Journal of cellular signaling最新文献

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Purinergic P2X7 Receptor as a Potential Targeted Therapy for COVID-19-associated Lung Cancer Progression 嘌呤能P2X7受体作为covid -19相关肺癌进展的潜在靶向治疗

Journal of cellular signaling

Pub Date : 2023-03-07 DOI: 10.33696/signaling.4.087

Hamidreza Zalpoor, A. Akbari, M. Nabi-Afjadi, Ali Norouzi, F. Seif, M. Pornour

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection is a serious threat to lung cancer patients. Hereby, we hypothesize that Coronavirus disease 2019 (COVID-19) may contribute to lung cancer progression by increasing extracellular adenosine triphosphate (ATP) levels and hyperactivating the purinergic P2X purinoceptor 7 receptor (P2X7R). Hyperactivation of P2X7R by increased extracellular ATP may stimulate multiple signaling pathways and factors such as NLRP3 inflammasome; as a result, interleukin (IL)-1β, and IL-18 pro-inflammatory cytokines are released, JNK, Rho kinase, HMGB1-RAGE, PI3K/AKT, hypoxia-inducible factor-1 alpha (HIF-1α), and ERK. NLRP3 activation may play a pivotal role in fatal cytokine storm in critically ill patients with COVID-19 and tumor progression in patients with lung cancer. Consequently, inhibiting these signaling pathways may deviate immune responses toward anti-tumoral responses, and suppress lung cancer progression and cytokine storms. Therefore, targeting P2X7R by means of oxidized ATP and anti-P2X7 monoclonal antibodies may provide promising therapeutic approaches to prevent lung cancer progression in COVID-19 patients; however, no clinical trials have yet been conducted, and their clinical efficacy remains to be elucidated.

严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)感染是肺癌患者的严重威胁。因此，我们假设2019冠状病毒病(COVID-19)可能通过增加细胞外三磷酸腺苷(ATP)水平和过度激活嘌呤能P2X嘌呤受体7受体(P2X7R)来促进肺癌的进展。细胞外ATP增加导致P2X7R的过度激活可能刺激多种信号通路和因子，如NLRP3炎性体;因此，白细胞介素(IL)-1β和IL-18促炎细胞因子、JNK、Rho激酶、HMGB1-RAGE、PI3K/AKT、缺氧诱导因子-1α (HIF-1α)和ERK被释放。NLRP3激活可能在COVID-19危重患者致死性细胞因子风暴和肺癌患者肿瘤进展中发挥关键作用。因此，抑制这些信号通路可能使免疫反应偏离抗肿瘤反应，并抑制肺癌的进展和细胞因子风暴。因此，通过氧化ATP和抗p2x7单克隆抗体靶向P2X7R可能为预防COVID-19患者肺癌进展提供有希望的治疗方法;但尚未进行临床试验，其临床疗效有待阐明。

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引用次数: 1

Targeting SCUBE3 in Hepatocellular Carcinoma 靶向SCUBE3治疗肝细胞癌

Journal of cellular signaling

Pub Date : 2023-03-07 DOI: 10.33696/signaling.4.088

Teng Liu, Xia Yang, Ke Wang, Q. Luo

HCC is one of the most common malignant tumors. The life and health of humans are gravely threatened by HCC because of its hidden onset, high recurrence rate, poor therapeutic effect, and high mortality. It is essential to explore the particular pathological mechanisms of HCC in order to increase the rate of early diagnosis and enhance patient therapy outcomes. Recent research has demonstrated that SCUBE3 can influence HCC cell proliferation by regulating the TGFβ/PI3K/AKT/GSK3β pathway. The molecular regulatory network of HCC proliferation is improved by this research, which also offers a solid theoretical and experimental foundation for SCUBE3 as a potential new therapeutic target for HCC.

HCC是最常见的恶性肿瘤之一。HCC发病隐匿、复发率高、治疗效果差、死亡率高，严重威胁着人类的生命健康。为了提高HCC的早期诊断率和提高患者的治疗效果，有必要探讨HCC的特殊病理机制。最近的研究表明，SCUBE3可以通过调节TGFβ/PI3K/AKT/GSK3β通路影响HCC细胞增殖。本研究完善了HCC增殖的分子调控网络，也为SCUBE3作为HCC潜在的新治疗靶点提供了坚实的理论和实验基础。

引用次数: 0

Radiation-induced Bystander Effect and Its Possible Countermeasures 辐射诱发的旁观者效应及其可能的对策

Journal of cellular signaling

Pub Date : 2023-03-07 DOI: 10.33696/signaling.4.086

G. Ghosh

Ionizing radiation has been indispensable to medical diagnosis. In cancer, radiation therapy or radiotherapy (RT) offers patients a better chance of survival. It destroys cancer by depositing high-energy radiation on the cancer tissues, though it may directly damage a few normal cells. Therefore, the total radiation dose is administered in fractionated modalities over weeks or months. However, experimental evidence indicates that the irradiated cancer cells subsequently release cytokines in the blood that enter into nearby unirradiated nuclei/cells through several signaling pathways and cause radiation-induced bystander effects (RIBEs) such as DNA damage, chromosomal instability, mutation, and apoptosis in them as side effects of RT. Recently, many combined therapeutic protocols consisting of a few natural and synthetic products have been proposed to minimize RIBEs. This article reviews the present understanding of RIBEs and their possible countermeasures. Besides, a new protocol of combined therapy of nanoparticle-based ion treatment (NIT) and RT to minimize RIBEs has been proposed.

