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Dihydroartemisinin breaks the immunosuppressive tumor niche during cisplatin treatment in Hepatocellular carcinoma 双氢青蒿素在顺铂治疗肝细胞癌的过程中打破了免疫抑制肿瘤生态位
IF 2.3 4区 生物学 Q2 Medicine Pub Date : 2024-05-01 DOI: 10.1016/j.acthis.2024.152171
Yanguang Yang , Yuting Gao , Yi Gong , Junlan Lu , Shenghao Li , Yajun Xiong , Yuman Zhang , Dan Wang , Peng Gong , Yunfeng Li , Xinli Shi

Objective

Hepatocellular carcinoma, characterized by high mortality rates, often exhibits limited responsiveness to conventional treatments such as surgery, radiotherapy, and chemotherapy. Therefore, identifying a sensitizer for cisplatin has become crucial. Dihydroartemisinin, known for its potent role of tumor treatment, arises as a prospective candidate for cisplatin sensitization in clinical settings.

Methods

A mouse model of liver tumor was established through chemical induction of DEN/TCPOBOP. Upon successful model establishment, ultrasound was employed to detect tumors, Hematoxylin and eosin staining was conducted for observation of liver tissue pathology, and ELISA was utilized to assess cytokine changes (IFN-γ, IL-2, IL-4, IL-10, TGF-β, IL-1β, CCL2, and CCL21) in peripheral blood, para-tumor tissues, and tumor tissues. The infiltration of CD8+T cells and macrophages in tumor tissue sections was detected by immunofluorescence.

Results

Dihydroartemisinin combined with cisplatin obviously restrained the growth of liver tumors in mice and improved the weight and spleen loss caused by cisplatin. Cisplatin treatment of liver tumor mice increased the content of CCL2 and the number of macrophages in tumor tissues and promoted the formation of an immunosuppressive microenvironment. The combination therapy decreased the content of TGF-β in tumor tissues while increasing CCL2 levels in para-tumor tissues. Both combination therapy and cisplatin alone increased the number of CD8+T cells in tumor tissue, but there was no difference between them.

Conclusion

Dihydroartemisinin combined with cisplatin obviously prevented the deterioration of liver tumor in hepatocellular carcinoma mice and improve the therapeutic effect of cisplatin by improving the immunosuppressive microenvironment induced by cisplatin. Our findings provide a theoretical basis for considering dihydroartemisinin as an adjuvant drug for cisplatin in the treatment of hepatocellular carcinoma in the future.

目的肝细胞癌死亡率高,通常对手术、放疗和化疗等传统疗法反应有限。因此,找到顺铂的增敏剂变得至关重要。双氢青蒿素因其治疗肿瘤的强效作用而闻名,有望成为顺铂在临床上增敏的候选药物。成功建立模型后,用超声波检测肿瘤,用苏木精和伊红染色观察肝组织病理变化,用酶联免疫吸附法评估外周血、瘤旁组织和肿瘤组织中细胞因子(IFN-γ、IL-2、IL-4、IL-10、TGF-β、IL-1β、CCL2和CCL21)的变化。结果 双氢青蒿素联合顺铂能明显抑制小鼠肝脏肿瘤的生长,改善顺铂引起的体重和脾脏损失。顺铂治疗肝肿瘤小鼠增加了肿瘤组织中 CCL2 的含量和巨噬细胞的数量,促进了免疫抑制微环境的形成。联合疗法降低了肿瘤组织中 TGF-β 的含量,同时增加了瘤旁组织中 CCL2 的含量。结论双氢青蒿素与顺铂联合用药能明显阻止肝癌小鼠肝脏肿瘤的恶化,并通过改善顺铂诱导的免疫抑制微环境来提高顺铂的治疗效果。我们的研究结果为今后将双氢青蒿素作为顺铂的辅助药物治疗肝癌提供了理论依据。
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引用次数: 0
Immunohistochemical localization and expression of heat shock proteins (HSP27, HSP60, HSP70, and HSP90) during the oestrous cycle, pregnancy, and lactation in rat ovaries 大鼠卵巢发情周期、妊娠和哺乳期热休克蛋白(HSP27、HSP60、HSP70 和 HSP90)的免疫组织化学定位和表达
IF 2.5 4区 生物学 Q2 Medicine Pub Date : 2024-04-01 DOI: 10.1016/j.acthis.2024.152157
Banu Kandil , Nevin Kurtdede , Alev Gürol Bayraktaroglu

