Life sciences最新文献_第9页

CLEC14A facilitates angiogenesis and alleviates inflammation in diabetic wound healing CLEC14A 可促进血管生成，减轻糖尿病伤口愈合过程中的炎症反应。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-24 DOI: 10.1016/j.lfs.2024.123176

Yan Liao , Na Wu , Li Guo , Deqin Yang

{"title":"CLEC14A facilitates angiogenesis and alleviates inflammation in diabetic wound healing","authors":"Yan Liao , Na Wu , Li Guo , Deqin Yang","doi":"10.1016/j.lfs.2024.123176","DOIUrl":"10.1016/j.lfs.2024.123176","url":null,"abstract":"<div><h3>Background</h3><div>Delayed wound healing is a serious complication of diabetic wounds, posing a significant challenge to the treatment of patients with diabetes. Diabetic wound healing is a complex dynamic process involving angiogenesis and inflammatory responses. Currently, there are limited targeted therapies to promote diabetic wound healing. This study aimed to reveal the role of CLEC14A in the process of diabetic wound healing, with the hope of identifying new therapeutic targets to accelerate the healing of diabetic wounds.</div></div><div><h3>Methods</h3><div><em>In vivo</em>, diabetic mice were generated by combined streptozotocin (STZ) and high-fat diet treatment. The wound healing model was established in wild-type and <em>Clec14a</em><sup><em>−/−</em></sup> diabetic mice. The degree of wound healing, as well as angiogenesis and inflammation during the healing process, were evaluated through Hematoxylin and Eosin (H&E) staining, immunohistochemical staining, and immunofluorescence staining. <em>In vitro</em>, the angiogenic activities of Human Umbilical Vein Endothelial Cells (HUVECs) were assessed following treatment with high glucose and adenoviruses overexpressing CLEC14A, using scratch assays and tube formation assays. Interleukin-1β (IL-1β) and Tumor Necrosis Factor-α (TNF-α) were utilized to evaluate the levels of inflammation in HUVECs.</div></div><div><h3>Results</h3><div>CLEC14A expression was suppressed in diabetic wounds. Deletion of the <em>Clec14a</em> inhibited angiogenesis and activated inflammatory responses <em>in vivo</em>. High-glucose treatment led to decreased CLEC14A expression, impaired angiogenic capacity, and elevated inflammatory levels <em>in vitro</em>. However, adenoviral-mediated overexpression of CLEC14A reversed the response induced by high glucose.</div></div><div><h3>Conclusion</h3><div>CLEC14A accelerates diabetic wound healing by promoting angiogenesis and reducing wound inflammation.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123176"},"PeriodicalIF":5.2,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503174","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

A retrospective cohort analysis of factors influencing continuous antibiotic therapy with ampicillin 对氨苄西林持续抗生素治疗影响因素的回顾性队列分析。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-23 DOI: 10.1016/j.lfs.2024.123168

