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1.
Mol Cancer ; 23(1): 55, 2024 03 16.
Article in English | MEDLINE | ID: mdl-38491348

ABSTRACT

BACKGROUND: Long noncoding RNAs (lncRNAs) have emerged as key players in tumorigenesis and tumour progression. However, the biological functions and potential mechanisms of lncRNAs in colorectal cancer (CRC) are unclear. METHODS: The novel lncRNA POU6F2-AS1 was identified through bioinformatics analysis, and its expression in CRC patients was verified via qRT-PCR and FISH. In vitro and in vivo experiments, such as BODIPY staining, Oil Red O staining, triglyceride (TAG) assays, and liquid chromatography mass spectrometry (LC-MS) were subsequently performed with CRC specimens and cells to determine the clinical significance, and functional roles of POU6F2-AS1. Biotinylated RNA pull-down, RIP, Me-RIP, ChIP, and patient-derived organoid (PDO) culture assays were performed to confirm the underlying mechanism of POU6F2-AS1. RESULTS: The lncRNA POU6F2-AS1 is markedly upregulated in CRC and associated with adverse clinicopathological features and poor overall survival in CRC patients. Functionally, POU6F2-AS1 promotes the growth and lipogenesis of CRC cells both in vitro and in vivo. Mechanistically, METTL3-induced m6A modification is involved in the upregulation of POU6F2-AS1. Furthermore, upregulated POU6F2-AS1 could tether YBX1 to the FASN promoter to induce transcriptional activation, thus facilitating the growth and lipogenesis of CRC cells. CONCLUSIONS: Our data revealed that the upregulation of POU6F2-AS1 plays a critical role in CRC fatty acid metabolism and might provide a novel promising biomarker and therapeutic target for CRC.


Subject(s)
Colorectal Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Up-Regulation , Cell Line, Tumor , Cell Proliferation/genetics , MicroRNAs/genetics , Colorectal Neoplasms/pathology , Fatty Acids , Gene Expression Regulation, Neoplastic , Cell Movement/genetics , POU Domain Factors/genetics , POU Domain Factors/metabolism , Methyltransferases/metabolism , Fatty Acid Synthase, Type I/genetics , Fatty Acid Synthase, Type I/metabolism
2.
J Stroke Cerebrovasc Dis ; 33(8): 107752, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38701939

ABSTRACT

BACKGROUND: Observational studies have suggested a potential association between abdominal viscera volume and increased risk of stroke. However, the causal relationship remains unclear. This study aims to utilize Mendelian randomization (MR) to explore the genetic causal relationship between them. METHODS: We conducted MR analysis to study the causal effects of five abdominal viscera volumes on stroke. The genetic variations of abdominal viscera volume were obtained from the UK Biobank, and the summary data for stroke and ischemic stroke were acquired from the MEGASTROKE consortium. This study employed inverse variance weighting (IVW), MR Egger, and weighted median methods. IVW served as the primary MR analysis method, supplemented by other sensitivity analyses to validate the robustness of the results. RESULTS: We found that liver volume can causally increase the risk of stroke [odds ratio (OR): 1.13, 95 % confidence interval (CI): 1.03-1.25, P = 0.013] and ischemic stroke (OR: 1.14, 95 % CI: 1.03-1.26, P = 0.012). No causal relationships between other abdominal viscera volumes and stroke and ischemic stroke appeared to be present (P > 0.05). Sensitivity analyses confirmed the robustness of the results. CONCLUSION: Our research findings indicate a causal relationship between liver volume and stroke, highlighting the potential role of liver volume in the onset of stroke. However, further basic and clinical research is needed to delve into the specific mechanisms underlying the relationship between liver volume and stroke, and to implement interventions aimed at reducing the impact of liver volume on stroke risk.


