Life sciences最新文献_第4页

Paeoniae radix overcomes resistance to EGFR-TKIs via aurora B pathway suppression in lung adenocarcinoma 芍药通过抑制极光 B 通路克服肺腺癌对表皮生长因子受体-TKIs 的耐药性

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-01 DOI: 10.1016/j.lfs.2024.123097

{"title":"Paeoniae radix overcomes resistance to EGFR-TKIs via aurora B pathway suppression in lung adenocarcinoma","authors":"","doi":"10.1016/j.lfs.2024.123097","DOIUrl":"10.1016/j.lfs.2024.123097","url":null,"abstract":"<div><div>Targeted therapies using epidermal growth factor receptor (EGFR) inhibitors have markedly improved survival rates and quality of life for patients with EGFR-mutant lung adenocarcinoma (LUAD). Despite these advancements, resistance to EGFR inhibitors remains a significant challenge, limiting the overall effectiveness of the treatment. This study explored the synergistic effects of combining Paeoniae Radix (PR) with first-generation EGFR-tyrosine kinase inhibitors (TKIs), erlotinib and gefitinib, to overcome this resistance. Transcriptomic analysis of EGFR-mutant LUAD cell lines revealed that PR treatment could potentially reverse the gene signatures associated with resistance to EGFR-TKIs, primarily through the suppression of the Aurora B pathway. Experimental validation demonstrated that combining PR with erlotinib and gefitinib enhanced drug responsiveness by inhibiting Aurora kinase activity and inducing apoptosis in LUAD cells. Additionally, gene expression changes confirmed these combined effects, with the suppression of the Aurora B pathway and upregulation of the apoptotic pathway, which was accompanied by increased expression of multiple pro-apoptotic genes. Our findings contribute to the development of natural product-based therapeutic strategies to mitigate drug resistance in LUAD.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372246","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

Elevated serum GDF15 level as an early indicator of proximal tubular cell injury in acute kidney injury 血清 GDF15 水平升高是急性肾损伤近端肾小管细胞损伤的早期指标。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-01 DOI: 10.1016/j.lfs.2024.123093

{"title":"Elevated serum GDF15 level as an early indicator of proximal tubular cell injury in acute kidney injury","authors":"","doi":"10.1016/j.lfs.2024.123093","DOIUrl":"10.1016/j.lfs.2024.123093","url":null,"abstract":"<div><div>Acute kidney injury (AKI) is a high-burden medical condition, and current diagnostic criteria can only assess AKI after full manifestation. Stress marker growth differentiation factor 15 (GDF15) was reported to have a role in kidney injury of critical patients. Herein, we evaluated dynamic changes in GDF15 across diverse AKI scenarios and explored the underlying mechanisms of its induction. Serum parameters and renal lesions were analyzed in mouse models of unilateral ischemia-reperfusion injury (uni-IRI) and unilateral ureteral obstruction (UUO). The human proximal tubular (HK−2) cell line was stimulated with various conditions, and induction of GDF15 expression was determined. Serum GDF15 levels were rapidly induced within hours after injury in both animal models and declined thereafter. Renal GDF15 expression exhibited a temporary and early increased induction and was mainly located in aquaporin 1-positive proximal tubules in both unilateral AKI model tissues. In cell experiments, rapid GDF15 production was highly induced by t-BHP and CoCl<sub>2</sub>. Treatment with either an antioxidant or mitogen-activated protein kinase inhibitors abolished t-BHP- and CoCl<sub>2</sub>-mediated GDF15 expression. In addition, silencing nuclear factor erythroid 2-related factor 2 expression also reduced the basal and t-BHP- or CoCl<sub>2</sub>-mediated GDF15 expression level in HK-2 cells. Our data showed that elevated serum GDF15 levels could be detected early in unilateral AKI models without notable alterations in kidney function parameters. GDF15 expression was associated with oxidative stress- and hypoxia-mediated proximal tubular cell injury. These data document that elevated serum GDF15 can possibly serve as an early biomarker for proximal tubular cell injury in AKI.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372242","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

