Accumulating evidence has illustrated that the E3 ubiquitin ligases critically participate in the development and progression of cardiovascular diseases. Dysregulation of E3 ubiquitin ligases exacerba Show more
Accumulating evidence has illustrated that the E3 ubiquitin ligases critically participate in the development and progression of cardiovascular diseases. Dysregulation of E3 ubiquitin ligases exacerbates cardiovascular diseases. Blockade or activation of E3 ubiquitin ligases mitigates cardiovascular performance. Therefore, in this review, we mainly introduced the critical role and underlying molecular mechanisms of E3 ubiquitin ligase NEDD4 family in governing the initiation and progression of cardiovascular diseases, including ITCH, WWP1, WWP2, Smurf1, Smurf2, Nedd4-1 and Nedd4-2. Moreover, the functions and molecular insights of other E3 ubiquitin ligases, such as F-box proteins, in cardiovascular disease development and malignant progression are described. Furthermore, we illustrate several compounds that alter the expression of E3 ubiquitin ligases to alleviate cardiovascular diseases. Therefore, modulation of E3 ubiquitin ligases could be a novel and promising strategy for improvement of therapeutic efficacy of deteriorative cardiovascular diseases. Show less
Apolipoproteins and cortical morphology are closely associated with memory complaints, and both may contribute to the development of Alzheimer's disease. To examine whether apolipoprotein B (ApoB), ap Show more
Apolipoproteins and cortical morphology are closely associated with memory complaints, and both may contribute to the development of Alzheimer's disease. To examine whether apolipoprotein B (ApoB), apolipoprotein A-1 (ApoA1), and their ratio (ApoB/ApoA1) are associated with cortical morphology in patients with memory complaints. Ninety-seven patients underwent neuropsychological testing, measurements of ApoB, ApoA1, ApoB/ApoA1, plasma Alzheimer's biomarker, apolipoprotein E (ApoE) genotyping, and 3T structural magnetic resonance imaging (sMRI) scans. Based on sMRI scanning locations, patients were categorized into the University of Electronic Science and Technology (UESTC) and the Fourth People's Hospital of Chengdu (FPHC). The Computational Anatomy Toolbox within Statistical Parametric Mapping was used to calculate each patient's cortical morphology index based on sMRI data. The cortical morphology index and apolipoproteins were also analyzed. Significant positive correlations were found between ApoB and sulcal depth in the lateral occipital cortex among the UESTC, the FPHC, and the total sample groups, and negative correlations were observed between sulcal depth in the lateral occipital cortex and the scores of the Shape Trails Test Part A and B. In the FPHC group, the scores of the Montreal Cognitive Assessment Basic, delayed recall of the Auditory Verbal Learning Test, Animal Fluency Test and Boston Naming Test were positively correlated with the sulcal depth. ApoB is associated with the sulcal depth in the lateral occipital cortex, potentially relating to speed/executive function in individuals with memory complaints. Show less
Epidermal growth factor receptor (EGFR) over-expression is commonly observed in advanced head and neck squamous cell carcinoma (HNSCC) and is correlated with poor patient outcomes. However, the role o Show more
Epidermal growth factor receptor (EGFR) over-expression is commonly observed in advanced head and neck squamous cell carcinoma (HNSCC) and is correlated with poor patient outcomes. However, the role of dual-specificity phosphatase 6 (DUSP6) in EGFR-associated HNSCC progression remains poorly understood. This study aimed to investigate the correlation between DUSP6 expression and EGFR signaling in malignant HNSCC tissues. Data mining and in vitro assays were employed to assess DUSP6 expression levels in HNSCC tissues compared to normal tissues. Additionally, the correlation between DUSP6 and EGFR expression was examined. Functional assays were conducted to investigate the modulation of DUSP6 expression by EGFR signaling and its involvement in EGF-induced cell migration and anoikis resistance. Our analysis revealed a significant elevation in DUSP6 expression in HNSCC tissues compared to normal tissues and a strong correlation between DUSP6 and EGFR expression. EGFR signaling modulated DUSP6 expression in a dose- and time-dependent manner, primarily through the extracellular signal-regulated kinase (ERK) pathway. Knockdown experiments demonstrated the functional role of DUSP6 in EGF-induced cell migration and anoikis resistance. The findings of this study elucidate the intricate signaling networks governing DUSP6 expression and its interplay with EGFR signaling in HNSCC. Moreover, the results provide insights into the potential role of DUSP6 as a therapeutic target and highlight the importance of personalized treatment strategies in HNSCC management. Show less
Sisi Zheng, Sitong Feng, Nan Song+8 more · 2024 · The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry · Taylor & Francis · added 2026-04-24
Depersonalisation-derealization disorder (DPD) is a dissociative disorder that impairs cognitive function and occupational performance. Emerging evidence indicate the levels of tumour necrosis factor- Show more
