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Adipose tissue- derived mesenchymal stem cells versus puerarin for ameliorating nicotine- induced pancreatic fibrosis in rats 脂肪组织源性间充质干细胞与葛根素对尼古丁诱导大鼠胰腺纤维化的改善作用。
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2025-12-26 DOI: 10.1016/j.tice.2025.103295
Heba F. Ibrahim , Eman H. Thabet , Sara Assem , Basma Mady , Soha Elatrebi , Manal Ahmed Ali , Eiman I. Zaki
Chronic pancreatitis is a critical health problem that is usually complicated by pancreatic fibrosis and diabetes mellitus. Nicotine is a considerable etiological risk factor for this condition. Our research was constructed to explore and compare between the possible therapeutic roles of adipose tissue- derived mesenchymal stem cells (AT- MSCs) and puerarin (Pue) in improving nicotine-induced pancreatic fibrosis. Rats were randomly distributed into: group I; control rats and group II; nicotine- treated rats. Group II was further divided into; model, AT-MSCs- treated, Pue-treated and withdrawal groups. Weight gain study and intraperitoneal glucose tolerance tests were assessed. Pancreatic tissue was processed for measurement of amylase, lipase, interleukin- 6, malondialdehyde and superoxide dismutase. Furthermore, quantitative RT-PCR of caspase-3, transforming growth factor-beta1 (TGF- β1), alpha-smooth muscle actin (α-SMA) and collagen I, was performed. Histopathological, immunohistochemical and ultra-structural examinations were conducted as well. We found that administration of AT- MSCs and Pue helped to increase insulin secretion and suppress inflammatory oxidative stress parameters. In addition, apoptosis and fibrosis were receded through declining of caspase-3 and elements of TGF-β1/α-SMA/collagen I fibrotic pathway. The pancreatic architecture was restored to a great extent. However, AT-MSCs caused a marked pancreatic improvement and regeneration when compared to Pue which resulted in only a moderate amelioration. Insignificant and difficultly detectable spontaneous recovery was noticed in the withdrawal group. Both AT-MSCs and Pue have a promising effectiveness as targeted therapeutic agents against nicotine- induced pancreatic fibrosis, with a higher efficiency of AT- MSCs.
慢性胰腺炎是一种严重的健康问题,通常并发胰腺纤维化和糖尿病。尼古丁是这种情况的一个相当大的病因危险因素。我们的研究旨在探讨和比较脂肪组织源性间充质干细胞(AT- MSCs)和葛根素(Pue)在改善尼古丁诱导的胰腺纤维化中的可能治疗作用。大鼠随机分为:第一组;对照大鼠和II组;尼古丁治疗的老鼠。第二组进一步分为;模型组、AT-MSCs处理组、pue处理组和戒断组。评估体重增加研究和腹腔内葡萄糖耐量试验。处理胰腺组织,测定淀粉酶、脂肪酶、白细胞介素- 6、丙二醛和超氧化物歧化酶。对caspase-3、转化生长因子- β1 (TGF- β1)、α-平滑肌肌动蛋白(α-SMA)和I型胶原进行定量RT-PCR检测。并行组织病理学、免疫组化及超微结构检查。我们发现给药AT- MSCs和Pue有助于增加胰岛素分泌和抑制炎症氧化应激参数。此外,通过降低caspase-3和TGF-β1/α-SMA/ I型胶原纤维化通路的元件,减少细胞凋亡和纤维化。胰腺结构在很大程度上得到了恢复。然而,与Pue相比,AT-MSCs引起了显着的胰腺改善和再生,而Pue仅导致中度改善。停药组自发性恢复不明显且难以检测。AT-MSCs和Pue作为靶向治疗尼古丁诱导的胰腺纤维化的药物具有良好的疗效,AT-MSCs的疗效更高。
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引用次数: 0
The unique biogenesis pathway of extracellular vesicles in Hirudo nipponia salivary gland cells 日本水蛭唾液腺细胞胞外囊泡的独特生物发生途径。
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2025-12-24 DOI: 10.1016/j.tice.2025.103296
Ya-Li Zhu, Meng-Xiang Jia, Ru-Yu Qu, Qian Li, Xia Qiu, Wen-Chen Zhao, Yuan-Yuan Luo
Extracellular vesicles (EVs) serve as crucial vehicles for the intercellular transfer of bioactive molecules. While the mechanisms of EV biogenesis are well characterized in mammals, they remain comparatively understudied in invertebrates. This knowledge gap is particularly notable for the medicinal leech, Hirudo nipponia. In this study, the ultrastructural features of Hirudo nipponia salivary glands in resting and secretory states were analyzed using scanning and transmission electron microscopy to investigate the biogenesis and release of EVs. For the first time, it is demonstrated that salivary gland cells possess dual pathways for EV biogenesis: a classical pathway and a unique pathway derived from secretory granules. These findings provide critical morphological evidence for the conservation of EV biogenesis in invertebrates and highlight a key secretory adaptation for specialized physiological functions.
细胞外囊泡(EVs)是生物活性分子在细胞间转移的重要载体。虽然EV的生物发生机制在哺乳动物中有很好的特征,但在无脊椎动物中的研究相对较少。这种知识差距对于药用水蛭日本水蛭来说尤其明显。本研究利用扫描电镜和透射电镜对日本水蛭静息和分泌状态下唾液腺的超微结构特征进行了分析,探讨了EVs的生物发生和释放。首次证明唾液腺细胞具有EV生物发生的双重途径:经典途径和来源于分泌颗粒的独特途径。这些发现为无脊椎动物EV生物发生的保护提供了重要的形态学证据,并强调了特殊生理功能的关键分泌适应。
