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Baicalein suppresses inflammation and attenuates acute lung injury by inhibiting glycolysis via HIF‑1α signaling. 黄芩素通过 HIF-1α 信号传导抑制糖酵解,从而抑制炎症并减轻急性肺损伤。
IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2025-01-01 Epub Date: 2024-11-08 DOI: 10.3892/mmr.2024.13383
Zhongyou Liu, Xiaona Zheng, Ning Li, Zongyao Wang

Baicalein, a flavonoid monomer compound isolated from the dried root of the traditional Chinese herb Scutellaria baicalensis, has several pharmacological activities, such as anti‑inflammatory, anti‑angiogenic, antitumor, antimicrobial and antiviral properties. Acute lung injury (ALI) is characterized by injury of the alveolar epithelium and capillary endothelium, which results in decreased lung volume, decreased lung compliance, ventilation/perfusion mismatch, intrapulmonary edema, alveolar edema and even acute hypoxemic respiratory failure. The present study aimed to investigate the effects of baicalein on lung injury and inflammation. Bioinformatics analysis using network pharmacology predicted that the hypoxia inducible factor‑1α (HIF‑1α) and glycolysis signaling pathways were involved in the mechanism underlying the therapeutic effects of baicalein. Further in vitro and in vivo experiments, such as immunohistochemistry, immunofluorescence and PCR, verified that baicalein could inhibit HIF‑1α signaling, thus suppressing glycolysis, and improving inflammatory responses and ALI. Taken together, the results of the present study suggested that the anti‑inflammatory effects of baicalein on treating ALI were associated with its ability to suppress glycolysis via the HIF‑1α signaling pathway.

黄芩素是从传统中草药黄芩的干燥根中分离出来的一种黄酮类单体化合物,具有多种药理活性,如抗炎、抗血管生成、抗肿瘤、抗菌和抗病毒等特性。急性肺损伤(ALI)的特点是肺泡上皮和毛细血管内皮损伤,导致肺容量减少、肺顺应性降低、通气/灌注不匹配、肺内水肿、肺泡水肿,甚至急性低氧血症呼吸衰竭。本研究旨在探讨黄芩苷对肺损伤和炎症的影响。利用网络药理学进行的生物信息学分析预测,低氧诱导因子-1α(HIF-1α)和糖酵解信号通路参与了黄芩苷的治疗作用机制。进一步的体外和体内实验,如免疫组化、免疫荧光和 PCR,验证了黄芩苷能抑制 HIF-1α 信号传导,从而抑制糖酵解,改善炎症反应和 ALI。综上所述,本研究结果表明,黄芩苷治疗 ALI 的抗炎作用与其通过 HIF-1α 信号通路抑制糖酵解的能力有关。
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引用次数: 0
Enocyanin promotes osteogenesis and bone regeneration by inhibiting MMP9. Enocyanin 可通过抑制 MMP9 促进成骨和骨再生。
IF 8.3 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2025-01-01 Epub Date: 2024-11-08 DOI: 10.3892/ijmm.2024.5450
Wei Mao, Yinfeng Zheng, Wencong Zhang, Jinrong Yin, Zhiyi Liu, Peiliang He, Guodong Hou, Guowei Huang, Huan Chen, Junyan Lin, Jiake Xu, Aiguo Li, Shengnan Qin

Enocyanin (ENO), an anthocyanin extracted from grapes, has been shown to exert inhibitory effects on acid phosphatase and inflammation; however, its role in osteogenesis and bone formation is currently unknown. The present study aimed to investigate the effects of ENO on osteogenesis in vitro and bone formation in vivo, and to explore the rudimentary mechanisms. KusaO cells were employed to evaluate the osteogenic role of ENO in vitro by Alizarin red S staining, ALP staining, quantitative PCR and western blotting, and an in vivo analysis of the therapeutic effects of ENO on a femoral fracture model was performed using stereo microscope, micro‑CT and histological staining. To further investigate the underlying mechanisms, mRNA sequencing was employed to investigate the changes in gene expression and the downstream pathways after ENO treatment. The results showed that ENO could promote the osteogenic differentiation of KusaO cells in vitro and bone fracture regeneration in vivo. Mechanistically, ENO was highly related to bone formation, including the 'Wnt signalling pathway', 'bone development' and 'bone mineralization'. In addition, matrix metalloproteinase 9 (MMP9) was identified as one of the targets of ENO in its promotional role in osteogenesis. In conclusion, ENO may represent a therapeutic candidate for bone regeneration in bone fractures by regulating osteogenesis and bone formation via MMP9.

