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Stress hyperglycemia in acute pancreatitis: From mechanisms to prognostic implications

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-02-15 DOI: 10.1016/j.lfs.2025.123469

Yuting Guan , Guoqing Liu , Feimin Tang , Xiangmin Wu , Jian Shi , Qiongguang Huang

Acute pancreatitis (AP) is an inflammatory reaction of the pancreas. When the disease is severe, it is often accompanied by destruction of the pancreatic islets, resulting in dysfunction of the endocrine system of the pancreas. Stress hyperglycemia is a transient increase in glucose during a critical illness, and its possible mechanism is related to abnormal glucose metabolism and insulin resistance due to the increased release of counterregulatory hormones and cytokines, such as glucagon, cortisol, and catecholamines. Numerous studies have shown that stress hyperglycemia is strongly associated with morbidity, mortality, and increased risk of post-acute pancreatitis diabetes in AP patients. Therefore, stress hyperglycemia may be a significant independent risk factor for poor clinical outcomes and prognosis in patients with AP. This article reviews the clinical features, risk factors, and mechanisms of action of stress hyperglycemia in AP and its influence on adverse clinical outcomes and the prognosis of inpatients with AP. For AP patients with stress hyperglycemia, it is necessary to comprehensively consider their blood glucose levels, daily habits, and complications to develop an appropriate treatment plan for hyperglycemia. Limited evidence indicates that in the case of acute hyperglycemia in critically ill patients, especially during the first 3 days of hospitalization, insulin therapy should not be undertaken if the blood glucose level does not exceed 10 mmol/L. However, some important questions related to clinical practice remain to be answered. More clinical trials and studies are needed in the future to provide a sufficient basis for clinical practice.

{"title":"Stress hyperglycemia in acute pancreatitis: From mechanisms to prognostic implications","authors":"Yuting Guan , Guoqing Liu , Feimin Tang , Xiangmin Wu , Jian Shi , Qiongguang Huang","doi":"10.1016/j.lfs.2025.123469","DOIUrl":"10.1016/j.lfs.2025.123469","url":null,"abstract":"<div><div>Acute pancreatitis (AP) is an inflammatory reaction of the pancreas. When the disease is severe, it is often accompanied by destruction of the pancreatic islets, resulting in dysfunction of the endocrine system of the pancreas. Stress hyperglycemia is a transient increase in glucose during a critical illness, and its possible mechanism is related to abnormal glucose metabolism and insulin resistance due to the increased release of counterregulatory hormones and cytokines, such as glucagon, cortisol, and catecholamines. Numerous studies have shown that stress hyperglycemia is strongly associated with morbidity, mortality, and increased risk of post-acute pancreatitis diabetes in AP patients. Therefore, stress hyperglycemia may be a significant independent risk factor for poor clinical outcomes and prognosis in patients with AP. This article reviews the clinical features, risk factors, and mechanisms of action of stress hyperglycemia in AP and its influence on adverse clinical outcomes and the prognosis of inpatients with AP. For AP patients with stress hyperglycemia, it is necessary to comprehensively consider their blood glucose levels, daily habits, and complications to develop an appropriate treatment plan for hyperglycemia. Limited evidence indicates that in the case of acute hyperglycemia in critically ill patients, especially during the first 3 days of hospitalization, insulin therapy should not be undertaken if the blood glucose level does not exceed 10 mmol/L. However, some important questions related to clinical practice remain to be answered. More clinical trials and studies are needed in the future to provide a sufficient basis for clinical practice.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"365 ","pages":"Article 123469"},"PeriodicalIF":5.2,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420386","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}

引用次数: 0

Intercellular communication via exosomes: A new paradigm in the pathophysiology of neurodegenerative disorders

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-02-13 DOI: 10.1016/j.lfs.2025.123468

Kiran S. Satao, Gaurav M. Doshi

Neurodegenerative disorders are one of the leading causes of death and disability and pose a great economic burden on healthcare systems. Generally, these neurodegenerative disorders have a progressive deterioration in neural function and structure, and deposition of misfolded proteins commonly occurs, such as amyloid-β in AD and α-synuclein in PD. However, there exists a special class of exosomes, which acts like a transmitter and enhances communication between cells. The present review discusses the significant role of exosomes in neurodegenerative diseases, with a focus on Amyotrophic lateral Sclerosis (ALS), AD, PD, and Huntington's disease (HD). In this review, the biogenesis of exosomes is discussed from multivesicular bodies and onwards to their release into the extracellular environment. The present review focuses on recent data concerning the possible use of modified exosomes as ND therapy. Indeed, future work is needed to explain the processes driving exosome biogenesis and cargo selection, while opening new routes by the use of exosome-based therapeutics in neurodegenerative disease diagnosis and treatment.

