Biochemical and biophysical research communications最新文献_第5页

Amplitude dependence in extracellular vesicle release from cultured myotubes under vibration stimulation 振动刺激下培养肌管细胞外囊泡释放的振幅依赖性

IF 2.2 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-12-29 DOI: 10.1016/j.bbrc.2025.153218

Qingcheng Guo , Yunfei Fu , Xiaoqi Ma , Jihao Xing , Yudai Kawamoto , Atomu Yamaguchi , Chengzhou Xiong , Mikiko Uemura , Hidemi Fujino , Noriaki Maeshige

Background

Skeletal muscle–derived extracellular vesicles (SkM-EVs) are promising mediators of intercellular communication, yet practical strategies to safely and efficiently enhance their release remain limited. Vibration is a non-invasive, parameter-controlled mechanical stimulus that is already widely used in musculoskeletal rehabilitation, making it an attractive candidate for enhancing SkM-EV release. However, it remains unclear whether vibration increases EV release and which vibration parameter (amplitude, frequency, or acceleration) regulates this effect. Accordingly, we investigated the parameter dependence of this process and the corresponding effective intensity.

Methods

Differentiated C2C12 myotubes were exposed to sinusoidal vibration using a custom-built device. Two parameter-decoupled series were designed: an acceleration-variation series and an amplitude-variation series. EVs were isolated by ultracentrifugation and analyzed by western blotting and tunable resistive pulse sensing (TRPS). RNA sequencing with gene set enrichment analysis (GSEA) was used to identify pathways associated with vibration-induced EV secretion.

Results

Vibration did not reduce cell viability. SkM-EV concentration remained unchanged across acceleration conditions but significantly increased under medium-amplitude (MAm) stimulation. Transcriptomic analysis showed that MAm downregulated Wnt signaling and upregulated the NOD-like receptor pathway, with specific upregulation of Rab27a and Nlrp4e.

Conclusion

Vibration promotes SkM-EV secretion in an amplitude-dependent manner, with the medium-amplitude (MAm) condition being the most effective. This effect appears to be mediated by modulation of the Wnt–Rab27a axis and NLR–Nlrp4e signaling.

骨骼肌来源的细胞外囊泡（skm - ev）是一种很有前途的细胞间通讯介质，但安全有效地促进其释放的实用策略仍然有限。振动是一种非侵入性、参数控制的机械刺激，已广泛应用于肌肉骨骼康复，使其成为增强SkM-EV释放的有吸引力的候选者。然而，目前尚不清楚振动是否会增加EV释放，以及哪种振动参数（振幅、频率或加速度）调节这种影响。因此，我们研究了该过程的参数依赖性和相应的有效强度。方法采用特制装置对分化后的C2C12肌管进行正弦振动。设计了两个参数解耦序列：加速度变化序列和幅值变化序列。采用超离心分离ev， western blotting和可调电阻脉冲传感（TRPS）对其进行分析。RNA测序和基因集富集分析（GSEA）被用于鉴定振动诱导EV分泌的相关途径。结果振动不影响细胞活力。SkM-EV浓度在加速条件下保持不变，但在中振幅（MAm）刺激下显著增加。转录组学分析显示，MAm下调Wnt信号通路，上调nod样受体通路，并特异性上调Rab27a和Nlrp4e。结论振动促进SkM-EV分泌具有幅值依赖性，其中中幅值（MAm）条件下效果最好。这种效应似乎是通过调节Wnt-Rab27a轴和NLR-Nlrp4e信号通路介导的。

{"title":"Amplitude dependence in extracellular vesicle release from cultured myotubes under vibration stimulation","authors":"Qingcheng Guo , Yunfei Fu , Xiaoqi Ma , Jihao Xing , Yudai Kawamoto , Atomu Yamaguchi , Chengzhou Xiong , Mikiko Uemura , Hidemi Fujino , Noriaki Maeshige","doi":"10.1016/j.bbrc.2025.153218","DOIUrl":"10.1016/j.bbrc.2025.153218","url":null,"abstract":"<div><h3>Background</h3><div>Skeletal muscle–derived extracellular vesicles (SkM-EVs) are promising mediators of intercellular communication, yet practical strategies to safely and efficiently enhance their release remain limited. Vibration is a non-invasive, parameter-controlled mechanical stimulus that is already widely used in musculoskeletal rehabilitation, making it an attractive candidate for enhancing SkM-EV release. However, it remains unclear whether vibration increases EV release and which vibration parameter (amplitude, frequency, or acceleration) regulates this effect. Accordingly, we investigated the parameter dependence of this process and the corresponding effective intensity.</div></div><div><h3>Methods</h3><div>Differentiated C2C12 myotubes were exposed to sinusoidal vibration using a custom-built device. Two parameter-decoupled series were designed: an acceleration-variation series and an amplitude-variation series. EVs were isolated by ultracentrifugation and analyzed by western blotting and tunable resistive pulse sensing (TRPS). RNA sequencing with gene set enrichment analysis (GSEA) was used to identify pathways associated with vibration-induced EV secretion.</div></div><div><h3>Results</h3><div>Vibration did not reduce cell viability. SkM-EV concentration remained unchanged across acceleration conditions but significantly increased under medium-amplitude (MAm) stimulation. Transcriptomic analysis showed that MAm downregulated Wnt signaling and upregulated the NOD-like receptor pathway, with specific upregulation of Rab27a and Nlrp4e.</div></div><div><h3>Conclusion</h3><div>Vibration promotes SkM-EV secretion in an amplitude-dependent manner, with the medium-amplitude (MAm) condition being the most effective. This effect appears to be mediated by modulation of the Wnt–Rab27a axis and NLR–Nlrp4e signaling.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153218"},"PeriodicalIF":2.2,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145882135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Quinones as promising agents for managing metabolic syndrome: Therapeutic and toxicological considerations 醌类药物作为治疗代谢综合征的有前途的药物：治疗和毒理学考虑。

IF 2.2 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-12-29 DOI: 10.1016/j.bbrc.2025.153221

