Tissue & cell最新文献_第9页

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。

{"title":"P2Y2 receptor as a favorable predictor of gastric cancer","authors":"Yu-qing Wu , Wen-long Wang","doi":"10.1016/j.tice.2025.103278","DOIUrl":"10.1016/j.tice.2025.103278","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":23201,"journal":{"name":"Tissue & cell","volume":"99 ","pages":"Article 103278"},"PeriodicalIF":2.5,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794958","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

Distribution of PGP 9.5- and nNOS-containing nerve fibers in the temporomandibular joint disk attachments of the elderly human 老年人颞下颌关节盘附着物中PGP 9.5和nnos神经纤维的分布。

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-12-16 DOI: 10.1016/j.tice.2025.103282

Tadasu Sato , Hirotaka Ishigaki , Takehiro Yajima , Daisuke Tachiya , Hiroyuki Ichikawa

Innervation of the human temporomandibular joint (TMJ) disk and its surrounding structures posterior vascular plexus portion was investigated by immunohistochemistry for protein gene product 9.5 (PGP 9.5) and neuronal nitric oxide synthase (nNOS). The TMJ disk was free of PGP 9.5- and nNOS-immunoreactive (-ir) nerve fibers. In the TMJ disk attachments and posterior vascular plexus portion, however, PGP 9.5- and nNOS-immunoreactivity was detected. PGP 9.5-ir nerve fibers within nerve bundles were common in these regions. Perivascular PGP 9.5-ir nerve fibers were common in the attachments and posterior vascular plexus portion but not in the posterior attachment inferior. Isolated PGP 9.5-ir nerve fibers were also scattered throughout the TMJ attachments but not in the posterior vascular plexus portion. There was no significant difference about the density of PGP 9.5-ir nerve fibers among all of the attachments and posterior vascular plexus portion. NOS-ir nerve fibers within nerve bundles were common in the anterior and posterior attachments inferior, and the posterior vascular plexus portion. Perivascular nNOS-ir nerve fibers in the anterior attachment inferior were more abundant than in other regions. Isolated nNOS-ir nerve fibers were common in the anterior attachment inferior but not in other regions. Fine isolated nerve fibers with varicose appearance occasionally had small swellings in their terminals. Thick isolated nerve fibers rarely showed unencapsulated corpuscular endings with multiple large and spindle-shaped swellings. The density of nNOS-ir nerve fibers in the anterior attachment inferior was significantly higher than in the posterior attachment superior. In addition, the double immunofluorescence method demonstrated that vascular and isolated nNOS-ir nerve fibers were also immunoreactive for PGP 9.5 in the anterior attachment inferior. The present study suggests that nNOS-ir nerve fibers with a parasympathetic nature can control blood flow mainly in the anterior attachment inferior and slightly in other attachments and the posterior vascular plexus portion. nNOS-ir nerve fibers with a sensory nature may be associated with nociceptive transmission in the TMJ disk attachments.

采用免疫组化方法对人颞下颌关节（TMJ）盘及其周围结构后血管丛部分的神经支配进行了蛋白基因产物9.5 （PGP 9.5）和神经元型一氧化氮合酶（nNOS）的检测。颞下颌关节盘无PGP 9.5和nnos免疫反应（-ir）神经纤维。然而，在TMJ椎间盘附着体和后血管丛部分，检测到PGP 9.5和nnos免疫反应性。神经束内PGP 9.5-ir神经纤维在这些区域普遍存在。血管周围PGP 9.5-ir神经纤维常见于附着物和后血管丛部分，而不见于后附着物下方。离体PGP 9.5-ir神经纤维也分布在TMJ附着物中，但未分布在后血管丛部分。PGP - 9.5-ir神经纤维密度在各附着体及后血管丛部分间无显著差异。神经束内NOS-ir神经纤维常见于前、后附着体、下、后血管丛部分。前附着下血管周围nNOS-ir神经纤维较其他区域丰富。分离的nNOS-ir神经纤维在前附着下常见，而在其他区域不常见。有静脉曲张表现的细分离神经纤维偶尔在其末端有小的肿胀。粗的分离神经纤维很少有未包封的小体末梢，并有多个大的梭形肿胀。前附着下方的nNOS-ir神经纤维密度明显高于后附着上方。此外，双免疫荧光法显示前附着下的血管和离体nNOS-ir神经纤维对PGP 9.5也有免疫反应。本研究表明，具有副交感神经性质的nNOS-ir神经纤维主要控制前附著、下附著和后血管丛部分的血流，其他附著和后血管丛部分的血流控制较少。具有感觉性质的nNOS-ir神经纤维可能与颞下颌关节盘附着物的伤害性传递有关。