{"title":"Intercellular communication via exosomes: A new paradigm in the pathophysiology of neurodegenerative disorders","authors":"Kiran S. Satao, Gaurav M. Doshi","doi":"10.1016/j.lfs.2025.123468","DOIUrl":"10.1016/j.lfs.2025.123468","url":null,"abstract":"<div><div>Neurodegenerative disorders are one of the leading causes of death and disability and pose a great economic burden on healthcare systems. Generally, these neurodegenerative disorders have a progressive deterioration in neural function and structure, and deposition of misfolded proteins commonly occurs, such as amyloid-β in AD and α-synuclein in PD. However, there exists a special class of exosomes, which acts like a transmitter and enhances communication between cells. The present review discusses the significant role of exosomes in neurodegenerative diseases, with a focus on Amyotrophic lateral Sclerosis (ALS), AD, PD, and Huntington's disease (HD). In this review, the biogenesis of exosomes is discussed from multivesicular bodies and onwards to their release into the extracellular environment. The present review focuses on recent data concerning the possible use of modified exosomes as ND therapy. Indeed, future work is needed to explain the processes driving exosome biogenesis and cargo selection, while opening new routes by the use of exosome-based therapeutics in neurodegenerative disease diagnosis and treatment.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"365 ","pages":"Article 123468"},"PeriodicalIF":5.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143420462","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}

引用次数: 0

Neuronal calcium sensor 1: A key factor in the development of diseases.

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-02-11 DOI: 10.1016/j.lfs.2025.123461

Duo Liu, Lingzhi Wang, Zhen Huang, Linxi Chen

Neuronal calcium sensor 1 (NCS1) belongs to the family of neuronal calcium sensing proteins, which are distributed in various tissues of the human body, mainly in nerve tissues. NCS1 has multiple functions, including participating in the transduction of intracellular calcium signals, neuronal morphology, development and exocytosis. NCS1 performs related functions by interacting with a variety of proteins, including inositol 1,4,5-trisphosphate receptors (InsP3Rs), voltage-gated K+ and Ca²⁺ channels, phosphatidylinositol 4-kinase IIIβ (PI (4) KIIIβ). Over the years, researches on NCS1 and diseases have mostly focused on the nervous system and cardiovascular system, it is found that the abnormal expression of NCS1 is also related to cancer. Starting from the structure of NCS1 and the proteins that interact with it, this review expounds the mechanism or potential mechanism of NCS1 imbalance leading to various diseases.

引用次数: 0

Oral microbiota in colorectal cancer: Unraveling mechanisms and application potential

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-02-11 DOI: 10.1016/j.lfs.2025.123462

Xinran Zhang , Yixin Chen , Yuwei Xia , Shenghao Lin , Xinlei Zhou , Xi Pang , Jieru Yu , Leitao Sun

Colorectal cancer (CRC), with a rising prevalence, is the third most commonly diagnosed cancer and the third leading cause of cancer-related death. Studies have shown that a complex interplay between the development of CRC and alterations in the oral microbiome. Recent advancements in genomics and metagenomics have highlighted the significant roles of certain oral microbes, particularly Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum), in the progression of CRC. However, the detailed mechanisms by which the oral microbiota influence CRC development remain unclear. This review aims to elucidate the role of oral microbiota in CRC progression, evaluate their potential as biomarkers, and explore therapeutic strategies targeting these microbes. This review offers insights into the mechanisms underlying the interaction between oral microbiota and CRC, underscoring the potential of oral microbes as diagnostic and prognostic biomarkers, as well as therapeutic targets. Future research should focus on clarifying the exact pathways and developing innovative therapeutic strategies to enhance the diagnosis and treatment.

