Biomedicine & Pharmacotherapy最新文献_第5页

UHPLC-MS/MS method for the simultaneous quantification of five calcium channel antagonists’ drugs in human plasma

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-05 DOI: 10.1016/j.biopha.2025.117873

Alice Palermiti , Martina Billi , Amedeo De Nicolò , Jessica Cusato , Alessandra Manca , Miriam Antonucci , Giorgia Menegatti , Marco Pappaccogli , Lara Ponsa , Chiara Fasano , Francesco Giuseppe De Rosa , Marco Cantù , Franco Rabbia , Franco Veglio , Antonio D’Avolio

{"title":"UHPLC-MS/MS method for the simultaneous quantification of five calcium channel antagonists’ drugs in human plasma","authors":"Alice Palermiti , Martina Billi , Amedeo De Nicolò , Jessica Cusato , Alessandra Manca , Miriam Antonucci , Giorgia Menegatti , Marco Pappaccogli , Lara Ponsa , Chiara Fasano , Francesco Giuseppe De Rosa , Marco Cantù , Franco Rabbia , Franco Veglio , Antonio D’Avolio","doi":"10.1016/j.biopha.2025.117873","DOIUrl":"10.1016/j.biopha.2025.117873","url":null,"abstract":"<div><div>One of the principal challenges in managing hypertension is suboptimal medication adherence, which can result in up to 50 % of patients experiencing pseudo-resistant hypertension and inadequate blood pressure control. The intricate nature of antihypertensive regimens, the high cost of therapy, the prevalence of numerous adverse effects and the therapeutic inertia commonly lead to inconsistent drug use and premature discontinuation of treatment. Consequently, nonadherence significantly elevates the risk of cardiovascular events.</div><div>Drug concentrations in the patient's serum or urine (also known as therapeutic drug monitoring, or TDM) and blood pressure measurements following supervised medication ingestion are two techniques for assessing treatment adherence. In alignment with guideline from the Food and Drug Administration (FDA) and European Medicines Agency (EMA), this study aims to design, develop, and validate a single UHPLC method for the plasma quantification of five antihypertensive drugs within the calcium channel blocker class: amlodipine, nifedipine, barnidipine, lercanidipine and lacidipine.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117873"},"PeriodicalIF":6.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143229161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of the effect of Hashimoto's Thyroiditis on fatty acids involved in inflammation in the thyroid tissue

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-05 DOI: 10.1016/j.biopha.2025.117894

Andrzej Hellmann , Agata Zwara , Oliwia Weryszko , Monika Czapiewska , Justyna Korczynska , Alicja Sztendel , Tomasz Śledziński , Adriana Mika

{"title":"Evaluation of the effect of Hashimoto's Thyroiditis on fatty acids involved in inflammation in the thyroid tissue","authors":"Andrzej Hellmann , Agata Zwara , Oliwia Weryszko , Monika Czapiewska , Justyna Korczynska , Alicja Sztendel , Tomasz Śledziński , Adriana Mika","doi":"10.1016/j.biopha.2025.117894","DOIUrl":"10.1016/j.biopha.2025.117894","url":null,"abstract":"<div><div>Hashimoto’s thyroiditis (HT) is one of the most common autoimmune diseases associated with inflammation of the thyroid gland. Some fatty acids (FAs) are involved in inflammation. The aim of the study was to investigate how HT affects FA metabolism in thyroid tissue. We examined normal thyroid tissue from 92 patients with and without HT. We determined total FA panel, pro-inflammatory and specialized pro-resolving lipid mediators (SPMs) concentrations and measured the expression levels of genes encoding the corresponding enzymes of FA metabolism and mediator’s synthesis. In HT tissue, we observed increased total lipid levels (p < 0.05), decreased carnitine palmitoyltransferase I (p < 0.05) and increased tumor necrosis factor alpha (p < 0.001) compared to healthy tissue. Simultaneously, we observed an overexpression of enzymes responsible for the synthesis of polyunsaturated FAs and their higher levels in HT tissue. However, despite the overexpression of phospholipase A<sub>2</sub> (p < 0.001), FA translocase CD36 (p < 0.05) and higher levels of free arachidonic acid in HT tissue (p < 0.05), we observed no differences in the expression of COX-2 in both tissues and, interestingly, a downregulation of 15-LOX (p = 0.001) and lower concentrations of SPMs. Finally, the opposite effect of HT on enzymes responsible for anti-inflammatory BCFAs synthesis in mitochondria and cytosol could indicate a compensatory mechanism. To summarize, the mechanism of the effect of HT on FA metabolism is certainly complex. Thyrocytes are perturbed by the inflammatory effects associated with HT, leading to mitochondrial dysfunction and consequently decreased β-oxidation and BCFA metabolism in mitochondria. Furthermore, despite a significant synthesis of PUFAs, SPMs are also not produced.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117894"},"PeriodicalIF":6.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143229166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Innovative cyclic peptide disrupts IL-17RB–MLK4 interaction for targeted pancreatic cancer therapy

