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Efficacy of pumpkin seed oil on paclitaxel-induced tongue mucosal injury in rat: Structural and biochemical insights 南瓜籽油对紫杉醇所致大鼠舌黏膜损伤的保护作用:结构和生化观察
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2026-01-08 DOI: 10.1016/j.tice.2026.103314
Amira Adly Kassab , Hani Ayman Alajou , Hadi Ali Alshihmani , Layan Suliman Hussein , Dareen Mahmoud Nofal , Zain Said Al-moudi , Leen Yousef Alkhateeb , Haneen Mustafa Alnasaa , Asmaa Mohamed Kharsa , Lara Mazen Aljabaly , Ruba Ahmad Alslehat , Adel Mohamed Aboregela , Darwish Badran
Oral mucositis is a common yet often overlooked complication of chemotherapy. Although paclitaxel (PTX) is a potent anticancer agent, it induces various pathologies in the oral tissues. Pumpkin seed oil (PSO) was prized significant pharmacological properties that can produce health-protective effects. The study aimed to highlight the effects of PTX on the dorsal tongue mucosa of rats and assess the alleviative role of PSO focusing on the underlying mechanisms. Forty rats were divided into: Control, PSO, PTX, and PTX + PSO. PTX was administered intraperitoneally at a dose of 2 mg/kg once weekly, while PSO was given orally at 1.5 ml/kg daily, both for 6 consecutive weeks. Tongue tissues were subjected to histological, immunohistochemical, biochemical and RT-qPCR analyses. PTX group exhibited a loss of the normal papillary architecture of the dorsal tongue mucosa. There was a statistically significant reduction in the epithelial thickness, the height and width of the papillae and proliferating cell nuclear antigen (PCNA) immunoreactivity. Malondialdehyde (MDA) levels were significantly elevated, while glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) levels were markedly decreased. A significant upregulation of NF-κβ, TNF-α, IL-1β, IL-18, and IL-6 mRNA expression was observed denoting markedly fired inflammatory cascade. PSO + PTX group showed significant mitigation of these molecular alterations which were translated into structural conservation with no significant difference when compared to the control group. PTX triggers inflammation and oxidative stress, leading to epithelial proliferation arrest. PSO, antioxidant and anti-inflammatory rescuer, effectively preserves the structural integrity of the dorsal tongue mucosa.
口腔黏膜炎是化疗中一种常见却常被忽视的并发症。虽然紫杉醇(PTX)是一种有效的抗癌药物,但它会引起口腔组织的各种病变。南瓜籽油(PSO)具有重要的药理作用,具有保健作用。本研究旨在观察PTX对大鼠舌背黏膜的影响,并探讨PSO的缓解作用,重点探讨其机制。40只大鼠分为:对照组、PSO、PTX、PTX + PSO。PTX腹腔注射剂量为2 mg/kg,每周1次;PSO口服剂量为1.5 ml/kg,连续6周。对舌组织进行组织学、免疫组织化学、生化和RT-qPCR分析。PTX组表现为舌背黏膜正常乳头状结构的丧失。上皮细胞的厚度、乳头的高度和宽度以及增殖细胞核抗原(PCNA)的免疫反应性均有统计学意义的降低。丙二醛(MDA)水平显著升高,谷胱甘肽(GSH)、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)水平显著降低。NF-κβ、TNF-α、IL-1β、IL-18和IL-6 mRNA表达显著上调,表明炎症级联反应明显。PSO + PTX组显示出这些分子改变的显著缓解,这些改变转化为结构守恒,与对照组相比无显著差异。PTX引发炎症和氧化应激,导致上皮细胞增殖停滞。PSO是抗氧化和抗炎救援剂,有效地保持舌背黏膜的结构完整性。
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引用次数: 0
HAX1 overexpression induces osteogenic differentiation of periodontal ligament stem cells via the MEK/ERK signaling cascade HAX1过表达通过MEK/ERK信号级联诱导牙周韧带干细胞成骨分化
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2026-01-06 DOI: 10.1016/j.tice.2026.103311
Peiqi Hao , Xin-yu Zhang , Mengting Wang, Fan Bao, Hui Guo

Background

Periodontitis is characterized by periodontal tissue destruction and subsequent tooth loss, significantly impacting quality of life. The potential of HAX1, a gene implicated in periodontitis pathogenesis, to modulate the differentiation of periodontal ligament stem cells (PDLSCs) and its therapeutic potential remains unexplored.

Methods

PDLSCs were randomly divided into seven experimental groups, undergoing either HAX1 overexpression or knockdown treatments, followed by lipogenic or osteogenic induction. Lipogenic differentiation was assessed via Oil Red O staining, while osteogenic differentiation was evaluated by ALP staining. Mineralization capacity was determined by Alizarin red staining, and proliferative activity was measured with CCK-8 assays. RT-qPCR and Western blot analyses were employed to quantify mRNA and protein expression of genes associated with the RAF/MEK/ERK signaling pathway and to validate the efficacy of HAX1 manipulation.