{"title":"Oral microbiota in colorectal cancer: Unraveling mechanisms and application potential","authors":"Xinran Zhang , Yixin Chen , Yuwei Xia , Shenghao Lin , Xinlei Zhou , Xi Pang , Jieru Yu , Leitao Sun","doi":"10.1016/j.lfs.2025.123462","DOIUrl":"10.1016/j.lfs.2025.123462","url":null,"abstract":"<div><div>Colorectal cancer (CRC), with a rising prevalence, is the third most commonly diagnosed cancer and the third leading cause of cancer-related death. Studies have shown that a complex interplay between the development of CRC and alterations in the oral microbiome. Recent advancements in genomics and metagenomics have highlighted the significant roles of certain oral microbes, particularly <em>Porphyromonas gingivalis (P. gingivalis</em>) and <em>Fusobacterium nucleatum</em> (<em>F. nucleatum</em>), in the progression of CRC. However, the detailed mechanisms by which the oral microbiota influence CRC development remain unclear. This review aims to elucidate the role of oral microbiota in CRC progression, evaluate their potential as biomarkers, and explore therapeutic strategies targeting these microbes. This review offers insights into the mechanisms underlying the interaction between oral microbiota and CRC, underscoring the potential of oral microbes as diagnostic and prognostic biomarkers, as well as therapeutic targets. Future research should focus on clarifying the exact pathways and developing innovative therapeutic strategies to enhance the diagnosis and treatment.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"365 ","pages":"Article 123462"},"PeriodicalIF":5.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143403272","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}

引用次数: 0

Effects of high levels of androgens on oocyte maturation and potential regulatory role of retinoic acid

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-02-11 DOI: 10.1016/j.lfs.2025.123463

Yongfeng Zhou , Qi Zhang , Ran Ding, Xinyuan Fan, Qi Li, Ziyi Li

Aims

Polycystic ovary syndrome (PCOS) is a prevalent condition among women, characterized by hyperandrogenism. This study aims to investigate the underlying mechanisms by which testosterone impact oocyte maturation and potential methods for addressing this condition.

Materials and methods

Testosterone propionate (TP) was incorporated into the oocyte maturation medium to simulate the typical hyperandrogenic environment associated with PCOS, facilitating an investigation the effect of hyperandrogen on oocyte maturation in vitro. The gene expression profiles of porcine cumulus-oocyte complexes (COCs) during in vitro maturation (IVM) following TP treatment were analyzed using RNA-seq.

Key findings

TP downregulated two genes, TNFAIP6 and EREG, associated with follicular development process. Additionally, GSEA analysis indicated that TP upregulated the retinol metabolism gene set. Both TP and retinoic acid (RA) were added to the oocyte maturation medium. Subsequently, we evaluated the molecular characteristics of COCs in various treatment groups and assessed the blastocyst formation rate following parthenogenetic activation of COCs. The results indicated that RA effectively reversed TP-induced meiotic repression by downregulating the elevated expression level of WEE2 in TP-treated oocytes. However, RA exhibited distinct effects on TP-induced alterations in gene expression, including EREG and TNFAIP6, at different stages.

Significance

RA could mitigate the adverse effects of hyperandrogenism on oocytes during maturation. Moreover, RA and testosterone exert a dual regulatory effect on extracellular matrix remodeling in cumulus cells. These findings suggest the potential therapeutic application of RA in androgen-induced PCOS.

{"title":"Effects of high levels of androgens on oocyte maturation and potential regulatory role of retinoic acid","authors":"Yongfeng Zhou , Qi Zhang , Ran Ding, Xinyuan Fan, Qi Li, Ziyi Li","doi":"10.1016/j.lfs.2025.123463","DOIUrl":"10.1016/j.lfs.2025.123463","url":null,"abstract":"<div><h3>Aims</h3><div>Polycystic ovary syndrome (PCOS) is a prevalent condition among women, characterized by hyperandrogenism. This study aims to investigate the underlying mechanisms by which testosterone impact oocyte maturation and potential methods for addressing this condition.</div></div><div><h3>Materials and methods</h3><div>Testosterone propionate (TP) was incorporated into the oocyte maturation medium to simulate the typical hyperandrogenic environment associated with PCOS, facilitating an investigation the effect of hyperandrogen on oocyte maturation <em>in vitro</em>. The gene expression profiles of porcine cumulus-oocyte complexes (COCs) during <em>in vitro</em> maturation (IVM) following TP treatment were analyzed using RNA-seq.</div></div><div><h3>Key findings</h3><div>TP downregulated two genes, TNFAIP6 and EREG, associated with follicular development process. Additionally, GSEA analysis indicated that TP upregulated the retinol metabolism gene set. Both TP and retinoic acid (RA) were added to the oocyte maturation medium. Subsequently, we evaluated the molecular characteristics of COCs in various treatment groups and assessed the blastocyst formation rate following parthenogenetic activation of COCs. The results indicated that RA effectively reversed TP-induced meiotic repression by downregulating the elevated expression level of WEE2 in TP-treated oocytes. However, RA exhibited distinct effects on TP-induced alterations in gene expression, including EREG and TNFAIP6, at different stages.</div></div><div><h3>Significance</h3><div>RA could mitigate the adverse effects of hyperandrogenism on oocytes during maturation. Moreover, RA and testosterone exert a dual regulatory effect on extracellular matrix remodeling in cumulus cells. These findings suggest the potential therapeutic application of RA in androgen-induced PCOS.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"365 ","pages":"Article 123463"},"PeriodicalIF":5.2,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143386736","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}

