International Journal of Molecular Sciences最新文献_第9页

The Role of PTEN in Chemoresistance Mediated by the HIF-1α/YY1 Axis in Pediatric Acute Lymphoblastic Leukemia PTEN 在由 HIF-1α/YY1 轴介导的小儿急性淋巴细胞白血病化疗抗药性中的作用

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-07-16 DOI: 10.3390/ijms25147767

Gabriela Antonio-Andrés, M. Morales-Martínez, E. Jiménez‐Hernández, Sara Huerta-Yepez

{"title":"The Role of PTEN in Chemoresistance Mediated by the HIF-1α/YY1 Axis in Pediatric Acute Lymphoblastic Leukemia","authors":"Gabriela Antonio-Andrés, M. Morales-Martínez, E. Jiménez‐Hernández, Sara Huerta-Yepez","doi":"10.3390/ijms25147767","DOIUrl":"https://doi.org/10.3390/ijms25147767","url":null,"abstract":"Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. Current chemotherapy treatment regimens have improved survival rates to approximately 80%; however, resistance development remains the primary cause of treatment failure, affecting around 20% of cases. Some studies indicate that loss of the phosphatase and tensin homolog (PTEN) leads to deregulation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, increasing the expression of proteins involved in chemoresistance. PTEN loss results in deregulation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and induces hypoxia-inducible factor 1-alpha (HIF-1α) expression in various cancers. Additionally, it triggers upregulation of the Yin Yang 1 (YY1) transcription factor, leading to chemoresistance mediated by glycoprotein p-170 (Gp-170). The aim of this study was to investigate the role of the PTEN/NF-κB axis in YY1 regulation via HIF-1α and its involvement in ALL. A PTEN inhibitor was administered in RS4;11 cells, followed by the evaluation of PTEN, NF-κB, HIF-1α, YY1, and Gp-170 expression, along with chemoresistance assessment. PTEN, HIF-1α, and YY1 expression levels were assessed in the peripheral blood mononuclear cells (PBMC) from pediatric ALL patients. The results reveal that the inhibition of PTEN activity significantly increases the expression of pAkt and NF-κB, which is consistent with the increase in the expression of HIF-1α and YY1 in RS4;11 cells. In turn, this inhibition increases the expression of the glycoprotein Gp-170, affecting doxorubicin accumulation in the cells treated with the inhibitor. Samples from pediatric ALL patients exhibit PTEN expression and higher HIF-1α and YY1 expression compared to controls. PTEN/Akt/NF-κB axis plays a critical role in the regulation of YY1 through HIF-1α, and this mechanism contributes to Gp-170-mediated chemoresistance in pediatric ALL.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141640359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring Mitochondrial Interactions with Pulsed Electromagnetic Fields: An Insightful Inquiry into Strategies for Addressing Neuroinflammation and Oxidative Stress in Diabetic Neuropathy 探索线粒体与脉冲电磁场的相互作用：糖尿病神经病变中神经炎症和氧化应激应对策略的深刻探索

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-07-16 DOI: 10.3390/ijms25147783

Diego Chianese, Massimo Bonora, Maria Sambataro, Luisa Sambato, Luca Dalla Paola, E. Tremoli, Ilenia Pia Cappucci, Marco Scatto, P. Pinton, Massimo Picari, L. Ferroni, B. Zavan

{"title":"Exploring Mitochondrial Interactions with Pulsed Electromagnetic Fields: An Insightful Inquiry into Strategies for Addressing Neuroinflammation and Oxidative Stress in Diabetic Neuropathy","authors":"Diego Chianese, Massimo Bonora, Maria Sambataro, Luisa Sambato, Luca Dalla Paola, E. Tremoli, Ilenia Pia Cappucci, Marco Scatto, P. Pinton, Massimo Picari, L. Ferroni, B. Zavan","doi":"10.3390/ijms25147783","DOIUrl":"https://doi.org/10.3390/ijms25147783","url":null,"abstract":"Pulsed electromagnetic fields (PEMFs) are recognized for their potential in regenerative medicine, offering a non-invasive avenue for tissue rejuvenation. While prior research has mainly focused on their effects on bone and dermo-epidermal tissues, the impact of PEMFs on nervous tissue, particularly in the context of neuropathy associated with the diabetic foot, remains relatively unexplored. Addressing this gap, our preliminary in vitro study investigates the effects of complex magnetic fields (CMFs) on glial-like cells derived from mesenchymal cell differentiation, serving as a model for neuropathy of the diabetic foot. Through assessments of cellular proliferation, hemocompatibility, mutagenicity, and mitochondrial membrane potential, we have established the safety profile of the system. Furthermore, the analysis of microRNAs (miRNAs) suggests that CMFs may exert beneficial effects on cell cycle regulation, as evidenced by the upregulation of the miRNAs within the 121, 127, and 142 families, which are known to be associated with mitochondrial function and cell cycle control. This exploration holds promise for potential applications in mitigating neuropathic complications in diabetic foot conditions.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141640538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-07-16 DOI: 10.3390/ijms25147778

