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The Role of Quercetin for the Treatment of Endometriosis and Endometrial Cancer: A Comprehensive Review. 槲皮素在治疗子宫内膜异位症和癌症中的作用:综述。
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-01 DOI: 10.2174/0109298673269733230921092509
Shahla Chaichian, Banafsheh Nikfar, Sepideh Arbabi Bidgoli, Bahram Moazzami

Endometrial glands and stroma can be seen outside the uterine cavity in endometriosis, a gynecological disorder linked to estrogen dependency. Hormonal therapies, surgical excision, and non-steroidal anti-inflammatory drug therapy are among the traditional endometriosis treatments, however, various side effects limit their efficacy. Therefore, it is vital to research complementary and alternative therapeutic modalities to decrease the side effects of conventional therapies. While the search for the best endometriosis treatment continues, the focus is being paid to the assistance provided by polyphenols, notably quercetin. A broad spectrum of health-improving benefits of quercetin includes interactions with endometriosis-related molecular targets such as cell proliferation, apoptosis, invasiveness, inflammation, and oxidative stress. According to already-known research, medicines that mimic the physiological effects of quercetin are good candidates for creating novel endometriosis therapies. This review aims to comprehensively review quercetin's potential as a non-pharmacological treatment for endometriosis by interacting with several cellular and molecular targets.

