Tissue & cell最新文献_第10页

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

Tissue & cell

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

Tissue & cell

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

Tissue & cell

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

Tissue & cell

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

Tissue & cell

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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引用次数: 0

Therapeutic targeting of oxidative-inflammatory crosstalk by Apelin-12 in neonatal hyperoxia-induced lung injury Apelin-12靶向治疗新生儿高氧性肺损伤的氧化-炎症串扰。

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-12-17 DOI: 10.1016/j.tice.2025.103285

QiuXiang Xu , Pei Li , Jizhao Gao , Wenpeng Wang

Hyperoxia-induced neonatal acute lung injury (ALI) constitutes a significant clinical challenge with limited therapeutic options. This study investigates the protective role of Apelin-12, an endogenous peptide, in a neonatal mouse model of hyperoxia-induced ALI. We demonstrate that hyperoxia exposure significantly reduces serum and pulmonary Apelin-12 levels and downregulates APJ receptor expression. Administration of Apelin-12 (15 μg/kg) markedly attenuated lung injury, evidenced by improved lung function (restored peak expiratory flow, reduced airway resistance, enhanced dynamic compliance), decreased pathological damage (lower lung injury score, reduced wet/dry ratio), and diminished neutrophil infiltration (suppressed myeloperoxidase activity). Apelin-12 significantly mitigated oxidative stress by lowering malondialdehyde levels while restoring superoxide dismutase activity and glutathione content. Furthermore, it reduced inflammatory cell counts and protein leakage in bronchoalveolar lavage fluid (BALF), along with suppressing IL-1β and IL-18 cytokine release. Mechanistically, Apelin-12 activated the Nrf2/HO-1 antioxidant pathway and inhibited NF-κB signaling. Notably, hyperoxia paradoxically suppressed NLRP1 inflammasome components (NLRP1, ASC, Caspase-1) at mRNA and protein levels, which were restored by Apelin-12 treatment. These results indicate that Apelin-12 protects against hyperoxic neonatal ALI by alleviating oxidative stress, inflammation, and lung dysfunction through coordinated modulation of the NLRP1 inflammasome, Nrf2/HO-1, and NF-κB pathways, highlighting its therapeutic potential for neonatal lung injury.

高氧诱导的新生儿急性肺损伤（ALI）是一个具有有限治疗选择的重大临床挑战。本研究探讨了内源性肽Apelin-12在新生儿小鼠高氧诱导ALI模型中的保护作用。我们证明高氧暴露显著降低血清和肺Apelin-12水平，下调APJ受体表达。给药Apelin-12（15 μg/kg）显著减轻肺损伤，表现为肺功能改善（恢复呼气峰流量，降低气道阻力，增强动态依从性），减少病理损伤（降低肺损伤评分，降低湿/干比），减少中性粒细胞浸润（抑制髓过氧化物酶活性）。Apelin-12通过降低丙二醛水平，同时恢复超氧化物歧化酶活性和谷胱甘肽含量，显著减轻氧化应激。此外，它还能减少支气管肺泡灌洗液（BALF）中的炎症细胞计数和蛋白质渗漏，同时抑制IL-1β和IL-18细胞因子的释放。机制上，Apelin-12激活Nrf2/HO-1抗氧化途径，抑制NF-κB信号传导。值得注意的是，高氧在mRNA和蛋白水平上矛盾地抑制了NLRP1炎性体成分（NLRP1， ASC, Caspase-1），这些成分通过Apelin-12治疗得到恢复。这些结果表明，Apelin-12通过协调调节NLRP1炎性体、Nrf2/HO-1和NF-κB通路，减轻氧化应激、炎症和肺功能障碍，从而保护新生儿抗高氧性ALI，突出了其治疗新生儿肺损伤的潜力。

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引用次数: 0

Pumpkin seed oil improves hepatotoxicity in rats through inhibition of CYP2E1 and activation of Nrf2 signaling pathways 南瓜籽油通过抑制CYP2E1和激活Nrf2信号通路改善大鼠肝毒性

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-12-17 DOI: 10.1016/j.tice.2025.103286