Results

Validation of mRNA and protein expression confirmed successful establishment and screening of HAX1-overexpressing and -knockdown cell lines. Subsequent investigations revealed that HAX1 overexpression enhanced osteogenic differentiation and mineralization of PDLSCs while suppressing proliferation and lipogenic differentiation. Conversely, HAX1 knockdown yielded opposing effects. Analysis of the RAF/MEK/ERK signaling pathway demonstrated that HAX1 overexpression significantly promoted MEK/ERK phosphorylation and pathway activation, without affecting the RAF family.

Conclusion

HAX1 overexpression activates the ERK/MEK-mediated MAPK signaling pathway, which promotes osteogenic differentiation and inhibits lipid differentiation in PDLSCs, with positive therapeutic implications in periodontitis.
牙周炎的特点是牙周组织破坏和随后的牙齿脱落,严重影响生活质量。HAX1是一种与牙周炎发病机制有关的基因,其调节牙周韧带干细胞(PDLSCs)分化的潜力及其治疗潜力仍未被探索。方法将spdlscs随机分为7个实验组,分别进行HAX1过表达或敲低处理,然后诱导成脂或成骨。油红O染色评估成脂分化,ALP染色评估成骨分化。采用茜素红染色法测定矿化能力,CCK-8法测定增殖活性。采用RT-qPCR和Western blot分析定量RAF/MEK/ERK信号通路相关基因的mRNA和蛋白表达,验证HAX1操作的有效性。结果mRNA和蛋白表达验证证实了hax1过表达和低表达细胞系的成功建立和筛选。随后的研究表明,HAX1过表达增强了PDLSCs的成骨分化和矿化,同时抑制了增殖和脂质分化。相反,HAX1基因敲低会产生相反的效果。对RAF/MEK/ERK信号通路的分析表明,HAX1过表达可显著促进MEK/ERK磷酸化和通路激活,而不影响RAF家族。结论hax1过表达激活ERK/ mek介导的MAPK信号通路,促进PDLSCs成骨分化,抑制脂质分化,对牙周炎具有积极的治疗意义。
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引用次数: 0
Polystyrene microplastics impact on cardiac and pulmonary physiology and microenvironment in a mouse model: Role of taurine supplementation and molecular docking insights 聚苯乙烯微塑料对小鼠模型中心肺生理和微环境的影响:牛磺酸补充的作用和分子对接见解
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2026-01-06 DOI: 10.1016/j.tice.2026.103313
Amany Abdel-Rahman Mohamed , Badriyah S. Alotaibi , Yasmina M. Abd El-Hakim , Ibrahim Jafri , Samah S. Abuzahrah , Tarek Khamis , Ahmed E. Noreldin , Ali H. El-Far , Nawal Alsubaie , Wesam K. Bakhsh , Mohamed El-Gamal
Polystyrene microplastics (PS-MPs) have recently gained attention as widespread environmental contaminants posing risks to both human and animal health. In this study, we investigated the potential protective effect of taurine (200 mg/kg b.wt) against cardiopulmonary toxicity induced by PS-MPs (10 mg/kg b.wt) in male Swiss mice following a 60-day oral exposure. Molecular docking investigation for both proteins and mRNA targets was carried out utilizing a global, flexible docking strategy that allowed for full ligand conformational freedom and binding surface exploration. We designed an experimental model comprising four groups: Control, Taurine, PS-MPs, and a combined group (PS-MPs + Taurine). The results indicated that taurine significantly protected against PS-MPs-induced biochemical, histopathological, and molecular alterations that occurred in the cardiac and pulmonary tissues of mice. PS-MPs exposure disrupted the redox balance by suppressing enzymatic antioxidants (CAT, SOD, GPx) and increasing lipid peroxidation, while elevating cardiac injury markers (LDH, CK-MB, CPK, cTnI). These oxidative changes were accompanied by increased pro-inflammatory cytokines (TNF-α, IL-1β) in both tissues, histopathological lesions in the heart and lungs, and upregulation of gene expressions of inflammatory and pyroptotic mediators (NLRP3, Caspase-1, ASC, GSDMD, NF-κB, COX-2, IL-1β, IL-18). Co-administration of taurine with PS-MPs markedly ameliorated these alterations, restoring antioxidant defenses, reducing lipid peroxidation and cytokine levels, downregulating inflammasome and pyroptosis-related gene expression, and improving tissue architecture. Molecular docking supported these findings by showing taurine’s potential interactions with inflammatory mediators, while styrene exhibited affinity for antioxidant enzymes, consistent with in vivo oxidative disruption. Collectively, the study highlights oxidative stress and inflammation as key mechanisms of PS-MPs-induced cardiopulmonary toxicity and highlights taurine’s promise as a protective agent against microplastics-related health risks.
