JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

{"title":"A novel homozygous mutation in the DNAAF3 gene leads to severe asthenozoospermia and teratospermia","authors":"Dongjia Chen,&nbsp;Guoqing Fan,&nbsp;Yan Xu,&nbsp;Peng Luo,&nbsp;Qinyun Chen,&nbsp;Xuren Chen,&nbsp;Zexin Guo,&nbsp;Xianqing Zhu,&nbsp;Yong Gao","doi":"10.1111/jcmm.70092","DOIUrl":"https://doi.org/10.1111/jcmm.70092","url":null,"abstract":"<p>Primary ciliary dyskinesia (PCD) is an autosomal recessive genetic disorder characterized by ultrastructural defects in the cilia or flagella of cells, causing respiratory abnormalities, sinusitis, visceral transposition, and male infertility. DNAAF3 plays an important role in the assembly and transportation of axonemal dynein complexes in cilia or flagella and has been shown to be associated with PCD. To date, only two cases of PCD with infertility associated with <i>DNAAF3</i> mutations have been reported, and no mouse models for this gene have been successfully constructed. This study was conducted on an infertile Chinese male patient with a history of bronchitis. Examination of the patient's semen revealed severe asthenozoospermia and teratospermia. Whole exome sequencing revealed a new homozygous loss-of-function <i>DNAAF3</i> mutation. CRISPR-Cas9 gene-editing technology was used to construct the same mutation in C57/B6 mice, revealing that homozygous C57/B6 mice were characterized by severe hydrocephalus and early death. The results of this study expand the mutation spectrum of <i>DNAAF3</i> and confirm its correlation with PCD pathogenesis. This study provides new insights on the mechanisms underlying male infertility related to <i>DNAAF3</i> mutation and PCD.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Farrerol alleviates insulin resistance and hepatic steatosis of metabolic associated fatty liver disease by targeting PTPN1","authors":"Jingwen Gao,&nbsp;Xiaomin Cang,&nbsp;Lu Liu,&nbsp;Jiaxi Lin,&nbsp;Shiqi Zhu,&nbsp;Lihe Liu,&nbsp;Xiaolin Liu,&nbsp;Jinzhou Zhu,&nbsp;Chunfang Xu","doi":"10.1111/jcmm.70096","DOIUrl":"https://doi.org/10.1111/jcmm.70096","url":null,"abstract":"<p>Metabolic associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide, characterized by excess lipid deposition. Insulin resistance (IR) serves as a fundamental pathogenic factor in MAFLD. However, currently, there are no approved specific agents for its treatment. Farrerol, a novel compound with antioxidant and anti-inflammatory effects, has garnered significant attention in recent years due to its hepatoprotective properties. Despite this, the precise underlying mechanisms of action remain unclear. In this study, a network pharmacology approach predicted protein tyrosine phosphatase non-receptor type 1 (PTPN1) as a potential target for farrerol's action in the liver. Subsequently, the administration of farrerol improved insulin sensitivity and glucose tolerance in MAFLD mice. Furthermore, farrerol alleviated lipid accumulation by binding to PTPN1 and reducing the dephosphorylation of the insulin receptor (INSR) in HepG2 cells and MAFLD mice. Thus, the phosphoinositide 3-kinase/serine/threonine-protein kinases (PI3K/AKT) signalling pathway was active, leading to downstream protein reduction. Overall, the study demonstrates that farrerol alleviates insulin resistance and hepatic steatosis of MAFLD by targeting PTPN1.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wharton's Jelly mesenchymal stem cell-derived extracellular vesicles induce liver fibrosis-resolving phenotype in alternatively activated macrophages","authors":"Shukoofeh Torabi,&nbsp;Morteza Zarrabi,&nbsp;Faezeh Shekari,&nbsp;Hedie Poorkazem,&nbsp;Majid Lotfinia,&nbsp;Stefan Bencina,&nbsp;Roberto Gramignoli,&nbsp;Moustapha Hassan,&nbsp;Mustapha Najimi,&nbsp;Massoud Vosough","doi":"10.1111/jcmm.18507","DOIUrl":"https://doi.org/10.1111/jcmm.18507","url":null,"abstract":"<p>The potential of extracellular vesicles (EVs) isolated from mesenchymal stromal cells in guiding macrophages toward anti-inflammatory immunophenotypes, has been reported in several studies. In our study, we provided experimental evidence of a distinctive effect played by Wharton Jelly mesenchymal stromal cell-derived EVs (WJ-EVs) on human macrophages. We particularly analyzed their anti-inflammatory effects on macrophages by evaluating their interactions with stellate cells, and their protective role in liver fibrosis. A three-step gradient method was used to isolate monocytes from umbilical cord blood (UCB). Two subpopulations of WJ-EVs were isolated by high-speed (20,000 <i>g</i>) and