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An Innovative Telomere-associated Prognosis Model in AML: Predicting Immune Infiltration and Treatment Responsiveness. 一种创新的急性髓细胞白血病端粒相关预后模型:预测免疫渗透和治疗反应性
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-05 DOI: 10.2174/0109298673334218241021044800
Binyang Song, Jinzhan Lou, Lijun Mu, Xiao Lu, Jian Sun, Bo Tang

Aims: To build an innovative telomere-associated scoring model to predict prognosis and treatment responsiveness in acute myeloid leukemia (AML).

Background: AML is a highly heterogeneous malignant hematologic disorder with a poor prognosis. While telomere maintenance is frequently observed in tumors, investigations into telomere-related genes (TRGs) in AML remain limited.

Objectives: This study aimed to identify prognostic TRGs using the least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox regression, evaluate their predictive value, explore the association between TRG scores and immune cell infiltration, and assess the sensitivity of high-scoring AML patients to chemotherapeutic agents.

Method: Univariate Cox regression analysis was conducted on the TCGA cohort to identify prognostic TRGs and to develop the TRG scoring model using LASSO-Cox and multivariate Cox regression. Validation was performed on the GSE37642 cohort. Immune cell infiltration patterns were assessed through computational analysis, and the sensitivity to chemotherapeutic agents was evaluated.

Results: Thirteen prognostic TRGs were identified, and a seven-TRG scoring model (including NOP10, OBFC1, PINX1, RPA2, SMG5, MAPKAPK5, and SMN1) was developed. Higher TRG scores were associated with a poorer prognosis, as confirmed in the GSE37642 cohort, and remained an independent prognostic factor even after adjusting for other clinical characteristics. The high-score group was characterized by elevated infiltration of B cells, T helper cells, natural killer cells, tumor-infiltrating lymphocytes, regulatory T (Treg) cells, M2 macrophages, neutrophils, and monocytes, along with reduced infiltration of gamma delta T cells, CD4- T cells, and resting mast cells. Moreover, high infiltration of M2 macrophages and Tregs was associated with poor overall survival compared to low infiltration. Notably, high-risk AML patients were resistant to Erlotinib, Parthenolide, and Nutlin-3a, but sensitive to AC220, Midostaurin, and Tipifarnib. Additionally, using RT-qPCR, we observed significantly higher expression of two model genes, OBFC1 and SMN1, in AML tissues compared to control tissues.

Conclusion: This innovative TRG scoring model demonstrates considerable predictive value for AML patient prognosis, offering valuable insights for optimizing treatment strategies and personalized medicine approaches. The identified TRGs and associated scoring models could aid in risk stratification and guide tailored therapeutic interventions in AML patients.

目的:建立一个创新的端粒相关评分模型,以预测急性髓性白血病(AML)的预后和治疗反应性:背景:急性髓性白血病是一种预后不良的高度异质性恶性血液病。背景:急性髓性白血病是一种高度异质性的恶性血液病,预后较差。虽然在肿瘤中经常观察到端粒的维持,但对急性髓性白血病中端粒相关基因(TRGs)的研究仍然有限:本研究旨在利用最小绝对收缩和选择算子(LASSO)Cox回归和多变量Cox回归确定预后TRG,评估其预测价值,探讨TRG评分与免疫细胞浸润之间的关联,并评估高分AML患者对化疗药物的敏感性:方法:对TCGA队列进行单变量Cox回归分析,以确定预后性TRG,并利用LASSO-Cox和多变量Cox回归建立TRG评分模型。在GSE37642队列中进行了验证。通过计算分析评估了免疫细胞浸润模式,并评估了对化疗药物的敏感性:结果:发现了13个预后TRGs,并建立了7个TRGs评分模型(包括NOP10、OBFC1、PINX1、RPA2、SMG5、MAPKAPK5和SMN1)。TRG 评分越高,预后越差,这一点在 GSE37642 队列中得到了证实,即使在调整了其他临床特征后,TRG 评分仍然是一个独立的预后因素。高分组的特点是 B 细胞、T 辅助细胞、自然杀伤细胞、肿瘤浸润淋巴细胞、调节性 T(Treg)细胞、M2 巨噬细胞、中性粒细胞和单核细胞浸润增加,而γ δ T 细胞、CD4- T 细胞和静止肥大细胞浸润减少。此外,与低浸润率相比,M2 巨噬细胞和 Tregs 的高浸润率与总生存率低有关。值得注意的是,高风险急性髓细胞白血病患者对厄洛替尼、帕替诺利特和Nutlin-3a耐药,但对AC220、米多司他林和替法尼敏感。此外,通过 RT-qPCR,我们观察到 AML 组织中两个模型基因 OBFC1 和 SMN1 的表达明显高于对照组织:这一创新的TRG评分模型对急性髓细胞性白血病患者的预后具有相当高的预测价值,为优化治疗策略和个性化医疗方法提供了宝贵的见解。鉴定出的TRGs和相关评分模型有助于对AML患者进行风险分层,并指导有针对性的治疗干预。
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引用次数: 0
Design, Synthesis, and Antitumor Potential of New Thiazole--contained 5-Fluoro-2-Oxindole Derivatives as Sunitinib Analogues. 作为舒尼替尼类似物的新型含噻唑 5-氟-2-吲哚衍生物的设计、合成和抗肿瘤潜力。
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-04 DOI: 10.2174/0109298673346427241016100726
Ivan Semenyuta, Oleksandr Los, Vitalii Sinenko, Victor Zhirnov, Lyudmyla Potikha, Oleksandr Kobzar, Volodymyr Brovarets