Subject(s)
Genetic Predisposition to Disease , Ischemic Stroke , Liver , Mendelian Randomization Analysis , Humans , Liver/pathology , Risk Factors , Organ Size , Risk Assessment , Ischemic Stroke/genetics , Ischemic Stroke/epidemiology , Ischemic Stroke/etiology , Phenotype , Stroke/genetics , Stroke/epidemiology , Stroke/etiology , Male , Female , Polymorphism, Single Nucleotide , Middle Aged
3.
Int J Mol Sci ; 25(3)2024 Feb 04.
Article in English | MEDLINE | ID: mdl-38339157

ABSTRACT

YTH N6-methyladenosine RNA binding protein 1 (YTHDF1), an m6A reader, has a role in the development and progression of breast cancer as well as the immunological microenvironment. The networks of competing endogenous RNA in cancer have received much attention in research. In tumor gene therapy, the regulatory networks of m6A and competing endogenous RNA are increasingly emerging as a new route. We evaluated the relationship between the YTHDF1 expression, overall survival, and clinicopathology of breast cancer using TCGA, PrognoScan, and other datasets. We used Western blot to demonstrate that YTHDF1 is substantially expressed in breast cancer tissues. Furthermore, we explored YTHDF1's functions in the tumor mutational burden, microsatellite instability, and tumor microenvironment. Our findings indicate that YTHDF1 is a critical component of the m6A regulatory proteins in breast cancer and may have a particular function in the immunological microenvironment. Crucially, we investigated the relationship between YTHDF1 and the associated competitive endogenous RNA regulatory networks, innovatively creating three such networks (Dehydrogenase/Reductase 4-Antisense RNA 1-miR-378g-YTHDF1, HLA Complex Group 9-miR-378g-YTHDF1, Taurine Up-regulated 1-miR-378g-YTHDF1). Furthermore, we showed that miR-378g could inhibit the expression of YTHDF1, and that miR-378g/YTHDF1 could impact MDA-MB-231 proliferation. We speculate that YTHDF1 may serve as a biomarker for poor prognosis and differential diagnosis, impact the growth of breast cancer cells via the ceRNA network axis, and be a target for immunotherapy against breast cancer.


Subject(s)
Breast Neoplasms , MicroRNAs , RNA-Binding Proteins , Humans , Blotting, Western , MicroRNAs/genetics , Neoplasms , RNA, Antisense , RNA, Competitive Endogenous/genetics , RNA, Competitive Endogenous/metabolism , RNA-Binding Proteins/genetics , Tumor Microenvironment/genetics , Breast Neoplasms/genetics , Breast Neoplasms/immunology , Breast Neoplasms/metabolism
4.
BMC Plant Biol ; 23(1): 625, 2023 Dec 07.
Article in English | MEDLINE | ID: mdl-38062401

ABSTRACT

BACKGROUND: Fusarium oxysporum is a prevalent fungal pathogen that diminishes soybean yield through seedling disease and root rot. Preventing Fusarium oxysporum root rot (FORR) damage entails on the identification of resistance genes and developing resistant cultivars. Therefore, conducting fine mapping and marker development for FORR resistance genes is of great significance for fostering the cultivation of resistant varieties. In this study, 350 soybean germplasm accessions, mainly from Northeast China, underwent genotyping using the SoySNP50K Illumina BeadChip, which includes 52,041 single nucleotide polymorphisms (SNPs). Their resistance to FORR was assessed in a greenhouse. Genome-wide association studies utilizing the general linear model, mixed linear model, compressed mixed linear model, and settlement of MLM under progressively exclusive relationship models were conducted to identify marker-trait associations while effectively controlling for population structure. RESULTS: The results demonstrated that these models effectively managed population structure. Eight SNP loci significantly associated with FORR resistance in soybean were detected, primarily located on Chromosome 6. Notably, there was a strong linkage disequilibrium between the large-effect SNPs ss715595462 and ss715595463, contributing substantially to phenotypic variation. Within the genetic interval encompassing these loci, 28 genes were present, with one gene Glyma.06G088400 encoding a protein kinase family protein containing a leucine-rich repeat domain identified as a potential candidate gene in the reference genome of Williams82. Additionally, quantitative real-time reverse transcription polymerase chain reaction analysis evaluated the gene expression levels between highly resistant and susceptible accessions, focusing on primary root tissues collected at different time points after F. oxysporum inoculation. Among the examined genes, only this gene emerged as the strongest candidate associated with FORR resistance. CONCLUSIONS: The identification of this candidate gene Glyma.06G088400 improves our understanding of soybean resistance to FORR and the markers strongly linked to resistance can be beneficial for molecular marker-assisted selection in breeding resistant soybean accessions against F. oxysporum.