differential ultracentrifugation (110,000 <i>g</i>). Further to their characterization, they were designated as EV20K and EV110K and incubated at different concentrations with UCB-derived monocytes for 7 days. Their anti-fibrotic effect was assessed by studying the differentiation and functional levels of generated macrophages and their potential to modulate the survival and activity of LX2 stellate cells. The EV20K triggers the polarization of UCB-derived monocytes towards a peculiar M2-like functional phenotype more effectively than the M-CSF positive control. The EV20K treated macrophages were characterized by a higher expression of scavenger receptors, increased phagocytic capacity and production level of interleukin-10 and transforming growth factor-β. Conditioned medium from those polarized macrophages attenuated the proliferation, contractility and activation of LX2 stellate cells. Our data show that EV20K derived from WJ-MSCs induces activated macrophages to suppress immune responses and potentially play a protective role in the pathogenesis of liver fibrosis by directly inhibiting HSC’s activation.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.18507","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EphrinB2-mediated chondrocyte autophagy induces post-traumatic arthritis via rupture of cartilage homeostasis","authors":"Zhengsheng Bao,&nbsp;Pinger Wang,&nbsp;Yanan Li,&nbsp;Huiqin Ding,&nbsp;Jingyuan Wen,&nbsp;Kaiao Zou,&nbsp;Xu Wang,&nbsp;Yang Yu,&nbsp;Xuefeng Li,&nbsp;Yingquan Liu,&nbsp;Hongting Jin,&nbsp;Lianguo Wu,&nbsp;Jun Ying","doi":"10.1111/jcmm.70095","DOIUrl":"https://doi.org/10.1111/jcmm.70095","url":null,"abstract":"<p>EphrinB2, a member of the Ephrin family, has been linked to several orthopaedic conditions. Nevertheless, the correlation between ephrinB2 and post-traumatic arthritis (PTOA) remains unclear. Human PTOA cartilage from human and mouse knee joints was systematically analysed to investigate the relationship between EphrinB2 and PTOA using SO-FG and toluidine blue staining, micro-CT, histomorphometry, immunohistochemistry, immunofluorescence, lentiviral articular injection and in situ end labeling (TUNEL) assays. EphrinB2 expression was significantly downregulated in PTOA chondrocytes. Blocking EphrinB2 increased the breakdown of cartilage matrix in mice with PTOA via reducing the process of chondrocyte autophagy. The presence of severe cartilage damage was evident, as indicated by a considerable decrease in both cartilage thickness and area, accompanied by an increase in chondrocyte death. Altogether, EphrinB2 is required for the maintenance of cartilage homeostasis in post-traumatic arthritis, and EphrinB2 ablation is associated with accelerated chondrocyte matrix degeneration, finally causing damage to the articular cartilage.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142244388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Luteolin exerts anti-tumour immunity in hepatocellular carcinoma by accelerating CD8+ T lymphocyte infiltration","authors":"Shijiao Cai,&nbsp;Yidan Gou,&nbsp;Yanyan Chen,&nbsp;Xiaoran Hou,&nbsp;Jing Zhang,&nbsp;Chongwen Bi,&nbsp;Peng Gu,&nbsp;Miao Yang,&nbsp;Hanxu Zhang,&nbsp;Weilong Zhong,&nbsp;Hengjie Yuan","doi":"10.1111/jcmm.18535","DOIUrl":"https://doi.org/10.1111/jcmm.18535","url":null,"abstract":"<p>Luteolin, a commonly used traditional Chinese medicine, has been utilized for several decades in the treatment of hepatocellular carcinoma (HCC). Previous research has demonstrated its anti-tumour efficacy, but its underlying mechanism remains unclear. This study aimed to assess the therapeutic effects of luteolin in H22 tumour-bearing mice. luteolin effectively inhibited the growth of solid tumours in a well-established mouse model of HCC. High-throughput sequencing revealed that luteolin treatment could enhance T-cell activation, cell chemotaxis and cytokine production. In addition, luteolin helped sustain a high ratio of CD8⁺ T lymphocytes in the spleen, peripheral blood and tumour tissues. The effects of luteolin on the phenotypic and functional changes in tumour-infiltrating CD8⁺ T lymphocytes were also investigated. Luteolin restored the cytotoxicity of tumour-infiltrating CD8⁺ T lymphocytes in H22 tumour-bearing mice. The CD8⁺ T lymphocytes exhibited intensified phenotype activation and increased production of granzyme B, IFN-γ and TNF-α in serum. The combined administration of luteolin and the PD-1 inhibitor enhanced the anti-tumour effects in H22 tumour-bearing mice. Luteolin could exert an anti-tumour immune response by inducing CD8⁺ T lymphocyte infiltration and enhance the anti-tumour effects of the PD-1 inhibitor on H22 tumour-bearing mice.