Current Research in Translational Medicine最新文献

{"title":"Cardiovascular diseases in patients after hematopoietic stem cell transplantation: Systematic review and Meta-analysis","authors":"Azin Alizadehasl ,&nbsp;Nashmil Ghadimi ,&nbsp;Hossein Hosseinifard ,&nbsp;Kamran Roudini ,&nbsp;Amir Hossein Emami ,&nbsp;Ardeshir Ghavamzadeh ,&nbsp;Davood khoda-Amorzideh","doi":"10.1016/j.retram.2022.103363","DOIUrl":"10.1016/j.retram.2022.103363","url":null,"abstract":"<div><h3>Background</h3><p><span><span>Hematopoietic Stem Cell Transplantation (HSCT), is performed to treat many </span>malignancies such as autologous or allogenic. Despite the success of this method in treating patients, - sometimes some HSCT recipients face problems such as cardiovascular complications. Therefore, this </span>systematic review and meta-analysis aimed to evaluate the prevalence of cardiovascular complications in post-transplant patients.</p></div><div><h3>Method</h3><p><span>In order to review the published studies, we examined PubMed, MEDLINE, Cochrane Library, </span>Scopus, and web of science databases from the beginning to the end of January 2022, and we used tools by the Newcastle–Ottawa Scale to evaluate the quality of the studies.</p></div><div><h3>Result</h3><p><span><span>In this study, 37 articles were included in the meta-analysis and 30,957 patients were examined. Also, the mean age of patients was 35.37 years. Based on the results of the meta-analysis, the prevalence of cardiovascular disease (CVD), was 16.84%. In addition, other complications related to CVD which include Arrhythmias, Congestive Heart Failure (CHF), Hypertension, stroke, and mortality were examined </span>in patients who had hematopoietic stem cell transplantation and the resulting amounts were 3.91%, 3.66, 17.71, 0.22%, and 1.53%, respectively</span><strong>.</strong></p></div><div><h3>Conclusion</h3><p>This study showed that the prevalence of cardiovascular disease after hematopoietic stem cell transplantation is high and needs special attention.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 1","pages":"Article 103363"},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9166936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AML-derived extracellular vesicles negatively regulate stem cell pool size: A step toward bone marrow failure","authors":"Bahrampour Shahrokh ,&nbsp;Farsani Mehdi Allahbakhshian ,&nbsp;Gharehbaghian Ahmad ,&nbsp;Feizi Fatemeh ,&nbsp;Mohammadi Mohammad Hossein","doi":"10.1016/j.retram.2022.103375","DOIUrl":"10.1016/j.retram.2022.103375","url":null,"abstract":"<div><h3>Purpose of the study</h3><p><span><span>Long-term repopulating hematopoietic stem cells<span> (LTR-HSCs) have been previously shown to reside in close proximity to osteoblasts<span>, where they take shelter in the bone marrow (BM) microenvironment against cytotoxic and apoptotic stimuli. Nevertheless, the function of the HSC niche is believed to undergo an adaptive evolutionary modification during </span></span></span>leukemogenesis. Recent studies have demonstrated that leukemic clones can impact BM homing through extracellular vesicle (EV) secretion. However, the exact mechanism driving BM conversion is still unclear. In the present study, the human </span>osteoblast cell line<span> (MG-63) were subjected to various concentration of sera-derived EVs of patients with acute myeloid leukemia (AML) and healthy volunteers to assess if they are associated strongly enough to alter the expression pattern of cross-talk molecules involved in niche interactions.</span></p></div><div><h3>Method</h3><p><span>To gain a brief insight into the EVs secretion criteria, we first conducted a comparative analysis of sera-derived EVs by dynamic light scattering<span> (DLS), transmission electron microscopy<span> (TEM), and Bradford assay. After incubating MG-63 cell lines with increasing concentrations of the EVs, Trypan-blue and microculture tetrazolium test (MTT) assays were used to evaluate the cell survival, logarithmic growth, and metabolic activity. Finally, the expression levels of </span></span></span><span><em>OPN</em><em>, ANGPT-1</em></span>, and <em>JAG-1</em> transcripts were evaluated through the qRT-PCR technique.</p></div><div><h3>Results</h3><p>Here, we report that AML-derived EVs can affect the viability, cell growth, and metabolic activity of the human osteoblasts cell line (MG-63) compared to those that received healthy-derived EVs. We also found that leukemic EVs tend to induce overexpression of <em>OPN</em> but reduce the expression of <em>ANGPT-1</em> and <em>JAG-1</em><span> genes in the osteoblast transcriptome, which may provide a potential context imposing selective suppression of HSC pool size.