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Research progress of non-coding RNA regulating the role of PANoptosis in diabetes mellitus and its complications. 非编码RNA调控PANoptosis在糖尿病及其并发症中的作用研究进展。
IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-04 DOI: 10.1007/s10495-024-02066-w
Guangyu Han, Kaibo Hu, Tianfeng Luo, Wenting Wang, Deju Zhang, Liu Ouyang, Xiao Liu, Jianping Liu, Yuting Wu, Jianqi Liang, Jitao Ling, Yixuan Chen, Rui Xuan, Jing Zhang, Peng Yu

Diabetes is a chronic metabolic disease that is endemic worldwide and is characterized by persistent hyperglycemia accompanied by multiple severe complications, including cardiovascular disease, kidney dysfunction, neuropathy, and retinopathy. The pathogenesis of diabetes mellitus and its complications is multifactorial, involving various molecular and cellular pathways. In recent years, research has indicated that mechanisms of cell death play a significant role in the advancement of diabetes and its complications. PANoptosis is a complex phenomenon caused by three cell death pathways: programmed apoptosis, necroptosis and pyroptosis. The contribution of PANoptosis to diabetes and its complications remains incompletely understood. Non-coding RNA, an important molecule in gene expression regulation, has shown significant regulatory functions in a variety of diseases. This paper reviews the underlying mechanisms of diverse types of non-coding RNAs (including lncRNA, miRNA and circRNA) in regulating PANoptosis and their specific contributions in diabetes, aiming to explore how non-coding RNAs influence PANoptosis and their effects in diabetes.

糖尿病是一种慢性代谢性疾病,在世界范围内流行,其特征是持续高血糖并伴有多种严重并发症,包括心血管疾病、肾功能障碍、神经病变和视网膜病变。糖尿病及其并发症的发病是多因素的,涉及多种分子和细胞途径。近年来的研究表明,细胞死亡机制在糖尿病及其并发症的进展中起着重要作用。PANoptosis是由程序性凋亡、坏死坏死和焦亡三种细胞死亡途径引起的复杂现象。PANoptosis对糖尿病及其并发症的影响尚不完全清楚。非编码RNA是调控基因表达的重要分子,在多种疾病中显示出重要的调控作用。本文综述了不同类型的非编码rna(包括lncRNA、miRNA和circRNA)调控PANoptosis的潜在机制及其在糖尿病中的具体作用,旨在探讨非编码rna如何影响PANoptosis及其在糖尿病中的作用。
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引用次数: 0
Molecular mechanisms of antiproliferative and pro-apoptotic effects of essential oil active constituents in MCF7 and T24 cancer cell lines: in vitro insights and in silico modelling of proapoptotic gene product-compound interactions. MCF7和T24癌细胞中精油活性成分抗增殖和促凋亡作用的分子机制:促凋亡基因产物-化合物相互作用的体外观察和计算机模拟
IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-31 DOI: 10.1007/s10495-024-02065-x
Deepika Saini, Pankaj Kumar Chaudhary, Jitendra Kumar Chaudhary, Harry Kaur, Ganesh Kumar Verma, Siddhartha Das Pramanik, Partha Roy, Anissa Atif Mirza-Shariff, Ramasare Prasad

This study aims to investigate the in vitro antiproliferative and pro-apoptotic/apoptotic potential of active constituents of essential oils on two cancer cell lines; namely, breast adenocarcinoma (MCF-7) and urinary bladder cancer (T24). Essential oils active constituents (EO-ACs) entail a spectrum of phytochemicals with widely demonstrated anticancer potential. We assessed the effects of eight essential oils active constituents on T24 and MCF-7 cell lines in both dose- (16-1024 µg/mL) and time-dependent manners. Among these, five EO-ACs (citral, carvacrol, eugenol, geraniol, and thymol) exhibited IC50 values, ranging from 24 µg/mL to 34 µg/mL, as determined by the MTT assay over 72 h. It was observed that the mitochondrial membrane potential decreased while ROS generation increased substantially in treated cells compared to the control. The underlying apoptotic pathway with regard to pro-apoptotic/apoptotic genes was explored through qRT-PCR and western blotting, which showed significant (p < 0.05) upregulation of Bax, Bak, caspase 7, caspase 9, and downregulation of Bcl-2, pERK, and pAkt. The in-silico study showed strong interaction of thymol and carvacrol with Caspase 9, with complex binding energies of -6.1 Kcal/mol and - 6.3 Kcal/mol, respectively. In conclusion, EO-ACs, particularly thymol and carvacrol, effectively reduced cell viability, and triggered caspase-dependent apoptosis in both MCF-7 and T-24 cell lines. These findings categorically underscore EO-ACs as promising active compounds for anticancer therapy, warranting further in-depth exploration through in vivo studies.

