Tissue & cell最新文献_第9页

Phosphocreatine ameliorates hepatocellular apoptosis mediated by protecting mitochondrial damage in liver ischemia/reperfusion injury through inhibiting TLR4 and Agonizing Akt Pathway 磷酸肌酸通过抑制 TLR4 和激动 Akt 通路，改善肝缺血再灌注损伤中由保护线粒体损伤介导的肝细胞凋亡

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2024-10-30 DOI: 10.1016/j.tice.2024.102599

Fu Han Wang , Eskandar Qaed , Waleed Aldahmash , Mueataz A. Mahyoub , Zhongyuan Tang , Peng Chu , Ze Yao Tang

Hepatic ischemia/reperfusion (HI/R) presents significant challenges in surgical liver transplantation and hepatic ischemic shock, with few effective clinical preventive measures available. This study explores the potential protective effects and underlying mechanisms of phosphocreatine (PCr) in the context of HI/R. We established an in vitro ischemia/reperfusion model using hepatocellular carcinoma HepG2 cells and normal liver L02 cells. For in vivo assessments, C57BL/6 mice were subjected to the HI/R model to evaluate the impact of PCr on liver protection. PCr pretreatment significantly improved liver cell survival rates, maintained mitochondrial membrane potential (MMP), reduced apoptosis, and alleviated oxidative damage and inflammatory responses. Importantly, PCr exerted its protective effects by downregulating TLR4 and activating the Akt signaling pathway, which suppressed inflammation, mitigated oxidative stress, inhibited apoptosis, and modulated key biomarkers, including ALT, AST, IL-6, IL-1β, TNF-α, SOD, MDA, and reactive oxygen species (ROS). Western blot analyses demonstrated PCr's anti-inflammatory effects through the regulation of UCP2, Cyp-D, Cyt-C, and PGC-1α, thereby preserving mitochondrial structure and function, maintaining MMP, and regulating membrane pores. Transmission electron microscopy further highlighted PCr's role in sustaining mitochondrial integrity. In conclusion, our findings suggest that PCr helps maintain mitochondrial homeostasis by intervening in the TLR4 inflammatory pathway and activating the Akt signaling pathway, ultimately reducing liver injury. This study offers new insights and potential treatment strategies for HI/R, providing valuable guidance for future clinical applications.

肝脏缺血/再灌注（HI/R）给外科肝移植和肝缺血性休克带来了巨大挑战，而目前有效的临床预防措施却很少。本研究探讨了磷酸肌酸（PCr）对 HI/R 的潜在保护作用及其内在机制。我们使用肝癌 HepG2 细胞和正常肝脏 L02 细胞建立了体外缺血/再灌注模型。为了进行体内评估，我们对 C57BL/6 小鼠进行了 HI/R 模型，以评估 PCr 对肝脏保护的影响。PCr 预处理明显提高了肝细胞存活率，维持了线粒体膜电位（MMP），减少了细胞凋亡，减轻了氧化损伤和炎症反应。重要的是，PCr 通过下调 TLR4 和激活 Akt 信号通路发挥其保护作用，从而抑制炎症、减轻氧化应激、抑制细胞凋亡，并调节关键生物标志物，包括谷丙转氨酶（ALT）、谷草转氨酶（AST）、IL-6、IL-1β、TNF-α、SOD、MDA 和活性氧（ROS）。Western 印迹分析表明，PCr 可通过调节 UCP2、Cyp-D、Cyt-C 和 PGC-1α 发挥抗炎作用，从而保护线粒体结构和功能、维持 MMP 和调节膜孔。透射电子显微镜进一步凸显了 PCr 在维持线粒体完整性方面的作用。总之，我们的研究结果表明，PCr 可通过干预 TLR4 炎症通路和激活 Akt 信号通路来帮助维持线粒体的稳态，最终减轻肝损伤。这项研究为 HI/R 提供了新的见解和潜在的治疗策略，为未来的临床应用提供了宝贵的指导。

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引用次数: 0

Evaluating the involvement and mutual interaction of wbp2 and yap in embryogenesis with an emphasis on liver function in zebrafish embryos 以斑马鱼胚胎的肝功能为重点，评估 wbp2 和 yap 在胚胎发育过程中的参与和相互作用