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-05 DOI: 10.1016/j.biopha.2025.117892

Chun-Mei Hu , Sui-Chih Tien , Yung-Chen Lo , Ching-Hsuan Huang , Yi-Ling Ko , Dan-Ni Wu , Jiin Horng Lee , Ying-Ta Wu , Hui-Ming Yu , Kuo-Ging Lin , Lee Zong-You , Wei-Chieh Cheng

{"title":"Innovative cyclic peptide disrupts IL-17RB–MLK4 interaction for targeted pancreatic cancer therapy","authors":"Chun-Mei Hu , Sui-Chih Tien , Yung-Chen Lo , Ching-Hsuan Huang , Yi-Ling Ko , Dan-Ni Wu , Jiin Horng Lee , Ying-Ta Wu , Hui-Ming Yu , Kuo-Ging Lin , Lee Zong-You , Wei-Chieh Cheng","doi":"10.1016/j.biopha.2025.117892","DOIUrl":"10.1016/j.biopha.2025.117892","url":null,"abstract":"<div><div>The IL-17B/IL-17RB oncogenic signaling axis promotes pancreatic cancer progression through interaction with mixed-lineage kinase 4 (MLK4). Here, we improved the effectiveness of a therapeutic peptide (TAT-IL17RB<sub>403–416</sub>, loop peptide) that disrupted IL-17RB/MLK4 interaction by converting its linear structure into a cyclic form. The modified cyclic peptide with higher uptake efficiency inhibited pancreatic cancer cell growth and metastasis, outperforming the original linear peptide both <em>in vitro</em> and in an orthotopic mouse model. At the molecular level, cysteine 408 in IL-17RB was important for mediating interactions with arginine 216 within MLK4 kinase domain. This interaction was fundamental to the efficacy of the cyclic peptide. Additionally, lysine 410 in IL-17RB was essential for maintaining the structural integrity of the cyclic peptide as a protein–protein disruptor These findings provide a deeper understanding of the IL-17RB–MLK4 interaction, offering insights for developing therapeutic agents targeting this pathway in pancreatic cancer.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117892"},"PeriodicalIF":6.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143229167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protective effects of CoQ10 and L-carnitine against antidepressant-induced mitochondrial dysfunction and teratogenicity in chicken embryos

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-04 DOI: 10.1016/j.biopha.2025.117882

Hsun-Hua Lee , Hsiang-Cheng Chi , Kent Lin , Yu-Ting Cheng , Zih-Ling Shen , Shang-Ming Huang , Chiu-Lan Hsieh