聚苯乙烯微塑料(PS-MPs)作为一种广泛存在的环境污染物,对人类和动物的健康构成了威胁,最近引起了人们的关注。在这项研究中,我们研究了牛磺酸(200 mg/kg b.wt)对雄性瑞士小鼠口服暴露60天后PS-MPs(10 mg/kg b.wt)诱导的心肺毒性的潜在保护作用。利用全局灵活的对接策略,对蛋白质和mRNA靶点进行分子对接研究,允许完全的配体构象自由和结合表面探索。我们设计了一个实验模型,包括四组:对照组、牛磺酸组、PS-MPs组和PS-MPs +牛磺酸组。结果表明,牛磺酸对ps - mps诱导的小鼠心脏和肺组织的生化、组织病理和分子改变具有显著的保护作用。PS-MPs暴露通过抑制酶促抗氧化剂(CAT, SOD, GPx)和增加脂质过氧化作用而破坏氧化还原平衡,同时升高心脏损伤标志物(LDH, CK-MB, CPK, cTnI)。这些氧化变化伴随着两种组织中促炎细胞因子(TNF-α, IL-1β)的增加,心脏和肺部的组织病理学病变,以及炎症和焦亡介质(NLRP3, Caspase-1, ASC, GSDMD, NF-κB, COX-2, IL-1β, IL-18)基因表达的上调。牛磺酸与PS-MPs联合使用可显著改善这些改变,恢复抗氧化防御,降低脂质过氧化和细胞因子水平,下调炎性体和热缩相关基因表达,改善组织结构。分子对接显示牛磺酸与炎症介质的潜在相互作用支持了这些发现,而苯乙烯则表现出与抗氧化酶的亲和力,与体内氧化破坏一致。总的来说,该研究强调了氧化应激和炎症是ps - mps诱导的心肺毒性的关键机制,并强调了牛磺酸作为微塑料相关健康风险的保护剂的前景。
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引用次数: 0
CRViT-YOLO: A method for multi-morphological blood cell detection using convolution-restructured vision transformer crvityolo:一种基于卷积重构视觉变压器的多形态血细胞检测方法。
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2026-01-06 DOI: 10.1016/j.tice.2026.103312
Yaning Du , Yuliang Ma , Qingshan She , Xugang Xi
Complete blood cell counting plays a critical role in medical diagnostics; however, conventional manual examination is time-consuming and prone to errors due to variations in data sources, image quality, cell morphology, and staining characteristics. Deep learning has emerged as a promising solution to enhance both the accuracy and efficiency of blood cell detection. In this study, we present CRViT-YOLO, a novel detection framework built upon the YOLOv9 architecture. The proposed framework incorporates a Convolutional-Reconstructed Vision Transformer (CRViT) module to improve feature extraction by effectively capturing both local and global contextual information. Furthermore, a Feature Enhancement Module (FEM) is introduced to refine local feature representations, while the integration of the EIoU loss function enhances localization accuracy, particularly for densely packed or overlapping cells across diverse scales and types, and demonstrates robust performance in detecting polymorphic, healthy, and pathological cells. Extensive experiments conducted on four publicly available datasets—BCCD, BCDD, LISC, and BBBC041—validate the effectiveness and generalizability of the proposed approach, achieving mean average precision (mAP@50) scores of 93.9 %, 99.4 %, 98.8 %, and 76.0 %, respectively, in multi-class blood cell detection tasks.
全血细胞计数在医学诊断中起着至关重要的作用;然而,由于数据源、图像质量、细胞形态和染色特征的变化,传统的人工检查既耗时又容易出错。深度学习已经成为一种很有前途的解决方案,可以提高血细胞检测的准确性和效率。在本研究中,我们提出了一种基于YOLOv9架构的新型检测框架crviti - yolo。该框架结合了卷积重建视觉变换(CRViT)模块,通过有效捕获局部和全局上下文信息来改进特征提取。此外,引入了一个特征增强模块(FEM)来细化局部特征表示,而EIoU损失函数的集成提高了定位精度,特别是对于不同尺度和类型的密集排列或重叠细胞,并在检测多态、健康和病理细胞方面表现出强大的性能。在四个公开可用的数据集(bccd, BCDD, LISC和bbbc041)上进行的大量实验验证了所提出方法的有效性和可推广性,在多类别血细胞检测任务中,平均精度(mAP@50)分别达到93.9 %,99.4 %,98.8 %和76.0 %。
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引用次数: 0
Protective effects of polydatin on cyclophosphamide-induced ovarian and uterine damage in rats via modulation of hormonal, oxidative, inflammatory, and histopathological alterations 多丹素通过调节激素、氧化、炎症和组织病理学改变对环磷酰胺诱导的大鼠卵巢和子宫损伤的保护作用
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2026-01-06 DOI: 10.1016/j.tice.2026.103309
Ramazan Bülbül , Sefa Küçükler , Selim Çomaklı , Özge Kandemir , Elif Dalkılınç , Sevda Sağ Bayav , Cuneyt Caglayan , Fatih Mehmet Kandemir