Tamsheel Fatima Roohi , Zahoor Ahmad Parray , Syed Faizan , Deepak Solanki , MD Awaise Iqbal Baig , Seema Mehdi , Nabeel Kinattingal

Metabolic syndrome, characterized by insulin resistance, hypertension, dyslipidemia, and obesity, poses significant global health concerns. Quinones, a class of natural and synthetic compounds containing a fully conjugated cyclic unsaturated dione structure, demonstrate cytoprotective activity through redox modulation and antioxidant effects, while their cytotoxicity arises from pro-oxidant behavior and the generation of reactive oxygen species (ROS). This review explores the therapeutic potential of quinones for metabolic syndrome by examining their chemical structure, pharmacological actions, and interactions with key metabolic pathways. Particular attention is given to their influence on insulin signaling, mitochondrial dysfunction, lipid metabolism, and associated metabolic disorders including type 2 diabetes, obesity, cardiovascular disease, and non-alcoholic fatty liver disease. Evidence from preclinical and early clinical studies indicates that quinones can enhance insulin signaling, improve mitochondrial function, reduce oxidative stress, and modulate lipid metabolism and blood pressure. However, the generation of ROS and associated cytotoxicity present challenges for their clinical application. Key limitations in bioavailability, optimal dosage, pharmacokinetics, and long-term safety also hinder successful translation into clinical practice. Further research is needed to define therapeutic windows, develop improved delivery strategies, and clarify toxicological risks. A better understanding of these factors will be essential for advancing quinones as promising therapeutic candidates for metabolic disorders while ensuring safety and efficacy in future clinical applications.

代谢综合征以胰岛素抵抗、高血压、血脂异常和肥胖为特征，引起了重大的全球健康问题。醌是一类天然和人工合成的含有全共轭环不饱和二酮结构的化合物，通过氧化还原调节和抗氧化作用显示出细胞保护活性，而它们的细胞毒性来自促氧化行为和活性氧（ROS）的产生。本文通过研究醌类化合物的化学结构、药理作用以及与关键代谢途径的相互作用，探讨了醌类化合物治疗代谢综合征的潜力。特别关注它们对胰岛素信号传导、线粒体功能障碍、脂质代谢和相关代谢紊乱的影响，包括2型糖尿病、肥胖、心血管疾病和非酒精性脂肪性肝病。临床前和早期临床研究表明，醌类药物可以增强胰岛素信号，改善线粒体功能，减少氧化应激，调节脂质代谢和血压。然而，ROS的产生和相关的细胞毒性对其临床应用提出了挑战。生物利用度、最佳剂量、药代动力学和长期安全性方面的关键限制也阻碍了成功转化为临床实践。需要进一步的研究来确定治疗窗口，制定改进的给药策略，并澄清毒理学风险。更好地了解这些因素对于推进醌类药物作为代谢紊乱的有希望的治疗候选者，同时确保其在未来临床应用中的安全性和有效性至关重要。

{"title":"Quinones as promising agents for managing metabolic syndrome: Therapeutic and toxicological considerations","authors":"Tamsheel Fatima Roohi , Zahoor Ahmad Parray , Syed Faizan , Deepak Solanki , MD Awaise Iqbal Baig , Seema Mehdi , Nabeel Kinattingal","doi":"10.1016/j.bbrc.2025.153221","DOIUrl":"10.1016/j.bbrc.2025.153221","url":null,"abstract":"<div><div>Metabolic syndrome, characterized by insulin resistance, hypertension, dyslipidemia, and obesity, poses significant global health concerns. Quinones, a class of natural and synthetic compounds containing a fully conjugated cyclic unsaturated dione structure, demonstrate cytoprotective activity through redox modulation and antioxidant effects, while their cytotoxicity arises from pro-oxidant behavior and the generation of reactive oxygen species (ROS). This review explores the therapeutic potential of quinones for metabolic syndrome by examining their chemical structure, pharmacological actions, and interactions with key metabolic pathways. Particular attention is given to their influence on insulin signaling, mitochondrial dysfunction, lipid metabolism, and associated metabolic disorders including type 2 diabetes, obesity, cardiovascular disease, and non-alcoholic fatty liver disease. Evidence from preclinical and early clinical studies indicates that quinones can enhance insulin signaling, improve mitochondrial function, reduce oxidative stress, and modulate lipid metabolism and blood pressure. However, the generation of ROS and associated cytotoxicity present challenges for their clinical application. Key limitations in bioavailability, optimal dosage, pharmacokinetics, and long-term safety also hinder successful translation into clinical practice. Further research is needed to define therapeutic windows, develop improved delivery strategies, and clarify toxicological risks. A better understanding of these factors will be essential for advancing quinones as promising therapeutic candidates for metabolic disorders while ensuring safety and efficacy in future clinical applications.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153221"},"PeriodicalIF":2.2,"publicationDate":"2025-12-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Comprehensive pharmacological insights into Glaucocalyxin A: Mechanisms and therapeutic potential 青光素A的综合药理学研究：机制和治疗潜力。

IF 2.2 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-12-29 DOI: 10.1016/j.bbrc.2025.153220

Yizhou Zheng , Lin Liu , Lilong Liu , Yiran Qin , Shuping Jiang

Glaucocalyxin A (GLA) is an ent-kauranoid diterpenoid isolated from Rabdosia japonica (Burm. f.) var. glaucocalyx (Maxim.) Hara. As a promising compound with significant therapeutic potential, GLA has garnered attention for its diverse range of biological activities. These include anti-tumor, anti-inflammatory, and anti-fibrotic effects, as well as cardioprotective effects. The results of network pharmacology and molecular docking predict that GLA may regulate the PI3K/Akt and p53 signaling pathways by interacting with targets including CHEK1, MDM2, and CDK2. Among these, PTGS2 is proposed as the most promising candidate for a direct target, a hypothesis that necessitates further experimental validation. This review comprehensively discusses the development potential of GLA based on its biological activities, molecular targets, signaling pathways, and future translational prospects.