{"title":"Protective effects of CoQ10 and L-carnitine against antidepressant-induced mitochondrial dysfunction and teratogenicity in chicken embryos","authors":"Hsun-Hua Lee , Hsiang-Cheng Chi , Kent Lin , Yu-Ting Cheng , Zih-Ling Shen , Shang-Ming Huang , Chiu-Lan Hsieh","doi":"10.1016/j.biopha.2025.117882","DOIUrl":"10.1016/j.biopha.2025.117882","url":null,"abstract":"<div><div>Fluoxetine (FXT) and alprazolam (APZ), widely used for mental disorders, have poorly studied adverse effects on mitochondrial function, including oxidative phosphorylation, electron transport, and membrane permeability. This study represents the first investigation using a chick embryo model (HH-stage 10, day 1.5) to analyze the teratogenic effects of FXT and APZ and explore the protective potential of coenzyme Q10 (CoQ10) and L-carnitine (CNT). Administration of FXT (10 μM) and APZ (1 μM) resulted in high teratogenic rates of 53 % and 80 %, respectively, predominantly manifesting as lipid myopathy in hatching muscles, characterized by lipid accumulation, myofibril disruption, inflammation, and edema. Gene expression analysis revealed upregulation of acetyl-CoA carboxylase (ACC) and downregulation of carnitine palmitoyltransferase 1 (CPT1), leading to impaired lipid peroxidation and excessive reactive oxygen species (ROS) production. Markers of oxidative stress, including superoxide dismutase (SOD), hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), and nitric oxide (NO), were significantly elevated, correlating with glutathione (GSH) depletion and mitochondrial ultrastructural damage, resulting in reduced ATP production. Notably, co-administration of CoQ10 and CNT with FXT or APZ significantly improved teratogenic and mortality rates and reduced oxidative stress levels. Specifically, CoQ10 (2 μM) in the FXT group significantly reduced SOD, H<sub>2</sub>O<sub>2</sub>, and NO levels, while co-treatment with CNT and CoQ10 (2 μM) in the APZ group significantly alleviated NO levels. This pioneering study highlights the novel and crucial potential of CoQ10 and CNT as nutritional supplements to mitigate mitochondrial damage and antioxidant system imbalance caused by FXT and APZ, providing an innovative strategy for clinical application.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117882"},"PeriodicalIF":6.9,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143228935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A novel supramolecular nanodrugs for improving the cognitive function of schizophrenia by protecting active lactone of arecoline 一种保护槟榔碱活性内酯改善精神分裂症认知功能的新型超分子纳米药物。

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-01 DOI: 10.1016/j.biopha.2025.117845

Xianhua Zhang , Kaining Zhang , Kejun Liu , Shujie Yu , Xu Fu , Qianfa Yuan , Chuan'an Zhu , Duoduo Lin , Zhongxiong Fan

{"title":"A novel supramolecular nanodrugs for improving the cognitive function of schizophrenia by protecting active lactone of arecoline","authors":"Xianhua Zhang , Kaining Zhang , Kejun Liu , Shujie Yu , Xu Fu , Qianfa Yuan , Chuan'an Zhu , Duoduo Lin , Zhongxiong Fan","doi":"10.1016/j.biopha.2025.117845","DOIUrl":"10.1016/j.biopha.2025.117845","url":null,"abstract":"<div><div>Over 30 % of patients with schizophrenia experience treatment resistance and severe side effects. The limited efficacy of antipsychotic therapies poses a challenge, partly due to the blood-brain barrier (BBB) and the non-selective targeting of these drugs. Herein, we report on arecoline (ARE), a water soluble natural small molecule, which was successfully constructed a phospholipid complex by noncovalent interactions. Most striking, this arecoline-phospholipid complex nanoplatforms (ARE-PC NPs) could prevent the hydrolyzation of its ester group by carboxylesterases, which showed sustained release, superior physiological stability and long circulatory capability. Both <em>in vitro</em> cells and <em>in vivo</em> mice speculated that this ARE-PC NPs might has a high cellular uptake and stronger penetration ability of the BBB. Additionally, our results demonstrated that this phospholipid complex might facilitate ARE delivery to the brain tissue and obviously improve the schizophrenia-like behavior in cuprizone induced animal models. This study highlights ARE-PC NPs as a promising antipsychotic nanodrug for the therapy of schizophrenia.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117845"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microenvironment-responsive sodium alginate hydrogel loaded with MnO2 and pachymic acid for the treatment of gastric ulcer 微环境响应型海藻酸钠水凝胶载MnO2和厚青酸治疗胃溃疡。

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-01 DOI: 10.1016/j.biopha.2025.117835