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引用次数: 0

Huang Qi Decoction inhibits differentiation of hepatic oval cells to cholangiocytes via the β-catenin pathway to ameliorate hepatic fibrosis 黄芪汤通过β-catenin途径抑制肝卵圆细胞向胆管细胞分化，改善肝纤维化

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-12-16 DOI: 10.1016/j.tice.2025.103283

Zhi-dong Liu , Ke-pei Zhang , Dan-yang Wang , Xiao Zhang

Excessive cholangiocyte expansion promotes liver diseases progression. Wnt/β-catenin signaling is crucial in regulating cell differentiation. Our previous studies showed that Huang Qi Decoction (HQD) could ameliorate progression of cholestatic liver fibrosis (CLF) through inhibition of hepatic oval cells (HOCs) differentiation into cholangiocytes. However, the role of HQD in β-catenin signaling in cholangiocyte differentiation remains unclear. In this study, bile duct ligation (BDL) model was established in rats for in vivo experiment and hepatic oval cell line (WB-F344) via stimulation with sodium butyrate for in vitro experiment. Histology analysis showed that HQD ameliorated BDL-induced hepatic fibrosis (HF) with the reduction of alpha smooth muscle actin and collagen I expression. HQD inhibited CK-19 and EpCam protein expression and decreased hydroxyproline level in BDL rat liver. HQD inhibited Cyclin D1 and c-myc mRNA and protein expression levels and blocked β-catenin nuclear translocation in liver. Moreover, HQD inhibited Wnt3a expression in BDL rat liver. In vitro results showed that HQD inhibited differentiation of WB‑F344 cells into cholangiocyte with a decreased CK-19, Cyclin D1 and c-myc mRNA and protein expression. HQD blocked β-catenin nuclear translocation during hepatic oval cell differentiation to cholangiocytes in WB-F344 cells. In addition, overexpression of β-catenin promoted hepatic oval cell differentiation into cholangiocytes and abolished the inhibitory effect of HQD. Taken together, this study has highlighted that HQD could prevent CLF by inhibiting differentiation of HOCs into cholangiocytes via the β-catenin signaling pathway, which suggests that β-catenin may be considered as a potential target for HQD during CLF treatment.

胆管细胞过度扩张促进肝脏疾病的进展。Wnt/β-catenin信号在调节细胞分化中起着至关重要的作用。我们前期研究发现，黄芪汤通过抑制肝卵圆细胞向胆管细胞的分化，改善胆汁淤积性肝纤维化（CLF）的进展。然而，HQD在β-catenin信号在胆管细胞分化中的作用尚不清楚。本研究建立大鼠胆管结扎（BDL）模型进行体内实验，并通过丁酸钠刺激肝卵圆细胞株WB-F344进行体外实验。组织学分析显示，HQD通过降低α -平滑肌肌动蛋白和I型胶原的表达，改善bdl诱导的肝纤维化（HF）。HQD抑制BDL大鼠肝脏CK-19和EpCam蛋白表达，降低羟脯氨酸水平。HQD抑制肝脏细胞周期蛋白D1和c-myc mRNA和蛋白表达水平，阻断β-catenin核易位。此外，HQD可抑制BDL大鼠肝脏中Wnt3a的表达。体外结果显示，HQD抑制WB‑F344细胞向胆管细胞的分化，降低CK-19、Cyclin D1和c-myc mRNA和蛋白的表达。HQD阻断WB-F344细胞肝卵圆细胞向胆管细胞分化过程中β-catenin核易位。此外，β-catenin过表达可促进肝卵圆细胞向胆管细胞分化，消除HQD的抑制作用。综上所述，本研究强调了HQD可以通过β-catenin信号通路抑制hoc向胆管细胞的分化来预防CLF，这表明β-catenin可能被认为是CLF治疗过程中HQD的潜在靶点。