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2024-10-29 DOI: 10.1016/j.tice.2024.102600

Nikita Lykov , Huiling Wang , Mogellah John Panga, Zhanxiang Du, Ziyi Chen, Shitian Chen, Lin Zhu, Ye Zhao

The Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) play complex roles in liver health, influencing processes such as fibrosis, cancer development, and regeneration. WW domain binding protein-2 (WBP2) primarily enhances the co-translational activity of YAP/TAZ, which is crucial for the progression of liver diseases. Despite existing knowledge, the specific functions of WBP2 and its interactions with YAP remain inadequately understood. This study investigates the expression levels of WBP2 in zebrafish embryos and its molecular interaction with YAP. We employed morpholino-mediated knockdown of wbp2 and yap, followed by assessments of liver histology, immunofluorescence, and co-immunoprecipitation. Subsequently, RNA sequencing analyses were conducted to elucidate the signaling pathways and mechanisms underlying the interplay between YAP and WBP2 in liver injury. Our findings highlight the significant interaction between WBP2 and YAP, emphasizing their potential as therapeutic targets for liver diseases.

Yes相关蛋白（YAP）和具有PDZ结合基调的转录辅激活因子（TAZ）在肝脏健康中发挥着复杂的作用，影响着肝纤维化、癌症发展和再生等过程。WW结构域结合蛋白-2（WBP2）主要增强YAP/TAZ的共翻译活性，这对肝脏疾病的进展至关重要。尽管已有相关知识，但人们对 WBP2 的具体功能及其与 YAP 的相互作用仍不甚了解。本研究调查了 WBP2 在斑马鱼胚胎中的表达水平及其与 YAP 的分子相互作用。我们采用吗啉诺介导的方法敲除了 WBP2 和 YAP，然后对肝脏组织学、免疫荧光和共免疫沉淀进行了评估。随后进行了 RNA 测序分析，以阐明 YAP 和 WBP2 在肝损伤中相互作用的信号通路和机制。我们的研究结果突显了 WBP2 和 YAP 之间的重要相互作用，强调了它们作为肝病治疗靶点的潜力。

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引用次数: 0

Dose and time dependent morphodynamic changes in the ovary of nano-nickel treated rats A SEM study 纳米镍处理过的大鼠卵巢中与剂量和时间相关的形态变化 SEM 研究

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2024-10-29 DOI: 10.1016/j.tice.2024.102598

Meenu Singh, Yeshvandra Verma, SV S. Rana

Aims

Present study demonstrates dose and time dependent effects of NiONPs (<30 nm) on the ovaries of Wistar rat.

Methods

Female rats were gavaged NiONPs or NiOMPs (5 mg/kg b.w.) for 24 h, 15 days and 30 days, euthanized and ovaries thus removed were analyzed for nickel bioaconcentration and processed for scanning electron microscopy. Serum samples were analyzed to compare the effects of nickel nano & microparticles on progesterone and estradiol values.

Results

Results confirmed the bioaccumulation of Ni in ovarian tissue. Its concentration was higher in NiONPs treated rats than NiOMPs treated rats. Progesterone level increased whereas estradiol values decreased in NiONPs and NiOMPs treated rats. SEM results also exhibited dose dependent effects on the morphology of corpoluteal complex. The structural changes varied from formation of blebs to distorted microvilli and germinal epithelium.

Conclusion

It is hypothesized that NiONPs/NiOMPs are biodegraded into smaller fragments that conjugate with amino acids and or alter downstream signaling pathways, generate ROS and modulate protein structure activity relationships. Finally, these processes manifest into morphological alterations in the ovary. Biopersistence of nickel in female reproductive system may compromise with fertility and reproductive performance of exposed population.

