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Recent Advances in Bio-Based Production of Free Heme Using Microbial Metabolic Engineering 微生物代谢工程生物基生产游离血红素的研究进展。
IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-12-01 DOI: 10.1002/adbi.202500434
Wenya Wang, Haitao Geng, Xuting Sun, Junsheng Huo, Jian Huang, Zhen Guo, Yuwenbin Li, Guimin Zhang

Heme is an iron-containing porphyrin that plays an indispensable role in biological system, involved in oxygen transport, electron transfer, gas sensing, enzyme catalysis, etc. Beyond its physiological functions, heme also has wide-ranging applications in pharmaceuticals, food additives, and biotechnology. However, conventional production methods—such as chemical synthesis and extraction from animal blood are hindered by high costs, ethical concerns, environmental burdens, and safety risks. Recent progresses in metabolic engineering and synthetic biology have made it possible to produce free heme using microorganisms, offering a scalable, cost-effective, and sustainable alternative. This review provides a comprehensive overview of bio-based heme production, focusing on: 1) Structure, functions, and synonyms of different heme types; 2) Conserved and divergent heme biosynthetic pathways; 3) Heme biosynthesis regulation involving transcription factors, protein interactions, and small molecules; 4) Recent advances in microbial production of heme and porphyrin intermediates using metabolic engineering strategies; 5) Methods for heme detection, including spectroscopy, chromatography, enzyme-linked immunosorbent assays (ELISA) and whole-cell biosensors. Finally, current challenges and future opportunities, highlighting microbial heme production as a transformative and sustainable strategy to meet growing global demand are discussed.

血红素是一种含铁卟啉,在生物系统中起着不可缺少的作用,参与氧传递、电子传递、气体传感、酶催化等。除了其生理功能外,血红素在制药、食品添加剂和生物技术等方面也有广泛的应用。然而,传统的生产方法——如化学合成和从动物血液中提取——受到高成本、伦理问题、环境负担和安全风险的阻碍。代谢工程和合成生物学的最新进展使利用微生物生产游离血红素成为可能,提供了一种可扩展、经济高效和可持续的替代方案。本文综述了生物血红素的合成,主要包括:1)不同类型血红素的结构、功能和同义词;2)血红素生物合成途径的保守性和差异性;3)涉及转录因子、蛋白相互作用、小分子的血红素生物合成调控;4)利用代谢工程策略微生物生产血红素和卟啉中间体的研究进展;5)血红素检测方法,包括光谱、色谱、酶联免疫吸附法(ELISA)和全细胞生物传感器。最后,讨论了当前的挑战和未来的机遇,强调微生物血红素生产是满足日益增长的全球需求的变革和可持续战略。
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引用次数: 0
Differentiation Treatment Applied to Lung Cancer Model Reduces Pathogenic Traits in Vitro 分化治疗在肺癌模型中的应用降低了体外致病性状。
IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-29 DOI: 10.1002/adbi.202500371
Alice Grossi, Paola Fulghieri, Abdurakhmon Aduvaliev, Karen Soffiantini, Irene Oldrati, Margherita Cavallo, Marco Biggiogera, Giorgia Pellavio, Umberto Laforenza, Monica Savio, Virginie Sottile

Non-small cell lung cancer (NSCLC) relapse after therapy is linked to the high aggressiveness, chemoresistance and metastatic potential of tumor cells due, in part, to the presence of cancer stem cells (CSCs). Pro-differentiation approaches have shown promising results for leukemia and in some solid cancer models, offering a possibility to enhance current anti-cancer therapies. Here, the human NSCLC line A549 is exposed to a serum-containing medium supplemented with pro-differentiation factors (DM), and effects on the cells’ proliferation, migration and adhesion properties are assessed in vitro, alongside CSC marker expression analyzed after treatment in 2D or 3D culture conditions. A549 cells exposed to DM exhibited notable morphological changes, with significant increase in cellular footprint and vesicle accumulation. These phenotypic alterations coincided with significant inhibition of proliferation and migration, whereas adhesion properties increased, similar to alkaline phosphatase activity. DM treatment of A549 cells also caused a significant reduction in clonogenic ability by two thirds, as well as halving anchorage-independent colony formation and spheroid growth, alongside a reduced expression of stemness markers SOX2, NANOG, CD44 and ABCG2, and of ALDH activity and aquaporin function. These results indicate decreased pathogenic features of NSCLC cells after DM exposure, suggesting that pro-differentiation treatment may represent a valuable option for further preclinical testing.

