Acta histochemica最新文献_第4页

Retraction notice to “Targeting TEAD would be a potential strategy for scarless wound repair: A preliminary study" [ Acta Histochem. 127 (2025), 152223] “靶向TEAD可能是无疤痕伤口修复的潜在策略：一项初步研究”[Acta Histochem. 127(2025), 152223]。

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2025-09-01 Epub Date: 2025-06-10 DOI: 10.1016/j.acthis.2025.152271

Ming-Yan Yang , Hong-Yuan Quan , Da-Lei Li , Jian Ruan , Hua-Ying Fan

引用次数: 0

Exosomal delivery of AZD5582 to overcome TRAIL resistance as an optimal therapy against triple-negative breast cancer 外泌体递送AZD5582克服TRAIL耐药是治疗三阴性乳腺癌的最佳方法

IF 2.3 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2025-09-01 Epub Date: 2025-05-24 DOI: 10.1016/j.acthis.2025.152270

Wanting Zhang , Quanjiang Li , Rui Tian , Zhujie Deng , Ronghui Sun , Xiubin Kuang , Jun Peng , Bin Xie , Chen Huang , Zhengqiang Yuan

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks effective targeted therapies mainly due to drug resistance. Therefore, there is an urgent need to develop highly effective therapeutic strategies for TNBC. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in transformed and cancerous cells, indicating its potential for anti-cancer therapy. Unfortunately, the clinical trials of recombinant TRAIL (rTRAIL) had actually failed due to the very common TRAIL resistance in cancers. Exosomal delivery of TRAIL (EV-T) has been shown to greatly improve the cytotoxicity of TRAIL. Moreover, the TRAIL resistance was closely correlated with the upregulation of inhibitors of apoptosis proteins (IAPs) in cancer cells. As a potent antagonist of IAPs, AZD5582 (AZD) was previously shown to drastically sensitize TRAIL response. Herein, we hypothesize that AZD may be loaded into EV-T for co-delivery of AZD and TRAIL to make a synergistic combination anticancer therapy against TNBC. First, TRAIL-expressing mesenchymal stem cells (MSCs) were used to prepare EV-Ts. Then, AZD was loaded into EV-T by ultrasound to prepare the composite nanodrug AZD@EV-T. EV encapsulation significantly improved AZD stability and cellular delivery efficiency, leading to the synergistically augmented cytotoxicity and apoptosis induction in both breast and kidney cancer cell lines, whilst sparing the normal MSCs. The potential mechanisms underlying the synergism appeared to be associated with the concomitant upregulation of death receptor 5 (DR5) and expressional suppression of various anti-apoptotic factors. Importantly, the AZD@EV-T therapy triggered strikingly enhanced growth inhibition and apoptosis in the subcutaneously established BT549 xenograft tumors, consequently leading to the complete tumor regression. It also demonstrated significant potential for treating kidney cancer in A498 kidney tumor organoids. Together, AZD@EV-T effectively overcomes TRAIL resistance and may represent a highly effective and innovative anticancer therapy for both TNBC and kidney cancers.

三阴性乳腺癌（TNBC）是一种高度侵袭性的乳腺癌亚型，主要由于耐药而缺乏有效的靶向治疗。因此，迫切需要开发高效的TNBC治疗策略。肿瘤坏死因子（Tumor necrosis factor， TNF）相关凋亡诱导配体（apoptosis-inducing ligand， TRAIL）在转化细胞和癌细胞中选择性诱导凋亡，表明其具有抗癌治疗的潜力。不幸的是，重组TRAIL （rTRAIL）的临床试验实际上失败了，因为TRAIL在癌症中非常常见。外泌体递送TRAIL （EV-T）已被证明可大大改善TRAIL的细胞毒性。此外，TRAIL耐药与癌细胞中凋亡蛋白抑制剂（IAPs）的上调密切相关。作为一种有效的IAPs拮抗剂，AZD5582 （AZD）先前被证明能显著致敏TRAIL反应。在此，我们假设AZD可能被装载到EV-T中，共同递送AZD和TRAIL，从而形成针对TNBC的协同联合抗癌治疗。首先，利用表达trail的间充质干细胞（MSCs）制备EV-Ts。然后，通过超声将AZD加载到EV-T中，制备复合纳米药物AZD@EV-T。EV包封显著提高了AZD的稳定性和细胞递送效率，从而协同增强了乳腺癌和肾癌细胞系的细胞毒性和凋亡诱导，同时保留了正常的MSCs。协同作用的潜在机制似乎与死亡受体5 （DR5）的上调和各种抗凋亡因子的表达抑制有关。重要的是，AZD@EV-T治疗在皮下建立的BT549异种移植肿瘤中引发了显著增强的生长抑制和细胞凋亡，从而导致肿瘤完全消退。在A498肾肿瘤类器官中也显示出治疗肾癌的显著潜力。总之，AZD@EV-T有效地克服了TRAIL耐药性，可能代表了TNBC和肾癌的一种高效和创新的抗癌疗法。