Noran W. Esmail , Sawsan M. El-sheikh , Reda M.S. Korany , Arwa A. Hassan , Sara M. Baraka , Hanan M. Alharbi , Ayman K. Ismail , Doaa A. Mansour , Heba H. Mahboub , Esraa.M. Fahmy

Pumpkin seed oil (PSO) possesses multiple pharmacological properties, including antioxidant, anti-inflammatory, and anti-apoptotic effects. Given that paracetamol (PCM) is a common cause of drug-induced hepatic injury, the present study aimed to evaluate the hepatoprotective potential of PSO against PCM-induced liver toxicity in rats and to elucidate its underlying mechanisms. Male albino rats were allocated into six groups (n = 6): control, PCM, silymarin (SLM, 50 mg/kg/day), PSO (1.5 mg/kg/day), SLM + PCM, and PSO + PCM. Serum and liver samples were examined for biochemical, molecular, and histopathological changes. GC–MS analysis identified six major fatty acid methyl esters in PSO, which may contribute to its biological activity. PSO significantly mitigated PCM-induced hepatotoxicity by restoring liver function markers, enhancing antioxidant defenses via downregulation of CYP2E1 and activation of Nrf2, and attenuating inflammation through suppression of TNF-α and IL-1β while elevating IL-10 levels. Moreover, PSO reduced TGF-β expression and improved hepatic regeneration. Histopathological evaluation confirmed the protective effects, and modulation of BAX/Bcl-2 balance indicated its anti-apoptotic action. In conclusion, PSO exerts potent hepatoprotective effects against PCM-induced liver injury, likely mediated by its bioactive constituents through modulation of CYP2E1 and Nrf2 signaling pathways. These findings highlight PSO as a promising natural candidate for further preclinical and clinical evaluation in hepatoprotection.

南瓜籽油（PSO）具有多种药理作用，包括抗氧化、抗炎和抗凋亡作用。鉴于对乙酰氨基酚（paracetamol， PCM）是药物性肝损伤的常见原因，本研究旨在评估PSO对PCM诱导的大鼠肝毒性的肝保护潜力，并阐明其潜在机制。雄性白化大鼠分为6组（n = 6）：对照、PCM、水飞蓟素（SLM, 50 mg/kg/day）、PSO（1.5 mg/kg/day）、SLM + PCM和PSO + PCM。检测血清和肝脏样本的生化、分子和组织病理学变化。GC-MS分析鉴定出PSO中6种主要的脂肪酸甲酯，这可能与PSO的生物活性有关。PSO通过恢复肝功能标志物，通过下调CYP2E1和激活Nrf2增强抗氧化防御，以及通过抑制TNF-α和IL-1β并提高IL-10水平来减轻炎症，从而显著减轻pcm诱导的肝毒性。此外，PSO降低TGF-β表达，促进肝脏再生。组织病理学评价证实了其保护作用，BAX/Bcl-2平衡的调节表明其具有抗凋亡作用。综上所述，PSO对pcm诱导的肝损伤具有有效的肝保护作用，可能是其生物活性成分通过调节CYP2E1和Nrf2信号通路介导的。这些发现突出了PSO作为进一步临床前和临床评估肝保护的有希望的天然候选物。

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引用次数: 0

5-Aza-CdR increases expression of the tight junction protein ZO-1 via upregulation of miR-126 through promoter hypomethylation in HMEC-1 cells 5-Aza-CdR在HMEC-1细胞中通过启动子低甲基化上调miR-126，从而增加紧密连接蛋白ZO-1的表达

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-12-16 DOI: 10.1016/j.tice.2025.103280

Xi Zhang , Shaohan Zhang , Yuzhi Shao , You Liu , Kerui Gong , Chunyang Zhang , Zhijun Zhao , Xuguo Ma , Gang Fu , Guo Shao