非小细胞肺癌(NSCLC)治疗后复发与肿瘤细胞的高侵袭性、化疗耐药和转移潜力有关,部分原因是癌症干细胞(CSCs)的存在。促分化方法在白血病和一些实体癌模型中显示出有希望的结果,为增强当前的抗癌治疗提供了可能。本研究将人NSCLC细胞系A549暴露于添加促分化因子(pro-differentiation factors, DM)的含血清培养基中,在体外评估其对细胞增殖、迁移和粘附特性的影响,并分析在2D或3D培养条件下处理后CSC标志物的表达。暴露于DM的A549细胞表现出明显的形态学变化,细胞足迹和囊泡积累显著增加。这些表型改变与显著抑制增殖和迁移相一致,而粘附特性增加,类似于碱性磷酸酶活性。A549细胞经DM处理后,克隆生成能力也显著降低了三分之二,不依赖锚定的集落形成和球形生长减少了一半,茎干标记物SOX2、NANOG、CD44和ABCG2的表达降低,ALDH活性和水通道蛋白功能也降低。这些结果表明,DM暴露后NSCLC细胞的致病特征降低,表明促分化治疗可能是进一步临床前试验的一个有价值的选择。
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引用次数: 0
Electroacupuncture Improves Cardiac Function in Mice with Myocardial Infarction through Glu Neurons in Ventrolateral Periaqueductal Gray 电针通过腹外侧导水管周围灰质谷氨酸神经元改善心肌梗死小鼠心功能。
IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-25 DOI: 10.1002/adbi.202500158
Liu Yang, Nan Deng, Fan Zhang, Wenxiu Duan, Kanghong Zhu, Hao Chu, Zizhan Gao, Ling Hu, Zijian Wu, Jie Wang

Ischemic heart disease, a leading global cause of mortality, highlights the need for novel therapies. Electroacupuncture (EA) shows cardioprotective potential, yet the central neural mechanisms, particularly the role of the midbrain periaqueductal gray (PAG), remain unclear. This study investigated how EA at Shen men (HT7) improves cardiac function post-myocardial infarction (MI) via Ventrolateral Periaqueductal Gray Matter (vlPAG) glutamatergic(Glu) neurons. Neuronal activity monitored via c-Fos immunofluorescence and fiber photometry is detected. Chemogenetic tools selectively inhibited or activated vlPAG glutamatergic neurons. Cardiac function is assessed by echocardiography and histopathology, while inflammation is analyzed via Western blot and Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction. Improvement of cardiac function: electroacupuncture significantly elevated cardiac function in MI mice to improve the prognostic level of mice; verification of neural mechanism: electroacupuncture selectively activated vlPAG glutamatergic neurons, and the cardioprotective effect of electroacupuncture is suppressed by inhibition of the vlPAGGlu, whereas specific activation of this neuron can mimic the effect of electroacupuncture(EA). This study unveils a central “acupoint-brain-heart” axis, where EA at HT7 engages vlPAG to restore cardiac homeostasis. These findings bridge traditional acupuncture and modern neuroscience, proposing vlPAG glutamatergic pathways as novel targets for cardiovascular therapy.

缺血性心脏病是全球主要的死亡原因,它强调了对新疗法的需求。电针(EA)显示出心脏保护潜力,但其中枢神经机制,特别是中脑导水管周围灰质(PAG)的作用尚不清楚。本研究探讨了肾门(HT7) EA如何通过腹外侧导水管周围灰质(vlPAG)谷氨酸能(Glu)神经元改善心肌梗死(MI)后心功能。通过c-Fos免疫荧光和纤维光度法监测神经元活动。化学发生工具选择性地抑制或激活vlPAG谷氨酸能神经元。通过超声心动图和组织病理学评估心功能,通过Western blot和逆转录定量实时聚合酶链反应分析炎症。改善心功能:电针可显著提高心肌梗死小鼠心功能,改善小鼠预后水平;神经机制验证:电针选择性激活vlPAG谷氨酸能神经元,抑制vlPAGGlu可抑制电针的心脏保护作用,而特异性激活该神经元可模拟电针(EA)的作用。这项研究揭示了一个中央“穴位-脑-心”轴,其中HT7的EA参与vlPAG恢复心脏稳态。这些发现连接了传统针灸和现代神经科学,提出vlPAG谷氨酸能通路作为心血管治疗的新靶点。
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引用次数: 0
FOXP3 Polymorphism and Upregulation of the CXCL12-CXCR4-SNAIL Axis with High Infiltration of M2TAM by STAT3/NFKB Pathways Influence the Survival of Cervical Cancer Patients STAT3/NFKB通路M2TAM高浸润的FOXP3多态性及CXCL12-CXCR4-SNAIL轴的上调影响宫颈癌患者的生存
IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-20 DOI: 10.1002/adbi.202500354
George A. Lira, Fábio M. de Azevedo, Ingrid G. S. Lins, Janaína C. O. Crispim, Giovanna A. Lira, Rômulo S. Cavalcante, Ricardo Cobucci, Carolina O. Mendes-Aguiar, Rafaela Torres Dantas Da Silva, Vinícius E. da Silva, Ryan C. Q. Aquino, Raimundo F. Araújo Júnior

