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Two-dimensional semiconductor-based nanomaterials have shown to be an effective substrate for Surface-enhanced Raman Scattering (SERS) spectroscopy. However, the enhancement factor (EF) tends to be relatively weak compared to that of noble metals and does not allow for trace detection of molecules. In this work, we report the successful preparation of two-dimensional (2D) amorphous non-van der Waals heterostructures MoO3-x/GDYO nanomaterials using supercritical CO2. Due to the synergistic effect of the localized surface plasmon resonance (LSPR) effect and the charge transfer effect, it exhibits excellent SERS performance in the detection of methylene blue (MB) molecules, with a detection limit as low as 10-14â M while the enhancement factor (EF) can reach an impressive 2.55×1011. More importantly, the chemical bond bridging at the MoO3-x/GDYO heterostructures interface can accelerate the electron transfer between the interfaces, and the large number of defective surface structures on the heterostructures surface facilitates the chemisorption of MB molecules. And the charge recombination lifetime can be proved by a ~1.7-fold increase during their interfacial electron-transfer process for MoO3-x/GDYO@MB mixture, achieving highly sensitive SERS detection.
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Objective: To investigate the association of serum MMP-2, Siglec-1, and Th1/Th2 cell ratio with disease activity in rheumatoid arthritis (RA). Methods: Between August and November 2020, Peking University People's Hospital recruited 40 patients with RA and 40 healthy individuals. Various methods such as ELISA, flow cytometry, and RT-PCR were used to assess the levels of sCR1, MMP-2, MMP-9, and Siglec-1 in the participants. Correlation analysis was conducted between Siglec-1 expression and DAS28 and hs-CRP. T lymphocyte subsets; cytokines IFN-γ and IL-4, were assessed using flow cytometry and ELISA in both patient groups. Results: Rheumatoid arthritis was linked to lower levels of serum sCR1 and higher levels of MMP-2 and MMP-9 compared to healthy individuals (P < .05). The percentage of Siglec-1-positive cells in PBMCs was significantly higher in patients with RA than in the healthy group (P < .05), with monocytes being the predominant cells expressing Siglec-1. Patients with RA exhibited a significantly higher expression of Siglec-1 mRNA compared to those in a healthy condition (P < .05), and the expression of Siglec-1 in these patients was positively correlated with DAS28 and hs-CRP (P < .05). Study patients demonstrated a notably lower level of peripheral blood CD8+ cells and a higher CD4+/CD8+ ratio when compared to healthy individuals (P < .05). There was no statistically significant difference in CD3+CD4+ levels between the 2 groups (P > .05). Rheumatoid arthritis was associated with a higher level of peripheral blood IFN-γ and a lower IL-4 level than healthy individuals (P < .05). Conclusion: There was a strong link between sCRl, MMP-2, and MMP-9 and the progression of rheumatoid arthritis. These markers can effectively monitor disease activity in patients with rheumatoid arthritis. Siglec-1 is highly expressed in peripheral blood and can be used to track disease activity and inflammation in these patients. Regulating Th1/Th2-mediated homeostasis may help alleviate symptoms in individuals with rheumatoid arthritis.
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Objective: To investigate the efficacy and clinical value of alfacalcidol combined with exercise rehabilitation in therapy of the postoperative dysfunction of patients with patella fractures. Methods: In this study, 100 patients who underwent patella fracture surgery at Peking University People's Hospital between April 2018 and December 2019 were randomly selected and divided into a control group (n=50) and an experimental group (n=50) by lottery. The control group received exercise therapy, while the experimental group received alfacalcidol based on exercise rehabilitation. The functional assessment measure (FAM) score, visual analog scale (VAS) score, therapy efficiency, adverse effects, callus volume, and callus density were compared between the two groups. Results: The FAM score and therapy efficiency in the experimental group were significantly higher than in the control group [P < .001, RR: 95%CI (10.28, 5.12 to 15.52)], but the VAS score was lower [P < .001 RR: 95% CI (22.83, 1.99 to 3.31)]. Patients in the experimental group had fewer adverse effects [P < .001, RR: 95% CI (14.62, 6.49 to 32.92)] than those in the control group but significantly larger callus volume and density [both P < .001, RR: 95% CI (26.03, 3.21 to 4.07): (17.92, 2.83 to 3.34)]. Conclusion: Alfacalcidol combined with exercise rehabilitation therapy could significantly improve motor function, callus volume, and callus density in patients with patella fracture, resulting in a high applicable value in managing postoperative functional impairment of patellar fractures.