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引用次数: 0

Inducible gankyrin overexpression drives hepatocarcinogenesis in a liver-specific zebrafish model 在肝脏特异性斑马鱼模型中诱导gankyrin过表达驱动肝癌发生

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2025-09-01 Epub Date: 2025-08-01 DOI: 10.1016/j.acthis.2025.152280

Zhiyuan Gong , Yuxi Sun , Yueh-Min Lin , Jeng-Wei Lu

Background

Hepatocarcinogenesis is a complex, multistep process that begins with fatty liver, progresses to fibrosis, and ultimately leads to cancer. Numerous etiological factors contribute to this progression, highlighting the importance of developing animal models to facilitate both basic and translational research aimed at discovering new therapeutic strategies. Gankyrin is a key oncoprotein involved in the genetic regulation of liver pathology.

Material and method

To investigate its oncogenic role without the need for cancer cell inoculation or drug treatment, we employed a Tet-On system to drive zebrafish gankyrin overexpression in hepatocytes under the control of the fabp10a promoter. Results: After eight weeks of induction, fabp10a:eGFP-gankyrin transgenic zebrafish spontaneously developed persistent hyperplasia, bile duct hyperplasia, and hepatocellular carcinoma (HCC), demonstrating the oncogenic potential of gankyrin in liver tumorigenesis. In this study, we demonstrate that gankyrin activation drives the progressive development of HCC in zebrafish. Liver-specific overexpression of gankyrin in wild-type zebrafish led to hyperplasia, bile duct hyperplasia, and HCC, establishing a robust zebrafish model for studying liver cancer. Our findings highlight the utility of this model for investigating the molecular mechanisms underlying tumorigenesis.

Conclusion

This study establishes a robust zebrafish model in which liver-specific overexpression of gankyrin induces spontaneous progression from hyperplasia to hepatocellular carcinoma. The model provides a valuable platform for investigating the molecular mechanisms of hepatocarcinogenesis and exploring potential therapeutic strategies.

肝癌的发生是一个复杂的多步骤过程，从脂肪肝开始，发展到纤维化，最终导致癌症。许多病因因素促成了这一进展，强调了开发动物模型以促进旨在发现新的治疗策略的基础和转化研究的重要性。Gankyrin是参与肝脏病理遗传调控的关键癌蛋白。材料和方法为了研究其在不需要癌细胞接种或药物治疗的情况下的致癌作用，我们采用Tet-On系统在fabp10a启动子的控制下驱动斑马鱼肝细胞中gankyrin的过表达。结果：诱导8周后，转基因fabp10a:eGFP-gankyrin斑马鱼自发发生持续性增生、胆管增生和肝细胞癌（HCC），显示了gankyrin在肝脏肿瘤发生中的致癌潜力。在这项研究中，我们证明了gankyrin激活推动了斑马鱼HCC的进行性发展。野生型斑马鱼肝脏特异性过表达gankyrin导致增生、胆管增生和HCC，为研究肝癌建立了稳健的斑马鱼模型。我们的研究结果强调了该模型在研究肿瘤发生的分子机制方面的实用性。结论本研究建立了一个稳健的斑马鱼模型，在该模型中肝脏特异性过表达gankyrin可诱导从增生到肝细胞癌的自发进展。该模型为研究肝癌发生的分子机制和探索潜在的治疗策略提供了一个有价值的平台。

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引用次数: 0

Corrigendum to “AARS1-mediated Osterix lactylation promotes its transcriptional activity during osteoblast differentiation” [Acta Histochem. 127 (2025) 152273] “aars1介导的Osterix乳酸化促进成骨细胞分化过程中的转录活性”的更正[Acta Histochem. 127(2025) 152273]。

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2025-09-01 Epub Date: 2025-06-23 DOI: 10.1016/j.acthis.2025.152275