方法分别给雌性大鼠灌胃NiONPs或NiOMPs（5毫克/千克体重）24小时、15天和30天，然后安乐死，取出卵巢分析镍的生物累积浓度并进行扫描电子显微镜检查。对血清样本进行分析，以比较纳米镍& 微颗粒对孕酮和雌二醇值的影响。结果证实了镍在卵巢组织中的生物蓄积性，镍纳米微粒处理大鼠的镍浓度高于镍氧化微粒处理大鼠。NiONPs和NiOMPs处理大鼠的孕酮水平升高，而雌二醇值降低。扫描电子显微镜（SEM）结果也显示了剂量对冠突复合体形态的影响。结论据推测，NiONPs/NiOMPs 被生物降解成更小的片段，这些片段与氨基酸结合，或改变下游信号通路，产生 ROS 并调节蛋白质结构和活性关系。最后，这些过程表现为卵巢的形态改变。镍在女性生殖系统中的生物持久性可能会影响接触人群的生育能力和生殖能力。

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引用次数: 0

Comparative microanatomy and histology of spinal and cerebral veins: Implications for dural arteriovenous fistula clinical presentations 脊髓静脉和大脑静脉的显微解剖学和组织学比较：对硬脑膜动静脉瘘临床表现的启示

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2024-10-28 DOI: 10.1016/j.tice.2024.102597

Etienne Lefevre , Mégane Le Quang , Vincent Jecko , Maxime Nogues , Dominique Liguoro , Franck Bielle , Paul Roblot

Cranial dural arteriovenous fistulas (DAVFs) that display cortical venous drainage are at risk of hemorrhage, unlike spinal DAVFs, which seldom bleed. The underlying mechanism for this difference is poorly understood. We hypothesized that cerebral veins are more fragile than spinal veins due to differences in histologic compositions. Thus, spinal and cerebral veins from five formalin-fixed human cadavers were examined through macroscopic and histological analysis, using hematoxylin, eosin and safran (HES), and orcein stains to compare them. Twenty-four cerebral veins and thirteen spinal veins were analyzed. The mean diameter of the cerebral veins was 1.02 ± 0.59 mm, while that of spinal veins was 0.52 ± 0.26 mm (p = 0.003). The mean thickness of cerebral veins was similar to their spinal counterparts (0.09 ± 0.07 mm vs 0.06 ± 0.02 mm; p = 0.12). The mean diameter-to-thickness ratio was 13.76 ± 6.05 mm for cerebral veins and 10.06 ± 7.23 mm for spinal veins (p = 0.023). In most of the analyzed vessels, the venous wall was composed of endothelial cells resting on layers of smooth muscle, separated by elastica lamina. Cerebral and spinal veins exhibit distinct calibers while maintaining comparable wall thicknesses, resulting in a greater diameter-to-thickness ratio for cerebral veins compared to spinal veins. This difference may after their resistance to pressure. Furthermore, variations in the transparietal pressure gradient between cranial and spinal subarachnoid space, along with differences in arterial blood flow through the fistulous veins, might contribute to the observed differences in clinical presentation.

显示皮质静脉引流的颅硬脑膜动静脉瘘（DAVF）有出血的风险，而脊髓动静脉瘘（DAVF）很少出血。造成这种差异的潜在机制尚不清楚。我们假设，由于组织学成分的差异，脑静脉比脊髓静脉更脆弱。因此，我们对五具福尔马林固定的人体尸体上的脊髓静脉和大脑静脉进行了宏观和组织学分析，并使用苏木精、伊红和沙夫兰（HES）以及orcein染色法对它们进行了比较。共分析了二十四条脑静脉和十三条脊静脉。脑静脉的平均直径为 1.02 ± 0.59 毫米，而脊静脉的平均直径为 0.52 ± 0.26 毫米（P = 0.003）。脑静脉的平均厚度与脊静脉相似（0.09 ± 0.07 mm vs 0.06 ± 0.02 mm; p = 0.12）。脑静脉的平均直径-厚度比为 13.76 ± 6.05 毫米，脊静脉为 10.06 ± 7.23 毫米（p = 0.023）。在大多数被分析的血管中，静脉壁由内皮细胞和平滑肌层组成，平滑肌层之间由弹性层隔开。脑静脉和脊髓静脉的口径不同，但管壁厚度相当，因此脑静脉的直径与厚度之比大于脊髓静脉。这种差异可能会影响它们的抗压能力。此外，颅内和脊髓蛛网膜下腔之间跨椎压力梯度的变化，以及动脉血流流经瘘管静脉的差异，也可能是造成临床表现差异的原因。