This study aimed to determine the expressions of HSP27, HSP60, HSP70, and HSP90 in rat ovaries during the oestrous cycle, pregnancy, and lactation. In follicle cells, HSP27 and HSP70 expression was not observed. HSP60 in oocytes was higher in the early stages of follicular development but decreased and disappeared as the follicle grew. HSP60 in granulosa and theca cells increased with follicle development and decreased with atresia. HSP90 in follicle cells did not change during follicle development or atresia. The expression of HSPs in interstitial cells was higher in the proestrus and estrus phases of the estrous cycle. The expression of HSPs in these cells was higher on day 5 of pregnancy, decreased on day 10, and decreased further on days 15 and 20. The expression of HSPs, which decreased in the second half of pregnancy, increased again on the first day of lactation. The expression of HSPs then decreased on day 5 of lactation and further decreased on days 10 and 20. HSP60 and HSP90 were positive in new and old corpus luteums (CLs) and their expression did not change during luteal development or regression. HSP27 and HSP70 were absent in new CLs. HSP27 was positive in old CLs and showed the same staining pattern during luteal regression. HSP70 expression was determined in old cyclic CLs during the oestrous cycle and pregnancy and decreased with luteal regression. HSP70 expression in old pregnancy CLs during lactation was very weak compared to the oestrous cycle and pregnancy. In conclusion, HSP60 and HSP90 may participate in folliculogenesis, luteal development, and steroidogenesis in luteal cells, and HSP27, HSP60, HSP70, and HSP90 may be effective in luteal regression and steroidogenesis in interstitial cells. HSP27 and HSP70 may be used as markers to identify old CLs in rats.

本研究旨在确定发情周期、妊娠期和哺乳期大鼠卵巢中 HSP27、HSP60、HSP70 和 HSP90 的表达情况。在卵泡细胞中,未观察到 HSP27 和 HSP70 的表达。卵泡发育早期,卵母细胞中的 HSP60 表达量较高,但随着卵泡的长大,HSP60 的表达量逐渐降低并消失。颗粒细胞和癌细胞中的 HSP60 随卵泡发育而增加,随闭锁而减少。卵泡细胞中的HSP90在卵泡发育或闭锁期间没有变化。在发情周期的预发情期和发情期,间质细胞中 HSPs 的表达量较高。这些细胞中 HSPs 的表达量在妊娠第 5 天较高,第 10 天下降,第 15 天和第 20 天进一步下降。妊娠后半期,HSPs 的表达量有所下降,但在哺乳期的第一天,HSPs 的表达量又有所增加。随后,HSPs 的表达在哺乳期第 5 天下降,在第 10 天和第 20 天进一步下降。HSP60和HSP90在新黄体和旧黄体中均呈阳性,其表达在黄体发育或退化过程中没有变化。新黄体中没有 HSP27 和 HSP70。HSP27在老黄体中呈阳性,并在黄体退化过程中显示出相同的染色模式。HSP70在发情周期和妊娠期的旧周期性CL中表达,并随着黄体退化而减少。与发情周期和妊娠期相比,哺乳期妊娠期CL中HSP70的表达非常弱。总之,HSP60和HSP90可能参与黄体细胞的卵泡生成、黄体发育和类固醇生成,而HSP27、HSP60、HSP70和HSP90可能对黄体退化和间质细胞的类固醇生成有效。HSP27 和 HSP70 可用作鉴定大鼠老旧 CL 的标记物。
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引用次数: 0
Neuropeptides in the rat claustrum – An immunohistochemical detection 大鼠视网膜中的神经肽--免疫组织化学检测
IF 2.5 4区 生物学 Q2 Medicine Pub Date : 2024-03-21 DOI: 10.1016/j.acthis.2024.152156
Anna Lipiec-Borowicz , Artur Pałasz , Aleksandra Suszka-Świtek , Łukasz Filipczyk , Alessandra Della Vecchia , John J. Worthington , Aneta Piwowarczyk-Nowak

