Pub Date : 2025-02-01DOI: 10.1016/j.lfs.2025.123374
Anita Chopra , Nicholas Franko , Eric J. Chow
This review aims to describe the neurologic post-COVID-19 conditions (PCC, also known as “long COVID”), a complex array of diagnoses that can occur following recovery from acute COVID-19. The review also includes clinical considerations for the recognition, diagnosis and management of neurologic manifestations of PCC. Cognitive impairment (“Brain Fog”), headaches, and neuropathies are specifically reviewed.
{"title":"Navigating neurologic post-COVID-19 conditions in adults: Management strategies for cognitive dysfunction, headaches and neuropathies","authors":"Anita Chopra , Nicholas Franko , Eric J. Chow","doi":"10.1016/j.lfs.2025.123374","DOIUrl":"10.1016/j.lfs.2025.123374","url":null,"abstract":"<div><div>This review aims to describe the neurologic post-COVID-19 conditions (PCC, also known as “long COVID”), a complex array of diagnoses that can occur following recovery from acute COVID-19. The review also includes clinical considerations for the recognition, diagnosis and management of neurologic manifestations of PCC. Cognitive impairment (“Brain Fog”), headaches, and neuropathies are specifically reviewed.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123374"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142962058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.lfs.2024.123365
Hamza Malik Okuyan , Ayça Coşkun , Mehmet A. Begen
Osteoarthritis (OA) is a progressive joint disease that is a frequent reason for pain and physical dysfunction in adults, with enormous social and economic burden. Although ongoing scientific efforts in recent years have made considerable progress towards understanding of the disease's molecular mechanism, the pathogenesis of OA is still not fully known, and its clinical challenge remains. Thus, elucidating molecular events underlying the initiation and progression of OA is crucial for developing novel diagnostic and therapeutic approaches that could facilitate effective clinical management of the illness. Exosomes, extracellular vesicles containing various cellular components with approximately a diameter of 100 nm, act as essential mediators in physiological and pathological processes by modulating cell-to-cell communications. Exosomes have crucial roles in biological events such as intercellular communication, regulation of gene expression, apoptosis, inflammation, immunity, maturation and differentiation due to their inner composition, which includes nucleic acids, proteins, and lipids. We focus on the roles of exosomes in OA pathogenesis and discuss how they might be used in clinical practice for OA diagnosis and treatment. Our paper not only provides a comprehensive review of exosomes in OA but also contributes to the development efforts of diagnostic and therapeutic tools for OA.
{"title":"Current status, opportunities, and challenges of exosomes in diagnosis and treatment of osteoarthritis","authors":"Hamza Malik Okuyan , Ayça Coşkun , Mehmet A. Begen","doi":"10.1016/j.lfs.2024.123365","DOIUrl":"10.1016/j.lfs.2024.123365","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a progressive joint disease that is a frequent reason for pain and physical dysfunction in adults, with enormous social and economic burden. Although ongoing scientific efforts in recent years have made considerable progress towards understanding of the disease's molecular mechanism, the pathogenesis of OA is still not fully known, and its clinical challenge remains. Thus, elucidating molecular events underlying the initiation and progression of OA is crucial for developing novel diagnostic and therapeutic approaches that could facilitate effective clinical management of the illness. Exosomes, extracellular vesicles containing various cellular components with approximately a diameter of 100 nm, act as essential mediators in physiological and pathological processes by modulating cell-to-cell communications. Exosomes have crucial roles in biological events such as intercellular communication, regulation of gene expression, apoptosis, inflammation, immunity, maturation and differentiation due to their inner composition, which includes nucleic acids, proteins, and lipids. We focus on the roles of exosomes in OA pathogenesis and discuss how they might be used in clinical practice for OA diagnosis and treatment. Our paper not only provides a comprehensive review of exosomes in OA but also contributes to the development efforts of diagnostic and therapeutic tools for OA.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123365"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.lfs.2024.123305
Meilin Yu , Yajie Xiong , Hongyun He , Yihao Deng
Ischemic stroke is a serious cerebrovascular disease that brings a significant threat to human health. Considerable factors are involved in occurrence of cerebral ischemia. Among them, autophagy is an important intracellular process that is activated after ischemic stroke, which plays a crucial role in maintaining homeostasis and survival of neurons. The fusion of lysosomes with autophagosomes is a key step in autophagic processes. In recent decades, investigations have found that acetylation, a common post-translational modification of proteins, has an important regulatory effect on autophagy. The present article focuses on elucidating mechanism and roles of acetylation in fusion of lysosomes with autophagosomes in neurons after ischemic stroke, to seek novel targets and strategies for deeper understanding of the pathogenesis of ischemic stroke. This review is also to provide clues for clinical treatment of ischemic stroke.