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引用次数: 0

ω-9 monounsaturated fatty acids in Sapindus mukorossi seed oil enhance calcium deposition expression of Wharton’s jelly mesenchymal stem cells 无患子种子油中的ω-9 单不饱和脂肪酸可增强沃顿果冻间充质干细胞的钙沉积表达

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2024-10-25 DOI: 10.1016/j.tice.2024.102595

Yu-Xuan Huang , Yen-Chung Lin , Chin-Kai Lin , Haw-Ming Huang

Promoting osteogenesis is crucial to improve successful bone regeneration in bone tissue engineering. Several studies on osteogenesis have reported positive effects of ω-9 monounsaturated fatty acids (MUFA) on bone regeneration. This study examined the potential of ω-9 monounsaturated fatty acid abundant seed oil mechanically extracted from Sapindus mukorossi (S. mukorossi) fruit to improve osteogeneses. After showing the presence of ω-9 MUFA in S. mukorossi seed oil (SM oil) through GC-MS spectrum analysis, the proliferation and differentiation of human umbilical cord Wharton’s jelly mesenchymal stem cells (WJMSCs) under SM treatment was evaluated. Our results indicate that WJMSC differentiation was induced by adding an osteogenesis-induced medium combined with SM oil. A high level of calcium deposition expression in WJMSCs induced by SM oil appears to be due to the effect of oleic acid and eicosenoic acid, both of which are ω-9 monounsaturated fatty acids. In addition, we found major contributors of SM oil-promoted WJMSC osteogenesis to be extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinase (JNKs), and the p38 MAPK pathway. The enhancement of WJMSC osteogenesis via ERK/MAPK pathways as demonstrated by qPCR analysis indicates the promise of SM oil for stem cell-based bone tissue engineering applications.

在骨组织工程学中，促进成骨是提高骨再生成功率的关键。一些关于骨生成的研究报告称，ω-9 单不饱和脂肪酸（MUFA）对骨再生有积极作用。本研究考察了从无患子（S. mukorossi）果实中机械提取的富含ω-9 单一不饱和脂肪酸的种子油改善骨生成的潜力。在通过气相色谱-质谱（GC-MS）分析表明无患子种子油（SM 油）中含有ω-9 MUFA 后，评估了人脐带沃顿果冻间充质干细胞（WJMSCs）在 SM 处理下的增殖和分化情况。我们的研究结果表明，通过添加结合了 SM 油的成骨诱导培养基，WJMSC 得到了诱导分化。SM油诱导的WJMSCs中高水平的钙沉积表达似乎是由于油酸和二十烯酸的作用，这两种酸都是ω-9单不饱和脂肪酸。此外，我们发现SM油促进WJMSC成骨的主要因素是细胞外信号调节激酶（ERKs）、c-Jun N-末端激酶（JNKs）和p38 MAPK通路。qPCR分析表明，通过ERK/MAPK途径促进WJMSC成骨，表明SM油有望用于基于干细胞的骨组织工程应用。

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引用次数: 0

Mesenchymal stem cells alleviate autoimmune thyroiditis by modulating macrophage phenotypes and through influencing the STING pathway 间充质干细胞通过调节巨噬细胞表型和影响STING通路缓解自身免疫性甲状腺炎

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2024-10-25 DOI: 10.1016/j.tice.2024.102596

Haoran Ding , Jiabo Qin , Zhijian Liu , Xianbiao Shi , Wenxian Guan , Jianfeng Sang

Background

Hashimoto's thyroiditis is a chronic autoimmune inflammatory disease with a high prevalence and currently lacks effective treatment options. Previous preclinical and clinical trials have established mesenchymal stem cells (MSCs) as a promising therapeutic approach; however, there is limited research on MSC treatment for Hashimoto's thyroiditis, and the underlying molecular mechanisms remain unclear.