Depersonalisation-derealization disorder (DPD) is a dissociative disorder that impairs cognitive function and occupational performance. Emerging evidence indicate the levels of tumour necrosis factor-α and interleukin associated with the dissociative symptoms. In this study, we aimed to explore the role of the immune system in the pathology of DPD. We screened the protein expression in serum samples of 30 DPD patients and 32 healthy controls. Using a mass spectrometry-based proteomic approach, we identified differential proteins that were verified in another group of 25 DPD patients and 30 healthy controls using immune assays. Finally, we performed a correlation analysis between the expression of differential proteins and clinical symptoms of patients with DPD. We identified several dysregulated proteins in patients with DPD compared to HCs, including decreased levels of C-reactive protein (CRP), complement C1q subcomponent subunit B, apolipoprotein A-IV, and increased levels of alpha-1-antichymotrypsin (SERPINA3). Moreover, the expression of CRP was positively correlated with visuospatial memory and the ability to inhibit cognitive interference of DPD. The expression of SERPINA3 was positively correlated with the ability to inhibit cognitive interference and negatively correlated with the perceptual alterations of DPD. The dysregulation of the immune system may be the underlying biological mechanism in DPD. And the expressions of CRP and SERPINA3 can be the potential predictors for the cognitive performance of DPD. Show less
Autophagy is a ubiquitous pathological/physiological antioxidant cellular reaction in eukaryotic cells. Vacuolar protein sorting 34 (Vps34 or PIK3C3), which plays a crucial role in autophagy, has rece Show more
Autophagy is a ubiquitous pathological/physiological antioxidant cellular reaction in eukaryotic cells. Vacuolar protein sorting 34 (Vps34 or PIK3C3), which plays a crucial role in autophagy, has received much attention. As the only Class III phosphatidylinositol-3 kinase in mammals, Vps34 participates in vesicular transport, nutrient signaling and autophagy. Dysfunctionality of Vps34 induces carcinogenesis, and abnormal autophagy mediated by dysfunction of Vps34 is closely related to the pathological progression of various human diseases, which makes Vps34 a novel target for tumor immunotherapy. In this review, we summarize the molecular mechanisms underlying macroautophagy, and further discuss the structure-activity relationship of Vps34 inhibitors that have been reported in the past decade as well as their potential roles in anticancer immunotherapy to better understand the antitumor mechanism underlying the effects of these inhibitors. Show less
Chronic itch is a common and complex symptom often associated with skin diseases such as atopic dermatitis (AD). Although IL-27 is linked to AD, its role and clinical significance in itch remain undef Show more
Chronic itch is a common and complex symptom often associated with skin diseases such as atopic dermatitis (AD). Although IL-27 is linked to AD, its role and clinical significance in itch remain undefined. We sought to investigate IL-27 function in itch using tissue-specific transgenic mice, various itch models, behavior scoring, RNA sequencing, and cytokine/kinase array. Our findings show that IL-27 receptors were overexpressed in human AD skin. Intradermal IL-27 injection failed to directly induce itch in mice but upregulated skin protease-activated receptor 2 (PAR2) transcripts, a key factor in itch and AD. IL-27 activated human keratinocytes, increasing PAR2 transcription and activity. Coinjection of SLIGRL (PAR2 agonist) and IL-27 in mice heightened PAR2-mediated itch. In addition, IL-27 boosted BST2 transcription in sensory neurons and keratinocytes. BST2 was upregulated in AD skin, and its injection in mice induced itch-like response. BST2 colocalized with sensory nerve branches in AD skin from both human and murine models. Sensory neurons released BST2, and mice with sensory neuron-specific BST2 knockout displayed reduced itch responses. Overall, this study provides evidence that skin IL-27/PAR2 and neuronal IL-27/BST2 axes are implicated in cutaneous inflammation and pruritus. The discovery of neuronal BST2 in pruritus shed light on BST2 in the itch cascade. Show less
Yu-Fan Chen · 2024 · Research square · added 2026-04-24
Macrophages play a crucial role in coordinating the skeletal muscle repair response, but their phenotypic diversity and the transition of specialized subsets to resolution-phase macrophages remain poo Show more
Macrophages play a crucial role in coordinating the skeletal muscle repair response, but their phenotypic diversity and the transition of specialized subsets to resolution-phase macrophages remain poorly understood. To address this issue, we induced injury and performed single-cell RNA sequencing on individual cells in skeletal muscle at different time points. Our analysis revealed a distinct macrophage subset that expressed high levels of Show less
Prunetin is an O-methylated isoflavone, known for its beneficial properties. However, its specific pharmacological effects in the treatment of osteoporosis (OP) remain poorly understood. This study ai Show more
