The relationship between conjugated linoleic acid (CLA) and lipogenesis has been extensively studied in mammals and some cell lines, but it is relatively rare in fish, and the potential mechanism of a Show more
The relationship between conjugated linoleic acid (CLA) and lipogenesis has been extensively studied in mammals and some cell lines, but it is relatively rare in fish, and the potential mechanism of action of CLA reducing fat mass remains unclear. The established primary culture model for studying lipogenesis in grass carp (Ctenopharyngodon idella) preadipocytes was used in the present study, and the objective was to explore the effects of CLA on intracellular lipid and TG content, fatty acid composition, and mRNA levels of adipogenesis transcription factors, lipase, and apoptosis genes in grass carp adipocytes in vitro. The results showed that CLA reduced the size of adipocyte and lipid droplet and decreased the content of intracellular lipid and TG, which was accompanied by a significant down-regulation of mRNA abundance in transcriptional regulators including peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding protein (C/EBP) α, sterol regulatory element-binding protein (SREBP) 1c, lipase genes including fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), lipoprotein lipase (LPL). Meanwhile, it decreased the content of saturated fatty acids (SFAs) and n - 6 polyunsaturated fatty acid (n-6 PUFA) and increased the content of monounsaturated fatty acid (MUFA) and n - 3 polyunsaturated fatty acid (n-3 PUFA) in primary grass carp adipocyte. In addition, CLA induced adipocyte apoptosis through downregulated anti-apoptotic gene B-cell CLL/lymphoma 2 (Bcl-2) mRNA level and up-regulated pro-apoptotic genes tumor necrosis factor-α (TNF-α), Bcl-2-associated X protein (Bax), Caspase-3, and Caspase-9 mRNA level in a dose-dependent manner. These findings suggest that CLA can act on grass carp adipocytes through various pathways, including decreasing adipocyte size, altering fatty acid composition, inhibiting adipocyte differentiation, promoting adipocyte apoptosis, and ultimately decreasing lipid accumulation. Show less
Sargassum fusiforme is a brown seaweed that grows abundantly along the rocky coastlines of Asian countries. The polysaccharides derived from Sargassum fusiforme (SFPS) have received much interest due Show more
Sargassum fusiforme is a brown seaweed that grows abundantly along the rocky coastlines of Asian countries. The polysaccharides derived from Sargassum fusiforme (SFPS) have received much interest due to their various bioactivities, such as hypolipidemic, hypoglycemic, and antioxidant activities. In this study, we extracted and purified SFPS, and obtained the ultrasonic degradation product (SFPSUD). The lipid regulatory effects of SFPS and SFPSUD were investigated in a zebrafish model fed a high-fat diet. The results showed that SFPS significantly decreased the levels of total cholesterol (TC) and triglycerides (TG), and increased the activities of lipoprotein lipase (LPL) and hepatic lipase (HL). SFPSUD was more effective than the SFPS in reducing the TC and TG levels in zebrafish, as well as increasing the LPL and HL activities. Histopathological observations of zebrafish livers showed that SFPSUD significantly improved lipid metabolism disorder in the hepatocytes. The possible lipid-lowering mechanism in zebrafish associated with SFPS and SFPSUD may involve acceleration of the lipid metabolism rate by increasing the activities of LPL and HL. Thus, SFPSUD could be tested as a highly effective hypolipidemic drug. Our results suggest that SFPS and SFPSUD have potential uses as functional foods for the prevention and treatment of hyperlipidemia. Ultrasound can be effectively applied to degrade SFPS to improve its physicochemical properties and bioactivities. Show less
High altitude pulmonary edema (HAPE) is an idiopathic, noncardiogenic form of pulmonary edema that occurs at high altitudes. It is characterized by a severe clinical course and carries a significant m Show more
High altitude pulmonary edema (HAPE) is an idiopathic, noncardiogenic form of pulmonary edema that occurs at high altitudes. It is characterized by a severe clinical course and carries a significant mortality risk. Despite its clinical relevance, the molecular mechanisms underlying HAPE are not well understood. We conducted whole-transcriptome RNA sequencing on blood samples from 6 pairs of HAPE patients and healthy controls to identify differentially expressed (DE) mRNAs, miRNAs, circRNAs, lncRNAs, along with alternative splicing (AS) events, gene fusions, and novel transcripts. To explore the regulatory dynamics, we constructed ceRNA networks and analyzed immune cell infiltration patterns, further annotating the biological functions of these transcripts. For empirical validation, we selected five circRNAs from the ceRNA network and conducted RT-qPCR on 50 paired samples. Additionally, we assessed the correlations between circRNA expression levels and clinical data to evaluate their diagnostic potential. We observed 2,023 differentially expressed mRNAs (DEmRNAs), 84 DEmiRNAs, 200 DEcircRNAs, and 3,573 DElncRNAs. A total of 139 'A3SS' events, 103 'A5SS' events, 545 'MXE' events, 14 'RI' events, and 1,482 'SE' events were identified in the AS events analysis between the two groups. Two ceRNA networks were constructed. T cells, follicular helper, and Macrophages M1 cells exhibited the strongest positive