Subject(s)
Fusarium , Glycine max , Glycine max/genetics , Genome-Wide Association Study , Plant Breeding , Fusarium/physiology , Polymorphism, Single Nucleotide/genetics , Disease Resistance/genetics , Plant Diseases/genetics , Plant Diseases/microbiology
5.
Theor Appl Genet ; 136(6): 125, 2023 May 10.
Article in English | MEDLINE | ID: mdl-37165285

ABSTRACT

KEY MESSAGE: Here, a novel pleiotropic QTL qSS14 simultaneously regulating four seed size traits and two consistently detected QTLs qSW17 and qSLW02 were identified across multiple years. Seed-related traits were the key agronomic traits that have been artificially selected during the domestication of wild soybean. Identifying the genetic loci and genes that regulate seed size could clarify the genetic variations in seed-related traits and provide novel insights into high-yield soybean breeding. In this study, we used a high-density genetic map constructed by F10 RIL populations from a cross between Glycine max and Glycine soja to detect additive QTLs for seven seed-related traits over the last three years. As a result, we identified one novel pleiotropic QTL, qSS14, that simultaneously controlled four seed size traits (100-seed weight, seed length, seed width, and seed thickness) and two consistently detected QTLs, qSW17, and qSLW02, in multiple years of phenotypic data. Furthermore, we predicted two, two and three candidate genes within these three critical loci based on the parental resequencing data and gene function annotations. And the relative expression of four candidate genes GLYMA_14G155100, GLYMA_17G061000, GLYMA_02G273100, and GLYMA_02G273300 showed significant differences among parents and the extreme materials through qRT-PCR analysis. These findings could facilitate the determination of beneficial genes in wild soybean and contribute to our understanding of the soybean domestication process.


Subject(s)
Glycine max , Plant Breeding , Glycine max/genetics , Glycine max/metabolism , Chromosome Mapping , Quantitative Trait Loci , Seeds/genetics , Seeds/metabolism
6.
Biomed Chromatogr ; 37(10): e5710, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37593801

ABSTRACT

Polycystic ovary syndrome (PCOS) is a common endocrine syndrome, and obesity is the most common clinical manifestation. Acupuncture is effective in treating PCOS, but the differences in the biological mechanisms of acupuncture therapy and Western medicine treatment have not been determined. Thus, the purpose of this study was to find glucose metabolism-related pathways in acupuncture treatment and differentiate them from Western medical treatment. Sixty patients with PCOS-related obesity were randomly distributed into three groups: patients receiving (1) acupuncture treatment alone, (2) conventional Western medicine treatment, and (3) acupuncture combined with Western medicine treatment. A targeted metabolomics approach was used to identify small molecules and metabolites related to glucose metabolism in the serum of each group, and ultra-high-performance liquid chromatography-tandem mass spectrometry was used to analyze different metabolic fractions. The results showed acupuncture treatment modulates the activity of citric and succinic acids in the tricarboxylic acid cycle, regulates glycolytic and gluconeogenesis pathways, and improves the levels of sex hormones and energy metabolism. The intervention effects on the metabolic pathways were different between patients receiving combination therapy and patients receiving acupuncture therapy alone, suggesting that the dominant modulatory effect of Western drugs may largely conceal the efficacy of acupuncture intervention.


Subject(s)
Acupuncture Therapy , Polycystic Ovary Syndrome , Female , Humans , Polycystic Ovary Syndrome/therapy , Metabolomics , Obesity , Citric Acid Cycle , Glucose
7.
Chem Biodivers ; 20(6): e202201197, 2023 Jun.
Article in English | MEDLINE | ID: mdl-37073748

ABSTRACT

Four undescribed biflavonoid alkaloids, sinenbiflavones A-D, were isolated from Cephalotaxus sinensis using a MS/MS-based molecular networking guided strategy. Their structures were elucidated by series of spectroscopic methods (HR-ESI-MS, UV, IR, 1D, and 2D NMR). Sinenbiflavones A-D are the first examples of amentoflavone-type (C-3'-C-8'') biflavonoid alkaloids. Meanwhile, sinenbiflavones B and D are the unique C-6-methylated amentoflavone-type biflavonoid alkaloids. Sinenbiflavone D showed weak SARS-CoV-2 3CLpro inhibitory activity with 43 % inhibition rate at 40 µM.