Background: Indole is considered the most promising scaffold for anticancer drug design due to its high bioavailability, unique chemical properties, and broad spectrum of pharmacological action.

Objective: Twelve novel thiazole-containing the 5-fluoro-1,3-dihydro-2H-indol-2-one derivatives as sunitinib analogs were designed and synthesized, and their anticancer activity was evaluated against the NCI-60 cancer cell lines.

Method: The thiazole-contained 5-fluoro-1,3-dihydro-2H-indol-2-one derivatives were synthesized using Knoevenagel condensation of 1,3-thiazole-5-carboxylic acid 1. Their anticancer activities were evaluated by NCI-60 one-dose screen assay. The molecular docking studies were performed using AutoDock tools and the AutoDock Vina programs. The ADMETlab 2.0 web server predicted the physicochemical properties of compounds.

Results: Among the synthesized new 5-fluoro-2-oxindole derivatives, compound 3g demonstrated high antitumor activity (GI>70%) against eight types of cancer: leukemia, breast cancer, ovarian cancer, lung cancer, melanoma, CNS cancer, renal cancer, and colon cancer. The most activity was observed against breast cancer (T-47D, GI=96.17%), lung cancer (HOP-92, GI=95.95%), ovarian cancer (NCI/ADR-RES, GI=95.13%), and CNS cancer (SNB-75, GI=89.91%). The molecular docking results of compound 3g demonstrated the possibility of inhibiting VEGF2 receptors as his potential anticancer mechanism. The physicochemical properties predicted for compounds 3f and 3g showed positive results.

Conclusion: Compound 3g demonstrated high in vitro NCI-60 anticancer activity against nine cancer types and showed cell growth inhibition against leukemia, CNS, and breast cancer at 6 - 31% higher than Sunitinib, and may represent the basis for further modification of the thiazole-containing analogs of the anticancer drug Sunitinib.