Glaucocalyxin A （GLA）是从日本芥花（Rabdosia japonica, Burm.）中分离得到的一种对kauroid二萜。f.)变种蓝萼（Maxim.）Hara。GLA作为一种具有显著治疗潜力的有前途的化合物，其广泛的生物活性引起了人们的关注。这些包括抗肿瘤，抗炎，抗纤维化作用，以及心脏保护作用。网络药理学和分子对接结果预测GLA可能通过与CHEK1、MDM2、CDK2等靶点相互作用调控PI3K/Akt和p53信号通路。其中，PTGS2被认为是最有希望的直接靶点，这一假设需要进一步的实验验证。本文从GLA的生物学活性、分子靶点、信号通路和未来的转化前景等方面综述了GLA的发展潜力。

引用次数: 0

Force transmission in an actomyosin cytoskeletal network revealed by particle fluctuation analysis 粒子波动分析揭示的肌动球蛋白细胞骨架网络中的力传递。

IF 2.2 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-12-27 DOI: 10.1016/j.bbrc.2025.153217

Masato Ito, Yusuke T. Maeda

Actomyosin cytoskeleton, composed of actin filaments and myosin motor proteins, functions as nanoscale force generators within the cytoskeleton. While they generate contractile forces in the cytosol of living cells, the nature of non-thermal fluctuations driven by spontaneous generation of active force remains little understood. Here, by using in vitro reconstituted systems, we quantitatively analyzed the fluctuations of optically trapped microparticles within the bath of actomyosin cytoskeletons using optical tweezers. Statistical analysis of the trapped particles revealed active forces of approximately 0.16 pN under spontaneous advective flows with mean velocities of 0.25–0.29 µm/s. Notably, these excess fluctuations emerged specifically under flow-generating conditions, and the associated energy dissipation was found to be on the order of thermal energy. Our results provide a quantitative estimate of force transmission in the actomyosin cytoskeleton and offer insights into how force–mediated interactions may contribute to intracellular self-organization.

肌动球蛋白细胞骨架由肌动蛋白丝和肌动蛋白运动蛋白组成，在细胞骨架内起纳米级力发生器的作用。虽然它们在活细胞的细胞质中产生收缩力，但由自发产生的主动力驱动的非热波动的性质仍然知之甚少。在这里，我们利用体外重建系统，用光学镊子定量分析了肌动球蛋白细胞骨架浴中光学捕获的微粒子的波动。对被捕获粒子的统计分析表明，在平均速度为0.25-0.29µm/s的自发平流下，主动作用力约为0.16 pN。值得注意的是，这些多余的波动特别出现在产生流动的条件下，并且发现相关的能量耗散在热能量级。我们的研究结果提供了肌动球蛋白细胞骨架中力传递的定量估计，并提供了力介导的相互作用如何有助于细胞内自组织的见解。

{"title":"Force transmission in an actomyosin cytoskeletal network revealed by particle fluctuation analysis","authors":"Masato Ito, Yusuke T. Maeda","doi":"10.1016/j.bbrc.2025.153217","DOIUrl":"10.1016/j.bbrc.2025.153217","url":null,"abstract":"<div><div>Actomyosin cytoskeleton, composed of actin filaments and myosin motor proteins, functions as nanoscale force generators within the cytoskeleton. While they generate contractile forces in the cytosol of living cells, the nature of non-thermal fluctuations driven by spontaneous generation of active force remains little understood. Here, by using <em>in vitro</em> reconstituted systems, we quantitatively analyzed the fluctuations of optically trapped microparticles within the bath of actomyosin cytoskeletons using optical tweezers. Statistical analysis of the trapped particles revealed active forces of approximately 0.16 pN under spontaneous advective flows with mean velocities of 0.25–0.29µm/s. Notably, these excess fluctuations emerged specifically under flow-generating conditions, and the associated energy dissipation was found to be on the order of thermal energy. Our results provide a quantitative estimate of force transmission in the actomyosin cytoskeleton and offer insights into how force–mediated interactions may contribute to intracellular self-organization.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153217"},"PeriodicalIF":2.2,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Effect of L-theanine on the hippocampus, cerebral cortex and cerebellum of doxorubicin-treated rats l -茶氨酸对阿霉素治疗大鼠海马、大脑皮层和小脑的影响。

IF 2.2 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-12-27 DOI: 10.1016/j.bbrc.2025.153216

Birgül Kural , Sevil Kör , Meltem Arıkan Malkoç , Hilal Öztürk , Tenzile Beyza Durmuş , Esin Yuluğ , Selcen Aydin-Abi̇di̇n , İsmail Abidin , Asım Örem

Neurotoxicity is an important side-effect of many chemotherapeutic agents, including doxorubicin (DXR). L-Theanine (LT) is a non-protein amino acid with a variety of beneficial health effects, involving anti-inflammatory, antimicrobial, anti-aging, antioxidant, antitumor, antihypertensive, and antistress properties. The aim of this study was to investigate the modulatory roles of LT on the electrophysiological, histopathological and biochemical effects of DXR on the rat hippocampus, cerebral cortex and cerebellum. Sixty-four male Wistar rats were randomly divided into four groups: Sham, DXR, DXR + LT200 and DXR + LT400. LT was administered via oral gavage at doses of 200 and 400 mg/kg/day for 21 days, while DXR was given cumulatively at 18 mg/kg (intraperitoneally on days 4, 11, and 18). Half the rats were used for brain electrophysiological assessments, and the remaining half for histological and biochemical analyses. DXR reduced total power in the electrocorticogram (ECoG) between 0.1 and 50 Hz, across all frequency ranges. The application of 400 mg/kg/day, but not 200 mg/kg/day, reduced the total power even further (p < 0.05). Conversely, both doses of LT treatment significantly reduced DXR-induced cell degeneration in all regions (p < 0.001). LT treatments also tended to reduce the levels of DXR-induced oxidative stress parameters, although these effects were not significant for every region of the brain. Considering the capacity of DXR to cause pathological conditions and the multifaceted effects of LT treatments on different regions of the brain, we conclude that the simultaneous administration of LT supplement with DXR treatment should be performed with caution.