Cellular junctions are vital for endothelial cell (EC) function, with ZO-1 being a key tight junction protein influenced by miR-126. This study examines how 5-Aza-2′-deoxycytidine (5-Aza-CdR), a DNMT inhibitor, affects ZO-1 and miR-126 levels in HMEC-1 cells in vitro. HMEC-1 cells were treated with 5-Aza-CdR. ZO-1 expression was measured by real-time PCR and western blot. The expression level of miR-126 and its promoter DNA methylation level were determined by real-time PCR and MS-PCR. The mRNA and protein expression levels of DNMTs were detected by real-time PCR and western blot. The global methylation level was detected by 5-mC-positive signal using laser confocal microscopy and by combined bisulfite restriction analysis (COBRA) for Alu and Long interspersed element-1 (LINE-1) methylation patterns. Cell apoptotic and cell cycle were analyzed using cytometry. The expression of ZO-1 was enhanced with the upregulation of miR-126 via its promoter DNA hypomethylation. The DNMT1 and DNMT3A as well as global methylation levels were decreased with the S-phase cell cycle arrested in HMEC-1 cells which were treated with 5-Aza-CdR. This study indicated that 5-Aza-CdR can induce the ZO-1 expression related to the up-regulation of miR-126 through the DNA methylation mechanism in ECs.

细胞连接对内皮细胞（EC）功能至关重要，ZO-1是受miR-126影响的关键紧密连接蛋白。本研究探讨了DNMT抑制剂5-Aza-2 ' -脱氧胞苷（5-Aza-CdR）如何在体外影响HMEC-1细胞中ZO-1和miR-126的水平。用5-Aza-CdR处理HMEC-1细胞。采用实时荧光定量PCR和western blot检测ZO-1的表达。采用real-time PCR和MS-PCR检测miR-126的表达水平及其启动子DNA甲基化水平。采用实时荧光定量PCR和western blot检测DNMTs的mRNA和蛋白表达水平。利用激光共聚焦显微镜的5- mc阳性信号和亚硫酸氢盐限制性结合分析（COBRA）检测Alu和长分散元素-1 （LINE-1）甲基化模式的总体甲基化水平。用细胞术分析细胞凋亡和细胞周期。通过miR-126的启动子DNA低甲基化，ZO-1的表达增强。在5-Aza-CdR处理的HMEC-1细胞中，DNMT1和DNMT3A以及整体甲基化水平随着s期细胞周期的阻滞而降低。本研究表明，5-Aza-CdR可通过DNA甲基化机制诱导ec中与miR-126上调相关的ZO-1表达。

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引用次数: 0

The dual role of autophagy in breast cancer stemness and treatment resistance 自噬在乳腺癌发病和治疗耐药中的双重作用

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-12-16 DOI: 10.1016/j.tice.2025.103279

Anu Jayanthi Panicker , Kirti S. Prabhu , Ummu Habeeba , Zahwa Mariyam , Affan Asim , Sarada Prasad Dakua , Shahab Uddin

Autophagy is a fundamental, highly conserved cellular process with a complex dual role in breast cancer progression and therapy resistance. Initially, autophagy functions as a tumor suppressor by maintaining genomic stability through clearance of damaged organelles and reducing oxidative stress, preventing tumor initiation. In established tumors, autophagy supports cancer cell survival under metabolic stress, sustains cancer stem cell stemness, and facilitates adaptation to hypoxia and nutrient deprivation in the tumor microenvironment. This pro-survival role enhances tumor growth, metastasis, and resistance to chemotherapy, radiotherapy, and targeted therapies. Autophagy extensively interacts with key signaling pathways governing cancer stem cell renewal and immune evasion, underscoring its multifaceted impact on tumor biology. Given its pivotal role, autophagy modulation via established inhibitors such as chloroquine alone and in combination with several other novel agents are under clinical investigation to investigate if its action that could be used to overcome therapy resistance and improve patient outcomes in breast cancer.