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引用次数: 0
Microtubule-based cup-like structures appear during microparticle uptake in U2OS cells cultured on different substrate types 在不同底物类型培养的U2OS细胞中,微管基杯状结构出现在微粒摄取过程中。
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2025-12-24 DOI: 10.1016/j.tice.2025.103297
Carina Rząca , Agata Kubisiak , Dominik Panek , Marta Targosz-Korecka , Zenon Rajfur
Substrate type play a pivotal role in regulating the morphology, mechanical properties, and cytoskeletal organization of cancer cells. In this study, we examined the response of U2OS osteosarcoma cells to substrate stiffness, with a particular focus on cytoskeletal remodeling, cell elasticity, and microparticle internalization. To simulate environments of moderate and high stiffness, cells were cultured on polyacrylamide (PA) hydrogels with a stiffness of 40 kPa and on rigid glass substrates, respectively. Changes in cell morphology and cytoskeletal organization were assessed using fluorescence microscopy, while cell mechanical properties were measured using AFM. To investigate the relationship between substrate mechanics and endocytic activity, carboxylated fluorescent 2 µm latex microspheres were introduced to the cell culture system.
U2OS cells cultured on glass exhibited a significantly larger surface area, more actin stress fibers, and a more organized, stretched cytoskeletal architecture compared to cells grown on 40 kPa PA gels. AFM measurements further demonstrated that cells on glass were mechanically stiffer than those on PA substrates. Microparticle uptake was also strongly influenced by substrate stiffness. Cells cultured on 40 kPa PA gels internalized a significantly greater number of fluorescent microspheres and notably, on 40 kPa PA gel formed “cup-like” structures around the beads, composed of microtubules. Three-dimensional image reconstructions revealed that these structures frequently encapsulate the particles in an asymmetrical manner, indicative of an active cytoskeletal remodeling. To better understand the molecular composition of microtubule-based structures, we analyzed the localization of selected microtubule-associated proteins (MAPs), including IQGAP1, CLIP1, and MARK2. Interestingly, only IQGAP1 was localized prominently to the microtubule cups on 40 kPa gels, often forming ring-like structures surrounding the beads. In some cases, these rings were observed independently of microtubules, suggesting the involvement of IQGAP1 in an active, possibly microtubule-initiated, endocytic process.
In conclusion, our findings demonstrate that substrate type modulates multiple aspects of U2OS cell behavior, including morphology, cytoskeletal arrangement, mechanical properties, and microparticle uptake. These results underscore the mechanosensitive nature of osteosarcoma cells and highlight novel roles for microtubule cup-like structures and MAPs, particularly IQGAP1 in cellular uptake mechanisms.
底物类型在调节癌细胞的形态、力学特性和细胞骨架组织中起关键作用。在这项研究中,我们研究了U2OS骨肉瘤细胞对底物硬度的反应,特别关注细胞骨架重塑、细胞弹性和微粒内化。为了模拟中等和高刚度环境,细胞分别在刚度为40 kPa的聚丙烯酰胺(PA)水凝胶和刚性玻璃基质上培养。使用荧光显微镜评估细胞形态和细胞骨架组织的变化,使用原子力显微镜测量细胞力学性能。为了研究底物力学与内吞活性之间的关系,将羧化荧光2 µm乳胶微球引入细胞培养系统。与在40kpa PA凝胶上培养的细胞相比,在玻璃上培养的U2OS细胞表现出更大的表面积、更多的肌动蛋白应力纤维和更有组织、拉伸的细胞骨架结构。AFM测量进一步表明,玻璃上的细胞比PA基板上的细胞机械硬度更高。微颗粒的吸收也受到基质刚度的强烈影响。在40 kPa PA凝胶上培养的细胞内化荧光微球的数量明显增加,值得注意的是,在40 kPa PA凝胶上,微球周围形成了由微管组成的“杯状”结构。三维图像重建显示,这些结构经常以不对称的方式包裹颗粒,表明活跃的细胞骨架重塑。为了更好地了解微管结构的分子组成,我们分析了选定的微管相关蛋白(MAPs)的定位,包括IQGAP1、CLIP1和MARK2。有趣的是,只有IQGAP1定位在40 kPa凝胶的微管杯上,通常在微管杯周围形成环状结构。在某些情况下,这些环是独立于微管观察到的,这表明IQGAP1参与了一个活跃的,可能是微管启动的内吞过程。总之,我们的研究结果表明,底物类型调节了U2OS细胞行为的多个方面,包括形态、细胞骨架排列、机械性能和微粒摄取。这些结果强调了骨肉瘤细胞的机械敏感性,并强调了微管杯状结构和map的新作用,特别是IQGAP1在细胞摄取机制中的作用。
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引用次数: 0
Aldometanib attenuates OGD/R-induced cardiomyocyte injury via mitigation of mitochondrial dysfunction Aldometanib通过减轻线粒体功能障碍减轻OGD/ r诱导的心肌细胞损伤。
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2025-12-23 DOI: 10.1016/j.tice.2025.103294
Mian Xie , Jiajia Hao , Chen Chao , Xi Chen , Qiuling Chen , Yao-wang Lin , Jiang-hua Li , Qi-yun Liu , Cheng Liu

