Magnesium phosphate bone cements (MPC) have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability. However, their poor porosity and Show more
Magnesium phosphate bone cements (MPC) have been recognized as a viable alternative for bone defect repair due to their high mechanical strength and biodegradability. However, their poor porosity and permeability limit osteogenic cell ingrowth and vascularization, which is critical for bone regeneration. In the current study, we constructed a novel hierarchically-porous magnesium phosphate bone cement by incorporating extracellular matrix (ECM)-mimicking electrospun silk fibroin (SF) nanofibers. The SF-embedded MPC (SM) exhibited a heterogeneous and hierarchical structure, which effectively facilitated the rapid infiltration of oxygen and nutrients as well as cell ingrowth. Besides, the SF fibers improved the mechanical properties of MPC and neutralized the highly alkaline environment caused by excess magnesium oxide. Bone marrow stem cells (BMSCs) adhered excellently on SM, as illustrated by formation of more pseudopodia. CCK8 assay showed that SM promoted early proliferation of BMSCs. Our study also verified that SM increased the expression of OPN, RUNX2 and BMP2, suggesting enhanced osteogenic differentiation of BMSCs. We screened for osteogenesis-related pathways, including FAK signaing, Wnt signaling and Notch signaling, and found that SM aided in the process of bone regeneration by suppressing the Notch signaling pathway, proved by the downregulation of NICD1, Hes1 and Hey2. In addition, using a bone defect model of rat calvaria, the study revealed that SM exhibited enhanced osteogenesis, bone ingrowth and vascularization compared with MPC alone. No adverse effect was found after implantation of SM Show less
Lymph node metastasis (LNM) is the primary mode of metastasis in gastric cancer (GC). However, the precise mechanisms underlying this process remain elusive. Tumor cells necessitate lipid metabolic re Show more
Lymph node metastasis (LNM) is the primary mode of metastasis in gastric cancer (GC). However, the precise mechanisms underlying this process remain elusive. Tumor cells necessitate lipid metabolic reprogramming to facilitate metastasis, yet the role of lipoprotein lipase (LPL), a pivotal enzyme involved in exogenous lipid uptake, remains uncertain in tumor metastasis. Therefore, the aim of this study was to investigate the presence of lipid metabolic reprogramming during LNM of GC as well as the role of LPL in this process. Intracellular lipid levels were quantified using oil red O staining, BODIPY 493/503 staining, and flow cytometry. Lipidomics analysis was employed to identify alterations in intracellular lipid composition following LPL knockdown. Protein expression levels were assessed through immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assays. The mouse popliteal LNM model was utilized to investigate differences in LNM. Immunoprecipitation and mass spectrometry were employed to examine protein associations. In vitro phosphorylation assays and Phos-tag sodium dodecyl-sulfate polyacrylamide gel electrophoresis assays were conducted to detect angiopoietin-like protein 4 (ANGPTL4) phosphorylation. We identified that an elevated intracellular lipid level represents a crucial characteristic of node-positive (N+) GC and further demonstrated that a high-fat diet can expedite LNM. LPL was found to be significantly overexpressed in N+ GC tissues and shown to facilitate LNM by mediating dietary lipid uptake within GC cells. Leptin, an obesity-related hormone, intercepted the effect exerted by ANGPTL4/Furin on LPL cleavage. Circulating leptin binding to the leptin receptor could induce the activation of inositol-requiring enzyme-1 (IRE1) kinase, leading to the phosphorylation of ANGPTL4 at the serine 30 residue and subsequently reducing its binding affinity with LPL. Moreover, our research revealed that LPL disrupted lipid homeostasis by elevating intracellular levels of arachidonic acid, which then triggered the cyclooxygenase-2/prostaglandin E2 (PGE2) pathway, thereby promoting tumor lymphangiogenesis. Leptin-induced phosphorylation of ANGPTL4 facilitates LPL-mediated lipid uptake and consequently stimulates the production of PGE2, ultimately facilitating LNM in GC. Show less
Is there a relationship between serum uric acid and fructose levels in polycystic ovary syndrome (PCOS)? Elevated serum uric acid levels in women with PCOS positively correlate with serum fructose lev Show more
