhibited angiogenesis in IS mice. In vitro, exogenous SDF-1 promoted migration of OGD/R-induced bEnd.3 cells and activated the AKT/mTOR pathway. AMD3100, ARQ092, and rapamycin inhibited SDF-1-induced cell migration. Collectively, these findings demonstrate that EE enhances angiogenesis and improves the IS outcomes through SDF-1/CXCR4/AKT/mTOR pathway.
环境与基因之间的相互作用极大地影响着人体的各种功能。富集环境(EE)作为一种非药物治疗方法,可增强缺血性中风(IS)的血管生成。然而,EE在缺血性脑卒中后老年小鼠血管生成中的作用尚不清楚。本研究旨在确定EE介导12个月大的IS小鼠和氧-葡萄糖剥夺/再灌注(OGD/R)诱导的bEnd.3细胞血管生成的潜在机制。在体内,EE治疗缓解了神经功能缺损,增强了血管生成,上调了SDF-1、VEGFA和AKT/mTOR通路。此外,外源性SDF-1治疗对老年IS小鼠的保护作用与EE治疗相似。然而,SDF-1中和抗体、AMD3100(CXCR4抑制剂)、ARQ092(AKT抑制剂)和雷帕霉素(mTOR抑制剂)的治疗阻断了EE治疗对IS小鼠神经的保护作用,并抑制了血管生成。在体外,外源性 SDF-1 可促进 OGD/R 诱导的 bEnd.3 细胞迁移并激活 AKT/mTOR 通路。AMD3100、ARQ092和雷帕霉素抑制了SDF-1诱导的细胞迁移。总之,这些研究结果表明,EE可通过SDF-1/CXCR4/AKT/mTOR途径增强血管生成并改善IS的结果。
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引用次数: 0
Forkhead box C1 promotes the pathology of osteoarthritis in subchondral bone osteoblasts via the Piezo1/YAP axis 叉头盒 C1 通过 Piezo1/YAP 轴促进软骨下骨成骨细胞骨关节炎的病理变化
IF 4.4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-11 DOI: 10.1016/j.cellsig.2024.111463
Zhengyuan Li , Lin Hao , Shenghong Chen , Wenhan Fu , Hui Zhang , Zongsheng Yin , Yin Wang , Jun Wang
Subchondral bone sclerosis is a key characteristic of osteoarthritis (OA). Prior research has shown that Forkhead box C1 (FoxC1) plays a role in the synovial inflammation of OA, but its specific role in the subchondral bone of OA has not been explored. Our research revealed elevated expression levels of FoxC1 and Piezo1 in OA subchondral bone tissues. Further experiments on OA subchondral bone osteoblasts with FoxC1 or Piezo1 overexpression showed increased cell proliferation activity, expression of Yes-associated Protein 1 (YAP) and osteogenic markers, and secretion of proinflammatory factors. Mechanistically, the overexpression of FoxC1 through Piezo1 activation, in combination with downstream YAP signaling, led to increased levels of alkaline phosphatase (ALP), collagen type 1 (COL1) A1, RUNX2, Osteocalcin, matrix metalloproteinase (MMP) 3, and MMP9 expression. Notably, inhibition of Piezo1 reversed the regulatory function of FoxC1. The binding of FoxC1 to the targeted area (ATATTTATTTA, residues +612 to +622) and the activation of Piezo1 transcription were verified by the dual luciferase assays. Additionally, Reduced subchondral osteosclerosis and microangiogenesis were observed in knee joints from FoxC1-conditional knockout (CKO) and Piezo1-CKO mice, indicating reduced lesions. Collectively, our study reveals the significant involvement of FoxC1 in the pathologic process of OA subchondral bone via the Piezo1/YAP signaling pathway, potentially establishing a novel therapeutic target.
