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Qualitative evaluations of reactive microglial heterogeneity in cultured porcine retina. 对培养猪视网膜中反应性小胶质细胞异质性的定性评估。
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-06-03 DOI: 10.14670/HH-18-772
Kjell Johansson, Camilla Mohlin

A late stage of several retinal disorders is retinal detachment, a complication that results in rapid photoreceptor degeneration and synaptic damage. The porcine retina is a favorable in vitro model for studies of the degenerative processes that follow retinal detachment. Photoreceptor degeneration and synaptic injuries develop rapidly in the cultured porcine retina and correlate with resident microglial cell transition into a reactive phenotype. In this in vitro study, we used retinas cultured for five days and analyzed reactive CD11b and Iba1 immunoreactive microglia that localized close to/within the synaptic outer plexiform layer (OPL) and in the outer nuclear layer (ONL). A subpopulation of the CD11b and Iba1immunoreactive microglia also expressed CD68 immunoreactivity on lysosomal membranes or as a diffuse cytoplasmic stain. Some CD68 immunoreactive microglia were juxtaposed to L/M-opsin immunoreactive cone photoreceptors in the ONL. CD11b and Iba immunoelectron microscopy further suggests the presence of a dark microglial phenotype in the degenerating cultured porcine retina. For immunoelectron microscopy, nickel-enhanced diaminobenzidine (DAB) staining resulted in clearly distinguished reaction products in the cytosol of dark microglia.

视网膜脱离是多种视网膜疾病的晚期阶段,这种并发症会导致感光细胞迅速退化和突触受损。猪视网膜是研究视网膜脱离后变性过程的有利体外模型。光感受器变性和突触损伤在培养的猪视网膜中迅速发展,并与常驻小胶质细胞转变为反应表型相关。在这项体外研究中,我们使用培养了五天的视网膜,分析了反应性 CD11b 和 Iba1 免疫反应小胶质细胞,它们分布在突触外丛膜层(OPL)和核外层(ONL)附近/内部。CD11b和Iba1免疫反应性小胶质细胞的一个亚群还在溶酶体膜上或作为弥漫性胞质染色表达CD68免疫反应。一些具有 CD68 免疫活性的小胶质细胞与 ONL 中具有 L/M-opsin 免疫活性的锥体感光细胞并列。CD11b 和 Iba 免疫电镜进一步表明,在退化的培养猪视网膜中存在暗性小胶质细胞表型。在免疫电镜下,镍增强的二氨基联苯胺(DAB)染色可在暗色小胶质细胞的细胞液中发现明显不同的反应产物。
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引用次数: 0
Effect of 3D printing technology-assisted TKA on cartilage tissue in rabbit with knee osteoarthritis. 三维打印技术辅助膝关节置换术对膝关节骨性关节炎兔软骨组织的影响。
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-04-05 DOI: 10.14670/HH-18-743
Guoliang Wang, Feng Cheng, Jianxun Cui, Nan Chen, Qing Li

Background: Knee osteoarthritis (KOA) is a common chronic degenerative joint disease. 3D printing technology has become one of the important directions of medical development along with individualized precision treatment in orthopedics.

Objective: To investigate the effect of 3D printing technology-assisted total knee arthroplasty (TKA) on cartilage in rabbits with KOA.

Methods: A rabbit model of KOA was established and treated by TKA or 3D printing-assisted TKA. Four weeks after treatment, radiological evaluation of rabbit knees was performed by X-ray examination, in order to observe the severity of osteoarthritic lesions. Then the knee joints of rabbits were collected for Hematoxylin-eosin, Toluidine blue, and Safranin O-Fast green staining. The expressions of cartilage matrix metabolism-related and apoptosis-related genes were scrutinized by real-time quantitative reverse transcription-polymerase chain reaction, Western blot, and immunohistochemistry. The levels of inflammatory-related factors in the cartilage tissues of rabbits were tested by enzyme-linked immunosorbent assay.

Results: In rabbits with KOA, 3D printing technology-assisted TKA alleviated the inflammation and bone remodeling of the knee joint, relieved synovial hyperplasia and inflammatory cell infiltration in the articular cartilage, reduced articular cartilage degradation, suppressed cartilage matrix metabolism, and mitigated the inflammatory response and apoptosis of cartilage cells.

Conclusion: 3D printing technology-assisted TKA exhibits a good treatment effect in rabbit KOA. This study provides an important basis for the clinical application of 3D printing technology-assisted TKA in KOA treatment.

