Molecular immunology最新文献_第10页

Protocatechuic aldehyde promotes diabetic wound healing by enhancing angiogenesis via H3K18 lactylation-mediated Acvr1c expression 原儿茶醛通过H3K18乳酸化介导的Acvr1c表达促进血管生成，从而促进糖尿病伤口愈合。

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-09-30 DOI: 10.1016/j.molimm.2025.09.002

Weijing Fan , Yang You , Yin Qu, Guobin Liu

Delayed wound recovery is a major health issue affecting people with diabetes. Histone lactylation is involved in tissue repair. However, it is not clear whether protocatechuic aldehyde (PCA) promotes diabetic wound healing through histone lactylation. In this study, a diabetic wound mouse model was constructed to delve into the role of PCA in vivo. Chromatin immunoprecipitation sequencing (ChIP-seq) was used to determine genes affected by H3K18 lactylation (H3K18la) under PCA treatment. The effects and mechanisms of PCA on histone lactylation and angiogenesis were investigated through cellular experiments. We found that PCA accelerated wound healing and angiogenesis in diabetic mice, and significantly reduced the inflammatory response in wound tissues. Lactate and H3K18la levels were augmented in the model group in comparison with the control group, however, PCA treatment remarkably reversed their levels. ChIP-seq analysis revealed a significant enrichment of H3K18la at the Acvr1c locus, and this histone modification was downregulated by PCA treatment. PCA remarkably enhanced Acvr1c expression through H3K18la in HUVECs. Moreover, PCA treatment markedly elevated cell viability, migration and tube formation in comparison with the control group. However, this effect was counteracted by Acvr1c knockdown. In conclusion, PCA promoted HUVEC angiogenesis by increasing H3K18la-mediated Acvr1c expression, thereby promoting diabetic wound healing. This could offer a new treatment approach to enhance the effectiveness of healing diabetic wounds.

伤口恢复延迟是影响糖尿病患者的主要健康问题。组蛋白乳酸化参与组织修复。然而，原儿茶醛（PCA）是否通过组蛋白乳酸化促进糖尿病伤口愈合尚不清楚。本研究通过构建糖尿病创面小鼠模型，探讨PCA在体内的作用。采用染色质免疫沉淀测序（ChIP-seq）检测PCA处理下受H3K18乳酸化（H3K18la）影响的基因。通过细胞实验研究了PCA对组蛋白乳酸化和血管生成的影响及其机制。我们发现，PCA加速了糖尿病小鼠的伤口愈合和血管生成，并显著降低了伤口组织的炎症反应。与对照组相比，模型组乳酸和H3K18la水平升高，但PCA处理显著逆转了它们的水平。ChIP-seq分析显示，H3K18la在Acvr1c位点显著富集，这种组蛋白修饰在PCA处理下被下调。PCA通过H3K18la显著增强huvec中Acvr1c的表达。此外，与对照组相比，PCA治疗显著提高了细胞活力、迁移和管形成。然而，这种作用被Acvr1c敲低所抵消。综上所述，PCA通过增加h3k18la介导的Acvr1c表达促进HUVEC血管生成，从而促进糖尿病创面愈合。这可能为提高糖尿病伤口愈合的有效性提供一种新的治疗方法。

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引用次数: 0

The mechanism of SMAD4/ERK pathway in regulating Th17/Treg cell differentiation leading to olfactory dysfunction in chronic rhinosinusitis SMAD4/ERK通路调控Th17/Treg细胞分化导致慢性鼻窦炎嗅觉功能障碍的机制

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-09-25 DOI: 10.1016/j.molimm.2025.09.006

Shouming Cao , Yan Niu , Jinmei Ning , Nannan Wen , Rui Chen , Haiying Wu

Background

Chronic rhinosinusitis (CRS) is characterized by a high recurrence rate within five years post-surgery, posing a persistent challenge for otolaryngologists globally. Recent research has underscored the pivotal role of the Th17/Treg cell balance in the pathogenesis of CRS. This study aims to investigate the alterations in the Th17/Treg cell balance in CRS and elucidate the underlying molecular mechanisms.