Subject(s)
Alkaloids , Biflavonoids , COVID-19 , Cephalotaxus , Biflavonoids/chemistry , Molecular Structure , Cephalotaxus/chemistry , Tandem Mass Spectrometry , SARS-CoV-2 , Alkaloids/chemistry , Magnetic Resonance Spectroscopy
8.
Int J Mol Sci ; 23(19)2022 Oct 04.
Article in English | MEDLINE | ID: mdl-36233075

ABSTRACT

In recent years, malignant breast cancer metastasis has caused a great increase in mortality. Research on the genetic and molecular mechanisms of malignant breast cancer has continued to deepen, and targeted therapy has become the general trend. Among them, competing endogenous RNA (ceRNA)-related molecules have received much attention. Homeobox transcript antisense RNA (HOTAIR) has been reported to function extensively as a ceRNA in breast cancer. Notably, miR-203 and Caveolin 1 (CAV1) have also been found to play a role in breast cancer. However, the relationship between the three remains unclear. In this study, we present a new mechanic through bioinformatics tool and basic experiments: the HOTAIR/miR-203/CAV1 axis, which complemented the role network of HOTAIR as a ceRNA, thus, it will provide a novel potential idea for breast cancer research and therapy.


Subject(s)
Breast Neoplasms , Caveolin 1 , MicroRNAs , RNA, Long Noncoding , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Caveolin 1/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , RNA, Long Noncoding/genetics
9.
Europace ; 22(Suppl_2): ii54-ii60, 2020 12 26.
Article in English | MEDLINE | ID: mdl-33370801

ABSTRACT

AIMS: The present study was to evaluate the feasibility and clinical outcomes of left bundle branch area pacing (LBBAP) in cardiac resynchronization therapy (CRT)-indicated patients. METHODS AND RESULTS: LBBAP was performed via transventricular septal approach in 25 patients as a rescue strategy in 5 patients with failed left ventricular (LV) lead placement and as a primary strategy in the remaining 20 patients. Pacing parameters, procedural characteristics, electrocardiographic, and echocardiographic data were assessed at implantation and follow-up. Of 25 enrolled CRT-indicated patients, 14 had left bundle branch block (LBBB, 56.0%), 3 right bundle branch block (RBBB, 12.0%), 4 intraventricular conduction delay (IVCD, 16.0%), and 4 ventricular pacing dependence (16.0%). The QRS duration (QRSd) was significantly shortened by LBBAP (intrinsic 163.6 ± 29.4 ms vs. LBBAP 123.0 ± 10.8 ms, P < 0.001). During the mean follow-up of 9.1 months, New York Heart Association functional class was improved to 1.4 ± 0.6 from baseline 2.6 ± 0.6 (P < 0.001), left ventricular ejection fraction (LVEF) increased to 46.9 ± 10.2% from baseline 35.2 ± 7.0% (P < 0.001), and LV end-diastolic dimensions (LVEDD) decreased to 56.8 ± 9.7 mm from baseline 64.1 ± 9.9 mm (P < 0.001). There was a significant improvement (34.1 ± 7.4% vs. 50.0 ± 12.2%, P < 0.001) in LVEF in patients with LBBB. CONCLUSION: The present study demonstrates the clinical feasibility of LBBAP in CRT-indicated patients. Left bundle branch area pacing generated narrow QRSd and led to reversal remodelling of LV with improvement in cardiac function. LBBAP may be an alternative to CRT in patients with failure of LV lead placement and a first-line option in selected patients such as those with LBBB and heart failure.