L. Weber , O. Moerer , J. Wieditz , M.S. Winkler , S. Scheithauer , C. Stephani

{"title":"A retrospective cohort analysis of factors influencing continuous antibiotic therapy with ampicillin","authors":"L. Weber , O. Moerer , J. Wieditz , M.S. Winkler , S. Scheithauer , C. Stephani","doi":"10.1016/j.lfs.2024.123168","DOIUrl":"10.1016/j.lfs.2024.123168","url":null,"abstract":"<div><h3>Aims</h3><div>There are limited data on ampicillin/sulbactam, both for continuous infusion and for use in critically ill patients. We aimed to identify factors that help predict ampicillin plasma levels during continuous antibiotic therapy in intensive care patients.</div></div><div><h3>Main methods</h3><div>We retrospectively reviewed and retrieved a large dataset of patients who received continuous ampicillin infusion with therapeutic drug monitoring between 2015 and 2022. Patients initially received standard dosing (single shot of 2/1 g followed by continuous infusion of 6/3 g ampicillin/sulbactam per day), which was then adjusted based on the results of regular therapeutic drug monitoring and according to a target range of 30–60 mg/l (equivalent to four to eight times the minimum inhibitory concentration of ampicillin for Enterobacterales).</div></div><div><h3>Main results</h3><div>466 measurements from 225 patients (152 male, mean age 61 years) were analyzed. Initial measurements of ampicillin plasma levels were below the predefined optimal therapeutic range in 50 %, within the range in 30 % and above the range in 20 %. Target attainment increased to 70 % by the 4th measurement. There was a significant negative correlation between ampicillin plasma levels and estimated glomerular filtration rate (eGFR) (<em>r</em> = −0.74; <em>p</em> < 0.001) and, to a lesser extent, with height (<em>r</em> = −0.31; p < 0.001). Based on multiple linear regression, eGFR and body weight or height were the factors accounting for 63 % of the variability in the data.</div></div><div><h3>Significance</h3><div>To optimise target achievement, ampicillin dosing in critically ill patients requires a personalized approach based on renal function. Importantly, patients with normal or augmented eGFR require higher standard doses of ampicillin/sulbactam.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123168"},"PeriodicalIF":5.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503171","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

Association between hepatocyte TM4SF5 expression and gut microbiome dysbiosis during non-alcoholic fatty liver disease development 非酒精性脂肪肝发展过程中肝细胞 TM4SF5 表达与肠道微生物群失调之间的关系

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-23 DOI: 10.1016/j.lfs.2024.123164

Yangie Dwi Pinanga , Kyung-hee Pyo , Eun-Ae Shin , Haesong Lee , Eun Hae Lee , Wonsik Kim , Soyeon Kim , Ji Eon Kim , Semi Kim , Jung Weon Lee

{"title":"Association between hepatocyte TM4SF5 expression and gut microbiome dysbiosis during non-alcoholic fatty liver disease development","authors":"Yangie Dwi Pinanga , Kyung-hee Pyo , Eun-Ae Shin , Haesong Lee , Eun Hae Lee , Wonsik Kim , Soyeon Kim , Ji Eon Kim , Semi Kim , Jung Weon Lee","doi":"10.1016/j.lfs.2024.123164","DOIUrl":"10.1016/j.lfs.2024.123164","url":null,"abstract":"<div><div>Gut microbiome dysbiosis is involved in non-alcoholic fatty liver disease (NAFLD) development. Hepatic transmembrane 4 L six family member 5 (TM4SF5) overexpression promotes NAFLD. However, how gut microbiota are associated with TM4SF5-mediated NAFLD remains unexplored. We analyzed the gut microbiome using feces from hepatocyte-specific TM4SF5-overexpressing transgenic (<em>Alb</em>-TG<sup>Tm4sf5</sup><sup>-Flag</sup>, TG) or <em>Tm4sf5</em><sup>−/−</sup> knock-out (KO) mice fed a normal chow diet (NCD), high-fat diet (HFD) for 2 weeks (HFD<sub>2W</sub>), or methionine-choline-deficient diet (MCD) for 4 weeks to investigate associations among Tm4sf5 expression, diet, and the gut microbiome. TG-NCD mice showed a higher <em>Firmicutes</em>-to-<em>Bacteroidetes</em> (F/B) ratio, with less enrichment of <em>Akkermansia muciniphila</em> and <em>Lactobacillus reuteri</em>. NASH-related microbiomes in feces were more abundant in TG-HFD<sub>2w</sub> mice than in KO-HFD<sub>2w</sub> mice. Further, TG-MCD showed a higher F/B ratio than TG-NCD or KO mice, with decreases or increases in microbiomes beneficial or detrimental to the liver, respectively. Such effects in TG-MCD animals were correlated with functional pathways producing short-chain fatty acids (SCFAs). Furthermore, potential functional pathways of the gut microbiome were metabolically parallel to NAFLD features in TG-MCD mice. These results suggest that hepatocyte Tm4sf5 supports gut microbiome dysbiosis and metabolic activity, leading to SCFA production and hepatic inflammation during NAFLD development.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123164"},"PeriodicalIF":5.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503185","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