{"title":"The mechanism of acetylation-mediated fusion of lysosomes with autophagosomes in neurons after ischemic stroke","authors":"Meilin Yu , Yajie Xiong , Hongyun He , Yihao Deng","doi":"10.1016/j.lfs.2024.123305","DOIUrl":"10.1016/j.lfs.2024.123305","url":null,"abstract":"<div><div>Ischemic stroke is a serious cerebrovascular disease that brings a significant threat to human health. Considerable factors are involved in occurrence of cerebral ischemia. Among them, autophagy is an important intracellular process that is activated after ischemic stroke, which plays a crucial role in maintaining homeostasis and survival of neurons. The fusion of lysosomes with autophagosomes is a key step in autophagic processes. In recent decades, investigations have found that acetylation, a common post-translational modification of proteins, has an important regulatory effect on autophagy. The present article focuses on elucidating mechanism and roles of acetylation in fusion of lysosomes with autophagosomes in neurons after ischemic stroke, to seek novel targets and strategies for deeper understanding of the pathogenesis of ischemic stroke. This review is also to provide clues for clinical treatment of ischemic stroke.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123305"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.lfs.2025.123373
Yu-Fei Wang, Cong-Ya Chen, Lan Lei, Yi Zhang
Major depressive disorder (MDD), as a multimodal neuropsychiatric and neurodegenerative illness with high prevalence and disability rates, has become a burden to world health and the economy that affects millions of individuals worldwide. Neuroinflammation, an atypical immune response occurring in the brain, is currently gaining more attention due to its association with MDD. Microglia, as immune sentinels, have a vital function in regulating neuroinflammatory reactions in the immune system of the central nervous system. From the perspective of steady-state branching states, they can transition phenotypes between two extremes, namely, M1 and M2 phenotypes are pro-inflammatory and anti-inflammatory, respectively. It has an intermediate transition state characterized by different transcriptional features and the release of inflammatory mediators. The timing regulation of inflammatory cytokine release is crucial for damage control and guiding microglia back to a steady state. The dysregulation can lead to exorbitant tissue injury and neuronal mortality, and targeting the cellular signaling pathway that serves as the regulatory basis for microglia is considered an essential pathway for treating MDD. However, the specific intervention targets and mechanisms of microglial activation pathways in neuroinflammation are still unclear. Therefore, the present review summarized and discussed various signaling pathways and effective intervention targets that trigger the activation of microglia from its branching state and emphasizes the mechanism of microglia-mediated neuroinflammation associated with MDD.
{"title":"Regulation of the microglial polarization for alleviating neuroinflammation in the pathogenesis and therapeutics of major depressive disorder","authors":"Yu-Fei Wang, Cong-Ya Chen, Lan Lei, Yi Zhang","doi":"10.1016/j.lfs.2025.123373","DOIUrl":"10.1016/j.lfs.2025.123373","url":null,"abstract":"<div><div>Major depressive disorder (MDD), as a multimodal neuropsychiatric and neurodegenerative illness with high prevalence and disability rates, has become a burden to world health and the economy that affects millions of individuals worldwide. Neuroinflammation, an atypical immune response occurring in the brain, is currently gaining more attention due to its association with MDD. Microglia, as immune sentinels, have a vital function in regulating neuroinflammatory reactions in the immune system of the central nervous system. From the perspective of steady-state branching states, they can transition phenotypes between two extremes, namely, M1 and M2 phenotypes are pro-inflammatory and anti-inflammatory, respectively. It has an intermediate transition state characterized by different transcriptional features and the release of inflammatory mediators. The timing regulation of inflammatory cytokine release is crucial for damage control and guiding microglia back to a steady state. The dysregulation can lead to exorbitant tissue injury and neuronal mortality, and targeting the cellular signaling pathway that serves as the regulatory basis for microglia is considered an essential pathway for treating MDD. However, the specific intervention targets and mechanisms of microglial activation pathways in neuroinflammation are still unclear. Therefore, the present review summarized and discussed various signaling pathways and effective intervention targets that trigger the activation of microglia from its branching state and emphasizes the mechanism of microglia-mediated neuroinflammation associated with MDD.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123373"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932348","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.lfs.2025.123380
Xinghua Qin , Haoyu Gong , Lingyan Jin , Yixin Wang , Kai Dang , Hui Li , Qiangsun Zheng
Aims
Glucosamine, a widely used dietary supplement, has been linked to potential cardiovascular risks, including atrial fibrillation (AF). This study aimed to investigate the effects of long-term glucosamine supplementation on AF susceptibility and the underlying mechanisms.