Cyclophosphamide (Cyclo) is a chemotherapeutic agent whose clinical use is limited by its toxic effects on ovarian and uterine tissues. Polydatin (Poly), a resveratrol derivative with antioxidant and anti-inflammatory properties, was evaluated for its protective potential against Cyclo-induced reproductive toxicity. Female rats were divided into five groups: control, Poly (100 mg/kg), Cyclo, and combination groups (Cyclo + Poly 50 mg/kg, Cyclo + Poly 100 mg/kg). Poly was administered orally and Cyclo was administered intraperitoneally. Serum hormone levels (AMH, FSH, E2, LH), antioxidant parameters (SOD, CAT, GPx, GSH), inflammatory markers (NF-κB, TNF-α, IL-1β), gene expression (Pgr, Esr1, Esr2, Cyp19a1, Foxl2, Amh, Hoxa10, Lhcgr, Hsd3b1, Cyp11a1, Sohlh2), and protein levels (BAX, BCL-2, ERK1/2, CREB) were analyzed using ELISA, RT-PCR, Western blot and immunohistochemistry methods. Histopathological analyses were also performed. The results showed that Cyclo significantly disrupted hormonal balance, reduced antioxidant activity, increased inflammatory markers, and induced apoptosis in ovary and uterine tissues. Poly administered with Cyclo dose-dependently attenuated these changes, restoring hormone levels, gene expressions, antioxidant status, and tissue integrity. Consequently, Poly may be a potential therapeutic agent for alleviating Cyclo-induced reproductive toxicity.
环磷酰胺(Cyclophosphamide, Cyclo)是一种化疗药物,其临床应用因其对卵巢和子宫组织的毒性作用而受到限制。聚datatin (Poly)是一种具有抗氧化和抗炎特性的白藜芦醇衍生物,被评价其对环诱导的生殖毒性的保护潜力。雌性大鼠分为5组:对照组、Poly(100 mg/kg)组、Cyclo组、Cyclo + Poly 50 mg/kg组、Cyclo + Poly 100 mg/kg组。Poly口服,Cyclo腹腔注射。采用ELISA、RT-PCR、Western blot和免疫组化方法分析血清激素水平(AMH、FSH、E2、LH)、抗氧化参数(SOD、CAT、GPx、GSH)、炎症标志物(NF-κB、TNF-α、IL-1β)、基因表达(Pgr、Esr1、Esr2、Cyp19a1、Foxl2、AMH、Hoxa10、Lhcgr、Hsd3b1、Cyp11a1、Sohlh2)和蛋白水平(BAX、BCL-2、ERK1/2、CREB)。同时进行组织病理学分析。结果表明,Cyclo显著破坏卵巢和子宫组织的激素平衡,降低抗氧化活性,增加炎症标志物,诱导细胞凋亡。Poly与Cyclo一起剂量依赖性地减弱了这些变化,恢复了激素水平、基因表达、抗氧化状态和组织完整性。因此,Poly可能是一种潜在的治疗药物,以减轻循环诱导的生殖毒性。
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引用次数: 0
Deciphering the dose-dependent nephrotoxic mechanisms of etoxazole: Insights from redox signaling and Wnt/β-catenin axis 解读乙恶唑剂量依赖性肾毒性机制:来自氧化还原信号和Wnt/β-catenin轴的见解
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2026-01-05 DOI: 10.1016/j.tice.2026.103310
Abdullah Alghamdi , Mohammed Alissa , Alaa S. Alhegaili , Abdulkarim S. Binshaya , Awaji Y. Safhi , Ghada M. Alnafesah , Adil Abalkhail
Etoxazole (ETZ) is a selective acaricide that is reported to induce severe organ toxicity including renal impairments. The current research was conducted to evaluate the dose-dependent toxic effects of ETZ on renal tissues. Thirty-six male Sprague Dawley rats were divided into control, ETZ (2.2 mg/kg b.w/day), ETZ (11 mg/kg b.w/day), and ETZ (22 mg/kg b.w/day) treated group. It was found that ETZ intoxication upregulated the mRNA expressions of Wnt family member 1 (Wnt1), Wnt family member 4 (Wnt4), β-catenin, and dickkopf Wnt signaling pathway inhibitor 1 (DKK1) while downregulating the expression of glycogen synthase kinase 3 beta (GSK-3β) in dose-dependent manner. Moreover, ETZ exposure provoked renal oxidative stress via inhibiting the activities of catalase (CAT), glutathione peroxidase (GPx), hemoxygenase-1 (HO-1), glutathione reductase (GSR), glutathione S-transferase (GST), superoxide dismutase (SOD), and contents of glutathione (GSH) while increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA). Similarly, ETZ showed severe alterations in renal function markers as evidenced by increased concentration of Neutrophil gelatinase-associated lipocalin (NGAL), urea, creatinine, cystatin C, osteopontin, Kidney injury molecule 1 (KIM-1), and endothelin-1 while reducing the concentrations of creatinine clearance. Renal tissues showed pro-inflammatory responses at all the tested doses of ETZ as indicated by elevated levels of nuclear factor-kappa B (NF-κB), interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) & cyclooxygenase-2 (COX-2). Furthermore, a sharp escalation in the levels of cysteine–aspartic acid protease-3 (Caspase-3), Bcl-2-associated X protein (Bax), and cysteine–aspartic acid protease-9 (Caspase-9) coupled with a significant reduction in the levels of B-cell lymphoma 2 (Bcl-2) was observed following the administration of ETZ. Besides, renal tissues showed high rate of disruption in morphology at all the tested doses of ETZ thereby suggesting its reno-toxic effects. Our computation analysis showed that ETZ strongly bind with key regulatory genes thereby altering their expressions. These findings suggest that ETZ is a potent reno-toxic agent at low, moderate, and high dose administration.
乙恶唑(ETZ)是一种选择性杀螨剂,据报道可引起包括肾损害在内的严重器官毒性。本研究旨在评估ETZ对肾组织的剂量依赖性毒性作用。将36只雄性sd大鼠分为对照组、ETZ组(2.2 mg/kg b.w/day)、ETZ组(11 mg/kg b.w/day)和ETZ组(22 mg/kg b.w/day)。结果发现,ETZ中毒使Wnt家族成员1 (Wnt1)、Wnt家族成员4 (Wnt4)、β-catenin、dickkopf Wnt信号通路抑制剂1 (DKK1) mRNA表达上调,糖原合成酶激酶3β (GSK-3β) mRNA表达下调,且呈剂量依赖性。此外,ETZ暴露通过抑制过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GPx)、血氧合酶-1 (HO-1)、谷胱甘肽还原酶(GSR)、谷胱甘肽s -转移酶(GST)、超氧化物歧化酶(SOD)活性和谷胱甘肽(GSH)含量,增加活性氧(ROS)和丙二醛(MDA)水平,引起肾脏氧化应激。同样,ETZ显示出肾功能标志物的严重改变,中性粒细胞明胶酶相关的脂钙蛋白(NGAL)、尿素、肌酐、胱抑素C、骨桥蛋白、肾损伤分子1 (KIM-1)和内皮素-1的浓度升高,而肌酐清除率的浓度降低。在所有试验剂量下,肾组织均表现出促炎反应,如核因子-κB (NF-κB)、白细胞介素-1β (IL-1β)、肿瘤坏死因子-α (TNF-α)、白细胞介素-6 (IL-6)和环氧化酶-2 (COX-2)水平升高。此外,在服用ETZ后,观察到半胱氨酸-天冬氨酸蛋白酶-3 (Caspase-3)、Bcl-2相关X蛋白(Bax)和半胱氨酸-天冬氨酸蛋白酶-9 (Caspase-9)水平急剧上升,同时b细胞淋巴瘤2 (Bcl-2)水平显著降低。此外,在所有测试剂量下,肾组织形态学破坏率都很高,从而提示其肾毒性作用。我们的计算分析表明,ETZ与关键调控基因强烈结合,从而改变其表达。这些发现表明,ETZ在低、中、高剂量下都是一种强效的肾毒性药物。
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引用次数: 0
The oxidative stress regulatory mechanism of autophagy and apoptosis in lens epithelial cells 氧化应激对晶状体上皮细胞自噬和凋亡的调控机制
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2026-01-02 DOI: 10.1016/j.tice.2025.103308
Mengyi Lin , Yalan Chen , Gangjin Kang
Cataract is the leading cause of blindness worldwide, and its incidence rate is still on the rise. Oxidative stress plays a key role in the formation of cataracts. Oxidative stress not only causes damage to lens epithelial cells (LECs) but also activates autophagy and apoptosis. Specifically, under oxidative stress conditions, the apoptosis of LECs is significantly activated, which in turn leads to accelerated lens opacity and cataract development. Meanwhile, autophagy, as a cellular self-protection mechanism, exhibits bidirectional regulatory characteristics in response to oxidative stress. In addition, in diabetic cataracts, high glucose levels can disrupt the balance between autophagy and oxidative stress, exacerbating LECs damage. This cross-effect of apoptosis and autophagy highlights the core position of both in the pathogenesis of cataracts, but the specific molecular mechanism still needs to be further clarified. Although antioxidants can alleviate apoptosis and autophagy damage induced by oxidative stress, the clinical treatment of cataracts still urgently needs prevention and treatment strategies targeting molecular mechanisms.
白内障是全球致盲的主要原因,其发病率仍在上升。氧化应激在白内障的形成中起着关键作用。氧化应激不仅会导致晶状体上皮细胞损伤,还会激活晶状体上皮细胞的自噬和凋亡。在氧化应激条件下,lec细胞的凋亡被显著激活,从而加速晶状体混浊和白内障的发生。同时,自噬作为细胞的一种自我保护机制,在氧化应激反应中表现出双向调节的特点。此外,在糖尿病性白内障中,高葡萄糖水平会破坏自噬和氧化应激之间的平衡,加剧LECs损伤。细胞凋亡与细胞自噬的交叉作用凸显了两者在白内障发病中的核心地位,但具体的分子机制仍需进一步阐明。虽然抗氧化剂可以减轻氧化应激引起的细胞凋亡和自噬损伤,但临床治疗白内障仍迫切需要针对分子机制的预防和治疗策略。
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引用次数: 0
Hepatoprotective effect of chitosan-vitamin C based hydrogel on alpha-Naphthylisothiocyanate-induced cholestasis in infant rats 壳聚糖-维生素C水凝胶对α -萘基异硫氰酸酯诱导的幼鼠胆汁淤积的肝保护作用。
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2025-12-31 DOI: 10.1016/j.tice.2025.103307
Sarah Ali Qutb , Dalia Y. Saad , Ayman Saber Mohamed