This study explores the interaction between immune and cancer cells in the tumor microenvironment (TME) of cervical carcinoma (CC), with emphasis on tumor-associated macrophages (M2-TAMs) and the STAT3-NF-κB signaling pathway. It investigates how Treg cell polymorphisms and TAM infiltration through these pathways influence overall survival (OS) in CC patients. This prospective study follows 100 CC patients from 2018 to 2023 using qRT-PCR and immunohistochemistry on tumor samples, and flow cytometry on blood samples to evaluate immunosuppressive cytokines and Treg cell polymorphisms. High stromal CD163+204+ TAM density, mediated by STAT3/NF-κB, correlates with biomarkers such as Ki-67, VEGFα, and FOXP3 (p < 0.001). XPO5 expression is associated with increased STAT3, SNAIL, and HPV 16/18 levels. FOXP3 T allele deletion and HLA-G polymorphism in the blood of patients correlate with higher STAT3 tumor expression and elevated IL-4 and IL-17 blood cytokines. The CXCL12-CXCR4 axis shows a strong association with STAT3, SNAIL in TME and blood cytokines, including IL-6 and IL-12. Elevated CXCL12, CXCR4, and SNAIL expression in TME significantly increases mortality risk. These findings underscore the role of M2TAM infiltration and immune modulation in tumor progression and clinical outcomes in CC.

本研究探讨宫颈癌(CC)肿瘤微环境(tumor microenvironment, TME)中免疫细胞与癌细胞的相互作用,重点关注肿瘤相关巨噬细胞(tumor-associated macrophages, m2 - tam)和STAT3-NF-κB信号通路。研究Treg细胞多态性和TAM通过这些途径浸润如何影响CC患者的总生存率(OS)。本前瞻性研究对2018年至2023年的100例CC患者进行了随访,采用肿瘤样本的qRT-PCR和免疫组织化学,血液样本的流式细胞术评估免疫抑制细胞因子和Treg细胞多态性。STAT3/NF-κB介导的高间质CD163+204+ TAM密度与Ki-67、VEGFα和FOXP3等生物标志物相关(p < 0.001)。XPO5表达与STAT3、SNAIL和HPV 16/18水平升高相关。患者血液中FOXP3 T等位基因缺失和HLA-G多态性与STAT3肿瘤表达升高和IL-4、IL-17血液细胞因子升高相关。CXCL12-CXCR4轴显示与STAT3、TME中的SNAIL和血液细胞因子(包括IL-6和IL-12)密切相关。TME中CXCL12、CXCR4和SNAIL表达升高可显著增加死亡风险。这些发现强调了M2TAM浸润和免疫调节在CC肿瘤进展和临床结果中的作用。
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引用次数: 0
Lung Microphysiological System Validates Novel Cell Therapy for Acute Respiratory Distress Syndrome 肺微生理系统验证急性呼吸窘迫综合征的新型细胞疗法。
IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-20 DOI: 10.1002/adbi.202500225
Bokyong Kim, So-Hui Kim, Jieun Kim, Eun-Young Eo, Hyung-Jun Kim, Jae Ho Lee, Choon-Taek Lee, Taeho Kong, Su Kyoung Seo, Seunghee Lee, Jeongbin Park, Young-Jae Cho