Materials and methods
C57BL/6 J mice were treated with low-dose (15 mg/kg/day) or high-dose (250 mg/kg/day) glucosamine via drinking water for 6 weeks. AF susceptibility was assessed through transesophageal electrical stimulation. Atrial remodeling was characterized through electrophysiological and echocardiography studies, histological analysis, and molecular examination. AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) was used to validation the underlying mechanism in mice and isolated neonatal atrial cardiomyocytes.
Key findings
Long-term high-dose glucosamine supplementation increased AF susceptibility in mice, as indicated by an elevated AF incidence and duration. Glucosamine induced notable electrical remodeling, evidenced by intra-atrial conduction slowing (P wave duration, amplitude, and area), likely attributable to reduced conduction velocity, as confirmed by two-dimensional electrical mapping. Structural remodeling including increased left atrial weight, cardiomyocyte hypertrophy and fibrosis was evident in the atria of glucosamine-treated mice, despite unaffected cardiac function. Mechanistically, glucosamine suppressed atrial AMPK signaling, leading to lipid and glycogen accumulation. Intriguingly, despite impaired atrial AMPK signaling, high-dose glucosamine improved systemic insulin sensitivity. Pharmacological activation of AMPK with AICAR mitigated glucosamine-induced AF susceptibility and associated pathological changes both in vivo and in vitro.
Significance
Our findings demonstrate that long-term glucosamine supplementation enhances AF susceptibility, potentially by impairing atrial AMPK signaling, underscoring the importance of caution in the utilization of glucosamine.
{"title":"Long-term glucosamine supplementation aggravates atrial fibrillation susceptibility by impairing AMPK signaling","authors":"Xinghua Qin , Haoyu Gong , Lingyan Jin , Yixin Wang , Kai Dang , Hui Li , Qiangsun Zheng","doi":"10.1016/j.lfs.2025.123380","DOIUrl":"10.1016/j.lfs.2025.123380","url":null,"abstract":"<div><h3>Aims</h3><div>Glucosamine, a widely used dietary supplement, has been linked to potential cardiovascular risks, including atrial fibrillation (AF). This study aimed to investigate the effects of long-term glucosamine supplementation on AF susceptibility and the underlying mechanisms.</div></div><div><h3>Materials and methods</h3><div>C57BL/6 J mice were treated with low-dose (15 mg/kg/day) or high-dose (250 mg/kg/day) glucosamine via drinking water for 6 weeks. AF susceptibility was assessed through transesophageal electrical stimulation. Atrial remodeling was characterized through electrophysiological and echocardiography studies, histological analysis, and molecular examination. AMP-activated protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) was used to validation the underlying mechanism in mice and isolated neonatal atrial cardiomyocytes.</div></div><div><h3>Key findings</h3><div>Long-term high-dose glucosamine supplementation increased AF susceptibility in mice, as indicated by an elevated AF incidence and duration. Glucosamine induced notable electrical remodeling, evidenced by intra-atrial conduction slowing (P wave duration, amplitude, and area), likely attributable to reduced conduction velocity, as confirmed by two-dimensional electrical mapping. Structural remodeling including increased left atrial weight, cardiomyocyte hypertrophy and fibrosis was evident in the atria of glucosamine-treated mice, despite unaffected cardiac function. Mechanistically, glucosamine suppressed atrial AMPK signaling, leading to lipid and glycogen accumulation. Intriguingly, despite impaired atrial AMPK signaling, high-dose glucosamine improved systemic insulin sensitivity. Pharmacological activation of AMPK with AICAR mitigated glucosamine-induced AF susceptibility and associated pathological changes both in vivo and in vitro.</div></div><div><h3>Significance</h3><div>Our findings demonstrate that long-term glucosamine supplementation enhances AF susceptibility, potentially by impairing atrial AMPK signaling, underscoring the importance of caution in the utilization of glucosamine.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123380"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-31DOI: 10.1016/j.lfs.2025.123438
Lu Zhang , Jean Marie Wernet , Andreas Rothgangel , Susy Braun , Darcy Ummels , Emmylou Beekman , Tanja de Jong-van Luxzenburg , Martijn D. de Kruif , Wei Yang , Lieke Lamont , Alida Kindt , Thomas Hankemeier , Amy Harms , Herman van Wietmarschen
Aims
This study aimed to elucidate clinically-relevant classifications of COPD using a targeted metabolomics approach focusing on signaling lipids.