子宫内膜异位症是一种与雌激素依赖有关的妇科疾病,子宫内膜腺体和间质可见于子宫腔外。激素治疗、手术切除和非甾体抗炎药治疗是传统的子宫内膜异位症治疗方法,然而,各种副作用限制了它们的疗效。因此,研究互补和替代的治疗方式以减少传统疗法的副作用至关重要。虽然寻找最佳子宫内膜异位症治疗方法的工作仍在继续,但重点是多酚,尤其是槲皮素提供的帮助。槲皮素对健康的广泛益处包括与子宫内膜异位症相关分子靶点的相互作用,如细胞增殖、凋亡、侵袭性、炎症和氧化应激。根据已知的研究,模仿槲皮素生理作用的药物是创造新型子宫内膜异位症疗法的良好候选药物。本综述旨在通过与几个细胞和分子靶点的相互作用,全面综述槲皮素作为子宫内膜异位症非药物治疗的潜力。
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引用次数: 0
Defective Mitophagy Impairs Response to Inflammatory Activation of Macrophage-Like Cells. 有丝分裂缺陷会影响类巨噬细胞对炎症激活的反应
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-01 DOI: 10.2174/0109298673294643240228105957
Alexander Nikolaevich Orekhov, Alexander Dmitrievich Zhuravlev, Andrey Yurievich Vinokurov, Nikita Gennadievich Nikiforov, Andrey Vladimirovich Omelchenko, Vasily Nikolaevich Sukhorukov, Vasily Vladimirovich Sinyov, Igor Alexandrovich Sobenin
<p><strong>Background and aims: </strong>The role of mitophagy in atherosclerosis has been extensively studied during the last few years. It was shown that mitophagy is involved in the regulation of macrophages, which are important players as immune cells in atherosclerosis development. In this study, we investigated the relationship between mitophagy and response to inflammatory stimulation of macrophage-like cells. Six cybrid cell lines with normal mitophagy, that is, increasing in response to stimulation, and 7 lines with defective mitophagy not responding to stimulation were obtained. The objective of the study was to compare the nature of the inflammatory response in normal and defective mitophagy in order to elucidate the role of mitophagy defects in inflammation.</p><p><strong>Methods: </strong>We used cytoplasmic hybrids (cybrids) as cellular models, created using mitochondrial DNA from different atherosclerosis patients. Mitophagy was stimulated by carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and assessed as the degree of colocalization of mitochondria with lysosomes using confocal microscopy. Western blotting methods were used for the determination of proteins involved in the exact mechanism of mitophagy. Experiments with stimulation of mitophagy show a high correlation between these two approaches (microscopy and blotting). The pro-inflammatory response of cybrids was stimulated with bacterial lipopolysaccharide (LPS). The extent of the inflammatory response was assessed by the secretion of cytokines CCL2, IL8, IL6, IL1β, and TNF measured by ELISA.</p><p><strong>Results: </strong>Basal level of secretion of cytokines CCL2, IL8 and TNF was 1.5-2 times higher in cultures of cybrids with defective mitophagy compared to cells with normal mitophagy. This suggests a persistently elevated inflammatory response in cells with defective mitophagy, even in the absence of an inflammatory stimulus. Such cells in the tissue will constantly recruit other immune cells, which is characteristic of macrophages derived from monocytes circulating in the blood of patients with atherosclerosis. We observed significant differences in the degree and type of response to inflammatory activation in cybrids with defective mitophagy. These differences were not so much quantitative as they were dramatically qualitative. Compared with cells with normal mitophagy, in cells with defective mitophagy, the relative (to basal) secretion of IL8, IL6 and IL1b increased after the second LPS activation. This indicates a possible lack of tolerance to inflammatory activation in cells with defective mitophagy, since typically, re-activation reveals a smaller pro-inflammatory cytokine response, allowing the inflammatory process to resolve. In cells with normal mitophagy, exactly this normal (tolerant) inflammatory reaction was observed.</p><p><strong>Conclusion: </strong>Data on the involvement of mitophagy, including defective mitophagy, in disturbances of the inflammatory re
背景和目的:在过去几年中,人们对有丝分裂在动脉粥样硬化中的作用进行了广泛研究。研究表明,有丝分裂参与了巨噬细胞的调控,而巨噬细胞作为免疫细胞在动脉粥样硬化的发展中扮演着重要角色。在这项研究中,我们探讨了有丝分裂与巨噬细胞样细胞对炎症刺激的反应之间的关系。我们获得了 6 个有丝分裂正常(即对刺激有反应)的细胞杂交系和 7 个有丝分裂缺陷(对刺激无反应)的细胞杂交系。研究的目的是比较有丝分裂正常和有丝分裂缺陷的炎症反应的性质,以阐明有丝分裂缺陷在炎症中的作用:我们使用细胞质杂交体(cybrids)作为细胞模型,该模型由不同动脉粥样硬化患者的线粒体DNA创建。通过间氯苯基腙(CCCP)刺激线粒体吞噬,并使用共聚焦显微镜评估线粒体与溶酶体的共聚焦程度。采用 Western 印迹法测定参与有丝分裂确切机制的蛋白质。刺激有丝分裂的实验表明,这两种方法(显微镜和印迹法)之间具有很高的相关性。用细菌脂多糖(LPS)刺激细胞杂交体的促炎反应。炎症反应的程度通过 ELISA 检测细胞因子 CCL2、IL8、IL6、IL1β 和 TNF 的分泌来评估:结果:与有丝分裂正常的细胞相比,有丝分裂缺陷的细胞杂交种的细胞因子 CCL2、IL8 和 TNF 的基础分泌水平高出 1.5-2 倍。这表明,即使在没有炎症刺激的情况下,有丝分裂缺陷细胞的炎症反应也会持续升高。组织中的此类细胞会不断招募其他免疫细胞,这正是动脉粥样硬化患者血液中循环的单核细胞衍生的巨噬细胞的特征。我们观察到,有丝分裂缺陷的细胞杂交体对炎症激活的反应程度和类型存在明显差异。这些差异与其说是数量上的,不如说是质量上的。与有丝分裂正常的细胞相比,有丝分裂缺陷的细胞在第二次LPS激活后,IL8、IL6和IL1b的相对(与基础)分泌量增加。这表明有丝分裂缺陷的细胞可能缺乏对炎症激活的耐受性,因为通常情况下,再次激活会显示较小的促炎细胞因子反应,使炎症过程得以缓解。在有丝分裂正常的细胞中,观察到的正是这种正常(耐受)的炎症反应:关于有丝分裂(包括有丝分裂缺陷)参与败血症、病毒感染、自身免疫性疾病和其他病症的炎症反应紊乱的数据此前已有报道。在这项研究中,我们以动脉粥样硬化为例,研究了有丝分裂缺陷在非感染性慢性炎症疾病中的作用。我们发现,有丝分裂缺陷会极大地破坏炎症反应。与有丝分裂正常的细胞杂交种相比,在有丝分裂缺陷的细胞杂交种中,所有研究细胞因子的分泌在数量和质量上都发生了显著变化。特别是,5 种细胞因子中有 3 种的分泌表现出不耐受炎症反应,即在反复炎症刺激后分泌增加。这种不耐受反应可能表明巨噬细胞的促炎反应受到了严重破坏,从而导致炎症慢性化。阐明炎症慢性化的机制对于寻找新的药理靶点、开发预防和治疗慢性炎症性疾病(包括动脉粥样硬化和炎症性疾病)的药物极为重要。此类疾病占发病率和死亡率的 80%。
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引用次数: 0
Identification and Characterization of Prognostic Macrophage Subpopulations for Human Esophageal Carcinoma. 人类食管癌预后巨噬细胞亚群的鉴定和特征描述
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-01 DOI: 10.2174/0109298673284207240108105724
Penghui Li, Xiaohui Gao, Di Huang, Xinyu Gu

Aims: The aim of the present study was to investigate the relationship between the cellular ecosystem and the progression of esophageal carcinoma (ESCA) based on the evolution of macrophages and to analyze the potential of using macrophages as a new therapeutic approach in ESCA treatment.