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Exposure to fine particulate matter (PM2.5) has been linked to an increased incidence and mortality of hepatocellular carcinoma (HCC). However, the impact of PM2.5 exposure on HCC progression and the underlying mechanisms remain largely unknown. This study aimed to investigate the effects of PM2.5 exposure on the stem cell-like properties of HCC cells. Our findings indicate that PM2.5 exposure significantly enhances the stemness of HCC cells (p < 0.01). Subsequently, male nude mice were divided into two groups (n = 8/group for tumor-bearing assay, n = 5/group for metastasis assay) for control and PM2.5 exposure. In vivo assays revealed that exposure to PM2.5 promoted the growth, metastasis, and epithelial-mesenchymal transition (EMT) of HCC cells (p < 0.01). Further exploration demonstrated that PM2.5 enhances the stemness of HCC cells by inducing cellular reactive oxygen species (ROS) generation (p < 0.05). Mechanistic investigation indicated that elevated intracellular ROS inhibited kelch-like ECH-associated protein 1 (Keap1) levels, promoting the upregulation and nucleus translocation of NFE2-like bZIP transcription factor 2 (Nrf2). This, in turn, induced autophagy activation, thereby promoting the stemness of HCC cells (p < 0.01). Our present study demonstrates the adverse effects of PM2.5 exposure on HCC development and highlights the mechanism of ROS/Nrf2/Keap1-mediated autophagy. For the first time, we reveal the impact of PM2.5 exposure on the poor prognosis-associated cellular phenotype of HCC and its underlying mechanism, which is expected to provide new theoretical basis for the improvement of public health.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animales , Ratones , Masculino , Carcinoma Hepatocelular/metabolismo , Material Particulado/toxicidad , Especies Reactivas de Oxígeno/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Neoplasias Hepáticas/genética , Ratones Desnudos , Células Madre/patología , AutofagiaRESUMEN
Single-atom catalysts (SACs), distinguished by their maximum atom efficiency and precise control over the coordination and electronic properties of individual atoms, show great promise in electrocatalysis. Gaining a comprehensive understanding of the electrochemical performance of SACs requires the screening of electron transfer process at micro/nano scale. This research pioneers the use of electrogenerated chemiluminescence microscopy (ECLM) to observe the electrocatalytic reactions at individual SACs. It boasts sensitivity at the single photon level and temporal resolution down to 100â ms, enabling real-time capture of the electrochemical behavior of individual SACs during potential sweeping. Leveraging the direct correlation between ECL emission and heterogeneous electron transfer processes, we introduced photon flux density for quantitative analysis, unveiling the electrocatalytic efficiency of individual SACs. This approach systematically reveals the relationship between SACs based on different metal atoms and their peroxidase (POD)-like activity. The outcomes contribute to a fundamental understanding of SACs and pave the way for designing SACs with diverse technological and industrial applications.
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Natural enzymes are crucial in biological systems and widely used in biology and medicine, but their disadvantages, such as insufficient stability and high-cost, have limited their wide application. Since Fe3O4 nanoparticles were found to show peroxidase-like activity, researchers have designed and developed a growing number of nanozymes that mimic the activity of natural enzymes. Nanozymes can compensate for the defects of natural enzymes and show higher stability with lower cost. Iron, a nontoxic and low-cost transition metal, has been used to synthesize a variety of iron-based nanozymes with unique structural and physicochemical properties to obtain different enzymes mimicking catalytic properties. In this perspective, catalytic mechanisms, activity modulation, and their recent research progress in sensing, tumor therapy, and antibacterial and anti-inflammatory applications are systematically presented. The challenges and perspectives on the development of iron-based nanozymes are also analyzed and discussed.
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Nanopartículas , Nanoestructuras , Hierro , Catálisis , Antibacterianos , Nanoestructuras/químicaRESUMEN
Postoperative neurocognitive impairment (POCD) is a common complication after surgery and anesthesia, especially in elderly patients. Avenanthramide-C (AVC) test is a vascular endothelial cell adhesion molecule inhibitor with strong anti-inflammatory and antioxidant effects. The aim of this study was to investigate the effect and mechanism of AVC on POCD in aged rats to clarify the effect of AVC on POCD in aged rats. The aging rat model was established by continuous 200 mg/kg propofol anesthesia. Repeated propofol anesthesia could severely impair spatial learning ability, memory and cognitive function, and could promote hippocampal apoptosis, oxidative stress injury, neuroinflammation and ferroptosis in aging rats. In addition, AVC not only improved cognitive dysfunction, but also significantly inhibited apoptosis, neuroinflammatory response, ferroptosis and oxidative stress level in the hippocampus of aging rats induced by repeated anesthesia. Further mechanistic studies manifested that the above protective effects of AVC on aging rats induced by repeated propofol anesthesia may be achieved by activating Nrf2/ARE pathway activity. AVC pretreatment has a preventive effect on cognitive dysfunction induced by repeated propofol anesthesia in aging rats, and the preventive effect of AVC may be realized by activating the Nrf2/ARE signaling pathway activity. Our results demonstrate that AVC preconditioning reduces postoperative neuronal loss and neuroinflammation, activates the Nrf2/ARE pathway, reduces oxidative stress injury, and improves POCD in aged rats.
