Biochemical and biophysical research communications最新文献_第6页

PIKFYVE deficiency induces vacuole-like cataract via perturbing late endosome homeostasis PIKFYVE缺乏通过扰乱晚期核内体稳态诱发空泡样白内障。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-02 DOI: 10.1016/j.bbrc.2024.151123

Xiaochen Ma , Sejie Yu , Min Zhang , Shaoyi Mei , Yunzhi Ling , Xiaosheng Huang , Songguo Dong , Baojian Fan , Jun Zhao

Phosphoinositide kinase, FYVE-type zinc finger containing (PIKFYVE) was recently identified as a causative gene for cataract. Pikfyve phosphatidylinositol phosphate kinase domain-deficient (pikfyve^Δ8) zebrafish lens and PIKFYVE-inhibited human lens epithelial cells developed vacuoles, colocalized with late endosome marker RAB7. In this study, the pikfyve^Δ8zebrafish with vacuole-like cataract underwent transcriptomic and proteomic analyses to explore the underlying mechanisms of vacuole formation. PIKFYVE-knockout and PIKFYVE-inhibited human lens epithelial cells with vacuoles further verified these omics results and rescued with Bafilomycin A1(Baf-A1) and U18666A. We discovered no significant differences in lysosomal fusion, but upregulation in acid hydrolase. The composition of late endosomal membrane was changed, and vacuolar ATPase and endosomal sorting complexes required for transport (ESCRT) at late endosome were upregulated. These changes are related with the late endosome homeostasis. Strikingly, vacuoles in human lens epithelial cells could be partially rescued by Baf-A1 and almost completely rescued by U18666A. Collectively, these findings suggest that vacuoles in pikfyve^Δ8 zebrafish lens and PIKFYVE-inhibited cells were colocalized with swollen late endosomes, and generated by perturbing late endosome homeostasis due to enhanced ESCRT mechanisms and decreased stability in late endosomal membrane. This study expands our understanding of the mechanisms underlying cataract development and reveals potentially effective therapeutic targets.

磷酸肌肽激酶（Phosphoinositide kinase, FYVE-type zinc finger containing， PIKFYVE）最近被发现是白内障的致病基因。Pikfyve磷脂酰肌醇磷酸激酶结构域缺陷（pikfyveΔ8）斑马鱼晶体和Pikfyve抑制的人晶体上皮细胞形成液泡，与内核体晚期标记物RAB7共定位。本研究对患有液泡样白内障的pikfyveΔ8zebrafish进行了转录组学和蛋白质组学分析，以探索液泡形成的潜在机制。敲除pikfyve和抑制pikfyve的人晶状体上皮细胞空泡进一步验证了这些组学结果，并用巴菲霉素A1（Baf-A1）和U18666A进行了拯救。我们发现溶酶体融合没有显著差异，但酸水解酶上调。内体晚期膜组成发生改变，空泡atp酶和内体转运所需分选复合物（ESCRT）上调。这些变化与内核体后期稳态有关。引人注目的是，人晶状体上皮细胞中的液泡可以被Baf-A1部分拯救，而被U18666A几乎完全拯救。总之，这些发现表明pikfyveΔ8斑马鱼晶态和pikfyve抑制细胞中的液泡与肿胀的晚期核内体共定位，并且由于ESCRT机制增强和晚期核内体膜稳定性降低而扰乱了晚期核内体的稳态。这项研究扩大了我们对白内障发展机制的理解，并揭示了潜在的有效治疗靶点。

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引用次数: 0

Chemical inhibition of eIF4A3 abolishes UPF1 recruitment onto mRNA encoding NMD factors and restores their expression 化学抑制eIF4A3可消除UPF1在编码NMD因子的mRNA上的募集，并恢复其表达。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-02 DOI: 10.1016/j.bbrc.2024.151270

Chloé Mercier , Jules Durand , Annick Fraichard , Valérie Perez , Eric Hervouet , Paul Peixoto , Regis Delage-Mourroux , Michaël Guittaut , Aurélie Baguet