Feige Nian , Linfeng Guo , Zhangli Fei , Mingfeng Yang , Lihong Chen , Ye Zhang , Zhufeng Zhang , Yezhou Qian , Bin Zhang

引用次数: 0

Lysophosphatidic acid (LPA) receptor signaling enhances malignant potential in highly migratory lung cancer cells under hypoxic conditions 溶血磷脂酸（LPA）受体信号在缺氧条件下增强高迁移肺癌细胞的恶性潜能

IF 2.3 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2025-09-01 Epub Date: 2025-05-23 DOI: 10.1016/j.acthis.2025.152268

Moemi Tamura, Miwa Takai, Mao Yamamoto, Narumi Yashiro, Anri Taniguchi, Yuka Kusumoto, Shion Nagano, Nanami Shimomura, Toshifumi Tsujiuchi

Hypoxia contributes to tumor progression, promoting cancer cell motility, invasion and metastasis. Lysophosphatidic acid (LPA) receptors are implicated in the pathogenesis of cancer. In this study, we investigated the role of LPA receptor signaling in modulating malignant behavior under hypoxic conditions (1 % O₂) in lung cancer cells. We generated highly migratory A549-R12 cells from the parental lung cancer A549 cells for this purpose. LPAR1 and LPAR2 expression levels were lower in both A549 and A549-R12 cells cultured at 1 % O₂ compared to those cultured at 21 % O₂, while LPAR3 expression remained unchanged between the two cell lines. Cell motility increased in both A549 and A549-R12 cells cultured at 1 % O₂. Notably, A549-R12 cells exhibited greater motility under 1 % O₂ conditions than A549 cells. Treatment with AM966 (an LPA₁ antagonist) and (2S)-OMPT (an LPA₃ agonist) further increased the motility of A549-R12 cells, while GRI-977143 (an LPA₂ agonist) decreased their motility. Moreover, the invasion activity of A549-R12 cells was higher than that of A549 cells, with 1 % O₂ conditions significantly enhancing A549-R12 cell invasion. AM966 and (2S)-OMPT stimulated, whereas GRI-977143 inhibited, the invasion of A549-R12 cells. In the presence of LPA, cell viability to cisplatin (CDDP) was higher in A549-R12 cells cultured at both 21 % and 1 % O₂ compared to A549 cells. These results suggest that LPA receptor signaling plays a key role in regulating malignant progression in highly migratory lung cancer cells under hypoxic conditions.

缺氧有助于肿瘤的进展，促进癌细胞的运动、侵袭和转移。溶血磷脂酸（LPA）受体与癌症的发病机制有关。在这项研究中，我们研究了LPA受体信号在低氧条件下（1 % O2）在肺癌细胞中调节恶性行为的作用。为此，我们从亲代肺癌A549细胞中产生了高度迁移的A549- r12细胞。在1 % O2下培养的A549和A549- r12细胞中，LPAR1和LPAR2的表达水平低于在21 % O2下培养的细胞，而LPAR3的表达在两种细胞系之间保持不变。在1 % O2条件下培养的A549和A549- r12细胞的细胞活力均增加。值得注意的是，A549- r12细胞在1 % O2条件下比A549细胞表现出更大的运动性。AM966 （LPA1拮抗剂）和(2S)-OMPT （LPA3激动剂）进一步增加了A549-R12细胞的运动性，而GRI-977143 （LPA2激动剂）降低了它们的运动性。此外，A549- r12细胞的侵袭活性高于A549细胞，1 % O2条件显著增强A549- r12细胞的侵袭活性。AM966和(2S)-OMPT刺激A549-R12细胞的侵袭，而GRI-977143抑制A549-R12细胞的侵袭。在LPA存在的情况下，与A549细胞相比，在21 %和1 % O2下培养的A549- r12细胞对顺铂（CDDP）的存活率更高。这些结果表明LPA受体信号在缺氧条件下调节高迁移性肺癌细胞的恶性进展中起关键作用。

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引用次数: 0

Dihydroartemisinin inhibited tongue squamous cell carcinoma progression and tongue-to-lymph node metastasis through inhibiting RalB expression 双氢青蒿素通过抑制RalB表达抑制舌鳞癌的进展和舌向淋巴结转移

IF 2.3 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2025-09-01 Epub Date: 2025-06-30 DOI: 10.1016/j.acthis.2025.152276

Yuman Zhang , Yuting Gao , Yanli Gong , Yanguang Yang , Yi Gong , Xiaoyong Song , Yajun Xiong , Dan Wang , Zhihan Liu , Xinli Shi

Background

Lymph node metastasis is a key determinant of the poor survival rate in patients with tongue squamous cell carcinoma (TSCC). Therefore, inhibiting lymph node metastasis is a primary strategy for TSCC treatment. Our previous research found that dihydroartemisinin (DHA) inhibited the migration in human tongue squamous carcinoma Cal-27 cells. However, the effect and mechanism of DHA on lymph node metastasis are unknown in TSCC.