</span></p></div><div><h3>Conclusion</h3><p>These findings extend the general concept of a novel mechanism in which leukemic EVs would make it possible to create a specialized pre-metastatic microenvironment in the interest of tumor expansion, allowing leukemic clones to overcome their HSCs counterparts.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 1","pages":"Article 103375"},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9167623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical-to-clinical innovations in stem cell therapies for liver regeneration","authors":"Shilpa Chawla ,&nbsp;Amitava Das","doi":"10.1016/j.retram.2022.103365","DOIUrl":"10.1016/j.retram.2022.103365","url":null,"abstract":"<div><p>Acute and chronic liver diseases<span><span><span> are the major cause of high morbidity and mortality globally. Liver transplantation is a widely used therapeutic option for liver failure. However, the shortage of availability of liver donors has encouraged research on the alternative approach to </span>liver regeneration<span>. Cell-based regenerative medicine is the best alternative therapy to cater to this need. To date, advanced preclinical approaches have been undertaken on stem cell differentiation and their use in liver </span></span>tissue engineering<span> for generating efficacious and promising regenerative therapies<span>. Advancements in the bioengineering of stem cells, and organoid generation are the way forward to efficient therapies against liver injury. This review summarizes the recent approaches for stem cell therapy-based liver regeneration and their proof of concepts for clinical application, bioengineering liver organoids to alleviate the liver failure caused due to chronic liver diseases.</span></span></span></p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 1","pages":"Article 103365"},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9166935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal analysis of plasma IL-8 on carotid intima media thickness, a measure of subclinical atherosclerosis","authors":"Ilais Moreno Velásquez ,&nbsp;Anders Malarstig ,&nbsp;Damiano Baldassarre ,&nbsp;Yan Borne ,&nbsp;Ulf de Faire ,&nbsp;Gunnar Engström ,&nbsp;Per Eriksson ,&nbsp;Philippe Giral ,&nbsp;Steve E. Humphries ,&nbsp;Sudhir Kurl ,&nbsp;Karin Leander ,&nbsp;Lars Lind ,&nbsp;Anders Lindén ,&nbsp;Nicola Orsini ,&nbsp;Matteo Pirro ,&nbsp;Angela Silveira ,&nbsp;Andries J. Smit ,&nbsp;Elena Tremoli ,&nbsp;Fabrizio Veglia ,&nbsp;Rona J. Strawbridge ,&nbsp;Bruna Gigante","doi":"10.1016/j.retram.2022.103374","DOIUrl":"10.1016/j.retram.2022.103374","url":null,"abstract":"<div><h3>Background</h3><p>We investigated the causality of IL-8 on carotid intima-media thickness (c-IMT), a measure of sub-clinical atherosclerosis.</p></div><div><h3>Methods</h3><p>The IMPROVE is a multicenter European study (<em>n</em> = 3,711). The association of plasma IL-8 with c-IMT (mm) was estimated by quantile regression. Genotyping was performed using the Illumina CardioMetabo and Immuno chips. Replication was attempted in three independent studies and a meta-analysis was performed using a random model.</p></div><div><h3>Results</h3><p>In IMPROVE, each unit increase in plasma IL-8 was associated with an increase in median c-IMT measures (all <em>p</em>&lt;0·03) in multivariable analyses. Linear regression identified rs117518778 and rs8057084 as associated with IL-8 levels and with measures of c-IMT. The two SNPs were combined in an IL-8-increasing genetic risk that showed causality of IL-8 on c-IMT in IMPROVE and in the UK Biobank (<em>n</em> = 22,179). The effect of IL-8 on c-IMT measures was confirmed in PIVUS (<em>n</em> = 1,016) and MDC<img>CC (<em>n</em> = 6,103). The association of rs8057084 with c-IMT was confirmed in PIVUS and UK Biobank with a pooled estimate effect (β) of -0·006 with 95%CI (-0·008- -0·003).</p></div><div><h3>Conclusion</h3><p>Our results indicate that genetic variants associated with plasma IL-8 also associate with c-IMT. However, we cannot infer causality of this association, as these variants lie outside of the <em>IL8</em> locus.