背景:吲哚具有高生物利用度、独特的化学性质和广谱的药理作用,被认为是抗癌药物设计中最有前景的支架:目的:设计并合成了 12 种新型含噻唑的 5-氟-1,3-二氢-2H-吲哚-2-酮衍生物作为舒尼替尼类似物,并评估了它们对 NCI-60 癌细胞株的抗癌活性:方法:采用 1,3-噻唑-5-羧酸 1 的 Knoevenagel 缩合反应合成了含噻唑的 5-氟-1,3-二氢-2H-吲哚-2-酮衍生物,并通过 NCI-60 单剂量筛选试验评估了它们的抗癌活性。分子对接研究使用了 AutoDock 工具和 AutoDock Vina 程序。ADMETlab 2.0网络服务器预测了化合物的理化性质:在新合成的 5-氟-2-吲哚衍生物中,化合物 3g 对八种癌症(白血病、乳腺癌、卵巢癌、肺癌、黑色素瘤、中枢神经系统癌症、肾癌和结肠癌)具有很高的抗肿瘤活性(GI>70%)。对乳腺癌(T-47D,GI=96.17%)、肺癌(HOP-92,GI=95.95%)、卵巢癌(NCI/ADR-RES,GI=95.13%)和中枢神经系统癌(SNB-75,GI=89.91%)的活性最高。化合物 3g 的分子对接结果表明,其潜在的抗癌机制可能是抑制 VEGF2 受体。化合物 3f 和 3g 的理化性质预测结果显示良好:化合物 3g 在体外 NCI-60 中对 9 种癌症类型表现出较高的抗癌活性,对白血病、中枢神经系统和乳腺癌的细胞生长抑制率比舒尼替尼高 6 - 31%,可能是进一步改造抗癌药物舒尼替尼的含噻唑类似物的基础。
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引用次数: 0
Pressure Ulcers and Nutrients: From Established Evidence to Gaps in Knowledge. 压疮与营养素:从已有证据到知识空白。
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-04 DOI: 10.2174/0109298673322825241018174928
Laura Kassym, Zhuldyz Zhetmekova, Assiya Kussainova, Yuliya Semenova, Anastassiya Vetrova, Sholpan Nurzhan, Gauhar Sarbassova, Almira Akhmetova, Ainash Orazalina, Saltanat Uzbekova, Geir Bjørklund

Pressure ulcers (PUs) are caused by continuous pressure or friction on the skin that damages tissue, especially over bony prominences. A critical factor in the development and progression of PUs is poor nutritional status, which often involves deficiencies in essential nutrients such as proteins, vitamins (A, C, D, E, K, and the B complex), and trace elements (including zinc, selenium, copper, iron, and manganese). These micronutrients are vital for effective wound healing, as they play significant roles in cellular repair, immune function, and tissue regeneration. Laboratory tests for serum albumin, prealbumin, transferrin, retinol-binding protein, and anthropometric measures like height, weight, and body mass index (BMI) are used to evaluate a patient's nutritional status. Screening tools such as the Mini Nutritional Assessment (MNA), Malnutrition Universal Screening Tool (MUST), LPZ questionnaire, and Subjective Global Assessment (SGA) are commonly employed. Emerging evidence from various studies, including in vitro, in vivo, and clinical trials, underscores the importance of personalized nutritional interventions in managing PUs. Unlike generic dietary plans, tailored nutrition that addresses the specific needs of individuals shows greater potential in promoting wound healing and improving clinical outcomes. This synthesis of existing research highlights the critical influence of micronutrients on the healing process of PUs. It suggests that a personalized approach to nutrition, which takes into account individual patient requirements and deficiencies, is likely to be more effective than a one-size-fits- all strategy in the management of these complex wounds.

压迫性溃疡(PU)是由于皮肤受到持续的压力或摩擦而导致组织受损,尤其是在骨突部位。褥疮发生和发展的一个关键因素是营养状况不良,这通常包括缺乏必要的营养素,如蛋白质、维生素(A、C、D、E、K 和 B 群)和微量元素(包括锌、硒、铜、铁和锰)。这些微量元素对伤口的有效愈合至关重要,因为它们在细胞修复、免疫功能和组织再生方面发挥着重要作用。血清白蛋白、前白蛋白、转铁蛋白、视黄醇结合蛋白的实验室检测以及身高、体重和体重指数(BMI)等人体测量指标可用于评估患者的营养状况。通常采用的筛查工具包括:迷你营养评估(MNA)、营养不良通用筛查工具(MUST)、LPZ 问卷和主观全面评估(SGA)。包括体外、体内和临床试验在内的各种研究的新证据强调了个性化营养干预在管理 PU 方面的重要性。与一般的饮食计划不同,针对个人特定需求的定制营养在促进伤口愈合和改善临床效果方面显示出更大的潜力。这份现有研究综述强调了微量营养素对 PU 愈合过程的重要影响。它表明,在处理这些复杂伤口时,考虑到患者个体需求和不足的个性化营养方法可能比 "一刀切 "的策略更有效。
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引用次数: 0
The Mechanism of Action of Exosomes Derived from Glioblastoma Cells. 胶质母细胞瘤细胞外泌体的作用机制
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-04 DOI: 10.2174/0109298673344390241017065119
Ozal Beylerli, Ilgiz Gareev, Tatiana Ilyasova, Elmar Musaev, Vladimir Chekhonin