correlation (R=0.82), while naive B cells and memory B cells demonstrated the strongest negative correlation (R=-0.62). In total, the expression of three circRNAs was significantly different in a larger cohort. Hsa_circ₀₀₅₈₄₉₇, hsa_circ₀₀₈₁₀₀₆, and hsa_circ₀₀₈₃₂₂₀ demonstrated consistent with the RNA sequencing results. These three circRNAs strongly correlate with clinical indicators and exhibit potential as diagnostic biomarkers. Finally, we verified five genes (CXCR4, HSD17B2, ANGPTL4, TIMP3, N4BP3) that were differentially expressed in endothelial cells under normoxia and hypoxia through bioinformatics and RT-qPCR analyses. This study elucidates the differential expression of coding and non-coding RNAs (ncRNAs) in HAPE, identifies new transcripts and genes, and enhances our understanding of the transcriptional characteristics of HAPE. Moreover, it highlights the potential role of circRNAs in advancing the diagnosis and treatment of HAPE. Show less
Neurexins, essential synaptic proteins, are linked to neurodevelopmental and neuropsychiatric disorders like autism spectrum disorder (ASD) and schizophrenia. Through this systematic review, we aimed Show more
Neurexins, essential synaptic proteins, are linked to neurodevelopmental and neuropsychiatric disorders like autism spectrum disorder (ASD) and schizophrenia. Through this systematic review, we aimed to shed light on the relationship between neurexin dysfunction and its implications in neurodevelopmental and neuropsychiatric manifestations. Both animal and human-induced pluripotent stem cell (hiPSC) models served as our primary investigative platforms. Utilizing the PRISMA 2020 guidelines, our search strategy involved scouring articles from the PubMed and Google Scholar databases covering a span of two decades (2003-2023). Of the initial collection, 27 rigorously evaluated studies formed the essence of our review. Our review suggested the significant ties between neurexin anomalies and neurodevelopmental and neuropsychiatric outcomes, most notably ASD. Rodent-based investigations delineated pronounced ASD-associated behaviors, and hiPSC models derived from ASD-diagnosed patients revealed the disruptions in calcium dynamics and synaptic activities. Additionally, our review underlined the integral role of specific neurexin variants, primarily NRXN1, in the pathology of schizophrenia. It was also evident from our observation that neurexin malfunctions were implicated in a broader array of these disorders, including ADHD, intellectual challenges, and seizure disorders. This review accentuates the cardinal role neurexins play in the pathological process of neurodevelopmental and neuropsychiatric disorders. The findings underscore a critical need for standardized methodologies in developing animal and hiPSC models for future studies, aiming to minimize heterogeneity. Moreover, we highlight the need to expand research into less studied neurexin variants (i.e., NRXN2 and NRXN3), broadening the scope of our understanding in this field. Our observation also projects hiPSC models as potent tools for bridging research gaps, promoting translational research, and fostering the development of patient-specific therapeutic interventions. Show less
The goat breeding industry on the Tibetan Plateau faces strong selection pressure to enhance fertility. Consequently, there is an urgent need to develop goat lines with higher fertility and adaptabili Show more
The goat breeding industry on the Tibetan Plateau faces strong selection pressure to enhance fertility. Consequently, there is an urgent need to develop goat lines with higher fertility and adaptability. The ovary, as a key organ determining reproductive performance, is regulated by a complex transcriptional network involving numerous protein-coding and non-coding genes. However, the molecular mechanisms of the key mRNA-miRNA-lncRNA regulatory network in goat ovaries remain largely unknown. This study focused on the histology and differential mRNA/miRNA/lncRNA between Chuanzhong black goat (CBG, high productivity, multiple births) and Tibetan goat (TG, strong adaptability, single birth) ovaries. Histomorphological analysis showed that the medulla proportion in CBG ovaries was significantly reduced compared to TG. RNA-Seq and small RNA-Seq analysis identified 1218 differentially expressed (DE) mRNAs, 100 DE miRNAs, and 326 DE lncRNAs, which were mainly enriched in ovarian steroidogenesis, oocyte meiosis, biosynthesis of amino acids and protein digestion, and absorption signaling pathways. Additionally, five key mRNA-miRNA-lncRNA interaction networks regulating goat reproductive performance were identified, including Show less
Retinopathy is a common complication of diabetes mellitus and the leading cause of visual impairment. Danggui Buxue decoction (RRP) has been used as a traditional drug for the treatment of diabetic ne Show more
