Journal of Investigative Medicine最新文献_第9页

Strengthening research capacity of early-mid career researchers: Implementation and evaluation of the Excellence in Non-COmmunicable disease REsearch (ENCORE) program. EXPRESS：加强中早期研究人员的研究能力：非传染性研究卓越计划（ENCORE）的实施与评估。

IF 2.5 4区医学

Journal of Investigative Medicine Pub Date : 2024-06-01 Epub Date: 2024-03-19 DOI: 10.1177/10815589241236156

Nitin Kapoor, Tilahun Haregu, Kavita Singh, Anu Mary Oommen, Jennifer Audsley, Priti Gupta, Smitha Jasper, G K Mini, Sathish Thirunavukkarasu, Brian Oldenburg

{"title":"Strengthening research capacity of early-mid career researchers: Implementation and evaluation of the Excellence in Non-COmmunicable disease REsearch (ENCORE) program.","authors":"Nitin Kapoor, Tilahun Haregu, Kavita Singh, Anu Mary Oommen, Jennifer Audsley, Priti Gupta, Smitha Jasper, G K Mini, Sathish Thirunavukkarasu, Brian Oldenburg","doi":"10.1177/10815589241236156","DOIUrl":"10.1177/10815589241236156","url":null,"abstract":"High-quality training and networking are pivotal for enhancing the research capacity of early- to mid-career researchers in the prevention and control of non-communicable diseases. Beyond building research skills, these professionals gain valuable insights from interdisciplinary mentorship, networking opportunities, and exposure to diverse cultures and health systems. Despite the significance of such initiatives, their implementation remains underexplored. Here, we describe the implementation and evaluation of the Excellence in Non-COommunicable disease REsearch (ENCORE) program, a collaborative initiative between Australia and India that was launched in 2016 and spanned a duration of 3 years. Led by a consortium that included the University of Melbourne and leading Indian research and medical institutions, ENCORE involved 15 faculty members and 20 early-mid career researchers. The program comprised various elements, including face-to-face forums, masterclasses, webinars, a health-technology conference, and roundtable events. ENCORE successfully trained the early-career researchers, resulting in over 30 peer-reviewed articles, 36 conference presentations, and the submission of seven grant applications, three of which received funding. Beyond individual achievements, ENCORE fostered robust research collaboration between Australian and Indian institutions, showcasing its broader impact on strengthening research capacities across borders.","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"475-486"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912770","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}

引用次数: 0

YAP1-induced RBM24 promotes the tumorigenesis of triple-negative breast cancer through the β-catenin pathway. 表达：YAP1诱导的RBM24通过β-catenin通路促进三阴性乳腺癌的肿瘤发生。

IF 2.5 4区医学

Journal of Investigative Medicine Pub Date : 2024-06-01 Epub Date: 2024-03-22 DOI: 10.1177/10815589241239577

Xiaohua Chen, Xiao Lin, Xiaodong Xia, Xiao Xiang

{"title":"YAP1-induced RBM24 promotes the tumorigenesis of triple-negative breast cancer through the β-catenin pathway.","authors":"Xiaohua Chen, Xiao Lin, Xiaodong Xia, Xiao Xiang","doi":"10.1177/10815589241239577","DOIUrl":"10.1177/10815589241239577","url":null,"abstract":"Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and refractory to current treatments. RBM24 is an RNA-binding protein and shows the ability to regulate tumor progression in multiple cancer types. However, its role in TNBC is still unclear. In this study, we analyzed publicly available profiling data from TNBC tissues and cells. Loss- and gain-of-function experiments were performed to determine the function of RBM24 in TNBC cells. The mechanism for RBM24 action in TNBC was investigated. RBM24 was deregulated in TNBC tissues and TNBC cells with depletion of SIPA1, YAP1, or ARID1A, three key regulators of TNBC. Compared to MCF10A breast epithelial cells, TNBC cells had higher levels of RBM24. Knockdown of RBM24 inhibited TNBC cell proliferation, colony formation, and tumorigenesis, while overexpression of RBM24 promoted aggressive phenotype in TNBC cells. YAP1 overexpression induced the expression of RBM24 and the RBM24 promoter-driven luciferase reporter. YAP1 was enriched at the promoter region of RBM24. Overexpression of RBM24 increased β-catenin-dependent transcriptional activity. Most importantly, knockdown of CTNNB1 rescued RBM24 aggressive phenotype in TNBC cells. Collectively, the YAP1/RBM24/β-catenin axis plays a critical role in driving TNBC progression. RBM24 may represent a novel therapeutic target for TNBC treatment.","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"403-413"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140028168","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}