背景:膝关节骨关节炎(KOA)是一种常见的慢性退行性关节疾病。3D打印技术与骨科的个体化精准治疗已成为医学发展的重要方向之一:研究3D打印技术辅助全膝关节置换术(TKA)对KOA兔软骨的影响:方法:建立 KOA 兔子模型,并采用全膝关节置换术或 3D 打印辅助全膝关节置换术进行治疗。治疗四周后,通过 X 射线检查对兔子膝关节进行放射学评估,以观察骨关节炎病变的严重程度。然后采集兔子的膝关节,进行苏木精-伊红、甲苯胺蓝和赛福宁 O-快绿染色。通过实时定量反转录聚合酶链反应、Western 印迹和免疫组化等方法检测软骨基质代谢相关基因和细胞凋亡相关基因的表达。用酶联免疫吸附试验检测了兔子软骨组织中炎症相关因子的水平:结论:3D 打印技术辅助 TKA 对兔 KOA 具有良好的治疗效果。本研究为 3D 打印技术辅助 TKA 在 KOA 治疗中的临床应用提供了重要依据。
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引用次数: 0
Brain endothelial cell activation and dysfunction associate with and contribute to the development of enlarged perivascular spaces and cerebral small vessel disease. 脑内皮细胞活化和功能障碍与血管周围间隙扩大和脑小血管疾病的发生有关,并对其起到促进作用。
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-10 DOI: 10.14670/HH-18-792
Melvin Ray Hayden

Multiple injurious stimuli to the brain's endothelium results in brain endothelial cell activation and dysfunction (BECact/dys) with upregulation of inflammatory signaling cascades and a decrease in bioavailable nitric oxide respectively. These injurious stimuli initiate a brain injury and a response to injury wound healing genetically programed cascade of events, which result in cellular remodeling of the neurovascular unit and blood-brain barrier with increased inflammation and permeability. These remodeling changes also include the perivascular spaces that become dilated to form enlarged perivascular spaces (EPVS) that may be identified noninvasively by magnetic resonance imaging. These EPVS are associated with and considered to be a biomarker for cerebral small vessel disease (SVD) and a dysfunctional glymphatic system with impaired removal of neurotoxic waste, which ultimately results in neurodegeneration with impaired cognition and dementia. The penultimate section discusses the understudied role of venous cerebral circulation in relation to EPVS, SVD, and the vascular contribution to cognitive impairment (VCID). The focus of this review will be primarily on BECact/dys that associates with and contributes to the development of EPVS, SVD, and impaired glymphatic system efflux. Importantly, BECact/dys may be a key piece of the puzzle to unlock this complicated story of EPVS and SVD. Multiple transmission electron micrographs and illustrations will be utilized to depict anatomical ultrastructure and allow for the discussion of multiple functional molecular cascades.

对大脑内皮的多重伤害性刺激会导致脑内皮细胞活化和功能障碍(BECact/dys),并分别导致炎症信号级联上调和生物可用一氧化氮减少。这些损伤性刺激引发了脑损伤和损伤伤口愈合基因编程级联反应,导致神经血管单元和血脑屏障的细胞重塑,炎症和渗透性增加。这些重塑变化还包括血管周围空间扩张,形成扩大的血管周围空间(EPVS),可通过磁共振成像进行无创识别。这些 EPVS 与脑小血管疾病(SVD)和功能失调的淋巴系统有关,并被认为是脑小血管疾病(SVD)和功能失调的生物标志物,神经毒性废物的清除功能受损,最终导致神经变性,认知功能受损和痴呆。倒数第二部分讨论了未被充分研究的脑静脉循环在 EPVS、SVD 和血管性认知障碍(VCID)中的作用。本综述的重点将主要放在 BECact/dys 上,因为它与 EPVS、SVD 和受损的血液回流系统有关,并导致其发展。重要的是,BECact/dys可能是揭开EPVS和SVD这一复杂谜题的关键部分。我们将利用多种透射电子显微镜和插图来描述解剖超微结构,并对多种功能分子级联进行讨论。
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引用次数: 0
Correlation of NAT10 expression with clinical data and survival profiles in esophageal squamous cell carcinoma patients, and its impact on cell proliferation and apoptosis. 食管鳞状细胞癌患者 NAT10 表达与临床数据和生存状况的相关性及其对细胞增殖和凋亡的影响。
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-04-22 DOI: 10.14670/HH-18-752
Wei Sun, Xiaoying Shen, Xinyi Wang, Xiaoyan Zhang, Yongling Ji, Jin Wang

Background: This study investigates the association between NAT10 expression and clinical parameters while assessing prognostic outcomes in esophageal squamous cell carcinoma (ESCC) patients. Furthermore, the study seeks to elucidate the functional role of NAT10 in neoplastic cell proliferation and apoptosis.

Materials and methods: NAT10 expression was assessed in ESCC tissue microarrays through immunohistochemistry (IHC) tests. We employed SPSS software to analyze the correlation between NAT10 staining data, clinical indicators, and their implications for patient prognosis. Small interference RNA (siRNA) was utilized to inhibit NAT10 expression in two esophageal cancer cell lines, TE-1 and KYSE150. Subsequently, we meticulously quantified and compared cellular proliferation and apoptotic ratios among experimental groups. NAT10, Ki67, and Caspase3 expression levels in different groups were evaluated using quantitative polymerase chain reaction (qPCR) and Western blot (WB) assays. Statistical analyses were conducted using GraphPad Prism software, with significance at P<0.05.