Hippocampal sharp-wave ripples and hippocampal-prefrontal synchrony regulate memory-enhancing effects of intranasal insulin in an STZ-induced Alzheimer's model 在STZ诱导的阿尔茨海默氏症模型中，海马尖波涟漪和海马-前额叶同步调节鼻内胰岛素的记忆增强效应。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-01 DOI: 10.1016/j.lfs.2024.123094

{"title":"Hippocampal sharp-wave ripples and hippocampal-prefrontal synchrony regulate memory-enhancing effects of intranasal insulin in an STZ-induced Alzheimer's model","authors":"","doi":"10.1016/j.lfs.2024.123094","DOIUrl":"10.1016/j.lfs.2024.123094","url":null,"abstract":"<div><h3>Aims</h3><div>Alzheimer's disease is characterized by memory loss and pathological changes in the brain, such as amyloid beta and tau pathology, disruptions in neural circuits and neuronal oscillations are also significant indicators of this disease and potential therapeutic targets. We studied how intranasal insulin impacts memory and neural oscillations in an Alzheimer's disease rat model induced by STZ.</div></div><div><h3>Main methods</h3><div>Male Wistar rats were intracerebroventricularly injected with STZ, followed by intranasal insulin therapy. Electrophysiological recordings were conducted in the hippocampus and medial prefrontal cortex to assess local field potentials. Memory was assessed using novel object recognition and Y-maze tests. Amyloid and tau pathology and neuronal loss were also evaluated in the hippocampus.</div></div><div><h3>Key finding</h3><div>Alterations in theta-gamma oscillations following insulin treatment were not significant. However, insulin administration ameliorated hippocampal sharp-wave ripples deficit and augmented hippocampal-prefrontal theta coherence. Concurrently, insulin therapy enhanced spatial memory and object recognition memory performance in behavioral tests. Insulin mitigated tau and amyloid pathology and hippocampal neuronal loss.</div></div><div><h3>Significance</h3><div>Our findings underscore the potential of intranasal insulin to enhance memory function by modulating hippocampal-prefrontal cortical synchronization and alleviating impairments in hippocampal sharp-wave ripples.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372243","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

Compound (E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one downregulation of Galectin-3 ameliorates Aβ pathogenesis-induced neuroinflammation in 5 × FAD mice 化合物(E)-2-(3,4-二羟基苯乙烯基)-3-羟基-4H-吡喃-4-酮下调Galectin-3可改善5×FAD小鼠Aβ发病机制诱发的神经炎症。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-01 DOI: 10.1016/j.lfs.2024.123085

{"title":"Compound (E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one downregulation of Galectin-3 ameliorates Aβ pathogenesis-induced neuroinflammation in 5 × FAD mice","authors":"","doi":"10.1016/j.lfs.2024.123085","DOIUrl":"10.1016/j.lfs.2024.123085","url":null,"abstract":"<div><h3>Aims</h3><div>Alzheimer's disease (AD) is characterized by β-amyloid (Aβ) aggregation and neuroinflammation, leading to progressive synaptic loss and cognitive decline. Recent evidence suggests that Galectin-3 (Gal-3) plays a critical role in Aβ pathogenesis. However, strategies to simultaneously target Gal-3 and Aβ are currently insufficient. This study evaluates the therapeutic efficacy of (<em>E</em>)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one (D30), in reducing Gal-3 and Aβ pathogenesis.</div></div><div><h3>Materials and methods</h3><div>We applied exogenous oligomeric Aβ and used 5 × FAD mice to assess the impact of Aβ on Gal-3 deposition, microglial activation, and cognitive function. Thy1-EGFP mice were employed to observe dendritic spines. Comprehensive evaluations of D30's effects included behavioral studies, transcriptomic analysis, Western blotting, and immunofluorescent staining. The interaction between D30 and Gal-3 was examined using fluorescence resonance energy transfer (FRET) and microscale thermophoresis (MST).</div></div><div><h3>Key findings</h3><div>D30 effectively reduced Aβ monomer production by inhibiting Amyloid Precursor Protein (APP) and presenilin 1 (PS1) expression, and decreased Aβ aggregation. Treatment with D30 improved cognitive functions, reversed dendritic spine loss, and increased PSD95 expression in 5 × FAD mice. Additionally, D30 significantly lowered Gal-3 levels in both plasma and hippocampal tissues. D30 binds to Gal-3 and disrupts the interaction between Gal-3 and TREM2, as confirmed by FRET and MST.</div></div><div><h3>Significance</h3><div>Our findings underscore the interaction between Gal-3 and Aβ in AD and its role in systemic inflammation using the 5 × FAD mouse model. Being able to target and regulate Gal-3 together with Aβ is crucial for preventing neuroinflammation and protecting synapses, D30 emerged as a novel compound with promising potential for AD treatment.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372241","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