Methods

MSCs isolated from 4 to 6-week-old Lewis rats were employed for thyroiditis treatment. The efficacy of MSCs was assessed through histological and serological parameters. Molecular mechanisms of MSC therapy for Hashimoto's thyroiditis were explored by examining macrophage presence within thyroid tissue and relevant pathways.

Results

In this study, we observed elevated oxidative stress and endoplasmic reticulum stress within the thyroid tissue of Hashimoto's thyroiditis patients, and MSC therapy effectively mitigated this process. Furthermore, we found that the therapeutic potential of MSCs in the EAT model depended on the STING pathway. MSCs reduced endoplasmic reticulum stress and inflammasome levels within the thyroid tissue by modulating the STING pathway. Additionally, MSCs inhibited the expression of IRE1α in thyroid tissue macrophages, thereby reducing the polarization of M1-type macrophages

Conclusions

The STING pathway appears to be a crucial mechanism by which MSCs modulate macrophage polarization in thyroid tissue, offering a potential treatment for thyroiditis.

背景桥本氏甲状腺炎是一种慢性自身免疫性炎症疾病，发病率很高，目前缺乏有效的治疗方法。以往的临床前和临床试验已证实间充质干细胞（MSCs）是一种很有前景的治疗方法；然而，目前关于间充质干细胞治疗桥本氏甲状腺炎的研究还很有限，其潜在的分子机制仍不清楚。通过组织学和血清学参数评估了间充质干细胞的疗效。结果在这项研究中，我们观察到桥本氏甲状腺炎患者的甲状腺组织中氧化应激和内质网应激升高，而间叶干细胞治疗有效地缓解了这一过程。此外，我们还发现间充质干细胞在EAT模型中的治疗潜力取决于STING通路。间充质干细胞通过调节STING通路降低了甲状腺组织内的内质网应激和炎性体水平。结论 STING通路似乎是间充质干细胞调节甲状腺组织中巨噬细胞极化的一个重要机制，为甲状腺炎提供了一种潜在的治疗方法。

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引用次数: 0

Coloprotective effects of chebulic myrobalan extract by regulation of AMPK-SIRT1 signaling: A pharmacological and histopathological evaluation 诃子肉苁蓉提取物通过调节 AMPK-SIRT1 信号发挥结肠保护作用：药理学和组织病理学评估

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2024-10-23 DOI: 10.1016/j.tice.2024.102592

Mandeep Kaur , Debanjan Chatterjee , Shivani Singla , Inder Pal Singh , Gopabandhu Jena

Ulcerative colitis is a chronic, refractory disease caused by dysregulation of mucosal immune responses to the indigenous bacterial flora as well as genetic and environmental variables. Recently, there has been increasing interest towards the use of herbal medicines for the treatment of ulcerative colitis and the potential benefits could lie in their high patient acceptability, effectiveness, safety, and relatively low cost. It has been reported that Chebulic myrobalan (Terminalia chebula) exhibits anti-oxidant, anti-inflammatory and immunomodulatory properties. The present study was designed to evaluate the protective potential of extract of dried fruit pulp of T. chebula against Dextran sulphate sodium (DSS)-induced ulcerative colitis in male BALB/c mice. Three cycles of DSS (3 % w/v in drinking water), each followed by a seven-day remission phase were used to induce ulcerative colitis in mice. Animals were treated with T. chebula (300 mg/kg and 600 mg/kg) starting from I^st remission period to the end of the study. Different biochemical assays, histological evaluation and molecular analysis were performed to evaluate the protective effects of T. chebula extract in DSS induced colitis. T. chebula modulates the expression of nuclear factor kappa B, adenosine monophosphate kinase, tumour necrosis factor-alpha, sirtuin 1 and interleukin-1β. Furthermore, it also accorded coloprotective effects against DNA damage, apoptosis, inflammation and nitrosative stress. Finally, it was found that the high dose of the T. chebula extract (600 mg/kg) was found to be more effective than a low dose (300 mg/kg) in restoring the ulcerative colitis induced colonic damage.