Retinopathy is a common complication of diabetes mellitus and the leading cause of visual impairment. Danggui Buxue decoction (RRP) has been used as a traditional drug for the treatment of diabetic nephropathy for many years. The aim of this study was to investigate the effects of RRP on hypoxia-induced retinal Müller cell injury. A model of retinal Müller cell damage was created using high glucose levels (25 mmol/L) and/or exposure to low oxygen conditions (1% O2). RRP was given to rats by continuous gavage for 7 days to obtain drug-containing serum. After sterilization, the serum was added to the culture medium at a ratio of 10%. Cell viability, apoptosis, and cell proliferation were assessed using the CCK-8 kit, Annexin V-FITC/propidium iodide apoptosis kit, and EdU kit. The mRNA levels of angiogenesis factors (ANGPTL4, VEGF) and inflammatory factors (IL-1B, ICAM-1) were detected by RT-qPCR. Western blot analysis was employed to assess the levels of proteins related to the ATF4/CHOP pathway. Following hypoxia for 48 h and 72 h, there was a significant decrease in cell viability and proliferation, as well as a notable increase in apoptosis compared to the control group (21% O2). However, high glucose stimulation had no significant effect, and high glucose combined with hypoxia had no further damage to cells. After 48 h of exposure to low oxygen levels, the mRNA expression levels of ANGPTL4, VEGF, IL-1B, and ICAM-1 in retinal Müller cells were significantly higher than in the control group (21% O2). RRP treatment significantly alleviated the increase of cell apoptosis and the upregulation of IL-1B and-1 in retinal Müller cells induced by hypoxia. RRP has the potential to reduce the suppression of the ATF4/CHOP pathway in hypoxia-induced retinal Müller cells, and it significantly alleviates cell apoptosis through regulating inflammatory factors and the ATF4/CHOP pathway. Show less
The purpose of this study was to identify biomarkers associated with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and to develop a new combination with good diagnostic performance. Show more
The purpose of this study was to identify biomarkers associated with hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and to develop a new combination with good diagnostic performance. This study was divided into four phases: discovery, verification, validation, and modeling. A total of four candidate tumor-associated autoantibodies (TAAb; anti-ZIC2, anti-PCNA, anti-CDC37L1, and anti-DUSP6) were identified by human proteome microarray (52 samples) and bioinformatics analysis. Subsequently, these candidate TAAbs were further confirmed by indirect ELISA with two testing cohorts (120 samples for verification and 663 samples for validation). The AUC for these four TAAbs to identify patients with HBV-HCC from chronic hepatitis B (CHB) patients ranged from 0.693 to 0.739. Finally, a diagnostic panel with three TAAbs (anti-ZIC2, anti-CDC37L1, and anti-DUSP6) was developed. This panel showed superior diagnostic efficiency in identifying early HBV-HCC compared with alpha-fetoprotein (AFP), with an AUC of 0.834 [95% confidence interval (CI), 0.772-0.897] for this panel and 0.727 (95% CI, 0.642-0.812) for AFP (P = 0.0359). In addition, the AUC for this panel to identify AFP-negative patients with HBV-HCC was 0.796 (95% CI, 0.734-0.858), with a sensitivity of 52.4% and a specificity of 89.0%. Importantly, the panel in combination with AFP significantly increased the positive rate for early HBV-HCC to 84.1% (P = 0.005) and for late HBV-HCC to 96.3% (P < 0.001). Our findings suggest that AFP and the autoantibody panel may be independent but complementary serologic biomarkers for HBV-HCC detection. We developed a robust diagnostic panel for identifying patients with HBV-HCC from patients with CHB. This autoantibody panel provided superior diagnostic performance for HBV-HCC at an early stage and/or with negative AFP results. Our findings suggest that AFP and the autoantibody panel may be independent but complementary biomarkers for HBV-HCC detection. Show less
The purpose of this study was to screen the genes and pathways that are involved in spermatogonia stem cell (SSC) differentiation regulation during the transition from A The GO analysis showed that RN Show more
The purpose of this study was to screen the genes and pathways that are involved in spermatogonia stem cell (SSC) differentiation regulation during the transition from A The GO analysis showed that RNA transport, the MAPK pathway and the p53 pathway may play vital roles in early SSC differentiation, and Show less
Liver metastasis (LM) stands as a primary cause of mortality in metastatic colorectal cancer (mCRC), posing a significant impediment to long-term survival benefits from targeted therapy and immunother Show more
Liver metastasis (LM) stands as a primary cause of mortality in metastatic colorectal cancer (mCRC), posing a significant impediment to long-term survival benefits from targeted therapy and immunotherapy. However, there is currently a lack of comprehensive investigation into how senescent and exhausted immune cells contribute to LM. We gathered single-cell sequencing data from primary colorectal cancer (pCRC) and their corresponding matched LM tissues from 16 mCRC patients. In this study, we identified senescent and exhausted immune cells, performed enrichment analysis, cell communication, cell trajectory, and cell-based We identified senescent-like myeloid cells (SMCs) and exhausted T cells (TEXs) as the primary senescent and exhausted immune cells. Our findings indicate that SMCs and TEXs can potentially activate transcription factors downstream via ANGPTL4-SDC1/SDC4, this activation plays a role in regulating the epithelial-mesenchymal transition (EMT) program and facilitates the development of LM, the results of cell-based This study elucidates the potential molecular mechanisms underlying the occurrence of LM from various angles through single-cell multi-omics analysis in CRC. It also constructs a network illustrating the role of senescent or exhausted immune cells in regulating EMT. Show less