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 1","pages":"Article 103374"},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9167619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiomics and artificial intelligence enabled peripheral blood-based prediction of amnestic mild cognitive impairment","authors":"Yota Tatara ,&nbsp;Hiromi Yamazaki ,&nbsp;Fumiki Katsuoka ,&nbsp;Mitsuru Chiba ,&nbsp;Daisuke Saigusa ,&nbsp;Shuya Kasai ,&nbsp;Tomohiro Nakamura ,&nbsp;Jin Inoue ,&nbsp;Yuichi Aoki ,&nbsp;Miho Shoji ,&nbsp;Ikuko N. Motoike ,&nbsp;Yoshinori Tamada ,&nbsp;Katsuhito Hashizume ,&nbsp;Mikio Shoji ,&nbsp;Kengo Kinoshita ,&nbsp;Koichi Murashita ,&nbsp;Shigeyuki Nakaji ,&nbsp;Masayuki Yamamoto ,&nbsp;Ken Itoh","doi":"10.1016/j.retram.2022.103367","DOIUrl":"10.1016/j.retram.2022.103367","url":null,"abstract":"<div><h3>Background</h3><p>Since dementia is preventable with early interventions, biomarkers that assist in diagnosing early stages of dementia, such as mild cognitive impairment (MCI), are urgently needed.</p></div><div><h3>Methods</h3><p>Multiomics analysis of amnestic MCI (aMCI) peripheral blood (<em>n</em> = 25) was performed covering the transcriptome, microRNA, proteome, and metabolome. Validation analysis for microRNAs was conducted in an independent cohort (<em>n</em> = 12). Artificial intelligence was used to identify the most important features for predicting aMCI.</p></div><div><h3>Findings</h3><p>We found that hsa-miR-4455 is the best biomarker in all omics analyses. The diagnostic index taking a ratio of hsa-miR-4455 to hsa-let-7b-3p predicted aMCI patients against healthy subjects with 97% overall accuracy. An integrated review of multiomics data suggested that a subset of T cells and the GCN (general control nonderepressible) pathway are associated with aMCI.</p></div><div><h3>Interpretation</h3><p>The multiomics approach has enabled aMCI biomarkers with high specificity and illuminated the accompanying changes in peripheral blood. Future large-scale studies are necessary to validate candidate biomarkers for clinical use.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 1","pages":"Article 103367"},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9521663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fludarabine and antithymocyte globulin-based conditioning regimen combined with post-transplantation cyclophosphamide for haploidentical allogeneic hematopoietic stem cell transplantation in patients with high-risk acute myeloid leukemia and myelodysplastic syndrome","authors":"Junjie Cao ,&nbsp;Renzhi Pei ,&nbsp;Ying Lu ,&nbsp;Zhongzheng Zheng ,&nbsp;Zhiyang Yuan ,&nbsp;Daiyang Li ,&nbsp;Pisheng Zhang ,&nbsp;Xuhui Liu ,&nbsp;Dong Chen ,&nbsp;Xiaohong Du ,&nbsp;Lieguang Chen ,&nbsp;Shuangyue Li ,&nbsp;Peipei Ye ,&nbsp;Tiantian Wang","doi":"10.1016/j.retram.2022.103360","DOIUrl":"10.1016/j.retram.2022.103360","url":null,"abstract":"<div><h3>Introduction</h3><p><span><span>Relapse and graft-versus-host disease (GVHD) are the important complications influencing mortality for patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) after </span>allogeneic hematopoietic stem cell transplantation (allo-HSCT). GVHD prophylaxis based on post-transplant </span>cyclophosphamide<span> (PTCy) or antithymocyte globulin (ATG) is widely used in haploidentical HSCT (haplo-HSCT).</span></p></div><div><h3>Objective</h3><p>We developed a modified intensified conditioning regimen including fludarabine (Flu) and investigated the effect of ATG-PTCy combination on transplant outcomes in high-risk AML and MDS compared with those patients who received only ATG as GVHD prophylaxis.</p></div><div><h3>Methods</h3><p>A total of 80 patients with high-risk AML and MDS were divided into two groups and assigned to one-to-one pairing.</p></div><div><h3>Results</h3><p><span>The modified ATG-PTCy group had more infused mononuclear cells, CD34-positive cells and CD3-positive cells than those in the ATG group (</span><em>P</em><span> &lt; 0.05). The amount of platelet transfusion was higher in the ATG group than the modified ATG-PTCy group [2 (range, 1–6) U vs 2 (range, 1–5) U, </span><em>P</em> = 0.005]. The median of platelet recovery was better in the modified ATG-PTCy group than in the ATG group (12 days vs 13 days,<em>P</em><span> = 0.041). The infection rates of bacteria, fungi and virus at 100 days after transplantation were similar in both groups. Compared with the ATG group, individuals who received the modified ATG-PTCy regimen had higher 2-year GVHD- and relapse-free survival(GRFS) [60.0% (95%CI, 44.9–75.1%) vs 34.8% (95%CI, 19.9–49.7%), </span><em>P</em><span> = 0.028]; lower 180-day incidence of II-IV acute GVHD (aGVHD) [15.0% (95%CI, 4.0–26.0%) vs 39.8% (95%CI, 23.9–55.7%), </span><em>P</em><span> = 0.029]; lower 1-year incidence of moderate to severe chronic GVHD (cGVHD) [2.9% (95%CI, 2.0–3.8%) vs 19.6% (95%CI, 5.3–33.9%), </span><em>P</em> = 0.039]; and without an increase in the 2-year cumulative incidence of relapse (CIR) [19.5% (95%CI, 6.6–32.4%) vs 30.4% (95%CI, 15.3–45.5%), <em>P</em> = 0.291].