Methods

The expression level of Ras related GTP binding protein B (RalB) was measured in TSCC samples by immunohistochemical staining. Wound healing, invasion, and cell adhesion assays were used to investigate cell motility. Western blot was used to investigate RalB expression level. An orthotopic nude mouse model of TSCC was established to investigate the effect and mechanism of DHA on lymph node metastasis.

Results

First, DHA inhibited the progression of tongue tumor and tongue-to-lymph node metastasis of TSCC. Secondly, DHA inhibited RalB expression level in vitro and in vivo. Finally, DHA inhibited tongue-to-lymph node metastasis through RALB.

Conclusions

DHA inhibited tongue-to-lymph node metastasis through RALB, providing a novel therapeutic strategy for TSCC metastasis.

背景：淋巴结转移是舌鳞状细胞癌（TSCC）患者生存率低的关键决定因素。因此，抑制淋巴结转移是治疗TSCC的主要策略。我们前期研究发现，双氢青蒿素（DHA）对人舌鳞癌Cal-27细胞的迁移具有抑制作用。然而，DHA对TSCC淋巴结转移的影响和机制尚不清楚。方法采用免疫组化染色法检测TSCC组织中Ras相关GTP结合蛋白B （RalB）的表达水平。伤口愈合、侵袭和细胞粘附试验用于研究细胞运动。Western blot检测RalB表达水平。建立原位裸鼠TSCC模型，探讨DHA对TSCC淋巴结转移的影响及其机制。结果首先，DHA抑制舌癌的进展和舌向淋巴结转移；其次，DHA抑制体外和体内RalB表达水平。最后，DHA通过RALB抑制舌向淋巴结转移。结论dha通过RALB抑制舌向淋巴结转移，为TSCC转移提供了新的治疗策略。

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引用次数: 0

Retraction notice to “miR-103–3p attenuates liver injury with severe acute pancreatitis by inhibiting pyroptosis through miR-103-3p/NLRP1 axis” [Acta Histochem. 126 (2024) 152211] 关于“miR-103-3p通过miR-103-3p/NLRP1轴抑制焦亡减轻重症急性胰腺炎肝损伤”的撤回通知[journal of histochemistry . 126(2024) 152211]。

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2025-09-01 Epub Date: 2025-05-15 DOI: 10.1016/j.acthis.2025.152258

Wenquan Zhang , Min Du , Yingjian Jiang , Jiang Wang , Yue Yu , DianLiang Zhang

引用次数: 0

Non-specific background in immunoglobulin G staining can be effectively eliminated using heating or a catalase inhibitor 免疫球蛋白G染色中的非特异性背景可以通过加热或过氧化氢酶抑制剂有效地消除

IF 2.3 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2025-09-01 Epub Date: 2025-05-19 DOI: 10.1016/j.acthis.2025.152269

Kairan Yang , Ting Xu , Chengkang Lin , Zuisu Yang , Haiyan Lyu , Falei Yuan

Immunoglobulin G (IgG) staining is a widely used method for assessing blood-brain barrier (BBB) integrity. However, significant non-specific binding is often observed in many studies, which can interfere with the accurate interpretation of results. In this study, the horseradish peroxidase (HRP)-based polymer method and the streptavidin-biotin complex (SABC) method were used to perform IgG staining. The effects of hydrogen peroxide, heating, and a catalase inhibitor on reducing background staining were evaluated in brain sections from untreated mice and those subjected to middle cerebral artery occlusion (MCAO). The results showed that immunohistochemistry without hydrogen peroxide pretreatment still produced minimal background in paraffin-embedded sections. However, IgG staining with hydrogen peroxide pretreatment led to substantial background in vibratome sections. Compared to the SABC method, a mixture of the catalase inhibitor 3-amino-1,2,4-triazole and hydrogen peroxide reduced background staining by 35.4 % ± 5.7 % in the cortex of untreated mouse brains and by 36.9 % ± 1.8 % in the contralateral cortex of MCAO mice when using the polymer method. Additionally, heating at 75°C was sufficient to eliminate non-specific binding in brain sections from both untreated and MCAO mice. Hydrogen peroxide pretreatment alone was ineffective in removing background staining in brain sections from either untreated or MCAO mice. In summary, this study demonstrates that hydrogen peroxide pretreatment is effective in reducing background only when combined with a catalase inhibitor but is unnecessary when the tissue is heated. Heating is a simple and effective method for removing the IgG staining background when detecting BBB leakage.