Is there a relationship between serum uric acid and fructose levels in polycystic ovary syndrome (PCOS)? Elevated serum uric acid levels in women with PCOS positively correlate with serum fructose levels, and elevated serum fructose levels are an independent risk factor for hyperuricemia in women with PCOS. Our previous study suggested a link between elevated serum fructose levels and PCOS. Fructose is unique as it generates uric acid during metabolism, and high uric acid levels are associated with metabolic disorders and an increased risk of anovulation. However, the relationship between serum uric acid and fructose levels in women with PCOS remains unclear. In a case-control study of 774 women (482 controls and 292 patients with PCOS) between May and October 2020 at the Shengjing Hospital of China Medical University, the relationship between uric acid and fructose levels in women with PCOS was examined. Participants were divided into subgroups based on various factors, including BMI, insulin resistance, dyslipidemia, metabolic syndrome, and hyperuricemia. Serum uric acid concentrations were measured using enzymatic assays, and serum fructose levels were determined using a fluorescent enzyme immunoassay. Dietary fructose data were collected through a validated food-frequency questionnaire of 81 food items. We applied restricted cubic splines to a flexibly model and visualized the linear/nonlinear relationships between serum uric acid and fructose levels in PCOS. Multivariate logistic analysis was executed to assess the association between serum fructose levels and hyperuricemia in PCOS. Human granulosa cell and oocyte mRNA profile sequencing data were downloaded for mapping uric acid and fructose metabolism genes in PCOS. Further downstream analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and protein-protein interactions were then carried out on the differentially expressed genes (DEGs). The correlation between uric acid and fructose metabolism genes was calculated using the Pearson correlation coefficient. The GeneCards database was used to identify DEGs related to uric acid and fructose metabolism in PCOS, and then several DEGs were confirmed by quantitative real-time PCR. Both serum fructose and uric acid levels were significantly increased in women with PCOS compared with the control women (P < 0.001), and there was no statistically significant difference in dietary fructose intake between PCOS and controls, regardless of metabolic status. There was a positive linear correlation between serum uric acid and fructose levels in women with PCOS (Poverall < 0.001, Pnon-linear = 0.30). In contrast, no correlation was found in control women (Poverall = 0.712, Pnon-linear = 0.43). Additionally, a non-linear association was observed in the obese subgroup of patients with PCOS (Poverall < 0.001, Pnon-linear = 0.02). Serum uric acid levels were linearly and positively associated with serum fructose levels in patients with PCOS with insulin resistance, dyslipidemia, and metabolic syndrome. Furthermore, even after adjusting for confounding factors, elevated serum fructose levels were an independent risk factor for hyperuricemia in patients with PCOS (P = 0.001; OR, 1.380; 95% CI, 1.207-1.577). There were 28 uric acid and 25 fructose metabolism genes which showed a significant correlation in PCOS. Seven upregulated genes (CAT, CRP, CCL2, TNF, MMP9, GCG, and APOB) related to uric acid and fructose metabolism in PCOS ovarian granulosa cells were ultimately successfully validated using quantitative real-time PCR. Due to limited conditions, more possible covariates (such as smoking and ethnicity) were not included, and the underlying molecular mechanism between fructose and uric acid levels in women with PCOS remains to be further investigated. The results of this study and our previous research indicate that the high uric acid status of PCOS may be mediated by fructose metabolism disorders, highlighting the importance of analyzing fructose metabolism, and especially its metabolic byproduct uric acid, during the clinical diagnosis of PCOS. These results suggest the adverse effects of high uric acid in PCOS, and the importance of taking early interventions regarding uric acid levels to reduce the occurrence and development of further clinical signs, such as metabolic disorders in women with PCOS. This work was supported by: the National Natural Science Foundation of China (No. 82371647, No. 82071607, and No. 32100691); LiaoNing Revitalization Talents Program (No. XLYC1907071); Fok Ying Tung Education Foundation (No. 151039); and Outstanding Scientific Fund of Shengjing Hospital (No. 202003). No competing interests were declared. N/A. Show less
Liver hepatocellular carcinoma (LIHC) is a significant global health issue with limited treatment options. In this study, single-cell RNA sequencing (scRNA-seq) data were used to explore the molecular Show more