Subject(s)
Cardiac Resynchronization Therapy , Heart Failure , Bundle-Branch Block/diagnosis , Bundle-Branch Block/therapy , Electrocardiography , Feasibility Studies , Heart Failure/diagnosis , Heart Failure/therapy , Humans , Stroke Volume , Treatment Outcome , Ventricular Function, Left
10.
J Cardiovasc Electrophysiol ; 30(11): 2569-2577, 2019 11.
Article in English | MEDLINE | ID: mdl-31535747

ABSTRACT

INTRODUCTION: Left bundle branch pacing (LBBP) is characterized with a low and stable pacing capture threshold, relatively narrow QRS duration due to fast left ventricular activation, and direct excitation of the diseased left bundle branch. This report aims to describe the methods, procedural skills, and clinical implications of performing LBBP implantation. METHODS AND RESULTS: LBBP is achieved by transventricular-septal approach. There are two methods to identify the location for LBBP lead placement: the single-lead method and the dual-lead method. During implantation, the unique transition of the paced QRS morphology and pacing parameter changes are important for guiding the lead - advancement to the left side of the interventricular septum. In our experience, LBBP can be safely performed in most patients requiring pacemaker therapy. CONCLUSION: Clinical development of LBBP is at an early but encouraging phase with increasing clinical use, and a standardized procedure with improved delivery tools and pacing leads is needed, as well as long-term efficacy and safety.


Subject(s)
Bundle-Branch Block/physiopathology , Bundle-Branch Block/surgery , Cardiac Pacing, Artificial/methods , Pacemaker, Artificial , Bundle-Branch Block/diagnostic imaging , Electrocardiography/methods , Humans
11.
J Cardiovasc Electrophysiol ; 30(9): 1714-1717, 2019 09.
Article in English | MEDLINE | ID: mdl-31206858

ABSTRACT

A 57-year-old male presented with symptomatic systolic heart failure and complete left bundle branch block (LBBB). Left bundle branch pacing corrected LBBB at a low capture threshold (0.5V @0.4ms) with right bundle branch conduction delay and paced QRS morphology changed to near-normal by adjusting AV delay with diminished RBBD. At 1-year follow-up, the patient had a significant improvement in heart failure and LBBB automatically resolved with a rate-dependent pattern. LBBP may be an alternative to conventional cardiac resynchronization therapy with the likelihood of recovery of LBBB. More research is needed to evaluate the potential use of this pacing strategy in patients with LBBB and heart failure.


Subject(s)
Bundle of His/physiopathology , Bundle-Branch Block/therapy , Cardiac Pacing, Artificial , Heart Failure/therapy , Action Potentials , Bundle-Branch Block/diagnosis , Bundle-Branch Block/physiopathology , Heart Failure/diagnostic imaging , Heart Failure/physiopathology , Heart Rate , Humans , Male , Middle Aged , Recovery of Function , Stroke Volume , Time Factors , Treatment Outcome , Ventricular Function, Left
12.
Europace ; 21(4): 673-680, 2019 Apr 01.
Article in English | MEDLINE | ID: mdl-30462207

ABSTRACT

AIMS: This study explores the feasibility of left bundle branch pacing (LBBP) and characterizes electrocardiogram (ECG) patterns during the pacing in comparison with conventional right ventricular pacing (RVP). METHODS AND RESULTS: Forty pacing-indicated patients were prospectively enrolled. Twenty patients underwent LBBP (the LBBP group), and 20 patients underwent RVP (the RVP group). Left bundle branch pacing was achieved by transseptal method in the basal ventricular septum. Electrocardiogram characteristics, pacing parameters, pacing sites, and safety events were assessed at implantation and 3-month follow-up. In the LBBP group, the pacing lead was successfully placed near the endocardium of the left side of the septum. Electrocardiogram pattern during LBBP showed right bundle branch conduction delay. Left bundle branch block (LBBB) in two patients was corrected by LBBP. Post-implantation 3D echocardiography confirmed the pacing location. In the RVP group, ECG showed LBBB pattern. The paced QRS duration was 111.85 ± 10.77 ms in LBBP group and 160.15 ± 15.04 ms in the RVP group (P < 0.001). Pacing thresholds (at implantation: 0.73 ± 0.20 V in the LBBP group and 0.61 ± 0.23 V in the RVP group) remained low and stable at 3-month follow-up. No adverse event was observed during 3-month follow-up. CONCLUSION: This study demonstrates the clinical feasibility of LBBP. Left bundle branch pacing that has a low pacing threshold and produces narrow ECG QRS duration may be a new pacing strategy for patients in need of ventricular pacing.