本研究旨在探讨精油有效成分对两种癌细胞的体外抗增殖和促凋亡/凋亡潜能;即乳腺腺癌(MCF-7)和膀胱癌(T24)。精油活性成分(EO-ACs)是一类具有广泛抗癌潜力的植物化学物质。我们评估了8种精油有效成分在剂量(16-1024µg/mL)和时间依赖性下对T24和MCF-7细胞系的影响。其中,5种EO-ACs(柠檬醛、香芹酚、丁香酚、香叶醇和百里香酚)的IC50值在24µg/mL至34µg/mL之间,通过MTT法测定72 h。观察到,与对照组相比,处理细胞的线粒体膜电位下降,而ROS生成显著增加。通过qRT-PCR和western blotting研究促凋亡/凋亡基因相关的潜在凋亡途径,结果显示(p
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引用次数: 0
Retraction Note: Progesterone induces apoptosis by activation of caspase-8 and calcitriol via activation of caspase-9 pathways in ovarian and endometrial cancer cells in vitro. 注:在体外实验中,黄体酮通过激活caspase-8和骨化三醇通过激活caspase-9通路诱导卵巢癌和子宫内膜癌细胞凋亡。
IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-30 DOI: 10.1007/s10495-024-02062-0
Latoya McGlorthan, Ana Paucarmayta, Yovanni Casablanca, G Larry Maxwell, Viqar Syed
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引用次数: 0
The role of TIGIT-CD226-PVR axis in mediating T cell exhaustion and apoptosis in NSCLC. TIGIT-CD226-PVR轴在非小细胞肺癌中介导T细胞衰竭和凋亡的作用。
IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-26 DOI: 10.1007/s10495-024-02052-2
Liang Qian, Ling Wu, Xiaohui Miao, Jiao Xu, Yao Zhou

The treatment of non-small cell lung cancer (NSCLC) remains a critical challenge in oncology, primarily due to the dysfunction and exhaustion of T cells within the tumor microenvironment, which greatly limits the effectiveness of immunotherapy. This study investigates the regulatory role of the T cell immunoglobulin and ITIM domain (TIGIT)-CD226-PVR signaling axis in the exhaustion and apoptosis of cluster of differentiation (CD)27+/CD127+T cells in NSCLC. Utilizing single-cell sequencing technology, we conducted a comprehensive gene expression analysis of T cells in a mouse model of NSCLC. Bioinformatics analysis revealed that the TIGIT-CD226-PVR signaling axis is highly active in the CD27+/CD127+T cell subset and is closely associated with their functional decline and exhaustion. In vitro experiments further demonstrated that inhibiting the TIGIT-PVR pathway while activating the CD226-PVR pathway significantly restored T cell proliferation and effector function. Importantly, in vivo studies showed that targeting this axis can significantly alleviate T cell exhaustion, enhance their cytotoxicity against NSCLC cells, and promote apoptosis, thereby improving the efficacy of immunotherapy.

非小细胞肺癌(NSCLC)的治疗仍然是肿瘤学的一个关键挑战,主要是由于肿瘤微环境中T细胞的功能障碍和衰竭,这极大地限制了免疫治疗的有效性。本研究探讨T细胞免疫球蛋白和ITIM结构域(TIGIT)-CD226-PVR信号轴在分化簇(CD)27+/CD127+T细胞衰竭和凋亡中的调控作用。利用单细胞测序技术,我们对非小细胞肺癌小鼠模型中的T细胞进行了全面的基因表达分析。生物信息学分析显示,TIGIT-CD226-PVR信号轴在CD27+/CD127+T细胞亚群中高度活跃,并与它们的功能下降和衰竭密切相关。体外实验进一步证明,抑制TIGIT-PVR通路而激活CD226-PVR通路可显著恢复T细胞增殖和效应物功能。重要的是,体内研究表明,靶向该轴可显著缓解T细胞衰竭,增强其对NSCLC细胞的细胞毒性,促进细胞凋亡,从而提高免疫治疗的疗效。
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引用次数: 0
Arsenic unsettles the cerebellar balance between neurodegeneration and neurogenesis: reversal by folic acid. 砷扰乱了神经退行性变和叶酸逆转神经发生的小脑平衡。
IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-25 DOI: 10.1007/s10495-024-02054-0
Ankur Das, Ankan Mitra, Swaimanti Sarkar, Sourav Ghosh, Debasish Bandyopadhyay, Sreya Chattopadhyay