Liver hepatocellular carcinoma (LIHC) is a significant global health issue with limited treatment options. In this study, single-cell RNA sequencing (scRNA-seq) data were used to explore the molecular mechanisms of LIHC development and identify potential targets for therapy. The expression of peroxisome proliferator-activated receptors (PPAR)-related genes was analysed in LIHC samples, and primary cell populations, including natural killer cells, T cells, B cells, myeloid cells, endothelial cells, fibroblasts and hepatocytes, were identified. Analysis of the differentially expressed genes (DEGs) between normal and tumour tissues revealed significant changes in gene expression in various cell populations. PPAR activity was evaluated using the 'AUCell' R software, which indicated higher scores in the normal versus the malignant hepatocytes. Furthermore, the DEGs showed significant enrichment of pathways related to lipid and glucose metabolism, cell development, differentiation and inflammation. A prognostic model was then constructed using 8 PPARs-related genes, including FABP5, LPL, ACAA1, PPARD, FABP4, PLIN1, HMGCS2 and CYP7A1, identified using least absolute shrinkage and selection operator-Cox regression analysis, and validated in the TCGA-LIHC, ICGI-LIRI and GSE14520 datasets. Patients with low-risk scores had better prognosis in all cohorts. Based on the expression of the eight model genes, two clusters of patients were identified by ConsensusCluster analysis. We also predicted small-molecule drugs targeting the model genes, and identified perfluorohexanesulfonic acid, triflumizole and perfluorononanoic acid as potential candidates. Finally, wound healing assay confirmed that PPARD can promote the migration of liver cancer cells. Overall, our study offers novel perspectives on the molecular mechanisms of LIHC and potential areas for therapeutic intervention, which may facilitate the development of more effective treatment regimens. Show less
Fasting and refeeding systems can cause significant short-term fluctuations in nutrient and energy levels, triggering adaptive physiological responses in animals. This study examines the effects of fa Show more
Fasting and refeeding systems can cause significant short-term fluctuations in nutrient and energy levels, triggering adaptive physiological responses in animals. This study examines the effects of fasting and refeeding on blood biochemical indicators and transcriptional profiles in the hypothalamus and subcutaneous adipose tissue of geese. Biochemical assays reveal that fasting significantly increases levels of free fatty acids and glucagon, while reducing concentrations of triglycerides, leptin, and insulin. Transcriptomic analyses identify a complex transcriptional response in both the hypothalamus and subcutaneous adipose tissue, affecting several metabolic pathways and key genes associated with feed intake and energy metabolism. In subcutaneous adipose tissue, fasting downregulates genes involved in fatty acid synthesis ( Show less
Purinergic signaling plays a causal role in the modulation of immune inflammatory response in the course of psoriasis, but its regulatory mechanism remains unclear. As a member of purinoceptors, P2Y
Long-term exposure to lead (Pb) can result in chronic damage to the body through accumulation in the central nervous system (CNS) leading to neurodegenerative diseases, such as Alzheimer's disease (AD Show more
Long-term exposure to lead (Pb) can result in chronic damage to the body through accumulation in the central nervous system (CNS) leading to neurodegenerative diseases, such as Alzheimer's disease (AD). This study delves into the intricate role of miR-671/CDR1as regulation in the etiology of AD-like lesions triggered by chronic Pb exposure in adult mice. To emulate the chronic effects of Pb, we established a rodent model spanning 10 months of controlled Pb administration, dividing 52 C57BL/6J mice into groups receiving varying concentrations of Pb (1, 2, or 4 g/L) alongside an unexposed control. Blood Pb levels were monitored using serum samples to ensure accurate dosing and to correlate with observed toxicological outcomes. Utilizing the Morris water maze, a robust behavioral assay for assessing cognitive functions, we documented a dose-dependent decline in learning and memory capabilities among the Pb-exposed mice. Histopathological examination of the hippocampal tissue revealed tell-tale signs of AD-like neurodegeneration, characterized by the accumulation of amyloid plaques and neurofibrillary tangles. At the molecular level, a significant upregulation of AD-associated genes, namely amyloid precursor protein (APP), β-secretase 1 (BACE1), and tau, was observed in the hippocampal tissue of Pb-exposed mice. This was accompanied by a corresponding surge in the protein levels of APP, BACE1, amyloid-β (Aβ), and phosphorylated tau (p-tau), further implicating Pb in the dysregulation of these key AD markers. The expression of CDR1as, a long non-coding RNA implicated in AD pathogenesis, was found to be suppressed in Pb-exposed mice. This observation suggests a potential mechanistic link between Pb-induced neurotoxicity and the dysregulation of the CDR1as/miR-671 axis, which warrants further investigation. Moreover, our study identified a dose-dependent alteration in the intracellular and extracellular levels of the transcription factor nuclear factor-kappa B (NF-κB). This finding implicates Pb in the modulation of NF-κB signaling, a pathway that plays a pivotal role in neuroinflammation and neurodegeneration. In conclusion, our findings underscored the deleterious effects of Pb exposure on the CNS, leading to the development of AD-like pathology. The observed modulation of NF-κB signaling and miR-671/CDR1as regulation provides a plausible mechanistic framework for understanding the neurotoxic effects of Pb and its potential contribution to AD pathogenesis. 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