Acute Respiratory Distress Syndrome (ARDS) is a life-threatening condition characterized by severe inflammation and lung damage, leading to critical hypoxemia. Despite its high mortality rate, the only currently available treatment, Dexamethasone, is associated with significant side effects. This study aims to evaluate the efficacy of primed human umbilical cord blood-derived mesenchymal stem cells (hUCB-pMSCs) as a potential alternative treatment for ARDS. A novel lung microphysiological system (MPS) modeling the lung environment is developed and treated with lipopolysaccharide (LPS) to simulate ARDS. The effects of hUCB-pMSCs and dexamethasone are compared using state-of-the-art methods, including fluorescence-based imaging and single-cell RNA sequencing. The hUCB-pMSCs significantly activated angiogenesis-related pathways in endothelial cells and enhanced the formation of tip-like endothelial cells involved in new blood vessel formation. These findings are corroborated by fluorescence microscopy, demonstrating the robust potential of hUCB-pMSCs as a therapeutic approach. Overall, the results support the potential of hUCB-pMSCs as a promising alternative treatment for ARDS.

急性呼吸窘迫综合征(ARDS)是一种危及生命的疾病,其特征是严重的炎症和肺损伤,导致严重的低氧血症。尽管其死亡率很高,但目前唯一可用的治疗方法地塞米松与严重的副作用有关。本研究旨在评估引物人脐带血源性间充质干细胞(hub - pmscs)作为ARDS潜在替代治疗方法的有效性。建立了一种模拟肺环境的肺微生理系统(MPS),并用脂多糖(LPS)对其进行处理以模拟ARDS。使用最先进的方法,包括基于荧光的成像和单细胞RNA测序,比较hub - pmscs和地塞米松的效果。hub - pmscs显著激活内皮细胞血管生成相关通路,促进参与新血管形成的尖端样内皮细胞的形成。这些发现被荧光显微镜证实,证明hub - pmscs作为一种治疗方法的强大潜力。总的来说,结果支持hub - pmscs作为ARDS的一种有希望的替代治疗方法的潜力。
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引用次数: 0
RAN Promotes Autophagy and Malignant Progression of Lung Adenocarcinoma through ATG101 RAN通过ATG101促进肺腺癌自噬和恶性进展。
IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-20 DOI: 10.1002/adbi.202500262
Weiyun Bi, Hongtao Li, Xiaoyong Wu, Cailin Zhu

This study investigates the role and mechanisms of Ras-related nuclear protein (RAN) in lung adenocarcinoma (LUAD). The expression of RAN in LUAD is studied using the The Cancer Genome Atlas (TCGA) database. Clinical samples are collected, and immunohistochemical (IHC) staining is performed to analyze the positive cell rate of RAN in normal and LUAD tissues. The study analyzes the effects of RAN overexpression in A549 and H1299 LUAD cell lines. Various methodologies are employed, including RT-PCR, Western blot, Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2′-deoxyuridine (EdU) staining, wound healing, Transwell assays, immunofluorescence, and 3,3′-ctetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining, to evaluate RAN’s influence on cell proliferation, migration, and autophagy with mitochondrial homeostasis dysregulation. The findings reveal that RAN is significantly overexpressed in LUAD and associated with poorer prognosis. IHC analysis shows that the positive cell rate of RAN is significantly higher in LUAD tissues than in normal tissues. RAN overexpression facilitates proliferation and migration while enhancing autophagic activity, mitochondrial dysregulation, and increasing ATG101 expression. Suppression of ATG101 effectively counteracts the enhanced proliferation induced by RAN overexpression, highlighting ATG101 as a key mediator of RAN’s effects. This study underscores the critical molecular dynamics of LUAD driven by RAN, suggesting that the RAN-ATG101 axis can serve as a novel therapeutic target.