Arsenic-mediated neurodegenerative disorders affect millions of individuals globally, but the specific impact of environmental arsenic on adult cerebellar degeneration and neurogenesis is incompletely understood. Of particular concern is arsenic-induced apoptosis-driven neurodegeneration. Our major objective was to investigate the molecular signaling intricacies associated with arsenic-induced death of cerebellar neurons and to propose folic acid as a possible intervention. Swiss albino mice were treated with sodium arsenite (orally: 0.05 mg/L) and folic acid (orally:10 mg/kg) for 28 days. We observed that arsenic caused noticeable cell loss with morphological alterations in cerebellum, which was remarkably restored by folic acid. Arsenic-induced morphological alterations consequently perturbed transcriptional activities of neural stem cell factors-SOX2 and KLF9, which resulted in the suppression of pro-neurogenic mediators NeuroD1, Neurogenin2, calbindin and NeuN. Interestingly, folic acid reversed the expression of these critical pro-neurogenic mediators to mitigate these degenerative changes to promote neurogenesis. Delving deep, we found that folic acid rescued arsenic-exposed cerebellum from severe oxidative and pro-inflammatory insults by increasing antioxidants like SOD, Catalase, GSH, upregulating Nrf2 and downregulating M1 macrophages, JNK, NF-κB, and STAT3 activities. For the first time, we are reporting that arsenic induced a G1/S cell cycle arrest and triggered apoptosis in mouse cerebellum by activating the p53-p21 axis, downregulating CDKs and instigated p21-mediated suppression of SOX2 transcriptional activity. Folic acid abated such alterations by modulating the p53/p21/SOX2 axis. Collectively, the anti-apoptotic and pro-neurogenic effects of folic acid present it as a promising therapeutic candidate, warranting further research into its efficacy against metal-induced neurodegenerative disorders.

砷介导的神经退行性疾病影响全球数百万人,但环境砷对成人小脑变性和神经发生的具体影响尚不完全清楚。特别值得关注的是砷诱导的细胞凋亡驱动的神经变性。我们的主要目的是研究与砷诱导的小脑神经元死亡相关的分子信号复杂性,并提出叶酸作为可能的干预措施。采用亚砷酸钠(口服:0.05 mg/L)和叶酸(口服:10 mg/kg)治疗瑞士白化小鼠28 d。我们观察到砷引起小脑明显的细胞损失和形态改变,叶酸显著恢复。砷诱导的形态学改变扰乱了神经干细胞因子sox2和KLF9的转录活性,从而抑制了前神经源性介质NeuroD1、Neurogenin2、calbindin和NeuN。有趣的是,叶酸逆转了这些关键的前神经发生介质的表达,以减轻这些退行性变化,促进神经发生。深入研究后,我们发现叶酸可以通过增加抗氧化剂如SOD、过氧化氢酶、谷胱甘肽、上调Nrf2和下调M1巨噬细胞、JNK、NF-κB和STAT3活性来保护砷暴露的小脑免受严重的氧化和促炎损伤。我们首次报道了砷通过激活p53-p21轴、下调CDKs和诱导p21介导的SOX2转录活性抑制,诱导小鼠小脑G1/S细胞周期阻滞并引发凋亡。叶酸通过调节p53/p21/SOX2轴来减弱这种改变。总的来说,叶酸的抗凋亡和促神经原性作用使其成为一种有希望的治疗候选者,值得进一步研究其对金属诱导的神经退行性疾病的疗效。
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引用次数: 0
Brazilin alleviates acute lung injury via inhibition of ferroptosis through the SIRT3/GPX4 pathway. Brazilin通过SIRT3/GPX4通路抑制铁下垂减轻急性肺损伤。
IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-25 DOI: 10.1007/s10495-024-02058-w
Xiaopei Yan, Li Xu, Chang Qi, Yiling Chang, Juanjuan Zhang, Ning Li, Baoyu Shi, Bo Guan, Siming Hu, Chao Huang, Hui Wang, Ying Chen, Xiao Xu, Jian Lu, Guopeng Xu, Chao Chen, Su Li, Yuqiong Chen