花青素(ENO)是从葡萄中提取的一种花青素,已被证明具有抑制酸性磷酸酶和炎症的作用,但其在成骨和骨形成中的作用目前尚不清楚。本研究旨在研究ENO对体外成骨和体内骨形成的影响,并探索其基本机制。本研究利用茜素红S染色、ALP染色、定量PCR和Western印迹技术评估了ENO对KusaO细胞的体外成骨作用,并利用立体显微镜、显微CT和组织学染色技术分析了ENO对股骨骨折模型的体内治疗作用。为进一步探究其潜在机制,研究人员采用mRNA测序技术研究了ENO治疗后基因表达的变化及其下游通路。结果表明,ENO能促进KusaO细胞体外成骨分化和体内骨折再生。从机制上看,ENO与骨形成高度相关,包括 "Wnt信号通路"、"骨发育 "和 "骨矿化"。此外,基质金属蛋白酶9(MMP9)被确定为ENO促进骨形成的靶标之一。总之,ENO可通过MMP9调节骨生成和骨形成,从而成为骨折骨再生的候选疗法。
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引用次数: 0
Engineering of in-plane SnS2-SnO2 nanosheets heterostructures for enhanced H2S sensing. 设计平面内 SnS2-SnO2 纳米片异质结构以增强 H2S 传感。
IF 8.3 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2025-01-01 Epub Date: 2024-10-16 DOI: 10.1016/j.talanta.2024.127059
Xuan-Yu Yang, Jian-Yong Yuan, Yang Ye, Li-Juan Yue, Fei-Long Gong, Ke-Feng Xie, Yong-Hui Zhang

In-plane heterostructures has attracted considerable interest due to exceptional electron transport properties, high specific surface area, and abundant active sites. However, synthesis of in-plane SnS2-SnO2 heterostructures are rarely reported, and the deep investigation of the fine structure on reactivity is of great significance. Here, we propose partial in-situ oxidation strategy to construct the in-plane SnS2-SnO2 heterostructures and the surface properties, the ratio of two components can be finely tuned by precisely adjusting the treatment temperature. In particular, the SnS2-SnO2 heterostructures formed after annealing of SnS2 nanosheets at 350 °C exhibits a unique electronic structure and surface properties due to rich grain boundaries, which exhibits excellent gas sensing performance to H2S (Ra/Rg = 169.81 for 5 ppm H2S at 160 °C, fast response and recovery dynamic (41/101 s), excellent reliability (σ = 0.01) and sensing stability (φ = 0.11 %)). Notably, the in-plane heterostructures endow the material with abundant grain boundaries and effectively regulates the electronic structure of the Sn p-orbital, which facilitate the formation of active oxygen species (O-(ad)), thus contributing to the sensing performance. Our work provides a promising platform to design in-plane heterostructures for various advanced applications.

面内异质结构具有优异的电子传输性能、高比表面积和丰富的活性位点,因此引起了广泛的关注。然而,面内 SnS2-SnO2 异质结构的合成却鲜有报道,深入研究其精细结构对反应活性的影响意义重大。在此,我们提出了部分原位氧化策略来构建面内SnS2-SnO2异质结构及其表面性质,通过精确调节处理温度可以微调两种组分的比例。其中,SnS2 纳米片在 350 ℃ 退火后形成的 SnS2-SnO2 异质结构因其丰富的晶界而呈现出独特的电子结构和表面特性,对 H2S 具有优异的气体传感性能(160 ℃ 时 5 ppm H2S 的 Ra/Rg = 169.81,快速响应和动态恢复(41/101 s),优异的可靠性(σ = 0.01)和传感稳定性(φ = 0.11 %))。值得注意的是,面内异质结构使材料具有丰富的晶界,并有效调节了锡 p-轨道的电子结构,从而促进了活性氧物种(O-(ad))的形成,从而提高了传感性能。我们的工作为设计用于各种先进应用的面内异质结构提供了一个前景广阔的平台。
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引用次数: 0
Quantitative analysis of transferrin uptake into living cells at single-molecule level. 在单分子水平上定量分析活细胞对转铁蛋白的吸收。
IF 8.3 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2025-01-01 Epub Date: 2024-10-18 DOI: 10.1016/j.talanta.2024.127031
Marta Pilz, Tomasz Kalwarczyk, Krzysztof Burdzy, Robert Hołyst