本研究探讨ras相关核蛋白(RAN)在肺腺癌(LUAD)中的作用及其机制。利用The Cancer Genome Atlas (TCGA)数据库研究了RAN在LUAD中的表达。收集临床样本,免疫组化(IHC)染色分析正常组织和LUAD组织中RAN的阳性细胞率。本研究分析了RAN过表达对A549和H1299 LUAD细胞系的影响。采用多种方法,包括RT-PCR、Western blot、Cell Counting Kit-8 (CCK-8)、5-乙基-2'-脱氧尿苷(EdU)染色、伤口愈合、Transwell试验、免疫荧光和3,3'- ctetraethylbenzimidazolyccarbocyanine ioide (JC-1)染色,来评估RAN对线粒体稳态失调的细胞增殖、迁移和自噬的影响。研究结果显示,RAN在LUAD中显著过表达,并与较差的预后相关。免疫组化分析显示,LUAD组织中RAN的阳性细胞率明显高于正常组织。RAN过表达促进增殖和迁移,同时增强自噬活性,线粒体失调,增加ATG101表达。抑制ATG101可有效抵消RAN过表达诱导的增殖增强,表明ATG101是RAN作用的关键中介。这项研究强调了RAN驱动LUAD的关键分子动力学,表明RAN- atg101轴可以作为一种新的治疗靶点。
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引用次数: 0
Biologics, Biosimilars, and Biobetters: Therapeutic Innovations Reshaping Modern Medicine 生物制剂、生物仿制药和生物改良剂:重塑现代医学的治疗创新。
IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-17 DOI: 10.1002/adbi.202500326
Joseph Carmelo Kalaw San Pascual, Thaned Kangsamaksin

Biologic medicines (or biologics) have revolutionized the treatment of cancer, autoimmune disorders, and genetic conditions. Their therapeutic success stems from complex structural properties that confer high target specificity and biological compatibility. However, their high cost and complex manufacturing limit patient access, with annual treatment expenses often reaching tens of thousands of dollars per patient. Biosimilars, developed to match reference biologics in quality, safety, and efficacy, provide a pathway to curb escalating costs. Having generated more than 36 billion USD in healthcare savings over the past decade, their wider adoption remains challenged by stringent regulatory pathways and the market exclusivity of reference products. These limitations have spurred the development of biobetters, which are engineered biologics with enhanced stability, potency, half-life, or reduced immunogenicity that maximize patient benefit. This review explores the distinctions, development strategies, and regulatory challenges of biologics, biosimilars, and biobetters. Biosimilarity establishment and biobetter design strategies are examined with emphasis on enzyme-based examples such as L-asparaginase and glucarpidase. Advanced delivery technologies have also been demonstrated to improve drug stability, bioavailability, and patient adherence. Finally, emerging innovations and future directions underscore the transformative potential of these biopharmaceuticals in addressing unmet medical needs and expanding global access.

生物药物(或生物制剂)已经彻底改变了癌症、自身免疫性疾病和遗传疾病的治疗。它们的治疗成功源于复杂的结构特性,赋予了高靶点特异性和生物相容性。然而,它们的高成本和复杂的制造限制了患者的获取,每位患者每年的治疗费用往往高达数万美元。生物仿制药是为了在质量、安全性和有效性方面与参考生物制剂相匹配而开发的,它为遏制不断上涨的成本提供了一条途径。在过去十年中,医疗保健节省了超过360亿美元,但它们的广泛采用仍然受到严格的监管途径和参考产品的市场排他性的挑战。这些限制刺激了生物改善剂的发展,这些生物改善剂是具有增强稳定性、效力、半衰期或降低免疫原性的工程生物制剂,可最大限度地提高患者的益处。这篇综述探讨了生物制剂、生物仿制药和生物改良药的区别、发展策略和监管挑战。生物相似性的建立和生物更好的设计策略进行了研究,重点是基于酶的例子,如l -天冬酰胺酶和葡萄糖苷酶。先进的给药技术也被证明可以提高药物的稳定性、生物利用度和患者的依从性。最后,新兴的创新和未来的方向强调了这些生物制药在解决未满足的医疗需求和扩大全球可及性方面的变革潜力。
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引用次数: 0
Qingxin Jianpi Decoction Alleviates Cyclophosphamide-Induced Diminished Ovarian Reserve Via Activation of the PI3K/AKT/Nrf2 Axis and Suppression of Ferroptosis 清心健脾汤通过激活PI3K/AKT/Nrf2轴和抑制铁下沉减轻环磷酰胺诱导的卵巢储备功能下降。
IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-17 DOI: 10.1002/adbi.202500448
Donglai Hu, Jiayu Shi, Yao Peng, Ruxin Wang, Wenchen Du, Guicheng Xia