Background

Infant cholestasis is characterized by the buildup of biliary substances in blood and extrahepatic tissues because of impaired canalicular biliary flow, which harm the liver and bile ducts. Vitamin C (Vit C) is antioxidant which has demonstrated encouraging outcomes in the treatment of different liver disorders, including fibrosis.

Aim

The present study seeks to assess the synergistic protective effect of chitosan and vitamin C based hydrogel (CSVC hydrogel) on alpha-Naphthylisothiocyanate (ANIT)-induced cholestasis in infant rats.

Method

Thirty male Wister rats were divided into five groups: control, ANIT, and cholestatic rats treated with chitosan hydrogel (60 mg/kg body weight, orally), Vit C (40 mg/kg body weight, orally), and CSVC hydrogel (60 mg/kg body weight, orally). Liver functions, oxidative stress, inflammatory, and apoptotic markers were investigated.

Results

CSVC hydrogel had remarkable antioxidant and anti-inflammatory properties in vitro. The administration of CSVC hydrogel significantly improved liver function, evidenced by decreased hepatic enzyme activity such as AST (28.11 ± 0.83###), ALT (16.56 ± 0.95###), ALP (126.49 ± 3.06###), GGT (0.11 ± 0.02###), total bilirubin (1.71 ± 0.05###) and a rise in albumin levels to 3.11 ± 0.10###. Moreover, CSVC hydrogel resulted in an increase in reduced glutathione and the activity of antioxidant enzymes (GST, SOD, GPx, and catalase), while simultaneously decreasing the production of malondialdehyde and nitric oxide. CSVC hydrogel decreased DNA damage in cholestatic rats and partially corrected the abnormal structure of hepatic tissues in ANIT rats. CSVC hydrogel decreased inflammation by decreasing concentrations of interleukin 6 (IL-6) and interleukin 1β (IL-1β) while enhancing the antiapoptotic protein BCL2. The immunohistochemistry analysis revealed a reduction in inflammation and apoptosis, through the decreased production of tumor necrosis factor alpha (TNF-α) and Caspase 3.

Conclusion

CSVC hydrogel mitigated liver fibrosis via its anti-inflammatory, anti-apoptotic, antioxidant properties, and its DNA protective effects.
背景:婴儿胆汁淤积症的特点是由于小管胆道流动受损,导致血液和肝外组织中胆道物质积聚,从而损害肝脏和胆管。维生素C (Vit C)是一种抗氧化剂,在治疗包括纤维化在内的各种肝脏疾病方面显示出令人鼓舞的结果。目的:探讨壳聚糖和维生素C基水凝胶(CSVC水凝胶)对α -萘基异硫氰酸酯(ANIT)诱导的幼鼠胆汁淤积的协同保护作用。方法:将30只雄性Wister大鼠分为5组:对照组、ANIT组和胆汁淤积大鼠,分别给予壳聚糖水凝胶(60 mg/kg体重,口服)、Vit C(40 mg/kg体重,口服)和CSVC水凝胶(60 mg/kg体重,口服)。研究肝功能、氧化应激、炎症和凋亡标志物。结果:CSVC水凝胶具有明显的体外抗氧化和抗炎作用。管理CSVC水凝胶明显改善肝功能,证明通过减少肝酶活性,如AST(28.11 ± 0.83 # # #)、ALT(16.56 ± 0.95 # # #),高山(126.49 ± 3.06 # # #)、GGT(0.11 ± 0.02 # # #)、总胆红素(1.71 ± 0.05 # # #)和白蛋白水平上升到3.11 ± 0.10 # # #。此外,CSVC水凝胶导致还原性谷胱甘肽和抗氧化酶(GST、SOD、GPx和过氧化氢酶)活性的增加,同时减少丙二醛和一氧化氮的产生。CSVC水凝胶能减轻胆汁淤积大鼠DNA损伤,部分纠正ANIT大鼠肝脏组织结构异常。CSVC水凝胶通过降低白细胞介素6 (IL-6)和白细胞介素1β (IL-1β)浓度,增强抗凋亡蛋白BCL2来减轻炎症反应。免疫组化分析显示,通过降低肿瘤坏死因子α (TNF-α)和Caspase 3的产生,炎症和细胞凋亡减少。结论:CSVC水凝胶通过抗炎、抗凋亡、抗氧化及DNA保护作用减轻肝纤维化。
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引用次数: 0
Empagliflozin as a potential therapy for PCOS: Restoring hormonal balance and ovarian function in a letrozole-induced rat model 恩帕列净作为多囊卵巢综合征的潜在疗法:在来曲唑诱导的大鼠模型中恢复激素平衡和卵巢功能
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2025-12-31 DOI: 10.1016/j.tice.2025.103298
Heba A. Habib , Mahmoud El-Daly , Yahya I. Asiri , Saud Alqahtani , Eman M. Awad , Sara MN. Abdel Hafez , Al-Shaimaa F. Ahmed , Aliaa F. Anter