溃疡性结肠炎是一种慢性难治性疾病，是由于粘膜对本地细菌菌群的免疫反应失调以及遗传和环境变量引起的。最近，人们对使用草药治疗溃疡性结肠炎的兴趣日益浓厚，草药的潜在优势在于患者接受度高、有效、安全且成本相对较低。有报道称，诃子肉苁蓉（Terminalia chebula）具有抗氧化、抗炎和免疫调节的特性。本研究旨在评估诃子干果肉提取物对硫酸钠右旋糖酐（DSS）诱导的雄性 BALB/c 小鼠溃疡性结肠炎的保护潜力。用三个周期的右旋糖酐硫酸钠（在饮用水中的浓度为 3 % w/v）诱导小鼠患上溃疡性结肠炎，每个周期后有七天的缓解期。从第一个缓解期开始到研究结束，小鼠分别接受了300毫克/千克和600毫克/千克的星云草治疗。研究人员进行了不同的生化测定、组织学评价和分子分析，以评估星云树提取物对DSS诱导的结肠炎的保护作用。星云树提取物能调节核因子卡巴B、单磷酸腺苷激酶、肿瘤坏死因子-α、sirtuin 1和白细胞介素-1β的表达。此外，它还具有保护结肠免受 DNA 损伤、细胞凋亡、炎症和亚硝酸应激的作用。最后，研究发现，在恢复溃疡性结肠炎引起的结肠损伤方面，高剂量（600 毫克/千克）比低剂量（300 毫克/千克）更有效。

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引用次数: 0

Hepatoprotective effect of silymarin-chitosan nanocomposite against aluminum-induced oxidative stress, inflammation, and apoptosis 水飞蓟素-壳聚糖纳米复合材料对铝诱导的氧化应激、炎症和细胞凋亡的肝保护作用

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2024-10-22 DOI: 10.1016/j.tice.2024.102591

Fatma M. El-Demerdash , Manal M. Ahmed , Wenyi Kang , Tarek M. Mohamed , Aliaa M. Radwan

Aluminum (Al) is abundant in the environment, and its toxicity is attributed to free radical formation and subsequent oxidative stress. While silymarin is a well-known antioxidant, its low water solubility and bioavailability limit its therapeutic effects. This study was designated to formulate silymarin chitosan nanoparticles (SM-CS-NPs) and evaluate its ameliorative effect against hepatotoxicity induced by aluminum chloride (AlCl₃). SM-CS-NPs were prepared by ionotropic gelation method and characterized using different techniques. Rats were distributed into six groups (n=7/group), control, silymarin (SM; 15 mg/kg B.W), silymarin-chitosan nanoparticles (SM-CS-NPs; 15 mg/kg), aluminum chloride (AlCl₃, 34 mg/kg), SM or SM-CS-NPs administrated orally one hour before the treatment with AlCl₃ for 30 days, respectively. Results showed that supplementation of SM-CS-NPs or SM solo improved the antioxidant state and reduced oxidative stress. On the other hand, the pretreatment with SM-CS-NPs or SM followed by AlCl₃ significantly restored liver functions (AST, ALT, ALP, LDH, total protein, albumin, globulin, and bilirubin) and modulated oxidative stress biomarkers (TBARS and H₂O₂), with improved cellular antioxidant defense (SOD, CAT, GPx, GR, GST, and GSH) and maintained normal liver histological structure compared to rats treated with AlCl₃ alone. Furthermore, they alleviated the inflammation and apoptosis by downregulating the expression level of COX-2, caspase-3, and TNFα. This ameliorative effect was stronger with silymarin nanoform than in bulk-state silymarin. According to the findings, silymarin preparation in nanoform boosts its ameliorative and protective effects against AlCl₃ hepatotoxicity.