引用次数: 0

The relationship of the methylation status and polymorphism of glucocorticoid receptor gene (NR3C1) with attempted suicide or non-suicidal self-injury patients in schizophrenia. 表达：糖皮质激素受体基因（NR3C1）的甲基化状态和多态性与精神分裂症患者自杀未遂或非自杀性自伤的关系。

IF 2.5 4区医学

Journal of Investigative Medicine Pub Date : 2024-06-01 Epub Date: 2024-04-25 DOI: 10.1177/10815589241242715

Yasemin Oyaci, Yusuf Ezel Yildirim, Hasan Mervan Aytac, Sacide Pehlivan, Pinar Cetinay Aydin

{"title":"The relationship of the methylation status and polymorphism of glucocorticoid receptor gene (NR3C1) with attempted suicide or non-suicidal self-injury patients in schizophrenia.","authors":"Yasemin Oyaci, Yusuf Ezel Yildirim, Hasan Mervan Aytac, Sacide Pehlivan, Pinar Cetinay Aydin","doi":"10.1177/10815589241242715","DOIUrl":"10.1177/10815589241242715","url":null,"abstract":"We aim to investigate the methylation of NR3C1 gene promotor and NR3C1 BclI polymorphism in schizophrenia (SCZ) patients with attempted suicide or non-suicidal self-injury (NSSI). A sample of 112 patients with SCZ was included in the study. Structured Clinical Interview for Diagnostic and Statistical Manual-Fourth Edition Axis I Disorders was used to confirm the diagnosis according to The Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision criteria. The patients were evaluated by data forms that had sociodemographic, suicidal behavior, and NSSI information. Methylation-specific polymerase chain reaction (PCR) was used to identify the methylation of the NR3C1 gene. The analysis of the BclI polymorphism of the NR3C1 gene was evaluated by using the PCR restriction fragment length polymorphism. Our results revealed that although the NR3C1 gene methylation was not statistically significantly different, there was a significant difference in NR3C1 genotype distribution among the SCZ groups with and without attempted suicide. SCZ patients carrying the CC genotype had a lower risk of attempted suicide (Odds Ratio [OR]: 0.421; 95% Confidence Interval [CI]: 0.183-0.970; p = 0.040), while having the GG genotype in SCZ patients was associated with a higher risk of attempted suicide (OR: 3.785; 95% Cl: 1.107-12.945; p = 0.042). Additionally, due to NSSI in SCZ patients, there were no significant differences in NR3C1 gene methylation and NR3C1 genotype distribution among the groups. We propose that the NR3C1 BclI polymorphism may be associated with attempted suicide in Turkish patients diagnosed with SCZ.","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"449-456"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143667","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}

引用次数: 0

A new therapeutic perspective: Erastin inhibits tumor progression by driving ferroptosis in myelodysplastic syndromes. 表达：新的治疗视角：依拉斯汀通过驱动骨髓增生异常综合征中的铁变态反应抑制肿瘤进展。

IF 2.5 4区医学

Journal of Investigative Medicine Pub Date : 2024-06-01 Epub Date: 2024-05-11 DOI: 10.1177/10815589241246541