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
Endometriosis (EMT) is a common gynecological disease with a strong genetic component, while its precise etiology remains elusive. This study aims to integrate transcriptome-wide association study (TW Show more
Endometriosis (EMT) is a common gynecological disease with a strong genetic component, while its precise etiology remains elusive. This study aims to integrate transcriptome-wide association study (TWAS), Mendelian randomization (MR), and bioinformatics analyses to reveal novel putatively causal genes and potential mechanisms. We obtained summary-level data of the Genotype-Tissue Expression Project (GTEx), v8 expression quantitative loci (eQTL) data, and the genome-wide association study (GWAS) data of EMT and its subtypes from the R11 release results of the FinnGen consortium for analysis. GWAS data of modifiable risk factors were collected from IEU Open GWAS. Cross-tissue TWAS analyses were performed using the unified test for molecular signature (UTMOST), while functional summary-based imputation (FUSION) was employed for single-tissue TWAS analyses. Furthermore, we also conducted multi-marker analysis of genomic annotation (MAGMA) analyses to validate the significant associations. Subsequent Mendelian randomization (MR) and colocalization analysis elucidated the causal associations between the identified genes across various tissues and EMT. To further delve into mechanisms, two-sample network MR analyses were conducted. At last, bioinformatics analyses were employed to enhance our understanding of the functional implications and expression patterns of these identified genes. For EMT, 22 significant gene signals were identified by UTMOST, 615 by FUSION, and 354 by MAGMA. Ultimately, six genes, including CISD2, EFRB, GREB1, IMMT, SULT1E1, and UBE2D3, were identified as candidate susceptibility genes for EMT. Through similar procedures, we identified GREB1, IL1A, and SULT1E1 for EMT of the ovary, and we identified GREB1 for EMT of the pelvic peritoneum, EMT of rectovaginal septum and vagina, and deep EMT. In MR analyses, the expression of IMMT in 21 tissues, EFR3B in the adrenal gland, CISD2 in 17 tissues, and UBE2D3 in 7 tissues demonstrated causal relationships with EMT risk. In addition, CISD2, IMMT, and UBE2D3, across different tissues, exhibited strong colocalization with EMT (PPH4 > 0.7). Two-sample network MR analyses revealed that CISD2, EFR3B, and UBE2D3 could potentially regulate the levels of blood lipids and hip circumference so as to influence the risk of EMT. Furthermore, bioinformatics analyses confirmed our findings and delved into the biological functions of the identified genes. Our study unveiled seven novel candidate genes whose predicted expression was associated with the risk of EMT, providing new insights into the underlying genetic framework of EMT. These findings will facilitate a deeper comprehension of the tissue-specific transcriptional regulatory mechanisms associated with EMT, paving the way for optimizing the management and treatment of EMT. Show less
Although tumor cells undergoing epithelial-mesenchymal transition (EMT) typically exhibit spindle morphology in experimental models, such histomorphological evidence of EMT has predominantly been obse Show more
Although tumor cells undergoing epithelial-mesenchymal transition (EMT) typically exhibit spindle morphology in experimental models, such histomorphological evidence of EMT has predominantly been observed in rare primary spindle carcinomas. The characteristics and transcriptional regulators of spontaneous EMT in genetically unperturbed non-spindled carcinomas remain underexplored. We used primary culture combined with RNA sequencing (RNA-seq), single-cell RNA-seq (scRNA-seq), and in situ RNA-seq to explore the characteristics and transcription factors (TFs) associated with potential spontaneous EMT in non-spindled breast carcinoma. Our primary culture revealed carcinoma cells expressing diverse epithelial-mesenchymal traits, consistent with epithelial-mesenchymal plasticity. Importantly, carcinoma cells undergoing spontaneous EMT did not necessarily exhibit spindle morphology, even when undergoing complete EMT. EMT was a favored process, whereas mesenchymal-epithelial transition appeared to be crucial for secondary tumor growth. Through scRNA-seq, we identified TFs that were sequentially and significantly upregulated as carcinoma cells progressed through the EMT process, which correlated with increasing VIM expression. Once upregulated, the TFs remained active throughout the EMT process. ZEB1 was a key initiator and sustainer of EMT, as indicated by its earliest significant upregulation in the EMT process, its exact correlation with VIM expression, and the reversal of