Objective

Myocardial ischemia-reperfusion injury (MIRI) is a secondary condition following the reestablishment of blood flow to the heart, resulting in myocardial damage such as cardiomyocyte death, ferroptosis, fibrosis, and hypertrophy. However, there is still a lack of targeted therapeutic drugs to date.Aldometanib is a newly developed activator of AMP-activated protein kinase (AMPK) located on the lysosomal membrane, which exhibits significant pharmacological potential. Nevertheless, its role in MIRI remains incompletely understood.

Methods

This study assessed aldometanib's impact on myocardial ischemia-reperfusion injury using H9c2 and AC16 cardiomyocyte lines as in vitro models.

Results

Experimental data demonstrated that aldometanib promoted cardiomyocyte proliferation, reduced oxidative stress, and alleviated inflammatory responses. Furthermore, we identified that aldometanib could inhibit ferroptosis in cardiomyocytes. Mechanistically, our investigations revealed that aldometanib exerted a cardioprotective effect by alleviating cardiomyocyte damage through the regulation of mitochondrial function. Specifically, aldometanib enhanced mitophagy by activating lysosomal AMPK. Additionally, we found that aldometanib exerted an antioxidant effect via Nrf2, thereby mitigating ferroptosis. In animal models, we preliminarily confirmed that aldometanib treatment attenuated tissue damage and functional impairment following myocardial ischemia-reperfusion, further supporting its therapeutic potential.

Conclusions

This study uncovers the protective effect of aldometanib against MIRI and its underlying mechanism, providing experimental evidence and a potential candidate drug for targeting MIRI.
目的:心肌缺血-再灌注损伤(心肌缺血-再灌注损伤,MIRI)是心脏血流重建后的继发性疾病,可导致心肌细胞死亡、上铁、纤维化、肥厚等心肌损伤。然而,迄今为止仍缺乏靶向治疗药物。Aldometanib是一种新开发的位于溶酶体膜上的amp活化蛋白激酶(AMPK)激活剂,具有重要的药理潜力。然而,它在MIRI中的作用仍然不完全清楚。方法:本研究以H9c2和AC16心肌细胞系为体外模型,评估aldometanib对心肌缺血再灌注损伤的影响。结果:实验数据表明,aldometanib促进心肌细胞增殖,降低氧化应激,减轻炎症反应。此外,我们发现aldometanib可以抑制心肌细胞的铁下垂。从机制上讲,我们的研究表明aldometanib通过调节线粒体功能减轻心肌细胞损伤,从而发挥心脏保护作用。具体来说,aldometanib通过激活溶酶体AMPK来增强线粒体自噬。此外,我们发现aldometanib通过Nrf2发挥抗氧化作用,从而减轻铁下垂。在动物模型中,我们初步证实aldometanib治疗可减轻心肌缺血-再灌注后的组织损伤和功能损害,进一步支持其治疗潜力。结论:本研究揭示了aldometanib对MIRI的保护作用及其机制,为靶向MIRI提供了实验证据和潜在的候选药物。
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引用次数: 0
Engineering bone regeneration: Strontium fluorophosphate, incorporation into collagen and gelatin-based hydrogels promotes osteogenesis in human adipose-derived mesenchymal stem cells 工程骨再生:将氟磷酸锶掺入胶原蛋白和明胶水凝胶中,可促进人脂肪来源的间充质干细胞成骨
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2025-12-22 DOI: 10.1016/j.tice.2025.103292
Sahel Noori , Faezeh Norouz , Raheleh Halabian , Hossein Aghamollaei , Elahe Eftekhari , Ali Salimi