Methods

CRS model was established to assess the levels of inflammatory cytokines, olfactory marker protein expression, SMAD4 expression, and ERK1/2 phosphorylation. We then overexpressed SMAD4 or treated CRS mice with ERK1/2 inhibitors, measuring the impact on Th17/Treg marker expression. Moreover, the influence of the SMAD4/ERK signaling axis on the Th17/Treg balance within the CD4 + T cell population was investigated.

Results

CRS mice exhibited significantly reduced olfactory marker protein and SMAD4 expression, alongside increased ERK1/2 phosphorylation. Histological analysis revealed an increased infiltration of eosinophils. Of particular note, the expression of Treg markers was markedly decreased, while Th17 marker expression exhibited a corresponding increase, suggesting a potential shift in the Th17/Treg balance. Interventions involving SMAD4 overexpression or ERK1/2 inhibition led to a reduction in eosinophil infiltration and successfully reversed the aberrant expression patterns of the aforementioned markers. Furthermore, SMAD4 knockdown resulted in a decreased proportion of Treg cells and an increased proportion of Th17 cells. This alteration in the Th17/Treg balance was effectively counteracted by ERK inhibitor.

Conclusions

The deletion of SMAD4 regulates the differentiation of Th17/Treg cells via ERK1/2 phosphorylation, thereby exacerbating the olfactory dysfunction of CRS.

慢性鼻窦炎（CRS）的特点是术后5年内复发率高，对全球耳鼻喉科医生构成了持续的挑战。最近的研究强调了Th17/Treg细胞平衡在CRS发病机制中的关键作用。本研究旨在探讨CRS中Th17/Treg细胞平衡的改变，并阐明其分子机制。方法建立scrs模型，评估炎症因子、嗅觉标志蛋白表达、SMAD4表达和ERK1/2磷酸化水平。然后，我们过表达SMAD4或用ERK1/2抑制剂治疗CRS小鼠，测量对Th17/Treg标记物表达的影响。此外，我们还研究了SMAD4/ERK信号轴对CD4 + T细胞群中Th17/Treg平衡的影响。结果scrs小鼠嗅觉标记蛋白和SMAD4表达显著降低，ERK1/2磷酸化水平升高。组织学分析显示嗜酸性粒细胞浸润增加。特别值得注意的是，Treg标记物的表达明显下降，而Th17标记物的表达则相应增加，这表明Th17/Treg平衡可能发生了变化。涉及SMAD4过表达或ERK1/2抑制的干预导致嗜酸性粒细胞浸润减少，并成功逆转上述标记物的异常表达模式。此外，SMAD4敲除导致Treg细胞比例下降，Th17细胞比例增加。这种Th17/Treg平衡的改变被ERK抑制剂有效地抵消了。结论SMAD4缺失通过ERK1/2磷酸化调控Th17/Treg细胞的分化，从而加重CRS的嗅觉功能障碍。

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引用次数: 0

Therapeutic targeting of neuroinflammation in sphingolipidosis 鞘脂病神经炎症的靶向治疗

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-09-23 DOI: 10.1016/j.molimm.2025.09.005

Ebru Ada , Volkan Seyrantepe

Lysosomal storage diseases (LSDs) are a class of hereditary metabolic disorders primarily caused by lysosomal enzyme defects, leading to the accumulation of undegraded substrates. Sphingolipidoses, a subset of LSDs, are primarily associated with profound involvement of the central nervous system (CNS), characterized by progressive neurodegeneration due to massive sphingolipid accumulation. A common pathological feature among many CNS-involved LSDs is the early activation of microglia and astrocytes, which often precedes and predicts regions of subsequent neuronal loss. The extent to which neuroinflammation disrupts CNS homeostasis appears to be determined by its onset, magnitude, and duration. Although neuroinflammatory processes are increasingly recognized as critical contributors to disease progression in sphingolipidoses, the molecular mechanisms underlying glial activation and the initiation of inflammatory cascades remain incompletely understood. Therefore, mouse models of sphingolipidoses have been instrumental in elucidating these pathogenic processes and provide valuable platforms for evaluating therapeutic strategies. This review critically examines the role of neuroinflammation in sphingolipidoses, summarizes insights derived from pre-clinical models, and discusses the therapeutic potential of anti-inflammatory interventions to mitigate CNS pathology and improve clinical outcomes.