神经毒性是许多化疗药物的重要副作用，包括阿霉素（DXR）。l -茶氨酸（LT）是一种非蛋白质氨基酸，具有多种有益健康的作用，包括抗炎、抗菌、抗衰老、抗氧化、抗肿瘤、抗高血压和抗应激等特性。本研究旨在探讨LT对DXR对大鼠海马、大脑皮层和小脑的电生理、组织病理和生化作用的调节作用。雄性Wistar大鼠64只，随机分为Sham组、DXR组、DXR + LT200组和DXR + LT400组。LT以200和400 mg/kg/天的剂量灌胃给药，连续21天，而DXR以18 mg/kg的剂量累积给药（在第4、11和18天腹腔注射）。一半的大鼠用于脑电生理评估，其余一半用于组织学和生化分析。在所有频率范围内，DXR降低了皮质电图（ECoG）在0.1至50 Hz之间的总功率。施用400mg /kg/天，而不是200mg /kg/天，进一步降低了总功率(p

{"title":"Effect of L-theanine on the hippocampus, cerebral cortex and cerebellum of doxorubicin-treated rats","authors":"Birgül Kural , Sevil Kör , Meltem Arıkan Malkoç , Hilal Öztürk , Tenzile Beyza Durmuş , Esin Yuluğ , Selcen Aydin-Abi̇di̇n , İsmail Abidin , Asım Örem","doi":"10.1016/j.bbrc.2025.153216","DOIUrl":"10.1016/j.bbrc.2025.153216","url":null,"abstract":"<div><div>Neurotoxicity is an important side-effect of many chemotherapeutic agents, including doxorubicin (DXR). L-Theanine (LT) is a non-protein amino acid with a variety of beneficial health effects, involving anti-inflammatory, antimicrobial, anti-aging, antioxidant, antitumor, antihypertensive, and antistress properties. The aim of this study was to investigate the modulatory roles of LT on the electrophysiological, histopathological and biochemical effects of DXR on the rat hippocampus, cerebral cortex and cerebellum. Sixty-four male Wistar rats were randomly divided into four groups: Sham, DXR, DXR + LT200 and DXR + LT400. LT was administered via oral gavage at doses of 200 and 400 mg/kg/day for 21 days, while DXR was given cumulatively at 18 mg/kg (intraperitoneally on days 4, 11, and 18). Half the rats were used for brain electrophysiological assessments, and the remaining half for histological and biochemical analyses. DXR reduced total power in the electrocorticogram (ECoG) between 0.1 and 50 Hz, across all frequency ranges. The application of 400 mg/kg/day, but not 200 mg/kg/day, reduced the total power even further (p < 0.05). Conversely, both doses of LT treatment significantly reduced DXR-induced cell degeneration in all regions (p < 0.001). LT treatments also tended to reduce the levels of DXR-induced oxidative stress parameters, although these effects were not significant for every region of the brain. Considering the capacity of DXR to cause pathological conditions and the multifaceted effects of LT treatments on different regions of the brain, we conclude that the simultaneous administration of LT supplement with DXR treatment should be performed with caution.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153216"},"PeriodicalIF":2.2,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Progranulin is increased during prodromal pathology in LRRK2 G2019S mice 在LRRK2 G2019S小鼠的前驱病理过程中，前颗粒蛋白增加。

IF 2.2 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-12-27 DOI: 10.1016/j.bbrc.2025.153219

Soung-Hee Moon, Hyun Jin Choi

The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is a major genetic risk factor for Parkinson's disease (PD). Most studies have shown that this mutation alone is insufficient to induce marked motor impairment or notable dopaminergic loss, and that pathological changes have been reported mainly in aging models or when additional stressors are applied. A decrease in progranulin (PGRN) is a major cause of frontotemporal dementia and has also been observed in patients with LRRK2 G2019S PD. In this study, we sought to determine how PGRN is regulated during the prodromal stage of PD. In 12-week-old female G2019S mice, overt degeneration of nigral dopaminergic neurons or motor impairments was not observed; however, these mice exhibited increased non-motor behavior. Pathological analyses revealed elevated NOD-like receptor protein 3 (NLRP3) inflammasome activation and Iba-1 expression. Additionally, abnormal protein accumulation was observed in the brain. Notably, PGRN levels increased in both brain tissue and plasma, accompanied by a concurrent reduction in elastase expression in the brains of G2019S mice. Increased levels of PGRN and its colocalization with phosphorylated LRRK2 were also observed in primary microglia derived from day-1 pups. Collectively, our findings demonstrate that PGRN is upregulated during the prodromal stage of pathology and the emergence of non-motor symptoms in young LRRK2 G2019S transgenic mice. This early increase in PGRN, which occurs alongside neuroinflammation and abnormal protein accumulation, suggests that PGRN regulation may follow a stage-dependent trajectory and provides new insights into the initial pathogenic processes associated with LRRK2 G2019S–linked PD.

富亮氨酸重复激酶2 (LRRK2) G2019S突变是帕金森病（PD）的主要遗传危险因素。大多数研究表明，这种突变本身不足以引起明显的运动损伤或显著的多巴胺能丧失，并且主要在衰老模型或施加额外压力源时报道了病理变化。颗粒前蛋白（PGRN）的减少是额颞叶痴呆的主要原因，在LRRK2 G2019S PD患者中也有观察到。在这项研究中，我们试图确定PGRN在PD前驱期是如何被调节的。在12周龄雌性G2019S小鼠中，未观察到明显的黑质多巴胺能神经元变性或运动损伤；然而，这些小鼠表现出增加的非运动行为。病理分析显示nod样受体蛋白3 （NLRP3）炎性体激活和Iba-1表达升高。此外，在大脑中观察到异常的蛋白质积累。值得注意的是，G2019S小鼠脑组织和血浆中PGRN水平升高，同时大脑中弹性蛋白酶表达降低。PGRN水平的升高及其与磷酸化LRRK2的共定位也在第1天幼犬的初级小胶质细胞中被观察到。总之，我们的研究结果表明，在年轻的LRRK2 G2019S转基因小鼠的病理前驱阶段和非运动症状出现期间，PGRN表达上调。PGRN的早期增加与神经炎症和异常蛋白积累一起发生，表明PGRN调节可能遵循阶段依赖的轨迹，并为与LRRK2 g2019s相关的PD相关的初始致病过程提供了新的见解。