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引用次数: 0

Nano-selenium ameliorates lead oxide nanoparticle-induced reproductive toxicity in japanese quails via restoring gonadal antioxidant activity and normalization of sex hormones 纳米硒通过恢复日本鹌鹑性腺抗氧化活性和性激素正常化，改善了氧化铅纳米颗粒诱导的日本鹌鹑生殖毒性。

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-12-16 DOI: 10.1016/j.tice.2025.103281

Omnia I. Eleouny , Magda I. Abo-Samaha , Hanan A. Ghoneim , Sahar F. Mahmoud , Adel H. Saad , Yasser S. El-Sayed

This study investigated the protective effects of nano-selenium (Nano-Se) against lead oxide nanoparticle (PbNPs)-induced reproductive toxicity in Japanese quails (Coturnix japonica). Birds (n = 288) were allocated into control, Nano-Se (0.2 mg/kg diet), PbNPs (0.25 or 0.50 µg/ml drinking water), and combined Nano-Se + PbNPs groups. PbNP exposure caused dose-dependent growth suppression and severe reproductive toxicity, marked by diminished sperm quality, reduced gonadal weights, and deteriorated egg quality (reduced shell thickness and Haugh units). These effects were associated with elevated gonadal oxidative stress (increased malondialdehyde, decreased glutathione-S-transferase) and disruption of the hypothalamic-pituitary-gonadal axis, evidenced by suppressed serum testosterone, FSH, and LH. Histopathological analysis confirmed testicular degeneration, follicular atresia, and oviduct inflammation. Concurrent Nano-Se supplementation effectively mitigated these impairments, restoring antioxidant capacity, normalizing endocrine profiles, and preserving gonadal histoarchitecture. The results demonstrate that Nano-Se significantly protects against PbNP-induced reproductive dysfunction by enhancing antioxidant defenses and supporting hormonal balance, indicating its potential as a dietary intervention against nanoscale heavy metal toxicity in avian species.

本研究探讨了纳米硒（Nano-Se）对氧化铅纳米颗粒（PbNPs）诱导的日本鹌鹑生殖毒性的保护作用。将雏鸟（n = 288）分为对照组、纳米硒组（0.2 mg/kg日粮）、PbNPs组（0.25或0.50 µg/ml饮用水）和纳米硒+ PbNPs联合组。pbb暴露导致剂量依赖性生长抑制和严重的生殖毒性，其特征是精子质量下降，性腺重量减少，卵子质量恶化（壳厚度和哈夫单位减少）。这些影响与性腺氧化应激升高（丙二醛升高，谷胱甘肽- s -转移酶降低）和下丘脑-垂体-性腺轴的破坏有关，可以通过抑制血清睾酮、FSH和LH来证明。组织病理学分析证实睾丸变性、卵泡闭锁和输卵管炎症。同时补充纳米硒有效地减轻了这些损伤，恢复抗氧化能力，使内分泌谱正常化，并保留性腺组织结构。结果表明，纳米硒通过增强抗氧化防御和支持激素平衡，显著保护鸟类免受pbnp诱导的生殖功能障碍，这表明纳米硒有可能作为一种饮食干预措施，对抗纳米级重金属中毒。

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引用次数: 0

Corrigendum to “Formononetin enhances angiogenesis in diabetic wounds by inhibiting ferroptosis through suppression of mtROS-mediated xCT/GPX4 upregulation” [Tissue Cell 98(2026) 103141] “芒柄花素通过抑制mtros介导的xCT/GPX4上调来抑制铁凋亡，从而促进糖尿病伤口血管生成”[Tissue Cell 98(2026) 103141]。

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-12-16 DOI: 10.1016/j.tice.2025.103275