Background

The incorporation of nanoparticles into hydrogels enhances their properties for biomedical applications. Strontium can enhance osteogenesis through osteoblast formation by substituting calcium in osteoblast-mediated processes.

Materials and methods

Collagen-gelatin hydrogels (COL-GEL) were synthesized with and without strontium fluorophosphate (SrFP) to study their effect on osteogenic differentiation of adipose-derived mesenchymal stem cells (AD-MSCs). Scaffolds were characterized using XRD and FTIR. Biocompatibility of SrFP and scaffolds was assessed using the MTT assay and acridine orange. Their osteogenic differentiation potential was evaluated by ALP activity, calcium content, alizarin red, von Kossa staining, real-time RT-PCR and immunocytochemistry.

Results

SrFP at 50 μg/ml significantly promoted proliferation by 1.5-fold over 3 days. The COL-GEL-0.1 %SrFP scaffold showed higher cell proliferation compared to COL-GEL-0.5 %SrFP. The COL-GEL-SrFP exhibited high ALP activity (1.5-fold enhancement) and calcium content (2.1-fold enhancement), consistent with the results of alizarin red (p ≤ 0.05) and von Kossa (p ≤ 0.01). Gene and protein analyses revealed the elevated levels of ALP, Col-I (1.6-fold), osteocalcin (1.7-fold) and RUNX2 (2.3-fold) gene expression, as well as a significant upregulation of osteocalcin and osteopontin protein levels (more than 3-fold) in the COL-GEL-SrFP after 14 day-differentiation.