Gastrointestinal pathophysiology in long COVID: Exploring roles of microbiota dysbiosis and serotonin dysregulation in post-infectious bowel symptoms 长期 COVID 的胃肠道病理生理学：探索微生物群失调和血清素失调在感染后肠道症状中的作用。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-23 DOI: 10.1016/j.lfs.2024.123153

Linda Chia-Hui Yu

{"title":"Gastrointestinal pathophysiology in long COVID: Exploring roles of microbiota dysbiosis and serotonin dysregulation in post-infectious bowel symptoms","authors":"Linda Chia-Hui Yu","doi":"10.1016/j.lfs.2024.123153","DOIUrl":"10.1016/j.lfs.2024.123153","url":null,"abstract":"<div><div>The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) triggered an unprecedented public health crisis known as the coronavirus disease 2019 (COVID-19) pandemic. Gastrointestinal (GI) symptoms develop in patients during acute infection and persist after recovery from airway distress in a chronic form of the disease (long COVID). A high incidence of irritable bowel syndrome (IBS) manifested by severe abdominal pain and defecation pattern changes is reported in COVID patients. Although COVID is primarily considered a respiratory disease, fecal shedding of SARS-CoV-2 antigens positively correlates with bowel symptoms. Active viral infection in the GI tract was identified by human intestinal organoid studies showing SARS-CoV-2 replication in gut epithelial cells. In this review, we highlight the key findings in post-COVID bowel symptoms and explore possible mechanisms underlying the pathophysiology of the illness. These mechanisms include mucosal inflammation, gut barrier dysfunction, and microbiota dysbiosis during viral infection. Viral shedding through the GI route may be the primary factor causing the alteration of the microbiome ecosystem, particularly the virome. Recent evidence in experimental models suggested that microbiome dysbiosis could be further aggravated by epithelial barrier damage and immune activation. Moreover, altered microbiota composition has been associated with dysregulated serotonin pathways, resulting in intestinal nerve hypersensitivity. These mechanisms may explain the development of post-infectious IBS-like symptoms in long COVID. Understanding how coronavirus infection affects gut pathophysiology, including microbiome changes, would benefit the therapeutic advancement for managing post-infectious bowel symptoms.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123153"},"PeriodicalIF":5.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503187","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

Polygoni Cuspidati Rhizoma et Radix extract activates TFEB and alleviates hepatic steatosis by promoting autophagy 何首乌提取物可激活 TFEB，并通过促进自噬缓解肝脏脂肪变性。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-23 DOI: 10.1016/j.lfs.2024.123158

Chang Li , Chenyu Li , Yi Wang , Sikun You , Ka Yi Man , Zhunming Fan , Qian Yu , Meng Zhang , Kenneth King-yip Cheng , Daniel Kam-Wah Mok , Shun-Wan Chan , Huan Zhang

{"title":"Polygoni Cuspidati Rhizoma et Radix extract activates TFEB and alleviates hepatic steatosis by promoting autophagy","authors":"Chang Li , Chenyu Li , Yi Wang , Sikun You , Ka Yi Man , Zhunming Fan , Qian Yu , Meng Zhang , Kenneth King-yip Cheng , Daniel Kam-Wah Mok , Shun-Wan Chan , Huan Zhang","doi":"10.1016/j.lfs.2024.123158","DOIUrl":"10.1016/j.lfs.2024.123158","url":null,"abstract":"<div><div>Hepatic steatosis, characterized by excessive lipid accumulation in the liver, can be ameliorated by autophagy activation. Polygoni Cuspidati rhizome et Radix (PCRR), traditionally used to treat atherosclerosis, hepatitis, and gallstones, has recently demonstrated anti-steatotic effects in the liver. However, the active compounds and underlying mechanisms remain unclear. This study investigated whether PCRR water extract improves steatosis by modulating hepatic autophagic flux. We found that PCRR water extract promoted autophagic flux, enhanced lysosomal biogenesis, and alleviated lipid accumulation in the liver cell lines as well as in the livers of rats with steatosis. Mechanistically, PCRR water extract inhibited mechanistic target of rapamycin complex 1 (mTORC1) activity, leading to dephosphorylation and subsequent nuclear translocation of transcription factor EB (TFEB), a key regulator of lipophagy. TFEB knockdown attenuated PCRR-mediated lipophagy promotion in the liver cell lines. Furthermore, chloroquine (CQ)-mediated autophagy blockage abrogated the therapeutic effect of PCRR against hepatic steatosis in high-fat diet (HFD)-fed rats. These findings suggest that PCRR water extract acts as a novel autophagy enhancer and holds therapeutic potential for hepatic steatosis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123158"},"PeriodicalIF":5.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503179","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