EMT and downregulation of EMT-upregulated TFs upon ZEB1 knockdown. The correlation between ZEB1 and vimentin expression in triple-negative breast cancer and metaplastic breast carcinoma tumor cohorts further highlighted its role. The immediate upregulation of ZEB2 following that of ZEB1, along with the observation that the knockdown of ZEB1 or ZEB2 downregulates both ZEB1 and ZEB2 concomitant with the reversal of EMT, suggests their functional cooperation in EMT. This finding, together with that of a lack of correlation of SNAI1, SNAI2, and TWIST1 expression with the mesenchymal phenotype, indicated EMT-TFs have a context-dependent role in EMT. Upregulation of EMT-related gene signatures during EMT correlated with poor patient outcomes, highlighting the biological importance of the model. Elevated EMT gene signatures and increased ZEB1 and ZEB2 expression in vimentin-positive compared to vimentin-negative carcinoma cells within the corresponding primary tumor tissue confirmed ZEB1 and ZEB2 as intrinsic, instead of microenvironmentally-induced, EMT regulators, and vimentin as an in vivo indicator of EMT. Our findings provide insights into the characteristics and transcriptional regulators of spontaneous EMT in primary non-spindled carcinoma. Show less
Long-persistent luminescent (LPL) materials have attracted considerable research interest due to their extensive applications and outstanding afterglow performance. However, the performance of red LPL Show more
Long-persistent luminescent (LPL) materials have attracted considerable research interest due to their extensive applications and outstanding afterglow performance. However, the performance of red LPL materials lags behind that of green and blue materials. Therefore, it is crucial to explore novel red LPL materials. This study introduces a straightforward and viable strategy for organic-inorganic hybrids, wherein the organic ligand 1,3,6,8-Tetrakis(4-carboxyphenyl)pyrene (TCPP) is coordinated to the surface of a red persistent phosphor Sr 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
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
Recent studies have shown that epithelial-mesenchymal transition (EMT) plays an important role in paraquat (PQ)-induced tissue fibrosis, which is the main cause of death in patients with PQ poisoning. Show more
Recent studies have shown that epithelial-mesenchymal transition (EMT) plays an important role in paraquat (PQ)-induced tissue fibrosis, which is the main cause of death in patients with PQ poisoning. However, no effective treatment for pulmonary interstitial fibrosis caused by PQ poisoning exists. It is of great significance for us to find new therapeutic targets through bioinformatics in PQ-induced EMT. We conducted transcriptome sequencing to determine the expression profiles of 1210 messenger RNAs (mRNAs), 558 long noncoding RNAs, 28 microRNAs (miRNAs), including 18 known-miRNAs, 10 novel-miRNAs and 154 circular RNAs in the PQ-exposed EMT group mice. Using gene ontology and Kyoto Encyclopaedia of Genes and Genomes analyses, we identified the pathways associated with signal transduction, cancers, endocrine systems and immune systems were involved in PQ-induced EMT. Furthermore, we constructed long noncoding RNA-miRNA-mRNA interrelated networks and found that upregulated genes included Il22ra2, Mdm4, Slc35e2 and Angptl4, and downregulated genes included RGS2, Gabpb2, Acvr1, Prkd3, Sp100, Tlr12, Syt15 and Camk2d. Thirteen new potential competitive endogenous RNA targets were also identified for further treatment of PQ-induced pulmonary tissue fibrosis. Through further study of the pathway and networks, we may identify new molecular targets in PQ-induced pulmonary EMT. Show less
To explore the causal relationship between inflammatory protein markers and the risk of colorectal cancer using a Mendelian randomization (MR) approach. We obtained data pertaining to colorectal cance Show more
To explore the causal relationship between inflammatory protein markers and the risk of colorectal cancer using a Mendelian randomization (MR) approach. We obtained data pertaining to colorectal cancer from Genome-Wide Association Study (GWAS) datasets and used 91 inflammatory protein markers as the exposure variables. A two-sample MR analysis model was used to assess the causal link between the inflammatory markers and colorectal cancer risk. The robustness of the results was evaluated through heterogeneity, pleiotropy, and sensitivity analyses using 5 MR models: Inverse Variance Weighted (IVW), Weighted Median, MR Egger, Simple Mode, and Weighted Mode. We examined the mRNA expressions of Using the IVW model, MR analysis revealed significant causal associations between a reduced risk of colorectal cancer and lowered expressions of AXIN1 (OR=0.866, 95% Lowered expressions of inflammatory protein markers AXIN1, β-NGF, and PD-L1 are causally correlated with a reduced risk of colorectal cancer and their expression levels are associated with TNM staging and tumor differentiation. These markers may thus serve as potential targets for colorectal cancer treatment and prevention. Show less