Conclusion

Compared to the COL-GEL hydrogel, the COL-GEL-SrFP improved cell-scaffold interactions and demonstrated more effective osteogenic differentiation. These findings suggest that COL-GEL-SrFP represents a promising and biocompatible scaffold for increasing the osteogenic differentiation of AD-MSCs and subsequent mineralization. This study highlights the potential of collagen and gelatin-based hydrogels incorporated with SrFP nanoparticles as a novel alternative to current therapeutic approaches in bone regenerative medicine.
纳米颗粒掺入水凝胶增强了其生物医学应用的性能。锶可以通过在成骨细胞介导的过程中取代钙来促进成骨细胞的形成。材料与方法合成含氟磷酸锶(SrFP)和不含氟磷酸锶(SrFP)的胶原明胶水凝胶(COL-GEL),研究其对脂肪源性间充质干细胞(AD-MSCs)成骨分化的影响。采用XRD和FTIR对支架进行了表征。采用MTT法和吖啶橙评价SrFP与支架的生物相容性。通过ALP活性、钙含量、茜素红、von Kossa染色、实时RT-PCR和免疫细胞化学评价其成骨分化潜力。结果50 μg/ml的ssrfp在3 d内显著促进细胞增殖1.5倍。与COL-GEL-0.5 %SrFP相比,COL-GEL-0.1 %SrFP支架的细胞增殖能力更高。COL-GEL-SrFP表现出较高的ALP活性(提高1.5倍)和钙含量(提高2.1倍),与茜素红(p ≤ 0.05)和von Kossa (p ≤ 0.01)的结果一致。基因和蛋白分析显示,分化14天后,COL-GEL-SrFP中ALP、col - 1(1.6倍)、骨钙素(1.7倍)和RUNX2(2.3倍)基因表达水平升高,骨钙素和骨桥蛋白水平显著上调(3倍以上)。结论与COL-GEL水凝胶相比,COL-GEL- srfp改善了细胞-支架的相互作用,并表现出更有效的成骨分化。这些发现表明,COL-GEL-SrFP是一种很有前途的生物相容性支架,可以促进AD-MSCs的成骨分化和随后的矿化。这项研究强调了胶原蛋白和明胶基水凝胶与SrFP纳米颗粒结合的潜力,作为当前骨再生医学治疗方法的一种新的替代方案。
{"title":"Engineering bone regeneration: Strontium fluorophosphate, incorporation into collagen and gelatin-based hydrogels promotes osteogenesis in human adipose-derived mesenchymal stem cells","authors":"Sahel Noori ,&nbsp;Faezeh Norouz ,&nbsp;Raheleh Halabian ,&nbsp;Hossein Aghamollaei ,&nbsp;Elahe Eftekhari ,&nbsp;Ali Salimi","doi":"10.1016/j.tice.2025.103292","DOIUrl":"10.1016/j.tice.2025.103292","url":null,"abstract":"<div><h3>Background</h3><div>The incorporation of nanoparticles into hydrogels enhances their properties for biomedical applications. Strontium can enhance osteogenesis through osteoblast formation by substituting calcium in osteoblast-mediated processes.</div></div><div><h3>Materials and methods</h3><div>Collagen-gelatin hydrogels (COL-GEL) were synthesized with and without strontium fluorophosphate (SrFP) to study their effect on osteogenic differentiation of adipose-derived mesenchymal stem cells (AD-MSCs). Scaffolds were characterized using XRD and FTIR. Biocompatibility of SrFP and scaffolds was assessed using the MTT assay and acridine orange. Their osteogenic differentiation potential was evaluated by ALP activity, calcium content, alizarin red, von Kossa staining, real-time RT-PCR and immunocytochemistry.</div></div><div><h3>Results</h3><div>SrFP at 50 μg/ml significantly promoted proliferation by 1.5-fold over 3 days. The COL-GEL-0.1 %SrFP scaffold showed higher cell proliferation compared to COL-GEL-0.5 %SrFP. The COL-GEL-SrFP exhibited high ALP activity (1.5-fold enhancement) and calcium content (2.1-fold enhancement), consistent with the results of alizarin red (<em>p</em> ≤ 0.05) and von Kossa (<em>p</em> ≤ 0.01). Gene and protein analyses revealed the elevated levels of ALP, Col-I (1.6-fold), osteocalcin (1.7-fold) and RUNX2 (2.3-fold) gene expression, as well as a significant upregulation of osteocalcin and osteopontin protein levels (more than 3-fold) in the COL-GEL-SrFP after 14 day-differentiation.</div></div><div><h3>Conclusion</h3><div>Compared to the COL-GEL hydrogel, the COL-GEL-SrFP improved cell-scaffold interactions and demonstrated more effective osteogenic differentiation. These findings suggest that COL-GEL-SrFP represents a promising and biocompatible scaffold for increasing the osteogenic differentiation of AD-MSCs and subsequent mineralization. This study highlights the potential of collagen and gelatin-based hydrogels incorporated with SrFP nanoparticles as a novel alternative to current therapeutic approaches in bone regenerative medicine.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103292"},"PeriodicalIF":2.5,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145883477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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
Integrated strategies from stem cells to exosomes for amelioration of insulin resistance and promoting β-cell regeneration in diabesity 从干细胞到外泌体改善糖尿病患者胰岛素抵抗和促进β细胞再生的综合策略。
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2025-12-22 DOI: 10.1016/j.tice.2025.103293
Himadri Singh , Rakesh Bhaskar , Shampa Ghosh , Pradeep Kumar Mishra , Krishna Kumar Singh , Jitendra Kumar Sinha , Sung Soo Han