Results: Our findings indicate that NAT10 is overexpressed in ESCC tissues and exhibits a significant correlation with tumor diameter and overall patient survival. Decreasing NAT10 expression led to the inhibition of tumor cell proliferation and the promotion of apoptosis. Furthermore, siRNA-mediated NAT10 inhibition resulted in the downregulation of Ki67 expression and the concomitant upregulation of Caspase3.

Conclusion: The observed overexpression of NAT10 in ESCC tissues is associated with larger tumor diameters and reduced patient survival. NAT10 appears to play a pivotal role in the progression of esophageal cancer by influencing cell proliferation and apoptosis. These findings suggest potential clinical implications, with Ki67 and Caspase3 potentially participating in this intricate molecular biological process.

研究背景本研究在评估食管鳞状细胞癌(ESCC)患者预后结果的同时,还调查了NAT10表达与临床参数之间的关联。此外,该研究还试图阐明 NAT10 在肿瘤细胞增殖和凋亡中的功能作用:通过免疫组化(IHC)检测评估 ESCC 组织芯片中 NAT10 的表达。我们采用 SPSS 软件分析了 NAT10 染色数据与临床指标之间的相关性及其对患者预后的影响。我们利用小干扰 RNA(siRNA)抑制了 TE-1 和 KYSE150 两种食管癌细胞系中 NAT10 的表达。随后,我们对各实验组的细胞增殖和凋亡比率进行了细致的量化和比较。我们使用定量聚合酶链反应(qPCR)和 Western 印迹(WB)检测法评估了不同组中 NAT10、Ki67 和 Caspase3 的表达水平。使用 GraphPad Prism 软件进行统计分析,结果以 p 为显著性:我们的研究结果表明,NAT10 在 ESCC 组织中过表达,并与肿瘤直径和患者总生存期有显著相关性。降低 NAT10 的表达可抑制肿瘤细胞增殖并促进细胞凋亡。此外,siRNA 介导的 NAT10 抑制导致 Ki67 表达下调,同时 Caspase3 上调:结论:在 ESCC 组织中观察到的 NAT10 过表达与肿瘤直径增大和患者生存率降低有关。NAT10似乎通过影响细胞增殖和凋亡,在食管癌的进展过程中发挥着关键作用。这些发现具有潜在的临床意义,Ki67 和 Caspase3 可能参与了这一错综复杂的分子生物学过程。
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引用次数: 0
Oridonin alleviates inflammation and endoplasmic reticulum stress in pediatric pneumonia via regulating the SIRT1-mediated Wnt/β-catenin signaling pathway. 奥利多宁通过调节SIRT1介导的Wnt/β-catenin信号通路减轻小儿肺炎的炎症和内质网压力
IF 4.6 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-12-01 Epub Date: 2024-07-15 DOI: 10.14670/HH-18-795
Weijuan Han, Chen Qian, Peipei Fu, Junmei Xu

Background: Pediatric pneumonia is a prevalent and significant health concern worldwide, with elevated morbidity and mortality rates among affected children. This study was designed to elucidate the therapeutic impact of Oridonin (Ori) on pediatric pneumonia and unravel the underlying mechanisms involved.

Methods: A pediatric infantile pneumonia model was established in mice through intratracheal administration of LPS. Additionally, a cell damage model was created in WI-38 cells by administering LPS. Protein levels were assessed via western blotting, and cell viability was measured with CCK-8. Inflammatory cytokines were quantified through ELISA, and specific assays were employed to evaluate oxidative stress markers. Flow cytometry was utilized to assess cell apoptosis.

Results: Ori alleviated lung inflammation, oxidative stress, apoptosis, and endoplasmic reticulum stress (ERS) in LPS-induced pneumonia mice. In addition, Ori increased the viability of LPS-induced pneumonia cells but decreased cell apoptosis. Furthermore, Ori reduced oxidative stress, inflammation, and ERS in LPS-induced pneumonia cells by enhancing SIRT1 to activate the Wnt/β-catenin pathway.

Conclusion: This study suggested that Ori inhibited pediatric pneumonia by dampening the inflammatory response, oxidative stress, cell apoptosis, and ERS via the SIRT1/Wnt/β-catenin pathway.