Diminished ovarian reserve (DOR), marked by reduced oocyte quantity and quality, remains therapeutically challenging. This study evaluates the protective effects of Qingxin Jianpi Decoction (QXJP) against cyclophosphamide (CTX)-induced DOR via integrated network pharmacology and experimental validation. Bioactive compounds in QXJP are screened (TCMSP: OB ≥30%, DL ≥0.18) and targets predicted (SwissTargetPrediction). Functional enrichment analysis is performed using DAVID. CTX-induced DOR rats receive QXJP (low/medium/high doses) or resveratrol. Ovarian histology, hormone levels (FSH, LH, E2, and AMH), apoptosis (Bax/Bcl-2, cleaved Caspase-3), ferroptosis markers (SLC7A11, ACSL4, MDA, and 4-HNE), and PI3K/AKT/Nrf2 pathway activity are quantified by Western blot or ELISA. Network pharmacology identifies 176 bioactive compounds targeting 297 DOR-associated genes, highlighting the PI3K-AKT pathway. QXJP restores estrous cyclicity, increases follicle counts, reduces fibrosis, and rebalances FSH, LH, E2, and AMH levels (all p < 0.01). It suppresses granulosa cell apoptosis (decreased Bax/Cleaved Caspase-3, increased Bcl-2), attenuated ferroptosis-related alterations (upregulated SLC7A11, downregulated MDA, 4-HNE, and ACSL4), and activates PI3K/AKT/Nrf2 signaling (increased p-PI3K/PI3K, p-AKT/AKT ratios; upregulates Nrf2, HO-1, and GPX4, p < 0.05). QXJP ameliorates CTX-induced DOR by attenuating ovarian apoptosis and ferroptosis via the PI3K/AKT/Nrf2 pathway. This multi-target mechanism underscores its potential as a herbal therapy for DOR.

卵巢储备减少(DOR),以卵母细胞数量和质量减少为标志,仍然是治疗上的挑战。本研究通过综合网络药理学和实验验证,评价清心健脾汤(QXJP)对环磷酰胺(CTX)所致DOR的保护作用。筛选QXJP中的生物活性化合物(TCMSP: OB≥30%,DL≥0.18)并预测靶点(SwissTargetPrediction)。使用DAVID进行功能富集分析。ctx诱导DOR大鼠接受QXJP(低/中/高剂量)或白藜芦醇。卵巢组织学、激素水平(FSH、LH、E2和AMH)、细胞凋亡(Bax/Bcl-2、cleaved Caspase-3)、铁下垂标志物(SLC7A11、ACSL4、MDA和4-HNE)以及PI3K/AKT/Nrf2通路活性通过Western blot或ELISA进行定量。网络药理学鉴定出176种靶向297个dor相关基因的生物活性化合物,突出了PI3K-AKT通路。QXJP恢复发情周期,增加卵泡计数,减少纤维化,并重新平衡FSH, LH, E2和AMH水平(均p < 0.01)。它抑制颗粒细胞凋亡(Bax/Cleaved Caspase-3减少,Bcl-2增加),减弱铁毒相关的改变(SLC7A11上调,MDA、4-HNE和ACSL4下调),激活PI3K/AKT/Nrf2信号传导(p-PI3K/PI3K、p-AKT/AKT比值升高,Nrf2、HO-1和GPX4上调,p < 0.05)。QXJP通过PI3K/AKT/Nrf2通路减轻卵巢凋亡和铁下垂,从而改善ctx诱导的DOR。这种多靶点机制强调了其作为DOR草药治疗的潜力。
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引用次数: 0
The Paradox of Heme Oxygenase 1: From Cellular Defense to a Tug of War between Cancer Promotion and Prevention 血红素加氧酶1的悖论:从细胞防御到癌症促进和预防之间的拉锯战。
IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-14 DOI: 10.1002/adbi.202500390
Sidhant Jain, Meenakshi Rana, Nilza Angmo, Neha Vimal

The Hmox1 enzyme, which is the inducible enzyme among the Hmoxs, catalyzes the first and rate-limiting step in the heme degradation pathway, generating three byproducts, namely, carbon monoxide, free iron, and biliverdin. These byproducts can affect an array of biological processes; hence, Hmox1 modulates multiple metabolic processes. Along with the degradation of cytotoxic heme, Hmox1 provides protection against inflammation, apoptosis, and oxidative stress. It also ameliorates tissue injury, maintains iron homeostasis, and supports embryonic survival. Initially, different studies labeled it as an active cancer-assisting agent; however, multiple recent studies have shown that it also deters cancer progression. Hence, this review first looks into the traditional role of Hmox1 and various Hmox1 inducers. Second, there are multiple links between Hmox1 and different types of cancer, including how it acts as a promoter or plays an antitumor role in different or even the same cancers. On the basis of the available data, the work proposes a few speculations to explain this dual role of Hmox1 in cancer.