溶酶体贮积病（lsd）是一类主要由溶酶体酶缺陷引起的遗传性代谢疾病，导致未降解底物的积累。鞘脂病是lsd的一个亚型，主要与中枢神经系统（CNS）的深度受累有关，其特征是由于大量鞘脂积累导致的进行性神经退行性变。在许多涉及中枢神经系统的lsd中，一个共同的病理特征是小胶质细胞和星形胶质细胞的早期激活，这通常先于并预测随后的神经元丢失区域。神经炎症破坏中枢神经系统稳态的程度似乎取决于其发病、程度和持续时间。尽管神经炎症过程越来越多地被认为是鞘脂病疾病进展的关键因素，但神经胶质激活和炎症级联反应启动的分子机制仍不完全清楚。因此，小鼠鞘脂病模型有助于阐明这些致病过程，并为评估治疗策略提供有价值的平台。本文综述了神经炎症在鞘脂病中的作用，总结了从临床前模型中得到的见解，并讨论了抗炎干预减轻中枢神经系统病理和改善临床结果的治疗潜力。

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引用次数: 0

Hypocontractile airway smooth muscle phenotype exhibits enhanced β2 laminin chain expression in lung allergy model 肺变态反应模型中，低收缩气道平滑肌表型β2层粘连蛋白链表达增强

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-09-23 DOI: 10.1016/j.molimm.2025.09.003

Ivonne Pacheco-Alba , Blanca Bazán-Perkins

Sensitization with ovalbumin (OVA) in guinea pigs to induce anti-OVA IgE generates various allergic response phenotypes. One phenotype, characterized by the absence of bronchial obstruction and airway hyperresponsiveness in response to chronic antigen challenge, is termed non-responding (NR) and exhibits high IFN-γ levels. The Th1 cytokine profile is linked with high laminin β2 expression. This study evaluated laminin β2 expression in the chronic NR phenotype. Guinea pigs were sensitized and challenged with OVA three times (acute) or twelve times (chronic). Guinea pigs that responded to all challenges formed the asthma model phenotype. Controls were sensitized and challenged with saline. Immunohistochemistry was used to observe laminin β2 and its receptor, the α6 integrin subunit, in bronchial and arterial intrapulmonary smooth muscles. Only chronic NR guinea pigs showed increased laminin β2 expression in these muscles, while it remained similar in other groups. The α6 integrin subunit significantly increased in the acute and chronic asthma models, chronic controls, and NR guinea pigs in bronchial smooth muscle. In arterial intrapulmonary smooth muscle, the α6 integrin subunit increased in acute NR and chronic asthma model guinea pigs. The expression of laminin β2 in bronchial and arterial intrapulmonary smooth muscles correlates with α6 integrin subunit levels, and higher levels of laminin β2 were significantly related to reduced antigen-induced bronchial obstruction and reactivity to histamine. The expression of these proteins does not affect the proliferation of pulmonary blood vessels. Laminin β2 chain overexpression is likely involved in the chronic containment of the obstructive allergic response.