背景:小儿肺炎是全球普遍存在的重大健康问题,患儿的发病率和死亡率都很高。本研究旨在阐明奥利多宁(Ori)对小儿肺炎的治疗作用,并揭示其潜在机制:方法:通过气管内注射 LPS,在小鼠体内建立了小儿婴幼儿肺炎模型。方法:通过气管内注射 LPS 在小鼠体内建立了小儿肺炎模型,并通过注射 LPS 在 WI-38 细胞中建立了细胞损伤模型。蛋白质水平通过蛋白印迹法进行评估,细胞活力通过 CCK-8 法进行测量。炎症细胞因子通过酶联免疫吸附进行量化,氧化应激标记物则采用特定的检测方法进行评估。流式细胞术用于评估细胞凋亡:结果:Ori减轻了LPS诱导的肺炎小鼠的肺部炎症、氧化应激、细胞凋亡和内质网应激(ERS)。此外,Ori提高了LPS诱导的肺炎细胞的存活率,但减少了细胞凋亡。此外,Ori通过增强SIRT1激活Wnt/β-catenin通路,减少了LPS诱导的肺炎细胞的氧化应激、炎症和ERS:本研究表明,Ori可通过SIRT1/Wnt/β-catenin通路抑制炎症反应、氧化应激、细胞凋亡和ERS,从而抑制小儿肺炎。
{"title":"Oridonin alleviates inflammation and endoplasmic reticulum stress in pediatric pneumonia via regulating the SIRT1-mediated Wnt/β-catenin signaling pathway.","authors":"Weijuan Han, Chen Qian, Peipei Fu, Junmei Xu","doi":"10.14670/HH-18-795","DOIUrl":"10.14670/HH-18-795","url":null,"abstract":"<p><strong>Background: </strong>Pediatric pneumonia is a prevalent and significant health concern worldwide, with elevated morbidity and mortality rates among affected children. This study was designed to elucidate the therapeutic impact of Oridonin (Ori) on pediatric pneumonia and unravel the underlying mechanisms involved.</p><p><strong>Methods: </strong>A pediatric infantile pneumonia model was established in mice through intratracheal administration of LPS. Additionally, a cell damage model was created in WI-38 cells by administering LPS. Protein levels were assessed via western blotting, and cell viability was measured with CCK-8. Inflammatory cytokines were quantified through ELISA, and specific assays were employed to evaluate oxidative stress markers. Flow cytometry was utilized to assess cell apoptosis.</p><p><strong>Results: </strong>Ori alleviated lung inflammation, oxidative stress, apoptosis, and endoplasmic reticulum stress (ERS) in LPS-induced pneumonia mice. In addition, Ori increased the viability of LPS-induced pneumonia cells but decreased cell apoptosis. Furthermore, Ori reduced oxidative stress, inflammation, and ERS in LPS-induced pneumonia cells by enhancing SIRT1 to activate the Wnt/β-catenin pathway.</p><p><strong>Conclusion: </strong>This study suggested that Ori inhibited pediatric pneumonia by dampening the inflammatory response, oxidative stress, cell apoptosis, and ERS via the SIRT1/Wnt/β-catenin pathway.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"1685-1693"},"PeriodicalIF":4.6,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733977","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
TRIM22 mechanism promoting KAT2A ubiquitination degradation to regulate ferroptosis in hepatocellular carcinoma cell invasion and metastasis. TRIM22促进KAT2A泛素化降解调控铁凋亡在肝癌细胞侵袭转移中的作用机制。
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-11-29 DOI: 10.14670/HH-18-856
Wei Wang, Xiaoshan Chen, Wei Wei

Objective: Hepatocellular carcinoma (HCC) is a highly fatal cancer. This study aims to investigate the underlying mechanism of tripartite motif-containing 22 (TRIM22) in HCC cell invasion and metastasis through the K (lysine) acetyltransferase 2A (KAT2A)/glutathione peroxidase 4 (GPX4) axis.

Methods: Human HCC cells BEL7405 were cultured in vitro and treated with MG-132, Ferrostain-1, pcDNA3.1-TRIM22, pcDNA3.1-KAT2A, or pcDNA3.1-NC. TRIM22-KAT2A interaction and KAT2A ubiquitination level, cell proliferation, invasion, migration, and histone H3 lysine 9 acetylation (H3K9ac) enrichment level on the GPX4 promoter were assessed by Co-IP, CCK-8, Transwell, and ChIP-qPCR assays. Mice were injected subcutaneously with Lv-oe-NC or Lv-oe-TRIM22 BEL7405 cells via the tail vein. Tumor proliferation and levels of TRIM22, KAT2A, GPX4, Fe2+, malondialdehyde (MDA), reactive oxygen species (ROS), and glutathione (GSH) in tissues and cells were evaluated by immunohistochemistry, RT-qPCR, western blot, and kits.

Results: oe-TRIM22-treated BEL7405 cells exhibited increased TRIM22 expression, and abated KAT2A protein expression and malignant cell biological behaviors, which were partially reversed by upregulating KAT2A or suppressing ferroptosis. TRIM22 interacted with KAT2A, which was ubiquitinated to regulate GPX4 histone acetylation. TRIM22 overexpression elevated Fe2+, MDA, and ROS levels and cell death, and diminished GSH, GPX4, and H3K9ac enrichment levels, whereas further overexpression of KAT2A brought about opposite trends. TRIM22 suppressed HCC growth and metastasis by mediating ferroptosis through the KAT2A/GPX4 axis.

Conclusions: TRIM22 promoted KAT2A ubiquitination degradation to reduce H3K9ac enrichment levels in the GPX4 promoter region, and facilitated ferroptosis, thereby inhibiting HCC cell invasion and metastasis and in vivo growth and metastasis.