软骨下骨硬化是骨关节炎(OA)的一个主要特征。先前的研究表明,叉头盒 C1(FoxC1)在 OA 的滑膜炎症中发挥作用,但其在 OA 软骨下骨中的具体作用尚未得到探讨。我们的研究发现,FoxC1 和 Piezo1 在 OA 软骨下骨组织中的表达水平升高。对 FoxC1 或 Piezo1 过表达的 OA 软骨下骨成骨细胞的进一步实验显示,细胞增殖活性、Yes 相关蛋白 1(YAP)和成骨标志物的表达以及促炎因子的分泌均有所增加。从机理上讲,通过激活 Piezo1 过表达 FoxC1 与下游 YAP 信号结合,导致碱性磷酸酶(ALP)、1 型胶原蛋白(COL1)A1、RUNX2、骨钙蛋白、基质金属蛋白酶(MMP)3 和 MMP9 表达水平升高。值得注意的是,抑制 Piezo1 会逆转 FoxC1 的调控功能。双荧光素酶试验验证了 FoxC1 与靶区(ATATTTATTTA,残基 +612 至 +622)的结合以及对 Piezo1 转录的激活。此外,在 FoxC1 条件性基因敲除(CKO)和 Piezo1-CKO 小鼠的膝关节中观察到软骨下骨质硬化和微血管生成减少,表明病变减轻。总之,我们的研究揭示了FoxC1通过Piezo1/YAP信号通路在OA软骨下骨病理过程中的重要参与作用,有可能建立一个新的治疗靶点。
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引用次数: 0
Histone H4K12 lactylation promotes malignancy progression in triple-negative breast cancer through SLFN5 downregulation 组蛋白 H4K12 乳化通过 SLFN5 下调促进三阴性乳腺癌的恶性进展。
IF 4.4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-10 DOI: 10.1016/j.cellsig.2024.111468
Jingyi Li , Ziyu Chen , Mingming Jin , Xuefeng Gu , Yuhan Wang , Gang Huang , Weiming Zhao , Changlian Lu
Lactylation, a newly identified post-translational modification, is uncertain in its implication in triple-negative breast cancer (TNBC). In this study, we analyzed 60 TNBC samples using immunohistochemical staining and revealed elevated levels of pan-lactylated proteins and specific histone H4K12 lactylation in tumor tissues, correlating with TNBC progression. Lactate exposure in TNBC cell lines significantly induced lysine lactylation at the H4K12 site, leading to alterations in gene profiles and reduced apoptosis. These effects were attenuated by DCA or sodium Oxamate, inhibitors of endogenous lactate production. Gene sequencing showed an increase in Schlafen 5 (SLFN5) expression in TNBC cells treated with Oxamate, contrasting with the effects of lactate exposure. Analysis of TNBC tissues showed a negative correlation between H4K12 lactylation and SLFN5 protein levels. Overexpression of SLFN5 countered the effects of lactate on apoptosis and tumor growth, highlighting its pivotal role in TNBC malignancy. CUT&Tag sequencing indicated that lactylated H4K12 potentially binds to the SLFN5 promoter region. Luciferase reporter assays further verified that lactate-induced suppression of SLFN5 promoter activity is mediated by wild-type H4K12, but not by its R or A mutants, verified by both in vitro and in vivo apoptosis detection in response to lactate and Oxamate stimulation. These results establish that H4K12 lactylation, induced by lactate in TNBC cells, specifically suppresses SLFN5 expression, contributing to TNBC malignancy. Our findings illuminate a critical histone lactylation-dependent carcinogenic pathway in TNBC.