用卵清蛋白（OVA）致敏豚鼠诱导抗OVA IgE产生各种过敏反应表型。一种表型，其特征是对慢性抗原攻击没有支气管阻塞和气道高反应性，被称为无反应（NR），并表现出高IFN-γ水平。Th1细胞因子谱与层粘连蛋白β2的高表达有关。本研究评估了层粘连蛋白β2在慢性NR表型中的表达。用OVA致敏和攻毒豚鼠3次（急性）或12次（慢性）。对所有挑战都有反应的豚鼠形成了哮喘模型表型。对照组致敏并给予生理盐水刺激。采用免疫组化方法观察层粘连蛋白β2及其受体α6整合素亚基在支气管和动脉肺内平滑肌中的表达。只有慢性NR豚鼠在这些肌肉中表现出层粘连蛋白β2的表达增加，而在其他组中保持相似。α6整合素亚基在急、慢性哮喘模型、慢性对照和NR豚鼠支气管平滑肌中显著升高。急性NR和慢性哮喘模型豚鼠动脉肺内平滑肌α6整合素亚基升高。层粘连蛋白β2在支气管和动脉肺内平滑肌中的表达与α6整合素亚基水平相关，较高的层粘连蛋白β2水平与减少抗原诱导的支气管阻塞和组胺反应性显著相关。这些蛋白的表达不影响肺血管的增殖。层粘连蛋白β2链过表达可能参与了阻塞性过敏反应的慢性抑制。

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引用次数: 0

Monochromatic green light-mediated melatonin promotes cecal barrier function in broilers 单色绿光介导的褪黑素促进肉鸡盲肠屏障功能

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-09-19 DOI: 10.1016/j.molimm.2025.09.004

Tao Quan, Ran Li, Yaoxing Chen, Ting Gao

Light plays a crucial role as an environmental factor, greatly affecting chick behavior, production performance and health. Melatonin, an essential marker of photoelectric signaling, plays a role in regulating various physiological functions in broilers, such as gut health. However, whether monochromatic light can mediate melatonin secretion to regulate intestinal function and its regulatory mechanism are not known. In the present study, we showed that monochromatic green light significantly enhanced the mucosal barrier function of the broiler cecum, including the up-regulation of goblet cells and their secreted MUC2 content, tight junction protein expression and enterocyte proliferative viability. However, when the pineal gland was removed, accompanied by a decrease in melatonin content, the green light advantage disappeared and the intestinal mucosal barrier function was severely impaired. Mechanistically, we found that monochromatic green light promotes melatonin secretion, which enters the intestine to bind Mel1a receptors located on macrophage membranes in cecum, inhibits its downstream TLR4/ERK/JNK/NF-κB signaling pathway, promotes M2-type macrophage polarization, reduces intestinal inflammation levels while up-regulating intestinal antioxidant levels, and ultimately strengthens the cecum mucosal barrier function. Our findings provide new theoretical support for the future use of melatonin during intestinal development, as well as theoretical guidance for the proper application of artificial lighting in the modern chicken industry to improve chicken's intestinal health.

光作为一种环境因子，对雏鸡的行为、生产性能和健康有着重要的影响。褪黑素是一种重要的光电信号标志物，在调节肉鸡肠道健康等多种生理功能中发挥重要作用。然而，单色光是否能介导褪黑激素分泌调节肠道功能及其调节机制尚不清楚。在本研究中，我们发现单色绿光显著增强了肉鸡盲肠粘膜屏障功能，包括上调杯状细胞及其分泌MUC2含量、上调紧密连接蛋白表达和肠细胞增殖活力。然而，当松果体被切除时，伴随着褪黑激素含量的减少，绿光优势消失，肠黏膜屏障功能严重受损。在机制上，我们发现单色绿光促进褪黑激素分泌，褪黑激素进入肠道结合位于盲肠巨噬细胞膜上的Mel1a受体，抑制其下游TLR4/ERK/JNK/NF-κB信号通路，促进m2型巨噬细胞极化，降低肠道炎症水平，上调肠道抗氧化水平，最终增强盲肠黏膜屏障功能。我们的研究结果为未来肠道发育过程中褪黑素的使用提供了新的理论支持，也为现代养鸡业中合理应用人工照明改善鸡肠道健康提供了理论指导。

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引用次数: 0

Characterization of the heterogeneity in oxidative stress and transcriptional programs within the in vivo microenvironment of ulcerative colitis 溃疡性结肠炎体内微环境中氧化应激和转录程序异质性的表征

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-09-09 DOI: 10.1016/j.molimm.2025.08.017

Yongwei Zhuang , Ran Ye , Jingyu Chen , Gefei Chen , Luyi Chen , Yabi Zhu , Shufang Ye , Yangyang Liu

Objective

Oxidative stress exerts an essential role in the pathogenesis of ulcerative colitis (UC). This study aims to unveil the heterogeneity in oxidative stress among immune cell subpopulations in UC.