铝（Al）在环境中含量丰富，其毒性归因于自由基的形成和随后的氧化应激。水飞蓟素是一种著名的抗氧化剂，但其水溶性和生物利用度较低，限制了其治疗效果。本研究旨在制备水飞蓟素壳聚糖纳米颗粒（SM-CS-NPs），并评估其对氯化铝（AlCl3）诱导的肝毒性的改善作用。SM-CS-NPs采用离子凝胶法制备，并使用不同的技术对其进行表征。将大鼠分为六组（n=7/组），分别为对照组、水飞蓟素（SM；15 mg/kg B.W）组、水飞蓟素-壳聚糖纳米颗粒（SM-CS-NPs；15 mg/kg）组、氯化铝（AlCl3，34 mg/kg）组、在氯化铝治疗前一小时口服SM或SM-CS-NPs组，连续30天。结果表明，补充 SM-CS-NPs 或 SM 单体可改善抗氧化状态，降低氧化应激。另一方面，与单独使用 AlCl3 的大鼠相比，使用 SM-CS-NPs 或 SM 后再使用 AlCl3 的大鼠能显著恢复肝功能（AST、ALT、ALP、LDH、总蛋白、白蛋白、球蛋白和胆红素），调节氧化应激生物标志物（TBARS 和 H2O2），提高细胞抗氧化防御能力（SOD、CAT、GPx、GR、GST 和 GSH），维持正常的肝组织学结构。此外，它们还通过下调 COX-2、caspase-3 和 TNFα 的表达水平，缓解了炎症和细胞凋亡。与散装水飞蓟素相比，纳米水飞蓟素的这种改善作用更强。研究结果表明，以纳米形式制备的水飞蓟素可增强其对氯化铝肝毒性的改善和保护作用。

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引用次数: 0

Human amniotic membrane hydrogel loaded with exosomes derived from human placental mesenchymal stem cells accelerate diabetic wound healing 人羊膜水凝胶负载有提取自人胎盘间充质干细胞的外泌体，可加速糖尿病伤口愈合。

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2024-10-21 DOI: 10.1016/j.tice.2024.102590

Leila Varyani , Niloofar Ahmadpanah , Rozhin Kasiri , Shadman Shahzamani , Simindokht Tomraee , Aref Jafari , Hosna Mirjalili , Nassim Seyedi Asl

Diabetic wound is one of the most common and costly complication in diabetic patients. Hence, numerous studies have been carried out to discover a suitable approach to enhance the process of wound healing. Biological hydrogels are commonly utilized for wound healing due to their suitable properties among different materials available. Herein we investigated whether human amniotic membrane hydrogel (hAMH) loaded with human placental mesenchymal stem cells (PlaMSCs)-derived exosomes could promote healing in diabetic rats. Sixty diabetic rats were randomly assigned into the control group, hAMH group, exosome group, and hAMH+Exosome group. According to the phases of wound healing, sampling was done on days 7, 14, and 21 for further assessments. Our findings showed a significant increase in wound contraction rate, new epidermal length, fibroblast and blood vessel count, collagen density, and the levels of antioxidative factors (GSH, SOD, and CAT) in the treatment groups compared to the control group, with more pronounced effects observed in the hAMH+Exosome group. Furthermore, the levels of bFGF and VEGF gene expression significantly increased in each treatment group when compared to the control group, with the highest levels observed in the hAMH+Exosome group. This occurred as the hAMH+Exosome group showed a greater decrease in neutrophil count, the expression of TNF-α and IL-1β genes, and the levels of an oxidative factor (MDA) compared to the other groups. In summary, the combination of hAMH and PlaMSCs-derived exosomes was determined to have a more significant effect on healing diabetic wounds.

糖尿病伤口是糖尿病患者最常见、最昂贵的并发症之一。因此，人们开展了大量研究，以找到一种合适的方法来促进伤口愈合。生物水凝胶因其适用于不同材料的特性，通常被用于伤口愈合。在此，我们研究了负载人胎盘间充质干细胞（PlaMSCs）衍生的外泌体的人羊膜水凝胶（hAMH）是否能促进糖尿病大鼠的伤口愈合。60只糖尿病大鼠被随机分为对照组、hAMH组、外泌体组和hAMH+外泌体组。根据伤口愈合的不同阶段，分别在第 7 天、第 14 天和第 21 天取样进行进一步评估。我们的研究结果表明，与对照组相比，治疗组的伤口收缩率、新表皮长度、成纤维细胞和血管数量、胶原蛋白密度以及抗氧化因子（GSH、SOD 和 CAT）水平都有明显提高，其中 hAMH+Exosome 组的效果更明显。此外，与对照组相比，各治疗组的 bFGF 和 VEGF 基因表达水平均显著升高，其中 hAMH+Exosome 组的水平最高。这是因为与其他组相比，hAMH+Exosome 组的中性粒细胞计数、TNF-α 和 IL-1β 基因表达以及氧化因子（MDA）水平下降幅度更大。总之，hAMH和PlaMSCs衍生外泌体的组合对糖尿病伤口的愈合具有更显著的效果。