{"title":"Progranulin is increased during prodromal pathology in LRRK2 G2019S mice","authors":"Soung-Hee Moon, Hyun Jin Choi","doi":"10.1016/j.bbrc.2025.153219","DOIUrl":"10.1016/j.bbrc.2025.153219","url":null,"abstract":"<div><div>The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is a major genetic risk factor for Parkinson's disease (PD). Most studies have shown that this mutation alone is insufficient to induce marked motor impairment or notable dopaminergic loss, and that pathological changes have been reported mainly in aging models or when additional stressors are applied. A decrease in progranulin (PGRN) is a major cause of frontotemporal dementia and has also been observed in patients with LRRK2 G2019S PD. In this study, we sought to determine how PGRN is regulated during the prodromal stage of PD. In 12-week-old female G2019S mice, overt degeneration of nigral dopaminergic neurons or motor impairments was not observed; however, these mice exhibited increased non-motor behavior. Pathological analyses revealed elevated NOD-like receptor protein 3 (NLRP3) inflammasome activation and Iba-1 expression. Additionally, abnormal protein accumulation was observed in the brain. Notably, PGRN levels increased in both brain tissue and plasma, accompanied by a concurrent reduction in elastase expression in the brains of G2019S mice. Increased levels of PGRN and its colocalization with phosphorylated LRRK2 were also observed in primary microglia derived from day-1 pups. Collectively, our findings demonstrate that PGRN is upregulated during the prodromal stage of pathology and the emergence of non-motor symptoms in young LRRK2 G2019S transgenic mice. This early increase in PGRN, which occurs alongside neuroinflammation and abnormal protein accumulation, suggests that PGRN regulation may follow a stage-dependent trajectory and provides new insights into the initial pathogenic processes associated with LRRK2 G2019S–linked PD.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153219"},"PeriodicalIF":2.2,"publicationDate":"2025-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

HER3 enhances ATF4 induction and survival in breast cancer cells during endoplasmic reticulum stress HER3增强内质网应激时乳腺癌细胞ATF4的诱导和存活

IF 2.2 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-12-26 DOI: 10.1016/j.bbrc.2025.153215

Miku Otsuka , Yuka Okamoto , Akiko Hasebe , Hitomi Shirahama , Akihiro Tomida

Oncogenic signaling and stress response pathways interact to drive tumorigenesis and therapy resistance. However, little is known about such interactions for HER3, a member of the HER/ErbB receptor family that is aberrantly expressed in many tumors, including breast cancer. Here, we show that HER3 cooperates with HER2 to enhance induction of ATF4, a central transcription factor of the integrated stress response and the unfolded protein response, during endoplasmic reticulum (ER) stress. ATF4 induction was enhanced by ligand-activated HER3 and conversely reduced by genetic knockdown or pharmacological inhibition of HER2/HER3-mediated signaling in both HER2-overexpressing SKBR3 and non-overexpressing MCF7 breast cancer cells. HER3 knockdown in SKBR3 cells also increased cell death during ER stress. Notably, depletion of HER3, likely occurring through ER stress-associated downregulation mechanisms, was accompanied by attenuation of ATF4 induction during sustained stress. These findings suggest that the HER3-ATF4 axis functions as a dynamically regulated mechanism for tuning the cellular stress response.

致癌信号和应激反应途径相互作用，驱动肿瘤发生和治疗抵抗。HER3是HER/ErbB受体家族的一员，在包括乳腺癌在内的许多肿瘤中异常表达。然而，我们对HER3的这种相互作用知之甚少。本研究表明，在内质网（ER）应激过程中，HER3与HER2协同增强ATF4的诱导，ATF4是综合应激反应和未折叠蛋白反应的中心转录因子。在HER2过表达的SKBR3和非过表达的MCF7乳腺癌细胞中，配体激活的HER3增强了ATF4的诱导，而通过基因敲低或药物抑制HER2/HER3介导的信号传导，反过来降低了ATF4的诱导。HER3敲低SKBR3细胞也增加内质网应激时的细胞死亡。值得注意的是，HER3的缺失可能是通过内质网应激相关的下调机制发生的，在持续应激过程中，伴随着ATF4诱导的减弱。这些发现表明HER3-ATF4轴作为调节细胞应激反应的动态调节机制发挥作用。

{"title":"HER3 enhances ATF4 induction and survival in breast cancer cells during endoplasmic reticulum stress","authors":"Miku Otsuka , Yuka Okamoto , Akiko Hasebe , Hitomi Shirahama , Akihiro Tomida","doi":"10.1016/j.bbrc.2025.153215","DOIUrl":"10.1016/j.bbrc.2025.153215","url":null,"abstract":"<div><div>Oncogenic signaling and stress response pathways interact to drive tumorigenesis and therapy resistance. However, little is known about such interactions for HER3, a member of the HER/ErbB receptor family that is aberrantly expressed in many tumors, including breast cancer. Here, we show that HER3 cooperates with HER2 to enhance induction of ATF4, a central transcription factor of the integrated stress response and the unfolded protein response, during endoplasmic reticulum (ER) stress. ATF4 induction was enhanced by ligand-activated HER3 and conversely reduced by genetic knockdown or pharmacological inhibition of HER2/HER3-mediated signaling in both HER2-overexpressing SKBR3 and non-overexpressing MCF7 breast cancer cells. HER3 knockdown in SKBR3 cells also increased cell death during ER stress. Notably, depletion of HER3, likely occurring through ER stress-associated downregulation mechanisms, was accompanied by attenuation of ATF4 induction during sustained stress. These findings suggest that the HER3-ATF4 axis functions as a dynamically regulated mechanism for tuning the cellular stress response.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153215"},"PeriodicalIF":2.2,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Plant-derived efflux pump inhibitors potentiate Chlorin e6-based antimicrobial photodynamic therapy against Bacillus cereus and Escherichia coli 植物源外排泵抑制剂增强基于氯e6的抗蜡样芽孢杆菌和大肠杆菌的抗菌光动力疗法

