Life sciences最新文献

{"title":"Evidence for functional interaction between the CB1 and the mGlu7 receptors mediated signaling in modulation of anxiety behavior and cognition.","authors":"Barbara Chruścicka-Smaga ,&nbsp;Magdalena Sowa-Kućma ,&nbsp;Patrycja Pańczyszyn-Trzewik ,&nbsp;Bartosz Bobula ,&nbsp;Agata Korlatowicz ,&nbsp;Katarzyna Latocha ,&nbsp;Paulina Pabian ,&nbsp;Ewelina Czechowska ,&nbsp;Tomasz Lenda ,&nbsp;Agata Faron-Górecka ,&nbsp;Katarzyna Stachowicz","doi":"10.1016/j.lfs.2024.123313","DOIUrl":"10.1016/j.lfs.2024.123313","url":null,"abstract":"<div><div>Anxiety is a severe social problem. It is a disease entity that occurs alone or accompanies other diseases such as depression, phobia, or post-traumatic stress disorder. Our earlier studies demonstrated that blockage of arachidonic acid (AA) pathway via inhibition of cyclooxygenase-2 (COX-2) enzyme can modulate mGluRs-induced anxiety-like behavior. Here, we hypothesized that modulation of 2-arachidoglycerol (2-AG), a component of the AA pathway, concomitantly with modulation of mGluR7 signaling, should be adequate to trigger a similar response from the test organism. Since 2-AG is an endogenous agonist for CB1 receptors, we used a CB1/GPR55/μ-opioid receptor antagonist (AM251) alone and in combination with mGluR7 allosteric agonist (AMN082). Stress-induced hyperthermia (SIH) test was performed as a behavioral readout. AM251 has a dual mode on AMN082-mediated effects in SIH in CD-1 mice. Furthermore, the CB1 receptor ligand influenced adaptation to stress in repeated SIH procedures and learning possibilities of mice in the Barnes maze. We also found changes in mGluR7 protein expression levels in the prefrontal cortex (PFC) after mice were exposed to AM251, which showed the potential to attenuate the AMN082-induced decline in mGluR7 levels. The changes induced by AM251 on AMN082-mediated behavioral and biochemical effects were confirmed in electrophysiological experiments in which AM251 abolished AMN082-mediated LTP escalation in PFC. The mGluR7 overexpressed cell line was used to exclude the direct involvement of mGluR7 in AM251 activity. All the above results and the co-localization of CB1 and mGlu7 receptors detected in specific brain regions strongly suggest the specific interaction between CB1 and mGlu7 receptors and their signaling.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"361 ","pages":"Article 123313"},"PeriodicalIF":5.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142824287","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}

{"title":"Smooth muscle cell-specific CD47 deletion suppresses atherosclerosis","authors":"Naveed Pervaiz ,&nbsp;Rashid Mehmood ,&nbsp;Ravi Varma Aithabathula ,&nbsp;Ishita Kathuria ,&nbsp;WonMo Ahn ,&nbsp;Britney-Thuy Le ,&nbsp;Ki-Suk Kim ,&nbsp;Udai P. Singh ,&nbsp;Gabor Csanyi ,&nbsp;Bhupesh Singla","doi":"10.1016/j.lfs.2024.123315","DOIUrl":"10.1016/j.lfs.2024.123315","url":null,"abstract":"<div><h3>Background</h3><div>Recent smooth muscle cell (SMC)-lineage tracing and single-cell RNA sequencing (scRNA-seq) experiments revealed a significant role of SMC-derived cells in atherosclerosis development. Further, thrombospondin-1 (TSP1), a matricellular protein, and activation of its receptor cluster of differentiation (CD) 47 have been linked with atherosclerosis. However, the role of vascular SMC TSP1-CD47 signaling in regulating VSMC phenotype and atherogenesis remains unknown.</div></div><div><h3>Methods</h3><div>We investigated the role of SMC CD47 activation by TSP1 in regulating VSMC phenotype and atherosclerosis development using various <em>in vitro</em> cell-based assays, molecular biological techniques, immunohistological approaches, reanalysis of publicly available scRNA-seq data, and cell-specific knockout mice.