Hmox1酶是hmox中的诱导酶,催化血红素降解途径的第一步,也是限速步骤,产生三种副产物,即一氧化碳、游离铁和胆绿素。这些副产品可以影响一系列生物过程;因此,Hmox1调节多种代谢过程。随着细胞毒性血红素的降解,Hmox1提供抗炎症、细胞凋亡和氧化应激的保护。它还可以改善组织损伤,维持铁稳态,并支持胚胎存活。最初,不同的研究将其标记为一种有效的抗癌剂;然而,最近的多项研究表明,它也能阻止癌症的发展。因此,本文首先对Hmox1和各种Hmox1诱导剂的传统作用进行综述。其次,Hmox1与不同类型的癌症之间存在多种联系,包括它如何在不同甚至相同的癌症中充当启动子或发挥抗肿瘤作用。在现有数据的基础上,这项工作提出了一些推测来解释Hmox1在癌症中的双重作用。
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引用次数: 0
Osteocytes under Mechanical Loading Regulate PC-3 Cancer Cell–Mineral Interactions during Early-Stage Metastasis to Bone 骨细胞在机械负荷下调节PC-3癌细胞-矿物质在早期骨转移过程中的相互作用。
IF 2.6 3区 生物学 Q3 MATERIALS SCIENCE, BIOMATERIALS Pub Date : 2025-11-12 DOI: 10.1002/adbi.202500379
Kimberly Seaman, Bryan Guo, William W. Du, Burton Yang, Yu Sun, Lidan You

Bone metastasis causes severe complications for patients suffering from advanced-stage prostate cancer. Exercise is recommended to help maintain musculoskeletal health during treatment. As primary mechanosensors and regulators of bone homeostasis, osteocytes recently investigate for their roles in prostate cancer bone metastasis. Recently, in vivo studies show that exercise mitigates prostate tumor progression and preserves bone structure. In contrast, in vitro studies indicate direct prostate cancer–osteocyte interactions under mechanical loading conditions promote prostate cancer growth and migration but exclude other host cells present in the metastatic bone microenvironment. Thus, these in vitro findings are not consistent with recent in vivo results. In this study, the role of mechanically stimulated osteocytes during the initial stages of metastatis in osteoblast-rich areas is examined. When treated with conditioned media from flow-stimulated osteocytes, osteoblasts reduce PC-3 wound healing migration and invasion compared to static controls. Of interest, osteoblasts treated with flow-stimulated MLO-Y4 and primary osteocyte conditioned media suppress PC-3 cancer cell growth, alter cancer cell morphology, and preserve mineralized matrix in a microfluidic co-culture assay. Overall, the inhibitory role of mechanical loading of osteocytes on the early-stage metastasis of the endosteal surface during prostate cancer bone metastasis is demonstrated.

骨转移对晚期前列腺癌患者造成严重的并发症。建议在治疗期间锻炼以帮助维持肌肉骨骼健康。作为骨稳态的主要机械传感器和调节因子,骨细胞在前列腺癌骨转移中的作用最近被研究。最近,体内研究表明,运动可以减缓前列腺肿瘤的进展并保持骨骼结构。相比之下,体外研究表明,在机械负荷条件下,前列腺癌与骨细胞的直接相互作用促进了前列腺癌的生长和迁移,但排除了转移性骨微环境中存在的其他宿主细胞。因此,这些体外研究结果与最近的体内研究结果不一致。在这项研究中,机械刺激骨细胞在成骨细胞丰富的地区转移的初始阶段的作用进行了检查。当用流动刺激骨细胞的条件培养基处理时,与静态对照相比,成骨细胞减少了PC-3伤口愈合的迁移和侵袭。有趣的是,在微流体共培养实验中,用流动刺激的MLO-Y4和原代骨细胞条件培养基处理的成骨细胞抑制PC-3癌细胞生长,改变癌细胞形态,并保存矿化基质。总之,在前列腺癌骨转移过程中,骨细胞的机械负荷对骨内膜表面早期转移的抑制作用得到了证实。
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Advanced biology
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