Jiaojiao Li, Junlan Ma, Rui Zhang, Yan Zhai, Wei Zhang, Rong Fu

{"title":"A new therapeutic perspective: Erastin inhibits tumor progression by driving ferroptosis in myelodysplastic syndromes.","authors":"Jiaojiao Li, Junlan Ma, Rui Zhang, Yan Zhai, Wei Zhang, Rong Fu","doi":"10.1177/10815589241246541","DOIUrl":"10.1177/10815589241246541","url":null,"abstract":"Ferroptosis is a recently identified and evolutionarily conserved form of programmed cell death. This process is initiated by an imbalance in iron metabolism, leading to an overload of ferrous ions. These ions promote lipid peroxidation in the cell membrane through the Fenton reaction. As the cell's antioxidant defenses become overwhelmed, a fatal buildup of reactive oxygen species (ROS) occurs, resulting in the rupture of the plasma membrane. Ferroptosis is implicated in conditions such as ischemia-reperfusion injuries and a range of cancers. In our research, we explored ferroptosis in myelodysplastic syndromes (MDS) by measuring iron levels, transferrin receptor expression, and glutathione peroxidase 4 (GPX4) mRNA. Our findings revealed that MDS patients had significantly higher Fe2+ levels in CD33+ cells and increased transferrin receptor mRNA compared to healthy individuals. GPX4 expression was also higher in MDS but not statistically significant. To investigate potential treatments for myeloid hematological diseases through ferroptosis induction, we treated the myelodysplastic syndrome cell line (SKM-1) and two myeloid leukemia cell lines (KG-1 and K562) with erastin, an iron transfer inducer. We observed that erastin treatment led to glutathione depletion, reduced GPX4 activity, and increased ROS, culminating in cell death by ferroptosis. Furthermore, combining erastin with azacitidine demonstrated a synergistic effect on MDS and leukemia cell lines, suggesting a promising approach for treating these hematological conditions with this drug combination. Our experiments confirm erastin's ability to induce ferroptosis in MDS and highlight its potential synergistic use with azacitidine for treatment.","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"414-424"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335910","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}

引用次数: 0

Glucose ingestion does not lower testosterone concentrations in men on testosterone therapy. 摄入葡萄糖不会降低接受睾酮治疗的男性体内的睾酮浓度。

IF 2.5 4区医学

Journal of Investigative Medicine Pub Date : 2024-06-01 Epub Date: 2024-05-09 DOI: 10.1177/10815589241252510

Sandeep Dhindsa, Husam Ghanim, Michael J McPhaul, Amit K Ghoshal, Paresh Dandona

{"title":"Glucose ingestion does not lower testosterone concentrations in men on testosterone therapy.","authors":"Sandeep Dhindsa, Husam Ghanim, Michael J McPhaul, Amit K Ghoshal, Paresh Dandona","doi":"10.1177/10815589241252510","DOIUrl":"10.1177/10815589241252510","url":null,"abstract":"Oral calorie intake causes an acute and transient decline in serum testosterone concentrations. It is not known whether this decline occurs in men on testosterone therapy. In this study, we evaluated the change in testosterone concentrations following oral glucose ingestion in hypogonadal men before and after treatment with testosterone therapy. This is a secondary analysis of samples previously collected from a study of hypogonadal men with type 2 diabetes who received testosterone therapy. Study participants (n = 14) ingested 75 grams of oral glucose, and blood samples were collected over 2 h. The test was repeated after 23 weeks of intramuscular testosterone therapy. The mean age and body mass index of study volunteers were 53 ± 8 years and 38 ± 7 kg/m2, respectively. Following glucose intake, testosterone concentrations fell significantly prior to testosterone therapy (week 0, p = 0.04). The nadir of testosterone concentration was at 1 h, followed by recovery to baseline by 2 h. In contrast, there was no change in testosterone concentrations at week 23. The change in serum testosterone concentrations at 60 min was significantly more at week 0 than week 23 (-11 ± 10% vs 0 ± 16%, p = 0.05). We conclude that oral glucose intake has no impact on testosterone concentrations in men on testosterone therapy. Endocrinology societies should consider clarifying in their recommendations that fasting testosterone concentrations are required for the diagnosis of hypogonadism, but not for monitoring testosterone therapy.","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"487-491"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858550","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}

引用次数: 0

Intravenous iron infusions in pediatric patients: A retrospective review of efficacy and safety. 快讯儿科患者静脉输注铁剂：疗效和安全性的回顾性研究。

IF 2.5 4区医学

Journal of Investigative Medicine Pub Date : 2024-06-01 Epub Date: 2024-04-05 DOI: 10.1177/10815589241238219

Caitlin Strachan, Emmalee Kugler, Kartik Devgan, Jennifer Nestor, Faraz Afridi, Riya Raju, Krystal Hunter, Rafat Ahmed