Methods

Human colon epithelial cells were exposed to 100 ng/mL LPS to stimulate UC, which were administrated with antioxidants 500 mM butylated hydroxyanisole or 20 μM N-acetylcysteine. A single-cell atlas was constructed across UC, and heterogeneous cell subpopulations were evaluated at single-cell and bulk levels.

Results

Activation of oxidative stress and inflammatory response, enhanced migration capacity, and impaired tight junction were observed in LPS-induced UC cell models, which were ameliorated by antioxidants. Five cell types: plasma cells, T cells, myeloid cells, and B cells were clustered across UC and control gut biopsies, which were tightly interacted. Myeloid cells were sub-clustered into conventional dendritic cells, M1 macrophages, IL23R⁺ myeloid cells, mast cells, and follicular dendritic cells; T cells were sub-clustered into Th17, CD4⁺ naïve T cells, CD8⁺ cytotoxic T cells, CD4⁺ exhausted T cells, CD8⁺ memory T cells, Tregs, and Th1. The heterogeneous myeloid and T cells was confirmed at the single-cell and bulk levels. The activity of oxidative stress was heterogeneous among diverse myeloid cell or T cell subpopulations, with the strongest activity in M1 macrophages and CD4⁺ exhausted T cells, respectively. It was also found the specific transcriptional programs of M1 macrophages and CD8⁺ cytotoxic T cells.

Conclusion

Overall, our findings unveil the heterogeneity in oxidative stress and transcriptional programs among diverse myeloid and T cell subpopulations in UC.

目的氧化应激在溃疡性结肠炎（UC）的发病机制中发挥重要作用。本研究旨在揭示UC免疫细胞亚群中氧化应激的异质性。方法将人结肠上皮细胞暴露于100 ng/mL LPS刺激UC，并给予500 mM丁基羟基异黄酮或20 μM n -乙酰半胱氨酸抗氧化剂。在UC中构建单细胞图谱，并在单细胞和整体水平上评估异质细胞亚群。结果在lps诱导的UC细胞模型中观察到氧化应激和炎症反应激活，迁移能力增强，紧密连接受损，抗氧化剂改善。五种细胞类型：浆细胞、T细胞、骨髓细胞和B细胞聚集在UC和对照肠道活检中，它们紧密相互作用。髓样细胞亚簇分为常规树突状细胞、M1巨噬细胞、IL23R+髓样细胞、肥大细胞和滤泡树突状细胞；T细胞亚簇分为Th17、CD4+ naïve T细胞、CD8+细胞毒性T细胞、CD4+耗竭T细胞、CD8+记忆T细胞、Tregs和Th1。在单细胞和整体水平上证实了骨髓细胞和T细胞的异质性。氧化应激的活性在不同的骨髓细胞或T细胞亚群中是不均匀的，其中M1巨噬细胞和CD4+耗竭T细胞的活性最强。我们还发现了M1巨噬细胞和CD8+细胞毒性T细胞的特异性转录程序。总之，我们的发现揭示了UC不同髓细胞和T细胞亚群中氧化应激和转录程序的异质性。

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引用次数: 0

Profiling of SFTS virus and host protein interactions by affinity purification-mass spectrometry SFTS病毒与宿主蛋白相互作用的亲和纯化-质谱分析

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-09-09 DOI: 10.1016/j.molimm.2025.09.001