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor characterized by rapid growth, invasive behavior, and resistance to conventional therapies, such as surgery, radiotherapy, and chemotherapy. Despite these interventions, patient survival remains poor due to the tumor's ability to recur and adapt to treatments. The function of GBM-derived exosomes (GBM-exosomes) as essential mediators in tumor growth has drawn attention in recent years. These small extracellular vesicles are involved in the transfer of a variety of molecules, including cytokines, miRNAs, proteins, and DNA, facilitating intercellular communication that promotes GBM cell proliferation, angiogenesis, immune evasion, and resistance to therapies. This review aims to provide an in- -depth examination of the mechanisms through which GBM-exosomes contribute to these pathological processes, as well as to discuss the current methodologies for isolating and characterizing GBM exosomes. Additionally, we explore the potential of exosomes as biomarkers for diagnosis and prognosis and as novel therapeutic targets in the fight against GBM. By improving our understanding of GBM-exosomes, we can pave the way for the development of more effective, personalized treatment strategies that may improve patient outcomes and quality of life.

胶质母细胞瘤(GBM)是一种侵袭性极强的致死性脑肿瘤,其特点是生长迅速、侵袭性强,对手术、放疗和化疗等传统疗法具有抗药性。尽管采取了这些干预措施,但由于肿瘤具有复发和适应治疗的能力,患者的生存率仍然很低。近年来,GBM 衍生的外泌体(GBM-exosomes)作为肿瘤生长的重要介质的功能引起了人们的关注。这些小的细胞外囊泡参与了多种分子(包括细胞因子、miRNA、蛋白质和 DNA)的转移,促进了细胞间的交流,从而促进了 GBM 细胞的增殖、血管生成、免疫逃避和对疗法的抵抗。本综述旨在深入研究 GBM 外泌体促成这些病理过程的机制,并讨论目前分离和鉴定 GBM 外泌体的方法。此外,我们还探讨了外泌体作为诊断和预后生物标志物以及作为抗击 GBM 的新型治疗靶点的潜力。通过加深对 GBM 外泌体的了解,我们可以为开发更有效的个性化治疗策略铺平道路,从而改善患者的预后和生活质量。
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引用次数: 0
Chemical Synthesis and Enzymatic Modification of Mangostins: A Comprehensive Review on Structural Modifications for Drug Discover. 芒果苷的化学合成和酶促修饰:药物发现中的结构改造综述》。
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-01 DOI: 10.2174/0109298673312728241014025846
Jordan Joon-Yip Lew, Yeun-Mun Choo

Mangosteens, a prominent component of Garcinia mangostana, have been ex-tensively studied for their biological activities and structural modifications. Chemical methods, including cyclization reactions under acidic conditions, have yielded many de-rivatives, which often exhibit enhanced pharmacological properties compared to itself. Enzymatic biotransformation, such as glycosylation and oxidation mediated by fungal species and enzymes like horseradish peroxidase, have provided regioselective pathways to functionalized mangostin derivatives. These studies highlight the versatility of mangos-tin as a scaffold for designing compounds with tailored biological functions. Overall, mangosteen represents a promising platform for developing compounds with enhanced pharmacological activities, paving the way for innovative approaches in biomedicine and pharmaceutical sciences. This review provides a comprehensive examination of the chem-istry of mangosteens, detailing their total synthesis and the derivatives obtained through both chemical and enzymatic methodologies.

山竹果是藤黄科植物山竹果的主要成分,人们对其生物活性和结构改造进行了深入研究。化学方法,包括酸性条件下的环化反应,已经产生了许多去铆剂,这些去铆剂的药理特性往往比其本身更强。酶促生物转化(如由真菌和辣根过氧化物酶等酶介导的糖基化和氧化)为功能化芒果苷衍生物提供了区域选择性途径。这些研究凸显了山竹素作为设计具有定制生物功能的化合物支架的多功能性。总之,山竹素是开发具有更强药理活性的化合物的一个前景广阔的平台,为生物医学和制药科学的创新方法铺平了道路。本综述全面研究了山竹果的化学性质,详细介绍了山竹果的全合成以及通过化学和酶解方法获得的衍生物。
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引用次数: 0
Idebenone Attenuates Diabetic Retinopathy by Modulating Autophagy Via Targeting Akt Signaling. 艾地苯醌通过靶向 Akt 信号调节自噬作用减轻糖尿病视网膜病变
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-11-01 DOI: 10.2174/0109298673339172241017114810
Zhenqian Yu, Gang Liu

Introduction: Diabetic Retinopathy (DR) is a common microvascular issue caused by diabetes. Idebenone (IDE) is a coenzyme Q10 analog and antioxidant that has been utilized in the treatment of neurodegenerative diseases.