{"title":"Intravenous iron infusions in pediatric patients: A retrospective review of efficacy and safety.","authors":"Caitlin Strachan, Emmalee Kugler, Kartik Devgan, Jennifer Nestor, Faraz Afridi, Riya Raju, Krystal Hunter, Rafat Ahmed","doi":"10.1177/10815589241238219","DOIUrl":"10.1177/10815589241238219","url":null,"abstract":"Pediatric iron deficiency anemia (IDA) is often treated with oral iron supplementation as the first-line therapy despite poor adherence. This single-institution retrospective chart review of pediatric patients was conducted to assess the safety, efficacy, and adherence of intravenous (IV) iron infusions compared to oral iron therapy in patients who had failed a trial of oral iron supplementation. We reviewed medical records of patients aged 1-21 with IDA who received at least one IV iron infusion at Cooper University Hospital between 2016 and 2021. Paired t-tests compared pre-infusion and post-infusion hematologic indices of hemoglobin (Hgb), mean corpuscular volume, red blood cell count, red cell distribution width, ferritin, total iron binding capacity, iron stores, and iron saturation. We compared adherence and adverse reactions to both oral iron supplementation and IV iron infusions using McNemar's test. A total of 107 subjects were included (mean age of 12.7 years). Hgb, ferritin, iron, and iron saturation between pre-infusion and post-final infusion significantly improved (p < 0.001). Hgb, ferritin, and iron improved when subcategorizing by race and etiology of IDA. Adherence to IV iron infusions (70.1%) was significantly greater than adherence to oral iron therapy (43.0%). There were also significantly fewer adverse effects with IV iron infusions (3.7%) compared to oral iron (77.9%). We demonstrated the safety, efficacy, and improved adherence of IV iron infusions compared to oral iron supplementation for treatment of pediatric IDA in patients who were unable to tolerate oral iron supplementation. Future studies could compare adherence to multiple doses of IV iron infusions in contrast with other single-dosing IV iron formulations.","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"457-464"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140012736","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}

引用次数: 0

Troxerutin improves cognitive function and forkhead box F2 expression in the hippocampus via modulating the microbial composition and the intestinal barrier function in diabetes mellitus mice. 表达：曲克芦丁通过调节糖尿病小鼠的微生物组成和肠道屏障功能，改善认知功能和海马中 FOXF2 的表达。

IF 2.5 4区医学

Journal of Investigative Medicine Pub Date : 2024-06-01 Epub Date: 2024-03-14 DOI: 10.1177/10815589241235657

Jie Li, Ming Gao, Pin Wang, Hongyan Li, Jiankun Liu, Fang Yuan, Xiangjian Zhang, Songyun Zhang

{"title":"Troxerutin improves cognitive function and forkhead box F2 expression in the hippocampus via modulating the microbial composition and the intestinal barrier function in diabetes mellitus mice.","authors":"Jie Li, Ming Gao, Pin Wang, Hongyan Li, Jiankun Liu, Fang Yuan, Xiangjian Zhang, Songyun Zhang","doi":"10.1177/10815589241235657","DOIUrl":"10.1177/10815589241235657","url":null,"abstract":"Recent studies have found that gut microbes may affect blood-brain barrier (BBB) integrity. This study was to investigate the relationship between gut microbes and forkhead box F2 (FOXF2) and the mechanism of troxerutin improving diabetic cognitive dysfunction (DCD). Diabetic mice were used in this study for the prophylactic application of troxerutin (60 mg/kg/d) for 8 weeks. The cognitive function was assessed using the Morris water maze (MWM) and novel object recognition (NOR) tasks, and the changes of intestinal microbial composition were observed through 16S rRNA gene sequencing. The content of short-chain fatty acids (SCFAs) in feces was determined by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and the intestinal barrier function was assessed by enzyme-linked immunosorbent assay (ELISA) and western blotting. Troxerutin up-regulated FOXF2 expression in the hippocampus of mice, improving DCD. Meanwhile, it reversed the intestinal microbial composition (increased the abundance of the phylum Bacteroidota, as well as fecal propionic acid and butyric acid levels) and improved the intestinal barrier (increased the level of claudin-1 and significantly reduced the circulating lipopolysaccharide binding protein (LBP) levels). When intestinal microorganisms were removed with an antibiotic cocktail, the improvement of hippocampal FOXF2 expression and DCD by troxerutin attenuated accordingly, suggesting that troxerutin improved DCD by up-regulating the expression of hippocampal FOXF2 through the regulation of intestinal microbial composition and the intestinal barrier. In summary, troxerutin improved DCD by up-regulating the expression of hippocampal FOXF2 through the regulation of intestinal microbial composition and the intestinal barrier.","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"438-448"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139905768","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}