Wen Hou , Jiansen Lu , Hao Pan , Tao Wang , Hongyun Liu , Ruibing Chen

Severe Fever with Thrombocytopenia Syndrome (SFTS), caused by the novel phlebovirus SFTSV (SFTS bunyavirus), was first identified in 2009 across several Chinese provinces, with a case fatality rate reaching 30 %. Given its compact genome, SFTSV critically depends on host cellular machinery for replication and pathogenesis. In this study, we employed a systematic strategy combining co-immunoprecipitation of viral-host complexes with formaldehyde crosslinking and affinity purification-mass spectrometry (AP-MS) to comprehensively map SFTSV-host interactions. We systematically analyzed protein complexes associated with all five viral structural/non-structural proteins (NP, NSs, Gc, Gn, and L), identifying 432 host proteins as potential viral interactors. Subsequent bioinformatic analysis included Gene Ontology categorization and functional domain/pathway enrichment analysis via KEGG, with interaction networks visualized through Cytoscape. Importantly, we experimentally validated key interactions between NSs and host proteins VDAC1, Vimentin, and HSP90AB1, demonstrating robust consistency with our mass spectrometry findings.

由新型静脉病毒SFTSV （SFTS布尼亚病毒）引起的严重发热伴血小板减少综合征（SFTS）于2009年首次在中国几个省份被发现，病死率达到30% %。鉴于其紧凑的基因组，SFTSV严重依赖宿主细胞机制进行复制和发病。在这项研究中，我们采用了一种系统的策略，将病毒-宿主复合物的共免疫沉淀与甲醛交联和亲和纯化-质谱（AP-MS）相结合，以全面绘制sftsv -宿主相互作用。我们系统地分析了与所有五种病毒结构/非结构蛋白（NP、NSs、Gc、Gn和L）相关的蛋白复合物，确定了432种宿主蛋白是潜在的病毒相互作用物。随后的生物信息学分析包括通过KEGG进行基因本体分类和功能域/途径富集分析，并通过Cytoscape可视化相互作用网络。重要的是，我们通过实验验证了NSs与宿主蛋白VDAC1、Vimentin和HSP90AB1之间的关键相互作用，证明了与我们的质谱研究结果的强大一致性。

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引用次数: 0

SNHG16-loaded extracellular vesicles from hypoxic NSCLC cells drive M2 macrophage polarization to enhance cancer aggressiveness 缺氧NSCLC细胞中装载snhg16的细胞外囊泡驱动M2巨噬细胞极化以增强肿瘤侵袭性

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-09-08 DOI: 10.1016/j.molimm.2025.08.022

Yanshen Hou , Ximing Li , Lingfei Zeng , Yuan Zhang

Hypoxia plays a critical role in regulating the progression of non-small cell lung cancer (NSCLC) by modulating the tumor immune microenvironment (TIME). Tumor-associated macrophages (TAMs), important components of TIME, can be regulated by hypoxic conditions. Unfortunately, the molecular mechanisms by which hypoxia regulates TAMs in TIME to affect NSCLC progression has not been fully delineated. The present study evidenced that hypoxia-stimulated NSCLC cells secreted extracellular vesicles (EVs) were featured with highly expressed small nucleolar RNA host gene 16 (SNHG16), and SNHG16-containing EVs (SNHG16-EVs) synergistically promoted cell proliferation, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) properties in NSCLC cells, and induced M2-polarization of macrophages in THP-1 cells through delivering SNHG16. Notably, M2-polarized macrophages were capable of enhancing cancer aggressiveness in NSCLC cells through secreting tumor-initiating cytokines, including interleukin-10 (IL-10), transforming growth factor β (TGF-β), and vascular endothelial-derived growth factor (VEGF). Mechanistically, it was found that SNHG16 sponged miR-132–3p to positively regulate its downstream target, kinesin family member 5 A (KIF5A), via a competing endogenous RNA (ceRNA) mechanism-dependent manner. Rescue experiments confirmed that SNHG16-EVs induced NSCLC progression and M2 polarization of THP-1 cells were all reversed by overexpressing miR-132–3p and silencing KIF5A. Collectively, hypoxia-stimulated NSCLC cells transferred SNHG16-containing EVs to promote cancer aggressiveness and M2-polarized macrophages in NSCLC through modulating the downstream miR-132–3p/KIF5A axis, and this study verified that targeting SNHG16-EVs may be a novel strategy to hamper NSCLC progression via modulating TME.