Xin Qian , Fan Zhou , Jiawen Zheng , Yili Tao , Xiaoping Zou

{"title":"Microenvironment-responsive sodium alginate hydrogel loaded with MnO2 and pachymic acid for the treatment of gastric ulcer","authors":"Xin Qian , Fan Zhou , Jiawen Zheng , Yili Tao , Xiaoping Zou","doi":"10.1016/j.biopha.2025.117835","DOIUrl":"10.1016/j.biopha.2025.117835","url":null,"abstract":"<div><div>Gastric ulcer (GU), a common digestive system disorder in clinical practice, often arises from excessive alcohol consumption and other factors that irritate the gastric mucosa. Effective treatment of GU remains challenging due to the poor targeting, limited efficacy, and significant side effects associated with current therapeutic approaches. To address these limitations, we developed a microenvironment-responsive hydrogel composed of sodium alginate (SA) and chitosan (CS), incorporating MnO<sub>2</sub> nanoparticles and pachymic acid (PA). This hydrogel was designed to evaluate its therapeutic potential for GU treatment in both <em>in vitro</em> and <em>in vivo</em> models. The SA/CS hydrogel system rapidly formed in response to acidic gastric conditions, leveraging the microenvironment to enhance therapeutic efficacy. Encapsulated MnO<sub>2</sub> nanoparticles could scavenge reactive oxygen species (ROS), mitigating oxidative stress, while PA further alleviated oxidative damage. In vitro studies demonstrated that this hydrogel system significantly promoted the migration of gastric mucosal epithelial cells (GES-1) and reduced oxidative stress-induced damage under H<sub>2</sub>O<sub>2</sub> stimulation. Furthermore, <em>in vivo</em> evaluations using animal models of ethanol-induced acute GU and acetic acid-induced chronic GU confirmed the hydrogel’s pronounced anti-ulcer effects. These results underscore the potential of MnO<sub>2</sub>-and PA-loaded SA/CS hydrogels as a safe, targeted, and effective therapeutic strategy for ethanol-induced gastric injury. This novel approach offers a promising foundation for the development of future gastric ulcer treatments.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117835"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Activation of α7nAch receptors ameliorates α-synuclein pathology in the brain and gut of a subacute MPTP mouse model of Parkinson's disease

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-01 DOI: 10.1016/j.biopha.2025.117871

Yea-Hyun Leem , Jung-Eun Park , Jin-Sun Park , Do-Yeon Kim , Jae-Min Park , Seong-Eun Kim , Jihee Lee Kang , Hee-Sun Kim

{"title":"Activation of α7nAch receptors ameliorates α-synuclein pathology in the brain and gut of a subacute MPTP mouse model of Parkinson's disease","authors":"Yea-Hyun Leem , Jung-Eun Park , Jin-Sun Park , Do-Yeon Kim , Jae-Min Park , Seong-Eun Kim , Jihee Lee Kang , Hee-Sun Kim","doi":"10.1016/j.biopha.2025.117871","DOIUrl":"10.1016/j.biopha.2025.117871","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a neurological disorder that causes a gradual decrease in mobility. Abnormal α-synuclein (α-syn) levels and aggregation contribute to PD development. The dissemination of α-synuclein pathology via the gut-brain axis has emerged as a critical aspect in α-synucleinopathies, including PD. Recently, α7 nicotinic acetylcholine receptor (α7nAchR) agonists have been proposed as promising agents for treating PD, owing to their biological properties such as anti-inflammatory effects. This study aims to investigate whether activation of α7nAchR improves α-synuclein pathology in the brain and gut of a mouse model of PD. We found that α7nAchR agonists, GTS-21 and PNU-282987, induced behavioral recovery and improved nigrostriatal dopaminergic neurotransmission in a subacute MPTP mouse model of PD. In addition, GTS-21 and PNU-282987 facilitated α-syn clearance in the brain and distal colon, as evidenced by a considerable reduction in the accumulation of pathogenic forms of α-syn. Accordingly, GTS-21 and PNU-282987 were found to promote the AMPK-mTOR autophagy signaling pathway. Furthermore, GTS-21 and PNU-282987 exerted anti-inflammatory effects, reducing the levels of proinflammatory mediators such as inducible nitric oxide synthase, interleukin-6, and tumor necrosis factor-α in both the brain and gut. To validate the specific effects of α7nAchR agonists, subacute MPTP mice were pretreated with methyllycaconitine (MLA), a selective α7nAchR antagonist before GTS-21 administration. Pretreatment with MLA abolished the GTS-21-elicited behavioral recovery, α-syn clearance, and anti-inflammatory effects in the brain and gut. Therefore, α7nAchR activation may be a potential candidate strategy for the treatment of PD by altering α-syn aggregation in the brain and gut.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"184 ","pages":"Article 117871"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Radiopaque hydrogel-in-liposomes towards theranostic applications for malignant tumors 用于恶性肿瘤治疗的不透射线脂质体水凝胶。