Method: Our goal was to investigate how IDE might treat diabetic retinopathy. An in vivo DR model was established by injecting a single dose of streptozotocin (STZ). Rats were treated with IDE, and their vascular function was measured by ultrasound. The retina structure was checked by haematoxylin and eosin (HE) staining. The expression of biomarkers of autophagy and apoptosis was measured by western blotting assay. The retina endothelial cell line RF/6A was stimulated with high glucose (HG) and treated with IDE. Cell proliferation and apoptosis were assessed using the Edu assay, TUNEL assay, and flow cytometry, respectively.

Result: Reduced peak systolic velocity (PSV), mean velocity (MV), end-diastolic velocity (EDV), and increased pulsatility index (PI) and resistance index (RI) were observed in diabetic rats; however, these traits were reversed by IDE therapy. IDE alleviated the STZ-induced disordered retina structure. The IDE administration suppressed DR-induced apoptosis and autophagy both in vivo and in vitro. IDE suppressed the activation of Phosphatidylinositol 3 kinase (PI3K) signaling. Activation of PI3K abolished the IDE-alleviated retina damage and cell death.

Conclusion: IDE regulated the autophagy of retina cells to alleviate diabetic retinopathy via regulating the PI3K signaling pathway.

导言糖尿病视网膜病变(DR)是由糖尿病引起的常见微血管问题。艾地苯醌(IDE)是一种辅酶Q10类似物和抗氧化剂,已被用于治疗神经退行性疾病:我们的目标是研究 IDE 如何治疗糖尿病视网膜病变。通过注射单剂量链脲佐菌素(STZ),建立了体内 DR 模型。大鼠接受 IDE 治疗,并通过超声波测量其血管功能。通过血红素和伊红(HE)染色检查视网膜结构。自噬和细胞凋亡生物标志物的表达通过 Western 印迹法进行检测。用高糖(HG)刺激视网膜内皮细胞系 RF/6A,并用 IDE 处理。分别使用 Edu 试验、TUNEL 试验和流式细胞术评估细胞增殖和凋亡:结果:在糖尿病大鼠体内观察到收缩期峰值速度(PSV)、平均速度(MV)和舒张末期速度(EDV)降低,搏动指数(PI)和阻力指数(RI)升高,但 IDE 治疗可逆转这些特征。IDE 缓解了 STZ 引起的视网膜结构紊乱。在体内和体外,IDE都能抑制DR诱导的细胞凋亡和自噬。IDE抑制了磷脂酰肌醇3激酶(PI3K)信号的激活。PI3K的激活可消除IDE减轻的视网膜损伤和细胞死亡:结论:IDE通过调节PI3K信号通路来调节视网膜细胞的自噬,从而缓解糖尿病视网膜病变。
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引用次数: 0
Elucidating the Mechanisms of Astragalus Membranaceus in Colorectal Cancer Patients through Bioinformatics Analysis. 通过生物信息学分析阐明黄芪对结直肠癌患者的作用机制
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-31 DOI: 10.2174/0109298673344265241014114804
Shuwei Wang, Jiandong Tang, Gan Li, Songbing He

Background: Astragalus membranaceus has shown positive clinical efficacy in treating colorectal cancer (CRC).

Objective: This study aimed to identify the key active components of Astragalus and determine effective targets of these components in CRC patients.

Methods: We identified active components of Astragalus membranaceus and differentially expressed genes in traditional Chinese medicine systems pharmacology database and The Cancer Genome Atlas. Additionally, the enrichment analysis of differential target genes (DTGs) was performed using the R-package clusterProfiler. Immunocyte correlation analysis and non-coding regulatory network construction were performed for biomarkers using Spearman's method and NetworkAnalyst. Finally, molecular docking of biomarkers and their corresponding molecule drugs was done with Autodock Vina software.