Maria Ljungström, E. Oltra, Marta Pardo

{"title":"Stress-Related Chronic Fatigue Syndrome: A Case Report with a Positive Response to Alpha-Methyl-P-Tyrosine (AMPT) Treatment","authors":"Maria Ljungström, E. Oltra, Marta Pardo","doi":"10.3390/ijms25147778","DOIUrl":"https://doi.org/10.3390/ijms25147778","url":null,"abstract":"Chronic fatigue syndrome (CFS) is a heterogeneous disorder with a genetically associated vulnerability of the catecholamine metabolism (e.g., catechol O-methyltransferase polymorphisms), in which environmental factors have an important impact. Alpha-methyl-p-tyrosine (AMPT; also referred to as metyrosine) is an approved medication for the treatment of pheochromocytoma. As a tyrosine hydroxylase inhibitor, AMPT may be a potential candidate for the treatment of diseases involving catecholamine alterations. However, only small-scale clinical trials have tested AMPT repurposing in a few other illnesses. The current case report compiles genetic and longitudinal biochemical data for over a year of follow-up of a male patient sequentially diagnosed with sustained overstress, neurasthenia, CFS (diagnosed in 2012 as per the Center for Disease Control (CDC/Fukuda)), and postural orthostatic tachycardia syndrome (POTS) over a 10-year period and reports the patient’s symptom improvement in response to low–medium doses of AMPT. This case was recognized as a stress-related CFS case. Data are reported from medical records provided by the patient to allow a detailed response to treatment targeting the hyperadrenergic state presented by the patient. We highlight the lack of a positive response to classical approaches to treating CFS, reflecting the limitations of CFS diagnosis and available treatments to alleviate patients’ symptoms. The current pathomechanism hypothesis emphasizes monoamine alterations (hyperadrenergic state) in the DA/adrenergic system and a dysfunctional autonomic nervous system resulting from sympathetic overactivity. The response of the patient to AMPT treatment highlights the relevance of pacing with regard to stressful situations and increased activity. Importantly, the results do not indicate causality between AMPT and its action on the monoamine system, and future studies should evaluate the implications of other targets.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Platelet Storage—Problems, Improvements, and New Perspectives 血小板储存--问题、改进和新视角

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-07-16 DOI: 10.3390/ijms25147779

Natalia Trochanowska-Pauk, Tomasz Walski, R. Bohara, Julia Mikolas, Krystian Kubica

引用次数: 0

Adaptive and Maladaptive DNA Breaks in Neuronal Physiology and Alzheimer’s Disease 神经元生理学和阿尔茨海默病中的适应性和非适应性 DNA 断裂

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-07-16 DOI: 10.3390/ijms25147774

Anysja Roberts, Russell H. Swerdlow, Ning Wang

引用次数: 0

An Overview of Multiple Sclerosis In Vitro Models 多发性硬化症体外模型概述

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-07-16 DOI: 10.3390/ijms25147759

Joanna Czpakowska, Mateusz Kałuża, Piotr Szpakowski, Andrzej Głąbiński

引用次数: 0

The Structural Characterization of a Polysaccharide from the Dried Root of Salvia miltiorrhiza and Its Use as a Vaccine Adjuvant to Induce Humoral and Cellular Immune Responses 丹参干根多糖的结构特征及其作为疫苗佐剂诱导体液和细胞免疫反应的用途

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-07-16 DOI: 10.3390/ijms25147765

Yixuan Zhu, Xiaochen Yang, Pengfei Gu, Xiao Wang, Yongzhan Bao, Wanyu Shi

引用次数: 0

The Inflammasome Adaptor Protein ASC in Plasma as a Biomarker of Early Cognitive Changes 血浆中的炎症体适配蛋白 ASC 是早期认知变化的生物标志物

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-07-16 DOI: 10.3390/ijms25147758

Brianna Cyr, Rosie Curiel Cid, David Loewenstein, Regina T. Vontell, W. Dietrich, R. Keane, J. P. de Rivero Vaccari

{"title":"The Inflammasome Adaptor Protein ASC in Plasma as a Biomarker of Early Cognitive Changes","authors":"Brianna Cyr, Rosie Curiel Cid, David Loewenstein, Regina T. Vontell, W. Dietrich, R. Keane, J. P. de Rivero Vaccari","doi":"10.3390/ijms25147758","DOIUrl":"https://doi.org/10.3390/ijms25147758","url":null,"abstract":"Dementia is a group of symptoms including memory loss, language difficulties, and other types of cognitive and functional impairments that affects 57 million people worldwide, with the incidence expected to double by 2040. Therefore, there is an unmet need to develop reliable biomarkers to diagnose early brain impairments so that emerging interventions can be applied before brain degeneration. Here, we performed biomarker analyses for apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid-β 42/40 (Aβ42/40) ratio in the plasma of older adults. Participants had blood drawn at baseline and underwent two annual clinical and cognitive evaluations. The groups tested either cognitively normal on both evaluations (NN), cognitively normal year 1 but cognitively impaired year 2 (NI), or cognitively impaired on both evaluations (II). ASC was elevated in the plasma of the NI group compared to the NN and II groups. Additionally, Aβ42 was increased in the plasma in the NI and II groups compared to the NN group. Importantly, the area under the curve (AUC) for ASC in participants older than 70 years old in NN vs. NI groups was 0.81, indicating that ASC is a promising plasma biomarker for early detection of cognitive decline.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Di- and Triselenoesters—Promising Drug Candidates for the Future Therapy of Triple-Negative Breast Cancer 二硒酯和三硒酯--未来有望用于治疗三阴性乳腺癌的候选药物