</div></div><div><h3>Results</h3><div>We observed elevated TSP1 expression in human atherosclerotic vascular tissues and VSMCs. TSP1-treated VSMCs exhibited decreased expression of contractile SMC markers (<em>ACTA2, CNN1</em>, and <em>TAGLN</em>) and increased proliferation. Additional experiments and reanalysis of the scRNA-seq dataset showed CD47 as the major TSP1 receptor in VSMCs, with its expression increased in SMC-derived modulated cells of murine atherosclerotic arteries. Knockdown of <em>CD47</em> gene in human VSMCs upregulated expression of contractile SMC markers and abrogated TSP1's effects on these genes. SMC-specific <em>Cd47</em> deletion in mice suppressed atherosclerotic lesion formation, reduced macrophage accumulation, and decreased necrotic area. However, no significant differences were observed in weight gain, liver and adipose tissue mass, plasma total cholesterol, and fasting blood glucose between control and SMC-restricted <em>Cd47-</em>deficient mice. Further experiments demonstrated increased efferocytosis of apoptotic <em>CD47</em>-silenced VSMCs by macrophages.</div></div><div><h3>Conclusions</h3><div>These findings suggest that CD47 plays a crucial role in regulating VSMC phenotype, and SMC-specific-<em>Cd47</em> deletion suppresses atherosclerosis.</div></div><div><h3>New and noteworthy</h3><div>VSMC phenotypic switching contributes to atherosclerosis development. The present study reports the novel observations that <em>Cd47</em> levels are upregulated in phenotypically modulated SMCs within atherosclerotic arteries and targeted deletion of <em>Cd47</em> specifically in SMCs attenuates atherosclerosis. Mechanistic <em>in vitro</em> investigations further showed that TSP1-CD47 signaling regulates VSMC phenotype. Therefore, targeting SMC CD47 represents a promising therapeutic target to suppress atherogenesis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"361 ","pages":"Article 123315"},"PeriodicalIF":5.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828881","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}

{"title":"Bacillus pumilus SMU5927 protect mice from damage caused by Salmonella Enteritidis colonization","authors":"Longjun Ran ,&nbsp;Jiangying Lei ,&nbsp;Haifeng Liu ,&nbsp;Danni Wang ,&nbsp;Jiahao Liu ,&nbsp;Falong Yang ,&nbsp;Dechun Chen","doi":"10.1016/j.lfs.2024.123291","DOIUrl":"10.1016/j.lfs.2024.123291","url":null,"abstract":"<div><h3>Background</h3><div><em>Salmonella Enteritidis</em> is one of the main pathogens of foodborne diseases and an important pathogen causing diarrhea in yaks. Antibiotics are the mainstay of treatment for salmonellosis, but the widespread use of antibiotics has increased <em>Salmonella</em> resistance. Probiotics have been shown to antagonize <em>Salmonella</em> and reduce <em>Salmonella</em> infection. <em>Bacillus pumilus</em> is one of the microbial feed additives approved by the Chinese Ministry of Agriculture for use in animal breeding, which has the effect of improving animal growth performance and immunity, among others. Therefore, this paper explored the anti-infective effect of <em>Bacillus pumilus</em> against <em>Salmonella</em>.</div></div><div><h3>Results</h3><div><em>Bacillus pumilus</em> SMU5927 significantly enhances the intestinal mechanical barrier and reduces the number of <em>Salmonella</em> transferred to the organs. <em>Bacillus pumilus</em> SMU5927 ameliorated intestinal tissue damage and attenuated intestinal inflammatory responses in mice. In addition, <em>Bacillus pumilus</em> increased the ratio of the Firmicutes/Bacteroidetes in the intestinal flora, increased the abundance of beneficial bacteria such as <em>Lactobacillus</em>, and decreased the abundance of harmful bacteria.</div></div><div><h3>Conclusion</h3><div>This study confirmed the role of <em>Bacillus pumilus</em> SMU5927 in preventing and attenuating <em>Salmonella</em> damage and provided ideas for the development of novel antimicrobial drugs.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"361 ","pages":"Article 123291"},"PeriodicalIF":5.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142780467","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}