Subject(s)
Atrioventricular Block/therapy , Bundle of His , Bundle-Branch Block/therapy , Cardiac Pacing, Artificial/methods , Heart Ventricles , Sick Sinus Syndrome/therapy , Aged , Atrioventricular Block/physiopathology , Bundle-Branch Block/physiopathology , Cardiac Resynchronization Therapy/methods , Electrocardiography , Feasibility Studies , Female , Humans , Male , Middle Aged , Prospective Studies , Sick Sinus Syndrome/physiopathology
13.
Eur Arch Otorhinolaryngol ; 275(11): 2733-2738, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30218387

ABSTRACT

OBJECTIVE: Increasing evidence suggests that leptin is upregulated during allergic reactions in the airway and related to the severity of disease in allergic rhinitis (AR). In this study, we aimed to investigate the expression of leptin during sublingual immunotherapy (SLIT) in AR patients. METHODS: Forty AR patients without obesity were recruited in this study. Twenty patients received house dust mite (HDM) allergen extract for SLIT and twenty patients received placebo randomly. Protein expression of leptin in serum and nasal lavage was tested by enzyme-linked immuno sorbent assay (ELISA) 1 and 2 years after SLIT treatment, respectively. Peripheral blood mononuclear cells (PBMCs) and human nasal epithelial cell were prepared and stimulated by recombinant leptin after 24 months' SLIT treatment and the induction of Th2 cytokines (IL-4/IL-5/IL-13) were detected by ELISA. RESULTS: SLIT treatment decreased the expression of leptin protein in serum and nasal lavage significantly compared with placebo group 1 and 2 years after SLIT treatment. Nasal leptin level was correlated to decreased Th2 response (IL-4/IL-5/IL-13) and enhanced Treg (IL-10/TGF-beat) response after 2 years' SLIT. We also found that SLIT decreased the ability of leptin in promoting Th2 cytokines expression by PBMCs and human nasal epithelial cell after 2 years' SLIT treatment. CONCLUSION: Changes of leptin expression in serum and nasal lavage may be correlated with Th2/Treg regulation during SLIT. Our results suggested that leptin served as an important biomarker during SLIT.


Subject(s)
Leptin/administration & dosage , Rhinitis, Allergic/therapy , Sublingual Immunotherapy/methods , Adolescent , Adult , Cytokines/metabolism , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Recombinant Proteins , Rhinitis, Allergic/metabolism , Treatment Outcome , Young Adult
14.
Biochem Biophys Res Commun ; 490(1): 55-61, 2017 08 12.
Article in English | MEDLINE | ID: mdl-28595908

ABSTRACT

To date the molecular mechanism of cardiac hypertrophy has not been completely elucidated. Since oxidized low-density lipoprotein (ox-LDL) is considered a risk marker for early ventricular remodeling, we speculated that ox-LDL may be related to cardiac hypertrophy. We observed the significantly upregulation of plasma ox-LDL and hypertrophic responses, such as cardiomyocyte size and specific gene expressions in Apo E-/- mice fed with high fat diet, accompanied by the upregulation of AT1-R and lectin-like oxidized low-density protein receptor 1 (LOX-1). Ox-LDL treatment with neonatal rat cardiomyocyte for 24 h significantly induced similar hypertrophic responses and also upregulation of AT1-R and LOX-1. The analysis of co-immunoprecipitation and the bimolecular fluorescence complementation assay proved that LOX-1 and AT1-R could directly bind together in the presence of ox-LDL, suggesting a critical role of the association between LOX-1 and AT1-R in ox-LDL-induced cardiac hypertrophy. Furthermore, we found that the AT1-R blocker Losartan and LOX-1 neutralizing antibody through inhibiting AT1-R or LOX-1 could both decline ox-LDL-induced hypertrophic responses whereas angiotensin converting enzyme inhibitor Enalapril only partially inhibited the responses stimulated by ox-LDL. These findings suggested that ox-LDL could induce cardiac hypertrophy through the direct association of AT1-R and LOX-1.