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-07-16 DOI: 10.3390/ijms25147764

D. Radomska, R. Czarnomysy, A. Szymanowska, Dominik Radomski, Magda Chalecka, Arkadiusz Surażyński, Enrique Domínguez-Álvarez, A. Bielawska, K. Bielawski

{"title":"Di- and Triselenoesters—Promising Drug Candidates for the Future Therapy of Triple-Negative Breast Cancer","authors":"D. Radomska, R. Czarnomysy, A. Szymanowska, Dominik Radomski, Magda Chalecka, Arkadiusz Surażyński, Enrique Domínguez-Álvarez, A. Bielawska, K. Bielawski","doi":"10.3390/ijms25147764","DOIUrl":"https://doi.org/10.3390/ijms25147764","url":null,"abstract":"Breast cancer is a major malignancy among women, characterized by a high mortality rate. The available literature evidence indicates that selenium, as a trace element, has chemopreventive properties against many types of cancer; as such, compounds containing it in their structure may potentially exhibit anticancer activity. Accordingly, we have undertaken a study to evaluate the effects of novel selenoesters (EDAG-1, -7, -8, -10) on MCF-7 and MDA-MB-231 breast cancer cells. Our analysis included investigations of cell proliferation and viability as well as cytometric determinations of apoptosis/autophagy induction, changes in mitochondrial membrane polarity (ΔΨm), caspase 3/7, 8, and 9 activities, and Bax, Bcl-2, p53, Akt, AMPK, and LC3A/B proteins. The obtained data revealed that the tested derivatives are highly cytotoxic and inhibit cell proliferation even at nanomolar doses (0.41–0.79 µM). Importantly, their strong proapoptotic properties (↑ caspase 3/7) are attributable to the effects on both the extrinsic (↑ caspase 8) and intrinsic (↓ ΔΨm and Bcl-2, ↑ Bax, p53, and caspase 9) pathways of apoptosis. Moreover, the tested compounds are autophagy activators (↓ Akt, ↑ autophagosomes and autolysosomes, AMPK, LC3A/B). In summary, the potent anticancer activity suggests that the tested compounds may be promising drug candidates for future breast cancer therapy.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

From Molecular Mechanisms to Clinical Therapy: Understanding Sepsis-Induced Multiple Organ Dysfunction 从分子机制到临床治疗：了解败血症引发的多器官功能障碍

IF 4.9 2区生物学

International Journal of Molecular Sciences Pub Date : 2024-07-16 DOI: 10.3390/ijms25147770

Tijana Srdić, S. Đurašević, I. Lakić, Aleksandra Ružičić, P. Vujovic, Tanja Jevđović, T. Dakić, Jelena Đorđević, Tomislav Tosti, S. Glumac, Z. Todorović, N. Jasnić

{"title":"From Molecular Mechanisms to Clinical Therapy: Understanding Sepsis-Induced Multiple Organ Dysfunction","authors":"Tijana Srdić, S. Đurašević, I. Lakić, Aleksandra Ružičić, P. Vujovic, Tanja Jevđović, T. Dakić, Jelena Đorđević, Tomislav Tosti, S. Glumac, Z. Todorović, N. Jasnić","doi":"10.3390/ijms25147770","DOIUrl":"https://doi.org/10.3390/ijms25147770","url":null,"abstract":"Sepsis-induced multiple organ dysfunction arises from the highly complex pathophysiology encompassing the interplay of inflammation, oxidative stress, endothelial dysfunction, mitochondrial damage, cellular energy failure, and dysbiosis. Over the past decades, numerous studies have been dedicated to elucidating the underlying molecular mechanisms of sepsis in order to develop effective treatments. Current research underscores liver and cardiac dysfunction, along with acute lung and kidney injuries, as predominant causes of mortality in sepsis patients. This understanding of sepsis-induced organ failure unveils potential therapeutic targets for sepsis treatment. Various novel therapeutics, including melatonin, metformin, palmitoylethanolamide (PEA), certain herbal extracts, and gut microbiota modulators, have demonstrated efficacy in different sepsis models. In recent years, the research focus has shifted from anti-inflammatory and antioxidative agents to exploring the modulation of energy metabolism and gut microbiota in sepsis. These approaches have shown a significant impact in preventing multiple organ damage and mortality in various animal sepsis models but require further clinical investigation. The accumulation of this knowledge enriches our understanding of sepsis and is anticipated to facilitate the development of effective therapeutic strategies in the future.","PeriodicalId":49179,"journal":{"name":"International Journal of Molecular Sciences","volume":null,"pages":null},"PeriodicalIF":4.9,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0