</p></div><div><h3>Conclusions</h3><p>High-dose stem cells can promote blood cell implantation. The modified ATG-PTCy combination was associated with decreased risk of aGVHD and cGVHD, no increased risk of recurrence, and improved GRFS. It represents an effective strategy for high risk AML and MDS.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 1","pages":"Article 103360"},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9537108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The fecal microbiota of gravidas with fetal growth restriction newborns characterized by metagenomic sequencing","authors":"Xin He ,&nbsp;Zhengpeng Li ,&nbsp;Xiaohui Li ,&nbsp;Huanying Zhao ,&nbsp;Yanan Hu ,&nbsp;Wenli Han ,&nbsp;Chen Wang ,&nbsp;Chenghong Yin ,&nbsp;Yi Chen","doi":"10.1016/j.retram.2022.103354","DOIUrl":"10.1016/j.retram.2022.103354","url":null,"abstract":"<div><h3>Background</h3><p>Fetal growth restriction (FGR) is a complex obstetric complication with various causes and of great harm. However, the specific pathogenesis of FGR is unclear, which limits its effective treatment. Gut microbiota dysbiosis was found to be important in pathogenesis of various diseases. However, its role in FGR development remains unclear and needs to be clarified.</p></div><div><h3>Methods</h3><p>In our case-control study, we recruited eight FGR and eight control female participants and collected their fecal samples in third trimester before delivery. We performed metagenomic sequencing and bioinformatic analysis to compare the gut microbiota composition and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between the two groups.</p></div><div><h3>Results</h3><p>Our results showed that totally 20 gut microbes were significantly different between two groups (p&lt;0•05), and the correlation analysis found that g__Roseomonas and g__unclassified_f__Propionibacteriaceae were significantly positive correlated with both maternal body mass index (BMI) before delivery, placental weight, and neonatal birth weight (BW) percentile (all p&lt;0•05), while g__Marinisporobacter and g__Sphingomonas were significantly negative correlated with both neonatal BMI and neonatal BW percentile (all p&lt;0•05). Through KEGG pathway analysis, we found that the abundance of the Nitrogen metabolism pathway decreased significantly (p&lt;0•05) whereas the abundance of the Amoebiasis pathway increased significantly in the FGR group (p&lt;0•05).</p></div><div><h3>Conclusion</h3><p>In this study, we demonstrated that the occurrence of FGR is associated with the change of gut microbiota of pregnant women.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 1","pages":"Article 103354"},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9537109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro blood brain barrier models: Molecular aspects and therapeutic strategies in glioma management","authors":"Vinitha Rani,&nbsp;Ashwini Prabhu","doi":"10.1016/j.retram.2022.103376","DOIUrl":"10.1016/j.retram.2022.103376","url":null,"abstract":"<div><p><span>Glioma management is the most challenging task in clinical oncology due to numerous reasons. One of the major hurdles in glioma therapy is the presence of blood brain barrier which resists the entry of most of the drugs into the brain. However, in case of tumors, blood brain barrier integrity is compromised, which in turn can be advantageous in delivering the drugs, if the therapeutic module is strategically modified. For such improvised therapeutic strategy, it is necessary to understand the molecular composition and profiling of blood brain barrier and blood brain tumor barrier. This review mainly focuses on the composition, markers expressed on the blood brain barrier which will help the readers to understand its basic environment. It also gives a detailed account of the various </span><em>in vitro</em> models that are used to study the nature of the blood brain barrier and describes various strategies in improvising the drug delivery in glioma management.