引用次数: 0

Obesity modifies the association between diabetes and iron biomarkers and red cell indices in reproductive-aged women in the United States. 快讯肥胖改变了美国育龄妇女糖尿病与铁生物标志物和红细胞指数之间的关联。

IF 2.5 4区医学

Journal of Investigative Medicine Pub Date : 2024-06-01 Epub Date: 2024-05-14 DOI: 10.1177/10815589241240059

Sixtus Aguree, Arthur Owora, Misty Hawkins, Nana Gletsu-Miller

{"title":"Obesity modifies the association between diabetes and iron biomarkers and red cell indices in reproductive-aged women in the United States.","authors":"Sixtus Aguree, Arthur Owora, Misty Hawkins, Nana Gletsu-Miller","doi":"10.1177/10815589241240059","DOIUrl":"10.1177/10815589241240059","url":null,"abstract":"Obesity and diabetes are associated with impaired iron metabolism. We aimed to examine the independent relationship between diabetes and iron after controlling for body weight (or obesity) in women aged 20-49 years. The National Health and Nutrition Examination Survey data from 2015 to 2018 were used in this investigation. Body composition data, HbAc1, iron biomarkers (serum ferritin (SF), soluble transferrin receptor (sTfR), and body iron index (BII)), mean corpuscular volume (MCV), mean hemoglobin concentration (MCH), red cell distribution width (RDW), and hemoglobin were used. Linear regression models were used to examine how and to what extent body mass index (BMI) modified the relationship between diabetes and iron status biomarkers. A total of 1834 women aged 20-49 were included in the analysis with a mean (SD) age of 32 .2 ± 6.1 years and BMI of 29.5 ± 6.9 kg/m2. The mean SF (p = 0.014) and BII (p < 0.001) were lower, while sTfR (p < 0.001) was higher in women with diabetes than those with no diabetes. Mean estimates for MCV and MCH were lower, while RDW (p = 0.001) was higher in diabetes patients (all p < 0.001). Women with diabetes were more likely to have iron deficiency, anemia, and iron deficiency anemia than those without diabetes (18.1% vs 8.6%, p < 0.001), (24.4% vs 8.4%, p < 0.001), and (14.8% vs 5.2%, p < 0.001), respectively. Among women with obesity, those with diabetes had lower predicted ferritin (β = -0.19, p = 0.016), BII (β = -0.99, p = 0.016), and hemoglobin (β = -0.27, p = 0.042) than those without diabetes. The study shows that diabetes is linked to lower iron stores; this is exacerbated in those with obesity.","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"425-437"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140039580","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}

引用次数: 0

New plasma LC-MS/MS assays for the quantitation of beta-amyloid peptides and identification of apolipoprotein E proteoforms for Alzheimer's disease risk assessment. 快讯：新型血浆液相色谱-质谱/质谱测定法，用于定量检测β-淀粉样蛋白肽和鉴定脂蛋白E蛋白形式，以评估阿尔茨海默病风险。

IF 2.5 4区医学

Journal of Investigative Medicine Pub Date : 2024-06-01 Epub Date: 2024-04-30 DOI: 10.1177/10815589241246537