电离辐射对医学诊断是不可或缺的。在癌症中，放射治疗或放疗(RT)为患者提供了更好的生存机会。它通过在癌组织上沉积高能辐射来摧毁癌症，尽管它可能直接损害一些正常细胞。因此，总辐射剂量在数周或数月内以分段方式给予。然而，实验证据表明，受辐照的癌细胞随后在血液中释放细胞因子，这些细胞因子通过几种信号通路进入附近未受辐照的细胞核/细胞，并引起辐射诱导的旁观者效应(RIBEs)，如DNA损伤、染色体不稳定、突变和细胞凋亡，作为辐射的副作用。最近，已经提出了许多由几种天然和合成产物组成的联合治疗方案，以尽量减少RIBEs。本文回顾了目前对RIBEs的认识和可能的对策。此外，还提出了一种纳米颗粒离子治疗(NIT)和RT联合治疗以减少RIBEs的新方案。

引用次数: 0

Augmenting Venetoclax Activity Through Signal Transduction in AML. 在AML中通过信号转导增强Venetoclax活性。

Journal of cellular signaling

Pub Date : 2023-01-01 DOI: 10.33696/signaling.4.085

Ian Michael Bouligny, Keri Renee Maher, Steven Grant

Venetoclax, a small-molecule B-cell lymphoma 2 (BCL-2) inhibitor, selectively eradicates leukemic stem cells (LSCs). While venetoclax has revolutionized the treatment of acute myeloid leukemia (AML), treatment failure and disease relapse are common. Mechanisms underlying venetoclax resistance are surprisingly heterogeneous. Venetoclax resistance encompasses a spectrum of genetic and epigenetic changes, with numerous pathways contributing to the upregulation of additional anti-apoptotic proteins. In this review, we address the mechanisms of venetoclax resistance in the context of signal transduction. We emphasize how aberrant cell signaling impairs apoptosis and predisposes to venetoclax failure. Commonly activated pathways, such as FLT3, PI3K/AKT/mTOR, and RAS, contribute to upregulated anti-apoptotic mediators and are frequently responsible for refractory disease or disease relapse. We highlight novel combination strategies aimed at disabling constitutively active signal transduction to augment response and overcome venetoclax resistance.

Venetoclax是一种小分子b细胞淋巴瘤2 (BCL-2)抑制剂，可选择性根除白血病干细胞(LSCs)。虽然venetoclax已经彻底改变了急性髓性白血病(AML)的治疗，但治疗失败和疾病复发是常见的。令人惊讶的是，venetoclax耐药机制存在异质性。Venetoclax耐药包括一系列遗传和表观遗传变化，有许多途径有助于上调额外的抗凋亡蛋白。在这篇综述中，我们在信号转导的背景下讨论了venetoclax耐药的机制。我们强调异常的细胞信号是如何损害细胞凋亡和导致血管衰竭的。FLT3、PI3K/AKT/mTOR和RAS等通常激活的通路有助于上调抗凋亡介质，并经常导致难治性疾病或疾病复发。我们强调了新的联合策略，旨在使本构主动信号转导失能，以增强反应和克服venetoclax耐药性。

引用次数: 2

Optogenetics Sheds Light on Brown and Beige Adipocytes. 光遗传学揭示棕色和米色脂肪细胞。

Journal of cellular signaling

Pub Date : 2023-01-01 DOI: 10.33696/signaling.4.105

Aaron Clifford Brown

Excessive food intake leads to lipid accumulation in white adipose tissue, triggering inflammation, cellular stress, insulin resistance, and metabolic syndrome. In contrast, the dynamic energy expenditure and heat generation of brown and beige adipose tissue, driven by specialized mitochondria, render it an appealing candidate for therapeutic strategies aimed at addressing metabolic disorders. This review examines the therapeutic potential of brown and beige adipocytes for obesity and metabolic disorders, focusing on recent studies that employ optogenetics for thermogenesis control in these cells. The findings delve into the mechanisms underlying UCP1-dependent and UCP1-independent thermogenesis and how optogenetic approaches can be used to precisely modulate energy expenditure and induce thermogenesis. The convergence of adipocyte biology and optogenetics presents an exciting frontier in combating metabolic disorders and advancing our understanding of cellular regulation and energy balance.