Endocytosis, apart from providing a mechanism for cells to take up nutrients, is the principal route of entry for many nanomedicines. The evaluation of therapeutic delivery efficiency without providing quantitative parameters, like the number of molecules entering the cell and the time of their entry, is very limited. Despite advances in single-molecule methods for in-cell quantitative measurements, they have not become widely used in the study of endocytosis. Their application, however, is challenging owing to the appropriate experimental design and applicable analysis methods. Here, by using an integrated approach based on the multidimensional time-correlated single-photon counting (TCSPC) technique, we demonstrate the quantitative method to measure the time- and concentration-dependent uptake of TRITC-transferrin into living cells with single-molecule sensitivity. The methodology opens possibilities for quantitatively assessing the delivery efficiency of fluorescent molecules into living cells.

内吞作用除了为细胞提供摄取营养物质的机制外,还是许多纳米药物进入细胞的主要途径。如果不提供定量参数,如进入细胞的分子数量和进入细胞的时间,对治疗递送效率的评估就非常有限。尽管用于细胞内定量测量的单分子方法取得了进展,但这些方法尚未广泛应用于内吞研究。然而,由于适当的实验设计和适用的分析方法,这些方法的应用具有挑战性。在这里,我们利用基于多维时间相关单光子计数(TCSPC)技术的综合方法,展示了一种定量方法,以单分子灵敏度测量活细胞对TRITC-铁蛋白随时间和浓度变化的摄取。该方法为定量评估荧光分子进入活细胞的效率提供了可能。
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引用次数: 0
Development and Initial Validation of a Momentary Cannabis Craving Scale Within a Homogeneous Sample of U.S. Emerging Adults. 在美国新兴成年人的同质样本中开发并初步验证了瞬间大麻渴望量表。
IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2025-01-01 Epub Date: 2024-03-21 DOI: 10.1177/10731911241237055
Christal N Davis, Kathryn S Gex, Lindsay M Squeglia, Timothy J Trull, Denis M McCarthy, Nathaniel L Baker, Kevin M Gray, Aimee L McRae-Clark, Rachel L Tomko

Given the popularity and ease of single-item craving assessments, we developed a multi-item measure and compared it to common single-item assessments in an ecological momentary assessment (EMA) context. Two weeks of EMA data were collected from 48 emerging adults (56.25% female, 85.42% White) who frequently used cannabis. Eight craving items were administered, and multilevel factor analyses were used to identify the best fitting model. The resulting scale's factors represented purposefulness/general desire and emotionality/negative affect craving. Convergent validity was examined using measures of craving, cannabis use disorder symptoms, frequency of use, cannabis cue reactivity, cannabis use, negative affect, and impulsivity. The scale factors were associated with cue-reactivity craving, negative affect, impulsivity, and subfactors of existing craving measures. For researchers interested in using a single item to capture craving, one item performed particularly well. However, the new scale may provide a more nuanced assessment of mechanisms underlying craving.