缺氧通过调节肿瘤免疫微环境（TIME）在非小细胞肺癌（NSCLC）的进展中起关键作用。肿瘤相关巨噬细胞（tam）是TIME的重要组成部分，可在缺氧条件下调节。不幸的是，缺氧在时间内调节tam影响NSCLC进展的分子机制尚未完全描述。本研究证实，缺氧刺激的NSCLC细胞分泌的细胞外囊泡（EVs）具有高表达小核核RNA宿主基因16 （SNHG16）的特征，含SNHG16的EVs （SNHG16-EVs）通过传递SNHG16协同促进NSCLC细胞的细胞增殖、上皮-间质转化（EMT）和肿瘤干细胞（CSC）特性，并诱导THP-1细胞中巨噬细胞的m2极化。值得注意的是，m2极化巨噬细胞能够通过分泌肿瘤启动因子，包括白细胞介素-10 （IL-10）、转化生长因子β (TGF-β)和血管内皮源性生长因子（VEGF），增强NSCLC细胞的肿瘤侵袭性。在机制上，我们发现SNHG16海绵miR-132-3p通过竞争内源性RNA （ceRNA）依赖机制的方式正向调节其下游靶标激酶家族成员5 A （KIF5A）。救援实验证实，snhg16 - ev诱导的NSCLC进展和THP-1细胞的M2极化均可通过过表达miR-132-3p和沉默KIF5A逆转。总的来说，缺氧刺激的NSCLC细胞通过调节下游miR-132-3p /KIF5A轴，将含有snhg16的ev转移到NSCLC中，促进肿瘤侵袭性和m2极化巨噬细胞，本研究证实靶向snhg16 - ev可能是通过调节TME阻碍NSCLC进展的一种新策略。

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引用次数: 0

Drice negatively regulates cellular and humoral immunity of Drosophila melanogaster price负向调节果蝇的细胞免疫和体液免疫

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-09-06 DOI: 10.1016/j.molimm.2025.08.020

Priyanka Jaiswal, Madhu G. Tapadia

The innate immune response is a double-edged sword in insects, comprising the humoral and cellular mechanisms to fight and eliminate pathogens. The humoral response is achieved by the production of antimicrobial peptides, which are secreted in the hemolymph. The cellular responses are mediated by phagocytosis, encapsulation and melanization. Though the fat bodies are the primary immune tissues in Drosophila, secreting AMPs, the Malpighian tubules are also autonomous immune organs that constitutively secrete AMPs at basal levels, which increases after infection. Here we provide evidence to show that the caspase 3 homolog in Drosophila, Drice, negatively regulates both, cellular as well as humoral immunity. Depletion of Drice leads to the increased expression of transcription factor Relish, which enhances the expression of certain AMPs regulated by the IMD pathway. In the absence of Drice, both the Ecdysone receptor- B1 and Broad-core (Br-C) are also upregulated which are upstream regulators of the IMD pathway. The increase in crystal cells clearly indicates Drice to be a negative regulator of this form of cellular immunity. Collectively our findings suggest the role of Drice in the immune regulation of Drosophila melanogaster, and these results will add to the growing understanding of diverse roles of caspases in immune regulation.