目的:肝细胞癌是一种高致死率的肿瘤。本研究旨在通过K(赖氨酸)乙酰转移酶2A (KAT2A)/谷胱甘肽过氧化物酶4 (GPX4)轴探讨含TRIM22 (tripartite motif-containing 22)在HCC细胞侵袭转移中的潜在机制。方法:体外培养人肝癌细胞BEL7405,分别用MG-132、Ferrostain-1、pcDNA3.1-TRIM22、pcDNA3.1-KAT2A、pcDNA3.1-NC处理。通过Co-IP、CCK-8、Transwell和ChIP-qPCR检测评估TRIM22-KAT2A相互作用和KAT2A泛素化水平、细胞增殖、侵袭、迁移和GPX4启动子上组蛋白H3赖氨酸9乙酰化(H3K9ac)富集水平。小鼠经尾静脉皮下注射lv - e- nc或lv - e- trim22 BEL7405细胞。采用免疫组织化学、RT-qPCR、western blot和试剂盒检测肿瘤增殖及组织和细胞中TRIM22、KAT2A、GPX4、Fe2+、丙二醛(MDA)、活性氧(ROS)和谷胱甘肽(GSH)水平。结果:e-TRIM22处理的BEL7405细胞表现出TRIM22表达增加,KAT2A蛋白表达和恶性细胞生物学行为减弱,通过上调KAT2A或抑制铁凋亡可以部分逆转。TRIM22与KAT2A相互作用,KAT2A泛素化,调节GPX4组蛋白乙酰化。TRIM22过表达可提高Fe2+、MDA、ROS水平和细胞死亡,降低GSH、GPX4、H3K9ac富集水平,而KAT2A过表达则相反。TRIM22通过KAT2A/GPX4轴介导铁下垂抑制HCC生长和转移。结论:TRIM22促进KAT2A泛素化降解,降低GPX4启动子区H3K9ac富集水平,促进铁凋亡,从而抑制HCC细胞的侵袭转移和体内生长转移。
{"title":"TRIM22 mechanism promoting KAT2A ubiquitination degradation to regulate ferroptosis in hepatocellular carcinoma cell invasion and metastasis.","authors":"Wei Wang, Xiaoshan Chen, Wei Wei","doi":"10.14670/HH-18-856","DOIUrl":"10.14670/HH-18-856","url":null,"abstract":"<p><strong>Objective: </strong>Hepatocellular carcinoma (HCC) is a highly fatal cancer. This study aims to investigate the underlying mechanism of tripartite motif-containing 22 (TRIM22) in HCC cell invasion and metastasis through the K (lysine) acetyltransferase 2A (KAT2A)/glutathione peroxidase 4 (GPX4) axis.</p><p><strong>Methods: </strong>Human HCC cells BEL7405 were cultured <i>in vitro</i> and treated with MG-132, Ferrostain-1, pcDNA3.1-TRIM22, pcDNA3.1-KAT2A, or pcDNA3.1-NC. TRIM22-KAT2A interaction and KAT2A ubiquitination level, cell proliferation, invasion, migration, and histone H3 lysine 9 acetylation (H3K9ac) enrichment level on the GPX4 promoter were assessed by Co-IP, CCK-8, Transwell, and ChIP-qPCR assays. Mice were injected subcutaneously with Lv-oe-NC or Lv-oe-TRIM22 BEL7405 cells via the tail vein. Tumor proliferation and levels of TRIM22, KAT2A, GPX4, Fe<sup>2+</sup>, malondialdehyde (MDA), reactive oxygen species (ROS), and glutathione (GSH) in tissues and cells were evaluated by immunohistochemistry, RT-qPCR, western blot, and kits.</p><p><strong>Results: </strong>oe-TRIM22-treated BEL7405 cells exhibited increased TRIM22 expression, and abated KAT2A protein expression and malignant cell biological behaviors, which were partially reversed by upregulating KAT2A or suppressing ferroptosis. TRIM22 interacted with KAT2A, which was ubiquitinated to regulate GPX4 histone acetylation. TRIM22 overexpression elevated Fe<sup>2+</sup>, MDA, and ROS levels and cell death, and diminished GSH, GPX4, and H3K9ac enrichment levels, whereas further overexpression of KAT2A brought about opposite trends. TRIM22 suppressed HCC growth and metastasis by mediating ferroptosis through the KAT2A/GPX4 axis.</p><p><strong>Conclusions: </strong>TRIM22 promoted KAT2A ubiquitination degradation to reduce H3K9ac enrichment levels in the GPX4 promoter region, and facilitated ferroptosis, thereby inhibiting HCC cell invasion and metastasis and <i>in vivo</i> growth and metastasis.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18856"},"PeriodicalIF":2.5,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142852978","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
Xinnaotongluo liquid protects H9c2 cells against hypoxic damage through IRF2/HIF-1α-mediated oxidation, inflammation, and apoptosis. 心脑通络液通过IRF2/ hif -1α介导的氧化、炎症和凋亡保护H9c2细胞免受缺氧损伤。
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-11-28 DOI: 10.14670/HH-18-855
Jiankun Cui, Hui Liu, Yanmei Feng