Materials and methods
Using a targeted LC-MS/MS platform, 166 metabolites including free fatty acids, prostaglandins, isoprostanes, lysophospholipids, endocannabinoids, and bile acids were profiled in a cohort of 49 COPD patients. The study integrated metabolomic data with clinical parameters to identify key metabolites and related pathways for various COPD classification systems including Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading stages, Koninklijk Nederlands Genootschap voor Fysiotherapie (KNGF, Royal Dutch Society for Physiotherapy) profiles, and Systemic (SYS) subtypes and explored the association of these classification systems.
Key findings
The GOLD stages showed correlations with 15 metabolites, including lysophospholipids, oxylipins, and bile acids. KNGF profiles were linked to 13 metabolites, predominantly lysophospholipids, while SYS subtypes were associated with 9 metabolites, mainly oxylipins. A specific cluster of oxylipins, including HETEs and HDoHEs, was notably correlated to prognostic factors of COPD.
Significance
This study identified distinct metabolic patterns associated with GOLD stages, KNGF profiles, and SYS subtypes. Additionally, the findings indicate that 14-HDoHE/DHA may serve as a potential biomarker for COPD exacerbation and suggest possible therapeutic targets for COPD, including pathways involving lipoxygenases, G-protein coupled receptors, and the Farnesoid X receptor.
{"title":"Characterizing COPD phenotypes with a targeted signaling lipids metabolomics approach","authors":"Lu Zhang , Jean Marie Wernet , Andreas Rothgangel , Susy Braun , Darcy Ummels , Emmylou Beekman , Tanja de Jong-van Luxzenburg , Martijn D. de Kruif , Wei Yang , Lieke Lamont , Alida Kindt , Thomas Hankemeier , Amy Harms , Herman van Wietmarschen","doi":"10.1016/j.lfs.2025.123438","DOIUrl":"10.1016/j.lfs.2025.123438","url":null,"abstract":"<div><h3>Aims</h3><div>This study aimed to elucidate clinically-relevant classifications of COPD using a targeted metabolomics approach focusing on signaling lipids.</div></div><div><h3>Materials and methods</h3><div>Using a targeted LC-MS/MS platform, 166 metabolites including free fatty acids, prostaglandins, isoprostanes, lysophospholipids, endocannabinoids, and bile acids were profiled in a cohort of 49 COPD patients. The study integrated metabolomic data with clinical parameters to identify key metabolites and related pathways for various COPD classification systems including Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading stages, Koninklijk Nederlands Genootschap voor Fysiotherapie (KNGF, Royal Dutch Society for Physiotherapy) profiles, and Systemic (SYS) subtypes and explored the association of these classification systems.</div></div><div><h3>Key findings</h3><div>The GOLD stages showed correlations with 15 metabolites, including lysophospholipids, oxylipins, and bile acids. KNGF profiles were linked to 13 metabolites, predominantly lysophospholipids, while SYS subtypes were associated with 9 metabolites, mainly oxylipins. A specific cluster of oxylipins, including HETEs and HDoHEs, was notably correlated to prognostic factors of COPD.</div></div><div><h3>Significance</h3><div>This study identified distinct metabolic patterns associated with GOLD stages, KNGF profiles, and SYS subtypes. Additionally, the findings indicate that 14-HDoHE/DHA may serve as a potential biomarker for COPD exacerbation and suggest possible therapeutic targets for COPD, including pathways involving lipoxygenases, G-protein coupled receptors, and the Farnesoid X receptor.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"364 ","pages":"Article 123438"},"PeriodicalIF":5.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080577","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}
Pub Date : 2025-01-31DOI: 10.1016/j.lfs.2025.123414
Manar M. Esmail , Noha M. Saeed , Diana M.F. Hanna , Haidy E. Michel , Reem N. El-Naga , Samar S. Azab
{"title":"Corrigendum on “Hepatoprotective and neuroprotective effects of quinacrine against bile duct ligation-induced hepatic encephalopathy in rats: Role of bone morphogenetic proteins signaling” [Life Sci. 359 (2024) 123229]","authors":"Manar M. Esmail , Noha M. Saeed , Diana M.F. Hanna , Haidy E. Michel , Reem N. El-Naga , Samar S. Azab","doi":"10.1016/j.lfs.2025.123414","DOIUrl":"10.1016/j.lfs.2025.123414","url":null,"abstract":"","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"364 ","pages":"Article 123414"},"PeriodicalIF":5.2,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-30DOI: 10.1016/j.lfs.2025.123427