{"title":"Aerobic exercise training attenuates ischemia-reperfusion injury in mice by decreasing the methylation level of METTL3-associated m6A RNA in cardiomyocytes","authors":"Xinmin Zhang ,&nbsp;Dong-Xu Huang ,&nbsp;Chengluan Xuan ,&nbsp;Yanhui Li ,&nbsp;Yuting Jiang ,&nbsp;Xuehan Wu ,&nbsp;Wenqian Zhou ,&nbsp;Yang Lei ,&nbsp;Fan Yang ,&nbsp;Haichun Ma ,&nbsp;Kun Hou ,&nbsp;Xue Han ,&nbsp;Guichen Li","doi":"10.1016/j.lfs.2024.123294","DOIUrl":"10.1016/j.lfs.2024.123294","url":null,"abstract":"<div><h3>Background and aims</h3><div>Ischemic heart disease (IHD) presents a significant global health challenge, with myocardial ischemia-reperfusion injury (MIRI) being a major pathophysiological contributor and lacking effective interventions. While aerobic exercise training (AET) enhances cardiovascular health, its protective mechanism in MIRI remains elusive. This study aims to elucidate the protective effect of AET in MIRI and its underlying mechanism.</div></div><div><h3>Methods</h3><div>A mouse model of AET and MIRI was established to evaluate basic indices, cardiac ultrasound, and myocardial injury markers. Dot Blot, qRT-PCR, and Western blot were employed to assess m⁶A RNA methylation levels and related protein expression in myocardial tissue. In vitro, primary cardiomyocyte culture was utilized to mimic MIRI, evaluating cell viability, mitochondrial membrane potential, etc. Finally, myocardial tissues of MIRI mice were immunoprecipitated for m⁶A RNA methylation and sequenced to analyze related signaling pathways.</div></div><div><h3>Key results</h3><div>AET significantly improved cardiac function and mitigated myocardial injury and fibrosis. Moreover, AET protected myocardium from MIRI by reducing m⁶A RNA methylation levels and modulating METTL3 expression. In vitro experiments demonstrated that the decrease in m⁶A RNA methylation levels and METTL3 expression conferred resistance to hypoxia/reoxygenation-induced injury. Furthermore, sequencing results indicated elevated myocardial tissue m⁶A RNA methylation levels during MIRI, activation of the Nrf2-related signaling pathway, and AET-mediated regulation of the Nrf2/HO-1 signaling pathway, thereby attenuating MIRI through modulation of METTL3-related m⁶A methylation.</div></div><div><h3>Conclusion and significance</h3><div>AET attenuates MIRI by reducing the level of METTL3-related m⁶A RNA methylation in cardiomyocytes and activating the Nrf2/HO-1 antioxidant signaling pathway. This finding provides a novel insight and strategy for the prevention and treatment of IHD, holding significant clinical implications.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"361 ","pages":"Article 123294"},"PeriodicalIF":5.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792123","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}

{"title":"Sinomenine modulates the metabolic reprogramming induced by sepsis via CHRNA7","authors":"Jie Zhao,&nbsp;Zi Wang,&nbsp;Xinxin Zou,&nbsp;Jinlong Liao,&nbsp;Yan Zhang,&nbsp;Wenjie Zhang,&nbsp;Jingrong Yu,&nbsp;Fengjie Huang","doi":"10.1016/j.lfs.2024.123332","DOIUrl":"10.1016/j.lfs.2024.123332","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Sepsis is a condition capable of causing systemic inflammation and metabolic reprogramming. Previous studies have shown that sinomenine (SIN) can mitigate sepsis by reducing inflammation, while the effect on metabolic reprogramming is unclear. The aim of this study is to investigate the function of SIN in metabolic reprogramming in sepsis.</div></div><div><h3>Experimental approach</h3><div>Differential metabolites in lung tissue and serum were analyzed by 1H Nuclear Magnetic Resonance (¹H NMR) and metabolomics were used to compare metabolic changes in septic mice. Nicotinic acetylcholine receptors alpha7 subunit (CHRNA7)-Knockdown (KD) mice and other techniques, were used to detect the expression of markers of several metabolic pathways.