乳化是一种新发现的翻译后修饰,其在三阴性乳腺癌(TNBC)中的影响尚不确定。在这项研究中,我们使用免疫组化染色法分析了 60 例 TNBC 样本,结果发现肿瘤组织中泛乳化蛋白和特异性组蛋白 H4K12 乳化水平升高,这与 TNBC 的进展相关。TNBC 细胞系中的乳酸暴露会显著诱导 H4K12 位点的赖氨酸乳化,导致基因谱改变和细胞凋亡减少。内源性乳酸生成抑制剂DCA或草酸钠可减轻这些影响。基因测序显示,在使用草氨酸钠处理的 TNBC 细胞中,Schlafen 5 (SLFN5) 的表达增加,与乳酸盐暴露的影响形成鲜明对比。对 TNBC 组织的分析表明,H4K12 乳酸化与 SLFN5 蛋白水平呈负相关。SLFN5的过表达抵消了乳酸盐对细胞凋亡和肿瘤生长的影响,突显了它在TNBC恶性肿瘤中的关键作用。CUT&Tag测序表明,乳酸化的H4K12可能与SLFN5启动子区域结合。荧光素酶报告实验进一步验证了乳酸诱导的SLFN5启动子活性抑制是由野生型H4K12介导的,而不是由其R或A突变体介导的。这些结果证实,TNBC细胞中乳酸诱导的H4K12乳酸化能特异性地抑制SLFN5的表达,从而导致TNBC恶性肿瘤。我们的研究结果阐明了 TNBC 中一个关键的组蛋白乳酸化依赖性致癌途径。
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引用次数: 0
Effects of pomegranate exocarp extract on H. pylori-induced pancreatic EMT: Molecular mechanisms and therapeutic potential 石榴外果皮提取物对幽门螺杆菌诱导的胰腺 EMT 的影响:分子机制和治疗潜力。
IF 4.4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-10 DOI: 10.1016/j.cellsig.2024.111465
Mariam A. Abo-Saif , Ghada M. Al-Ashmawy , Amany E. Ragab , Lamiaa A. Al-Madboly , Ahmed B.M. Mehany , Sherin R. El-Afify
<div><h3>Background</h3><div>Previous studies have linked <em>Helicobacter pylori</em> infection with pancreatic diseases, including cancer.</div></div><div><h3>Purpose</h3><div>To explore the influence of pomegranate exocarp extract (PEE) on epithelial-mesenchymal transition (EMT) in <em>H. pylori</em>-induced pancreatic rat tissue and to uncover the underlying molecular mechanisms.</div></div><div><h3>Study design</h3><div>Twenty-eight rats were divided into six groups: group 1 (negative control), group 2 (<em>H. pylori-</em>infected), group 3 (infected + PEE pretreatment), group 4 (infected + PEE treatment), group 5 (infected + metronidazole treatment), and group 6 (infected + metronidazole/PEE co-treatment).</div></div><div><h3>Methods and results</h3><div>This study aimed to assess the effectiveness of pomegranate exocarp extract (PEE) in treating <em>Helicobacter pylori</em> infection and its associated pancreatic tissue changes in Wistar rats. The study involved Forty-eight male rats divided into six groups: <em>H. pylori</em>-infected control, PEE-preventive, PEE treatment, metronidazole treatment, PEE combined with metronidazole treatment, and negative control. The results showed a significant reduction in <em>H. pylori</em> concentration in the antrum in the PEE-treated groups (27.08 %) compared to that in the positive control group (<em>p</em> < 0.05). The group receiving the combined treatment exhibited the highest reduction (55.8 %) in <em>H. pylori</em> concentration (<em>p</em> < 0.005), with no significant difference observed between the PEE-preventive and metronidazole-treated groups. The ELISA results showed that the groups treated with PEE, PEE-preventive, and PEE combined with metronidazole experienced a significant increase in pancreatic E-cadherin levels by 47.7 %, 73.8 %, and 118.06 % respectively, and a substantial decrease in vimentin levels by 16.6 %, 31.6 %, and 43.5 % respectively, compared to the positive control group (<em>p</em> < 0.05). The results of the RT-qPCR analysis showed that the PEE treatment group, as well as the PEE preventive and PEE combined with metronidazole treatment groups, displayed significant downregulation of vimentin, sirtuin1, and lncRNA MALAT-1, and upregulation of E-cadherin compared to the positive control group. However, there was no significant difference between the PEE-preventive and metronidazole-treated groups (<em>p</em> < 0.05). Histopathological analysis showed considerable improvement in pancreatic tissue morphology in the PEE-treated groups. The inflammation score was significantly lower in these groups (<em>p</em> < 0.05), and the combined treatment group exhibited minimal signs of metaplasia and mononuclear cell infiltration. A computational study identified 54 human target genes of bioactive compounds in PEE. These findings shed light on the crucial interactions and pathways in treating pancreatic tumors. Additionally, GO enrichment and KEGG pathway analyses re