Subject(s)
Adaptor Proteins, Signal Transducing/metabolism , Cardiomegaly/metabolism , Lipoproteins, LDL/metabolism , Scavenger Receptors, Class E/metabolism , Animals , Cardiomegaly/pathology , Cells, Cultured , Male , Mice , Mice, Knockout , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/pathology , Rats , Rats, Sprague-Dawley
15.
Mar Drugs ; 15(9)2017 Sep 20.
Article in English | MEDLINE | ID: mdl-28930149

ABSTRACT

The hard-shelled mussel (Mytilus coruscus) has been used as Chinese traditional medicine for thousands of years; however, to date the ingredients responsible for the various beneficial health outcomes attributed to Mytilus coruscus are still unclear. An α-d-Glucan, called MP-A, was isolated from Mytilus coruscus, and observed to exert anti-inflammatory activity in THP-1 human macrophage cells. Specifically, we showed that MP-A treatment inhibited the production of inflammatory markers, including TNF-α, NO, and PGE2, inducible NOS (iNOS), and cyclooxygenase-2 (COX-2), in LPS-activated THP-1 cells. It was also shown to enhance phagocytosis in the analyzed cells, but to severely inhibit the phosphorylation of mitogen-activated protein kinases (MAPKs) and the nuclear translocation of NF-κB P65. Finally, MP-A was found to exhibit a high binding affinity for the cell surface receptor TLR4, but a low affinity for TLR2 and dectin-1, via surface plasmon resonance (SPR) analysis. The study indicates that MP-A suppresses LPS-induced TNF-α, NO and PEG2 production via TLR4/NF-κB/MAPK pathway inhibition, and suggests that MP-A may be a promising therapeutic candidate for diseases associated with TNF-α, NO, and/or PEG2 overproduction.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Glucans/pharmacology , Macrophages/drug effects , Medicine, Chinese Traditional , Mytilus , Signal Transduction/drug effects , Animals , Anti-Inflammatory Agents/chemistry , Glucans/chemistry , Humans , MAP Kinase Signaling System , NF-KappaB Inhibitor alpha , THP-1 Cells/drug effects , Toll-Like Receptor 4
16.
Am J Transl Res ; 16(5): 1678-1689, 2024.
Article in English | MEDLINE | ID: mdl-38883350

ABSTRACT

OBJECTIVE: To explore the risk factors for ventricular arrhythmia after percutaneous coronary intervention (PCI) in elderly patients with acute myocardial infarction (AMI). METHODS: A retrospective cohort of 201 elderly AMI patients who underwent PCI in the emergency department of No. 215 Hospital of Shaanxi Nuclear Industry from April 2020 to January 2023 was analyzed. The patients were randomly divided into a training set (n=134) for model development and a test set (n=67) for model validation. The training set was divided into a ventricular arrhythmia group (n=51) and a non-ventricular arrhythmia group (n=83), based on the occurrence of ventricular arrhythmia post-PCI. The factors affecting ventricular arrhythmias were analyzed by logistic regression and Lasso regression models. RESULTS: Lasso regression screened 12 characteristic factors at λ=0.1 se. In the training set, the area under the ROC curve (AUC) of the Lasso model for predicting ventricular arrhythmia was 0.954, which was significantly higher than 0.826 for the Logistic model (P < 0.001). In the test set, the AUC of the Lasso model was 0.962, which was also significantly higher than 0.825 for the Logistic model (P=0.003). CONCLUSION: Compared to the logistic regression model, the Lasso regression model can more accurately predict the occurrence of ventricular arrhythmia after PCI in elderly AMI patients. The Lasso regression model constructed in this study can provide a reference for the clinical identification of high-risk elderly AMI patients and the development of targeted monitoring and treatment.