Neuropeptides are involved in numerous brain activities and are responsible for a wide spectrum of higher mental functions. The main purpose of this outline structural qualitative study was to identify the possible immunoreactivity of classical neuropeptides, as well as novel ones such as nesfatin-1, phoenixin (PNX), spexin (SPX), neuromedin U (NMU) and respective receptors within the rat claustrum for the first time. The study shows the novel identification of peptidergic neurotransmission in the rat claustrum which potentially implicates a contribution of this neuropeptide to numerous central neurosecretory mechanisms.

神经肽参与多种脑部活动,并负责多种高级精神功能。这项结构定性研究的主要目的是首次鉴定大鼠鼓室中经典神经肽和新型神经肽(如内司肽-1、凤凰素(PNX)、矛肽(SPX)、神经美迪素 U(NMU))及其各自受体的可能免疫反应。该研究首次发现了大鼠鼓室中的肽能神经递质,这可能与这种神经肽对许多中枢神经分泌机制的贡献有关。
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引用次数: 0
Sheet-like interstitial cells connect epithelial and smooth muscle cells in the mouse prostate 连接小鼠前列腺上皮细胞和平滑肌细胞的片状间质细胞
IF 2.5 4区 生物学 Q2 Medicine Pub Date : 2024-03-14 DOI: 10.1016/j.acthis.2024.152153
Yoshihiro Kawaguchi , Keisuke Ohta , Tasuku Hiroshige , Kei-ichiro Uemura , Akinobu Togo , Kei-ichiro Nakamura , Tsukasa Igawa

Epithelial−stromal relationship in the prostate gland is crucial for maintaining homeostasis, including functional differentiation, proliferation, and quiescence. Pathological stromal changes are believed to cause benign prostatic hyperplasia (BPH). The prostate stromal tissue is known to have several subtypes of interstitial cells that connect the epithelium and smooth muscle. However, the characteristics of their morphology and connection patterns are not fully understood. Therefore, we aimed to investigated the three-dimensional morphology and intercellular interactions of interstitial cells in the prostate ventral lobe of mature wild-type mice using immunohistochemistry and focused ion beam–scanning electron microscopy tomography (FIB–SEM tomography). The prostate interstitial cells exhibited immunohistochemical subtypes, including PDGFRα single-positive, CD34 single-positive, and CD34 and PDGFRα double-positive. PDGFRα single-positive cells were observed as elongated cells just below the epithelium, CD34 single-positive cells were observed as polygonal cells in the area away from the epithelium, and double-positive cells were observed as elongated cells situated slightly deeper than PDGFRα single-positive cells. Furthermore, connexin43-immunoreactive puncta were observed on interstitial cells just beneath the epithelium, suggestive of possible electrical connections among the PDGFRα single-positive interstitial cells. Three-dimensional structural analysis using FIB–SEM tomography revealed sheet-like multilayered interstitial cells that appear to separate the glandular terminal from the deeper interstitial tissue, which includes smooth muscle and capillaries. Further, epithelial cells might be indirectly connected to the smooth muscle and nerve fibers via these sheet-like multilayered interstitial cellular networks. These findings suggest that the cellular network that separates the glandular terminals from the deep interstitial tissue functionally bridges the epithelium and smooth muscle, possibly playing a pivotal role in prostate tissue homeostasis through the epithelial−smooth muscle or epithelial−stromal relationships.