Background: Macrophage-based immunotherapy could be used for treating ESCA patients, but its clinical application is limited by the intra-tumor heterogeneity of macrophages.

Objective: The objective of this study was to analyze the diversity, differentiation trajectory, and intercellular communication of macrophages in ESCA and its prognostic significance.

Methods: Single-cell RNA sequencing (scRNA-seq) data in the GSE154763 dataset were downloaded from Gene Expression Omnibus (GEO) to identify cell clusters and annotate cell types using the Seurat R package. The scRNA-seq profiles of macrophages were extracted, and cluster analysis was performed to identify macrophage subsets. The differentiation trajectories of macrophage subgroups were visualized employing Monocle2. Finally, ligand-receptor pairs and communication intensity among the classified subgroups were analyzed using Cell Chat.

Results: A total of 8 cell types were identified between ESCA tissues and paracancer tissues. The most abundant macrophages in ESCA tissues were further divided into 5 cell clusters. Compared with the normal tissues, the proportion of HSPA6+ macrophages in ESCA tissues increased the most, and the number of ligand-receptor pairs that mediated the communication of HSPA6+ macrophages with mast cells and monocytes also increased significantly. More importantly, a high proportion of HSPA6+ macrophages was inversely correlated with the survival outcomes for ESCA patients.

Conclusions: This study analyzed the diversity, distribution and differentiation trajectory of macrophages in ESCA tissues at single-cell level and classified a prognostic macrophage subtype (HSPA6+ macrophages) of ESCA, providing a theoretical basis for macrophage-targeted therapy in ESCA.

目的:本研究旨在根据巨噬细胞的演变研究细胞生态系统与食管癌(ESCA)进展之间的关系,并分析利用巨噬细胞作为食管癌治疗新方法的潜力:背景:基于巨噬细胞的免疫疗法可用于治疗ESCA患者,但其临床应用因巨噬细胞的瘤内异质性而受到限制:本研究旨在分析ESCA中巨噬细胞的多样性、分化轨迹和细胞间通讯及其预后意义:从基因表达总库(Gene Expression Omnibus,GEO)下载GSE154763数据集中的单细胞RNA测序(scRNA-seq)数据,使用Seurat R软件包识别细胞集群并注释细胞类型。提取巨噬细胞的scRNA-seq图谱,并进行聚类分析以确定巨噬细胞亚群。巨噬细胞亚群的分化轨迹用 Monocle2 进行了可视化。最后,利用 CellChat 分析了配体-受体对和分类亚群之间的交流强度:结果:在ESCA组织和癌旁组织之间共发现了8种细胞类型。ESCA组织中最丰富的巨噬细胞被进一步分为5个细胞群。与正常组织相比,ESCA组织中HSPA6+巨噬细胞的比例增加最多,介导HSPA6+巨噬细胞与肥大细胞和单核细胞交流的配体-受体对的数量也显著增加。更重要的是,高比例的HSPA6+巨噬细胞与ESCA患者的生存结果成反比:本研究从单细胞水平分析了ESCA组织中巨噬细胞的多样性、分布和分化轨迹,并对ESCA的预后巨噬细胞亚型(HSPA6+巨噬细胞)进行了分类,为ESCA的巨噬细胞靶向治疗提供了理论依据。
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引用次数: 0
Pro-renin Receptor (PRR) as a Target to Reduce Non-alcoholic Fatty Liver Disease Post Liver Transplantation. 前肾素受体(PRR)作为减少肝移植后非酒精性脂肪肝的靶点。
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-01 DOI: 10.2174/0109298673345528241101092336
Rozita Khodashahi, Gordon A Ferns, Mohsen Aliakbarian, Mohammad-Hassan Arjmand

Nonalcoholic fatty liver disease (NAFLD) is one of the main causes of chronic liver disorders following liver transplantation. The prorenin receptor (PRR) plays a role in glucose and lipid metabolism, and the hepatic dysregulation of PRR is associated with the upregulation of several molecular pathways, such as the mammalian target of rapamycin (mTOR) and Peroxisome proliferator-activated receptor (PPAR) that promotes hepatic lipogenesis and leads to lipid accumulation in hepatocytes by upregulation of lipogenic genes. PRR inhibition leads to a reduction in the hepatic expression of sortilin-1 and low-density lipoprotein receptor (LDLR) levels and down-regulation of pyruvate dehydrogenase (PDH) and acetyl-CoA carboxylase (ACC) and reduces fatty acids synthesis in hepatocytes. In addition, β-oxidation regulatory genes are upregulated by PRR inhibition to attenuate liver lipid content and liver steatosis. This evidence suggests that targeting the dysregulated hepatic PRR may be effective in reducing liver steatosis postliver transplantation.