</div></div><div><h3>Key results</h3><div>Metabolomics studies showed that SIN could affect energy metabolism, particularly glucose metabolism, and this effect may be related to the activation of CHRNA7. Further studies showed that SIN could inhibit aerobic glycolysis, promote glutamine anaplerosis, reduce pentose phosphate pathway flux and ultimately mediate metabolic reprogramming.</div></div><div><h3>Conclusion and implications</h3><div>SIN restores glycolysis and glutamine anaplerosis by interacting with CHRNA7, thereby mediating metabolic reprogramming and mitigating sepsis. These findings shed light on the mechanism of SIN in attenuating sepsis from a metabolic perspective.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"361 ","pages":"Article 123332"},"PeriodicalIF":5.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895694","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}

{"title":"Alogliptin attenuates STZ-induced diabetic nephropathy in rats through the modulation of autophagy, apoptosis, and inflammation pathways: Targeting NF-κB and AMPK/mTOR pathway","authors":"Salma M. Selim ,&nbsp;Hassan M. El Fayoumi ,&nbsp;Norhan M. El-Sayed ,&nbsp;Eman T. Mehanna ,&nbsp;Reem M. Hazem","doi":"10.1016/j.lfs.2024.123307","DOIUrl":"10.1016/j.lfs.2024.123307","url":null,"abstract":"<div><h3>Aim</h3><div>Diabetic nephropathy (DN) is a type of microvascular complication that arises from diabetes mellitus and leads to further health issues. Most importantly, the prevalence of DN is steadily rising in developed countries. This research explored the therapeutic benefits of alogliptin, a dipeptidyl peptidase IV (DPP-4) inhibitor, on streptozotocin (STZ)-induced DN and its underlying mechanisms in rats.</div></div><div><h3>Main methods</h3><div>Ten rats were allocated to group 1, served as the normal group; and received saline. To develop diabetes, thirty rats were administered a single intraperitoneal dose of STZ (45 mg/kg). STZ-induced diabetic rats were randomly assigned to three groups: group 2 diabetic control; was given saline, groups 3 and 4 received alogliptin (10 mg/kg) and (20 mg/kg), respectively. The treatment began 8 weeks after diabetes onset and continued for four weeks. Histopathological alterations in the kidney were detected. Serum was collected to measure blood glucose levels (BGL), renal function, and lactate dehydrogenase (LDH). Tissue samples were collected to detect changes in oxidative stress (OS), inflammation, 5′ adenosine monophosphate-activated protein kinase (AMPK), and the mammalian target of Rapamycin (mTOR) signaling pathways in addition to apoptotic and autophagy changes.</div></div><div><h3>Key findings</h3><div>Alogliptin reduced STZ-induced histological changes in the kidney as well as OS, and inflammation. Alogliptin also ameliorated the AMPK/mTOR signaling pathways, enhanced autophagy, and reduced apoptosis.</div></div><div><h3>Significance</h3><div>These results demonstrate that alogliptin ameliorates inflammation and OS and consequently modulates the AMPK/mTOR axis along with targeting autophagy and apoptosis, leading to the alleviation of DN.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"361 ","pages":"Article 123307"},"PeriodicalIF":5.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813666","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}

{"title":"Nitazoxanide alleviates experimental pulmonary fibrosis by inhibiting the development of cellular senescence","authors":"Xianzhe Wang ,&nbsp;Yanyan Zhu ,&nbsp;Huilin Liu ,&nbsp;Xiangchuan Wang ,&nbsp;Hongjie Zhang ,&nbsp;Xiuping Chen","doi":"10.1016/j.lfs.2024.123302","DOIUrl":"10.1016/j.lfs.2024.123302","url":null,"abstract":"<div><div>Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease characterized by irreversible lung scarring with a poor prognosis. Emerging evidence has revealed that IPF is an aging-related disease, and the development of cellular senescence plays a pivotal role in persistent