A high-fat diet (HFD) is recognized as an important contributor to inflammatory bowel disease (IBD). However, the precise underlying mechanism of HFD on IBD remains elusive. This study aimed to invest Show more
A high-fat diet (HFD) is recognized as an important contributor to inflammatory bowel disease (IBD). However, the precise underlying mechanism of HFD on IBD remains elusive. This study aimed to investigate the potential mechanism by which HFD affects IBD using 16S rRNA-sequencing and RNA-seq technology. Results indicated that HFD-treated mice exhibited notable alternations in the structure and composition of the gut microbiota, with some of these alternations being associated with the pathogenesis of IBD. Analysis of the colon transcriptome revealed 11 hub genes and 7 hub pathways among control, DSS-induced colitis, and HFD + DSS-treated groups. Further analysis explores the relationship between the hub pathways and genes, as well as the hub genes and gut microbiota. Overall, the findings indicate that the impact of HFD on DSS-induced colitis may be linked to intestinal dysbiosis and specific genes such as 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
Major depressive disorder (MDD) is a common disease affecting 300 million people worldwide. The existing drugs are ineffective for approximately 30% of patients, so it is urgent to develop new antidep Show more
Major depressive disorder (MDD) is a common disease affecting 300 million people worldwide. The existing drugs are ineffective for approximately 30% of patients, so it is urgent to develop new antidepressant drugs with novel mechanisms. Here, we found that norisoboldine (NOR) showed an antidepressant efficacy in the chronic social defeat stress (CSDS) depression model in the tail suspension, forced swimming, and sucrose consumption tests. We then utilized the drug-treated CSDS mice paradigm to segregate and gain differential protein groups of CSDS versus CON (CSDS Show less
Baozhu Guo, Junfen Liu, Xiaoli Han+5 more · 2024 · Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · added 2026-04-24
Adverse cardiovascular events are the leading cause of death in peritoneal dialysis patients. Identifying indicators that can predict adverse cardiovascular events in these patients is crucial for pro Show more
Adverse cardiovascular events are the leading cause of death in peritoneal dialysis patients. Identifying indicators that can predict adverse cardiovascular events in these patients is crucial for prognosis. This study aims to assess the value of dual-specificity phosphatase 6 (DUSP6) in peripheral blood mononuclear cells as a predictor of adverse cardiovascular events after peritoneal dialysis in diabetic nephropathy patients. A total of 124 diabetic nephropathy patients underwent peritoneal dialysis treatment at the Department of Nephrology of the First Affiliated Hospital of Hebei North University from June to September 2022 were selected as study subjects. The levels of DUSP6 in peripheral blood mononuclear cells were determined using Western blotting. Patients were categorized into high-level and low-level DUSP6 groups based on the median DUSP6 level. Differences in body mass index, serum albumin, high-sensitivity C-reactive protein, and dialysis duration were compared between the 2 groups. Pearson, Spearman, and multiple linear regression analyses were performed to examine factors related to DUSP6. Patients were followed up to monitor the occurrence of adverse cardiovascular events, and risk factors for adverse cardiovascular events after peritoneal dialysis were analyzed using Kaplan-Meier and Cox regression. By the end of the follow-up, 33 (26.61%) patients had experienced at least one adverse cardiovascular event. The high-level DUSP6 group had higher body mass index, longer dialysis duration, and higher high-sensitivity C-reactive protein, but lower serum albumin levels compared to the low-level DUSP6 group (all Dialysis duration and high-sensitivity C-reactive protein are independently associated with DUSP6 levels in peripheral blood mononuclear cells of diabetic nephropathy patients undergoing peritoneal dialysis. High DUSP6 levels indicate a higher risk of adverse cardiovascular events. Show less
Heart failure (HF), an end-stage clinical syndrome secondary to cardiac impairment, significantly affects patients' quality of life and long-term prognosis. Myocardial fibrosis leads to systolic and d Show more