Myocardial ischemia is the primary reason for ischemic heart disease. Xinnaotongluo liquid has been reported to have an improving effect on cardiovascular diseases. In our study, we detected the effects of Xinnaotongluo liquid on H9c2 cell oxidation, inflammation, and apoptosis induced by hypoxia stimulation. H9c2 cells were exposed to hypoxia and/or Xinnaotongluo liquid stimulation. Cell viability, oxidation, inflammation, and apoptosis, along with HIF-1α expression were measured. Subsequently, si-HIF-1α was transfected into H9c2 cells to detect whether HIF-1α depletion was involved in the effect of Xinnaotongluo liquid on H9c2 cells stimulated by hypoxia. Then, the regulatory effect of IRF2 on HIF-1α was detected. Hypoxia exposure induced H9c2 cell viability reduction, oxidation, inflammation, and apoptosis. Xinnaotongluo liquid alleviated the H9c2 cell viability reduction, oxidation, inflammation, and apoptosis induced by hypoxia. HIF-1α was activated in hypoxia-exposed H9c2 cells, and the knockdown of HIF-1α strengthened the effects of Xinnaotongluo liquid on hypoxia-exposed H9c2 cells. Additionally, HIF-1α was transcriptionally regulated by IRF2, and IRF2 was associated with the upregulation of HIF-1α in hypoxia-exposed H9c2 cells. Xinnaotongluo liquid alleviated H9c2 cell apoptosis and inflammation induced by hypoxia, which might be achieved by regulating IRF2/HIF-1α expression.

心肌缺血是缺血性心脏病的主要原因。据报道,心脑通络液对心血管疾病有改善作用。在我们的研究中,我们检测了心脑通络液对缺氧刺激下H9c2细胞氧化、炎症和凋亡的影响。H9c2细胞暴露于缺氧和/或心脑通络液刺激。检测细胞活力、氧化、炎症、凋亡及HIF-1α表达。随后,将si-HIF-1α转染H9c2细胞,检测心脑通络液对缺氧刺激H9c2细胞的影响是否与HIF-1α缺失有关。然后检测IRF2对HIF-1α的调控作用。缺氧暴露导致H9c2细胞活力降低、氧化、炎症和凋亡。心脑通络液可减轻缺氧引起的H9c2细胞活力降低、氧化、炎症和凋亡。HIF-1α在缺氧暴露的H9c2细胞中被激活,HIF-1α的下调增强了心脑通络液对缺氧暴露的H9c2细胞的作用。此外,HIF-1α受IRF2的转录调节,而IRF2与缺氧暴露的H9c2细胞中HIF-1α的上调有关。心脑通络液减轻缺氧诱导的H9c2细胞凋亡和炎症反应,其机制可能与调节IRF2/HIF-1α表达有关。
{"title":"Xinnaotongluo liquid protects H9c2 cells against hypoxic damage through IRF2/HIF-1α-mediated oxidation, inflammation, and apoptosis.","authors":"Jiankun Cui, Hui Liu, Yanmei Feng","doi":"10.14670/HH-18-855","DOIUrl":"https://doi.org/10.14670/HH-18-855","url":null,"abstract":"<p><p>Myocardial ischemia is the primary reason for ischemic heart disease. Xinnaotongluo liquid has been reported to have an improving effect on cardiovascular diseases. In our study, we detected the effects of Xinnaotongluo liquid on H9c2 cell oxidation, inflammation, and apoptosis induced by hypoxia stimulation. H9c2 cells were exposed to hypoxia and/or Xinnaotongluo liquid stimulation. Cell viability, oxidation, inflammation, and apoptosis, along with HIF-1α expression were measured. Subsequently, si-HIF-1α was transfected into H9c2 cells to detect whether HIF-1α depletion was involved in the effect of Xinnaotongluo liquid on H9c2 cells stimulated by hypoxia. Then, the regulatory effect of IRF2 on HIF-1α was detected. Hypoxia exposure induced H9c2 cell viability reduction, oxidation, inflammation, and apoptosis. Xinnaotongluo liquid alleviated the H9c2 cell viability reduction, oxidation, inflammation, and apoptosis induced by hypoxia. HIF-1α was activated in hypoxia-exposed H9c2 cells, and the knockdown of HIF-1α strengthened the effects of Xinnaotongluo liquid on hypoxia-exposed H9c2 cells. Additionally, HIF-1α was transcriptionally regulated by IRF2, and IRF2 was associated with the upregulation of HIF-1α in hypoxia-exposed H9c2 cells. Xinnaotongluo liquid alleviated H9c2 cell apoptosis and inflammation induced by hypoxia, which might be achieved by regulating IRF2/HIF-1α expression.</p>","PeriodicalId":13164,"journal":{"name":"Histology and histopathology","volume":" ","pages":"18855"},"PeriodicalIF":2.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846577","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
Effects of combustible cigarettes and electronic nicotine delivery systems on the regenerative properties of mesenchymal stem cells derived from periodontal ligament (PDL-MSCs). 可燃香烟和电子尼古丁输送系统对牙周韧带间充质干细胞(PDL-MSCs)再生特性的影响。
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-11-27 DOI: 10.14670/HH-18-854
Nikolina Kastratovic, Olivera Milosevic-Djordjevic, Carl Randall Harrell, Valentin Djonov, Vladislav Volarevic

Introduction: Periodontal ligament-derived mesenchymal stem cells (PDL-MSCs) are promising cells with crucial roles in maintaining and repairing periodontal tissue. However, their regenerative capacity can be influenced by various factors, including cigarette smoke and electronic nicotine delivery system (ENDS) aerosols. Smoking and vaping can impair their regenerative potential, and even though ENDS are perceived as safer tobacco products, there is a lack of evidence to guarantee this assumption.