Prunetin is an O-methylated isoflavone, known for its beneficial properties. However, its specific pharmacological effects in the treatment of osteoporosis (OP) remain poorly understood. This study aims to elucidate the mechanisms underlying the antiosteoporotic effects of prunetin through a combination of bioinformatics analysis and cell experiments. We gathered predicted targets of prunetin from various online platforms. Differential expression analysis of mRNAs in patients with OP was conducted using the Limma package, based on the GSE35959 dataset. A PPI network diagram was visualized and analyzed using Cytoscape 3.7.2 software. Molecular docking was employed to assess the binding affinity between ligands and receptors, and selected key genes were further validated through cell experiments. A total of 4062 differentially expressed genes (DEGs) were identified from the GSE35959 dataset. Among these, 58 genes were found to overlap with the targets of prunetin, indicating their potential as therapeutic targets. The enrichment analysis indicated these targets were mainly enriched in MAPK, FoxO, and mTOR signaling pathways. The molecular docking analysis demonstrated that prunetin exhibited strong binding activity with the core targets. Furthermore, cell experiments revealed that prunetin effectively reversed the expression levels of ALB, ESR1, PTGS2, and FGFR1 mRNA in MC3T3-E1 cells treated with dexamethasone (DEX). Our research revealed the multi-pathway and multi-target features of prunetin in treating OP, shedding light on the potential mechanisms underlying the effectiveness of prunetin against OP. These findings serve as a theoretical foundation for future drug development in this field. Show less
The aim of this study is to develop and validate a nomogram that can assist clinicians in identifying female systemic lupus erythematosus (SLE) patients of reproductive age complicated with interstiti Show more
The aim of this study is to develop and validate a nomogram that can assist clinicians in identifying female systemic lupus erythematosus (SLE) patients of reproductive age complicated with interstitial lung disease (ILD). Clinical, laboratory data of SLE patients were first collected. Meteorological data were then gathered according to the geographical locations of the SLE patients. Diagnostic results, univariate logistic regression, elastic net regression, and multivariate logistic regression were used to screen for risk factors for female SLE patients of reproductive age complicated with ILD. A nomogram was constructed using these risk factors and was internally and externally validated through methods such as calculating the concordance index, plotting calibration curves, drawing receiver operating characteristic curves, and clinical decision curves. A total of 4798 SLE patients were included in this study, with 2488 patients in the development set and 2310 patients in the external validation set. The patients in the development set were randomly divided into a training set (N = 1742) and an internal testing set (N = 746) at a ratio of 7:3. Eight independent risk factors for ILD were identified, including APOB, APOA1, ALP, PLT, HCT, EOS-R, LYM-R, and age. The nomogram model was developed, and the areas under the receiver operating characteristic curve was 0.811 (0.748, 0.875), 0.820 (0.727,0.913), and 0.889 (0.869, 0.909) for the three sets, respectively. We established a nomogram model using easily accessible clinical and laboratory data to predict the probability of female SLE patients of reproductive age developing ILD. Show less
Primary aldosteronism (PA), a significant cause of secondary hypertension affecting ∼10% of patients with severe hypertension, exacerbates cardiovascular, and cerebrovascular complications even after Show more
Primary aldosteronism (PA), a significant cause of secondary hypertension affecting ∼10% of patients with severe hypertension, exacerbates cardiovascular, and cerebrovascular complications even after blood pressure control. PA is categorized into two main subtypes: unilateral aldosterone-producing adenomas (APA) and bilateral hyperaldosteronism (BHA), each requiring distinct treatment approaches. Accurate subtype classification is crucial for selecting the most effective treatment. The goal of this study was to develop novel blood-based proteomic biomarkers to differentiate between APA and BHA subtypes in patients with PA. Five subtyping differential protein biomarker candidates (APOC3, CD56, CHGA, KRT5, and AZGP1) were identified through targeted proteomic profiling of plasma. The subtyping efficiency of these biomarkers was assessed at both the tissue gene expression and blood protein expression levels. To explore the underlying biology of APA and BHA, significant differential pathways were investigated. The five-protein panel proved highly effective in distinguishing APA from BHA in both tissue and blood samples. By integrating these five protein biomarkers with aldosterone and renin, our blood-based predictive methods achieved remarkable receiver operating characteristic (ROC) area under the ROC curves of 0.986 (95% CI: 0.963-1.000) for differentiating essential hypertension from PA, and 0.922 (95% CI: 0.846-0.998) for subtyping APA versus BHA. These outcomes surpass the performance of the existing Kobayashi score subtyping system. Furthermore, the study validated differential pathways associated with the pathophysiology of PA, aligning with current scientific knowledge and opening new avenues for advancing PA care. The new blood-based biomarkers for PA subtyping hold the potential to significantly enhance clinical utility and advance the practice of PA care. Show less