IF 2.2 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-12-26 DOI: 10.1016/j.bbrc.2025.153214

Aleksandra Talarczyk , Agata Kublicka , Anna Matczuk , Alina Wieliczko , Agnieszka Ulatowska-Jarża , Igor Buzalewicz

Antimicrobial resistance

especially via efflux pump-mediated multidrug resistance is a major factor limiting antibacterial therapy efficacy. Antimicrobial photodynamic therapy (aPDT) is a non-antibiotic strategy that overcomes resistance through generation of reactive oxygen species. Plant-derived compounds exhibit efflux pump inhibitory activity and potential photosensitizing capabilities. This study evaluated the use of plant-derived efflux pump inhibitors (EPIs): berberine, capsaicin, coumarin 6, curcumin, palmatine, and piperine in combination with Chlorin e6 and aPDT against Bacillus cereus (Gram-positive) and Escherichia coli (Gram-negative). The aim was to enhance Chlorin e6 accumulation and reduce bacterial dry mass density. Both qualitative and quantitative methods were used in the study. Minimum inhibitory concentrations (MICs) of EPIs were determined to guide treatment concentrations. A modified resazurin assay assessed bacterial viability after 24-h incubation with EPIs. Spectroscopic properties of all compounds were recorded using UV-VIS spectroscopy. Digital holotomography (DHT) was applied to monitor changes in refractive index (RI) of bacterial cells induced by incubation and treatment, and results were validated using confocal fluorescence microscopy. Changes in RI values indicated structural and compositional changes in the bacteria. Naturally derived EPIs effectively potentiated aPDT by promoting photosensitizer uptake and induced a measurable reduction in dry mass density. Treatment efficacy using combination therapy for B.cereus and E.coli improved 273.90 % and 227.72 %, respectively. These findings suggest naturally derived EPIs effectively potentiate Chlorin e6-mediated aPDT and improve bactericidal capacity against bacteria. The study offers mechanistic insight into photodynamic enhancement via plant-based inhibitors and supports potential applications in clinical antimicrobial therapy, food safety, and industrial decontamination.

抗菌药物耐药特别是外排泵介导的多药耐药是限制抗菌药物治疗效果的主要因素。抗菌素光动力疗法（aPDT）是一种通过产生活性氧来克服耐药性的非抗生素策略。植物源性化合物表现出外排泵抑制活性和潜在的光敏能力。本研究评估了植物源性外排泵抑制剂（EPIs）：小檗碱、辣椒素、香豆素6、姜黄素、棕榈碱和胡椒碱与氯e6和aPDT联合对蜡样芽孢杆菌（革兰氏阳性）和大肠杆菌（革兰氏阴性）的作用。目的是促进氯e6积累，降低细菌干质量密度。本研究采用定性与定量相结合的方法。测定EPIs的最低抑制浓度（mic）以指导治疗浓度。用改良的瑞祖林法测定EPIs孵育24小时后的细菌活力，用紫外-可见光谱法记录所有化合物的光谱性质。采用数字全息成像技术（DHT）监测细菌细胞在孵育和处理后折射率（RI）的变化，并用共聚焦荧光显微镜对结果进行验证。RI值的变化表明细菌的结构和组成发生了变化。天然衍生的EPIs通过促进光敏剂的吸收，有效地增强了aPDT，并诱导干质量密度的显著降低。联合治疗蜡样芽孢杆菌和大肠杆菌的疗效分别提高273.90%和227.72%。这些发现表明，天然衍生的EPIs有效地增强了氯e6介导的aPDT，提高了对细菌的杀菌能力。该研究提供了通过植物基抑制剂增强光动力的机理，并支持在临床抗菌治疗、食品安全和工业净化方面的潜在应用。

{"title":"Plant-derived efflux pump inhibitors potentiate Chlorin e6-based antimicrobial photodynamic therapy against Bacillus cereus and Escherichia coli","authors":"Aleksandra Talarczyk , Agata Kublicka , Anna Matczuk , Alina Wieliczko , Agnieszka Ulatowska-Jarża , Igor Buzalewicz","doi":"10.1016/j.bbrc.2025.153214","DOIUrl":"10.1016/j.bbrc.2025.153214","url":null,"abstract":"<div><h3>Antimicrobial resistance</h3><div>especially via efflux pump-mediated multidrug resistance is a major factor limiting antibacterial therapy efficacy. Antimicrobial photodynamic therapy (aPDT) is a non-antibiotic strategy that overcomes resistance through generation of reactive oxygen species. Plant-derived compounds exhibit efflux pump inhibitory activity and potential photosensitizing capabilities. This study evaluated the use of plant-derived efflux pump inhibitors (EPIs): berberine, capsaicin, coumarin 6, curcumin, palmatine, and piperine in combination with Chlorin e6 and aPDT against <em>Bacillus cereus</em> (Gram-positive) and <em>Escherichia coli</em> (Gram-negative). The aim was to enhance Chlorin e6 accumulation and reduce bacterial dry mass density. Both qualitative and quantitative methods were used in the study. Minimum inhibitory concentrations (MICs) of EPIs were determined to guide treatment concentrations. A modified resazurin assay assessed bacterial viability after 24-h incubation with EPIs. Spectroscopic properties of all compounds were recorded using UV-VIS spectroscopy. Digital holotomography (DHT) was applied to monitor changes in refractive index (RI) of bacterial cells induced by incubation and treatment, and results were validated using confocal fluorescence microscopy. Changes in RI values indicated structural and compositional changes in the bacteria. Naturally derived EPIs effectively potentiated aPDT by promoting photosensitizer uptake and induced a measurable reduction in dry mass density. Treatment efficacy using combination therapy for <em>B.cereus</em> and <em>E.coli</em> improved 273.90 % and 227.72 %, respectively. These findings suggest naturally derived EPIs effectively potentiate Chlorin e6-mediated aPDT and improve bactericidal capacity against bacteria. The study offers mechanistic insight into photodynamic enhancement via plant-based inhibitors and supports potential applications in clinical antimicrobial therapy, food safety, and industrial decontamination.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153214"},"PeriodicalIF":2.2,"publicationDate":"2025-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838707","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Systematic genome-wide analysis and expression profiling of the NAC transcription factor family in Nicotiana benthamiana reveal potential regulators of salt and drought stress responses 本烟NAC转录因子家族的系统全基因组分析和表达谱揭示了盐和干旱胁迫反应的潜在调节因子