引用次数: 0

Peptide-driven strategies against lung cancer.

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-02-07 DOI: 10.1016/j.lfs.2025.123453

Vijayshree S Karankar, Saurabh Awasthi, Nidhi Srivastava

Lung cancer remains one of the most significant global health challenges, responsible for 18 % of all cancer-related deaths. While risk factors such as heavy metal exposure and cigarette smoking are well-known contributors, the limitations of conventional treatments including severe side effects and drug resistance highlight the urgent need for more targeted and safer therapeutic options. In this context, peptides emerge as a novel, precise, and effective class of therapies for lung cancer treatment. Peptides have shown promise in limiting lung cancer progression by targeting key molecular pathways involved in tumour growth. Anti-non-small cell lung cancer peptides that specifically target proteins like EGFR, TP53, BRAF, MET, ROS1, and ALK have demonstrated potential in improving lung cancer outcomes. Additionally, anti-inflammatory and apoptosis-inducing peptides offer further therapeutic benefits. This review provides a comprehensive overview of the peptides currently in use or under investigation for the treatment of lung cancer, highlighting their mechanisms of action and therapeutic potential. As evidence continues to accumulate, peptides are poised to become a promising new therapeutic option in the fight against lung cancer.

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引用次数: 0

DLGAP5 upregulates E2F1 to promote prostate adenocarcinoma neuroendocrine differentiation

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-02-07 DOI: 10.1016/j.lfs.2025.123442

Linghui Liang , Zhiyi Shen , Kaiyu Zhang , Chenglong Zhang , Lai Dong , Rongjie Shi , Lixin Hua , Ruizhe Zhao , Ninghan Feng

Aims

DLGAP5 plays a significant role in promoting cancer progression across various cancers. However, the specific role of DLGAP5 in neuroendocrine differentiation (NED) of prostate cancer (PCa) remains elusive. Our objective is to explore the mechanism by which DLGAP5 mediates NED in PCa.

Materials and methods

Utilizing diverse public databases, we conducted bioinformatics analysis to examine DLGAP5 expression in PCa. We confirmed aberrant DLGAP5 expression in various PCa cell lines through Western blotting. Functional assays both in vivo and in vitro have validated the oncogenic role of DLGAP5 in PCa. Furthermore, we sought to identify downstream key genes to elucidate the mechanisms underlying DLGAP5-mediated NED in PCa. We also identified a small molecule drug, AAPK-25, which specifically targets DLGAP5.

Key findings

DLGAP5 was highly expressed in NEPC. The suppression of AR signaling promoted DLGAP5 transcription. DLGAP5 endowed PCa cells with a robust ability to proliferate and migrate. E2F1 was an important downstream target of DLGAP5. DLGAP5 mediated the NED of PCa through E2F1. AAPK-25, as an inhibitor of DLGAP5, inhibited PRAD proliferation by repressing the DLGAP5/E2F1 axis both in vitro and in vivo.

Significance

We identified the AR/DLGAP5/E2F1 signaling pathway as a pivotal mechanism that facilitates the transition of PCa towards a neuroendocrine phenotype. This pathway may represent a promising therapeutic target for NEPC patients.