Xinying Li, Ding Zhu, Yanguo Wang, Chuanqi Zhao, Yuangang Lu

引用次数: 0

A practical workflow for fixation and autofluorescence reduction in correlative light and electron microscopy of postmortem human brain tissue 在相关光学和电子显微镜下对死后人脑组织进行固定和自身荧光还原的实用工作流程。

IF 2.5 4区生物学 Q1 ANATOMY & MORPHOLOGY

Tissue & cell

Pub Date : 2025-12-16 DOI: 10.1016/j.tice.2025.103284

Ha-Eon Lee , Hong Lim Kim , Ara Cho , Do-Gyun Kim , Min-Jin Park , Yuna Oh , Yong Soo Park , Rafael T. Han , Mun‑Yong Lee , Tae-Ryong Riew

Background

Correlative Light and Electron Microscopy (CLEM) on postmortem human brain tissue is limited by poor ultrastructural preservation and high endogenous autofluorescence. Furthermore, many existing protocols lack the flexibility required for brain banking, where tissues are preserved for diverse, unplanned future studies. The aim of this study was to establish an effective, flexible preservation and processing workflow for CLEM analysis of postmortem human brain tissue.

Methods

We evaluated different fixation protocols (4 % paraformaldehyde [PFA] vs. 4 % PFA + 0.2 % glutaraldehyde [GLA]) and autofluorescence quenching agents on cryopreserved human medial prefrontal cortex tissue. Immunofluorescence intensity for glial and neuronal markers and ultrastructural integrity was assessed via confocal and transmission electron microscopy (TEM).

Results

The addition of 0.2 % GLA to 4 % PFA significantly improved the ultrastructure without compromising immunoreactivity for most markers. In contrast, autofluorescence quenchers, while reducing background signal and autofluorescence, severely degraded ultrastructure, rendering them unsuitable for subsequent electron microscopy analysis. Using this established protocol (4 % PFA + 0.2 % GLA without quenchers), we successfully performed high-fidelity CLEM, correlating immunolabeled neuronal structures to their ultrastructural counterparts and identifying perinuclear autofluorescence as lipofuscin granules.

Conclusion

We established an adaptive workflow for postmortem human brain tissue that balances ultrastructural preservation and antigenicity. Fixation with 4 % PFA + 0.2 % GLA followed by cryopreservation creates a flexible, high-quality tissue archive. For high-fidelity CLEM or electron microscopy analysis, solvent-based quenchers like Sudan Black B must be omitted. This protocol enhances the utility of irreplaceable human brain samples for multimodal neuropathological studies.

背景：死后脑组织的相关光电子显微镜（CLEM）受超微结构保存差和内源性自身荧光高的限制。此外，许多现有的协议缺乏脑库所需的灵活性，在脑库中，组织被保存下来用于各种各样的、计划外的未来研究。本研究的目的是建立一种有效、灵活的保存和处理工作流程，用于人死后脑组织的CLEM分析。方法我们评估了不同的固定方案（4 %多聚甲醛[PFA] vs. 4 %多聚甲醛+ 0.2 %戊二醛[GLA]）和自身荧光猝灭剂在冷冻保存的人内侧前额叶皮层组织上的作用。通过共聚焦和透射电镜（TEM）评估神经胶质和神经元标记物的免疫荧光强度和超微结构完整性。结果：添加0.2 % GLA至4 % PFA可显著改善超微结构，且不影响大多数标记物的免疫反应性。相比之下，自荧光猝灭剂在降低背景信号和自身荧光的同时，严重破坏了超微结构，使其不适合后续的电镜分析。使用这种已建立的方案（4 % PFA + 0.2 % GLA，无猝灭剂），我们成功地进行了高保真CLEM，将免疫标记的神经元结构与其超微结构相关联，并将核周自身荧光识别为脂褐素颗粒。结论：我们建立了一套能够平衡超微结构保存和抗原性的人死后脑组织自适应工作流程。用4 % PFA + 0.2 % GLA固定，然后冷冻保存，形成灵活、高质量的组织档案。对于高保真CLEM或电子显微镜分析，溶剂型猝灭剂如苏丹黑B必须省略。该方案提高了不可替代的人脑样本在多模态神经病理研究中的效用。

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