背景:先前的研究表明幽门螺杆菌感染与胰腺疾病(包括癌症)有关:目的:探讨石榴外果皮提取物(PEE)对幽门螺杆菌诱导的胰腺大鼠组织上皮-间质转化(EMT)的影响,并揭示其潜在的分子机制:28只大鼠分为6组:第1组(阴性对照)、第2组(幽门螺杆菌感染)、第3组(感染+PEE预处理)、第4组(感染+PEE治疗)、第5组(感染+甲硝唑治疗)和第6组(感染+甲硝唑/PEE联合治疗):本研究旨在评估石榴外果皮提取物(PEE)治疗 Wistar 大鼠幽门螺杆菌感染及其相关胰腺组织变化的效果。研究将48只雄性大鼠分为六组:幽门螺杆菌感染对照组、PEE预防组、PEE治疗组、甲硝唑治疗组、PEE联合甲硝唑治疗组和阴性对照组。结果显示,与阳性对照组相比,PEE 治疗组胃窦中的幽门螺杆菌浓度明显降低(27.08 %)(p
{"title":"Effects of pomegranate exocarp extract on H. pylori-induced pancreatic EMT: Molecular mechanisms and therapeutic potential","authors":"Mariam A. Abo-Saif ,&nbsp;Ghada M. Al-Ashmawy ,&nbsp;Amany E. Ragab ,&nbsp;Lamiaa A. Al-Madboly ,&nbsp;Ahmed B.M. Mehany ,&nbsp;Sherin R. El-Afify","doi":"10.1016/j.cellsig.2024.111465","DOIUrl":"10.1016/j.cellsig.2024.111465","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Previous studies have linked &lt;em&gt;Helicobacter pylori&lt;/em&gt; infection with pancreatic diseases, including cancer.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;To explore the influence of pomegranate exocarp extract (PEE) on epithelial-mesenchymal transition (EMT) in &lt;em&gt;H. pylori&lt;/em&gt;-induced pancreatic rat tissue and to uncover the underlying molecular mechanisms.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Study design&lt;/h3&gt;&lt;div&gt;Twenty-eight rats were divided into six groups: group 1 (negative control), group 2 (&lt;em&gt;H. pylori-&lt;/em&gt;infected), group 3 (infected + PEE pretreatment), group 4 (infected + PEE treatment), group 5 (infected + metronidazole treatment), and group 6 (infected + metronidazole/PEE co-treatment).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods and results&lt;/h3&gt;&lt;div&gt;This study aimed to assess the effectiveness of pomegranate exocarp extract (PEE) in treating &lt;em&gt;Helicobacter pylori&lt;/em&gt; infection and its associated pancreatic tissue changes in Wistar rats. The study involved Forty-eight male rats divided into six groups: &lt;em&gt;H. pylori&lt;/em&gt;-infected control, PEE-preventive, PEE treatment, metronidazole treatment, PEE combined with metronidazole treatment, and negative control. The results showed a significant reduction in &lt;em&gt;H. pylori&lt;/em&gt; concentration in the antrum in the PEE-treated groups (27.08 %) compared to that in the positive control group (&lt;em&gt;p&lt;/em&gt; &lt; 0.05). The group receiving the combined treatment exhibited the highest reduction (55.8 %) in &lt;em&gt;H. pylori&lt;/em&gt; concentration (&lt;em&gt;p&lt;/em&gt; &lt; 0.005), with no significant difference observed between the PEE-preventive and metronidazole-treated groups. The ELISA results showed that the groups treated with PEE, PEE-preventive, and PEE combined with metronidazole experienced a significant increase in pancreatic E-cadherin levels by 47.7 %, 73.8 %, and 118.06 % respectively, and a substantial decrease in vimentin levels by 16.6 %, 31.6 %, and 43.5 % respectively, compared to the positive control group (&lt;em&gt;p&lt;/em&gt; &lt; 0.05). The results of the RT-qPCR analysis showed that the PEE treatment group, as well as the PEE preventive and PEE combined with metronidazole treatment groups, displayed significant downregulation of vimentin, sirtuin1, and lncRNA MALAT-1, and upregulation of E-cadherin compared to the positive control group. However, there was no significant difference between the PEE-preventive and metronidazole-treated groups (&lt;em&gt;p&lt;/em&gt; &lt; 0.05). Histopathological analysis showed considerable