Migrasomes: Emerging organelles for unveiling physiopathology and advancing clinical implications 移行体：用于揭示生理病理和推进临床意义的新兴细胞器。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-23 DOI: 10.1016/j.lfs.2024.123152

Jingyu Mei , Xiaoli Cao , Baocheng Zhou , Wei Zhu , Mei Wang

{"title":"Migrasomes: Emerging organelles for unveiling physiopathology and advancing clinical implications","authors":"Jingyu Mei , Xiaoli Cao , Baocheng Zhou , Wei Zhu , Mei Wang","doi":"10.1016/j.lfs.2024.123152","DOIUrl":"10.1016/j.lfs.2024.123152","url":null,"abstract":"<div><div>Migrasomes are newly identified cellular organelles with a pomegranate-like structure and specifically generated by migrating cells. The mechanisms underlying migrasome biogenesis and methods for their isolation are gradually being elucidated. These organelles are pivotal in cell-to-cell communication and the maintenance of mitochondrial homeostasis. Their involvement in a diverse array of physiological and pathological processes is increasingly recognized. Despite these advancements, research on migrasomes is still in its early stages. It is imperative to delve deeper into the intricate mechanisms and functions of migrasomes to fully understand their role in physiopathology. In this review, we summarize the current research progress on migrasomes, including their distribution, biogenesis, purification and identification techniques, biological functionalities, and roles in physiological and pathological processes. We particularly highlight their potentials in disease diagnosis and therapy and point out the challenges facing us, aiming to provide novel insights into the emerging organelles.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123152"},"PeriodicalIF":5.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503176","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

New insights into the function and therapeutic potential of RNA-binding protein TRBP in viral infection, chronic metabolic diseases, brain disorders and cancer 对 RNA 结合蛋白 TRBP 在病毒感染、慢性代谢性疾病、脑部疾病和癌症中的功能和治疗潜力的新认识。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-23 DOI: 10.1016/j.lfs.2024.123159

Minghui Ji , Lingyu Li , Jialing Yu , Zhao Wu , Yuwen Sheng , Fei Wang

{"title":"New insights into the function and therapeutic potential of RNA-binding protein TRBP in viral infection, chronic metabolic diseases, brain disorders and cancer","authors":"Minghui Ji , Lingyu Li , Jialing Yu , Zhao Wu , Yuwen Sheng , Fei Wang","doi":"10.1016/j.lfs.2024.123159","DOIUrl":"10.1016/j.lfs.2024.123159","url":null,"abstract":"<div><div>RNA-binding proteins (RBPs) and non-coding RNAs are crucial <em>trans</em>-acting factors that bind to specific <em>cis</em>-acting elements in mRNAs, thereby regulating their stability and translation. The trans-activation response (TAR) RNA-binding protein (TRBP) recognizes precursor microRNAs (pre-miRNAs), modulates miRNA maturation, and influences miRNA interference (mi-RNAi) mediated by the RNA-induced silencing complex (RISC). TRBP also directly binds and mediates the degradation of certain mRNAs. Thus, TRBP acts as a hub for regulating gene expression and influences a variety of biological processes, including immune evasion, metabolic abnormalities, stress response, angiogenesis, hypoxia, and metastasis. Aberrant TRBP expression has been proven to be closely related to the initiation and progression of diseases, such as viral infection, chronic metabolic diseases, brain disorders, and cancer. This review summarizes the roles of TRBP in cancer and other diseases, the therapeutic potential of TRBP inhibition, and the current status of drug discovery on TRBP.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123159"},"PeriodicalIF":5.2,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503177","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