Darren M Weber, Jueun C Kim, Scott M Goldman, Nigel J Clarke, Michael K Racke

{"title":"New plasma LC-MS/MS assays for the quantitation of beta-amyloid peptides and identification of apolipoprotein E proteoforms for Alzheimer's disease risk assessment.","authors":"Darren M Weber, Jueun C Kim, Scott M Goldman, Nigel J Clarke, Michael K Racke","doi":"10.1177/10815589241246537","DOIUrl":"10.1177/10815589241246537","url":null,"abstract":"Early detection of Alzheimer's disease (AD) represents an unmet clinical need. Beta-amyloid (Aβ) plays an important role in AD pathology, and the Aβ42/40 peptide ratio is a good indicator for amyloid deposition. In addition, variants of the apolipoprotein E (APOE) gene are associated with variable AD risk. Here, we describe the development and validation of high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for plasma Aβ40 and Aβ42 quantitation, as well as apolipoprotein E (ApoE) proteotype determination as a surrogate for APOE genotype. Aβ40 and Aβ42 were simultaneously immunoprecipitated from plasma, proteolytically digested, and quantitated by LC-MS/MS. ApoE proteotype status was qualitatively assessed by targeting tryptic peptides from the ApoE2, ApoE3, and ApoE4 proteoforms. Both assays were validated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Within-run precision was 1.8%-4.2% (Aβ40), 1.9%-7.2% (Aβ42), and 2.6%-8.3% (Aβ42/40 ratio). Between-run precision was 3.5%-5.9% (Aβ40), 3.8%-8.0% (Aβ42), and 3.3%-8.7% (Aβ42/40 ratio). Both Aβ40 and Aβ42 were linear from 10 to 2500 pg/mL. Identified ApoE proteotypes had 100% concordance with APOE genotypes. We have developed a precise, accurate, and sensitive high-throughput LC-MS/MS assay for plasma Aβ40, Aβ42, and proteoforms of ApoE.","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"465-474"},"PeriodicalIF":2.5,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318474","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}

引用次数: 0

Morinda officinalis polysaccharide promotes the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells via microRNA-210-3p/scavenger receptor class A member 3. 表达：巴戟天多糖通过 microRNA-210-3p / 清道夫受体 A 类成员 3 促进人骨髓间充质干细胞的成骨分化。

IF 2.5 4区医学

Journal of Investigative Medicine Pub Date : 2024-04-01 Epub Date: 2024-03-04 DOI: 10.1177/10815589241229693

Yue Wu, Dan Chen, Longguang Li

{"title":"Morinda officinalis polysaccharide promotes the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells via microRNA-210-3p/scavenger receptor class A member 3.","authors":"Yue Wu, Dan Chen, Longguang Li","doi":"10.1177/10815589241229693","DOIUrl":"10.1177/10815589241229693","url":null,"abstract":"Morinda officinalis polysaccharide (MOP) is the bioactive ingredient extracted from the root of Morinda officinalis, and Morinda officinalis is applied to treat osteoporosis (OP). The purpose of this study was to determine the role of MOP on human bone marrow mesenchymal stem cells (hBMSCs) and the underlying mechanism. HBMSCs were isolated from bone marrow samples of patients with OP and treated with MOP. Quantitative real-time polymerase chain reaction was adopted to quantify the expression of microRNA-210-3p (miR-210-3p) and scavenger receptor class A member 3 (SCARA3) mRNA. Cell Counting Kit-8 assay was employed to detect cell viability; Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling assay and flow cytometry were adopted to detect apoptosis; Alkaline Phosphatase (ALP) activity assay kit was applied to detect ALP activity; Western blot was executed to quantify the expression levels of SCARA3, osteogenic and adipogenic differentiation markers. Ovariectomized rats were treated with MOP. Bone mineral density (BMD), serum tartrate-resistant acid phosphatase 5b (TRACP 5b), and N-telopeptide of type I collagen (NTx) levels were assessed by BMD detector and Enzyme-linked immunosorbent assay kits. It was revealed that MOP could promote hBMSCs' viability and osteogenic differentiation and inhibit apoptosis and adipogenic differentiation. MOP could also upregulate SCARA3 expression through repressing miR-210-3p expression. Treatment with MOP increased the BMD and decreased the TRACP 5b and NTx levels in ovariectomized rats. MOP may boost the osteogenic differentiation and inhibit adipogenic differentiation of hBMSCs by miR-210-3p/SCARA3 axis.","PeriodicalId":16112,"journal":{"name":"Journal of Investigative Medicine","volume":" ","pages":"370-382"},"PeriodicalIF":2.5,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139542500","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}

引用次数: 0