The simultaneous epidemic of obesity and type 2 diabetes is driven by insulin resistance, chronic inflammation, and progressive β-cell dysfunction within an obese, lipotoxic microenvironment. Conventional therapies may improve glycemic control but rarely reverse the underlying metabolic damage or restore long-term homeostasis. Regenerative strategies based on stem cells such as mesenchymal stem cells (MSCs), adipose-derived stem cells (ASCs), and induced pluripotent stem cells (iPSCs), together with their extracellular vesicles (EVs) and exosomes have emerged as promising approaches to address both β-cell failure and obesity-related pathology. These interventions may restore β-cell mass and function, enhance insulin sensitivity, and remodel dysfunctional adipose tissue through direct cell replacement and paracrine signaling. This review emphasizes integrated strategies that combine stem cells, exosomes, pharmacological agents, and tissue-engineering platforms (3-D scaffolds, hydrogels, and exosome delivery systems) to achieve synergistic and more durable metabolic benefits in diabesity. Particular focus is placed on how these combinations address adipose tissue inflammation and fibrosis, ectopic lipid accumulation, brown/beige adipose tissue dysfunction, and enhance glycemic control indices. Although preclinical and early-phase clinical studies are encouraging, major challenges remain in achieving scalable manufacturing, immunological compatibility, product standardization, targeted delivery, and long-term safety. We critically discuss the pathophysiology of diabesity, highlighting current and future directions in stem cells and exosome-based therapies for developing safe, effective, and sustainable treatment strategies for diabesity.
肥胖和2型糖尿病的同时流行是由肥胖、脂毒性微环境中的胰岛素抵抗、慢性炎症和进行性β细胞功能障碍驱动的。常规疗法可以改善血糖控制,但很少能逆转潜在的代谢损伤或恢复长期的体内平衡。基于干细胞的再生策略,如间充质干细胞(MSCs)、脂肪来源干细胞(ASCs)和诱导多能干细胞(iPSCs),以及它们的细胞外囊泡(EVs)和外泌体,已经成为解决β细胞衰竭和肥胖相关病理的有希望的方法。这些干预可以恢复β细胞质量和功能,增强胰岛素敏感性,并通过直接细胞替代和旁分泌信号重塑功能失调的脂肪组织。这篇综述强调了将干细胞、外泌体、药物制剂和组织工程平台(3d支架、水凝胶和外泌体递送系统)结合起来的综合策略,以实现糖尿病的协同和更持久的代谢益处。特别关注这些组合如何解决脂肪组织炎症和纤维化,异位脂质积累,棕色/米色脂肪组织功能障碍,并提高血糖控制指标。尽管临床前和早期临床研究令人鼓舞,但在实现规模化生产、免疫兼容性、产品标准化、靶向给药和长期安全性方面仍存在主要挑战。我们批判性地讨论了糖尿病的病理生理,强调了干细胞和基于外泌体的治疗方法的当前和未来方向,以开发安全、有效和可持续的糖尿病治疗策略。
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引用次数: 0
Immediate and long-term effects of insufficient weight-bearing during growth on hip morphology and histopathology in rats 生长期间负重不足对大鼠髋关节形态和组织病理学的近期和长期影响。
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2025-12-21 DOI: 10.1016/j.tice.2025.103289
Marina Kanehara, Norikazu Nishida, Akinori Kaneguchi, Junya Ozawa
Reduced weight bearing during growth can induce bony morphological characteristics of developmental dysplasia of the hip, a risk factor for hip osteoarthritis (OA). However, the long-term effects of reloading remain unknown. This study aimed to evaluate the immediate and long-term effects of hindlimb suspension (HS) during growth on hip bone morphology, alignment, and histopathology. Four-week-old female rats were subjected to HS for four or eight weeks to reduce weight bearing. After 4 or 8 weeks of HS, the rats were reloaded until 54 weeks of age, which corresponds to human middle age. Age-matched animals served as controls. Bone morphology and alignment parameters were measured using three-dimensional reconstructed images from X-ray computed tomography. A histopathological analysis of the femoral head was also performed. Immediately after four and eight weeks of HS, increased femoral anteversion (FeAV) and acetabular anteversion (AcAV), as well as decreased femoral head diameter (characteristics of hip OA), were detected. After reloading until 54 weeks of age, these features persisted, and an increase of distraction index, which are indicators of structural instability, appeared in rats after 4 and/or 8weeks of HS. Furthermore, OA-like changes, such as articular cartilage thinning and subchondral bone sclerosis, were observed in the femoral head after long-term reloading. Additionally, FeAV was significantly correlated with several histopathological indices of femoral head cartilage. These results suggest that reduced weight bearing during growth may lead to hip morphological and alignment abnormalities, which could result in limited OA-like hip joint changes in the long term.
生长过程中体重的减少会引起髋关节发育不良的骨形态特征,这是髋关节骨关节炎(OA)的危险因素。然而,重新装填的长期影响仍然未知。本研究旨在评估后肢悬吊(HS)在生长过程中对髋骨形态、排列和组织病理学的近期和长期影响。4周龄的雌性大鼠进行4周或8周的HS以减轻体重。HS 4周或8周后,重新加载大鼠,直到54周龄,相当于人的中年。年龄匹配的动物作为对照。使用x射线计算机断层扫描三维重建图像测量骨形态和排列参数。还进行了股骨头的组织病理学分析。HS 4周和8周后,立即检测到股骨前倾(FeAV)和髋臼前倾(AcAV)增加,股骨头直径减小(髋关节OA的特征)。重新装填到54周龄后,这些特征持续存在,并且在HS 4周和/或8周后大鼠出现牵张指数的增加,牵张指数是结构不稳定的指标。此外,长期重装后,在股骨头中观察到oa样变化,如关节软骨变薄和软骨下骨硬化。此外,FeAV与股骨头软骨的多项组织病理学指标有显著相关性。这些结果表明,生长过程中体重的减少可能导致髋关节形态和排列异常,这可能导致长期有限的oa样髋关节变化。
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引用次数: 0
Boosting muscle health in aging rats: The synergistic effect of vitamin C, silymarin, and endurance swimming on a high-fat diet 促进衰老大鼠的肌肉健康:高脂肪饮食中维生素C、水飞蓟素和耐力游泳的协同作用。
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2025-12-21 DOI: 10.1016/j.tice.2025.103290
Fariba Aghaei , Ehsan Arabzadeh , Foad Feizolahi , Ali Nejati Bezdi , Majid Abasi , Mehdi Zargani