Fuel substrate switching between carbohydrates and fat is essential for maintaining metabolic homeostasis. During aerobic exercise, the predominant energy source gradually shifts from carbohydrates to Show more
Fuel substrate switching between carbohydrates and fat is essential for maintaining metabolic homeostasis. During aerobic exercise, the predominant energy source gradually shifts from carbohydrates to fat. While it is well known that exercise mobilizes fat storage from adipose tissues, it remains largely obscure how circulating lipids are distributed tissue-specifically according to distinct energy requirements. Here, we demonstrate that aerobic exercise is linked to nutrient availability to regulate tissue-specific activities of lipoprotein lipase (LPL), the key enzyme catabolizing circulating triglyceride (TG) for tissue uptake, through the differential actions of angiopoietin-like (ANGPTL) proteins. Exercise reduced the tissue binding of ANGPTL3 protein, increasing LPL activity and TG uptake in the heart and skeletal muscle in the postprandial state specifically. Mechanistically, exercise suppressed insulin secretion, attenuating hepatic Angptl8 transcription through the PI3K/mTOR/CEBPα pathway, which is imperative for the tissue binding of its partner ANGPTL3. Constitutive expression of ANGPTL8 hampered lipid utilization and resulted in cardiac dysfunction in response to exercise. Conversely, exercise promoted the expression of ANGPTL4 in white adipose tissues, overriding the regulatory actions of ANGPTL8/ANGPTL3 in suppressing adipose LPL activity, thereby diverting circulating TG away from storage. Collectively, our findings show an overlooked bifurcated ANGPTL-LPL network that orchestrates fuel switching in response to aerobic exercise. 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
Colorectal carcinogenesis and progression are associated with aberrant alternative splicing, yet its molecular mechanisms remain largely unexplored. Here, we find that Microrchidia family CW-type zinc Show more
Colorectal carcinogenesis and progression are associated with aberrant alternative splicing, yet its molecular mechanisms remain largely unexplored. Here, we find that Microrchidia family CW-type zinc finger 2 (MORC2) binds to RRM1 domain of RNA binding motif protein 39 (RBM39), and RBM39 interacts with site 1 of pre-CDK5RAP2 exon 32 via its UHM domain, resulting in a splicing switch of cyclin-dependent kinase 5 regulatory subunit associated protein 2 (CDK5RAP2) L to CDK5RAP2 S. CDK5RAP2 S promotes invasion of colorectal cancer cells in vitro and metastasis in vivo. Mechanistically, CDK5RAP2 S specifically recruits the PHD finger protein 8 to promote Slug transcription by removing repressive histone marks at the Slug promoter. Moreover, CDK5RAP2 S, but not CDK5RAP2 L, is essential for the promotion of epithelial-mesenchymal transition induced by MORC2 or RBM39. Importantly, high protein levels of MORC2, RBM39 and Slug are strongly associated with metastasis and poor clinical outcomes of colorectal cancer patients. Taken together, our findings uncover a novel mechanism by which MORC2 promotes colorectal cancer metastasis, through RBM39-mediated pre-CDK5RAP2 alternative splicing and highlight the MORC2/RBM39/CDK5RAP2 axis as a potential therapeutic target for colorectal cancer. Show less
Widespread metastasis is the primary reason for the high mortality associated with ovarian cancer (OC), and effective targeted therapy for tumor aggressiveness is still insufficient in clinical practi Show more
Widespread metastasis is the primary reason for the high mortality associated with ovarian cancer (OC), and effective targeted therapy for tumor aggressiveness is still insufficient in clinical practice. Therefore, it is urgent to find new targets to improve prognosis of patients. PDE4A is a cyclic nucleotide phosphodiesterase that plays a crucial role in the occurrence and development in various malignancies. Our study firstly reported the function of PDE4A in OC. Expression of PDE4A was validated through bioinformatics analysis, RT-qPCR, Western blot, and immunohistochemistry. Additionally, its impact on cell growth and motility was assessed via in vitro and in vivo experiments. PDE4A was downregulated in OC tissues compared with normal tissues and low PDE4A expression was correlated with poor clinical outcomes in OC patients. The knockdown of PDE4A significantly promoted the proliferation, migration and invasion of OC cells while overexpression of PDE4A resulted in the opposite effect. Furthermore, smaller and fewer tumor metastatic foci were observed in mice bearing PDE4A-overexpressing OVCAR3 cells. Mechanistically, downregulation of PDE4A expression can induce epithelial-mesenchymal transition (EMT) and nuclear translocation of Snail, which suggests that PDE4A plays a pivotal role in suppressing OC progression. Notably, Rolipram, the PDE4 inhibitor, mirrored the effects observed with PDE4A deletion. In summary, the downregulation of PDE4A appears to facilitate OC progression by modulating the Snail/EMT pathway, underscoring the potential of PDE4A as a therapeutic target against ovarian cancer metastasis. Show less
This study aimed to identify and validate a 9-gene signature for predicting overall survival (OS) in glioma patients. Analysis of multiple gene expression datasets led to the identification of 135 can Show more