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.18535","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to ‘Neprilysin inhibitors and risk of Alzheimer's disease: A future perspective’","authors":"","doi":"10.1111/jcmm.70058","DOIUrl":"https://doi.org/10.1111/jcmm.70058","url":null,"abstract":"<p>Ali NH, Al-Kuraishy HM, Al-Gareeb AI, et al. Neprilysin inhibitors and risk of Alzheimer's disease: a future perspective. <i>J Cell Mol Med</i>. 2024;28:e17993. doi:10.1111/jcmm.17993</p><p>In Introduction section, the sentence ‘AD is the most common type of dementia, accounting for about 70% of all dementia types’.¹ is incorrect. The sentence should have read: ‘AD is the most common type of dementia, accounting for about 60% to 80% of all dementia types’.^1,149</p><p>In Introduction section, the sentence ‘AD is the seventh leading cause of death in the United States, affecting 50 million people globally.³ Approximately 6% of the general population is affected, whereas more than 65% of affected cases are women; nonetheless, 10% of early-onset dementia affecting people aged 30–60 is attributed to AD’.³ is incorrect. The sentence should have read: ‘The global incidence of all-cause dementia is projected to rise from 50 million in 2010 to 113 million by 2050.³ Currently, over 55 million people suffer from AD, which ranks as the seventh leading cause of death in the United States.¹⁵⁰ Additionally, women constitute over 65% of those affected by AD in the United States.¹⁵¹ Nonetheless, 10% of early-onset dementia affecting people aged 30–60 is attributed to AD’.³</p><p>In the section 3 NEP INHIBITORS IN AD, the sentence ‘Sacubitril was the first NEP inhibitor approved in 2015 to manage heart failure’.⁴⁰ is incorrect. The sentence should have read: ‘Sacubitril was the first NEP inhibitor approved in 2015 to manage heart failure’.^40,152</p><p>Finally in Table 2 for the Bavishi et al.⁴³ the study type ‘Experimental study’ is incorrect. The correct is ‘Review’.</p><p>\u0000 <b>New References</b>\u0000 </p><p>(149) (2023), 2023 Alzheimer's disease facts and figures. <i>Alzheimer's Dement</i>. 19: 1598-1695. doi:10.1002/alz.13016</p><p>(150) 2024 Alzheimer's disease facts and figures. 1/6/2024. https://www.alz.org/media/Documents/alzheimers-facts-and-figures.pdf</p><p>(151) Rabinovici GD. Late-onset Alzheimer Disease. Continuum (Minneap Minn). 2019;25(1):14-33. doi: 10.1212/CON.0000000000000700. PMID: 30707185; PMCID: PMC6548536.</p><p>(152) Fala L. Entresto (Sacubitril/Valsartan): first-in-class angiotensin receptor neprilysin inhibitor FDA approved for patients with heart failure. <i>Am Health Drug Benefits</i>. 2015;8(6):330-334. PMID: 26557227; PMCID: PMC4636283.</p><p>We apologize for this error.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antiviral effect of cannabidiol on K18-hACE2 transgenic mice infected with SARS-CoV-2","authors":"Hivda Ulbegi Polat,&nbsp;Hicret Asli Yalcin,&nbsp;Deniz Köm,&nbsp;Özge Aksoy,&nbsp;Irem Abaci,&nbsp;Arzu Tas Ekiz,&nbsp;Müge Serhatli,&nbsp;Selma Onarici","doi":"10.1111/jcmm.70030","DOIUrl":"https://doi.org/10.1111/jcmm.70030","url":null,"abstract":"<p>The aim of this study was to determine the antiviral activity of cannabidiol (CBD) against SARS-CoV-2 infection. CBD is the second most studied cannabinoid obtained from <i>Cannabis</i> plants. We investigated the potential use of CBD, which has so far proven to have a positive effect on different diseases, in the SARS-CoV-2 infection. To test this, in vivo studies were carried out using K18-hACE2 transgenic mice. To reveal the potential therapeutic effect of the CBD at the histopathological and molecular level challenge experiments were performed. The study was designed with two groups (<i>n</i> = 10) and in the treatment group animals were infected with SARS-CoV-2 virus strain B.1.1.7 alpha before the administration of CBD. While the disease progressed and resulted in death in the control group that was infected by the virus alone, it was observed that the infection slowed down and the survival rate increased in the mice treated with CBD along with the virus. In this study, K18-hACE2 transgenic mice infected with the wild SARS-CoV-2 virus were used to investigate and prove the antiviral activity of CBD.