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 1","pages":"Article 103376"},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9177846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endovesical instillation of Cidofovir in the treatment of BK polyomavirus hemorrhagic cystitis after allogeneic hematopoietic cell transplantation","authors":"Adrien Voisot ,&nbsp;François Triffaux ,&nbsp;Isabelle Roland ,&nbsp;Cecile Meex ,&nbsp;Nancy Detrembleur ,&nbsp;Fréderic Baron ,&nbsp;Evelyne Willems ,&nbsp;Waltregny David ,&nbsp;Yves Beguin ,&nbsp;Sophie Servais","doi":"10.1016/j.retram.2022.103366","DOIUrl":"10.1016/j.retram.2022.103366","url":null,"abstract":"<div><h3>Background</h3><p><span><span>Hemorrhagic cystitis (HC) with </span>BK polyomavirus (BKPyV) is a common complication after allogeneic hematopoietic </span>cell transplantation (alloHCT) that may lead to severe discomfort for the patient and significant morbidity (urinary obstruction, increased transfusion requirements and prolonged hospitalization). So far, there is no clear consensus on how to manage this complication.</p></div><div><h3>Patients and methods</h3><p>Here, we report a single-center case series of 9 patients (4 children and 5 adults) treated with cidofovir endovesical (EV) instillation(s) for BKPyV-HC after alloHCT. EV Cidofovir was administered at a dose of 5 mg/kg, for 1 to 3 instillations (with a minimum delay between 2 successive doses of 5 days).</p></div><div><h3>Results</h3><p>Eight out of the 9 treated patients with EV Cidofovir achieved a complete resolution of HC after 1–3 instillation(s), without recurrence of symptomatic infection within the next 3 months. Only 1 adult patient did not improve after treatment and developed severe morbidity (emphysematous cystitis).</p></div><div><h3>Conclusion</h3><p>Although this single-center case series of EV cidofovir for BKPyV HC after alloHCT shows encouraging results, only large prospective studies will definitively establish the effectiveness of this therapy.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 1","pages":"Article 103366"},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9166937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APOE ε4 and Alzheimer's disease diagnosis associated differences in L-carnitine, GBB, TMAO, and acylcarnitines in blood and brain","authors":"Claire J.C. Huguenard ,&nbsp;Adam Cseresznye ,&nbsp;James E. Evans ,&nbsp;Teresa Darcey ,&nbsp;Aurore Nkiliza ,&nbsp;Andrew P. Keegan ,&nbsp;Cheryl Luis ,&nbsp;David A. Bennett ,&nbsp;Zoe Arvanitakis ,&nbsp;Hussein N. Yassine ,&nbsp;Michael Mullan ,&nbsp;Fiona Crawford ,&nbsp;Laila Abdullah","doi":"10.1016/j.retram.2022.103362","DOIUrl":"10.1016/j.retram.2022.103362","url":null,"abstract":"<div><h3>Background</h3><p><span>The apolipoprotein E (</span><em>APOE</em><span>) ε4 allele, involved in fatty acid (FA) metabolism, is a major genetic risk factor for Alzheimer's disease (AD). This study examined the influence of </span><em>APOE</em><span> genotypes on blood and brain markers of the L-carnitine system, necessary for fatty acid oxidation (FAO), and their collective influence on the clinical and pathological outcomes of AD.</span></p></div><div><h3>Methods</h3><p>L-carnitine, its metabolites γ-butyrobetaine (GBB) and trimethylamine-n-oxide (TMAO), and its esters (acylcarnitines) were analyzed in blood from predominantly White community/clinic-based individuals (<em>n</em> = 372) and in plasma and brain from the Religious Order Study (ROS) (<em>n</em><span> = 79) using liquid chromatography tandem mass spectrometry (LC-MS/MS).</span></p></div><div><h3>Findings</h3><p><span>Relative to total blood acylcarnitines, levels of short chain acylcarnitines (SCAs) were higher whereas long chain acylcarnitines (LCAs) were lower in AD, which was observed pre-clinically in </span><em>APOE</em> ε4s. Plasma medium chain acylcarnitines (MCAs) were higher amongst cognitively healthy <em>APOE</em> ε2 carriers relative to other genotypes. Compared to their respective controls, elevated TMAO and lower L-carnitine and GBB were associated with AD clinical diagnosis and these differences were detected preclinically among <em>APOE</em><span> ε4 carriers. Plasma and brain GBB, TMAO, and acylcarnitines were also associated with post-mortem brain amyloid, tau, and cerebrovascular pathologies.</span></p></div><div><h3>Interpretation</h3><p><span>Alterations in blood L-carnitine, GBB, TMAO, and acylcarnitines occur early in clinical AD progression and are influenced by </span><em>APOE</em> genotype. These changes correlate with post-mortem brain AD and cerebrovascular pathologies. Additional studies are required to better understand the role of the FAO disturbances in AD.</p></div>","PeriodicalId":54260,"journal":{"name":"Current Research in Translational Medicine","volume":"71 1","pages":"Article 103362"},"PeriodicalIF":4.1,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10066735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9346154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}