Ficolin-3 induces apoptosis and suppresses malignant property of hepatocellular carcinoma cells via the complement pathway Ficolin-3 通过补体途径诱导肝癌细胞凋亡并抑制其恶性特性。

IF 5.2 2区医学

Life sciences Pub Date : 2024-09-30 DOI: 10.1016/j.lfs.2024.123103

{"title":"Ficolin-3 induces apoptosis and suppresses malignant property of hepatocellular carcinoma cells via the complement pathway","authors":"","doi":"10.1016/j.lfs.2024.123103","DOIUrl":"10.1016/j.lfs.2024.123103","url":null,"abstract":"<div><h3>Aims</h3><div>Ficolin 3 (FCN3) has the highest complement-activating capacity through the lectin pathway and is synthesized mainly in the liver and lung. Yet, its potential molecular mechanism in hepatocarcinogenesis is not fully understood.</div></div><div><h3>Materials and methods</h3><div>The expression of FCN3 in hepatocellular carcinoma (HCC) tumor and non-tumor tissues was analyzed by RT-qPCR, Western blotting and immunofluorescence staining assays. Lentivector-mediated ectopic overexpression was performed to explore the role of FCN3 in vitro and in vivo. Whether FCN3 inhibited HCC cell growth and survival via complement pathway was determined with immunocytochemical staining for C3b, membrane attack complex (MAC) formation and complement killing assay using recombinant FCN3 (rFCN3) in combination with human serum with or without heat inactivation, and with C6 blocking antibody.</div></div><div><h3>Key findings</h3><div>The transcript and protein of FCN3 were found to be remarkably down-regulated in HCC tumor tissues. <em>FCN3</em> expression was found to be associated with better survival of HCC patients. Restoration of FCN3 expression significantly inhibited proliferation, migration and anchorage independent growth of HCC cell lines, and xenograft tumor growth. FCN3 expression induced apoptosis of HCC cells. C3 and MAC formation was stimulated by FCN3 overexpression or rFCN3 treatment. rFCN3 enhanced human serum-induced complement activation and cell death. C6 blocking antibody significantly attenuated complement-mediated cell death and restored the growth of FCN3-overexpressing HCC cells.</div></div><div><h3>Significance</h3><div>FCN3 has a malignant suppressor role in HCC cells. Our study provides new insights into the molecular mechanisms that drive HCC progression and potential therapeutic targets for treating HCC.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365762","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

Gastrointestinal manifestations of long COVID 长COVID的胃肠道表现。

IF 5.2 2区医学

Life sciences Pub Date : 2024-09-30 DOI: 10.1016/j.lfs.2024.123100

{"title":"Gastrointestinal manifestations of long COVID","authors":"","doi":"10.1016/j.lfs.2024.123100","DOIUrl":"10.1016/j.lfs.2024.123100","url":null,"abstract":"<div><div>Long COVID is estimated to have affected 6.9 % of US adults, 17.8 million people in the US alone, as of early 2023. While SARS-CoV-2 is primarily considered a respiratory virus, gastrointestinal (GI) symptoms are also frequent in patients with coronavirus disease 2019 (COVID-19) and in patients with Long COVID. The risk of developing GI symptoms is increased with increasing severity of COVID-19, the presence of GI symptoms in the acute infection, and psychological distress both before and after COVID-19. Persistence of the virus in the GI tract, ensuing inflammation, and alteration of the microbiome are all likely mediators of the effects of SARS Co-V-2 virus on the gut. These factors may all increase intestinal permeability and systemic inflammation. GI inflammation and dysbiosis can change the absorption and metabolism of tryptophan, an important neurotransmitter. Long COVID GI symptoms resemble a Disorder of Gut Brain Interaction (DGBI) such as post infection Irritable Bowel Syndrome (IBS). Current standards of treatment for IBS can guide our treatment of Long COVID patients. Dysautonomia, a frequent Long COVID condition affecting the autonomic nervous system, can also affect the GI tract, and must be considered in Long COVID patients with GI symptoms. Long COVID symptoms fall within the broader category of Infection Associated Chronic Conditions (IACCs). Research into the GI symptoms of Long COVID may further our understanding of other post infection chronic GI conditions, and elucidate the roles of therapeutic options including antivirals, probiotics, neuromodulators, and treatments of dysautonomia.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365763","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