This study aimed to identify and validate a 9-gene signature for predicting overall survival (OS) in glioma patients. Analysis of multiple gene expression datasets led to the identification of 135 candidate genes associated with OS in glioma patients. Further analysis revealed that IGFBP2, PBK, NRXN3, TGIF1, DNAJA4, and LGALS3BP were identified as risk factors for OS, while ENAH, PPP2R2C, and SPHKAP were found to be protective factors. Multifaceted validation using different databases confirmed their differential expression patterns in glioma tissues compared to normal brain tissue. By utilizing LASSO regression and multivariate Cox regression analysis, a risk score was developed based on the expression levels of the 9 crucial genes. The risk score showed a significant correlation with OS in both training and validation cohorts and yielded superior predictive accuracy compared to individual gene expression. Moreover, a predictive nomogram incorporating the risk score, WHO grade, age, IDH mutation, and 1p/19q co-deletion was constructed and validated, which exhibited high predictive capabilities for survival rates at different time points. Enrichment analysis revealed the involvement of extracellular matrix-related pathways and immune system signaling in glioma prognosis. Furthermore, the risk score showed a strong correlation with immune cell infiltration and immune checkpoint expression, suggesting its potential role in the tumor immune microenvironment. In conclusion, our study provides a robust 9-gene signature and a predictive nomogram for evaluating the prognosis of glioma patients, offering valuable insights into personalized treatment strategies. Show less
The pivotal role of lysosomal function in preserving neuronal homeostasis is recognized, with its dysfunction being implicated in neurodegenerative processes, notably in Parkinson's disease (PD). Yet, Show more
The pivotal role of lysosomal function in preserving neuronal homeostasis is recognized, with its dysfunction being implicated in neurodegenerative processes, notably in Parkinson's disease (PD). Yet, the molecular underpinnings of lysosome-related genes (LRGs) in the context of PD remain partially elucidated. We collected RNA-seq data from the brain substantia nigra of 30 PD patients and 20 normal subjects from the GEO database. We obtained molecular classification clusters from the screened lysosomal expression patterns. The lysosome-related diagnostic model of Parkinson's disease was constructed by XGBoost and Random Forest. And we validated the expression patterns of signature LRGs in the diagnostic model by constructing a PD rat model. Finally, the linkage between PD and cancer through signature genes was explored. The expression patterns of the 33 LRGs screened can be divided into two groups of PD samples, enabling exploration of the variance in biological processes and immune elements. Cluster A had a higher disease severity. Subsequently, critical genes were sieved through the application of machine learning methodologies culminating in the identification of two intersecting feature genes (ACP2 and LRP2). A PD risk prediction model was constructed grounded on these signature genes. The model's validity was assessed through nomogram evaluation, which demonstrated robust confidence validity. Then we analyzed the correlation analysis, immune in-filtration, biological function, and rat expression validation of the two genes with common pathogenic genes in Parkinson's disease, indicating that these two genes play an important role in the pathogenesis of PD. We then selected ACP2, which had a significant immune infiltration correlation, as the entry gene for the pan-cancer analysis. The pan-cancer analysis revealed that ACP2 has profound associations with prognostic indicators, immune infiltration, and tumor-related regulatory processes across various neoplasms, suggesting its potential as a therapeutic target in a range of human diseases, including PD and cancers. Our study comprehensively analyzed the molecular grouping of LRGs expression patterns in Parkinson's disease, and the disease progression was more severe in cluster A. And the PD diagnosis model related to LRGs is constructed. Finally, ACP2 is a potential target for the relationship between Parkinson's disease and tumor. Show less
Epithelial-to-mesenchymal transitions (EMTs) and extracellular matrix (ECM) remodeling are distinct yet important processes during carcinoma invasion and metastasis. Transforming growth factor β (TGF- Show more
Epithelial-to-mesenchymal transitions (EMTs) and extracellular matrix (ECM) remodeling are distinct yet important processes during carcinoma invasion and metastasis. Transforming growth factor β (TGF-β) and RAS, signaling through SMAD and RAS-responsive element-binding protein 1 (RREB1), jointly trigger expression of EMT and fibrogenic factors as two discrete arms of a common transcriptional response in carcinoma cells. Here, we demonstrate that both arms come together to form a program for lung adenocarcinoma metastasis and identify chromatin determinants tying the expression of the constituent genes to TGF-β and RAS inputs. RREB1 localizes to H4K16acK20ac marks in histone H2A.Z-loaded nucleosomes at enhancers in the fibrogenic genes interleukin-11 (IL11), platelet-derived growth factor-B (PDGFB), and hyaluronan synthase 2 (HAS2), as well as the EMT transcription factor SNAI1, priming these enhancers for activation by a SMAD4-INO80 nucleosome remodeling complex in response to TGF-β. These regulatory properties segregate the fibrogenic EMT program from RAS-independent TGF-β gene responses and illuminate the operation and vulnerabilities of a bifunctional program that promotes metastatic outgrowth. Show less