Nonsense-Mediated mRNA Decay (NMD) is a key control mechanism of RNA quality widely described to target mRNA harbouring Premature Termination Codon (PTC). However, recent studies suggested the existence of non-canonical pathways which remain unresolved. One of these alternative pathways suggested that specific mRNA could be targeted through their 3′ UTR (Untranslated Region), which contain various elements involved in mRNA stability regulation. This study focused on 3′UTR of mRNA encoding NMD factors, on which we observed an enrichment of binding sites for UPF1 and eIF4A3 proteins, two important NMD factors. Using GFP reporter constructs containing the 3′UTR of these NMD mRNA fused to the GFP cDNA, we showed that GFP expression was significantly increased upon eIF4A3 inhibition, suggesting mRNA level stabilization. Furthermore, co-immunoprecipitation targeting UPF1 revealed that its interaction with mRNA encoding NMD factors was disrupted when cells were previously treated with the eIF4A3 inhibitor. We therefore propose that eIF4A3 might be necessary to recruit UPF1 and trigger the degradation of these transcripts through a non-canonical 3′UTR-dependent mechanism.

无义介导的mRNA衰变（NMD）是RNA质量的关键控制机制，被广泛描述为针对含有过早终止密码子（PTC）的mRNA。然而，最近的研究表明，非规范途径的存在仍未得到解决。其中一种替代途径表明，特定的mRNA可以通过它们的3' UTR（非翻译区）靶向，其中包含参与mRNA稳定性调节的各种元件。本研究聚焦于编码NMD因子的mRNA的3'UTR，我们观察到两个重要的NMD因子UPF1和eIF4A3蛋白的结合位点富集。通过将含有这些NMD mRNA 3'UTR的GFP报告基因构建物与GFP cDNA融合，我们发现eIF4A3抑制后GFP表达显著增加，表明mRNA水平稳定。此外，针对UPF1的共免疫沉淀显示，当细胞先前用eIF4A3抑制剂处理时，UPF1与编码NMD因子的mRNA的相互作用被破坏。因此，我们提出eIF4A3可能是募集UPF1所必需的，并通过非规范的3' utr依赖机制触发这些转录本的降解。

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引用次数: 0

Abscisic acid improves non-alcoholic fatty liver disease in mice through the AMPK/NRF2/KEAP1 signaling axis 脱落酸通过AMPK/NRF2/KEAP1信号轴改善小鼠非酒精性脂肪肝疾病。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-02 DOI: 10.1016/j.bbrc.2025.151291

Lin Zhang , Fu Hua Du , Kai Xiao Kun , Yong Yan

Non-alcoholic fatty liver disease (NAFLD) has emerged as a global health concern, placing a substantial financial strain on public health systems. Currently, no specific pharmacological treatments are recommended in existing guidelines. Abscisic acid (ABA), a natural plant hormone, is recognized for its promising potential in the healthcare field due to its diverse biological activities. Therefore, this study is aimed at exploring the protective mechanism of ABA against NAFLD. In vitro, experiments were conducted using palmitic acid (PA) to establish a fatty liver cell model, whereas in vivo, an NAFLD model was established using a continuous high-fat diet (HFD). It was found that ABA, as a natural activator of NRF2 and AMPK, reduced lipid accumulation in hepatocytes and exerted anti-inflammatory and antioxidant effects by enhancing the nuclear expression of NRF2, thereby alleviating NAFLD in mice. Furthermore, AMPK was activated by ABA through the promotion of its phosphorylation, which subsequently enhanced the p62-dependent autophagic degradation of KEAP1, leading to the release and nuclear translocation of NRF2. In conclusion, it is indicated that ABA reduces lipid accumulation, inflammation, and oxidative stress in hepatocytes via the NRF2 and AMPK pathways, potentially serving as a promising candidate for alleviating NAFLD.