remodeling and fibrotic scarring, acting as a key mechanism in the pathophysiology of IPF. Exploring therapeutic strategies for modulating cellular senescence can provide crucial insights into unraveling IPF processes. Here, we have identified Nitazoxanide (NTZ), an FDA-approved antiprotozoal agent, has specific effects on inhibiting cellular senescence development. In the bleomycin and D-galactose-induced senescence model, NTZ effectively inhibits senescence associated-β-gal staining and preserves cell proliferation ability. We also found that NTZ effectively impedes senescence progression in the bleomycin-induced pulmonary fibrosis model, while mitigating the release of senescence-associated secretory phenotype and alleviating pulmonary fibrosis. The anti-senescence effect of NTZ is mechanistically dependent on the preservation of nuclear SIRT1 expression. We observed that PI3K induces a WIPI1-mediated nucleophagic degradation of SIRT1, while NTZ effectively inhibits PI3K and suppresses WIPI1 expression, thereby maintaining SIRT1 expression in the nucleus and exerting its anti-senescence function. Collectively, our research has shown that NTZ can inhibit PI3K in senescence progression, leading to the inhibition of WIPI1-mediated SIRT1 nucleophagic degradation. As a result, NTZ alleviates fibrosis by inhibiting senescence development.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"361 ","pages":"Article 123302"},"PeriodicalIF":5.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813670","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}

{"title":"Elucidating novel mechanism of action of spiperone for drug repurposing to prevent and treat murine colitis and sepsis","authors":"Luyun Zhang ,&nbsp;Jianxin Wang ,&nbsp;Shaoya Rong ,&nbsp;Hui Dong","doi":"10.1016/j.lfs.2024.123268","DOIUrl":"10.1016/j.lfs.2024.123268","url":null,"abstract":"<div><h3>Aims</h3><div>While Ca²⁺ signaling plays a vital role in maintaining normal endothelial function and vascular activity, aberrant Ca²⁺ signaling in endothelial dysfunction is involved in the pathogenesis of inflammation. As a safe anti-psychotic drug to mobilize Ca²⁺ signaling, we repurposed spiperone as a potential drug for two intestinal epithelial injury related diseases, colitis and sepsis.</div></div><div><h3>Materials and methods</h3><div>Spiperone-induced vasorelaxation of human submucosal arterioles and mesenteric arterioles from wide-type and TRPV4 KO mice was determined by Mulvany-style wire myograph. The action of spiperone in HUVEC was tested by Ca²⁺ imaging and patch clamp, and its action on murine mesenteric arterioles was measured in <em>vivo</em>. LPS- and CLP-induced septic mice and DSS-induced colitic mice were used to examine the anti-inflammatory effects of spiperone.</div></div><div><h3>Key findings</h3><div>Spiperone induced endothelium-dependent hyperpolarization (EDH)-mediated vasorelaxation of healthy arterioles with EC₅₀ of ∼50 nM predominately via PLC/IP₃/IP₃R pathway to induce endoplasmic reticulum (ER) Ca²⁺ release and further to promote Ca²⁺ entry via TRPV4-constituted SOCE. In both LPS- and CLP-induced septic mice, spiperone effectively prevented and treated sepsis by reducing serum proinflammatory factors, alleviating multiple organ dysfunction, rescuing the impaired EDH-mediated vasorelaxation and improving murine survival rate. Similarly, spiperone could also protect against murine colitis.</div></div><div><h3>Significance</h3><div>We reveal new action mode and mechanism of spiperone to induce EDH-mediated vasorelaxation of both human and murine arterioles to protect against colitis and sepsis by innovatively inducing PLC/IP₃R/Ca²⁺ signaling rather than canonically antagonizing GPCR. Spiperone could be repurposed as a potential new drug for the prevention/treatment of colitis and sepsis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"361 ","pages":"Article 123268"},"PeriodicalIF":5.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695509","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}