Ferroptosis is a novel type of programmed cell death dependent on iron and is characterized by the accumulation of lipid peroxides, which is involved in acute lung injury (ALI). Brazilin, an organic compound known for its potent antioxidant and anti-inflammatory properties, has not been thoroughly studied for its potential impact on lipopolysaccharide (LPS)-induced ALI. Here, we found that pretreatment of brazilin mitigated LPS-induced lung injury and inflammation by inhibiting mitochondrial oxidative stress and ferroptosis, both in vivo and in vitro. Sirtuin 3 (SIRT3) was identified as a downstream target of brazilin, and overexpression of SIRT3 mirrored the protective effects of brazilin against LPS-induced ALI. Additionally, SIRT3 contributed to the upregulation, mitochondrial translocation and deacetylation of glutathione peroxidase 4 (GPX4). Through screening potential acetylation sites on GPX4, we identified lysine 148 (K148) as the residue deacetylated by SIRT3. Mutating the acetylation site of GPX4 within mitochondria (mitoGPX4-K148R) reduced LPS or SIRT3 knockdown-induced GPX4 acetylation, oxidative stress, and ferroptosis, ultimately ameliorating ALI. In conclusion, our study demonstrates the beneficial effects of brazilin in treating LPS-induced ALI. Brazilin enhances SIRT3 expression, which in turn deacetylates and facilitates the mitochondrial translocation of GPX4, thereby reducing mitochondrial oxidative stress and ferroptosis. These findings suggest that the SIRT3/GPX4 pathway may represent a critical mechanism, and brazilin emerges as a promising therapeutic candidate for ALI.

铁凋亡是一种依赖于铁的新型程序性细胞死亡,其特征是脂质过氧化物的积累,这与急性肺损伤(ALI)有关。巴西林是一种有机化合物,以其有效的抗氧化和抗炎特性而闻名,但尚未对其对脂多糖(LPS)诱导的ALI的潜在影响进行深入研究。本研究发现,在体内和体外实验中,巴西巴西林预处理通过抑制线粒体氧化应激和铁下垂来减轻lps诱导的肺损伤和炎症。Sirtuin 3 (SIRT3)被确定为巴西蛋白的下游靶点,SIRT3的过表达反映了巴西蛋白对lps诱导的ALI的保护作用。此外,SIRT3还参与谷胱甘肽过氧化物酶4 (GPX4)的上调、线粒体易位和去乙酰化。通过筛选GPX4上潜在的乙酰化位点,我们确定了lysine 148 (K148)是SIRT3去乙酰化的残基。突变线粒体内GPX4乙酰化位点(mitoGPX4-K148R)可减少LPS或SIRT3敲低诱导的GPX4乙酰化、氧化应激和铁凋亡,最终改善ALI。总之,我们的研究证明了巴西林对lps诱导的ALI的有益作用。brasilin增强SIRT3表达,进而使GPX4脱乙酰并促进线粒体易位,从而减少线粒体氧化应激和铁凋亡。这些发现表明SIRT3/GPX4通路可能是一种关键的机制,巴西林是一种有希望的ALI治疗候选药物。
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引用次数: 0
PWP1 transcriptionally regulates p53, modulating apoptosis and cell cycle to promote gastric cancer progression. PWP1通过转录调控p53,调节细胞凋亡和细胞周期,促进胃癌进展。
IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-25 DOI: 10.1007/s10495-024-02049-x
Mingrui Jiang, Sen Wang, Jin Ji, Shantanu Baral, Qiannan Sun, Yong Wang, Bin Liu, Jun Ren, Wei Wang, Daorong Wang