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70030","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: SSRP1 Promotes Colorectal Cancer Progression and is Negatively Regulated by miR-28-5p","authors":"","doi":"10.1111/jcmm.70048","DOIUrl":"https://doi.org/10.1111/jcmm.70048","url":null,"abstract":"<p><b>Retraction</b>: Wu W, He K, Guo Q, et al. SSRP1 Promotes Colorectal Cancer Progression and is Negatively Regulated by miR-28-5p. <i>J Cell Mol Med</i>. 2019;23(5): 3118-3129. doi: 10.1111/jcmm.14134</p><p>The above article, published online on 14 February 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the Journal Editor-in-Chief, Stefan Constantinescu; The Foundation for Cellular and Molecular Medicine; and John Wiley &amp; Sons Ltd. The retraction has been agreed due to the authors' admission that some of the images were mistakenly included in this article, with some of the data belonging to another project. Additionally, the article was submitted for publication by Wei Wu without consent from the co-author Honggang Yu.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70048","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking reproducible transcriptomic signatures for acute myeloid leukaemia: Integration, classification and drug repurposing","authors":"Haoran Chen,&nbsp;Jinqi Lu,&nbsp;Zining Wang,&nbsp;Shengnan Wu,&nbsp;Shengxiao Zhang,&nbsp;Jie Geng,&nbsp;Chuandong Hou,&nbsp;Peifeng He,&nbsp;Xuechun Lu","doi":"10.1111/jcmm.70085","DOIUrl":"https://doi.org/10.1111/jcmm.70085","url":null,"abstract":"<p>Acute myeloid leukaemia (AML) is a highly heterogeneous disease, which lead to various findings in transcriptomic research. This study addresses these challenges by integrating 34 datasets, including 26 control groups, 6 prognostic datasets and 2 single-cell RNA sequencing (scRNA-seq) datasets to identify 10,000 AML-related genes (ARGs). We focused on genes with low variability and high consistency and successfully discovered 191 AML signatures (ASs). Leveraging machine learning techniques, specifically the XGBoost model and our custom framework, we classified AML subtypes with both scRNA-seq and bulk RNA-seq data, complementing the ELN2022 classification approach. Our research also identified promising treatments for AML through drug repurposing, with solasonine showing potential efficacy for high-risk AML patients, supported by molecular docking and transcriptomic analyses. To enhance reproducibility and customizability, we developed CSAMLdb, a user-friendly database platform. It facilitates the reuse and personalized analysis of nearly all results obtained in this research, including single-gene prognostics, multi-gene scoring, enrichment analysis, machine learning risk assessment, drug repositioning analysis and literature abstract named entity recognition. CSAMLdb is available at http://www.csamldb.com.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of sodium-glucose cotransporter-2 improves anaemia in mice and humans with sickle cell disease, and reduces infarct size in a murine stroke model","authors":"Jintao Wang,&nbsp;Paul Silaghi,&nbsp;Chiao Guo,&nbsp;David Harro,&nbsp;Daniel T. Eitzman","doi":"10.1111/jcmm.70091","DOIUrl":"https://doi.org/10.1111/jcmm.70091","url":null,"abstract":"<p>Sodium-glucose cotransporter-2 (SGLT-2) is expressed in the kidney and may contribute to anaemia and cardiovascular diseases. The effect of SGLT-2 inhibition on anaemia and vascular endpoints in sickle cell disease (SCD) is unknown. A murine model of SCD was studied to determine the effects of the SGLT-2 inhibitor, empagliflozin, on anaemia and stroke size. The University of Michigan's Precision Health Database was used to evaluate the effect of SGLT-2 inhibitors on anaemia in humans with SCD. SCD mice treated with daily empagliflozin for 8 weeks demonstrated increases in haemoglobin, haematocrit, erythrocyte counts, reticulocyte percentage and erythropoietin compared to vehicle-treated mice. Following photochemical-induced thrombosis of the middle cerebral artery, mice treated with empagliflozin demonstrated reduced stroke size compared to vehicle treated mice. In the electronic health records analysis, haemoglobin, haematocrit and erythrocyte counts increased in human SCD subjects treated with an SGLT-2 inhibitor. SGLT-2 inhibitor treatment of humans and mice with SCD is associated with improvement in anaemic parameters. Empagliflozin treatment is also associated with reduced stroke size in SCD mice suggesting SGLT-2 inhibitor treatment may be beneficial with regard to both anaemia and vascular complications in SCD patients.</p>","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":null,"pages":null},"PeriodicalIF":5.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70091","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}