前列腺上皮与基质的关系对于维持前列腺的平衡至关重要,包括功能分化、增殖和静止。病理基质变化被认为是导致良性前列腺增生(BPH)的原因。众所周知,前列腺基质组织有几种亚型的间质细胞,它们连接着上皮和平滑肌。然而,它们的形态特征和连接模式还不完全清楚。因此,我们采用免疫组化和聚焦离子束扫描电子显微断层扫描(FIB-SEM tomography)技术,研究了成熟野生型小鼠前列腺腹叶间质细胞的三维形态和细胞间相互作用。前列腺间质细胞呈现免疫组化亚型,包括 PDGFRα 单阳性、CD34 单阳性以及 CD34 和 PDGFRα 双阳性。PDGFRα单阳性细胞表现为上皮下方的拉长细胞,CD34单阳性细胞表现为远离上皮的多边形细胞,双阳性细胞表现为比PDGFRα单阳性细胞稍深的拉长细胞。此外,在上皮下方的间质细胞上观察到了具有免疫反应的连接蛋白43点,这表明PDGFRα单阳性间质细胞之间可能存在电连接。利用 FIB-SEM 层析成像技术进行的三维结构分析显示,片状多层间质细胞似乎将腺体末端与包括平滑肌和毛细血管在内的深层间质组织分隔开来。此外,上皮细胞可能通过这些片状多层间质细胞网络与平滑肌和神经纤维间接相连。这些研究结果表明,将腺体终端与深层间质组织分隔开来的细胞网络具有连接上皮细胞和平滑肌的功能,可能通过上皮细胞-平滑肌或上皮细胞-间质的关系在前列腺组织稳态中发挥关键作用。
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引用次数: 0
Sunset Yellow induced biochemical and histopathological alterations in rat brain sub-regions 日落黄诱导大鼠大脑亚区域的生化和组织病理学改变
IF 2.5 4区 生物学 Q2 Medicine Pub Date : 2024-03-14 DOI: 10.1016/j.acthis.2024.152155
Diksha Bhatt , Krati Vyas, Shakuntala Singh, P.J. John, I.P. Soni

Sunset Yellow, a synthetic orange azo food dye was examined in this study for its impact on the Wistar rat brain sub-regions. The dye was administered orally to weanling rats at the Acceptable Daily Intake level (4 mg/kg/bw) for 40 days, and brain sub-regions viz., frontal cortex, cerebellum and hippocampus were examined for biochemical and histopathological changes. The results showed a significant decrease in tissue protein levels, superoxide dismutase, and catalase activity, as well as a significant increase in lipid peroxide levels in all brain sub-regions. Glutathione-S-transferase and Glutathione Reductase activities decreased, while Glutathione peroxidase activity increased. The biogenic amine levels and Acetylcholinesterase activity were also altered, with the frontal cortex and hippocampus being the most affected. Additionally, the dye caused histopathological damage in all brain sub-regions examined. This study indicates that the ADI level of Sunset Yellow may adversely affect brain tissue by causing oxidative damage.

本研究考察了日落黄(一种合成橙色偶氮食品染料)对 Wistar 大鼠大脑亚区域的影响。按每日允许摄入量(4 毫克/千克/体重)给断奶大鼠口服该染料 40 天,然后检查大脑的额叶皮层、小脑和海马等亚区域的生化和组织病理学变化。结果显示,所有脑亚区域的组织蛋白质水平、超氧化物歧化酶和过氧化氢酶活性都明显下降,过氧化脂质水平也明显升高。谷胱甘肽-S-转移酶和谷胱甘肽还原酶活性降低,而谷胱甘肽过氧化物酶活性升高。生物胺水平和乙酰胆碱酯酶活性也发生了改变,其中额叶皮层和海马受影响最大。此外,染料还对所有受检大脑亚区域造成组织病理学损伤。这项研究表明,日落黄的每日允许摄入量可能会通过造成氧化损伤而对脑组织产生不利影响。
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引用次数: 0
Usefulness of sulfonated azo dyes to evaluate macromolecularly oriented protein substrates 磺化偶氮染料在评估大分子定向蛋白质底物方面的用途
IF 2.5 4区 生物学 Q2 Medicine Pub Date : 2024-03-12 DOI: 10.1016/j.acthis.2024.152154
Maria Luiza S. Mello, Eli H.M. dos Anjos, Benedicto de Campos Vidal