非酒精性脂肪性肝病（NAFLD）已成为一个全球性的健康问题，给公共卫生系统带来了巨大的财政压力。目前，在现有的指南中没有推荐具体的药物治疗方法。脱落酸（ABA）是一种天然植物激素，由于其具有多种生物活性，在医疗保健领域具有广阔的应用前景。因此，本研究旨在探讨ABA对NAFLD的保护机制。体外实验采用棕榈酸（PA）建立脂肪肝细胞模型，体内实验采用连续高脂饮食（HFD）建立NAFLD模型。发现ABA作为NRF2和AMPK的天然激活剂，通过增强NRF2的核表达，减少肝细胞脂质积累，发挥抗炎和抗氧化作用，从而缓解小鼠NAFLD。此外，ABA通过促进AMPK磷酸化激活AMPK，进而增强KEAP1的p62依赖性自噬降解，导致NRF2的释放和核易位。综上所述，ABA通过NRF2和AMPK途径减少肝细胞的脂质积累、炎症和氧化应激，可能是缓解NAFLD的有希望的候选药物。

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引用次数: 0

Ubiquitination-deficit of Cnot4 impairs the capacity of proliferation and differentiation in mouse embryonic stem cells Cnot4泛素化缺陷会损害小鼠胚胎干细胞的增殖和分化能力。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-02 DOI: 10.1016/j.bbrc.2024.151260

Wenxin Ding , Chenyao He , Xin Liu , Chunlei Hou , Qi Wang , Tiantian Gong , Jiahao Yang , Jingling Shen , Zhiyan Shan , Ruizhen Sun

Neurodevelopmental abnormalities are significant contributors to a variety of neurological disorders. Ubiquitination is essential for embryonic development and plays a pivotal role in neurodevelopment. Although Cnot4 possesses E3-ubiquitin ligase activity, its function in neurodevelopment and embryonic stem cells (ESCs) remains inadequately understood. This study examined the impact of Cnot4 ubiquitination-deficit in mouse ESCs using flow cytometry, CCK-8 assays, immunofluorescence, western blotting, RNA sequencing (RNA-seq), and intracellular Ca²⁺ measurement. Findings demonstrated that the lack of ubiquitination in Cnot4 reduced ESC proliferation rates and facilitated ectodermal differentiation during spontaneous ESC differentiation. RNA-seq analysis identified that the differentially expressed genes were primarily linked to glucose metabolism and Ca²⁺ signaling pathways. Additionally, results indicated that the ubiquitination-deficit in Cnot4 caused increased intracellular Ca²⁺ levels in mESCs. These findings suggest that Cnot4 plays a critical role in the regulation of proliferation and differentiation of mESCs through ubiquitination, providing a basis for further exploration of its involvement in embryonic and neural development.

神经发育异常是各种神经系统疾病的重要原因。泛素化对胚胎发育至关重要，在神经发育中起着关键作用。尽管connot4具有e3 -泛素连接酶活性，但其在神经发育和胚胎干细胞（ESCs）中的功能尚不清楚。本研究使用流式细胞术、CCK-8测定、免疫荧光、western blotting、RNA测序（RNA-seq）和细胞内Ca2+测量检测了小鼠ESCs中connot4泛素化缺陷的影响。研究结果表明，在ESC自发分化过程中，缺乏connot4泛素化可降低ESC增殖率，促进外胚层分化。RNA-seq分析发现，差异表达的基因主要与葡萄糖代谢和Ca2+信号通路有关。此外，结果表明，connot4的泛素化缺陷导致mESCs细胞内Ca2+水平升高。这些发现表明，connot4通过泛素化作用在mESCs的增殖和分化调控中发挥了关键作用，为进一步探索其在胚胎和神经发育中的作用奠定了基础。

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引用次数: 0

Itaconate drives pro-inflammatory responses through proteasomal degradation of GLO1 衣康酸通过蛋白酶体降解GLO1驱动促炎反应。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-02 DOI: 10.1016/j.bbrc.2025.151292