非酒精性脂肪性肝病(NAFLD)是肝移植后慢性肝脏疾病的主要原因之一。prorenin受体(PRR)在糖脂代谢中发挥作用,肝脏PRR的失调与几种分子通路的上调有关,如哺乳动物雷帕霉素靶蛋白(mTOR)和过氧化物酶体增殖激活受体(PPAR),通过上调脂质基因促进肝脏脂肪生成,导致肝细胞脂质积累。PRR抑制导致肝脏sortilin-1和低密度脂蛋白受体(LDLR)水平表达降低,丙酮酸脱氢酶(PDH)和乙酰辅酶a羧化酶(ACC)下调,并减少肝细胞脂肪酸合成。此外,β-氧化调节基因通过抑制PRR而上调,以减轻肝脏脂质含量和肝脏脂肪变性。这一证据表明,靶向肝脏PRR失调可能有效减少肝移植后肝脏脂肪变性。
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引用次数: 0
lncRNA-056298 Regulates GAP43 and Promotes Cardiac Intrinsic Autonomic Nerve Remodelling in a Canine Model of Atrial Fibrillation Induction after Ganglionated Plexus Ablation. lncRNA-056298在神经节丛消融后诱发心房颤动的犬模型中调控GAP43并促进心脏内在自主神经重塑
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-01 DOI: 10.2174/0109298673289298240129103537
Shuting Bai, Ximin Wang, Yinglong Hou, Yansong Cui, Qiyuan Song, Juanjuan Du, Yujiao Zhang, Jingwen Xu

Background: Cardiac intrinsic autonomic nerve remodelling has been reported to play an important role in the recurrence of atrial fibrillation after radiofrequency ablation, which significantly affects the long-term efficacy of this procedure. lncRNAs have been shown to interact in the pathological processes underlying heart diseases. However, the roles and mechanisms of lncRNAs in cardiac intrinsic autonomic nerve remodelling during atrial fibrillation reduction after ganglionated plexus ablation remain unknown.

Objective: The aim of this study was to investigate the mechanism by which lncRNA- 056298 modulates GAP43 to affect cardiac intrinsic autonomic nerve remodelling and facilitate the induction of atrial fibrillation after ganglionated plexus ablation.

Methods: A canine model of right atrial ganglionated plexus ablation was established. The atrial electrophysiological characteristics and neural markers were detected before and after 6 months of ganglionated plexus ablation. High-throughput sequencing was used to screen differentially expressed lncRNAs in target atrial tissues, and lncRNA- 056298 was selected to further explore its effects and mechanisms on cardiac intrinsic autonomic nerve remodelling.

Results: The induction rate of atrial fibrillation increased in dogs after ganglionated plexus ablation. Overexpression of lncRNA-056298 by lentivirus can shorten the atrial effective refractory period and increase the induction of atrial fibrillation. lncRNA- 056298 promoted cardiac intrinsic autonomic nerve remodelling via endogenous competition with cfa-miR-185 to induce transcription of its target gene GAP43, thereby affecting the induction of atrial fibrillation.

Conclusion: lncRNA-056298 regulates GAP43 by sponging miR-185, which affects cardiac intrinsic autonomic nerve remodelling and mediates atrial fibrillation induction after ganglionated plexus ablation.

背景:据报道,心脏固有自律神经重塑在射频消融术后心房颤动复发中起着重要作用,这严重影响了该手术的长期疗效。然而,lncRNAs在神经节丛消融术后心房颤动减弱过程中心脏固有自律神经重塑过程中的作用和机制仍然未知:本研究旨在探讨 lncRNA- 056298 调节 GAP43 影响心脏固有自律神经重塑并促进神经节丛消融术后房颤诱导的机制:方法:建立了右心房神经节丛消融的犬模型。方法:建立了一个犬右心房神经节丛消融模型,检测了神经节丛消融前后 6 个月的心房电生理特征和神经标记物。利用高通量测序技术筛选目标心房组织中差异表达的lncRNA,并选择lncRNA- 056298进一步探讨其对心脏固有自律神经重塑的影响和机制:结果:神经节丛消融术后,犬心房颤动的诱发率增加。lncRNA-056298通过内源性与cfa-miR-185竞争诱导其靶基因GAP43的转录,促进心脏固有自律神经重塑,从而影响心房颤动的诱发。结论:lncRNA-056298通过疏导miR-185调控GAP43,影响心脏固有自律神经重塑,介导神经节丛消融术后的心房颤动诱导。
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引用次数: 0
Analysis and Validation of Tyrosine Metabolism-related Prognostic Features for Liver Hepatocellular Carcinoma Therapy. 酪氨酸代谢相关肝癌治疗预后特征的分析与验证
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-01 DOI: 10.2174/0109298673290101240223074545
Zhongfeng Cui, Chunli Liu, Hongzhi Li, Juan Wang, Guangming Li