New insights into the mechanisms and prevention of central nervous system oxygen toxicity: A prospective review. 中枢神经系统氧中毒机制和预防的新见解：前瞻性综述。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-22 DOI: 10.1016/j.lfs.2024.123169

Ondrej Groborz, Petr Marsalek, Ludek Sefc

{"title":"New insights into the mechanisms and prevention of central nervous system oxygen toxicity: A prospective review.","authors":"Ondrej Groborz, Petr Marsalek, Ludek Sefc","doi":"10.1016/j.lfs.2024.123169","DOIUrl":"https://doi.org/10.1016/j.lfs.2024.123169","url":null,"abstract":"<p><p>Hyperbaric oxygen therapy (HBOT) elevates the pressure of life-sustaining oxygen (pO<sub>2</sub>), thereby saving lives. However, HBOT can also cause toxic effects like lung and retinal damage (peripheral oxygen toxicity) and violent myoclonic seizures (central nervous system (CNS) toxicity). The mechanisms behind these effects are not fully understood, hindering the development of effective therapies and preventive strategies. Herein, we critically reviewed the literature to understand CNS oxygen toxicity associated with HBOT to elucidate their mechanism, treatment, and prevention. We provide evidence that (1) increased pO<sub>2</sub> increases reactive oxygen species (ROS) concentration in tissues, which irreversibly alters cell receptors, causing peripheral oxygen toxicity and contributing to CNS oxygen toxicity. Furthermore, (2) increased ROS concentration in the brain lowers the activity of glutamic decarboxylase (GD), which lowers concentrations of inhibitory neurotransmitter γ-aminobutyric acid (GABA), thereby contributing to the onset of HBOT-derived seizures. We provide long-overlooked evidence that (3) elevated ambient pressure directly inhibits GABA<sub>A</sub>, glycine and other receptors, leading to the rapid onset of seizures. Additionally, (4) acidosis facilitates the onset of seizures by an unknown mechanism. Only a combination of these mechanisms explains most phenomena seen in peripheral and CNS oxygen toxicity. Based on these proposed intertwined mechanisms, we suggest administering antioxidants (lowering ROS concentrations), pyridoxine (restoring GD activity), low doses of sedatives/anesthetics (reversing inhibitory effects of pressure on GABA<sub>A</sub> and glycine receptors), and treatment of acidemia before routine HBOT to prevent peripheral and CNS oxygen toxicity. Theoretically, similar preventive strategies can be applied before deep-sea diving to prevent life-threatening convulsions.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123169"},"PeriodicalIF":5.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503178","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

CDK14 is regulated by IGF2BP2 and involved in osteogenic differentiation via Wnt/β-catenin signaling pathway in vitro CDK14受IGF2BP2调控，在体外通过Wnt/β-catenin信号通路参与成骨分化。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-22 DOI: 10.1016/j.lfs.2024.123148