Results: We identified 20 active components of Astragalus membranaceus and 1 403 target genes through screening. A total of 2 300 differentially expressed genes, and 3 035 hub genes in CRC were screened. The integration of the target genes with the significantly differentially expressed genes and Hub genes identified resulted in a total of 86 DTGs. Subsequently, the results showed 828 enriched GO biological processes, 184 enriched GO molecular functions, 59 enriched GO cellular components, and 46 enriched KEGG pathways. We also obtained a total of 143 PPI pairs involving 67 nodes. Additionally, we constructed 45 mRNA-TF pairs, 101 miRNA-mRNA pairs, and 200 miRNA- mRNA-TF triplets. Finally, molecular docking was performed for the active component quercetin with F2 and UGT1A1 and formic acid with FGA, AHSG, and KNG1.

Conclusion: This study identified the active components of Astragalus membranaceus and their corresponding targets in CRC. These findings provide robust evidence for precision drug therapy in patients with CRC.

背景黄芪在治疗结直肠癌(CRC)方面具有积极的临床疗效:本研究旨在确定黄芪的主要活性成分,并确定这些成分在 CRC 患者中的有效靶点:方法:我们在中药系统药理学数据库和癌症基因组图谱中鉴定了黄芪的活性成分和差异表达基因。此外,我们还使用 R 软件包 clusterProfiler 对差异靶基因(DTGs)进行了富集分析。利用斯皮尔曼法和 NetworkAnalyst 对生物标志物进行了免疫细胞相关性分析和非编码调控网络构建。最后,使用 Autodock Vina 软件对生物标志物及其相应的分子药物进行了分子对接:结果:通过筛选,我们发现了黄芪中的 20 种活性成分和 1 403 个靶基因。共筛选出 2 300 个差异表达基因和 3 035 个 CRC 中心基因。将目标基因与所发现的显著差异表达基因和枢纽基因整合后,共产生了 86 个 DTGs。随后,研究结果显示了 828 个富集的 GO 生物过程、184 个富集的 GO 分子功能、59 个富集的 GO 细胞组分和 46 个富集的 KEGG 通路。我们还获得了涉及 67 个节点的 143 对 PPI。此外,我们还构建了 45 个 mRNA-TF 对、101 个 miRNA-mRNA 对和 200 个 miRNA- mRNA-TF 三联体。最后,对活性成分槲皮素与 F2 和 UGT1A1 以及甲酸与 FGA、AHSG 和 KNG1 进行了分子对接:本研究确定了黄芪的活性成分及其在 CRC 中的相应靶点。这些发现为 CRC 患者的精准药物治疗提供了有力的证据。
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引用次数: 0
LNX1-AS2 as a Key Prognostic and Immunotherapy Response Biomarker for Lung Adenocarcinoma. LNX1-AS2是肺腺癌的关键预后和免疫疗法反应生物标记物
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-31 DOI: 10.2174/0109298673321029241015153958
Xiuxiu Wang, Guanzhong Yan, Xiaoying Zhang, Dongbing Li, Guangyi Li

Background: The role of LNX1 antisense RNA 2 (LNX1-AS2) in lung adenocarcinoma (LUAD) remains unclear.

Objective: This study aimed to investigate the association between LNX1-AS2 and LUAD by employing bioinformatics analysis and experimental validation.

Methods: Statistical analysis and database interrogation were utilized to assess correlations among LNX1-AS2 expression, clinical characteristics of LUAD patients, prognostic factors, regulatory networks, and immune infiltration. LNX1-AS2 expression in LUAD cell lines was quantified using quantitative real-time polymerase chain reaction (qRT-PCR).

Results: The study found significantly elevated levels of LNX1-AS2 expression in patients with LUAD. Furthermore, elevated LNX1-AS2 expression in LUAD patients did not significantly correlate with gender (p = 0.041) or race (p = 0.049). Importantly, high LNX1-AS2 expression levels were associated with poorer overall survival (OS, p = 0.042) and disease-specific survival (DSS, p = 0.040) in LUAD patients. Additionally, high LNX1-AS2 expression (p = 0.015) was independently correlated with OS in LUAD patients. The phenotype characterized by high LNX1-AS2 expression was also found to be enriched for asthma, allograft rejection, drug metabolism cytochrome P450, metabolism of xenobiotics by cytochrome P450, olfactory transduction, renin-angiotensin system, retinol metabolism, pentose and glucuronate interconversions, and porphyrin and chlorophyll metabolism. A significant correlation was identified between the expression levels of LNX1-AS2 and immune infiltration in the context of LUAD. Elevated expression of LNX1-AS2 was notably detected in LUAD cell lines as opposed to Beas-2B.