Aims: To explore tyrosine metabolism-related characteristics in liver hepatocellular carcinoma (LIHC) and to establish a risk signature for the prognostic prediction of LIHC. Novel prognostic signatures contribute to the mining of novel biomarkers, which are essential for the construction of a precision medicine system for LIHC and the improvement of survival.

Background: Tyrosine metabolism plays a critical role in the initiation and development of LIHC. Based on the tyrosine metabolism-related characteristics in LIHC, this study developed a risk signature to improve the prognostic prediction of patients with LIHC.

Objective: To investigate the correlation between tyrosine metabolism and progression of LIHC and to develop a tyrosine metabolism-related prognostic model.

Methods: Gene expression and clinicopathological information of LIHC were obtained from The Cancer Genome Atlas (TCGA) database. Distinct subtypes of LIHC were classified by performing consensus cluster analysis on the tyrosine metabolism-related genes. Univariate and Lasso Cox regression were used to develop a RiskScore prognosis model. Kaplan-Meier (KM) survival analysis with log-rank test and area under the curve (AUC) of receiver operating characteristic (ROC) were employed in the prognostic evaluation and prediction validation. Immune infiltration, tyrosine metabolism score, and pathway enrichment were evaluated using single-sample gene set enrichment analysis (ssGSEA). Finally, a nomogram model was developed with the RiskScore and other clinicopathological features.

Results: Based on the tyrosine metabolism genes in the TCGA cohort, we identified 3 tyrosine metabolism-related subtypes showing significant prognostic differences. Four candidate genes selected from the common differentially expressed genes (DEGs) between the 3 subtypes were used to develop a RiskScore model, which could effectively divide LIHC patients into high- and lowrisk groups. In both the training and validation sets, high-risk patients tended to have worse overall survival, less active immunotherapy response, higher immune infiltration and clinical grade, and higher oxidative, fatty, and xenobiotic metabolism pathways. Multivariate analysis confirmed that the RiskScore was an independent indicator for the prognosis of LIHC. The results from pan-- cancer analysis also supported that the RiskScore had a strong prognostic performance in other cancers. The nomogram demonstrated that the RiskScore contributed the most to the prediction of LIHC prognosis.

Conclusion: Our study developed a tyrosine metabolism-related risk model that performed well in survival prediction, showing the potential to serve as an independent prognostic predictor for LIHC treatment.

目的:探索肝肝细胞癌(LIHC)的酪氨酸代谢相关特征,建立肝肝细胞癌预后预测的风险特征。新的预后特征有助于挖掘新的生物标志物,这对构建肝癌精准医疗体系和提高生存率至关重要:背景:酪氨酸代谢在LIHC的发生和发展中起着关键作用。背景:酪氨酸代谢在LIHC的发生和发展中起着关键作用。基于LIHC中酪氨酸代谢相关特征,本研究建立了一个风险特征,以改善LIHC患者的预后预测:研究酪氨酸代谢与LIHC进展之间的相关性,并建立酪氨酸代谢相关预后模型:方法:从癌症基因组图谱(TCGA)数据库中获取LIHC的基因表达和临床病理信息。通过对酪氨酸代谢相关基因进行共识聚类分析,对LIHC的不同亚型进行了分类。利用单变量和Lasso Cox回归建立了RiskScore预后模型。在预后评估和预测验证中采用了带有对数秩检验的卡普兰-梅耶(KM)生存分析和接收器操作特征曲线下面积(AUC)。采用单样本基因组富集分析(ssGSEA)对免疫浸润、酪氨酸代谢评分和通路富集进行了评估。最后,利用 RiskScore 和其他临床病理特征建立了一个提名图模型:结果:基于TCGA队列中的酪氨酸代谢基因,我们发现了3种显示出显著预后差异的酪氨酸代谢相关亚型。从这3种亚型的共同差异表达基因(DEGs)中选出的4个候选基因被用于建立RiskScore模型,该模型能有效地将LIHC患者分为高危和低危两组。在训练集和验证集中,高危患者的总生存期较差,免疫治疗反应不积极,免疫浸润和临床分级较高,氧化、脂肪和异种生物代谢通路较多。多变量分析证实,RiskScore是影响LIHC预后的一个独立指标。泛癌症分析的结果也支持风险分数在其他癌症中具有很强的预后性能。提名图显示,RiskScore对预测LIHC预后的贡献最大:结论:我们的研究建立了一个酪氨酸代谢相关风险模型,该模型在生存预测方面表现良好,显示出其作为独立预后预测指标用于LIHC治疗的潜力。
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引用次数: 0
Clinical Trials of High-intensity Focused Ultrasound for Cancer: Concerns Arising from Low Post-Hoc Power. 高强度聚焦超声治疗癌症的临床试验:后验功率低引起的担忧。
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-01 DOI: 10.2174/0109298673281773240104142757
Tinghe Yu, Xinya Li