{"title":"DLGAP5 upregulates E2F1 to promote prostate adenocarcinoma neuroendocrine differentiation","authors":"Linghui Liang , Zhiyi Shen , Kaiyu Zhang , Chenglong Zhang , Lai Dong , Rongjie Shi , Lixin Hua , Ruizhe Zhao , Ninghan Feng","doi":"10.1016/j.lfs.2025.123442","DOIUrl":"10.1016/j.lfs.2025.123442","url":null,"abstract":"<div><h3>Aims</h3><div>DLGAP5 plays a significant role in promoting cancer progression across various cancers. However, the specific role of DLGAP5 in neuroendocrine differentiation (NED) of prostate cancer (PCa) remains elusive. Our objective is to explore the mechanism by which DLGAP5 mediates NED in PCa.</div></div><div><h3>Materials and methods</h3><div>Utilizing diverse public databases, we conducted bioinformatics analysis to examine DLGAP5 expression in PCa. We confirmed aberrant DLGAP5 expression in various PCa cell lines through Western blotting. Functional assays both in vivo and in vitro have validated the oncogenic role of DLGAP5 in PCa. Furthermore, we sought to identify downstream key genes to elucidate the mechanisms underlying DLGAP5-mediated NED in PCa. We also identified a small molecule drug, AAPK-25, which specifically targets DLGAP5.</div></div><div><h3>Key findings</h3><div>DLGAP5 was highly expressed in NEPC. The suppression of AR signaling promoted DLGAP5 transcription. DLGAP5 endowed PCa cells with a robust ability to proliferate and migrate. E2F1 was an important downstream target of DLGAP5. DLGAP5 mediated the NED of PCa through E2F1. AAPK-25, as an inhibitor of DLGAP5, inhibited PRAD proliferation by repressing the DLGAP5/E2F1 axis both in vitro and in vivo.</div></div><div><h3>Significance</h3><div>We identified the AR/DLGAP5/E2F1 signaling pathway as a pivotal mechanism that facilitates the transition of PCa towards a neuroendocrine phenotype. This pathway may represent a promising therapeutic target for NEPC patients.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"365 ","pages":"Article 123442"},"PeriodicalIF":5.2,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143382746","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}

引用次数: 0

2-Mercaptoethanol enhances the yield of exosomes showing therapeutic potency in alleviating spinal cord injury mice

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-02-07 DOI: 10.1016/j.lfs.2025.123451

Yang Wang , Hanxiao Yi , Keqi Huang , Yi Zeng , Ping Miao , Yating Zhang , Nan Hu

Background

Limited passage numbers of mesenchymal stem cells (MSCs) present challenges in producing sufficient exosomes for spinal cord injury (SCI) treatment.

Objectives

This study investigates whether β-mercaptoethanol (BME) preconditioning of MSCs can increase exosome yield for SCI therapy.

Methods

Exosomal content was analyzed using silver staining and SYBR Gold staining. Cell viability was assessed via CCK-8 and EdU assays. IL-1β, IL-6, TNF-α, and MCP-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). Neuronal differentiation influenced by astrocytes was evaluated through neurite outgrowth and migration assays. Neuronal survival and motor function recovery in SCI mice were assessed using TUNEL staining, the Basso Mouse Scale (BMS), muscle strength tests, and motor evoked potential (MEP) measurements.

Results

BME treatment significantly increased exosome quantity, including proteins and microRNAs, without drastic changes in exosomal content spectrum. Exosomes from BME-treated MSCs more effectively suppressed IL-1β, IL-6, TNF-α, and MCP-1 secretion by astrocytes, reducing neuronal inflammation. Yap1 activation reduced the exosomes' inhibitory effects on inflammatory cytokines. Mice treated with exosomes from BME-treated MSCs showed better outcomes: lower GFAP and C3 expression, reduced inflammation, increased NF-H levels, higher BMS scores, and greater MEP peaks. Exosome treatment also reduced bladder volume, residual urine, and the time to regain spontaneous urination after uroschesis.

Conclusion

BME preconditioning enhances exosome yield from hUC-MSCs, offering improved therapeutic potential for SCI.