Background

Polycystic ovarian syndrome (PCOS) is a prevalent endocrine disorder that often leads to infertility. The characteristic hyperandrogenemia and elevated luteinizing hormone /follicle stimulating hormone ratio, resulting in ovulation failure, are the hallmarks of PCOS. Recent preclinical and clinical studies revealed the potential of empagliflozin (EMPA; a sodium-glucose cotransporter-2 inhibitor) to improve PCOS symptoms. However, the effects of EMPA on endocrine disturbances and ovarian cyst formation were not thoroughly investigated. Objectives: The primary objective of this study was to explore the potential of EMPA as a treatment for PCOS. Methods: PCOS was induced by daily administration of letrozole (1 mg/kg for 21 days). The PCOS group was then divided into PCOS (untreated), PCOS+EMPA (10 mg/kg), and PCOS + metformin (300 mg/kg). All groups, except for the vehicle-treated group, continued to receive letrozole throughout the 21-day treatment period. Serum and ovaries were collected for various measurements at the end of the experiments. Results: The results of the study showed that induction of PCOS resulted in high testosterone levels, luteinizing hormone /follicle stimulating hormone ratio, and ovarian weights. Disturbed apoptosis and high transforming growth factor-β and inducible nitric oxide synthase expression were also evident in the PCOS group. EMPA treatment resulted in an ameliorative effect of these changes, comparable to metformin's effect. Conclusion: Our results suggest that EMPA could be a promising treatment for PCOS in rats, with its protective effect potentially mediated through its ability to restore hormonal imbalance and to restore transforming growth factor-β and inducible nitric oxide synthase expression, providing reassurance to the audience about its efficacy.
背景:多囊卵巢综合征(PCOS)是一种常见的内分泌紊乱,常导致不孕。特征性的高雄激素血症和黄体生成素/促卵泡激素比值升高,导致排卵失败,是多囊卵巢综合征的标志。最近的临床前和临床研究揭示了恩格列净(EMPA,一种钠-葡萄糖共转运蛋白-2抑制剂)改善多囊卵巢综合征症状的潜力。然而,EMPA对内分泌紊乱和卵巢囊肿形成的影响尚未深入研究。目的:本研究的主要目的是探讨EMPA作为PCOS治疗的潜力。方法:每日给药来曲唑(1 mg/kg)诱导PCOS 21 d。将PCOS组分为PCOS(未经治疗)、PCOS+EMPA(10 mg/kg)和PCOS+ 二甲双胍(300 mg/kg)。在整个21天的治疗期内,除载药组外,所有组均继续服用来曲唑。实验结束时采集血清和卵巢进行各项测量。结果:本研究结果显示,PCOS诱导患者睾酮水平升高,黄体生成素/促卵泡激素比值升高,卵巢重量增大。PCOS组细胞凋亡紊乱,转化生长因子-β和诱导型一氧化氮合酶表达升高。EMPA治疗导致这些变化的改善效果,与二甲双胍的效果相当。结论:EMPA可能是一种治疗PCOS大鼠的有效方法,其保护作用可能是通过恢复激素失衡、恢复转化生长因子-β和诱导型一氧化氮合酶的表达来实现的,为其疗效提供了保证。
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引用次数: 0
Phytochemicals in ethanolic extract of Cinnamomum tamala induce cell cycle arrest, DNA damage and apoptosis in human breast cancer cell lines MDA-MB-231 and MCF-7 肉桂醇提物中的植物化学物质诱导人乳腺癌细胞株MDA-MB-231和MCF-7细胞周期阻滞、DNA损伤和凋亡
IF 2.5 4区 生物学 Q1 ANATOMY & MORPHOLOGY Pub Date : 2025-12-31 DOI: 10.1016/j.tice.2025.103306
Ishrat Husain , Anu Chandra , Mrinal Ranjan Srivastava , Farzana Mahdi , Rumana Ahmad