Lulu Bai , Hanghui Yu , Yiqing Cai , Runliu Wu , Rui Kang , Yuanyuan Jia , Xinyue Zhang , Daolin Tang , Enyong Dai

Itaconate is a small-molecule metabolite generated by the enzyme aconitate decarboxylase 1 (ACOD1), which is upregulated during inflammation. Traditionally, itaconate has been recognized for its anti-inflammatory properties; however, this study reveals a pro-inflammatory mechanism of itaconate in macrophages. We demonstrate that itaconate promotes the proteasomal degradation of glyoxalase 1 (GLO1) via Cys139. GLO1 is crucial for detoxifying methylglyoxal (MGO), a glycolysis byproduct that leads to advanced glycation end-products (AGEs). Elevated concentrations of itaconate correlate with reduced GLO1 expression in peripheral blood mononuclear cells (PBMCs) from patients with sepsis, linking increased itaconate concentrations to heightened MGO and AGE production. Functionally, itaconate-induced degradation of GLO1 promotes the accumulation of MGO and AGEs, thereby exacerbating inflammatory responses. In vivo, itaconate-treated myeloid-specific Ager conditional knockout mice exhibited reduced inflammation and improved survival in experimental sepsis models compared to wild-type controls. Collectively, these findings reveal a novel function of itaconate in immunometabolism, shedding light on its complex involvement in lethal infections.

衣康酸是一种小分子代谢物，由乌头酸脱羧酶1 （ACOD1）产生，在炎症过程中上调。传统上，衣康酸被认为具有抗炎特性；然而，本研究揭示了衣康酸在巨噬细胞中的促炎机制。我们证明衣康酸通过Cys139促进乙二醛酶1 （GLO1）的蛋白酶体降解。GLO1对甲基乙二醛（MGO）解毒至关重要，甲基乙二醛是糖酵解的副产物，可导致晚期糖基化终产物（AGEs）。衣康酸浓度升高与脓毒症患者外周血单个核细胞（PBMCs） GLO1表达降低相关，衣康酸浓度升高与MGO和AGE生成升高有关。功能上，itaconate诱导的GLO1降解促进了MGO和AGEs的积累，从而加剧了炎症反应。在体内，与野生型对照相比，经itaconate处理的骨髓特异性Ager条件敲除小鼠在实验败血症模型中表现出炎症减轻和生存率提高。总的来说，这些发现揭示了衣康酸在免疫代谢中的新功能，揭示了它在致命感染中的复杂参与。

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引用次数: 0

Apo structure of Mycobacterium tuberculosis 1-deoxy-d-xylulose 5-phosphate synthase DXPS: Dynamics and implications for inhibitor design 结核分枝杆菌1-脱氧-d-木质素糖5-磷酸合成酶DXPS的载脂蛋白结构：动力学和抑制剂设计的意义。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-02 DOI: 10.1016/j.bbrc.2024.151246

Victor O. Gawriljuk , Alaa Alhayek , Anna K.H. Hirsch , Matthew R. Groves

The enzyme 1-deoxy-d-xylulose-5-phosphate synthase (DXPS) catalyses the first step of the MEP pathway, a key process for isoprenoid biosynthesis in bacteria that is absent in humans, making it a promising drug target. We present the structure of Mycobacterium tuberculosis DXPS in its apo form, obtained through a soaking method that removes thiamine diphosphate (ThDP) and metals from pre-formed crystals. The apo structure had three regions with absence of electron density near the active site that are unique to the apo form of the enzyme. Comparisons with other homologous DXPS structures highlight a similar dynamic response to cofactor absence. Despite the increased flexibility, key residues for the activity and ThDP binding retain their positions, preserving the structural integrity of the catalytic core. These findings demonstrate the critical role of ThDP in maintaining DXPS stability and suggest that dynamic structural changes in the apo state may influence inhibitor binding targeting the cofactor site.