Conclusion: A noteworthy relationship was established among increased LNX1-AS2 expression in LUAD patients, unfavorable prognosis, and heightened immune infiltration. These findings suggest that the LNX1-AS2 gene could serve as a valuable prognostic indicator for LUAD and a potential predictor of response to immunotherapy.

背景:LNX1反义RNA 2(LNX1-AS2)在肺腺癌(LUAD)中的作用尚不清楚:LNX1反义RNA 2(LNX1-AS2)在肺腺癌(LUAD)中的作用仍不清楚:本研究旨在通过生物信息学分析和实验验证,研究 LNX1-AS2 与 LUAD 之间的关联:方法:利用统计分析和数据库查询评估LNX1-AS2表达、LUAD患者临床特征、预后因素、调控网络和免疫浸润之间的相关性。使用定量实时聚合酶链反应(qRT-PCR)对LUAD细胞系中LNX1-AS2的表达进行量化:结果:研究发现,LUAD 患者的 LNX1-AS2 表达水平明显升高。此外,LUAD 患者 LNX1-AS2 表达的升高与性别(p = 0.041)或种族(p = 0.049)无明显相关性。重要的是,LNX1-AS2的高表达水平与LUAD患者较差的总生存期(OS,p = 0.042)和疾病特异性生存期(DSS,p = 0.040)相关。此外,LNX1-AS2的高表达(p = 0.015)与LUAD患者的OS独立相关。以 LNX1-AS2 高表达为特征的表型还富集于哮喘、异体移植排斥反应、药物代谢细胞色素 P450、细胞色素 P450 对异种生物的代谢、嗅觉传导、肾素-血管紧张素系统、视黄醇代谢、戊糖和葡萄糖醛酸的相互转化以及卟啉和叶绿素代谢。研究发现,LNX1-AS2 的表达水平与 LUAD 的免疫浸润之间存在明显的相关性。与 Beas-2B 细胞系相比,LNX1-AS2 在 LUAD 细胞系中的表达明显升高:结论:LUAD 患者 LNX1-AS2 表达增加、预后不良和免疫浸润加剧之间存在显著关系。这些研究结果表明,LNX1-AS2 基因可作为 LUAD 有价值的预后指标,也是预测免疫疗法反应的潜在指标。
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引用次数: 0
Exosomal Delivery of miR-155 Inhibitor can Suppress Migration, Invasion, and Angiogenesis Via PTEN and DUSP14 in Triple-negative Breast Cancer. 外泌体输送 miR-155 抑制剂可通过 PTEN 和 DUSP14 抑制三阴性乳腺癌的迁移、侵袭和血管生成
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-31 DOI: 10.2174/0109298673341499241016110341
Javad Razaviyan, Majid Sirati-Sabet, Razie Hadavi, Saeed Karima, Masoumeh Rajabi Bazl, Samira Mohammadi-Yeganeh

Introduction: Triple-Negative Breast Cancer (TNBC) is the most common type of breast cancer (BC). In order to develop effective treatments for TNBC, it is vital to identify potential therapeutic targets. Angiogenesis stimulates tumor growth and metastasis in TNBC, and miR-155 plays a crucial role in this process. The exosome is a nano-sized vesicle that carries many cargoes, including miRNAs. The present study investigated the effect of exosomal delivery of miR-155 antagomir on tumor migration, invasion, and angiogenesis in TNBC.

Materials and methods: From MDA-MB-231 cells, exosomes were extracted, characterized, and loaded with miR-155 antagomir using electroporation. The expression of miR-155 and its target genes, including PTEN and DUSP14, was analyzed using RTqPCR. The wound-healing and transwell assays were used to measure cell migration and invasion. Furthermore, angiogenesis was evaluated by tube formation and chorioallantoic membrane (CAM) assays.