Yunjia Chen, Ender Karaca, Nathaniel H Robin+6 more · 2024 · Genetics in medicine : official journal of the American College of Medical Genetics · Elsevier · added 2026-04-24
Multiple studies suggest an association between DLG2 and neurodevelopmental disorders and indicate the haploinsufficiency of this gene; however, few cases have been thoroughly described. We performed Show more
Multiple studies suggest an association between DLG2 and neurodevelopmental disorders and indicate the haploinsufficiency of this gene; however, few cases have been thoroughly described. We performed additional studies to confirm this clinical association and DLG2 haploinsufficiency. Chromosomal microarray analysis was performed on 11,107 patients at the Cytogenetics Laboratory at the University of Alabama at Birmingham. The Database of Genomic Variants-Gold Standard Variants and the Genome Aggregation Database were selected for the association analysis. Fifty-nine patients from the literature and DECIPHER, all having DLG2 intragenic deletions, were included for comprehensive analysis of the distribution of these deletions. A total of 13 patients with DLG2 intragenic deletions, from 10 families in our cohort, were identified. Nine of 10 probands presented with clinical features of neurodevelopmental disorders. Congenital anomalies and dysmorphism were common in our cohort of patients. Association analysis showed that the frequency of DLG2 deletions in our cohort is significantly higher than those in the Database of Genomic Variants-Gold Standard Variants and the Genome Aggregation Database. Most of DLG2 intragenic deletions identified in 69 unrelated patients from our cohort, the literature, and DECIPHER map to the 5' region of the gene, with a hotspot centered around HPin7, exon 8, and HPin8. Our findings reinforce the link between DLG2 intragenic deletions and neurodevelopmental disorders, strongly support the haploinsufficiency of this gene, and indicate that these deletions might also have an association with congenital anomalies and dysmorphism. Show less
As the prevalence of Type 2 Diabetes Mellitus (T2DM) and Glioblastoma (GBM) rises globally, the relationship between T2DM and GBM remains controversial. This study aims to investigate whether genetica Show more
As the prevalence of Type 2 Diabetes Mellitus (T2DM) and Glioblastoma (GBM) rises globally, the relationship between T2DM and GBM remains controversial. This study aims to investigate whether genetically predicted T2DM is causally associated with GBM. We performed bidirectional Mendelian randomization (MR) analysis using data from genome-wide studies on T2DM (N = 62,892) and GBM (N = 218,792) in European populations. The results of the inverse-variance weighted (IVW) approach served as the primary outcomes. We applied Cochran's Q test and MR-Egger regression for heterogeneity assessment. Leave-one-out analysis was used to evaluate whether any single SNP significantly influenced the observed effect. Our findings reveal a significant causal association between T2DM and an increased risk of GBM (OR [95% CI] 1.70 [1.09, 2.65], P = 0.019). Conversely, the reverse association between T2DM and GBM was insignificant (OR [95% CI] 1.00 [0.99, 1.01], P = 0.408) (P > 0.40). Furthermore, the results from Cochran's Q-test and funnel plots in the MR-Egger method indicated no evidence of pleiotropy between the SNPs and GBM. Additionally, we mapped causal SNPs to genes and identified 10 genes, including MACF1, C1orf185, PTGFRN, NOTCH2, ABCB10, GCKR, THADA, RBMS1, SPHKAP, and PPARG, located on chromosomes 1, 2, and 3. These genes are involved in key biological processes such as the BMP signaling pathway and various metabolic pathways relevant to both conditions. This study provides robust evidence of a significant causal relationship between T2DM and an increased risk of GBM. The identified SNP-mapped genes highlight potential biological mechanisms underlying this association. Show less
Reducing the levels of dietary protein is an effective nutritional approach in lowering feed cost and nitrogen emissions in ruminants. The purpose of this study was to evaluate the effects of dietary Show more
Reducing the levels of dietary protein is an effective nutritional approach in lowering feed cost and nitrogen emissions in ruminants. The purpose of this study was to evaluate the effects of dietary Lys/Met ratio in a low protein diet (10%, dry matter basis) on the growth performance and hepatic function (antioxidant capacity, immune status, and glycolytic activity) in Tibetan lambs. Ninety two-month-old rams with an average weight of 15.37 ± 0.92 kg were randomly assigned to LP-L (dietary Lys/Met = 1:1), LP-M (dietary Lys/Met = 2:1) and LP-H (dietary Lys/Met = 3:1) treatments. The trial was conducted over 100 d, including 10 d of adaption to the diets. Hepatic phenotypes, antioxidant capacity, immune status, glycolytic activity and gene expression profiling was detected after the conclusion of the feeding trials. The results showed that the body weight was higher in the LP-L group when compared to those on the LP-M group (P < 0.05). In addition, the activities of the catalase (CAT) and glutathione peroxidase (GSH-Px) in the LP-L group were significantly increased compared with the LP-M group (P < 0.05), while the malondialdehyde (MDA) levels in LP-H group were significantly decreased (P < 0.05). Compared with LP-H group, both hepatic glycogen (P < 0.01) and lactate dehydrogenase (LDH) (P < 0.05) were significantly elevated in LP-L group. For the LP-L group, the hepatocytes were arranged radially with the central vein in the center, and hepatic plates exhibited tight arrangement. Transcriptome analysis identified 29, 179, and 129 differentially expressed genes (DEGs) between the LP-M vs. LP-L, LP-H vs. LP-M, and LP-H vs. LP-L groups, respectively (Q-values < 0.05 and |log2Fold Change| > 1). Gene Ontology (GO) and correlation analyses showed that in the LP-L group, core genes (C1QA and JUNB) enriched in oxidoreductase activity were positively correlated with antioxidant indicators, while the MYO9A core gene enriched in the immune response was positively associated with immune indicators, and core genes enriched in molecular function (PDK3 and PDP2) were positively correlated with glycolysis indicators. In summary, low-protein diet with a low Lys/Met ratio (1:1) could reduce the hepatic oxidative stress and improve the glycolytic activity by regulating the expression of related genes of Tibetan sheep. Show less
This study investigated the molecular mechanisms of placenta-specific protein 1 (PLAC1) in cervical cancer (CCa), aiming to elucidate its role in tumorigenesis through in vitro and in vivo experiments Show more
This study investigated the molecular mechanisms of placenta-specific protein 1 (PLAC1) in cervical cancer (CCa), aiming to elucidate its role in tumorigenesis through in vitro and in vivo experiments. CCa cell lines with overexpressed or silenced PLAC1 were established to evaluate its impact on cell cycle, apoptosis and the expression of key proteins in the PLAC1/mTOR/HIF-1α/Snail signaling pathways. Functional assays were conducted to assess the influence of the PLAC1/mTOR/HIF-1α/Snail regulatory pathway on cell proliferation, migration and invasion. The role of the mTOR signaling pathway in PLAC1-mediated modulation of CCa characteristics was validated using mTOR activator MHY1485 and mTOR inhibitor rapamycin respectively. HIF1A siRNA was introduced to confirm the role of HIF1A. Furthermore, an in vivo nude mouse model was constructed to confirm PLAC1's influence on tumorigenesis and metastasis in CCa. PLAC1 promoted proliferation, migration, and invasion via the mTOR/HIF-1α/Snail pathway in CCa cells. Enrichment analysis of PLAC1-associated differentially expressed genes further implicated their involvement in CCa and tumor promotion. In a xenograft mouse model, PLAC1 exhibited a pro-tumorigenic effect, which can be reversed by siRNA targeting HIF1A. This study enhances our understanding of PLAC1's role and molecular mechanisms in CCa progression, highlighting its potential as a diagnostic, prognostic, and therapeutic marker for the management of CCa. Show less
Hertwig's epithelial root sheath (HERS) interacts with dental apical mesenchyme and guides development of the tooth root, which is integral to the function of the whole tooth. However, the key genes i Show more
Hertwig's epithelial root sheath (HERS) interacts with dental apical mesenchyme and guides development of the tooth root, which is integral to the function of the whole tooth. However, the key genes in HERS essential for root development are understudied. Here, we show that Axin1, a scaffold protein that negatively regulates canonical Wnt signaling, is strongly expressed in the HERS. Axin1 ablation in the HERS of mice leads to defective root development, but in a manner independent of canonical Wnt signaling. Further studies reveal that Axin1 in the HERS negatively regulates the AKT1-mTORC1 pathway through binding to AKT1, leading to inhibition of ribosomal biogenesis and mRNA translation. Sonic hedgehog (Shh) protein, a morphogen essential for root development, is over-synthesized by upregulated mTORC1 activity upon Axin1 inactivation. Importantly, either haploinsufficiency of the mTORC1 subunit Rptor or pharmacological inhibition of Shh signaling can rescue the root defects in Axin1 mutant mice. Collectively, our data suggest that, independently of canonical Wnt signaling, Axin1 controls ribosomal biogenesis and selective mRNA translation programs via AKT1-mTORC1 signaling during tooth root development. Show less
Rare study of the non-coding and regulatory regions of the genome limits our ability to decode the mechanisms of fatty liver hemorrhage syndrome (FLHS) in chickens. Herein, we constructed the high-fat Show more
Rare study of the non-coding and regulatory regions of the genome limits our ability to decode the mechanisms of fatty liver hemorrhage syndrome (FLHS) in chickens. Herein, we constructed the high-fat diet-induced FLHS chicken model to investigate the genome-wide active enhancers and transcriptome by H3K27ac target chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-Seq) profiles of normal and FLHS liver tissues. Concurrently, an integrative analysis combining ChIP-seq with RNA-Seq and a comparative analysis with chicken FLHS, rat non-alcoholic fatty liver disease (NAFLD) and human NAFLD at the transcriptome level revealed the enhancer and super enhancer target genes and conservative genes involved in metabolic processes. In total, 56 and 199 peak-genes were identified in upregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange) ≥1) (PP) and downregulated peak-genes positively regulated by H3K27ac (Cor (peak-gene correlation) ≥0.5 and log2(FoldChange)≤-1) (PN), respectively; then we screened key regulatory targets mainly distributing in lipid metabolism (PCK1, APOA4, APOA1, INHBE) and apoptosis (KIT, NTRK2) together with MAPK and PPAR signaling pathway in FLHS. Intriguingly, PCK1 was also significantly covered in up-regulated super-enhancers (SEs), which further implied the vital role of PCK1 during the development of FLHS. Together, our studies have identified potential therapeutic biomarkers of PCK1 and elucidated novel insights into the pathogenesis of FLHS, especially for the epigenetic perspective. Show less
Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and is commonly observed in patients with chronic kidney disease, diabetes, and aging individuals. W Show more
Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and is commonly observed in patients with chronic kidney disease, diabetes, and aging individuals. We previously showed that NR4A3 (nuclear receptor subfamily 4 group A member 3), an orphan nuclear receptor, is a key regulator in apo (apolipoprotein) A-IV-induced atherosclerosis progression; however, its role in vascular calcification is poorly understood. We generated NR4A3 NR4A3 expression was upregulated in calcified aortic tissues from chronic kidney disease mice, 1,25(OH) Taken together, our findings reveal that NR4A3-mediated histone lactylation is a novel metabolome-epigenome signaling cascade mechanism that participates in the pathogenesis of medial arterial calcification. Show less
D. Yan, D. Chen, H.-J. Im · 2024 · Journal of cellular biochemistry · Wiley · added 2026-04-24
D. Yan, D. Chen, and H.-J. Im, "Fibroblast Growth Factor-2 Promotes Catabolism via FGFR1-Ras-Raf-MEK1/2-ERK1/2 Axis That Coordinates With the PKCδ Pathway in Human Articular Chondrocytes," Journal of Show more
D. Yan, D. Chen, and H.-J. Im, "Fibroblast Growth Factor-2 Promotes Catabolism via FGFR1-Ras-Raf-MEK1/2-ERK1/2 Axis That Coordinates With the PKCδ Pathway in Human Articular Chondrocytes," Journal of Cellular Biochemistry 113, no. 9 (2012): 2856-2865, https://doi.org/10.1002/jcb.24160. The above article, published online on 5 April 2012 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Christian Behl; and Wiley Periodicals LLC. The retraction has occurred due to concerns related to the data presented in the article raised by the Office of Research Compliance at Rush University Medical Center following an investigation jointly conducted by Rush University and the Jesse Brown Veterans Affairs Medical Center (JBVAMC). Specifically, image elements of the experimental data in Figures 2, 4 A and 5 C were found to have been used by the same author(s) for publication elsewhere in a different scientific context. The corresponding author, Dr. Hee-Jeong Im Sampen, has been informed of the decision to retract but did not agree with it, as she is confident that any errors in the publication do not impact the reliability of the paper's findings. She also advised the editors that she stands ready to cooperate fully to make any necessary corrections. However, the article is retracted as the editors lost trust in the accuracy of the data and consider the conclusions invalid. Show less
Bone-fat balance is crucial to maintain bone homeostasis. As common progenitor cells of osteoblasts and adipocytes, bone marrow mesenchymal stem cells (BMSCs) are delicately balanced for their differe Show more
Bone-fat balance is crucial to maintain bone homeostasis. As common progenitor cells of osteoblasts and adipocytes, bone marrow mesenchymal stem cells (BMSCs) are delicately balanced for their differentiation commitment. However, the exact mechanisms governing BMSC cell fate are unclear. In this study, we discovered that fibroblast growth factor 9 ( Show less
Current genome-wide association studies of frontotemporal dementia (FTD) are underpowered due to limited samples. Further, common genetic etiologies between FTD and amyotrophic lateral sclerosis (ALS) Show more
Current genome-wide association studies of frontotemporal dementia (FTD) are underpowered due to limited samples. Further, common genetic etiologies between FTD and amyotrophic lateral sclerosis (ALS) remain unknown. Using the largest summary statistics of FTD (3526 cases and 9402 controls) and ALS (27,205 cases and 110,881 controls), we found a significant genetic correlation between them (rˆ Show less
Subprotocol K2 (EAY131-K2) of the NCI-MATCH platform trial was an open-label, single-arm, phase II study designed to evaluate the antitumor efficacy of the oral FGFR1-4 inhibitor, erdafitinib, in pati Show more
Subprotocol K2 (EAY131-K2) of the NCI-MATCH platform trial was an open-label, single-arm, phase II study designed to evaluate the antitumor efficacy of the oral FGFR1-4 inhibitor, erdafitinib, in patients with tumors harboring FGFR1-4 mutations or fusions. Central confirmation of tumor FGFR1-4 mutations or fusions was required for outcome analysis. Patients with urothelial carcinoma were excluded. Enrolled subjects received oral erdafitinib at a starting dose of 8 mg daily continuously until intolerable toxicity or disease progression. The primary end point was objective response rate (ORR) with key secondary end points of safety, progression-free survival (PFS), and overall survival (OS). Thirty-five patients were enrolled, and 25 patients were included in the primary efficacy analysis as prespecified in the protocol. The median age was 61 years, and 52% of subjects had received ≥3 previous lines of therapy. The confirmed ORR was 16% (4 of 25 [90% CI, 5.7 to 33.0], This study met its primary end point in patients with several pretreated solid tumor types harboring FGFR1-3 mutations or fusions. These findings support advancement of erdafitinib for patients with fibroblast growth factor receptor-altered tumors outside of currently approved indications in a potentially tumor-agnostic manner. Show less