Papillary thyroid carcinoma (PTC) is the most prevalent malignancy of the thyroid. Fibroblast growth factor receptor 1 (FGFR1) is highly expressed in PTC and works as an oncogenic protein in this dise Show more
Papillary thyroid carcinoma (PTC) is the most prevalent malignancy of the thyroid. Fibroblast growth factor receptor 1 (FGFR1) is highly expressed in PTC and works as an oncogenic protein in this disease. In this report, we wanted to uncover a new mechanism that drives overexpression of FGFR1 in PTC. Analysis of FGFR1 expression in clinical specimens and PTC cells revealed that FGFR1 expression was enhanced in PTC. Using siRNA/shRNA silencing experiments, we found that FGFR1 downregulation impeded PTC cell growth, invasion, and migration and promoted apoptosis in vitro, as well as suppressed tumor growth in vivo. Bioinformatic analyses predicted the potential USP7-FGFR1 interplay and the potential binding between YY1 and the FGFR1 promoter. The mechanism study found that USP7 stabilized FGFR1 protein via deubiquitination, and YY1 could promote the transcription of FGFR1. Our rescue experiments showed that FGFR1 re-expression had a counteracting effect on USP7 downregulation-imposed in vitro alterations of cell functions and in vivo suppression of xenograft growth. In conclusion, our study identifies the deubiquitinating enzyme USP7 and the oncogenic transcription factor YY1 as potent inducers of FGFR1 overexpression. Designing inhibitors targeting FGFR1 or its upstream inducers USP7 and YY1 may be foreseen as a promising strategy to control PTC development. Show less
The global burden of renal diseases is increasingly severe, underscoring the need for in-depth exploration of the molecular mechanisms underlying renal disease progression and the development of poten Show more
The global burden of renal diseases is increasingly severe, underscoring the need for in-depth exploration of the molecular mechanisms underlying renal disease progression and the development of potential novel biomarkers or therapeutic targets. Angiopoietin-like protein 4 (ANGPTL4) is a multifunctional cytokine involved in the regulation of key biological processes, such as glucose and lipid metabolism, inflammation, vascular permeability, and angiogenesis, all of which play crucial roles in the pathogenesis of kidney diseases. Over the past 2 decades, ANGPTL4 has been regarded as playing a pivotal role in the progression of various kidney diseases, prompting significant interest from the scientific community regarding its potential clinical utility in renal disorders. This review synthesizes the available literature, provides a concise overview of the molecular biological effects of ANGPTL4, and highlights its relationship with multiple renal diseases and recent research advancements. These findings underscore the important gaps that warrant further investigation to develop novel targets for the prediction or treatment of various renal diseases. Show less
Observational studies have preliminarily revealed an association between smoking and gastroesophageal reflux disease (GERD). However, little is known about the causal relationship and shared genetic a Show more
Observational studies have preliminarily revealed an association between smoking and gastroesophageal reflux disease (GERD). However, little is known about the causal relationship and shared genetic architecture between the two. This study aims to explore their common genetic correlations by leveraging genome-wide association studies (GWAS) of smoking behavior-specifically, smoking initiation (SI), never smoking (NS), ever smoking (ES), cigarettes smoked per day (CPD), age of smoking initiation(ASI) and GERD. Firstly, we conducted global cross-trait genetic correlation analysis and heritability estimation from summary statistics (HESS) to explore the genetic correlation between smoking behavior and GERD. Then, a joint cross-trait meta-analysis was performed to identify shared "pleiotropic SNPs" between smoking behavior and GERD, followed by co-localization analysis. Additionally, multi-marker analyses using annotation (MAGMA) were employed to explore the degree of enrichment of single nucleotide polymorphism (SNP) heritability in specific tissues, and summary data-based Mendelian randomization (SMR) was further utilized to investigate potential functional genes. Finally, Mendelian randomization (MR) analysis was conducted to explore the causal relationship between the smoking behavior and GERD. Consistent genetic correlations were observed through global and local genetic correlation analyses, wherein SI, ES, and CPD showed significantly positive genetic correlations with GERD, while NS and ASI showed significantly negative correlations. HESS analysis also identified multiple significantly associated loci between them. Furthermore, three novel "pleiotropic SNPs" (rs4382592, rs200968, rs1510719) were identified through cross-trait meta-analysis and co-localization analysis to exist between SI, NS, ES, ASI, and GERD, mapping the genes MED27, HIST1H2BO, MAML3 as new pleiotropic genes between SI, NS, ES, ASI, and GERD. Moreover, both smoking behavior and GERD were found to be co-enriched in multiple brain tissues, with GMPPB, RNF123, and RBM6 identified as potential functional genes co-enriched in Cerebellar Hemisphere, Cerebellum, Cortex/Nucleus accumbens in SI and GERD, and SUOX identified in Caudate nucleus, Cerebellum, Cortex in NS and GERD. Lastly, consistent causal relationships were found through MR analysis, indicating that SI, ES, and CPD increase the risk of GERD, while NS and higher ASI decrease the risk. We identified genetic loci associated with smoking behavior and GERD, as well as brain tissue sites of shared enrichment, prioritizing three new pleiotropic genes and four new functional genes. Finally, the causal relationship between smoking behavior and GERD was demonstrated, providing insights for early prevention strategies for GERD. Show less