Gastric cancer remains a leading cause of cancer-related mortality worldwide. The prognosis often depends on early detection and understanding the molecular mechanisms involved in its progression. Periodic tryptophan protein 1 (PWP1) has emerged as a novel diagnostic marker, potentially linked to gastric cancer progression. This study aims to elucidate the impact of PWP1 on gastric cancer development, focusing on apoptosis, cell cycle regulation, and the role of p53. This study utilized gastric cancer cell lines to investigate the expression and functional role of Pwp1. Quantitative PCR and Western blot analyses were conducted to measure PWP1 expression levels. Apoptosis was assessed by using flow cytometry and TUNEL assays, and cell cycle analysis was performed to evaluate the impact of PWP1 modulation. Additionally, animal experiments were conducted using mouse models injected with gastric cancer cells, with PWP1 knockdown or overexpression, to observe tumor growth and progression. Statistical significance was evaluated using t-tests and ANOVA where appropriate. Elevated PWP1 expression was observed in gastric cancer tissues compared to normal tissues. PWP1's knockdown resulted in increased apoptosis and cell cycle arrest at the G1 phase, suggesting its role in promoting invasion and proliferation. Furthermore, animal experiments demonstrated reduced tumor growth in mice with PWP1 knockdown. PWP1 was found to transcriptionally regulate p53, affecting its expression and thereby influencing apoptosis and cell cycle pathways in gastric cancer. Our study identifies PWP1 as a novel oncogene frequently overexpressed in gastric cancer (GC). Through transcriptional regulation of p53, PWP1 enhances cell growth by influencing apoptosis and inducing G1 phase cell cycle arrest. These findings underscore PWP1 as a promising therapeutic target for treating GC, suggesting its potential for future clinical applications.

胃癌仍然是世界范围内癌症相关死亡的主要原因。预后往往取决于早期发现和了解其进展的分子机制。周期性色氨酸蛋白1 (PWP1)已成为一种新的诊断标志物,可能与胃癌进展有关。本研究旨在阐明PWP1对胃癌发生发展的影响,重点关注细胞凋亡、细胞周期调控以及p53的作用。本研究利用胃癌细胞系研究Pwp1的表达及其功能作用。采用定量PCR和Western blot检测PWP1的表达水平。通过流式细胞术和TUNEL检测细胞凋亡,通过细胞周期分析评估PWP1调节对细胞凋亡的影响。动物实验采用小鼠模型注射PWP1敲低或过表达的胃癌细胞,观察肿瘤的生长和进展。采用t检验和方差分析评估统计显著性。与正常组织相比,胃癌组织中PWP1表达升高。PWP1的敲低导致细胞凋亡增加,细胞周期阻滞在G1期,提示其在促进侵袭和增殖中的作用。此外,动物实验表明,敲低PWP1小鼠的肿瘤生长减少。发现PWP1通过转录调控p53,影响其表达,从而影响胃癌细胞凋亡和细胞周期通路。我们的研究发现PWP1是胃癌(GC)中经常过表达的一种新型癌基因。PWP1通过转录调控p53,影响细胞凋亡,诱导G1期细胞周期阻滞,从而促进细胞生长。这些发现强调PWP1是治疗GC的一个有希望的治疗靶点,表明其未来的临床应用潜力。
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引用次数: 0
Intravenous immunoglobulin ameliorates doxorubicin-induced intestinal mucositis by inhibiting the Syk/PI3K/Akt axis and ferroptosis. 静脉注射免疫球蛋白通过抑制Syk/PI3K/Akt轴和铁下垂改善阿霉素诱导的肠黏膜炎。
IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-25 DOI: 10.1007/s10495-024-02064-y
Xiaochen Yan, Peng Jiang, Changqing Li, Fengjuan Liu, Ping Fu, Dengqun Liu, Xi Du, Li Ma, Tong Wang, Xin Yuan, Shengliang Ye, Zongkui Wang

Background: Chemotherapy-induced mucositis (CIM) significantly impacts quality of life and reduces survival in patients treated with specific chemotherapeutic agents. However, effective clinical treatments for CIM remain limited. Intravenous immunoglobulin (IVIg), a therapeutic derived from pooled human plasma, is widely used to treat inflammatory diseases. This study aimed to evaluate the therapeutic efficacy and underlying mechanisms of IVIg in CIM.

Methods: A murine model of doxorubicin (Dox)-induced intestinal mucositis and an organoid model of small intestinal injury were used to explore the protective effects of IVIg on CIM. Immunostaining, transmission electron microscopy (TEM), western blotting (WB), and proteomic analysis were used to further investigate ferroptosis in intestinal epithelial cells and the underlying mechanisms.