自噬是一个基本的、高度保守的细胞过程，在乳腺癌的进展和治疗抵抗中具有复杂的双重作用。最初，自噬作为肿瘤抑制因子，通过清除受损细胞器和减少氧化应激来维持基因组的稳定性，防止肿瘤的发生。在已建立的肿瘤中，自噬支持肿瘤细胞在代谢应激下存活，维持肿瘤干细胞的干性，并促进肿瘤微环境中对缺氧和营养剥夺的适应。这种促进生存的作用增强了肿瘤的生长、转移和对化疗、放疗和靶向治疗的耐药性。自噬广泛地与控制癌症干细胞更新和免疫逃避的关键信号通路相互作用，强调其对肿瘤生物学的多方面影响。鉴于其关键作用，通过已有的抑制剂如氯喹单独或与其他几种新型药物联合进行自噬调节正在进行临床研究，以研究其作用是否可用于克服治疗耐药并改善乳腺癌患者的预后。

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引用次数: 0

P2Y2 receptor as a favorable predictor of gastric cancer P2Y2受体作为胃癌的有利预测因子。

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-12-16 DOI: 10.1016/j.tice.2025.103278

Yu-qing Wu , Wen-long Wang

Background

Gastric cancer (GC) prevention and treatment have always been a difficult problem to solve. Therefore, mining the molecular genes related to the progression of GC and predicting the progression of GC has important clinical significance. Therefore, this study investigated whether the P2Y2 receptor (P2Y2R) has a certain effect on GC.

Methods

The correlation data of P2Y2R and GC tissues from public databases was collected, and the relationship between P2Y2R and the survival and prognosis of GC patients was analyzed. Moreover, the expression of P2Y2R in GC cells AGS, MGC803, HGC27 and normal GES-1 was detected by Western-blotting. Cell scratch, Transwell invasion and YF phalloidin assays were used to investigate the effects of P2Y2R on migration and invasion of GC cells.

Results

P2Y2R was highly expressed in GC tissues and was negatively correlated with poor survival and prognosis of patients with GC. Activation of the P2Y2R by UTP promoted the migration and invasion of GC cells. However, the P2Y2R-specific antagonist AR-C118925XX inhibited the migration and invasion of GC cells. In addition, P2Y2R activation enhanced cytoskeletal stress changes in GC cells and promoted GC motility, while inhibition of its activity yielded the opposite effect. In addition, activation of P2Y2R increased the expression levels of p-PKC, p-Src, and p-ERK1/2, while AR-C118925XX treatment significantly decreased the expression levels of p-PKC, p-Src, and p-ERK1/2.

Conclusion

High expression of P2Y2R is negatively correlated with survival and prognosis of GC patients. P2Y2R activation promotes GC progression may be related to PKC/Src and ERK signaling, indicating that P2Y2R may serve as a new molecular target for GC prevention and treatment.

背景：胃癌的防治一直是一个难以解决的问题。因此，挖掘与胃癌进展相关的分子基因，预测胃癌的进展具有重要的临床意义。因此，本研究探讨P2Y2受体（P2Y2R）是否对GC有一定影响。方法：收集公共数据库中P2Y2R与胃癌组织的相关数据，分析P2Y2R与胃癌患者生存及预后的关系。Western-blotting检测GC细胞AGS、MGC803、HGC27和正常GES-1中P2Y2R的表达。采用细胞划痕法、Transwell侵袭法和YF phalloidin法研究P2Y2R对胃癌细胞迁移和侵袭的影响。结果：P2Y2R在胃癌组织中高表达，与胃癌患者生存不良及预后呈负相关。UTP激活P2Y2R可促进GC细胞的迁移和侵袭。然而，p2y2r特异性拮抗剂AR-C118925XX抑制了GC细胞的迁移和侵袭。此外，P2Y2R的激活增强了GC细胞的细胞骨架应激变化，促进了GC运动，而抑制其活性则产生相反的效果。此外，P2Y2R的激活增加了p-PKC、p-Src和p-ERK1/2的表达水平，而AR-C118925XX处理显著降低了p-PKC、p-Src和p-ERK1/2的表达水平。结论：P2Y2R高表达与胃癌患者的生存和预后呈负相关。P2Y2R激活促进GC进展可能与PKC/Src和ERK信号通路有关，提示P2Y2R可能作为防治GC的新分子靶点。

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引用次数: 0