The apolipoprotein A5 ( In a case study conducted at the First Affiliated Hospital of Xinjiang Medical University between Jan 2019 and Dec 2021, we examined a total of 700 cases of EHT along with 700 Show more
The apolipoprotein A5 ( In a case study conducted at the First Affiliated Hospital of Xinjiang Medical University between Jan 2019 and Dec 2021, we examined a total of 700 cases of EHT along with 700 corresponding controls. The serum concentrations of various lipid parameters were measured by enzymatic method, while the genotyping of the SNP was performed using the improved multiplex ligation detection reaction (iMLDR) method. The independent risk factors of EHT were identified from multivariable logistic regression analysis. The nomogram prediction model that incorporated the Our study revealed a higher prevalence of the G allele of the rs662799 variant in individuals diagnosed with EHT compared to the control group. Logistic regression analysis indicated that with the adjustment of other confounders, the observed difference between the two groups remained statistically significant [odds ratio (OR) =1.519; 95% confidence interval (CI): 1.203-1.917; P<0.001]. Based on 8 independent risk factors including In our study, the rs662799 variant of the Show less
Androgen receptor (AR) pathway inhibition remains the cornerstone for prostate cancer therapies. However, castration-resistant prostate cancer (CRPC) tumors can resist AR signaling inhibitors through Show more
Androgen receptor (AR) pathway inhibition remains the cornerstone for prostate cancer therapies. However, castration-resistant prostate cancer (CRPC) tumors can resist AR signaling inhibitors through AR amplification and AR splice variants in AR-positive CRPC (ARPC), and conversion to AR-null phenotypes, such as double-negative prostate cancer (DNPC) and small cell or neuroendocrine prostate cancer (SCNPC). We have shown previously that DNPC can bypass AR-dependence through fibroblast growth factor receptor (FGFR) signaling. However, the role of the FGFR pathway in other CRPC phenotypes has not been elucidated. RNA-Seq analysis was conducted on patient metastases, LuCaP patient-derived xenograft (PDX) models, and CRPC cell lines. Cell lines (C4-2B, VCaP, and 22Rv1) and ex vivo LuCaP PDX tumor cells were treated with enzalutamide (ENZA) and FGFR inhibitors (FGFRi) alone or in combination and sensitivity was determined using cell viability assays. In vivo efficacy of FGFRi in ARPC, DNPC, and SCNPC were evaluated using PDX models. RNA-Seq analysis of FGFR signaling in metastatic specimens, LuCaP PDX models, and CRPC cell lines revealed significant FGF pathway activation in AR-low PC (ARLPC), DNPC, and SCNPC tumors. In vitro/ex vivo analysis of erdafitinib and CH5183284 demonstrated robust and moderate growth suppression of ARPC, respectively. In vivo studies using four ARPC PDX models showed that combination ENZA and CH5183284 significantly suppressed tumor growth. Additional in vivo studies using four ARPC PDX models revealed that erdafitinib monotherapy was as effective as ENZA in suppressing tumor growth, and there was limited combination benefit. Furthermore, two of three DNPC models and two of four SCNPC models responded to CH5183284 monotherapy, suggesting FGFRi responses were model dependent. RNA-Seq and gene set enrichment analysis of end-of-study ARPC tumors treated with FGFRi displayed decreased expression of E2F and MYC target genes and suppressed G2M checkpoint genes, whereas end-of-study SCNPC tumors had heterogeneous transcriptional responses. Although FGFRi treatments suppressed tumor growth across CRPC phenotypes, our analyses did not identify a single pathway or biomarker that would identify tumor response to FGFRi. This is very likely due to the array of FGFR1-4 expression and tumor phenotypes present in CRPC. Nevertheless, our data nominate the FGFR pathway as a clinically actionable target that promotes tumor growth in diverse phenotypes of treatment-refractory metastatic CRPC. Show less
To evaluate the impact of differential emergency treatment measures on the prognosis of patients with ACS. 76 patients with ACS treated in the emergency department of our hospital from January 2017 to Show more