昆虫的先天免疫反应是一把双刃剑，包括体液和细胞机制来对抗和消灭病原体。体液反应是通过产生在血淋巴中分泌的抗菌肽来实现的。细胞反应由吞噬、包被和黑化介导。虽然脂肪体是果蝇的主要免疫组织，分泌AMPs，但马尔比氏小管也是自主免疫器官，在基础水平上组成性地分泌AMPs，在感染后增加。在这里，我们提供的证据表明，在果蝇的caspase 3同源物，水稻，负调控，细胞和体液免疫。price的缺失导致转录因子flavor的表达增加，从而增强了受IMD途径调节的某些amp的表达。在没有price的情况下，Ecdysone受体- B1和Broad-core （Br-C）也上调，它们是IMD途径的上游调节因子。晶体细胞的增加清楚地表明，普莱斯是这种细胞免疫形式的负调节因子。总的来说，我们的研究结果提示了Drice在果蝇免疫调节中的作用，这些结果将增加对半胱天冬酶在免疫调节中的多种作用的理解。

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引用次数: 0

MAP30 inhibits proliferation and metastasis of bladder cancer by increasing EGR1 expression and promoting the transcriptional activation of DUSP1 MAP30通过增加EGR1的表达和促进DUSP1的转录激活来抑制膀胱癌的增殖和转移

IF 3 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular immunology

Pub Date : 2025-09-06 DOI: 10.1016/j.molimm.2025.08.024

Kaiyue Wang , Qiao Gu , Chunyan Xue , Junyu Shi , Kun Wang , Xiaozhou He

The confirmed tumor-inhibitory effects of the 30 kDa Momordica anti-human immunodeficiency virus protein (MAP30) have yet to be complemented by an exploration into its mechanism of action on tumor development and metastasis. For this purpose, we delved into the intrinsic mechanism of MAP30 in bladder cancer (BC). Here, we demonstrated that MAP30 markedly suppressed the proliferation, migration, invasion, and angiogenic capabilities of human BC cells in vitro, and the tumor metastatic potential in vivo. Furthermore, our findings showed that MAP30 suppressed the functional activities of BC cells by upregulating the expression levels of early growth response 1 (EGR1). Additionally, our investigation confirmed that EGR1 and dual specificity phosphatase 1 (DUSP1) were down-expressed in BC and had been identified as closely linked to the advancement of BC. DUSP1 was transcriptionally induced by EGR1, and the expression of EGR1 was found to be positively linked with DUSP1 in human BC tissues. The knockdown of EGR1 was found to boost cell invasion, migration, proliferation, and angiogenesis via the MAPK signaling pathway, however, the overexpression of DUSP1 inhibited EGR1 knockdown-induced promotion of these functional activities in BC cells. Furthermore, MAP30 inhibited the invasion, migration, proliferation, and angiogenesis of BC cells by regulating the EGR1-DUSP1 axis. Our study yielded an exhaustive insight into the suppressive actions of MAP30 on BC progression.

30 kDa Momordica anti-human immunodeficiency virus protein （MAP30）已证实具有肿瘤抑制作用，但其在肿瘤发生和转移中的作用机制还有待进一步研究。为此，我们深入探讨了MAP30在膀胱癌（BC）中的内在机制。在这里，我们证明了MAP30在体外显著抑制人BC细胞的增殖、迁移、侵袭和血管生成能力，以及体内肿瘤转移潜力。此外，我们的研究结果表明，MAP30通过上调早期生长反应1 （early growth response 1, EGR1）的表达水平来抑制BC细胞的功能活性。此外，我们的研究证实EGR1和双特异性磷酸酶1 （DUSP1）在BC中下调表达，并已被确定与BC的进展密切相关。DUSP1被EGR1转录诱导，在人BC组织中发现EGR1的表达与DUSP1呈正相关。研究发现，EGR1的敲低可通过MAPK信号通路促进细胞侵袭、迁移、增殖和血管生成，然而，在BC细胞中，DUSP1的过表达抑制了EGR1敲低诱导的这些功能活性的促进。此外，MAP30通过调节EGR1-DUSP1轴抑制BC细胞的侵袭、迁移、增殖和血管生成。我们的研究为MAP30对BC进展的抑制作用提供了详尽的见解。

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引用次数: 0