Irisin's emerging role in Parkinson's disease research: A review from molecular mechanisms to therapeutic prospects 鸢尾素在帕金森病研究中的新作用：从分子机制到治疗前景的综述。

IF 5.2 2区医学

Life sciences Pub Date : 2024-09-30 DOI: 10.1016/j.lfs.2024.123088

引用次数: 0

Therapeutic effect of exosomes derived from Schwann cells in the repair of peripheral nerve injury 源自 SC 的外泌体在修复周围神经损伤中的治疗效果。

IF 5.2 2区医学

Life sciences Pub Date : 2024-09-30 DOI: 10.1016/j.lfs.2024.123086

引用次数: 0

High-glucose impact on UVB responses in human epidermal keratinocytes: Insights on diabetic skin's resistance to photocarcinogenesis 高血糖对人体表皮角质细胞 UVB 反应的影响：洞察糖尿病皮肤对光致癌的抵抗力

IF 5.2 2区医学

Life sciences Pub Date : 2024-09-27 DOI: 10.1016/j.lfs.2024.123083

{"title":"High-glucose impact on UVB responses in human epidermal keratinocytes: Insights on diabetic skin's resistance to photocarcinogenesis","authors":"","doi":"10.1016/j.lfs.2024.123083","DOIUrl":"10.1016/j.lfs.2024.123083","url":null,"abstract":"<div><div>Ultraviolet (UV) B-induced damage in human epidermal keratinocytes (HEKs) initiates photocarcinogenesis. However, how diabetes influences photocarcinogenesis is not well understood. To investigate the impact of high-glucose environments on responses to UVB, we cultured HEKs in normal-glucose (NG) or high-glucose (HG) conditions (G6 and G26), followed by UVB irradiation at 25 mJ/cm<sup>2</sup> (G6UVB and G26UVB). We performed next-generation sequencing and analyzed HEKs' expression profiles bioinformatically to identify candidate genes and cellular responses involved. We found UVB induced consistent responses in both NG- and HG-cultivated HEKs, but it also triggered certain distinct processes and pathways specifically in the HG groups. The 459 differentially expressed (DE) genes in the HG groups revealed their roles in chromatin remodeling, nucleosome assembly, and interferon signaling activation. Moreover, the 29 DE genes identified in G26UVB/G6UVB comparison, including the potent tumor suppressor gene <em>TFPI2,</em> were considered key genes contributing to HEKs' altered response to UVB in HG environments. UVB irradiation induced significantly higher <em>TFPI2</em> expression in HG-cultivated HEKs than their NG-cultivated counterpart. Finally, HG-cultivation significantly increased oxidative stress, cyclobutane pyrimidine dimer formation, and apoptosis, while reducing HEKs' viability after UVB irradiation. These changes under HG conditions probably mediate cell fate toward death and tumor regression. Overall, our findings provide evidence and associated molecular basis on how HG conditions reduce keratinocytes' photocarcinogenic potential following UVB exposure.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":null,"pages":null},"PeriodicalIF":5.2,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349483","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

Post traumatic stress and sleep disorders in long COVID: Patient management and treatment 创伤后应激和长期 COVID 的睡眠障碍：患者管理和治疗。

IF 5.2 2区医学

Life sciences Pub Date : 2024-09-26 DOI: 10.1016/j.lfs.2024.123081

引用次数: 0