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-01 DOI: 10.1016/j.biopha.2025.117822

Sang Min Lee , So-Yeol Yoo , Taejung Kim , Nahyun Kim , JungHun Kang , Ka-Young Lim , Minkyung Kim , Suwon Choo , Han Sol Lee , Hyelim Kim , Nae-Won Kang , Mansingh Chaudhary , Khadka Bikram , Wonhwa Lee , Cheong-Weon Cho , Dae-Duk Kim , Ki-Taek Kim , Jae-Young Lee

{"title":"Radiopaque hydrogel-in-liposomes towards theranostic applications for malignant tumors","authors":"Sang Min Lee , So-Yeol Yoo , Taejung Kim , Nahyun Kim , JungHun Kang , Ka-Young Lim , Minkyung Kim , Suwon Choo , Han Sol Lee , Hyelim Kim , Nae-Won Kang , Mansingh Chaudhary , Khadka Bikram , Wonhwa Lee , Cheong-Weon Cho , Dae-Duk Kim , Ki-Taek Kim , Jae-Young Lee","doi":"10.1016/j.biopha.2025.117822","DOIUrl":"10.1016/j.biopha.2025.117822","url":null,"abstract":"<div><div>A radiopaque hydrogel-in-liposome (RHL) system was developed for micro-computed tomography (μCT) imaging of tumor tissue and simultaneous delivery of a cytotoxic agent. Iopamidol (IPD) and doxorubicin (DOX) were incorporated as the CT contrast and anti-cancer agents, respectively. The presence of a polyethylene glycol hydrogel core in the liposomes was confirmed <em>via</em> attenuated total reflectance Fourier transform infrared, proton nuclear magnetic resonance, and selective solvent extraction. Nano-sized (∼160 nm) spherical DOX/IPD-loaded RHLs with a narrow size distribution and negative zeta potential were successfully fabricated. The RHLs demonstrated enhanced cellular uptake of DOX in SCCVII cells compared to conventional radiopaque liposomes, likely due to clathrin-mediated endocytosis. Additionally, pH-dependent DOX release and reduced IPD leakage were observed. <em>In vivo</em> studies using SCCVII tumor-xenografted mice showed that RHLs exhibited improved CT contrast efficiency and anti-tumor efficacy, along with systemic biocompatibility, attributed to enhanced tumor-targeting properties. These findings suggest that the RHL system could serve as a promising nano-platform for tumor theranostics.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117822"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the interplay between soluble guanylate cyclase activation and redox signalling in stroke pathophysiology and treatment 揭示可溶性鸟苷酸环化酶激活和脑卒中病理生理和治疗中的氧化还原信号之间的相互作用。

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-01 DOI: 10.1016/j.biopha.2025.117829

Alexander G. Grønning , Sebastian E. Vonhof , Mahmoud Elbatreek , Anna Hamker , Rebecca D. Szepanowski , Svenja C. Erkelenz , Friederike Langhauser , Javier Egea , Manuela G. Lopez , Jan Baumbach , Christoph Kleinschnitz , Ana I. Casas