Zimo Zhou, Zhuoru Jin, Yicheng Tian, Chenghao Huangfu, Zheng Fan, Da Liu

{"title":"CDK14 is regulated by IGF2BP2 and involved in osteogenic differentiation via Wnt/β-catenin signaling pathway in vitro","authors":"Zimo Zhou, Zhuoru Jin, Yicheng Tian, Chenghao Huangfu, Zheng Fan, Da Liu","doi":"10.1016/j.lfs.2024.123148","DOIUrl":"10.1016/j.lfs.2024.123148","url":null,"abstract":"<div><h3>Aims</h3><div>Cyclin-dependent kinase (CDK) family proteins involve in various cellular processes via regulating the cell cycle; however, their expression during osteogenic differentiation and postmenopausal osteoporosis remains poorly understood.</div></div><div><h3>Main methods</h3><div>Using bioinformatics, we screened for CDK14 bound to Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) and explored its expression in vitro with time-gradient model and in a mouse model of postmenopausal osteoporosis, building on prior research. Subsequently, we investigated its effect on osteoblast proliferation, cell cycle dynamics, and osteogenic differentiation by administering CDK14 siRNA and the covalent inhibitor FMF-04-159-2. Furthermore, we examined the interaction between IGF2BP2 and CDK14. Finally, we validated the regulatory role of CDK14 on the Wnt/β-catenin pathway.</div></div><div><h3>Key findings</h3><div>Our findings demonstrate a time-dependent CDK14 expression patterns during osteogenic differentiation of MC3T3-E1 cell line, with an initial increase followed by gradual decline over time. Notably, CDK14 expression exhibited significant reduction in bone tissue of postmenopausal osteoporosis mouse model. CDK14 inhibition altered osteoblast cell cycle dynamics, significantly reduced cellular proliferation capacity, and impaired osteogenic differentiation ability. IGF2BP2 interacted with <em>CDK14</em> mRNA, and stabilizing mRNA's structure and inhibiting its degradation. Additionally, CDK14 facilitated Low-density lipoprotein receptor-related protein 6 (LRP6) and Glycogen synthase kinase 3β (GSK3β) phosphorylation, thus regulating β-catenin levels.</div></div><div><h3>Significance</h3><div>These findings provide further insight into the molecular mechanisms governing osteoblast proliferation, differentiation and osteoporosis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123148"},"PeriodicalIF":5.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503173","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

Phospholipase D2 drives cellular lipotoxicity and tissue inflammation in alcohol-associated liver disease 磷脂酶 D2 在酒精相关肝病中驱动细胞脂肪毒性和组织炎症。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-22 DOI: 10.1016/j.lfs.2024.123166

Yan Guo , Jichen Li , Xiulian Miao , Hansong Wang , Hailong Ge , Huihui Xu , Jianguo Wang , Yu Wang

{"title":"Phospholipase D2 drives cellular lipotoxicity and tissue inflammation in alcohol-associated liver disease","authors":"Yan Guo , Jichen Li , Xiulian Miao , Hansong Wang , Hailong Ge , Huihui Xu , Jianguo Wang , Yu Wang","doi":"10.1016/j.lfs.2024.123166","DOIUrl":"10.1016/j.lfs.2024.123166","url":null,"abstract":"<div><h3>Aims</h3><div>Excessive alcohol consumption leads to alcoholic liver disease (ALD), a major contributing factor to cirrhosis and hepatocellular carcinoma. In the present study we investigated the involvement of phospholipase D2 (PLD2) in the pathogenesis of ALD.</div></div><div><h3>Methods and materials</h3><div>ALD was induced in mice by chronic and binge ethanol feeding (the NIAAA model). Cellular transcriptome was examined by RNA-seq.</div></div><div><h3>Key findings</h3><div>Analysis of RNA-seq datasets indicated that PLD2 expression was up-regulated in liver tissues and in hepatocytes during ALD pathogenesis. Exposure of hepatocytes to ethanol treatment led to an increase in PLD2 expression. Similarly, ethanol feeding in mice stimulated PLD2 expression in the liver. On the contrary, PLD2 knockdown in hepatocytes down-regulated expression of pro-inflammatory and pro-lipogenic genes and dampened lipid accumulation. Consistently, PLD2 knockdown in mice significantly ameliorated ALD pathogenesis as evidenced by reduced steatosis and hepatic inflamamation. RNA-seq identified several metabolic pathways that were influenced by PLD2 deficiency.</div></div><div><h3>Significance</h3><div>Our data demonstrate that PLD2 is a novel regulator of ALD and suggest that small-molecule PLD2 inhibitors can be considered as a reasonable strategy for ALD treatment.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"358 ","pages":"Article 123166"},"PeriodicalIF":5.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503188","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