Background

This paper inspects the influence of 8-week endurance swimming supplemented with vitamin C and Silymarin on histopathological changes and some gene markers of skeletal muscle hypertrophy in aged rats receiving a high-fat diet (HFD).

Methods

Twenty-five aged male Wistar rats underwent random allocation to five groups, including a normal diet (Control), HFD, HFD + combined vitamin C and Silymarin supplementation (HFD+CS), HFD + endurance swimming (HFD+ES), and HFD + CS + ES. After six weeks of HFD, CS was gavaged to rats as the selected intervention together with HFD in the supplementation groups over eight weeks. Besides, the exercise groups received swimming exercise training five days/week over eight weeks.

Results

HFD increased the lipid profile and fat penetration into the liver tissue of elderly rats. Meanwhile, endurance swimming exercises and a combined supplement significantly improved the liver tissue and regulated the lipid profile. The examination of muscle tissue and gene changes revealed that HFD could increase muscle atrophy and reduce the 4E-BP1, S6K1, and mTOR gene levels, while the combination of exercise and supplementation could increase the 4E-BP1, S6K1, and IGF-1 gene levels and improve muscle fiber diameter in aged rats.

Conclusion

Endurance swimming training with vitamin C and silymarin supplementation in aging NAFLD model rats can improve lipid profile factors and skeletal muscle tissue fiber diameter.
背景:研究了在高脂饮食(HFD)老龄大鼠的基础上,补充维生素C和水飞蓟素进行8周耐力游泳对骨骼肌肥大组织病理变化和部分基因标记的影响。方法:25只老龄雄性Wistar大鼠随机分为正常饮食组(Control)、HFD组、HFD+ 维生素C和水飞蓟素联合补充组(HFD+CS)、HFD+ 耐力游泳组(HFD+ES)和HFD+ CS + ES。饲喂HFD 6周后,将CS灌胃给大鼠,作为8周内补充组HFD的选择干预。此外,运动组接受游泳运动训练,每周五天,为期八周。结果:HFD增加了老年大鼠肝组织的脂质分布和脂肪渗透。同时,耐力游泳运动和联合补充显著改善肝组织和调节血脂。肌肉组织和基因变化检测显示,高脂饮食可增加老龄大鼠肌肉萎缩,降低4E-BP1、S6K1和mTOR基因水平,而运动与补充相结合可增加4E-BP1、S6K1和IGF-1基因水平,提高肌纤维直径。结论:耐力游泳训练补充维生素C和水飞蓟素可以改善衰老NAFLD模型大鼠的脂质因子和骨骼肌组织纤维直径。
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引用次数: 0
Oroxindin promotes angiogenesis in pressure ulcers through activating PI3K/AKT signaling pathway by PTEN suppression Oroxindin通过抑制PTEN激活PI3K/AKT信号通路促进压疮血管生成。
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2025-12-21 DOI: 10.1016/j.tice.2025.103291
Tengyan Zhu , Shuzhen Fang , Xiaoqin Shang
Pressure ulcer (PU) is defined as localized tissue damage caused by prolonged pressure on any part of the body. Oroxindin (Oro) exhibits significant anti-inflammatory and anti-cancer effects. This study aimed to investigate the effect and underlying mechanism of Oro on PU. Angiogenesis was detected by CD31 immunohistochemistry and CD31/α-SMA immunofluorescence staining in vivo. Cell scratch assay, Transwell assay, and tube formation assay were performed to assess cell migration and angiogenesis in vitro. Phospho-kinase array was used to identify the pathway in Oro-treated human umbilical vein endothelial cells (HUVECs), and the mechanism was investigated by Western blot, luciferase reporter gene assay, biolayer interferometry assay, and molecular docking. Results showed that Oro accelerated wound healing and angiogenesis in the PU mouse model. Moreover, Oro promoted cell migration and tube formation in HUVECs. In addition, Oro activated the PI3K/AKT signaling pathway through the suppression of PTEN. PTEN overexpression reversed the effects of Oro on cell migration and tube formation in HUVECs. In conclusion, we demonstrated that Oro promoted PU wound healing in vivo and facilitated angiogenesis in HUVECs through activation of the PI3K/AKT signaling pathway via PTEN suppression, indicating the potential of Oro as an effective treatment for PU.
压疮(PU)被定义为由于长期压迫身体任何部位而引起的局部组织损伤。Oroxindin (Oro)具有显著的抗炎和抗癌作用。本研究旨在探讨Oro对PU的影响及其机制。采用CD31免疫组化和CD31/α-SMA免疫荧光染色检测血管新生。采用细胞划痕实验、Transwell实验和试管形成实验评估细胞在体外的迁移和血管生成。采用磷酸激酶阵列技术在oro处理的人脐静脉内皮细胞(HUVECs)中鉴定该通路,并通过Western blot、荧光素酶报告基因检测、生物层干涉检测和分子对接等方法研究其作用机制。结果表明,Oro能促进PU小鼠模型的创面愈合和血管生成。此外,Oro还能促进huvec细胞的迁移和管的形成。此外,Oro通过抑制PTEN激活PI3K/AKT信号通路。PTEN过表达逆转了Oro对huvec细胞迁移和管形成的影响。综上所述,我们证明Oro通过抑制PTEN激活PI3K/AKT信号通路,在体内促进PU伤口愈合,促进HUVECs血管生成,表明Oro可能是一种有效的PU治疗方法。
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引用次数: 0
Efficacy of prophylactic adoption of recombinant human granulocyte colony-stimulating factor in advanced lung cancer patients after chemotherapy 晚期肺癌化疗后预防性应用重组人粒细胞集落刺激因子的疗效观察。
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2025-12-21 DOI: 10.1016/j.tice.2025.103288
Dada Yao, Huaqiang Zhou, Qichen Chen