Shuai Yuan, Yuying Li, Lijuan Wang+13 more · 2023 · medRxiv : the preprint server for health sciences · Cold Spring Harbor Laboratory · added 2026-04-24
The study aimed to discover novel genetic loci for atrial fibrillation (AF), explore the shared genetic etiologies between AF and other cardiovascular and cardiometabolic traits, and uncover AF pathog Show more
The study aimed to discover novel genetic loci for atrial fibrillation (AF), explore the shared genetic etiologies between AF and other cardiovascular and cardiometabolic traits, and uncover AF pathogenesis using Mendelian randomization analysis. We conducted a genome-wide association study meta-analysis including 109,787 AF cases and 1,165,920 controls of European ancestry and identified 215 loci, among which 91 were novel. We performed Genomic Structural Equation Modeling analysis between AF and four cardiovascular comorbidities (coronary artery disease, ischemic stroke, heart failure, and vneous thromboembolism) and found 189 loci shared across these diseases as well as a universal genetic locus shared by atherosclerotic outcomes (i.e., rs1537373 near This genome-wide association study and trans-omic Mendelian randomization analysis provides insights into disease risk prediction, pathophysiology and downstream sequelae. Show less
Abnormalities of FGFR1 have been reported in multiple malignancies, suggesting FGFR1 as a potential target for precision treatment, but drug resistance remains a formidable obstacle. In this study, we Show more
Abnormalities of FGFR1 have been reported in multiple malignancies, suggesting FGFR1 as a potential target for precision treatment, but drug resistance remains a formidable obstacle. In this study, we explored whether FGFR1 acted a therapeutic target in human T-cell acute lymphoblastic leukemia (T-ALL) and the molecular mechanisms underlying T-ALL cell resistance to FGFR1 inhibitors. We showed that FGFR1 was significantly upregulated in human T-ALL and inversely correlated with the prognosis of patients. Knockdown of FGFR1 suppressed T-ALL growth and progression both in vitro and in vivo. However, the T-ALL cells were resistant to FGFR1 inhibitors AZD4547 and PD-166866 even though FGFR1 signaling was specifically inhibited in the early stage. Mechanistically, we found that FGFR1 inhibitors markedly increased the expression of ATF4, which was a major initiator for T-ALL resistance to FGFR1 inhibitors. We further revealed that FGFR1 inhibitors induced expression of ATF4 through enhancing chromatin accessibility combined with translational activation via the GCN2-eIF2α pathway. Subsequently, ATF4 remodeled the amino acid metabolism by stimulating the expression of multiple metabolic genes ASNS, ASS1, PHGDH and SLC1A5, maintaining the activation of mTORC1, which contributed to the drug resistance in T-ALL cells. Targeting FGFR1 and mTOR exhibited synergistically anti-leukemic efficacy. These results reveal that FGFR1 is a potential therapeutic target in human T-ALL, and ATF4-mediated amino acid metabolic reprogramming contributes to the FGFR1 inhibitor resistance. Synergistically inhibiting FGFR1 and mTOR can overcome this obstacle in T-ALL therapy. Show less
We present a 55-year-old man with chest tightness and dyspnoea after activity lasting for 2 months who was diagnosed with single coronary artery (SCA) and presented with dilated cardiomyopathy (DCM) w Show more
We present a 55-year-old man with chest tightness and dyspnoea after activity lasting for 2 months who was diagnosed with single coronary artery (SCA) and presented with dilated cardiomyopathy (DCM) with the c.1858C > T mutation in the Show less
Mesenchymal stem cell (MSC) therapy is a promising candidate for inflammatory bowel disease (IBD) treatment, while overcoming the limitations of naive seeding cells function and realizing efficient in Show more
Mesenchymal stem cell (MSC) therapy is a promising candidate for inflammatory bowel disease (IBD) treatment, while overcoming the limitations of naive seeding cells function and realizing efficient intestinal targeting remains a challenge. Here, a bioadhesive microparticle carrying interleukin-27 (IL-27) MSC-derived extracellular vesicles (MSC Show less
Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data fr Show more
Obesity is a major public health crisis associated with high mortality rates. Previous genome-wide association studies (GWAS) investigating body mass index (BMI) have largely relied on imputed data from European individuals. This study leveraged whole-genome sequencing (WGS) data from 88,873 participants from the Trans-Omics for Precision Medicine (TOPMed) Program, of which 51% were of non-European population groups. We discovered 18 BMI-associated signals ( Show less
Tumor metastasis is the main cause of death for breast cancer patients. Caffeic acid phenethyl ester (CAPE) has strong anti-tumor effects with very low toxicity and may be a potential candidate drug. Show more