Prospective controlled trials of high-intensity focused ultrasound (HIFU) for cancers were evaluated. Post-hoc power was <0.80 in 30/46 trials and in 22/38 trials with positive results, indicating low quality in most trials. Unscientific endpoints, small sample sizes, and high dropout rates led to low post-hoc power that caused inter-trial heterogeneity and overestimated the therapeutic effect. The objective response rate was not a substitute for survival time for estimating the sample size and assessing the efficacy. The present data can interpret a paradox: HIFU is considered to have slighter cytotoxicity to noncancer tissues and no radiation but is frequently combined with chemotherapy and/or radiotherapy in practice.

对高强度聚焦超声治疗癌症的前瞻性对照试验进行了评估。事后功率为
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引用次数: 0
WITHDRAWN: In Vitro and In Vivo Anti-lung Cancer Activity of Emodin: An RNAseq Transcriptome Analysis 大黄素的体外和体内抗肺癌活性:RNA-seq转录组分析
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-01 DOI: 10.2174/0929867329666220921120314
Aikebaier Maimaiti, Liu Xingliang, Linsen Shi

Since the authors are not responding to the editor’s requests to fulfill the editorial requirement, therefore, the article has been withdrawn.

Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.

The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php

Bentham science disclaimer: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

大黄素是一种天然的中草药蒽醌提取物。多项研究表明,这种提取物具有抗肿瘤活性,尤其是对肺癌。然而,大黄素的作用模式仍不明确。在这项研究中,我们评估了大黄素在体外和体内对人类肺腺癌的抗肺癌特性及其潜在的分子机制。结果表明,大黄素能显著抑制肺癌细胞的活力,并诱导其凋亡,其水平与正常上皮细胞的凋亡水平相当。此外,RNA-seq转录组分析发现,在大黄素处理的A549和H1650细胞中,65个常见基因(变化>2倍)有显著表达。体外 qRT-PCR 结果证实,在 A549 和 H1650 腺癌细胞系中,4 个基因(ATP6V0D2、C11orf96、TIPARP 和 CDKN1A)上调,9 个基因(TNFSF10、IFIT1、EGLN3、RCOR2、ARRB1、FLVCR2、BAIAP2-DT、FAM111B 和 TGFB2)下调。体内实验表明,与对照组相比,大黄素能显著减少小鼠的肿瘤体积和肿瘤重量。但大黄素对小鼠体重无明显影响。此外,体内qRT-PCR结果显示,与对照组相比,肿瘤组织中有3个基因(ATP6V0D2、C11orf96和TIPARP)上调,6个基因(TNFSF10、IFIT1、EGLN3、BAIAP2-DT、FAM111B和TGFB2)下调。这些研究结果表明,大黄素有助于治疗肺癌,具有作为抗肺癌药物进行进一步研究的潜力。
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引用次数: 0
Association of Body Mass Index and Abdominal Obesity with Incidence of Atrial Fibrillation in Heart Failure with Preserved Ejection Fraction 撤回:身体质量指数和腹部肥胖与保留射血分数的心力衰竭患者房颤发生率的关系
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-01 DOI: 10.2174/0929867330666230606100903
Xinyi Huang, Xiao Liu, Yuan Jiang, Zhengyu Cao, Maoxiong Wu, Zhiteng Chen, Runlu Sun, Peng Yu, Jianyong Ma, Wengen Zhu, Yangxin Chen, Guifu Wu, Yuling Zhang, Jingfeng Wang

Introduction: The association between obesity and atrial fibrillation (AF) incidence inheart failure with preserved ejection fraction (HFpEF) patients is currently unclear. Our analysesand results are based on the whole Treatment of Preserved Cardiac Function Heart Failure with anAldosterone Antagonist (TOPCAT) trial (placebo and spironolactone).

Methods: A total of 2138 subjects without baseline AF were included in the trial. Kaplan-Meier(K-M) curves and Cox regression with hazard ratios (HRs) and confidence intervals (CIs) wereused to assess the incidence of AF with obesity.