鉴于单项渴求评估的流行和简便,我们开发了一种多项目测量方法,并在生态瞬间评估(EMA)的背景下将其与常见的单项评估进行了比较。我们从 48 名经常吸食大麻的成年人(56.25% 为女性,85.42% 为白人)中收集了两周的 EMA 数据。对八个渴求项目进行了施测,并使用多层次因子分析确定了最佳拟合模型。由此得出的量表因子代表了目的性/一般渴望和情绪性/负面影响渴望。通过对渴求、大麻使用障碍症状、使用频率、大麻线索反应性、大麻使用、负面情绪和冲动性的测量,对收敛有效性进行了检验。量表因子与线索反应渴求、负面情绪、冲动以及现有渴求测量的子因子相关。对于有兴趣使用单个项目来捕捉渴求的研究人员来说,其中一个项目的表现尤为突出。然而,新量表可以对渴望的内在机制进行更细致的评估。
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引用次数: 0
Microgalvanic cell-mediated green synthesis of Cu2O nanocubes with (100) facets for boosting dopamine hydrochloride sensing performance. 微galvanic电池介导的具有(100)面的Cu2O纳米立方体的绿色合成,用于提高盐酸多巴胺的传感性能。
IF 8.3 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2025-01-01 Epub Date: 2024-10-10 DOI: 10.1016/j.talanta.2024.126995
Yiyue Ma, Xintong Wu, Haoyu Pan, Wenxin Zhu, Chengyi Lu, Jianlong Wang

Despite numerous efforts have been made on exploring the preparation, properties and application of Cu2O nanocrystal, there is still a lack of a facile and green synthesis strategy to obtain well-defined Cu2O nanocubes (NCs). And exploration of the superior low-index lattice plane of Cu2O in electrochemical sensing is also inadequate. Herein, we proposed a Ni(OH)2-mediated in-situ synthetic strategy for the preparation of Cu2O NCs enclosed by low-index facets with simple procedure, mild temperature and low energy-consumption. The Ni(OH)2 sites not only facilitated the contact between Cu2+ and the substrate Ni foam (NF), but also can combine with the NF to act as a primary battery to regulate the nucleation and growth rate of Cu2O (100) facets. Benefiting from the high ratio of exposed electroneutral (100) lattice planes of nanocubes, the Cu2O NCs formed on Ni(OH)2-abundant Ni Foam (Cu2O NCs/NFEO) exhibited a wide linear range (3.25-1178.8 μM), a low detection limit (1.86 μM) and a high sensitivity (900 μA mM-1 cm-2) in dopamine hydrochloride (DAH) electrochemical sensing. This work expects to provide more clues about the relationship between different dominant low-index facets of Cu2O NCs and electrochemical sensing performance towards DAH, and thereby contributes to the development of functional materials based on Cu2O nanocrystals with desirable facets.

尽管人们在探索 Cu2O 纳米晶的制备、性能和应用方面做了大量工作,但仍然缺乏一种简便、绿色的合成策略来获得定义明确的 Cu2O 纳米立方体(NCs)。此外,对 Cu2O 优越的低指数晶格面在电化学传感中的应用的探索也不充分。在此,我们提出了一种以 Ni(OH)2 为介导的原位合成策略来制备由低指数晶面包围的 Cu2O NCs,该策略具有操作简单、温度温和、能耗低等优点。Ni(OH)2位点不仅能促进Cu2+与基底泡沫镍(NF)的接触,还能与NF结合,作为原电池调节Cu2O(100)刻面的成核和生长速度。得益于纳米立方体暴露的电中性(100)晶格面的高比例,在富含 Ni(OH)2 的镍泡沫(Cu2O NCs/NFEO)上形成的 Cu2O NCs 在盐酸多巴胺(DAH)电化学传感中表现出了宽线性范围(3.25-1178.8 μM)、低检测限(1.86 μM)和高灵敏度(900 μA mM-1 cm-2)。这项工作有望为 Cu2O NCs 不同优势低指数面与 DAH 电化学传感性能之间的关系提供更多线索,从而有助于开发基于具有理想面的 Cu2O 纳米晶的功能材料。
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引用次数: 0
Near-infrared-driven dual-photoelectrode photoelectrochemical sensing for fumonisin B1: Integrating a photon up-conversion bio-photocathode with an enhanced light-capturing photoanode. 伏马菌素 B1 的近红外驱动双光电阴极光电化学传感:光子上转换生物光电阴极与增强型光捕获光阳极的集成。
IF 8.3 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2025-01-01 Epub Date: 2024-10-14 DOI: 10.1016/j.talanta.2024.127047
Jiang Guo, Xuqiao Liu, Jianqiao Liu, Kai Yan, Jingdong Zhang