Sulfonated azo dyes are crucial for the histochemical, topochemical, and electrophoretic demonstration of proteins. Additionally, these dyes may reveal the significance of evaluating the anisotropic phenomenon of linear dichroism in macromolecularly oriented stained proteins. However, this requires that the ordered –NH3+ groups available for electrostatic binding of the -SO3- dye groups are present in the protein substrate. Further, the reactive -SO3- dye groups should be positioned in a way to permit selective absorption of polarized light at the level of the dye –NN- chromophore azo groups. This review reports the usefulness of sulfonated azo dyes in revealing the extrinsic phenomenon of linear dichroism in dye-substrate complexes and changes in the oriented state of protein macromolecules.

磺化偶氮染料对蛋白质的组织化学、表观化学和电泳显示至关重要。此外,这些染料还能揭示评估大分子取向染色蛋白质线性二向色的各向异性现象的意义。不过,这需要蛋白质底物中存在有序的 -NH3+ 基团,以便静电结合 -SO3- 染料基团。此外,活性 -SO3- 染料基团的位置应允许染料 -NN- 发色团偶氮基团选择性地吸收偏振光。本综述报告了磺化偶氮染料在揭示染料-底物复合物线性二色性的外在现象以及蛋白质大分子定向状态变化方面的作用。
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引用次数: 0
Investigation of the differentiation potential of pericyte cells as an alternative source of mesenchymal stem cells 研究作为间充质干细胞替代来源的包膜细胞的分化潜力
IF 2.5 4区 生物学 Q2 Medicine Pub Date : 2024-03-02 DOI: 10.1016/j.acthis.2024.152145
Selen Polat , Yusufhan Yazir , Gökhan Duruksu , Kamil Can Kiliç , Serap Mert , Gülçin Gacar , Büşra Öncel Duman , Zehra Seda Halbutoğullari

Background

The mesenchymal stem cells (MSCs) with characterized by their multipotency and capacity to differentiate into various tissue cell types, have led to their incorporation in regenerative medicine research. However, the limited numbers of MSCs in the human body and their diverse differentiation capabilities in tissues highlight the need for exploring alternative regenerative cell sources. In this study, therefore, we conducted molecular level examinations to determine whether pericytes, specialized cell communities situated near blood vessels, could serve as a substitute for human bone marrow-derived mesenchymal stem cells (hBM-MSCs). In this context, the potential application of pericytes surrounds the vessels when MSCs are insufficient for functional purposes.

Methods

The pericytes utilized in this investigation were derived from the placenta and characterized at the third passage. Similarly, the hBM-MSCs were also characterized at the third passage. The pluripotent properties of the two cell types were assessed at the gene expression level. Thereafter, both pericytes and hBM-MSCs were directed towards adipogenic, osteogenic and chondrogenic differentiation. The cells in both groups were examined on days 7, 14, and, 21 and their differentiation status was compared both immunohistochemically and through gene expression analysis.

Results

Upon comparing the pluripotency characteristics of placental pericytes and hBM-MSCs, it was discovered that there was a substantial upregulation of the pluripotency genes FoxD3, Sox2, ZPF42, UTF1, and, Lin28 in both cell types. However, no significant expression of the genes Msx1, Nr6a1, Pdx1, and, GATA6 was observed in either cell type. It was also noted that pericytes differentiate into adipogenic, osteogenic and, chondrogenic lineages similar to hBM-MSCs.

Discussion

As a result, it has been determined that pericytes exhibit high differentiation and proliferation properties similar to those of MSCs, and therefore can be considered a suitable alternative cell source for regenerative medicine and tissue engineering research, in cases where MSCs are not available or insufficient. It is notable that pericytes have been suggested as a potential substitute in studies where MSCs are lacking.