Heart failure (HF), an end-stage clinical syndrome secondary to cardiac impairment, significantly affects patients' quality of life and long-term prognosis. Myocardial fibrosis leads to systolic and diastolic dysfunction, and promotes the progression of HF. Several studies involving the modulation of myocardial fibrosis have been conducted in an effort to improve cardiac function. Heat shock protein 27 (HSP27) is a small chaperone protein that is overexpressed in cellular stress states. HSP27 modulates epithelial-mesenchymal transition, playing a crucial role in the pathology of several fibrotic diseases. However, its association with myocardial fibrosis regulation is unknown. This study aimed to investigate the mechanisms by which HSP27 regulates myocardial fibrosis. We created cardiac-specific HSP25 (the murine ortholog of human HSP27) knockout mice and found that HSP25 knockdown inhibited endothelial-mesenchymal transition (EndMT), attenuated myocardial fibrosis, and ameliorated diastolic dysfunction in isoproterenol-induced HF mice via echocardiography, histology, and western bloting. In vitro, HSP27 knockdown attenuated transforming growth factor beta-induced EndMT, whereas HSP27 overexpression promoted EndMT. Furthermore, the SMAD3/SNAIL1 pathway was found to be crucial for HSP27-mediated EndMT regulation. As an essential molecule in EndMT regulation and myocardial fibrosis modulation, HSP27 may hold promise as a therapeutic target for patients with HF. Show less
Increasing evidence has indicated that long non-coding RNAs (lncRNAs) have been proven to regulate esophageal cancer progression. The lncRNA protein disulfide isomerase family A member 3 pseudogene 1 Show more
Increasing evidence has indicated that long non-coding RNAs (lncRNAs) have been proven to regulate esophageal cancer progression. The lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P1) has been shown to promote cancer stem cell properties; however, its mechanism of action remains unclear. In this study, we investigated the regulation of esophageal cancer stem cell properties by the interaction of PDIA3P1 with proteins. The GEPIA2 and Gene Expression Omnibus databases were used to analyze gene expression. PDIA3P1 expression in human esophageal squamous cell carcinoma (ESCC) tissues and cell lines was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Loss-of-function experiments were performed to determine the effects of PDIA3P1 on ESCC cell proliferation, migration, and invasion. The sphere formation assay, number of side population cells, and CD271 + /CD44 + cells were detected by flow cytometry to identify the cancer stem cell properties. RNA immunoprecipitation (RIP), RNA pull-down, co-immunoprecipitation (co-IP), dual luciferase reporter, and cleavage under targets and tagmentation (CUT&Tag) assays were performed to elucidate the underlying molecular mechanisms. PDIA3P1 expression was upregulated in ESCC cell lines and tissues. Functionally, higher PDIA3P1 expression promoted cell proliferation, invasion, and metastasis and inhibited apoptosis in esophageal cancer. Importantly, PDIA3P1 promoted cancer stem cell properties in ESCC. Mechanistically, PDIA3P1 interacted with and stabilized octamer-binding transcription factor 4 (OCT4) by eliminating its ubiquitination by the ubiquitinating enzyme WW domain-containing protein 2 (WWP2). Moreover, as a transcription factor, OCT4 bound to the PDIA3P1 promoter and promoted its transcription. Our research revealed a novel mechanism by which a positive feedback loop exists between PDIA3P1 and OCT4. It also demonstrated that the PDIA3P1-WWP2-OCT4 loop is beneficial for promoting the cancer stem cell properties of ESCC. Owing to this regulatory relationship, the PDIA3P1-WWP2-OCT4-positive feedback loop might be used in the diagnosis and prognosis, as well as in the development of novel therapeutics for esophageal cancer. Show less
Geese evolved from migratory birds, and when they consume excessive high-energy feed, glucose is converted into triglycerides. A large amount of triglyceride deposition can induce incomplete oxidation Show more
Geese evolved from migratory birds, and when they consume excessive high-energy feed, glucose is converted into triglycerides. A large amount of triglyceride deposition can induce incomplete oxidation of fatty acids, leading to lipid accumulation in the liver and the subsequent formation of fatty liver. In the Chaoshan region of Guangdong, China, Shitou geese develop a unique form of fatty liver through 24 h overfeeding of brown rice. To investigate the mechanisms underlying the formation of fatty liver in Shitou geese, we collected liver samples from normally fed and overfed geese. The results showed that the liver size in the treatment group was significantly larger, weighing 3.5 times more than that in the control group. Extensive infiltration of lipid droplets was observed in the liver upon staining of tissue sections. Biochemical analysis revealed that compared to the control group, the treatment group showed significantly elevated levels of total cholesterol (T-CHO), triglycerides (TG), and glycogen in the liver. However, no significant differences were observed in the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which are common indicators of liver damage. Furthermore, we performed a combined transcriptomic and lipidomic analysis of the liver samples and identified 1,510 differentially expressed genes (DEGs) and 1,559 significantly differentially abundant metabolites (SDMs). The enrichment analysis of the DEGs