Material and methods: Changes in the viability and proliferation of PDL-MSCs will be investigated after smoke and aerosol generation and cell exposure. In addition, the effects of smoke and aerosols on the immunomodulatory capacity of PDL-MSCs co-cultured with T lymphocytes will be further determined via the evaluation of cytokine profiles and flow cytometry analysis of T-cell phenotypes.

Results: Combustible cigarettes (CCs) induced more severe impairment in the viability and proliferation of PDL-MSCs compared with ENDS. Also, CCs promoted a proinflammatory immune response that could cause tissue damage to progress. On the other hand, ENDS had the potential to generate an immunosuppressive response that would prevent further cell decay.

Discussion: The regenerative capacity of PDL-MSCs decreased after treatment with both cigarette smoke and ENDS-aerosols. Even though the results demonstrate less severe effects with ENDS, further research is essential to evaluate their safety and impact on the capacity of PDL-MSCs to prevent and restore oral injuries caused by chronic exposure to aerosols.

简介:牙周韧带间充质干细胞(PDL-MSCs)是一种前景广阔的细胞,在维护和修复牙周组织方面发挥着至关重要的作用。然而,它们的再生能力会受到各种因素的影响,包括香烟烟雾和电子尼古丁输送系统(ENDS)气溶胶。吸烟和吸食电子烟会损害它们的再生潜力,尽管ENDS被认为是更安全的烟草产品,但缺乏证据来证明这一假设:材料和方法:将研究烟雾和气溶胶产生及细胞暴露后PDL-间充质干细胞活力和增殖的变化。此外,还将通过评估细胞因子谱和流式细胞仪分析 T 细胞表型,进一步确定烟雾和气溶胶对与 T 淋巴细胞共培养的 PDL 间充质干细胞免疫调节能力的影响:结果:与ENDS相比,可燃香烟(CC)对PDL-间充质干细胞的活力和增殖造成了更严重的损害。此外,CCs 还能促进炎症性免疫反应,导致组织损伤恶化。另一方面,ENDS有可能产生免疫抑制反应,防止细胞进一步衰亡:讨论:经香烟烟雾和ENDS气溶胶处理后,PDL-间充质干细胞的再生能力下降。尽管研究结果表明ENDS的影响较小,但仍有必要开展进一步研究,以评估其安全性及其对PDL-间充质干细胞预防和修复因长期暴露于气溶胶而造成的口腔损伤的能力的影响。
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引用次数: 0
Tumor necrosis factor receptor-associated protein 1 promotes aerobic glycolysis and cisplatin resistance by regulating the Wnt/β-catenin signaling pathway in lung cancer. 肿瘤坏死因子受体相关蛋白1通过调节肺癌中的Wnt/β-catenin信号通路促进有氧糖酵解和顺铂抗性
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-11-26 DOI: 10.14670/HH-18-853
Ruijie Li, Mengguo Lv, Juan Liu, Qian Sun

In this study, we investigated the effects of tumor necrosis factor receptor-associated protein 1 (TRAP1) on aerobic glycolysis in cisplatin-resistant lung cancer cells and explored the underlying mechanism. TRAP1 expression levels were determined in cisplatin-resistant lung cancer tissues and A549/CDDP cells. Subsequently, TRAP1 expression in A549/CDDP cells was silenced via small interfering RNA transfection. Moreover, changes in lactate content, glucose consumption, expression levels of lactate dehydrogenase A (LDHA), hexokinase 2 (HK2), and pyruvate kinase M2 (PKM2), and sensitivity to cisplatin were analyzed. Specifically, the Wnt/β-catenin signaling pathway was examined using the Wnt/β-catenin activator, BML-284. TRAP1 expression levels were higher in cisplatin-resistant tissues and A549/CDDP cells than in cisplatin-sensitive tissues and A549 cells (P<0.05). Moreover, the lactate content, glucose consumption, LDHA, HK2, PKM2 expression levels, and half-maximal inhibitory concentration of cisplatin were all significantly decreased after TRAP1 silencing (P<0.05). Compared with A549 cells, the Wnt/β-catenin pathway was activated in A549/CDDP cells, which was inhibited via TRAP1 silencing. BML-284 reversed the effects of TRAP1 silencing on the aerobic glycolysis and cisplatin sensitivity of A549/CDDP cells. Our findings suggest that TRAP1 affects the cisplatin resistance of lung cancer, possibly by regulating aerobic glycolysis via the Wnt/β-catenin pathway.