18.
Theranostics ; 13(7): 2301-2318, 2023.
Article in English | MEDLINE | ID: mdl-37153744

ABSTRACT

Breast cancer (BC) is one of the most commonly diagnosed cancers and the leading cause of cancer-related deaths in women worldwide. Metastasis is a major contributor to high cancer mortality and is usually the endpoint of a series of sequential and dynamic events. One of the critical events is forming a pre-metastatic niche (PMN) that occurs before macroscopic tumor cell invasion and provides a suitable environment for tumor cells to colonize and progress into metastases. Due to the unique characteristics of PMN in cancer metastasis, developing therapies to target PMN may bring new advantages in preventing cancer metastasis at an early stage. Various biological molecules, cells, and signaling pathways are altered in BC, regulating the functions of distinctive immune cells and stromal remodeling, inducing angiogenesis, and effect metabolic reprogramming and organotropism to promote PMN formation. In this review, we elucidate the multifaceted mechanisms contributing to the development of PMN in BC, discuss the characteristics of PMN, and highlight the significance of PMN in providing potential diagnostic and therapeutic strategies for BC metastasis, which may bring promising insights and foundations for future studies.


Subject(s)
Breast Neoplasms , Melanoma , Neoplasms, Second Primary , Skin Neoplasms , Female , Humans , Breast Neoplasms/pathology , Tumor Microenvironment , Neoplasm Metastasis , Melanoma, Cutaneous Malignant
19.
Life Sci ; 329: 121934, 2023 Sep 15.
Article in English | MEDLINE | ID: mdl-37460057

ABSTRACT

Exosomes are small extracellular vesicles that carry active substances (including proteins, lipids, and nucleic acids) and are essential for homeostasis and signal transmission. Recent studies have focused on the function of exosomal miRNAs in tumor progression. Researchers have expanded the use of exosomes and miRNAs as potential therapeutic tools and biomarkers to detect tumor progression. Immune cells, as an important part of the tumor microenvironment (TME), secrete a majority of exosome-derived miRNAs involved in the biological processes of malignancies. However, the underlying mechanisms remain unclear. Currently, there is no literature that systematically summarizes the communication of exosome-derived miRNAs between tumor cells and immune cells. Based on the cell specificity of exosome-derived miRNAs, this review provides the first comprehensive summary of the significant miRNAs from the standpoint of exosome sources, which are tumor cells and immune cells. Furthermore, we elaborated on the potential clinical applications of these miRNAs, attempting to propose existing difficulties and future possibilities in tumor diagnostics and therapy.


Subject(s)
Exosomes , Extracellular Vesicles , MicroRNAs , Neoplasms , Humans , MicroRNAs/metabolism , Neoplasms/therapy , Neoplasms/drug therapy , Exosomes/metabolism , Extracellular Vesicles/metabolism , Biomarkers/metabolism , Tumor Microenvironment/genetics
20.
Front Plant Sci ; 14: 1268706, 2023.
Article in English | MEDLINE | ID: mdl-38023859

ABSTRACT

Powdery mildew (PMD), caused by the pathogen Microsphaera diffusa, leads to substantial yield decreases in susceptible soybean under favorable environmental conditions. Effective prevention of soybean PMD damage can be achieved by identifying resistance genes and developing resistant cultivars. In this study, we genotyped 331 soybean germplasm accessions, primarily from Northeast China, using the SoySNP50K BeadChip, and evaluated their resistance to PMD in a greenhouse setting. To identify marker-trait associations while effectively controlling for population structure, we conducted genome-wide association studies utilizing factored spectrally transformed linear mixed models, mixed linear models, efficient mixed-model association eXpedited, and compressed mixed linear models. The results revealed seven single nucleotide polymorphism (SNP) loci strongly associated with PMD resistance in soybean. Among these, one SNP was localized on chromosome (Chr) 14, and six SNPs with low linkage disequilibrium were localized near or in the region of previously mapped genes on Chr 16. In the reference genome of Williams82, we discovered 96 genes within the candidate region, including 17 resistance (R)-like genes, which were identified as potential candidate genes for PMD resistance. In addition, we performed quantitative real-time reverse transcription polymerase chain reaction analysis to evaluate the gene expression levels in highly resistant and susceptible genotypes, focusing on leaf tissues collected at different times after M. diffusa inoculation. Among the examined genes, three R-like genes, including Glyma.16G210800, Glyma.16G212300, and Glyma.16G213900, were identified as strong candidates associated with PMD resistance. This discovery can significantly enhance our understanding of soybean resistance to PMD. Furthermore, the significant SNPs strongly associated with resistance can serve as valuable markers for genetic improvement in breeding M. diffusa-resistant soybean cultivars.

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