IF 2.2 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-12-25 DOI: 10.1016/j.bbrc.2025.153202

Xuebo Wang , Xiaoxu Li , Zhaohui Zong , Zheng Sun , Junling Tian , Weicai Zhao

The no apical meristem, Arabidopsis transcription activation factor 1/2, and cup-shaped cotyledon 2 (NAM, ATAF1/2, and CUC2; NAC) transcription factors constitute one of the largest plant-specific gene families crucial for development and stress responses. This study presents the first comprehensive genome-wide in silico analysis of the NAC family in Nicotiana benthamiana. A total of 224 non-redundant NAC genes (NbeNACs) were identified, unevenly distributed across 19 chromosomes. Phylogenetic analysis classified NbeNACs into three groups with divergent evolutionary trajectories—group I contained conserved duplicates from ancestral genomes, group III featured hyper-amplified loci (Nbe06g31470 with 10 copies), and the absence of group II members on chromosomes 4, 14, and 17 indicated lineage-specific gene loss. Although all NbeNACs possessed the conserved NAC domain, gene structure and motif analyses revealed significant diversification, with lineage-specific motifs (motifs 8 and 10) indicating functional specialization. Promoter analysis identified abundant stress- and hormone-responsive cis-elements, highlighting the NbeNAC family in environmental signal integration. Collinearity analysis revealed segmental duplication as a primary driver of family expansion. Integrating genomic data with expression profiling under drought and salt stress, we identified seven candidate genes (including Nbe01g07940.1 and Nbe06g31470.1) that were consistently upregulated. This systematic analysis provides a foundational resource and prioritizes key candidate genes for future functional validation of NAC-mediated stress responses in N. benthamiana.

拟南芥无顶分生组织、转录激活因子1/2和杯形子叶2 （NAM、ATAF1/2和CUC2； NAC）转录因子构成了对植物发育和胁迫应答至关重要的最大的植物特异性基因家族之一。本研究首次对烟叶NAC家族进行了全面的全基因组计算机分析。共鉴定出224个非冗余NAC基因（NbeNACs），不均匀分布在19条染色体上。系统发育分析将NbeNACs分为三组，它们具有不同的进化轨迹：第一组含有来自祖先基因组的保守重复，第三组具有超扩增的位点（Nbe06g31470有10个拷贝），第二组在染色体4、14和17上缺乏成员，表明谱系特异性基因丢失。尽管所有NbeNACs都具有保守的NAC结构域，但基因结构和基序分析显示出显著的多样性，谱系特异性基序（基序8和基序10）表明功能特化。启动子分析发现了大量应激和激素响应的顺式元件，突出了NbeNAC家族在环境信号整合中的作用。共线性分析显示，片段重复是家族扩张的主要驱动因素。将基因组数据与干旱和盐胁迫下的表达谱相结合，我们发现了7个持续上调的候选基因（包括Nbe01g07940.1和Nbe06g31470.1）。该系统分析为nac介导的benthamiana应激反应的功能验证提供了基础资源和优先考虑关键候选基因。

{"title":"Systematic genome-wide analysis and expression profiling of the NAC transcription factor family in Nicotiana benthamiana reveal potential regulators of salt and drought stress responses","authors":"Xuebo Wang , Xiaoxu Li , Zhaohui Zong , Zheng Sun , Junling Tian , Weicai Zhao","doi":"10.1016/j.bbrc.2025.153202","DOIUrl":"10.1016/j.bbrc.2025.153202","url":null,"abstract":"<div><div>The no apical meristem, Arabidopsis transcription activation factor 1/2, and cup-shaped cotyledon 2 (NAM, ATAF1/2, and CUC2; NAC) transcription factors constitute one of the largest plant-specific gene families crucial for development and stress responses. This study presents the first comprehensive genome-wide in silico analysis of the NAC family in <em>Nicotiana benthamiana</em>. A total of 224 non-redundant <em>NAC</em> genes (<em>NbeNACs</em>) were identified, unevenly distributed across 19 chromosomes. Phylogenetic analysis classified NbeNACs into three groups with divergent evolutionary trajectories—group I contained conserved duplicates from ancestral genomes, group III featured hyper-amplified loci (Nbe06g31470 with 10 copies), and the absence of group II members on chromosomes 4, 14, and 17 indicated lineage-specific gene loss. Although all NbeNACs possessed the conserved NAC domain, gene structure and motif analyses revealed significant diversification, with lineage-specific motifs (motifs 8 and 10) indicating functional specialization. Promoter analysis identified abundant stress- and hormone-responsive <em>cis</em>-elements, highlighting the NbeNAC family in environmental signal integration. Collinearity analysis revealed segmental duplication as a primary driver of family expansion. Integrating genomic data with expression profiling under drought and salt stress, we identified seven candidate genes (including <em>Nbe01g07940.1</em> and <em>Nbe06g31470.1</em>) that were consistently upregulated. This systematic analysis provides a foundational resource and prioritizes key candidate genes for future functional validation of NAC-mediated stress responses in <em>N. benthamiana</em>.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"797 ","pages":"Article 153202"},"PeriodicalIF":2.2,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145838706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Elevated miR-145/TLR4/NF-κB signaling correlates with myocardial PANoptosis in septic rats miR-145/TLR4/NF-κB信号的升高与脓毒症大鼠心肌PANoptosis相关