背景间充质干细胞(MSCs)具有多潜能和分化成各种组织细胞类型的能力,因此被纳入再生医学研究。然而,间充质干细胞在人体内的数量有限,而且它们在组织中的分化能力各不相同,这凸显了探索其他再生细胞来源的必要性。因此,在本研究中,我们进行了分子水平的检测,以确定位于血管附近的特殊细胞群--周细胞是否可作为人骨髓间充质干细胞(hBM-MSCs)的替代物。在这种情况下,当间叶干细胞不足以实现功能性目的时,血管周围的周细胞就有了潜在的应用价值。同样,hBM-间充质干细胞也在第三次通过时进行了鉴定。在基因表达水平上评估了这两种细胞的多能特性。此后,周细胞和 hBM-间充质干细胞都被引导向成脂、成骨和软骨分化。结果比较了胎盘周细胞和 hBM-MSCs 的多能性特征后发现,两种细胞中的多能性基因 FoxD3、Sox2、ZPF42、UTF1 和 Lin28 都有大量上调。然而,在这两种细胞中都没有观察到基因 Msx1、Nr6a1、Pdx1 和 GATA6 的明显表达。讨论结果表明,周细胞表现出与间充质干细胞相似的高分化和增殖特性,因此在间充质干细胞不可用或不足的情况下,可被视为再生医学和组织工程研究的合适替代细胞来源。值得注意的是,在缺乏间充质干细胞的研究中,周细胞被认为是一种潜在的替代品。
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引用次数: 0
Cancer-induced morphological changes in enteric glial cells in the jejunum of Walker-256 tumor-bearing rats 癌症诱导的 Walker-256 肿瘤大鼠空肠肠胶质细胞形态变化
IF 2.5 4区 生物学 Q2 Medicine Pub Date : 2024-02-28 DOI: 10.1016/j.acthis.2024.152146
Fabiana Galvão da Motta Lima , Maysa Pacheco Alvarez da Silva , Sabrina Silva Sestak , Flávia Alessandra Guarnier , Ana Paula de Oliveira , João Victor Kuller , Brian David Gulbransen , Juliana Vanessa Colombo Martins Perles , Jacqueline Nelisis Zanoni

Cancer-induced cachexia is associated with systemic inflammation and gastrointestinal dysfunction. How changes to cells of the enteric nervous system contribute to gut dysfunction in tumor development and cancer cachexia is unknown. Here, we tested the hypothesis that changes to enteric glia, a type of peripheral glia that surround enteric neurons and regulate gut homeostasis, are associated with tumor development and that supplementing with the antioxidant L-glutathione is protective against the changes induced. Immunohistochemistry for neurons, enteric glial cells and immune cells was performed in whole-mount preparations and frozen histological sections of the jejunum from 20 Wistar rats, distributed in 4 groups: control, tumor of Walker-256, control administered with 1 % L-glutathione, and tumor of Walker-256 administered with 1 % L-glutathione. Morphoquantitative analyses were made using Image-Pro® Plus 4.5 and ImageJ® 1.43° software. Tumor development significantly reduced neuronal and glial cell populations in the myenteric and submucosal plexuses and enlarged glial cell body area in the submucosal plexus. In contrast, tumors increased glia in the jejunal mucosa and this effect was accompanied by B-lymphocyte recruitment. GSH-supplemented diet was not sufficient to protect against changes to neurons and glia in the submucosal plexus but was partially protective in the myenteric plexus. L-glutathione had no effect on physiological parameters of cachexia but was sufficient to preserve enteric glial cell density in the myenteric plexus. These results suggest that changes to both enteric neurons and glia likely contribute to the gastrointestinal effects of tumor development and that oxidative stress contributes to these effects in the enteric nervous system.