Cinnamomum tamala (CT), commonly known as ‘Indian bay leaf’ in English and ‘Tejpatta’ in Hindi is a tree belonging to family Lauraceae and is widely used as a culinary condiment with well-known medicinal properties. In the present study, ethanolic extract of dried CT leaves (EECTL) was characterized by HPLC and the antioxidant activity was evaluated using DPPH radical scavenging assay. Anticancer activity of EECTL was evaluated against human breast cancer cell lines MDA-MB-231 and MCF-7 vis-à-vis normal HEK-293 and Vero cells using MTT assay, along with morphological analysis using phase-contrast microscopy. EECTL-induced chromatin condensation and apoptosis were studied using Hoechst and AO/EtBr staining by fluorescence microscopy, as well as by qRT-PCR analysis. Annexin V-FITC/PI double staining for apoptosis detection and cell cycle analysis using PI were performed using flow cytometry. Catechin (Rt = 6.085 min), eugenol (Rt = 7.211 min) and apigenin (Rt = 19.496 min) were identified as the major bioactive components. EECTL was found to induce apoptosis in MDA-MB-231 and MCF-7 cell lines in a dose-dependent manner with IC50 values of 47 and 110 µg/mL, respectively. Interestingly, EECTL did not exhibit any significant effect on normal HEK-293 and Vero cells. The selectivity indices of EECTL with respect to Vero/MDA-MB-231 and HEK-293/MDA-MB-231 were determined as 5.69 and 8.16, respectively, while those for Vero/MCF-7 and HEK-293/MCF-7 were 2.43 and 3.48, respectively. Mechanistically, EECTL caused cell cycle arrest at G0/G1 in MDA-MB-231 and sub-G0 phase in MCF-7 cells, leading to chromatin condensation and apoptosis. DNA damage and fragmentation were confirmed via comet assay. Expression analysis revealed that EECTL upregulated the expression of TP53 in MDA-MB-231 and MCF-7 cells. EECTL was found to have significant antioxidant potential against DPPH radicals, with an IC50 of 150 µg/mL. This study is the first to report anticancer potential and mechanism of action of EECTL against breast cancer MDA-MB-231 cells. EECTL shows potential to serve as an adjunct to the main line of treatment in breast cancer and may be of interest for future preclinical and clinical studies aimed at developing integrative breast cancer treatments.
Cinnamomum tamala (CT),在英语中通常被称为“印度月桂叶”,在印地语中被称为“Tejpatta”,是一种属于樟科的树,被广泛用作烹饪调味品,具有众所周知的药用特性。本研究采用高效液相色谱法(HPLC)对干叶乙醇提取物(EECTL)进行了表征,并采用DPPH自由基清除法对其抗氧化活性进行了评价。采用MTT法评价EECTL对人乳腺癌细胞株MDA-MB-231和MCF-7对-à-vis正常HEK-293和Vero细胞的抗癌活性,并采用相衬显微镜进行形态学分析。荧光显微镜下采用Hoechst染色、AO/EtBr染色及qRT-PCR方法研究eectl诱导的染色质凝集和凋亡。Annexin V-FITC/PI双染色用于细胞凋亡检测和PI细胞周期分析。主要活性成分为儿茶素(Rt = 6.085 min)、丁香酚(Rt = 7.211 min)和芹菜素(Rt = 19.496 min)。EECTL诱导MDA-MB-231和MCF-7细胞凋亡呈剂量依赖性,IC50值分别为47和110 µg/mL。有趣的是,EECTL对正常的HEK-293和Vero细胞没有明显的影响。EECTL对Vero/MDA-MB-231和HEK-293/MDA-MB-231的选择性指数分别为5.69和8.16,对Vero/MCF-7和HEK-293/MCF-7的选择性指数分别为2.43和3.48。在机制上,EECTL导致MDA-MB-231和MCF-7细胞的G0/G1期和亚G0期细胞周期停滞,导致染色质凝集和凋亡。通过彗星试验证实DNA损伤和断裂。表达分析显示,EECTL上调了MDA-MB-231和MCF-7细胞中TP53的表达。EECTL对DPPH自由基具有显著的抗氧化潜力,IC50为150 µg/mL。本研究首次报道了EECTL对乳腺癌MDA-MB-231细胞的抗癌潜力和作用机制。EECTL显示出作为乳腺癌主线治疗的辅助治疗的潜力,并可能对未来旨在开发乳腺癌综合治疗的临床前和临床研究感兴趣。
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