酶1-脱氧-d-木醛糖-5-磷酸合成酶（DXPS）催化MEP途径的第一步，这是细菌中不存在的类异戊二烯生物合成的关键过程，使其成为一个有希望的药物靶点。我们提出了结核分枝杆菌DXPS的载脂蛋白形式的结构，通过从预形成的晶体中去除二磷酸硫胺素（ThDP）和金属的浸泡方法获得。载脂蛋白结构在活性位点附近有三个没有电子密度的区域，这是载脂蛋白所特有的。与其他同源DXPS结构的比较突出了对辅因子缺失的相似动态响应。尽管灵活性增加了，但活性和ThDP结合的关键残基保留了它们的位置，保持了催化核心的结构完整性。这些发现证明了ThDP在维持DXPS稳定性方面的关键作用，并提示载脂蛋白状态的动态结构变化可能影响靶向辅助因子位点的抑制剂结合。

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引用次数: 0

Evolution and divergence of the role of plant ethylene receptor–related histidine kinases in abscisic acid signaling 植物乙烯受体相关组氨酸激酶在脱落酸信号传导中的作用演化与分化。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-02 DOI: 10.1016/j.bbrc.2025.151295

Marcos T. Miyabe , Taketo Sasaki , Tsukasa Toriyama , Rahul Sk , Daisuke Takezawa , Izumi Yotsui , Teruaki Taji , Yoichi Sakata

Plant responses to the water environment are mediated by ethylene (submergence response) and abscisic acid (ABA, drought response). Ethylene is perceived by a family of histidine kinase receptors (ETR-HKs), which regulate the activity of the downstream B3 Raf-like (RAF) kinase CONSTITUTIVE TRIPLE RESPONSE1 (CTR1) in an ethylene-dependent manner. We previously demonstrated in the moss Physcomitrium patens that SNF1-related protein kinase 2 (SnRK2), an essential kinase in osmostress responses in land plants, is activated by the B3-RAF kinase ARK, which is also regulated by ETR-HKs in an ABA- and osmostress-dependent manner. Whether this regulatory mechanism is evolutionarily conserved in land plants remains unknown. We demonstrate through a cross-species complementation assay that ETR-HKs from a terrestrial alga, bryophytes, and a lycophyte, but not those from angiosperms, retain the ability to activate ARK/SnRK2-mediated ABA signaling in the moss. This suggests that the role of ETR-HKs in ABA signaling was ancestral but lost in seed plants. The γ-loop in the C-terminal receiver domain is crucially involved in this specification of ETR-HK function.

植物对水环境的响应是由乙烯（淹没响应）和脱落酸（ABA，干旱响应）介导的。乙烯被一个家族的组氨酸激酶受体（etrk - hks）感知，该受体以乙烯依赖的方式调节下游B3 RAF样（RAF）激酶CONSTITUTIVE TRIPLE RESPONSE1 （CTR1）的活性。我们之前在藓类Physcomitrium patens中证明了snf1相关蛋白激酶2 （SnRK2）是陆地植物渗透胁迫反应的必需激酶，它被B3-RAF激酶ARK激活，而B3-RAF激酶ARK也受et - hks以ABA和渗透胁迫依赖的方式调节。这种调节机制在陆生植物中是否具有进化保守性尚不清楚。我们通过跨物种互补实验证明，来自陆生藻类、苔藓植物和石松的et - hk，而不是来自被子植物的et - hk，保留了激活苔藓中ARK/ snrk2介导的ABA信号的能力。这表明，etrk - hks在ABA信号传导中的作用是祖传的，但在种子植物中丢失了。c端接收域的γ环在ec - hk功能的规范中起着至关重要的作用。

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引用次数: 0

Structural snapshots of the aldol condensation reaction of the enzyme trans-o-hydroxybenzylidenepyruvate hydratase-aldolase from Pseudomonas fluorescens N3 荧光假单胞菌N3反式-羟基苄基乙酰丙酮酸水合酶醛缩酶缩合反应的结构快照。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-02 DOI: 10.1016/j.bbrc.2024.151281

Silvia Ferrara , Bianca Braggiotti , Eloise Mastrangelo , Patrizia Di Gennaro , Giovanni Bertoni , Mario Milani

Aldolases are crucial enzymes that catalyze the formation of carbon-carbon bonds in the context of the anabolic and catabolic pathways of various metabolites.