Tumor metastasis is the main cause of death for breast cancer patients. Caffeic acid phenethyl ester (CAPE) has strong anti-tumor effects with very low toxicity and may be a potential candidate drug. However, the anti-metastatic effect and molecular mechanism of CAPE on breast cancer need more research. MCF-7 and MDA-MB-231 breast cancer cells were used here. Wound healing and Transwell assay were used for migration and invasion detection. Western blot and RT-qPCR were carried out for the epithelial-to-myofibroblast transformation (EMT) process investigation. Western blot and immunofluorescence were performed for fibroblast growth factor receptor1 (FGFR1) phosphorylation and nuclear transfer detection. Co-immunoprecipitation was used for the FGFR1/myeloid differentiation protein2 (MD2) complex investigation. Our results suggested that CAPE blocks the migration, invasion, and EMT process of breast cancer cells. Mechanistically, CAPE inhibits FGFR1 phosphorylation and nuclear transfer while overexpression of FGFR1 reduces the anti-metastasis effect of CAPE. Further, we found that FGFR1 is bound to MD2, and silencing MD2 inhibits FGFR1 phosphorylation and nuclear transfer as well as cell migration and invasion. This study illustrated that CAPE restrained FGFR1 activation and nuclear transfer through MD2/FGFR1 complex inhibition and showed good inhibitory effects on the metastasis of breast cancer cells. Show less
Previous studies have demonstrated that high-density lipoprotein cholesterol (HDL-C) plays an anti-atherosclerosis role through reverse cholesterol transport. Several studies have validated the effica Show more
Previous studies have demonstrated that high-density lipoprotein cholesterol (HDL-C) plays an anti-atherosclerosis role through reverse cholesterol transport. Several studies have validated the efficacy and safety of natural products in treating atherosclerosis (AS). However, the study of raising HDL-C levels through natural products to treat AS still needs to be explored. The gene sets associated with AS were collected and identified by differential gene analysis and database query. By constructing a protein-protein interaction (PPI) network, the core submodules in the network are screened out. At the same time, by calculating node importance (Nim) in the PPI network of AS disease and combining it with Kyoto Encyclopedia of genes and genomes (KEGG) pathways enrichment analysis, the key target proteins of AS were obtained. Molecular docking is used to screen out small natural drug molecules with potential therapeutic effects. By constructing an in vitro foam cell model, the effects of small molecules on lipid metabolism and key target expression of foam cells were investigated. By differential gene analysis, 451 differential genes were obtained, and a total of 313 disease genes were obtained from 6 kind of databases, then 758 AS-related genes were obtained. The enrichment analysis of the KEGG pathway showed that the enhancement of HDL-C level against AS was related to Lipid and atherosclerosis, Cholesterol metabolism, Fluid shear stress and atherosclerosis, PPAR signaling pathway, and other pathways. Then we intersected 31 genes in the core module of the PPI network, the top 30 genes in Nims, and 32 genes in the cholesterol metabolism pathway, and finally found 3 genes. After the above analysis and literature collection, we focused on the following three related gene targets: APOA1, LIPC, and CETP. Molecular docking showed that Genistein has a good binding affinity for APOA1, CETP, and LIPC. In vitro, experiments showed that Genistein can up-regulated APOA1, LIPC, and CETP levels. Based on our research, Genistein may have the effects of regulating HDL-C and anti-atherosclerosis. Its mechanism of action may be related to the regulation of LIPC, CETP, and APOA1 to improve lipid metabolism. Show less
Several alterations in fibroblast growth factor receptor (FGFR) genes have been found in breast cancer; however, they have not been well characterized as therapeutic targets. Futibatinib (TAS-120; Tai Show more
Several alterations in fibroblast growth factor receptor (FGFR) genes have been found in breast cancer; however, they have not been well characterized as therapeutic targets. Futibatinib (TAS-120; Taiho) is a novel, selective, pan-FGFR inhibitor that inhibits FGFR1-4 at nanomolar concentrations. We sought to determine futibatinib's efficacy in breast cancer models. Nine breast cancer patient-derived xenografts (PDXs) with various FGFR1-4 alterations and expression levels were treated with futibatinib. Antitumor efficacy was evaluated by change in tumor volume and time to tumor doubling. Alterations indicating sensitization to futibatinib in vivo were further characterized in vitro. FGFR gene expression between patient tumors and matching PDXs was significantly correlated; however, overall PDXs had higher FGFR3-4 expression. Futibatinib inhibited tumor growth in 3 of 9 PDXs, with tumor stabilization in an FGFR2-amplified model and prolonged regression (> 110 days) in an FGFR2 Y375C mutant/amplified model. FGFR2 overexpression and, to a greater extent, FGFR2 Y375C expression in MCF10A cells enhanced cell growth and sensitivity to futibatinib. Per institutional and public databases, FGFR2 mutations and amplifications had a population frequency of 1.1%-2.6% and 1.5%-2.5%, respectively, in breast cancer patients. FGFR2 alterations in breast cancer may represent infrequent but highly promising targets for futibatinib. Show less