{"title":"Unveiling the interplay between soluble guanylate cyclase activation and redox signalling in stroke pathophysiology and treatment","authors":"Alexander G. Grønning , Sebastian E. Vonhof , Mahmoud Elbatreek , Anna Hamker , Rebecca D. Szepanowski , Svenja C. Erkelenz , Friederike Langhauser , Javier Egea , Manuela G. Lopez , Jan Baumbach , Christoph Kleinschnitz , Ana I. Casas","doi":"10.1016/j.biopha.2025.117829","DOIUrl":"10.1016/j.biopha.2025.117829","url":null,"abstract":"<div><div>Soluble guanylate cyclase (sGC) stands as a pivotal regulatory element in intracellular signalling pathways, mediating the formation of cyclic guanosine monophosphate (cGMP) and impacting diverse physiological processes across tissues. Increased formation of reactive oxygen species (ROS) is widely recognized to modulate cGMP signalling. Indeed, oxidatively damaged, and therefore inactive sGC, contributes to poor vascular reactivity and more severe neurological damage upon stroke. However, the specific involvement of cGMP in redox signalling remains elusive. Here, we demonstrate a significant cGMP-dependent reduction of reactive oxygen and nitrogen species upon sGC activation under hypoxic conditions, independent of any potential scavenger effects. Importantly, this reduction is directly mediated by downregulating NADPH oxidase (NOX) 4 and 5 during reperfusion. Using an <em>in silico</em> simulation approach, we propose a mechanistic link between increased cGMP signalling and reduced ROS formation, pinpointing NF-κB1 and RELA/p65 as key transcription factors regulating NOX4/5 expression. <em>In vitro</em> studies revealed that p65 translocation to the nucleus was reduced in hypoxic human microvascular endothelial cells following sGC activation. Altogether, these findings unveil the intricate regulation and functional implications of sGC, providing valuable insights into its biological significance and ultimately therapeutic potential.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117829"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Coptisine improves LPS-induced anxiety-like behaviors by regulating the Warburg effect in microglia via PKM2 黄柏碱通过PKM2调节小胶质细胞的Warburg效应，改善脂多糖诱导的焦虑样行为。

IF 6.9 2区医学

Biomedicine & Pharmacotherapy Pub Date : 2025-02-01 DOI: 10.1016/j.biopha.2025.117837

Yiyu Qi , Xin Zhao , Weizhen Wu , Ningjing Wang , Pingyuan Ge , Siqi Guo , Shaohua Lei , Peng Zhou , Li Zhao , Zhishu Tang , Jin’ao Duan , Nianyun Yang , Rui Guo , Yinfeng Dong , Xin Chai , Qichun Zhang , Antoine M. Snijders , Huaxu Zhu

{"title":"Coptisine improves LPS-induced anxiety-like behaviors by regulating the Warburg effect in microglia via PKM2","authors":"Yiyu Qi , Xin Zhao , Weizhen Wu , Ningjing Wang , Pingyuan Ge , Siqi Guo , Shaohua Lei , Peng Zhou , Li Zhao , Zhishu Tang , Jin’ao Duan , Nianyun Yang , Rui Guo , Yinfeng Dong , Xin Chai , Qichun Zhang , Antoine M. Snijders , Huaxu Zhu","doi":"10.1016/j.biopha.2025.117837","DOIUrl":"10.1016/j.biopha.2025.117837","url":null,"abstract":"<div><div>Neuroinflammation mediated by microglia is considered the primary cause and pathological process of anxiety. Abnormal glycolysis of microglia is observed during microglia activation. However, whether regulating the Warburg effect in microglia can effectively intervene anxiety and its potential mechanisms have not been elucidated. This study focused on coptisine (Cop), a natural alkaloid that regulates the glycolysis and function of microglia affecting anxiety. The effects of Cop on anxiety-like behaviors, hippocampal synaptic function, and excessive activation of microglia were assessed in lipopolysaccharide (LPS) induced mouse models of anxiety. Microglia expressing mutant pyruvate kinase isoform M2 (PKM2) were used to further investigate the molecular mechanism by which Cop regulates the phenotype of microglia. neuroinflammatory is emerging Further research revealed that Cop attaches to the amino acid residue phenylalanine 26 of PKM2, shifting the dynamic equilibrium of PKM2 towards tetramers, and enhancing its pyruvate kinase activity. This interaction prevented LPS-induced Warburg effect and inactivated PKM2/hypoxia-inducible factor-1α (HIF-1α) pathway in microglia. In conclusion, Cop attenuates anxiety by regulating the Warburg effect in microglia. Our work revealed the role of PKM2/(HIF-1α) pathway in anxiety for the first time. Importantly, the molecular mechanism by which Cop ameliorates anxiety-like behaviors is through modulation of the dimeric/tetrameric form of PKM2, indicating the usefulness of PKM2 as a key potential target for the treatment of anxiety.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"183 ","pages":"Article 117837"},"PeriodicalIF":6.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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