Miriam Toffoli , Giuseppina Campisciano , Aurora Santin , Silvia Pegoraro , Gabriella Zito , Beatrice Spedicati , Andrea Balduit , Federico Romano , Giovanni Di Lorenzo , Alessandro Mangogna , Paola Tesolin , Giuseppe Giovanni Nardone , Nunzia Zanotta , Serena Sanna , Francesca Crobu , Uday Kishore , Giuseppe Ricci , Roberta Bulla , Giorgia Girotto , Chiara Agostinis
Aims
Endometriosis (EM) is a chronic inflammatory disorder with multifactorial etiologies (i.e., genetics and environmental factors, hormonal and immunological changes, and microbiome alterations). The complement system is one of the most frequently dysregulated pathways in EM. Mannose-binding lectin (MBL), a carbohydrate pattern recognition molecule, is the first described recognition subcomponent of the complement lectin pathway (LP). Here, we unveiled the interplay among MBL polymorphisms, plasma levels, LP functionality, and microbiota as potential contributors to EM pathogenesis.
Materials and methods
A cohort of 38 EM patients and 20 healthy controls was enrolled, and the levels and functionality of the LP were assessed via ELISA. MBL genetic variants and the endometrial and vaginal microbiome were investigated and correlated.
Key findings
High MBL levels were related to the disease severity, although not accountable for the MBL2 genotype. MBL and MASP-2 were present in the uterine mucosa but appeared to have no activity at the endometriotic lesion. EM patients with LP functional deficit displayed pathogenic bacterial species more frequently in the endometrial microbiome. Moreover, women affected by EM showed a higher frequency of rare gene variants in the estrogen pathway genes, potentially affecting MBL plasma levels.
Significance
A lower functionality of LP in the uterine mucosa may contribute to an unbalanced bacterial environment that could activate endometrial cells. Not only the genotype and the inflammatory condition, but also the estrogen pathway can cause altered MBL levels, thus contributing to changes in the LP functionality.
{"title":"A possible association between low MBL/lectin pathway functionality and microbiota dysbiosis in endometriosis patients","authors":"Miriam Toffoli , Giuseppina Campisciano , Aurora Santin , Silvia Pegoraro , Gabriella Zito , Beatrice Spedicati , Andrea Balduit , Federico Romano , Giovanni Di Lorenzo , Alessandro Mangogna , Paola Tesolin , Giuseppe Giovanni Nardone , Nunzia Zanotta , Serena Sanna , Francesca Crobu , Uday Kishore , Giuseppe Ricci , Roberta Bulla , Giorgia Girotto , Chiara Agostinis","doi":"10.1016/j.lfs.2025.123427","DOIUrl":"10.1016/j.lfs.2025.123427","url":null,"abstract":"<div><h3>Aims</h3><div>Endometriosis (EM) is a chronic inflammatory disorder with multifactorial etiologies (<em>i.e.</em>, genetics and environmental factors, hormonal and immunological changes, and microbiome alterations). The complement system is one of the most frequently dysregulated pathways in EM. Mannose-binding lectin (MBL), a carbohydrate pattern recognition molecule, is the first described recognition subcomponent of the complement lectin pathway (LP). Here, we unveiled the interplay among MBL polymorphisms, plasma levels, LP functionality, and microbiota as potential contributors to EM pathogenesis.</div></div><div><h3>Materials and methods</h3><div>A cohort of 38 EM patients and 20 healthy controls was enrolled, and the levels and functionality of the LP were assessed <em>via</em> ELISA. MBL genetic variants and the endometrial and vaginal microbiome were investigated and correlated.</div></div><div><h3>Key findings</h3><div>High MBL levels were related to the disease severity, although not accountable for the <em>MBL2</em> genotype. MBL and MASP-2 were present in the uterine mucosa but appeared to have no activity at the endometriotic lesion. EM patients with LP functional deficit displayed pathogenic bacterial species more frequently in the endometrial microbiome. Moreover, women affected by EM showed a higher frequency of rare gene variants in the estrogen pathway genes, potentially affecting MBL plasma levels.</div></div><div><h3>Significance</h3><div>A lower functionality of LP in the uterine mucosa may contribute to an unbalanced bacterial environment that could activate endometrial cells. Not only the genotype and the inflammatory condition, but also the estrogen pathway can cause altered MBL levels, thus contributing to changes in the LP functionality.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"364 ","pages":"Article 123427"},"PeriodicalIF":5.2,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143075009","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}