{"title":"2-Mercaptoethanol enhances the yield of exosomes showing therapeutic potency in alleviating spinal cord injury mice","authors":"Yang Wang , Hanxiao Yi , Keqi Huang , Yi Zeng , Ping Miao , Yating Zhang , Nan Hu","doi":"10.1016/j.lfs.2025.123451","DOIUrl":"10.1016/j.lfs.2025.123451","url":null,"abstract":"<div><h3>Background</h3><div>Limited passage numbers of mesenchymal stem cells (MSCs) present challenges in producing sufficient exosomes for spinal cord injury (SCI) treatment.</div></div><div><h3>Objectives</h3><div>This study investigates whether β-mercaptoethanol (BME) preconditioning of MSCs can increase exosome yield for SCI therapy.</div></div><div><h3>Methods</h3><div>Exosomal content was analyzed using silver staining and SYBR Gold staining. Cell viability was assessed via CCK-8 and EdU assays. IL-1β, IL-6, TNF-α, and MCP-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). Neuronal differentiation influenced by astrocytes was evaluated through neurite outgrowth and migration assays. Neuronal survival and motor function recovery in SCI mice were assessed using TUNEL staining, the Basso Mouse Scale (BMS), muscle strength tests, and motor evoked potential (MEP) measurements.</div></div><div><h3>Results</h3><div>BME treatment significantly increased exosome quantity, including proteins and microRNAs, without drastic changes in exosomal content spectrum. Exosomes from BME-treated MSCs more effectively suppressed IL-1β, IL-6, TNF-α, and MCP-1 secretion by astrocytes, reducing neuronal inflammation. Yap1 activation reduced the exosomes' inhibitory effects on inflammatory cytokines. Mice treated with exosomes from BME-treated MSCs showed better outcomes: lower GFAP and C3 expression, reduced inflammation, increased NF-H levels, higher BMS scores, and greater MEP peaks. Exosome treatment also reduced bladder volume, residual urine, and the time to regain spontaneous urination after uroschesis.</div></div><div><h3>Conclusion</h3><div>BME preconditioning enhances exosome yield from hUC-MSCs, offering improved therapeutic potential for SCI.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"364 ","pages":"Article 123451"},"PeriodicalIF":5.2,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143369730","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}

引用次数: 0

Lycopene inhibits doxorubicin-induced heart failure by inhibiting ferroptosis through the Nrf2 signaling pathway

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-02-07 DOI: 10.1016/j.lfs.2025.123452

Rong Huang , Chao Zhou , Tianxiang Wang , Yuanli Chen , Zhouling Xie , Lingling Wei , Yajun Duan , Chenzhong Liao , Chuanrui Ma , Xiaoxiao Yang

Aims

Lycopene (LYC) is a dietary nutrient that plays a protective role in various cardiovascular diseases. Doxorubicin (DOX)-induced cardiotoxicity is an important cause of poor prognosis in many cancer patients treated with anthracyclines. This study aims to investigate the protective effects of LYC against DOX-induced heart failure (HF) and specific underlying mechanisms.

Materials and methods

DOX was used to establish HF model in cardiomyocytes and C57BL/6J mice to assess the protection of LYC against DOX-induced HF on inflammation, oxidative stress, and ferroptosis.

Key findings

LYC ameliorated DOX-induced deterioration of cardiac function. Mechanistically, LYC reduced collagen content and fibrosis by inhibiting the expression of matrix metalloproteinase 2 (MMP-2) and MMP-9. Additionally, LYC inhibited reactive oxygen species (ROS) production by upregulating antioxidant enzymes expression. LYC enhanced B-cell lymphoma 2 (Bcl-2), but reduced apoptosis positive cells by reducing tumor protein 53 (p53), Bcl-2 associated X protein (Bax), and cleaved-Caspase 3 (c-Casp3) levels. Besides, LYC reduced inflammatory cytokine levels through activating peroxisome proliferator activated receptor gamma (PPARγ). Moreover, LYC ameliorated DOX-induced ferroptosis both in vivo and in vitro. Furthermore, we showed that LYC inhibited DOX-induced ferroptosis via binding to nuclear factor-erythroid 2-related factor 2 (Nrf2) to enhance its expression.

Significance

LYC improved DOX-induced cardiac dysfunction by reducing oxidative stress and inflammation, which was contributed by the reduction of ferroptosis. At molecular levels, LYC ameliorated DOX-induced ferroptosis through activating the Nrf2 signaling pathway. These findings indicate the potential of LYC as a therapeutic option for HF treatment.