本研究调查了肿瘤坏死因子受体相关蛋白1(TRAP1)对顺铂耐药肺癌细胞有氧糖酵解的影响,并探讨了其潜在机制。研究人员测定了顺铂耐药肺癌组织和A549/CDDP细胞中TRAP1的表达水平。随后,通过小干扰 RNA 转染抑制了 TRAP1 在 A549/CDDP 细胞中的表达。此外,还分析了乳酸含量、葡萄糖消耗、乳酸脱氢酶A(LDHA)、己糖激酶2(HK2)和丙酮酸激酶M2(PKM2)表达水平的变化以及对顺铂的敏感性。具体而言,研究人员使用Wnt/β-catenin激活剂BML-284检测了Wnt/β-catenin信号通路。TRAP1在顺铂耐药组织和A549/CDDP细胞中的表达水平高于顺铂敏感组织和A549细胞(PTRAP1沉默)。BML-284 逆转了 TRAP1 沉默对 A549/CDDP 细胞有氧糖酵解和顺铂敏感性的影响。我们的研究结果表明,TRAP1可能通过Wnt/β-catenin通路调节有氧糖酵解,从而影响肺癌的顺铂耐药性。
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引用次数: 0
Modulation of the malignant behavior of tongue squamous cell carcinoma cells by matrix metallopeptidase 25 through the NF-κB pathway. 基质金属肽酶 25 通过 NF-κB 通路调节舌鳞状细胞癌细胞的恶性行为。
IF 2.5 4区 生物学 Q3 CELL BIOLOGY Pub Date : 2024-11-25 DOI: 10.14670/HH-18-852
Shuang Bai, Shao-Kang Sun, Zhen-Qi Xu, Ying-Bin Yan

Objective: Accumulating evidence has implicated matrix metalloproteinases (MMPs) in the progression of human cancers. Matrix metallopeptidase 25 (MMP25) is a membrane-type MMP whose role in tumorigenesis and cancer development is not well understood. Here, we investigated the functions of MMP25 in tongue squamous cell carcinoma (TSCC).

Methods: Gene expression was measured using real-time PCR and western blot. CCK-8 and Transwell assays were used to determine the proliferation, migration, and invasion of TSCC cells. An NK cell co-culture experiment was performed to evaluate the killing of TSCC cells by NK cells.

Results: MMP25 had higher expression levels in TSCC tissues than in adjacent non-cancerous tissues. MMP25-overexpressing and MMP25-silenced TSCC cell lines were established by lentiviral transduction. Overexpression of MMP25 promoted proliferation, migration, and invasion of TSCC cells, whereas knockdown of MMP25 had opposite effects. MMP25 modulated the levels of proliferation- and apoptosis-related proteins (PCNA, cyclin D, cyclin B1, p27, and cleaved caspase 3 and 9) and upregulated two invasion-related MMPs (mature MMP2 and MMP9). Additionally, MMP25 promoted tumor growth of TSCC cells in athymic nude mice. Notably, MMP25 upregulated PD-L1 in TSCC cells, attenuated NK cell killing of TSCC cells, and inhibited the secretion of anti-tumor cytokines (TNF-α and IFN-γ). Furthermore, MMP25 promoted the nuclear translocation of NF-κB p65, suggesting that activation of NF-κB signaling may mediate the pro-tumor functions of MMP25 in TSCC.

Conclusion: This study revealed a novel role for MMP25 in TSCC, highlighting the potential of MMP25 as a therapeutic target in TSCC.

目的:越来越多的证据表明基质金属蛋白酶(MMPs)与人类癌症的进展有关。基质金属肽酶 25(MMP25)是一种膜型 MMP,其在肿瘤发生和癌症发展中的作用尚不十分清楚。在此,我们研究了MMP25在舌鳞状细胞癌(TSCC)中的功能:方法:使用实时 PCR 和 Western 印迹检测基因表达。采用 CCK-8 和 Transwell 试验测定 TSCC 细胞的增殖、迁移和侵袭。进行了 NK 细胞共培养实验,以评估 NK 细胞对 TSCC 细胞的杀伤力:结果:MMP25在TSCC组织中的表达水平高于邻近的非癌组织。通过慢病毒转导建立了MMP25过表达和MMP25沉默的TSCC细胞系。过表达MMP25可促进TSCC细胞的增殖、迁移和侵袭,而敲除MMP25则会产生相反的效果。MMP25调节增殖和凋亡相关蛋白(PCNA、细胞周期蛋白D、细胞周期蛋白B1、p27以及裂解的caspase 3和9)的水平,并上调两种与侵袭相关的MMP(成熟的MMP2和MMP9)。此外,MMP25还能促进TSCC细胞在无胸腺裸鼠体内的生长。值得注意的是,MMP25 上调了 TSCC 细胞中的 PD-L1,削弱了 NK 细胞对 TSCC 细胞的杀伤力,并抑制了抗肿瘤细胞因子(TNF-α 和 IFN-γ)的分泌。此外,MMP25促进了NF-κB p65的核转位,表明NF-κB信号的激活可能介导了MMP25在TSCC中的促肿瘤功能:这项研究揭示了MMP25在TSCC中的新作用,突出了MMP25作为TSCC治疗靶点的潜力。
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引用次数: 0
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Histology and histopathology
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