Fumonisin B1 (FB1), the most prevalent and highly toxic mycotoxin within the fumonisins family, poses threats to humans, especially in children and infants, even at trace levels. Therefore, it is essential to design an easy and sensitive detection strategy. Herein, a brand-new dual-photoelectrode photoelectrochemical (PEC) sensing platform for FB1 detection under near-infrared irradiation was unveiled. This platform integrated a photon up-conversion bio-photocathode substrate (UCNPs/Au/CuInS2, UCNPs: NaYF4: Yb3+, Er3+, Nd3+) and used a SnO2/SnS2@Bi/Bi2S3 heterojunction photoanode to greatly enhance light capture. Additionally, ZnO coated with polydopamine (ZnO@PDA) was utilized as a signal inhibitor. The restoration of photocurrent occurred due to the strong binding affinity between FB1 and its aptamer (FB1-Apt), facilitating the dissociation of FB1-Apt/ZnO@PDA from the photoelectrode. The PEC sensing performance and the electron transfer process were thoroughly examined. The developed "signal-restoration" PEC aptasensor exhibited a wider dynamic linear range from 1.0 × 10-3 to 1.0 × 102 ng/mL, with a lower limit of detection (0.13 pg/mL). It has demonstrated excellent practical detection performance in unspiked real samples, such as corn paste, with the FB1 enzyme-linked immunosorbent assay (ELISA) Kit serving as a reference, indicating its potential for routine analysis of other mycotoxins. Thus, this research establishes a feasible dual-photoelectrode PEC framework for the effective detection of mycotoxins and other hazardous substances.

伏马菌毒素 B1(FB1)是伏马菌毒素家族中最常见、毒性最强的霉菌毒素,即使在痕量水平也会对人类,尤其是儿童和婴儿造成威胁。因此,设计一种简便灵敏的检测策略至关重要。本文揭示了一种用于在近红外照射下检测 FB1 的全新双光电电极光电化学(PEC)传感平台。该平台集成了光子上转换生物光阴极基底(UCNPs/Au/CuInS2,UCNPs:NaYF4:Yb3+、Er3+、Nd3+),并使用 SnO2/SnS2@Bi/Bi2S3 异质结光电阳极来大大提高光捕获能力。此外,还使用了涂有多巴胺的氧化锌(ZnO@PDA)作为信号抑制剂。光电流的恢复是由于 FB1 与其适配体(FB1-Apt)之间的强结合亲和力促进了 FB1-Apt/ZnO@PDA 与光电极的解离。对 PEC 传感性能和电子传递过程进行了深入研究。所开发的 "信号恢复型 "PEC灵敏传感器的动态线性范围从1.0 × 10-3到1.0 × 102 ng/mL,检测下限为0.13 pg/mL。以 FB1 酶联免疫吸附测定(ELISA)试剂盒为参照物,该传感器在玉米糊等未添加添加剂的真实样品中表现出卓越的实际检测性能,这表明它具有对其他霉菌毒素进行常规分析的潜力。因此,这项研究为有效检测霉菌毒素和其他有害物质建立了一个可行的双光电电极 PEC 框架。
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引用次数: 0
Two-pronged strategy: A mitochondria targeting AIE photosensitizer for hydrogen sulfide detection and type I and type II photodynamic therapy. 双管齐下的战略:一种线粒体靶向 AIE 光敏剂,用于硫化氢检测以及 I 型和 II 型光动力疗法。
IF 8.3 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2025-01-01 Epub Date: 2024-10-18 DOI: 10.1016/j.talanta.2024.127074
Jizhong Shi, Manshan Liang, Yiting Qiu, Jin Zhang, Shihua Wang, Heng Fang, Yongsheng Jiang, Xiaoxia Ye, Yanshu Luo, Zu-Sheng Huang, Yun-Yun Quan