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引用次数: 0

Carnosinase inhibition enhances reactive species scavenging in high fat diet

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences

Pub Date : 2025-02-07 DOI: 10.1016/j.lfs.2025.123448

Charlie Jr. Lavilla , Merell P. Billacura , Suniya. Khatun , Daniel P. Cotton , Vivian.K. Lee , Sreya. Bhattacharya , Paul W. Caton , Craig Sale , John D. Wallis , A. Christopher Garner , Mark D. Turner

Aims

Life expectancy is typically reduced by 2–4 years in people with a body mass index (BMI) of 30–35 kg/m² and by 8–10 years in people with a BMI of 40–50 kg/m². Obesity is also associated with onset, or exacerbation of, multiple chronic diseases. Mechanistically, this, in part, involves formation of advanced glycation and lipidation end-products that directly bond with proteins, lipids, or DNA, thereby perturbing typical cellular function. Here we seek to prevent these damaging adduction events through inhibition of carnosinase enzymes that rapidly degrade the physiological reactive species scavenger, carnosine, in the body.

Main methods

Herein we performed in silico computational modelling of a compound library of ∼53,000 molecules to identify carnosine-like molecules with intrinsic resistance to carnosinase turnover.

Key findings

We show that leading candidate molecules reduced reactive species in C2C12 myotubes, and that mice fed N-methyl-[6-(2-furyl)pyrid-3-yl]methylamine alongside a high fat diet had significantly decreased amounts of damaging plasma 4-hydroxynonenal and 3-nitrotyrosine reactive species. Oral administration of N-methyl-[6-(2-furyl)pyrid-3-yl]methylamine to high fat-fed mice also resulted in a modest ∼10 % reduction in weight gain when compared to mice fed only high fat diet.

Significance

Our findings suggest that inhibition of carnosinase enzymes can increase the life-span, and thereby enhance the efficacy, of endogenous carnosine in vivo, thereby offering potential therapeutic benefits against obesity and other cardiometabolic diseases characterised by metabolic stress.

{"title":"Carnosinase inhibition enhances reactive species scavenging in high fat diet","authors":"Charlie Jr. Lavilla , Merell P. Billacura , Suniya. Khatun , Daniel P. Cotton , Vivian.K. Lee , Sreya. Bhattacharya , Paul W. Caton , Craig Sale , John D. Wallis , A. Christopher Garner , Mark D. Turner","doi":"10.1016/j.lfs.2025.123448","DOIUrl":"10.1016/j.lfs.2025.123448","url":null,"abstract":"<div><h3>Aims</h3><div>Life expectancy is typically reduced by 2–4 years in people with a body mass index (BMI) of 30–35 kg/m<sup>2</sup> and by 8–10 years in people with a BMI of 40–50 kg/m<sup>2</sup>. Obesity is also associated with onset, or exacerbation of, multiple chronic diseases. Mechanistically, this, in part, involves formation of advanced glycation and lipidation end-products that directly bond with proteins, lipids, or DNA, thereby perturbing typical cellular function. Here we seek to prevent these damaging adduction events through inhibition of carnosinase enzymes that rapidly degrade the physiological reactive species scavenger, carnosine, in the body.</div></div><div><h3>Main methods</h3><div>Herein we performed in silico computational modelling of a compound library of ∼53,000 molecules to identify carnosine-like molecules with intrinsic resistance to carnosinase turnover.</div></div><div><h3>Key findings</h3><div>We show that leading candidate molecules reduced reactive species in C2C12 myotubes, and that mice fed <em>N</em>-methyl-[6-(2-furyl)pyrid-3-yl]methylamine alongside a high fat diet had significantly decreased amounts of damaging plasma 4-hydroxynonenal and 3-nitrotyrosine reactive species. Oral administration of <em>N</em>-methyl-[6-(2-furyl)pyrid-3-yl]methylamine to high fat-fed mice also resulted in a modest ∼10 % reduction in weight gain when compared to mice fed only high fat diet.</div></div><div><h3>Significance</h3><div>Our findings suggest that inhibition of carnosinase enzymes can increase the life-span, and thereby enhance the efficacy, of endogenous carnosine in vivo, thereby offering potential therapeutic benefits against obesity and other cardiometabolic diseases characterised by metabolic stress.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"364 ","pages":"Article 123448"},"PeriodicalIF":5.2,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349640","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

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