{"title":"Exploring the potential of CAR-macrophage therapy","authors":"Yongyu Shi ,&nbsp;Xia Li ,&nbsp;Yanlei Dong ,&nbsp;Hong Yuan ,&nbsp;Yingyue Wang ,&nbsp;Ruoxuan Yang","doi":"10.1016/j.lfs.2024.123300","DOIUrl":"10.1016/j.lfs.2024.123300","url":null,"abstract":"<div><div>Chimeric antigen receptor T cell (CAR-T) cell therapy has achieved significant success in treating hematologic malignancies, but its efficacy in solid tumor treatment is relatively limited. Therefore, researchers are exploring other genetically modified immune cells as potential treatment strategies to address the challenges in solid tumor therapy. Chimeric antigen receptor macrophage (CAR-M) involves the genetic engineering of macrophages to express chimeric antigen receptors, enabling them to recognize and attack tumor cells. In contrast to CAR-T cells, CAR-M cells offer distinct advantages such as enhanced infiltration and survival capabilities, along with a diverse array of anti-tumor mechanisms, making them a promising immunotherapy approach that may yield better results in solid tumor treatment. This article provides an overview of the research advancements in CAR-M-mediated tumor immunotherapy, encompassing topics such as the design and transduction of CAR, cell sources, anti-tumor mechanisms and clinical applications. The future research direction in this field will involve leveraging innovative biological technologies to augment the anti-tumor efficacy of CAR-M, understand the underlying mechanisms, and enhance the safety and efficacy of CAR-M therapy.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"361 ","pages":"Article 123300"},"PeriodicalIF":5.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792124","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}

{"title":"The matrix protease ADAMTS1 is transcriptionally activated by KLF6 and contributes to cardiac fibrosis in non-ischemic cardiomyopathy","authors":"Nan Li ,&nbsp;Chenghao Zhu ,&nbsp;Yujia Xue ,&nbsp;Naxia Chen ,&nbsp;Wenping Xu ,&nbsp;Mingzi Song ,&nbsp;Mengwen Qi ,&nbsp;Shan Huang ,&nbsp;Mingming Fang","doi":"10.1016/j.lfs.2024.123295","DOIUrl":"10.1016/j.lfs.2024.123295","url":null,"abstract":"<div><h3>Aims</h3><div>Aberrant cardiac fibrosis, defined as excessive production and deposition of extracellular matrix (ECM), is mediated by myofibroblasts. ECM-producing myofibroblasts are primarily derived from resident fibroblasts during cardiac fibrosis. The mechanism underlying fibroblast-myofibroblast transition is not fully understood.</div></div><div><h3>Methods</h3><div>Cardiac fibrosis was induced by transverse aortic constriction (TAC) or by angiotensin II (Ang II) infusion in C57B6/j mice. Cellular transcriptome was evaluated by RNA-seq and CUT&amp;Tag-seq.</div></div><div><h3>Results</h3><div>Integrated transcriptomic screening revealed that a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) was a novel transcriptional target for Kruppel-like factor 6 (KLF6) in cardiac fibroblasts. Treatment with either TGF-β or Ang II up-regulated ADAMTS1 expression. KLF6 knockdown attenuated whereas KLF6 over-expression enhanced ADAMTS1 induction. ChIP assay and reporter assay showed that KLF6 was recruited to the ADAMTS1 promoter to activate its transcription. Consistently, ADAMTS1 knockdown suppressed fibroblast-myofibroblast transition <em>in vitro</em>. Importantly, myofibroblast-specific ADAMTS1 depletion attenuated cardiac fibrosis and normalized heart function in mice.</div></div><div><h3>Significance</h3><div>In conclusion, our data demonstrate that ADAMTS1, as a downstream target of KLF6, contributes to cardiac fibrosis by regulating fibroblast-myofibroblast transition.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"361 ","pages":"Article 123295"},"PeriodicalIF":5.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792130","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}