免疫球蛋白G （IgG）染色是一种广泛使用的评估血脑屏障（BBB）完整性的方法。然而，在许多研究中经常观察到显著的非特异性结合，这可能会干扰结果的准确解释。本研究采用辣根过氧化物酶（HRP）聚合物法和链亲和素-生物素复合物（SABC）法进行IgG染色。过氧化氢、加热和过氧化氢酶抑制剂对降低背景染色的影响在未治疗的小鼠和大脑中动脉闭塞（MCAO）小鼠的脑切片中进行了评估。结果表明，未经双氧水预处理的免疫组织化学方法在石蜡包埋切片中仍产生极小的背景。然而，过氧化氢预处理的IgG染色在振动体切片中导致大量背景。与SABC方法相比，过氧化氢酶抑制剂3-氨基-1,2,4-三唑和过氧化氢的混合物在使用聚合物方法时，未处理小鼠大脑皮层的背景染色减少35.4% % ± 5.7 %，在MCAO小鼠对侧皮层的背景染色减少36.9 % ± 1.8 %。此外，在75°C下加热足以消除未处理和MCAO小鼠脑切片中的非特异性结合。单独过氧化氢预处理对未处理或MCAO小鼠脑切片的背景染色均无效。总之，这项研究表明，过氧化氢预处理只有在与过氧化氢酶抑制剂联合使用时才能有效地降低背景，而当组织被加热时则没有必要。加热是检测血脑屏障渗漏时去除IgG染色背景的一种简单有效的方法。

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引用次数: 0

USP22-mediated PNMA5 deubiquitination promotes proliferation, migration and invasion of prostate cancer cells. usp22介导的PNMA5去泛素化促进前列腺癌细胞的增殖、迁移和侵袭。

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2025-09-01 Epub Date: 2025-08-09 DOI: 10.1016/j.acthis.2025.152279

Hong Zhi, Tana, Nigemutu Bai, Wuenbilige Bai, Bowen Bai, Suo Liu

Background: Prostate cancer (PCa) stands as one of the primary contributors to cancer-related mortality among men globally. It is reported that USP22 functions as an oncogene, while PNMA5 exhibits a significant pro-metastatic effect. This research investigation centered on examining the interplay between USP22 and PNMA5 and their collaborative role in enhancing PCa progression.

Methods: The expression of USP22 and PNMA5 in tissue was determined by IHC. The differential expression of cellular USP22 and PNMA5 were detected using qPCR and immunoblotting, respectively. Cell viability and proliferation were assessed by MTT and sphere-formation assay. Transwell and wound-healing assay were conducted to evaluate the metastatic ability. The interaction between USP22 and PNMA5 was detected by Co-IP and IP. A tumor-bearing mice model was established for in vivo detection.

Results: USP22 and PNMA5 were highly expressed in both PCa tumor tissues and cells. Knocking down USP22 or PNMA5 inhibited the migration and invasion of PCa cells. USP22 mediated the deubiquitination of PNMA5. PNMA5 overexpression reversed the decrease in cell viability and proliferation rate, as well as the diminished migration and invasion ability induced by USP22 knockdown.

Conclusion: USP22 promotes migration and invasion of PCa cells by regulating PNMA5 deubiquitination.