Results: In the murine model of Dox-induced intestinal mucositis, intestinal epithelial barrier was destroyed and ferroptosis increased, characterized by weight loss, hematological injury, inflammation, mitochondrial atrophy in intestinal epithelial cells, lipid peroxidation, impairment of tight junctions, and damage to intestinal microvilli. IVIg treatment significantly ameliorated intestinal epithelial barrier damage and reduced ferroptosis both in vitro and in vivo. Proteomic analysis revealed that the FcγR-mediated phagocytosis signaling pathway was involved in the therapeutic effects of IVIg on CIM mice. WB results demonstrated that key proteins downstream of this pathway, Syk, PI3K, and Akt, showed increased phosphorylation in CIM mice, whereas IVIg treatment significantly reduced the phosphorylation levels. Furthermore, the inhibitory effects of IVIg on Dox-induced activation of the Syk/PI3K/Akt axis and ferroptosis, as well as its protective effects on intestinal inflammation and intestinal barrier damage, were reversed by 740Y-P (an PI3K activator) or SC79 (an Akt activator).

Conclusions: Our findings highlight that IVIg ameliorates CIM by inhibiting ferroptosis via the Syk/PI3K/Akt axis. These results suggest that IVIg may represent a potential therapeutic approach for CIM.

背景:化疗诱导的粘膜炎(CIM)显著影响特定化疗药物治疗患者的生活质量并降低生存率。然而,有效的临床治疗CIM仍然有限。静脉注射免疫球蛋白(IVIg)是一种从人血浆中提取的药物,被广泛用于治疗炎症性疾病。本研究旨在评价IVIg治疗CIM的疗效和潜在机制。方法:采用多柔比星(Dox)致小鼠肠黏膜炎模型和小肠类器官损伤模型,探讨IVIg对CIM的保护作用。采用免疫染色、透射电镜(TEM)、免疫印迹(WB)和蛋白质组学分析进一步研究肠上皮细胞铁下垂及其机制。结果:小鼠肠黏膜炎模型中,肠上皮屏障被破坏,上铁质增高,表现为体重减轻、血液学损伤、炎症、肠上皮细胞线粒体萎缩、脂质过氧化、紧密连接受损、肠微绒毛损伤。体外和体内IVIg治疗显著改善了肠上皮屏障损伤,减少了铁下垂。蛋白质组学分析显示,fc γ r介导的吞噬信号通路参与了IVIg对CIM小鼠的治疗作用。WB结果显示,该通路下游的关键蛋白Syk、PI3K和Akt在CIM小鼠中磷酸化增加,而IVIg处理显著降低了磷酸化水平。此外,IVIg对dox诱导的Syk/PI3K/Akt轴活化和铁凋亡的抑制作用,以及对肠道炎症和肠屏障损伤的保护作用,被740Y-P (PI3K激活剂)或SC79 (Akt激活剂)逆转。结论:我们的研究结果强调IVIg通过Syk/PI3K/Akt轴抑制铁下垂来改善CIM。这些结果表明IVIg可能是CIM的一种潜在治疗方法。
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引用次数: 0
TRIM23 promotes 5-Fluorouracil resistance in colorectal cancer by upregulating GALNT4 expression. TRIM23通过上调GALNT4表达促进结直肠癌5-氟尿嘧啶耐药。
IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-25 DOI: 10.1007/s10495-024-02060-2
Shanshan Wei, Wei Xia, Jun Feng, Jianwen Lu, Luo Zhang, Wei Wang, Wenwei Hu, Yiting Geng