Pub Date : 2025-01-30DOI: 10.1016/j.lfs.2025.123435
Marina Reva , Maria Mendes , João José Sousa , Alberto Pais , Carla Vitorino
This review delves into boron neutron capture therapy (BNCT), a targeted alpha-particle radiotherapy that holds promise in oncology and has the potential to address concerns of efficacy and safety associated to conventional cancer therapies. Information was gathered from literature searches that used the keywords “boron neutron capture therapy,” “clinical application,” “nanotechnology,” and “liposome” so as to analyze the clinical applications of BNCT in cancer over time. The methodology includes a thorough literature review, analysis of preclinical studies, and clinical trials to assess the viability of BNCT in treating glioblastoma (GB), as an example of a hard-to-treat cancer type.
Firstly, the fundamental principles of BNCT are outlined, followed by an extensive exploration of the respective application in oncology, particularly emphasizing its synergy with nanotechnology advancements. A key focus is placed on evaluating whether third-generation nanoparticles show superior efficacy compared to conventional boron-delivering systems used in BNCT. Additionally, attention is drawn to the critical analysis of safety concerns surrounding nanotechnology, which are crucial for clinical translation. Noteworthy is the clinical application of liposomes (LPs) in GB, highlighting their potential and limitations in clinical settings.
Overall, the collected evidence sheds light on the high potential of BNCT in the research and development of new treatment (and diagnosis) modalities for GB and other cancer types.
{"title":"boron neutron capture therapy for glioblastoma: The delivery dilemma","authors":"Marina Reva , Maria Mendes , João José Sousa , Alberto Pais , Carla Vitorino","doi":"10.1016/j.lfs.2025.123435","DOIUrl":"10.1016/j.lfs.2025.123435","url":null,"abstract":"<div><div>This review delves into boron neutron capture therapy (BNCT), a targeted alpha-particle radiotherapy that holds promise in oncology and has the potential to address concerns of efficacy and safety associated to conventional cancer therapies. Information was gathered from literature searches that used the keywords “boron neutron capture therapy,” “clinical application,” “nanotechnology,” and “liposome” so as to analyze the clinical applications of BNCT in cancer over time. The methodology includes a thorough literature review, analysis of preclinical studies, and clinical trials to assess the viability of BNCT in treating glioblastoma (GB), as an example of a hard-to-treat cancer type.</div><div>Firstly, the fundamental principles of BNCT are outlined, followed by an extensive exploration of the respective application in oncology, particularly emphasizing its synergy with nanotechnology advancements. A key focus is placed on evaluating whether third-generation nanoparticles show superior efficacy compared to conventional boron-delivering systems used in BNCT. Additionally, attention is drawn to the critical analysis of safety concerns surrounding nanotechnology, which are crucial for clinical translation. Noteworthy is the clinical application of liposomes (LPs) in GB, highlighting their potential and limitations in clinical settings.</div><div>Overall, the collected evidence sheds light on the high potential of BNCT in the research and development of new treatment (and diagnosis) modalities for GB and other cancer types.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"364 ","pages":"Article 123435"},"PeriodicalIF":5.2,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074926","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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