Results: The results indicated that exosomal delivery of miR-155 antagomir to HUVEC cells significantly suppressed miR-155 expression while upregulating PTEN and DUSP14. The tube formation properties of HUVEC cells were also significantly reduced following treatment with exosomes containing miR-155 antagomirs, and these results were confirmed using CAM assay. The migration and invasion of MDA-MB-231 cells were significantly reduced after treatment with miR-155 antagomir-loaded exosomes.

Conclusion: It was found that miR-155 antagomir delivery using exosomes can inhibit migration, invasion, and angiogenesis viaPTEN and DUSP14 in TNBC.

导言三阴性乳腺癌(TNBC)是最常见的乳腺癌(BC)类型。为了开发 TNBC 的有效治疗方法,确定潜在的治疗靶点至关重要。血管生成会刺激 TNBC 中肿瘤的生长和转移,而 miR-155 在这一过程中起着至关重要的作用。外泌体是一种纳米大小的囊泡,可携带多种货物,包括 miRNA。本研究探讨了外泌体递送 miR-155 antagomir 对 TNBC 肿瘤迁移、侵袭和血管生成的影响:从 MDA-MB-231 细胞中提取外泌体,对其进行表征,并使用电穿孔法装载 miR-155 antagomir。使用 RTqPCR 分析了 miR-155 及其靶基因(包括 PTEN 和 DUSP14)的表达。伤口愈合和跨孔试验用于测量细胞迁移和侵袭。此外,还通过管形成和绒毛膜(CAM)试验评估了血管生成:结果表明,向 HUVEC 细胞外泌体递送 miR-155 antagomir 能显著抑制 miR-155 的表达,同时上调 PTEN 和 DUSP14。用含有 miR-155 antagomirs 的外泌体处理 HUVEC 细胞后,其管形成特性也明显降低,这些结果在 CAM 试验中得到了证实。用含有 miR-155 抗配体的外泌体处理后,MDA-MB-231 细胞的迁移和侵袭能力显著降低:结论:研究发现,利用外泌体递送miR-155抗配体可以通过PTEN和DUSP14抑制TNBC细胞的迁移、侵袭和血管生成。
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引用次数: 0
TLR2 Activation as a Marker of Severe COVID-19 and a Potential Therapeutic Target. TLR2 激活是严重 COVID-19 的标记和潜在治疗靶点。
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-31 DOI: 10.2174/0109298673327301241016063917
Xianxian Mao, Yijia Wu, Xinyi Zhang, Tian Zhou, Houda Huang, Mingui Fu, Yisong Qian

SARS-CoV-2-induced COVID-19 has been a serious public health problem, resulting in millions of lives lost over the previous three years. Although the direct infection caused by virus invasion is important for the pathobiology of COVID-19, the hyperinflammatory response and tissue injury are major contributors in critically ill patients. As a host sensor, toll-like receptor 2 (TLR2) recognizes multiple pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), producing various inflammatory cytokines and inflammatory cell death signals, which are central to the inflammatory pathology observed in COVID-19. The objectives of this narrative review are to summarize the role of TLR2 activation during SARS-CoV-2 infection and emphasize the importance of SARS-CoV-2 viral proteins in TLR2 activation. Additionally, we presented some compounds related to TLR2 regulation clinically or experimentally, which may provide new insights into targets for pharmaceutical discovery and development.

由 SARS-CoV-2 引发的 COVID-19 一直是一个严重的公共卫生问题,在过去三年中导致数百万人丧生。虽然病毒入侵造成的直接感染对 COVID-19 的病理生物学非常重要,但在重症患者中,高炎症反应和组织损伤也是主要的致病因素。作为宿主传感器,类收费受体 2(TLR2)可识别多种病原体相关分子模式(PAMPs)或损伤相关分子模式(DAMPs),产生各种炎症细胞因子和炎症细胞死亡信号,这是 COVID-19 中观察到的炎症病理学的核心。本综述旨在总结 TLR2 在 SARS-CoV-2 感染过程中的激活作用,并强调 SARS-CoV-2 病毒蛋白在 TLR2 激活过程中的重要性。此外,我们还介绍了临床或实验中与 TLR2 调节有关的一些化合物,这些化合物可能为药物发现和开发的靶点提供新的见解。
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引用次数: 0
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Current medicinal chemistry
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