过量的食物摄入会导致白色脂肪组织中的脂质堆积，引发炎症、细胞应激、胰岛素抵抗和代谢综合征。相比之下，由专门的线粒体驱动的棕色和米色脂肪组织的动态能量消耗和热量产生，使其成为治疗代谢紊乱的有吸引力的候选治疗策略。这篇综述考察了棕色和米色脂肪细胞对肥胖和代谢紊乱的治疗潜力，重点是最近利用光遗传学控制这些细胞产热的研究。研究结果深入探讨了UCP1依赖性和UCP1非依赖性产热的机制，以及光遗传学方法如何用于精确调节能量消耗和诱导产热。脂肪细胞生物学和光遗传学的融合为对抗代谢紊乱和推进我们对细胞调节和能量平衡的理解提供了一个令人兴奋的前沿。

引用次数: 0

Targeting the Complex Protein Network of MYCN-amplified Anaplastic Ependymoma: A Case Report 靶向mycn扩增间变性室管膜瘤复杂蛋白网络1例

Journal of cellular signaling

Pub Date : 2022-12-22 DOI: 10.33696/signaling.3.082

MD Michael P. Castro

The MYCN oncoprotein has been notoriously undruggable and is infamous for causing aggressive cancer with poor outcomes in children and adults. Following surgery, radiation, and chemotherapy, patients who develop progressive disease have few treatment options. An analysis of the dysregulated protein network caused by MYCN amplification suggested co-targeting PLK1, AURKA, CKS1, AKT, MTOR, and USP7 would be useful to take advantage of synthetic lethal vulnerabilities while overcoming redundancies and resistance mechanisms that stabilize N-Myc by preventing its proteasome degradation. Naturopathic compounds, (genistein, tanshinone, resveratrol, betulinic acid) and fluoxetine were re-purposed to target the complex protein network in a patient with MYCN -amplified and PTEN -deficient multifocal, relapsed anaplastic ependymoma following standard therapy. The patient achieved a clinically meaningful and durable response for 6 months prior to developing disease progression characterized by chromosome 11q ( YAP1, BIRC2/3 ) amplification. The experience suggests molecularly-informed integration of naturopathic compounds can have utility for disease control and survival. The success, although anecdotal, suggests that the previous failure of single agent strategies could be overcome with a network targeting approach that simultaneously precipitates cell cycle arrest, rescues FBXW7 ubiquitination, and enhances oxidative stress. As such, MYCN may no longer be strictly unactionable but appears amenable to co-targeting key nodes in its self-sustaining disease network.

众所周知，MYCN癌蛋白是不可药物治疗的，并且因在儿童和成人中导致预后不良的侵袭性癌症而臭名昭著。在手术、放疗和化疗之后，进展性疾病的患者几乎没有治疗选择。对MYCN扩增引起的失调蛋白网络的分析表明，共同靶向PLK1、AURKA、CKS1、AKT、MTOR和USP7将有助于利用合成的致命脆弱性，同时克服冗余和耐药机制，通过阻止其蛋白酶体降解来稳定N-Myc。自然疗法化合物(染料木黄酮、丹参酮、白藜芦醇、白桦酸)和氟西汀被重新用于MYCN扩增和PTEN缺乏的多灶性复发间变性室管膜瘤患者的复杂蛋白网络。在以染色体11q (YAP1, BIRC2/3)扩增为特征的疾病进展之前，患者在6个月内获得了具有临床意义的持久缓解。这一经验表明，从分子上了解自然疗法化合物的整合对疾病控制和生存有帮助。这一成功，虽然是传闻，但表明先前单药策略的失败可以通过网络靶向方法来克服，同时沉淀细胞周期阻滞，挽救FBXW7泛素化，并增强氧化应激。因此，MYCN可能不再是严格不可操作的，而似乎可以共同靶向其自我维持疾病网络中的关键节点。

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引用次数: 0

New Insights into the Proteolytic Regulation of the Structural Protein Junctophilin-2 by Calpain Calpain对结构蛋白Junctophilin-2蛋白水解调控的新认识

Journal of cellular signaling

Pub Date : 2022-12-22 DOI: 10.33696/signaling.3.081

G. Weninger, S. Lehnart

Citation

引用

引用次数: 0

Can Mono- or Combination Therapy of Metformin with Cimetidine and Ibuprofen be a Promising Potential Therapy for Breast Cancer? 二甲双胍与西咪替丁和布洛芬单独或联合治疗乳腺癌是一种有希望的潜在治疗方法吗?

Journal of cellular signaling

Pub Date : 2022-12-22 DOI: 10.33696/signaling.3.080

S. Mostafavi, Hamidreza Zalpoor, Zuhair Mohammad Hassan

and Ibuprofen be a Promising Potential Therapy for

布洛芬是一种很有潜力的治疗方法

引用次数: 0

New Aspects in the Mechanism of Action of ALDH1A1 and 1A3 Isoforms in Carcinogenesis ALDH1A1和1A3亚型在癌变中作用机制的新进展

Journal of cellular signaling

Pub Date : 2022-09-12 DOI: 10.33696/signaling.3.078

引用次数: 0

MAGIs: Junctional Scaffolds Linking Inter-Cellular Junction Architecture, Actin Cytoskeleton Dynamics, and Signaling Pathways MAGIs:连接细胞间连接结构的连接支架，肌动蛋白细胞骨架动力学和信号通路

Journal of cellular signaling

Pub Date : 2022-08-31 DOI: 10.33696/signaling.3.076

引用次数: 0

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