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引用次数: 0

Ling-Gui-Zhu-Gan decoction inhibits cardiomyocyte pyroptosis via the NLRP3/Caspase-1 signaling pathway 苓桂术甘汤通过NLRP3/Caspase-1信号通路抑制心肌细胞脓毒症。

IF 2.7 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2024-10-20 DOI: 10.1016/j.tice.2024.102588

Xiao-ni Zhao , Hui-min Ding , Yao-yao Ma , Liang Wang , Peng Zhou

Objective

The objective of this study was to investigate the protective mechanism of Ling-Gui-Zhu-Gan decoction (LGZGD) against LPS-ATP-induced pyroptosis in H9c2 cells.

Methods

LPS and ATP were used to induce pyroptosis in the H9c2 cell, and the cells were divided into the control, model and LGZGD groups. LDH level was detected using a colorimetric assay. ELISA was used to detect the expressions of IL-1β. Flow cytometry was utilized to observe apoptosis, while Hoechst/PI staining was used to detect pyroptosis. Immunofluorescence was employed to observe the expression levels of NLRP3 in cardiomyocytes, and RT-PCR was used to detect NLRP3, Caspase-1, GSDMD, and ASC mRNA expression. The cells were separated into seven groups: control, model, LGZGD, MCC950, LGZGD+MCC950, Nigericin and LGZGD+Nigericin. The mRNA and protein expressions were determined by RT-PCR and Western blot.

Results

LPS (10 μg/mL) for 12 h and ATP (8 mM) for 2 h were used as modeling condition. LGZGD demonstrated a significant reduction in LDH, and IL-1β levels (P<0.05, P<0.01). LGZGD dramatically reduced apoptosis rate, inhibited pyroptosis, decreased the fluorescence expressions of NLRP3, and reduced the mRNA expressions of NLRP3, ASC, Caspase-1, and GSDMD (P<0.01). Further mechanism studies showed that NLRP3, ASC, Caspase-1, and GSDMD decreased significantly when combined with NLRP3 inhibitor MCC950. Furthermore, LGZGD was able to effectively reverse the upregulation of protein and gene expression of Nigericin group (P<0.01).

Conclusion

LGZGD inhibits LPS-ATP-induced pyroptosis in H9c2 cell via the NLRP3/Caspase-1 signaling pathway.

研究目的本研究旨在探讨灵桂术甘汤（LGZGD）对LPS-ATP诱导的H9c2细胞脓毒症的保护机制：方法：用LPS和ATP诱导H9c2细胞发生热休克，将细胞分为对照组、模型组和LGZGD组。用比色法检测 LDH 水平。用 ELISA 检测 IL-1β 的表达。流式细胞术用于观察细胞凋亡，Hoechst/PI 染色用于检测细胞凋亡。免疫荧光技术用于观察心肌细胞中 NLRP3 的表达水平，RT-PCR 技术用于检测 NLRP3、Caspase-1、GSDMD 和 ASC mRNA 的表达。将细胞分为七组：对照组、模型组、LGZGD组、MCC950组、LGZGD+MCC950组、尼格瑞辛组和LGZGD+尼格瑞辛组。通过 RT-PCR 和 Western 印迹检测 mRNA 和蛋白质的表达：LPS（10 μg/mL）作用12 h，ATP（8 mM）作用2 h作为模型条件。LGZGD可显著降低LDH和IL-1β水平（PConclusion：LGZGD可通过NLRP3/Caspase-1信号通路抑制LPS-ATP诱导的H9c2细胞的脓毒症。

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引用次数: 0