Multifunctional type-I photosensitizers (PSs) for hydrogen sulfide (H2S) detection and photodynamic therapy (PDT) of hypoxia tumors exhibits attractive curative effect but remains a challenging task. Herein, a mitochondria targeted aggregation-induced emission (AIE) photosensitizer TSPy-SS-P was designed and synthesized, which could be used for H2S detection and simultaneously type I and type II PDT. TSPy-SS-P had excellent selectivity and anti-interference abilities for endogenous and exogenous H2S detection in tumor cells. TSPy-SS-P was able to distinguish tumor cells with high level of H2S from normal cells by fluorescence "turn off" response to H2S. In addition, TSPy-SS-P showed type Ⅰ and type Ⅱ reactive oxygen species (ROS) generation ability to effectively ablate hypoxic tumor cells. TSPy-SS-P showed mitochondria targeting capacity which could produce ROS in situ to disrupt mitochondria and promote cell apoptosis. In vivo PDT experiments showcased that TSPy-SS-P had excellent tumor retention capability, effective tumor ablation ability and good biocompatibility. This work provided a two-pronged strategy to design organelles targeted photosensitizers for H2S detection and effective PDT of tumors.

用于硫化氢(H2S)检测和缺氧肿瘤光动力疗法(PDT)的多功能I型光敏剂(PSs)具有诱人的疗效,但仍是一项具有挑战性的任务。本文设计并合成了一种线粒体靶向聚集诱导发射(AIE)光敏剂TSPy-SS-P,它可用于硫化氢检测并同时进行I型和II型PDT。TSPy-SS-P 对肿瘤细胞中内源性和外源性 H2S 的检测具有良好的选择性和抗干扰能力。TSPy-SS-P 能够通过对 H2S 的荧光 "熄灭 "反应将高水平 H2S 的肿瘤细胞与正常细胞区分开来。此外,TSPy-SS-P 还具有生成Ⅰ型和Ⅱ型活性氧(ROS)的能力,能有效消融缺氧的肿瘤细胞。TSPy-SS-P具有线粒体靶向能力,可在原位产生ROS,破坏线粒体,促进细胞凋亡。体内光动力疗法实验表明,TSPy-SS-P具有良好的肿瘤保留能力、有效的肿瘤消融能力和良好的生物相容性。这项工作为细胞器靶向光敏剂的设计提供了一种双管齐下的策略,既能检测 H2S,又能有效地对肿瘤进行局部光疗。
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引用次数: 0
Circular RNAs in coronary heart disease: From molecular mechanism to promising clinical application (Review). 冠心病中的环状 RNA:从分子机制到前景广阔的临床应用(综述)。
IF 8.3 2区 材料科学 Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Pub Date : 2025-01-01 Epub Date: 2024-11-08 DOI: 10.3892/ijmm.2024.5452
Zengguang Fan, Xingxing Yuan, Ye Yuan

Coronary heart disease (CHD) remains a leading cause of morbidity and mortality worldwide, posing a substantial public health burden. Despite advancements in treatment, the complex etiology of CHD necessitates ongoing exploration of novel diagnostic markers and therapeutic targets. Circular RNAs (circRNAs), a distinct class of non‑coding RNAs with a covalently closed loop structure, have emerged as significant regulators in various diseases, including CHD. Their high stability, tissue‑specific expression and evolutionary conservation underscore their potential as biomarkers and therapeutic agents in CHD. This review discusses the current knowledge on circRNAs in the context of CHD and explores the molecular mechanisms by which circRNAs influence the pathophysiology of CHD, including cardiomyocyte death, endothelial injury, vascular dysfunction and inflammation. It also summarizes the emerging evidence highlighting the differential expression of circRNAs in patients with CHD and their potential utilities as non‑invasive diagnostic and prognostic biomarkers and therapeutic targets for this disease.

冠心病(CHD)仍然是全球发病率和死亡率的主要原因,给公共卫生造成了巨大负担。尽管在治疗方面取得了进展,但冠心病的病因复杂,需要不断探索新的诊断标志物和治疗靶点。环状 RNA(circRNA)是一类独特的非编码 RNA,具有共价闭环结构,已成为包括冠心病在内的多种疾病的重要调节因子。它们的高稳定性、组织特异性表达和进化保护凸显了其作为冠心病生物标志物和治疗药物的潜力。本综述讨论了当前有关冠心病循环RNA的知识,并探讨了循环RNA影响冠心病病理生理学的分子机制,包括心肌细胞死亡、内皮损伤、血管功能障碍和炎症。报告还总结了新出现的证据,强调了循环RNA在冠心病患者中的不同表达,以及循环RNA作为非侵入性诊断和预后生物标志物及该疾病治疗靶点的潜在作用。
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引用次数: 0
Denervation‑induced NRG3 aggravates muscle heterotopic ossification via the ErbB4/PI3K/Akt signaling pathway. 去神经诱导的 NRG3 通过 ErbB4/PI3K/Akt 信号通路加剧肌肉异位骨化
IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC Pub Date : 2025-01-01 Epub Date: 2024-10-25 DOI: 10.3892/mmr.2024.13374
Lin Ma, Xia Kang, Jindong Tan, Yunjiao Wang, Xiao Liu, Hong Tang, Lin Guo, Kanglai Tang, Xuting Bian