背景：前列腺癌（PCa）是全球男性癌症相关死亡的主要原因之一。据报道，USP22作为癌基因起作用，而PNMA5表现出显著的促转移作用。本研究的重点是研究USP22和PNMA5之间的相互作用以及它们在促进前列腺癌进展中的协同作用。方法：采用免疫组化法检测组织中USP22和PNMA5的表达。分别采用qPCR和免疫印迹法检测细胞USP22和PNMA5的差异表达。MTT法和成球法检测细胞活力和增殖能力。采用Transwell法和创面愈合法评价转移能力。通过Co-IP和IP检测USP22与PNMA5的相互作用。建立荷瘤小鼠模型进行体内检测。结果：USP22和PNMA5在前列腺癌组织和细胞中均有高表达。敲低USP22或PNMA5可抑制PCa细胞的迁移和侵袭。USP22介导PNMA5的去泛素化。PNMA5过表达逆转了USP22敲低引起的细胞活力和增殖率的下降，以及迁移和侵袭能力的降低。结论：USP22通过调控PNMA5去泛素化促进PCa细胞的迁移和侵袭。

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引用次数: 0

Calcipotriol inhibits the proliferation of psoriasis HaCaT cells by activating the ferroptosis pathway 钙化三醇通过激活铁下垂途径抑制银屑病HaCaT细胞的增殖

IF 2.3 4区生物学 Q4 CELL BIOLOGY

Acta histochemica

Pub Date : 2025-09-01 Epub Date: 2025-06-23 DOI: 10.1016/j.acthis.2025.152274

Lei Yang , Yue Zhang , Jiansong Wu , Lei Wang , Shan Liu , Li Zhou , Jigang Zhang , Chengxin Li

Calcipotriol is a well-established treatment for psoriasis and other dermatological conditions. This study aimed to investigate whether calcipotriol exerts its therapeutic effects through ferroptosis and to elucidate its underlying molecular mechanisms using bioinformatics and cellular experiments. Differentially expressed genes (DEGs) and their functional enrichment were analyzed in psoriatic skin lesions using bioinformatics. A lipopolysaccharide (LPS)-induced HaCaT cell model was established to simulate psoriatic inflammation. The effects of calcipotriol at various concentrations and time points on HaCaT cell proliferation, apoptosis, and expression of key markers were assessed. Additionally, ferrostatin-1 (a ferroptosis inhibitor) and RSL3 (a ferroptosis inducer) were used to evaluate ferroptosis-related changes, including cell proliferation, apoptosis, reactive oxygen species (ROS) levels, glutathione (GSH) content (via ELISA), and protein expression of GPX4 and Ki-67 (via Western blot). Bioinformatics analysis revealed significant differential expression of ferroptosis-related genes, such as GPX4 and SLC7A11, in psoriatic lesions. Calcipotriol treatment inhibited HaCaT cell proliferation in a dose- and time-dependent manner, elevated ROS levels, and reduced GSH, GPX4, and Ki-67 expression. These effects were reversed by ferrostatin-1, which restored antioxidant defenses and cell viability. Conversely, RSL3 increased ROS levels and partially negated the protective effects of ferrostatin-1. These findings suggest that calcipotriol regulates ferroptosis-related gene expression and inhibits keratinocyte proliferation through induction of oxidative stress and ferroptosis, offering new insights into its mechanism of action in psoriasis treatment.

钙化三醇是治疗牛皮癣和其他皮肤病的有效方法。本研究旨在通过生物信息学和细胞实验研究钙化三醇是否通过铁下垂发挥其治疗作用，并阐明其潜在的分子机制。应用生物信息学方法对银屑病皮损中的差异表达基因（DEGs）及其功能富集进行了分析。建立脂多糖（LPS）诱导HaCaT细胞模型，模拟银屑病炎症。观察不同浓度、不同时间点钙三醇对HaCaT细胞增殖、凋亡及关键标志物表达的影响。此外，利用铁抑素-1（一种铁下垂抑制剂）和RSL3（一种铁下垂诱诱剂）评估铁下垂相关的变化，包括细胞增殖、凋亡、活性氧（ROS）水平、谷胱甘肽（GSH）含量（通过ELISA）以及GPX4和Ki-67的蛋白表达（通过Western blot）。生物信息学分析显示，银屑病皮损中与铁中毒相关的基因GPX4和SLC7A11的表达存在显著差异。钙化三醇以剂量和时间依赖性的方式抑制HaCaT细胞增殖，升高ROS水平，降低GSH、GPX4和Ki-67的表达。这些作用被铁他汀-1逆转，恢复抗氧化防御和细胞活力。相反，RSL3增加ROS水平，部分抵消了铁stat -1的保护作用。这些发现提示钙化三醇通过诱导氧化应激和铁下垂调节铁中毒相关基因表达，抑制角化细胞增殖，为其治疗银屑病的作用机制提供了新的见解。

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引用次数: 0