Results: Of 2138 HFpEF patients without baseline AF, 1165 were obese (body mass index [BMI]≥30 kg/m2). The K-M curve showed obese patients developed AF more than overweight (25≤BMI ≤29.9 kg/m2) patients (p=0.013), confirmed by multivariable analysis, while there’s no statisticaldifference between overweight and normal weight (18.5≤ BMI ≤24.9 kg/m2) patients. The occurrenceof AF increased by 3% for every kg/m2 increase in BMI (adjusted HR, aHR: 1.03; 95%CI: 1.00-1.06), with a positive linear association (p for nonlinear: 0.145). Obesity was associatedwith AF incidence (aHR: 1.62; 95% CI: 1.05-2.50) compared with non-obesity (including overweightand normal-weight patients). Abdominal obesity was associated with increased AF incidence(aHR: 1.70; 95% CI: 1.04-2.77), and AF incidence rose by 18% per centimeter in circumference(aHR: 1.18; 95% CI:1.04-1.34).

Conclusion: Obesity and abdominal obesity increase the incidence of AF in HFpEF patients. Furtherstudies need to determine whether there is a difference in AF in response to spironolactoneacross obese HFpEF pheno groups.

Clinical trial registration: URL: https://clinicaltrials.gov. Unique identifier: NCT00094302. Registeredon October 15, 2004

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{"title":"Association of Body Mass Index and Abdominal Obesity with Incidence of Atrial Fibrillation in Heart Failure with Preserved Ejection Fraction","authors":"Xinyi Huang, Xiao Liu, Yuan Jiang, Zhengyu Cao, Maoxiong Wu, Zhiteng Chen, Runlu Sun, Peng Yu, Jianyong Ma, Wengen Zhu, Yangxin Chen, Guifu Wu, Yuling Zhang, Jingfeng Wang","doi":"10.2174/0929867330666230606100903","DOIUrl":"10.2174/0929867330666230606100903","url":null,"abstract":"<p><strong>Introduction: </strong>The association between obesity and atrial fibrillation (AF) incidence in\u0000heart failure with preserved ejection fraction (HFpEF) patients is currently unclear. Our analyses\u0000and results are based on the whole Treatment of Preserved Cardiac Function Heart Failure with an\u0000Aldosterone Antagonist (TOPCAT) trial (placebo and spironolactone).</p><p><strong>Methods: </strong>A total of 2138 subjects without baseline AF were included in the trial. Kaplan-Meier\u0000(K-M) curves and Cox regression with hazard ratios (HRs) and confidence intervals (CIs) were\u0000used to assess the incidence of AF with obesity.</p><p><strong>Results: </strong>Of 2138 HFpEF patients without baseline AF, 1165 were obese (body mass index [BMI]≥\u000030 kg/m2). The K-M curve showed obese patients developed AF more than overweight (25≤\u0000BMI ≤29.9 kg/m2) patients (p=0.013), confirmed by multivariable analysis, while there’s no statistical\u0000difference between overweight and normal weight (18.5≤ BMI ≤24.9 kg/m2) patients. The occurrence\u0000of AF increased by 3% for every kg/m2 increase in BMI (adjusted HR, aHR: 1.03; 95%\u0000CI: 1.00-1.06), with a positive linear association (p for nonlinear: 0.145). Obesity was associated\u0000with AF incidence (aHR: 1.62; 95% CI: 1.05-2.50) compared with non-obesity (including overweight\u0000and normal-weight patients). Abdominal obesity was associated with increased AF incidence\u0000(aHR: 1.70; 95% CI: 1.04-2.77), and AF incidence rose by 18% per centimeter in circumference\u0000(aHR: 1.18; 95% CI:1.04-1.34).</p><p><strong>Conclusion: </strong>Obesity and abdominal obesity increase the incidence of AF in HFpEF patients. Further\u0000studies need to determine whether there is a difference in AF in response to spironolactone\u0000across obese HFpEF pheno groups.</p><p><strong>Clinical trial registration: </strong>URL: https://clinicaltrials.gov. Unique identifier: NCT00094302. Registered\u0000on October 15, 2004</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9586696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Possible Roles of β-alanine and L-carnosine in Anti-aging. β-丙氨酸和左旋肉碱在抗衰老中的可能作用
IF 3.5 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-01-01 DOI: 10.2174/0109298673263561231117054447
Amin Gasmi, Pavan Kumar Mujawdiya, Roman Lysiuk, Mariia Shanaida, Massimiliano Peana, Salva Piscopo, Nataliya Beley, Svitlana Dzyha, Kateryna Smetanina, Volodymyr Shanaida, Stephane Resimont, Geir Bjorklund