癌症诱发的恶病质与全身炎症和胃肠功能紊乱有关。肠道神经系统细胞的变化如何在肿瘤发生和癌症恶病质过程中导致肠道功能障碍尚不清楚。在这里,我们测试了这样一个假设:肠胶质细胞(一种围绕在肠神经元周围并调节肠道平衡的外周胶质细胞)的变化与肿瘤发生有关,而补充抗氧化剂 L-谷胱甘肽对诱发的变化具有保护作用。对 20 只 Wistar 大鼠空肠的全装制备物和冷冻组织切片进行了神经元、肠胶质细胞和免疫细胞的免疫组化,这些大鼠分为 4 组:对照组、Walker-256 肿瘤组、添加 1% L-谷胱甘肽的对照组和添加 1% L-谷胱甘肽的 Walker-256 肿瘤组。使用Image-Pro® Plus 4.5和ImageJ® 1.43°软件进行形态定量分析。肿瘤的发展明显减少了肠肌丛和粘膜下丛的神经元和胶质细胞数量,并扩大了粘膜下丛的胶质细胞体面积。与此相反,肿瘤增加了空肠粘膜中的胶质细胞,这种效应伴随着 B 淋巴细胞的招募。补充 GSH 的饮食不足以防止粘膜下神经丛的神经元和胶质发生变化,但对肠肌丛有部分保护作用。左旋谷胱甘肽对恶病质的生理参数没有影响,但足以保护肠肌丛的肠胶质细胞密度。这些结果表明,肠神经元和神经胶质细胞的变化很可能是肿瘤发生对胃肠道的影响,而氧化应激则是肠神经系统产生这些影响的原因。
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引用次数: 0
Sialylation status and its relationship with morphofunctional changes in human adult testis during sexually mature life and aging: A narrative review 人类成年睾丸在性成熟和衰老过程中的唾液酰化状态及其与形态功能变化的关系:叙述性综述
IF 2.5 4区 生物学 Q2 Medicine Pub Date : 2024-02-01 DOI: 10.1016/j.acthis.2024.152143
Mirko Manetti , Mirca Marini , Angelica Perna , Alessia Tani , Eleonora Sgambati

Sialic acids (Sias) are a family of electronegatively charged nine-carbon monosaccharides containing a carboxylic acid, mostly found as terminal residues in glycans of glycoproteins and glycolipids. They are bound to galactose or N-acetylgalactosamine via α2,3 or α2,6 linkage, or to other Sias especially via α2,8 linkage, which results in monomeric, oligomeric, and polymeric forms. Sias play determinant roles in a multitude of biological processes in human tissues from development to adult life until aging. In this review, we summarized the current knowledge on the sialylation status in the human testis with a main focus on sexually mature life and aging, when this organ shows significant morphofunctional changes resulting into variations of hormonal levels, as well as changes in molecules involved in mitochondrial function, receptors, and signaling proteins. Evidence suggests that Sias may have crucial morphofunctional roles in the different testicular components during the sexually mature age. With advancing age, significant loss of Sias and/or changes in sialylation status occur in all the testicular components, which seems to contribute to morphofunctional changes characteristic of the aging testis. Based on the current knowledge, further in-depth investigations will be necessary to better understand the mechanistic role of Sias in the biological processes of human testicular tissue and the significance of their changes during the aging process. Future investigations might also contribute to the development of novel prophylactic and/or therapeutic approaches that, by maintaining/restoring the correct sialylation status, could help in slowing down the testis aging process, thus preserving the testicular structure and functionality and preventing age-related pathologies.