5-Fluorouracil (5-FU) is one of the most common chemotherapeutic agents for colorectal cancer (CRC), but its application is often limited by resistance. Tripartite motif containing 23 (TRIM23) has been reported to be dysregulated in various tumors and involved in tumor progression and chemotherapy resistance. However, its relationship with CRC 5-FU resistance and the underlying mechanism are still unclear. In this study, we found that TRIM23 was upregulated in CRC. Patients treated with 5-FU and with high TRIM23 expression had a lower disease control rate (DCR) and a poorer median progression-free survival (mPFS). In vitro, the expression of TRIM23 in CRC cells was elevated after 5-FU treatment. Compared to parental cells, TRIM23 was significantly overexpressed in 5-FU-resistant CRC cells. Mechanistically, TRIM23 mediated 5-FU resistance of CRC by upregulating the expression of N-acetylgalactosaminyltransferase-4 (GALNT4). Knocking down TRIM23 in 5-FU-resistant colon cancer cells restored the sensitivity to 5-FU, while overexpression of GALNT4 in TRIM23 knockdown cells counteracted the chemosensitization caused by TRIM23 downregulation. The TRIM23/GALNT4 axis may play a crucial role in 5-FU resistance in CRC, and targeted inhibition of this axis is expected to reverse resistance. As a potential biomarker for screening 5-FU-sensitive patients and predicting prognosis in clinical practice, TRIM23 deserves further investigation.

5-氟尿嘧啶(5-FU)是结直肠癌(CRC)最常用的化疗药物之一,但其应用往往受到耐药性的限制。Tripartite motif containing 23 (TRIM23)已被报道在多种肿瘤中失调,并参与肿瘤进展和化疗耐药。然而,其与CRC 5-FU耐药性的关系及其潜在机制尚不清楚。在本研究中,我们发现TRIM23在CRC中表达上调。接受5-FU治疗且TRIM23高表达的患者疾病控制率(DCR)较低,中位无进展生存期(mPFS)较差。在体外,5-FU处理后CRC细胞中TRIM23的表达升高。与亲代细胞相比,TRIM23在5- fu耐药CRC细胞中显著过表达。机制上,TRIM23通过上调n -乙酰半乳糖氨基转移酶4 (GALNT4)的表达介导CRC的5-FU耐药。在5-FU耐药的结肠癌细胞中,敲低TRIM23恢复了对5-FU的敏感性,而在TRIM23敲低的细胞中,GALNT4的过表达抵消了TRIM23下调引起的化学致敏。TRIM23/GALNT4轴可能在CRC的5-FU耐药中起关键作用,靶向抑制该轴有望逆转耐药。TRIM23作为临床筛选5- fu敏感患者和预测预后的潜在生物标志物,值得进一步研究。
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引用次数: 0
Involvement of copper in cell death and cancer. 铜在细胞死亡和癌症中的作用
IF 6.1 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-12-19 DOI: 10.1007/s10495-024-02059-9
Jiahao Xie, Yue Su, Wenzhong Shang, Yanfang Wu, Junjia He, Ting Li, Yeyu Shen, Youni Zhang, Xiangmin Tong, Qiong Bian

Copper (cu) is an essential micronutrient required for numerous metabolic processes. It plays a crucial role in cellular respiration by participating in the electron transport chain and facilitating numerous biological reactions. Various diseases, including cancer, demonstrate localized elevation of copper levels and/or alterations in the overall distribution of copper. Modulating local or systemic copper levels as a novel therapeutic approach for treating and ameliorating diseases has emerged as a prominent trend in disease management, particularly in the realm of cancer therapy, which is currently under investigation. The objective of this review is to offer a thorough examination of copper metabolism in both physiological and pathological contexts. Specifically, it delves into how copper ions can effectively target and stimulate tumor cell death via the process known as cuproptosis in cancer patients. Furthermore, this review explores the utilization of three categories of anticancer medications (copper ion carriers, copper complexes, and copper chelating agents) pertaining to copper metabolism within the realm of cancer therapy, elucidating on the distinct mechanisms through which they exert their effects.

铜(cu)是许多新陈代谢过程所必需的微量元素。它通过参与电子传递链和促进多种生物反应,在细胞呼吸中发挥着至关重要的作用。包括癌症在内的各种疾病都会导致局部铜含量升高和/或铜的整体分布发生改变。调节局部或全身铜含量作为治疗和改善疾病的一种新型治疗方法,已成为疾病管理的一个突出趋势,尤其是在目前正在研究的癌症治疗领域。本综述旨在对生理和病理情况下的铜代谢进行深入研究。具体而言,本综述将深入探讨铜离子如何通过癌症患者体内的杯突症过程有效靶向并刺激肿瘤细胞死亡。此外,本综述还探讨了与铜代谢有关的三类抗癌药物(铜离子载体、铜络合物和铜螯合剂)在癌症治疗领域中的应用,阐明了它们产生作用的不同机制。
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Apoptosis
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