IF 2.2 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochemical and biophysical research communications

Pub Date : 2025-12-24 DOI: 10.1016/j.bbrc.2025.153169

Zengfeng Wang , Yansheng Shan , Cang Li , Shihai Liu , Liang Shan

Background

Sepsis is a life-threatening organ dysfunction driven by dysregulated host responses to infection. While PANoptosis-a coordinated cell death pathway-has emerged as a critical process in inflammatory diseases, its role in sepsis and regulatory interactions with the miR-145/TLR4/NF-κB axis remains unexplored. This study aimed to determine PANoptosis activation in sepsis, elucidate the mechanistic involvement of miR-145/TLR4/NF-κB in PANoptosis regulation, and assess associated pathological outcomes.

Methods

Cross-dataset analyses revealed functional linkages between miR-145/TLR4/NF-κB signaling and PANoptotic pathways. Clinical validation included serum collection from sepsis patients and healthy controls, with miR-145 quantified via qPCR and PANoptosis-related proteins measured by ELISA. A rat sepsis model was established via cecal ligation and puncture, followed by miR-145 expression profiling, PANoptotic factor detection, and myocardial histopathological evaluation using HE/TUNEL staining.

Results

Results demonstrated significant upregulation of miR-145, TLR4, NF-κB, PANoptotic markers, and pro-inflammatory cytokines in sepsis patients versus controls. CLP rats exhibited parallel increases in these biomarkers alongside pronounced myocardial injury, including histopathological disruption and elevated apoptosis. Correlation analyses confirmed miR-145/TLR4/NF-κB axis activation as a key modulator of PANoptosis and tissue damage.

Conclusion

This study provides evidence of PANoptosis activation in sepsis, indicating a correlative link with elevated miR-145/TLR4/NF-κB signaling. These findings propose a novel pathogenic framework for sepsis-associated organ dysfunction and highlight therapeutic targets for modulating inflammatory cell death pathways.

脓毒症是一种由宿主对感染反应失调引起的危及生命的器官功能障碍。虽然panoptosis -一种协调的细胞死亡途径-已经成为炎症性疾病的一个关键过程，但其在败血症中的作用以及与miR-145/TLR4/NF-κB轴的调节相互作用仍未被探索。本研究旨在确定脓毒症中PANoptosis的激活情况，阐明miR-145/TLR4/NF-κB参与PANoptosis调节的机制，并评估相关病理结果。交叉数据集分析揭示了miR-145/TLR4/NF-κB信号通路与泛光通路之间的功能联系。临床验证包括收集脓毒症患者和健康对照者的血清，通过qPCR量化miR-145，通过ELISA检测panoptosis相关蛋白。通过盲肠结扎穿刺建立大鼠脓毒症模型，进行miR-145表达谱分析、PANoptotic因子检测、HE/TUNEL染色心肌组织病理学评价。结果结果显示，与对照组相比，败血症患者miR-145、TLR4、NF-κB、PANoptotic标志物和促炎细胞因子显著上调。CLP大鼠在心肌损伤的同时表现出这些生物标志物的平行增加，包括组织病理学破坏和细胞凋亡升高。相关分析证实miR-145/TLR4/NF-κB轴活化是PANoptosis和组织损伤的关键调节因子。结论本研究提供了PANoptosis在脓毒症中激活的证据，表明其与miR-145/TLR4/NF-κB信号的升高相关。这些发现提出了脓毒症相关器官功能障碍的新致病框架，并强调了调节炎症细胞死亡途径的治疗靶点。

{"title":"Elevated miR-145/TLR4/NF-κB signaling correlates with myocardial PANoptosis in septic rats","authors":"Zengfeng Wang , Yansheng Shan , Cang Li , Shihai Liu , Liang Shan","doi":"10.1016/j.bbrc.2025.153169","DOIUrl":"10.1016/j.bbrc.2025.153169","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis is a life-threatening organ dysfunction driven by dysregulated host responses to infection. While PANoptosis-a coordinated cell death pathway-has emerged as a critical process in inflammatory diseases, its role in sepsis and regulatory interactions with the miR-145/TLR4/NF-κB axis remains unexplored. This study aimed to determine PANoptosis activation in sepsis, elucidate the mechanistic involvement of miR-145/TLR4/NF-κB in PANoptosis regulation, and assess associated pathological outcomes.</div></div><div><h3>Methods</h3><div>Cross-dataset analyses revealed functional linkages between miR-145/TLR4/NF-κB signaling and PANoptotic pathways. Clinical validation included serum collection from sepsis patients and healthy controls, with miR-145 quantified via qPCR and PANoptosis-related proteins measured by ELISA. A rat sepsis model was established via cecal ligation and puncture, followed by miR-145 expression profiling, PANoptotic factor detection, and myocardial histopathological evaluation using HE/TUNEL staining.</div></div><div><h3>Results</h3><div>Results demonstrated significant upregulation of miR-145, TLR4, NF-κB, PANoptotic markers, and pro-inflammatory cytokines in sepsis patients versus controls. CLP rats exhibited parallel increases in these biomarkers alongside pronounced myocardial injury, including histopathological disruption and elevated apoptosis. Correlation analyses confirmed miR-145/TLR4/NF-κB axis activation as a key modulator of PANoptosis and tissue damage.</div></div><div><h3>Conclusion</h3><div>This study provides evidence of PANoptosis activation in sepsis, indicating a correlative link with elevated miR-145/TLR4/NF-κB signaling. These findings propose a novel pathogenic framework for sepsis-associated organ dysfunction and highlight therapeutic targets for modulating inflammatory cell death pathways.</div></div>","PeriodicalId":8779,"journal":{"name":"Biochemical and biophysical research communications","volume":"798 ","pages":"Article 153169"},"PeriodicalIF":2.2,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145876740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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