硅烷酸(Sias)是一系列带电荷的九碳单糖,含有一个羧酸,主要作为末端残基存在于糖蛋白和糖脂的聚糖中。它们通过 α2,3 或 α2,6 连接与半乳糖或 N-乙酰半乳糖胺结合,或通过 α2,8 连接与其他 Sias 结合,从而形成单体、低聚体和聚合体形式。从发育到成年直至衰老,Sias 在人体组织的多种生物过程中发挥着决定性作用。在这篇综述中,我们总结了目前有关人类睾丸中硅烷基化状态的知识,主要侧重于性成熟和衰老期,因为在这一时期,睾丸这一器官会出现显著的形态功能变化,导致激素水平的变化,以及线粒体功能、受体和信号蛋白等相关分子的变化。有证据表明,在性成熟期,Sias 可能在睾丸的不同组成部分中发挥关键的形态功能作用。随着年龄的增长,所有睾丸成分中都会出现 Sias 的显著缺失和/或 Sialylation 状态的变化,这似乎是老化睾丸特有的形态功能变化的原因。基于现有的知识,有必要进行进一步的深入研究,以更好地了解 Sias 在人类睾丸组织生物过程中的机理作用及其在衰老过程中发生变化的意义。未来的研究还可能有助于开发新型的预防和/或治疗方法,通过维持/恢复正确的硅烷化状态,有助于延缓睾丸的衰老过程,从而保护睾丸的结构和功能,预防与衰老相关的病症。
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引用次数: 0
Immunolocalization patterns of histone-deacetylases in salivary glands of mice during postnatal development 小鼠唾液腺中组蛋白-脱乙酰酶在出生后发育过程中的免疫定位模式
IF 2.5 4区 生物学 Q2 Medicine Pub Date : 2024-02-01 DOI: 10.1016/j.acthis.2024.152144
Chubo Yang , Xuejing Song , Jiaqi Kong , Huishu Li , Yuanbo Zhan

Objective

Histone-deacetylases (HDACs) are epigenetic modulators involved in the control of gene expression. No data are available on the expression or subcellular localization of HDACs in salivary glands. The present study aims to examine the subcellular distribution of HDACs in salivary glands during postnatal development.

Design

The major salivary glands of C57/BL6 mice were separately removed at 10, 25, 30,60 and 90 days after birth. Hematoxylin-eosin (H&E) and immunohistochemical staining were performed for HDACs. Gene Expression of HDACs in C57BL/6. NOD-Aec1Aec2 mice salivary glands during the development of Sjögren's syndrome-like illness were also analyzed by using the gene expression datasets (GSE 15640).

Results

In the mice salivary gland, HDACs were found to have different localization patterns at various stages of development (10, 25, 30, 60, and 90 days). Apart from HDAC6, ductal cells of salivary glands were the primary sites for HDAC localization. HDAC2, 8, 5, 10 and 11 were expressed at high levels in the salivary gland after birth while HDAC6 showed no expression during postnatal development. This suggests that these HDAC subtypes may have different roles in salivary gland function. In the context of Sjögren's syndrome-like illness, HDAC 2, 8 and 10 showed low expression while HDAC1, 6,5,3 and 11 had relatively high expression in the salivary gland.

Conclusions

This study has provided an important reference for understanding the spatiotemporal-specific expression of HDACs in the salivary gland. These results offer new clues for the experimenters and hold promise for developing innovative therapeutic strategies for salivary gland-related diseases.

目的组蛋白脱乙酰酶(HDACs)是一种参与控制基因表达的表观遗传调节剂。目前还没有关于 HDACs 在唾液腺中的表达或亚细胞定位的数据。本研究旨在研究 HDACs 在唾液腺中的亚细胞分布。设计分别在出生后 10、25、30、60 和 90 天取出 C57/BL6 小鼠的主要唾液腺。对HDACs进行血红素-伊红(H&E)和免疫组化染色。HDACs 在 C57BL/6.结果 在小鼠唾液腺的不同发育阶段(10、25、30、60 和 90 天),HDACs 有不同的定位模式。除 HDAC6 外,唾液腺导管细胞是 HDAC 的主要定位点。HDAC2、8、5、10和11在出生后的唾液腺中高水平表达,而HDAC6在出生后的发育过程中没有表达。这表明这些 HDAC 亚型可能在唾液腺功能中发挥着不同的作用。结论 本研究为了解 HDACs 在唾液腺中的时空特异性表达提供了重要参考。这些结果为实验者提供了新的线索,并为开发唾液腺相关疾病的创新治疗策略带来了希望。
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Acta histochemica
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