revealed their enrichment in metabolic pathways, cellular process-related signaling pathways, and specific lipid metabolism pathways. We also conducted KEGG enrichment analysis of the SDMs and compared them with the enriched signaling pathways obtained from the DEGs. In this study, we identified 3 key signaling pathways involved in the formation of fatty liver in Shitou geese, namely, the biosynthesis of unsaturated fatty acids, glycerol lipid metabolism, and glycerophospholipid metabolism. In these pathways, genes such as glycerol-3-phosphate acyltransferase, mitochondrial (GPAM), 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2), diacylglycerol O-acyltransferase 2 (DGAT2), lipase, endothelial (LIPG), lipoprotein lipase (LPL), phospholipase D family member 4 (PLD4), and phospholipase A2 group IVF (PLA2G4F) may regulate the synthesis of metabolites, including triacylglycerol (TG), phosphatidate (PA), 1,2-diglyceride (DG), phosphatidylethanolamine (PE), and phosphatidylcholine (PC). These genes and metabolites may play a predominant role in the development of fatty liver, ultimately promoting the accumulation of TG in the liver and leading to the progression of fatty liver. Show less
Yanhua Zhou, Dayu Yan, Xiulan Zhang+3 more · 2024 · Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · added 2026-04-24
Pelvic organ prolapse (POP) is a common condition in postmenopausal women, with an increasing prevalence due to aging. Some women experience POP recurrence after surgical treatment, significantly affe Show more
Pelvic organ prolapse (POP) is a common condition in postmenopausal women, with an increasing prevalence due to aging. Some women experience POP recurrence after surgical treatment, significantly affecting their physical and mental health. The uterosacral ligament is a critical pelvic support structure. This study aims to investigate the molecular pathological changes in the uterosacral ligament of postmenopausal women with recurrent POP using transcriptomic analysis. Transcriptomic data of uterosacral ligament tissues were obtained from the public dataset GSE28660, which includes samples from 4 postmenopausal women with recurrent POP, 4 with primary POP, and 4 without POP. Differentially expressed genes (DEGs) were identified between recurrent POP and both primary and non-POP groups. Further analysis included intersection analysis of DEGs, gene ontology enrichment, protein-protein interaction (PPI) network construction, gene set enrichment analysis (GSEA), single-sample GSEA, and xCell immune cell infiltration analysis to explore molecular pathological changes in recurrent POP. Additionally, histological and molecular differences in the uterosacral ligament were compared between simulated vaginal delivery (SVD) rat models with and without ovariectomy. Compared with primary POP and non-POP groups, recurrent POP exhibited activation of adipogenesis and inflammation-related pathways, while pathways related to muscle proliferation and contraction were downregulated in the uterosacral ligament. Nine key DEGs ( Adipogenesis and inflammation in the uterosacral ligament may contribute to its reduced supportive function, potentially leading to recurrence POP in postmenopausal women. Show less
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
S Uzuner, L P Li · 2024 · BMC musculoskeletal disorders · BioMed Central · added 2026-04-24
Anterior cruciate ligament (ACL) injuries are often caused by high impact loadings during competitive sports but may also happen during regular daily activities due to tissue degeneration or altered m Show more
Anterior cruciate ligament (ACL) injuries are often caused by high impact loadings during competitive sports but may also happen during regular daily activities due to tissue degeneration or altered mechanics after a previous knee injury or surgery such as meniscectomy. Most existing research on ACL injury has focused on impact loading scenarios or the consequence of ACL injury on meniscus. The objective of the present study was to investigate the effects of varying degrees of medial meniscectomy on the mechanics of intact ACL by performing a poromechanical finite element analysis under moderate creep loadings. Four clinical scenarios with 25%, 50%, 75% and total medial meniscectomy were compared with the intact knee finite element model. Our results suggested that different medial meniscal resections may increase, at different extents, the knee laxity and peak tensile stress in the ACL, potentially leading to collagen fiber fatigue tearing and altered mechanobiology under normal joint loadings. Interestingly, the ACL stress actually increased during early knee creep (~ 3 min) before it reached an equilibrium. In addition, meniscectomy accelerated ACL stress reduction during knee creep, transferred more loading to tibial cartilage, increased contact pressure, and shifted the contact center posteriorly. This study may contribute to a better understanding of the interaction of meniscectomy and ACL integrity during daily loadings. Show less