Background

Lung cancer (LC) is a prevalent and lethal malignancy with limited treatments for advanced stages. The aim was to investigate the outcome of prophylactic adoption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in advanced LC patients on the basis of concurrent chemoradiotherapy. Methods: A total of 150 patients with advanced LC who received concurrent chemoradiotherapy at The Third People’s Hospital of Yuhang District between April 2023 and April 2025 were randomly assigned to two groups: an observation group (AG) and a control group (BG). Subjects were treated with platinum-based doublet chemotherapy combined with intensity-modulated conformal radiotherapy. AG received prophylactic rhG-CSF administration within 24–72 h after chemotherapy. The white blood cell (WBC) count, neutrophil (NEU) count, immune function indicators, inflammatory factor levels, and clinical efficacy were compared. Results: Following treatment, the WBC and NEU counts in AG were higher as against BG; CD4+ T cells was higher, while CD8+ T cells, CD3+PD-1 T cells, etc., were lower in AG as against BG; IL-10, IL-6, and TNF-α in AG were lower as against BG; objective response rate (ORR) (44.0 %) and disease control rate (DCR) (88.0 %) in AG were elevated as against BG (26.7 %, 64.0 %) (P < 0.05). Conclusion: Prophylactic adoption of rhG-CSF during concurrent chemoradiotherapy in advanced LC patients can protect hematopoietic function, regulate immune balance, reduce inflammatory response, and improve clinical efficacy.
背景:肺癌(LC)是一种普遍和致命的恶性肿瘤,晚期治疗有限。目的是探讨在同步放化疗的基础上预防性采用重组人粒细胞集落刺激因子(rhG-CSF)治疗晚期LC患者的效果。方法:选取2023年4月~ 2025年4月余杭区第三人民医院同步放化疗的晚期LC患者150例,随机分为两组:观察组(AG)和对照组(BG)。受试者接受以铂为基础的双重化疗联合调强适形放疗。化疗后24-72 h内给予预防性rhG-CSF。比较两组患者白细胞(WBC)计数、中性粒细胞(NEU)计数、免疫功能指标、炎症因子水平及临床疗效。结果:治疗后,AG中WBC和NEU计数高于BG;AG中CD4+ T细胞高于BG, CD8+ T细胞、CD3+PD-1 T细胞等低于BG;AG中IL-10、IL-6、TNF-α较BG降低;AG客观缓解率(ORR)(44.0 %)和疾病控制率(DCR)(88.0 %)均高于BG(26.7 %,64.0 %)(P )结论:晚期LC患者同步放化疗中预防性应用rhG-CSF可保护造血功能,调节免疫平衡,减轻炎症反应,提高临床疗效。
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