The bacterium Pseudomonas fluorescens N3 can use naphthalene as its sole carbon and energy source by using, among other enzymes, the trans-o-hydroxybenzylidenepyruvate (tHBP) hydratase-aldolase (HA), encoded by the nahE gene.

In this study, we present the crystallographic structures of tHBP-HA in three different functional states: the apo enzyme with a phosphate ion in the active site, and the Schiff base adduct bound either to pyruvate or to the substitute with '(R)-4-hydroxy-4-(2-hydroxyphenyl)-2-oxobutanoate'(intermediate state). Our structures elucidate some of the phases of the aldol condensation reaction, proposing the role of a conserved water molecule (W2) in the deprotonation of the catalytic lysine. Moreover, our crystallographic data suggest potential pathways for substrate and product diffusion to and from the protein's active site. These insights advance our understanding of the molecular mechanisms of the aldolase function and can also be used for the design and optimization of new enzymes engineered for the chemical synthesis of different C–C adducts.

醛缩酶是在各种代谢产物的合成代谢和分解代谢途径中催化碳-碳键形成的关键酶。荧光假单胞菌N3可以利用由nahE基因编码的反式-邻羟基苄基乙酰丙酮酸（tHBP）水合酶-醛缩酶（HA）等酶，将萘作为其唯一的碳和能量来源。在这项研究中，我们展示了三种不同功能状态下tHBP-HA的晶体结构：载脂蛋白酶在活性位点上有一个磷酸离子，希夫碱加合物与丙酮酸结合或与‘(R)-4-羟基-4-（2-羟基苯基）-2-氧丁酸’（中间状态）结合。我们的结构阐明了醛醇缩合反应的一些阶段，提出了一个保守的水分子（W2）在催化赖氨酸的去质子化中的作用。此外，我们的晶体学数据表明了底物和产物扩散到蛋白质活性位点和从活性位点扩散的潜在途径。这些见解促进了我们对醛缩酶功能的分子机制的理解，也可用于设计和优化用于化学合成不同C-C加合物的新酶。

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引用次数: 0

Dissecting the anti-pancreatic cancer mechanism of gold nanorods mediate photothermal therapy through quantitative proteomics analysis 通过定量蛋白质组学分析，剖析金纳米棒介导光热治疗的抗胰腺癌机制。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-02 DOI: 10.1016/j.bbrc.2025.151288

Zhen Sun , Feng Zhang , Xixi Liu , Xiangning Du , Yan Xiao , Kai Sun , Ruoyu Wang

Gold nanorods (GNRs) mediated photothermal therapy (PTT) represents a promising technique for cancer treatment, utilizing GNRs in conjunction with near-infrared (NIR) laser irradiation to convert energy into heat. In the present study, we employed PTT to induce apoptosis in pancreatic cancer cells and investigated its underlying mechanisms through quantitative proteomics analysis. Initially, we established that temperatures ranging from 47 to 51°C significantly enhance cellular apoptosis without inducing necrosis. Furthermore, we identified key pathways involved in cell apoptosis, including apoptosis, oxidative stress, and proteasome pathways. Notably, thermal stimulation also resulted in the upregulation of proteins involved in autophagy, which intriguingly contribute to cellular apoptosis via autophagy regulation. Collectively, our findings demonstrate that GNRs-PTT is an effective therapeutic option for pancreatic cancer and provide a theoretical foundation for the clinical application of photothermal therapy. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium (https://proteomecentral.proteomexchange.org) via the iProX partner repository with the dataset identifier PXD058930.