improvement in pancreatic tissue morphology in the PEE-treated groups. The inflammation score was significantly lower in these groups (&lt;em&gt;p&lt;/em&gt; &lt; 0.05), and the combined treatment group exhibited minimal signs of metaplasia and mononuclear cell infiltration. A computational study identified 54 human target genes of bioactive compounds in PEE. These findings shed light on the crucial interactions and pathways in treating pancreatic tumors. Additionally, GO enrichment and KEGG pathway analyses re","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"Article 111465"},"PeriodicalIF":4.4,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Corrigendum to “Recent progress of protein kinase inhibitors derived from marine peptides for developing anticancer gents” [Cellular Signalling 124 (2024) 111411] 从海洋肽中提取蛋白激酶抑制剂用于开发抗癌剂的最新进展"[Cellular Signalling 124 (2024) 111411]的更正。
IF 4.4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-10 DOI: 10.1016/j.cellsig.2024.111449
Lanhong Zheng , Ning Wei , Ammad Ahmad Farooqi , Yan Zhang , Renald Blundell , Xiujun Liu , Yixin Xu , Xiukun Lin
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引用次数: 0
Fangchinoline inhibits metastasis and reduces inflammation-induced epithelial-mesenchymal transition by targeting the FOXM1-ADAM17 axis in hepatocellular carcinoma 方棘霉素通过靶向 FOXM1-ADAM17 轴抑制肝细胞癌转移并减少炎症诱导的上皮-间质转化
IF 4.4 2区 生物学 Q2 CELL BIOLOGY Pub Date : 2024-10-10 DOI: 10.1016/j.cellsig.2024.111467
Liyun Zheng , Vinothkumar Rajamanickam , Mengyuan Wang , Huajun Zhang , Shiji Fang , Michael Linnebacher , A.M. Abd El-Aty , Xinbin Zhang , Yeyu Zhang , Jianbo Wang , Minjiang Chen , Zhongwei Zhao , Jiansong Ji
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Efforts have been focused on developing new anti-HCC agents and understanding their pharmacology. However, few agents have been able to effectively combat tumor growth and invasiveness due to the rapid progression of HCC. In this study, we discovered that fangchinoline (FAN), a bisbenzylisoquinoline alkaloid derived from Stephania tetrandra S. Moore, effectively inhibited the migration, invasion, and epithelial-mesenchymal transition (EMT) of HCC cells. FAN treatment also led to the suppression of IL6 and IL1β release, as well as the expression of inflammation-related proteins such as COX-2 and iNOS, and the activation of the NF-κB pathway, thereby reducing inflammation-related EMT. Additionally, FAN directly bound to forkhead box protein M1 (FOXM1), resulting in decreased levels of FOXM1 proteins and disruption of the FOXM1-ADAM17 axis. Our in vivo findings confirmed that FAN effectively hindered the growth and lung metastasis of HCCLM3-xenograft tumors. Importantly, the upregulation of FOXM1 in HCC tissue suggested that targeting FOXM1 inhibition with FAN or its inhibitors could be a promising therapeutic approach for HCC. Overall, this study elucidated the anti-tumor effects and potential pharmacological mechanisms of FAN, and proposed that targeting FOXM1 inhibition may be an effective therapeutic strategy for HCC with potential clinical applications.
肝细胞癌(HCC)是全球癌症相关死亡的主要原因。人们一直致力于开发新的抗 HCC 药物并了解其药理学。然而,由于 HCC 病情进展迅速,能够有效抑制肿瘤生长和侵袭性的药物少之又少。在这项研究中,我们发现从Stephania tetrandra S. Moore中提取的一种双苄基异喹啉生物碱--fangchinoline(FAN)能有效抑制HCC细胞的迁移、侵袭和上皮-间质转化(EMT)。FAN 还能抑制 IL6 和 IL1β 的释放,以及 COX-2 和 iNOS 等炎症相关蛋白的表达和 NF-κB 通路的激活,从而减少炎症相关的 EMT。此外,FAN直接与叉头盒蛋白M1(FOXM1)结合,导致FOXM1蛋白水平下降和FOXM1-ADAM17轴的破坏。我们的体内研究结果证实,FAN 能有效抑制 HCCLM3 异种移植瘤的生长和肺转移。重要的是,FOXM1在HCC组织中的上调表明,用FAN或其抑制剂靶向抑制FOXM1可能是一种很有前景的HCC治疗方法。总之,本研究阐明了FAN的抗肿瘤作用和潜在药理机制,并提出靶向抑制FOXM1可能是一种有效的HCC治疗策略,具有潜在的临床应用前景。
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Cellular signalling
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