Peripheral nerve injury exacerbates progression of muscle heterotopic ossification (HO) and induces changes in expression of local cytokines in muscle tissue. The objective of the present study was to assess the impact of peripheral nerve injury on muscle HO development and the mechanism of cytokine modulation. A mouse model of gastrocnemius muscle HO was established and the sciatic nerve cut to simulate peripheral nerve injury. To evaluate the underlying factors contributing to the exacerbation of muscle HO resulting from denervation, fresh muscle tissue was collected and micro‑computed tomography, histochemical staining, RNA‑sequencing, reverse transcription‑quantitative PCR, Western blot, muscle tissue chip array were performed to analyze the molecular mechanisms. Sciatic nerve injury exacerbated HO in the gastrocnemius muscle of mice. Moreover the osteogenic differentiation of nerve‑injured muscle tissue‑derived fibro‑adipogenic progenitors (FAPs) increased in vitro. The expression of neuregulin 3 (NRG3) was demonstrated to be increased after nerve injury by muscle tissue chip array. Subsequent transcriptome sequencing analysis of muscle tissue revealed an enrichment of the PI3K/Akt pathway following nerve injury and an inhibitor of the PI3K/Akt pathway reduced the osteogenic differentiation of FAPs. Mechanistically, in vitro, peripheral nerve injury increased secretion of NRG3, which, following binding to ErbB4 on the cell surface of FAPs, promoted expression of osteogenesis‑associated genes via the PI3K/Akt signaling pathway, thus contributing to osteogenic differentiation of FAPs. In vivo, inhibition of the PI3K/Akt pathway effectively protected against muscle HO induced by peripheral nerve injury in mice. The present study demonstrated that the regulatory roles of NRG3 and the PI3K/Akt pathway in peripheral nerve injury exacerbated muscle HO and highlights a potential therapeutic intervention for treatment of peripheral nerve injury‑induced muscle HO.

周围神经损伤会加剧肌肉异位骨化(HO)的进展,并诱导肌肉组织中局部细胞因子的表达发生变化。本研究的目的是评估周围神经损伤对肌肉异位骨化发展的影响以及细胞因子的调节机制。研究人员建立了小鼠腓肠肌HO模型,并切断坐骨神经以模拟周围神经损伤。为了评估神经支配导致肌肉HO加重的潜在因素,研究人员采集了小鼠的新鲜肌肉组织,通过微计算机断层扫描、组织化学染色、RNA测序、逆转录定量PCR、Western印迹、肌肉组织芯片阵列等方法分析其分子机制。结果表明,坐骨神经损伤加剧了小鼠腓肠肌的HO。此外,神经损伤肌肉组织衍生的成纤维-成脂肪祖细胞(FAPs)体外成骨分化增加。肌肉组织芯片阵列证明神经损伤后神经胶质蛋白3(NRG3)的表达增加。随后的肌肉组织转录组测序分析表明,神经损伤后PI3K/Akt通路富集,PI3K/Akt通路抑制剂降低了FAPs的成骨分化。从机制上讲,在体外,周围神经损伤增加了NRG3的分泌,NRG3与FAPs细胞表面的ErbB4结合后,通过PI3K/Akt信号通路促进成骨相关基因的表达,从而促进FAPs的成骨分化。在体内,抑制 PI3K/Akt 通路可有效保护小鼠免受周围神经损伤引起的肌肉 HO 的损伤。本研究证明了NRG3和PI3K/Akt通路在周围神经损伤加重肌肉HO中的调控作用,并强调了治疗周围神经损伤诱导的肌肉HO的潜在治疗干预措施。
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