金纳米棒（GNRs）介导的光热疗法（PTT）是一种很有前途的癌症治疗技术，利用GNRs与近红外（NIR）激光照射将能量转化为热量。在本研究中，我们利用PTT诱导胰腺癌细胞凋亡，并通过定量蛋白质组学分析探讨其潜在机制。最初，我们确定温度范围从47到51°C显著促进细胞凋亡而不诱导坏死。此外，我们确定了参与细胞凋亡的关键途径，包括细胞凋亡、氧化应激和蛋白酶体途径。值得注意的是，热刺激还导致自噬相关蛋白的上调，有趣的是，这些蛋白通过自噬调节促进细胞凋亡。综上所述，我们的研究结果表明GNRs-PTT是一种有效的胰腺癌治疗选择，为光热疗法的临床应用提供了理论基础。质谱蛋白质组学数据已通过iProX合作伙伴存储库存储到ProteomeXchange Consortium (https://proteomecentral.proteomexchange.org)，数据集标识符为PXD058930。

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引用次数: 0

Usefulness of serial in vivo imaging to directly assess the role of inflammation in thrombus resolution and organization 系列体内成像直接评估炎症在血栓溶解和组织中的作用的有效性。

IF 2.5 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-02-02 DOI: 10.1016/j.bbrc.2025.151293

Aditya Adinata , Tetsuya Hara , Arinal Chairul Achyar , Yoko Suzuki , Ken-ichi Hirata , Hiromasa Otake , Noriaki Emoto

Deep vein thrombosis (DVT) remains a significant health problem. Although animal models have provided significant insights into the DVT pathophysiology, time-course assessment in a same animal is technically limited. Recently, we reported a novel murine saphenous DVT model for in vivo visualization of spatiotemporal dynamics of inflammatory cells. This study further shed a light on the resolution and organization process of DVT using serial in vivo imaging technique. Similar with ferric chloride-induced thrombus model, our saphenous DVT model allowed serial in vivo imaging with fluorescence microscopy. However, unlike ferric chloride-induced thrombus model, we observed a significant decrease of DVT burden. Red blood cells area gradually decreased followed by fibrin and collagen deposition over time, although ferric chloride model induced platelet-rich arterial thrombus. Histological assessment revealed that neutrophils influx peaked 3 h after DVT induction, followed by macrophages' migration at 120 h’ post-induction, indicating similar organization process with traditional stasis-induced DVT model. Ly6G/Ly6C positive cells at 3 h predicted the reduction of DVT burden (r > 0.8; P < 0.01), suggesting that inflammatory response at acute phase plays pivotal role in DVT resolution. MMP-9 expression was observed and colocalized with neutrophils at early timepoints in both traditional stasis-induced DVT model and our femoral imaging models. Taken together, our in vivo imaging model might allow better understanding of the resolution and organization processes in DVT.

深静脉血栓形成（DVT）仍然是一个重要的健康问题。尽管动物模型对深静脉血栓病理生理学提供了重要的见解，但同一动物的病程评估在技术上是有限的。最近，我们报道了一种新的小鼠隐静脉DVT模型，用于炎症细胞的时空动态的体内可视化。本研究进一步揭示了DVT在体内连续成像技术的分辨率和组织过程。与氯化铁诱导的血栓模型类似，我们的隐静脉血栓模型可以用荧光显微镜进行连续的体内成像。然而，与氯化铁诱导的血栓模型不同，我们观察到深静脉血栓负担明显减少。随着时间的推移，红细胞面积逐渐减少，纤维蛋白和胶原沉积，尽管氯化铁模型诱导了富含血小板的动脉血栓。组织学检查显示，中性粒细胞内流在DVT诱导后3 h达到峰值，巨噬细胞在诱导后120 h开始迁移，与传统停滞性DVT模型的组织过程相似。Ly6G/Ly6C阳性细胞在3 h预测DVT负荷的减少(r > 0.8；P

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引用次数: 0