β-alanine (BA), being a non-proteinogenic amino acid, is an important constituent of L-carnosine (LC), which is necessary for maintaining the muscle buffering capacity and preventing a loss of muscle mass associated with aging effects. BA is also very important for normal human metabolism due to the formation of a part of pantothenate, which is incorporated into coenzyme A. BA is synthesized in the liver, and its combination with histidine results in the formation of LC, which accumulates in the muscles and brain tissues and has a well-defined physiological role as a good buffer for the pH range of muscles that caused its rapidly increased popularity as ergogenic support to sports performance. The main antioxidant mechanisms of LC include reactive oxygen species (ROS) scavenging and chelation of metal ions. With age, the buffering capacity of muscles also declines due to reduced concentration of LC and sarcopenia. Moreover, LC acts as an antiglycation agent, ultimately reducing the development of degenerative diseases. LC has an anti-inflammatory effect in autoimmune diseases such as osteoarthritis. As histidine is always present in the human body in higher concentrations than BA, humans have to get BA from dietary sources to support the required amount of this critical constituent to supply the necessary amount of LC synthesis. Also, BA has other beneficial effects, such as preventing skin aging and intestinal damage, improving the stress-- fighting capability of the muscle cells, and managing an age-related decline in memory and learning. In this review, the results of a detailed analysis of the role and various beneficial properties of BA and LC from the anti-aging perspective are presented.

丙氨酸(BA)是一种非蛋白源氨基酸,是左旋肉碱(LC)的重要成分,而左旋肉碱是维持肌肉缓冲能力和防止肌肉质量因衰老而下降所必需的。BA 在肝脏中合成,与组氨酸结合后形成 LC,LC 在肌肉和脑组织中积聚,具有明确的生理作用,是肌肉 pH 值范围的良好缓冲剂,因此作为运动表现的生力支持物质而迅速流行。半胱氨酸的主要抗氧化机制包括清除活性氧和螯合金属离子。随着年龄的增长,肌肉的缓冲能力也会因低聚糖浓度降低和肌肉疏松症而下降。此外,LC 还可作为抗糖化剂,最终减少退行性疾病的发生。低聚半乳糖对骨关节炎等自身免疫性疾病有抗炎作用。由于组氨酸在人体内的含量总是高于 BA,因此人类必须从膳食中摄取 BA,以满足合成 LC 所需的组氨酸含量。此外,BA 还具有其他有益作用,如防止皮肤老化和肠道损伤、提高肌肉细胞的抗应激能力,以及控制与年龄有关的记忆力和学习能力下降。本综述从抗衰老的角度详细分析了 BA 和 LC 的作用和各种有益特性。
{"title":"The Possible Roles of <i>β</i>-alanine and L-carnosine in Anti-aging.","authors":"Amin Gasmi, Pavan Kumar Mujawdiya, Roman Lysiuk, Mariia Shanaida, Massimiliano Peana, Salva Piscopo, Nataliya Beley, Svitlana Dzyha, Kateryna Smetanina, Volodymyr Shanaida, Stephane Resimont, Geir Bjorklund","doi":"10.2174/0109298673263561231117054447","DOIUrl":"10.2174/0109298673263561231117054447","url":null,"abstract":"<p><p>β-alanine (BA), being a non-proteinogenic amino acid, is an important constituent of L-carnosine (LC), which is necessary for maintaining the muscle buffering capacity and preventing a loss of muscle mass associated with aging effects. BA is also very important for normal human metabolism due to the formation of a part of pantothenate, which is incorporated into coenzyme A. BA is synthesized in the liver, and its combination with histidine results in the formation of LC, which accumulates in the muscles and brain tissues and has a well-defined physiological role as a good buffer for the pH range of muscles that caused its rapidly increased popularity as ergogenic support to sports performance. The main antioxidant mechanisms of LC include reactive oxygen species (ROS) scavenging and chelation of metal ions. With age, the buffering capacity of muscles also declines due to reduced concentration of LC and sarcopenia. Moreover, LC acts as an antiglycation agent, ultimately reducing the development of degenerative diseases. LC has an anti-inflammatory effect in autoimmune diseases such as osteoarthritis. As histidine is always present in the human body in higher concentrations than BA, humans have to get BA from dietary sources to support the required amount of this critical constituent to supply the necessary amount of LC synthesis. Also, BA has other beneficial effects, such as preventing skin aging and intestinal damage, improving the stress-- fighting capability of the muscle cells, and managing an age-related decline in memory and learning. In this review, the results of a detailed analysis of the role and various beneficial properties of BA and LC from the anti-aging perspective are presented.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":"6-22"},"PeriodicalIF":3.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139511805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Current medicinal chemistry
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