To evaluate the impact of differential emergency treatment measures on the prognosis of patients with ACS. 76 patients with ACS treated in the emergency department of our hospital from January 2017 to September 2021 were selected as the research objects. According to their main symptoms, general signs, and various examination results when arriving at the hospital, differential emergency treatment measures were implemented, so as to ensure the curative effect. After comprehensive emergency treatment, the venous blood test indicators of patients, including creatinine (CR), uric acid (UA), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), lipoprotein A (LPA), Apolipoprotein AI (ApoAI), Apolipoprotein B (ApoB), Potassium ion (K+), glucose (GLU), Cardiac troponin I (cTn) returned to normal. In addition, the proportion of patients without cardiogenic shock, ventricular fibrillation, respiratory and cardiac arrest, cerebral infarction, cerebral hemorrhage, arrhythmia, heart rupture, and other adverse reactions are as high as 92% (70/76). For patients with ACS, it is necessary to take correct emergency rescue and treatment measures immediately, especially to actively implement the percutaneous coronary intervention (PCI) method, so as to give full play to the safety and effectiveness of emergency treatment and curb the possibility of patient death as much as possible. Show less
Lung adenocarcinoma (LUAD) is a malignant tumor of the respiratory system that has a poor 5-year survival rate. Anoikis, a type of programmed cell death, contributes to tumor development and metastasi Show more
Lung adenocarcinoma (LUAD) is a malignant tumor of the respiratory system that has a poor 5-year survival rate. Anoikis, a type of programmed cell death, contributes to tumor development and metastasis. The aim of this study was to develop an anoikis-based stratified model, and a multivariable-based nomogram for guiding clinical therapy for LUAD. Through differentially expressed analysis, univariate Cox, LASSO Cox regression, and random forest algorithm analysis, we established a 4 anoikis-related genes-based stratified model, and a multivariable-based nomogram, which could accurately predict the prognosis of LUAD patients in the TCGA and GEO databases, respectively. The low and high-risk score LUAD patients stratified by the model showed different tumor mutation burden, tumor microenvironment, gemcitabine sensitivity and immune checkpoint expressions. Through immunohistochemical analysis of clinical LUAD samples, we found that the 4 anoikis-related genes (PLK1, SLC2A1, ANGPTL4, CDKN3) were highly expressed in the tumor samples from clinical LUAD patients, and knockdown of these genes in LUAD cells by transfection with small interfering RNAs significantly inhibited LUAD cell proliferation and migration, and promoted anoikis. In conclusion, we developed an anoikis-based stratified model and a multivariable-based nomogram of LUAD, which could predict the survival of LUAD patients and guide clinical treatment. Show less
Centromere protein U (CENPU) is key for mitosis in the carcinogenesis of cancers. However, the roles of CENPU have not been inspected in nasopharyngeal carcinoma (NPC). Thus, we aimed to explore the f Show more
Centromere protein U (CENPU) is key for mitosis in the carcinogenesis of cancers. However, the roles of CENPU have not been inspected in nasopharyngeal carcinoma (NPC). Thus, we aimed to explore the functions and mechanisms of CENPU in NPC. Expression of CENPU was evaluated by real-time quantitative polymerase chain reaction, western blotting and immunohistochemistry. The biological functions of CENPU were evaluated CENPU was highly expressed in NPC. High expression of CENPU was associated with advanced tumor, node and metastasis (TNM) stage and poor overall survival. Cox regression analysis demonstrated that CENPU expression was an independent prognostic factor in NPC. Knockdown of CENPU inhibited proliferation and migration CENPU acts as an oncogene in NPC by interacting with DUSP6, and may represent a promising prognostic biomarker for patients with NPC. Show less
Bihui Jin, Guanyu Su, Xiao Zhou+6 more · 2024 · Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · added 2026-04-24
Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). This study aimed to develop and validate a novel genet Show more
Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism. This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram. Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD. Chictr.org.cn , ChiCTR2100049131. Show less
To investigate the mechanism underlying the regulation of blood-brain barrier permeability changes during cryptococcal meningitis by NLRP3 and Vimentin. Sprague-Dawley rats were treated with WT Crypto Show more
To investigate the mechanism underlying the regulation of blood-brain barrier permeability changes during cryptococcal meningitis by NLRP3 and Vimentin. Sprague-Dawley rats were treated with WT Cryptococcus neoformans (Cn) or CPS1-/- Cn. Neuronal apoptosis was assessed using TUNEL staining, and pathological changes were observed using electron microscopy and HE staining. The expressions of NLRP3, Vimentin, and NF-κB in the cerebral cortex and human brain microvascular endothelial cells (HBMECs) were examined through Western blot and qRT-PCR. siNLRP3 and siVimentin were separately transfected into HBMECs, the expressions of specific factors were assessed. NF-κB and Vimentin levels were detected through immunofluorescence, apoptosis was measured using flow cytometry, and changes in the optical density (OD) of HRP were determined using ELISA. The expressions of NLRP3, Vimentin, and NF-κB were upregulated following intervention with WT Cn Vimentin and the NLRP3 inflammasome are both implicated in the pathological process of cryptococcal meningitis. An interaction between Vimentin and the NLRP3 inflammasome is evident, likely mediated through the NF-κB signaling pathway. Show less