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Disfunción Cognitiva , Ferroptosis , Propofol , Ratas , Animales , Propofol/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Enfermedades Neuroinflamatorias , Disfunción Cognitiva/metabolismo , Envejecimiento , Hipocampo/metabolismoRESUMEN
BACKGROUND AND AIM: Endotoxin-induced acute lung injury (ALI) is a complicated and fatal condition with no specific or efficient clinical treatments. 5-Methoxytryptophan (5-MTP), an endogenous metabolite of tryptophan, was revealed to block systemic inflammation. However, the specific mechanism by which 5-MTP affects ALI still needs to be clarified. The purpose of this study was to determine whether 5-MTP protected the lung by inhibiting NLRP3 inflammasome-mediated pyroptosis through the Nrf2/HO-1 signaling pathway. METHODS AND RESULTS: We used lipopolysaccharide (LPS)-stimulated C57BL/6 J mice and MH-S alveolar macrophages to create models of ALI, and 5-MTP (100 mg/kg) administration attenuated pathological lung damage in LPS-exposed mice, which was associated with decreased inflammatory cytokines and oxidative stress levels, upregulated protein expression of Nrf2 and HO-1, and suppressed Caspase-1 activation and NLRP3-mediated pyroptosis protein levels. Moreover, Nrf2-deficient mice or MH-S cells were treated with 5-MTP to further confirm the protective effect of the Nrf2/HO-1 pathway on lung damage. We found that Nrf2 deficiency partially eliminated the beneficial effect of 5-MTP on reducing oxidative stress levels and inflammatory responses and abrogating the inhibition of NLRP3-mediated pyroptosis induced by LPS. CONCLUSION: These findings suggested that 5-MTP could effectively ameliorate ALI by inhibiting NLRP3-mediated pyroptosis via the Nrf2/HO-1 signaling pathway.
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Lesión Pulmonar Aguda , Inflamasomas , Ratones , Animales , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Triptófano/efectos adversos , Endotoxinas/farmacología , Lipopolisacáridos/farmacología , Piroptosis , Ratones Endogámicos C57BL , Transducción de Señal , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/metabolismoRESUMEN
BACKGROUND: Non-small cell lung cancer (NSCLC) is still one of the diseases with the highest mortality and morbidity, and lung adenocarcinoma (LUAD) accounts for more than half of all NSCLC cases in most countries. miRNA can be used as a potential biological marker and treatment for lung adenocarcinoma. However, the effect of miR-937-3p to the invasion and metastasis of LUAD cells is not clear. METHODS: miRNA microarray is used to analyze the expression of miRNA in lung adenocarcinoma tissue. Transwell migration, Wound-healing assay and Western blot analysis are used to analyze cell migration, invasion and epithelial-mesenchymal transition (EMT) capabilities. Tube formation is used to assess angiogenesis ability. In addition, dual luciferase reporter gene detection is used to identify the potential binding between miRNA and target mRNA. In vivo experiments were performed on male NOD/SCID nude mice by tail vein injection to establish a transplanted tumor model. The CHIP experiment is used to verify the transcription factors of miRNA. RESULT: In our study, miR-937-3p was high-regulated in LUAD cell lines and tissues, and its expression level was related to tumor progression. We found that miR-937-3p high-expression has an effect on cell invasion and metastasis. In molecular mechanism, miR-937-3p causes SOX11 reduction by directly binding to the 3'-UTR of SOX11.In addition, MYC affects miR-937-3p transcription by binding to its promoter region. CONCLUSIONS: Our research shows that miR-937-3p is mediated by MYC and can control the angiogenesis, invasion and metastasis of LUAD by regulating SOX11, thereby promoting the progress of LUAD. We speculate that miR-937-3p can be used as a therapeutic target and potential biomarker for LUAD.
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The glycosylative modification of peptides could improve the pharmacological properties of peptide drugs and deliver them efficiently to the target sites. Compared with O-/N-glycosides, C-glycosides exhibit more metabolic stability. We here disclose the first example of visible-light-promoted and Cu-catalyzed stereoselective C-glycosylation. The mild reaction conditions are compatible with various carbohydrate substrates, as demonstrated with a series of monosaccharides and a disaccharide, and are amenable to the synthesis of a wide variety of C-glycoamino acids and C-glycopeptidomimetics with good yields and excellent stereoselectivities. The dual-functional photocatalyst formed in situ via coordination of the glycine derivative and the chiral phosphine Cu complex could not only catalyze the photoredox process but also control the stereoselectivity of the glycosylation reaction.
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Aminoácidos , Glicopéptidos , Aminoácidos/química , Glicopéptidos/química , Glicósidos/química , Glicosilación , Péptidos/químicaRESUMEN
The asymmetric functionalization of C-H is one of the most attractive strategies in asymmetric synthesis. In the past decades, catalytic enantioselective C(sp3)-H functionalization has been intensively studied and successfully applied in various asymmetric bond formations, whereas asymmetric C(sp3)-H alkylation was not well developed. Photoredox catalysis has recently emerged as an efficient way to synthesize organic compounds under mild conditions. Despite many photoinduced stereoselective reactions that have been achieved, the related enantioselective C(sp3)-C(sp3) coupling is challenging, especially of the photocatalytic asymmetric C(sp3)-H radical alkylation. Here, we report a visible light induced Cu catalyzed asymmetric sp3 C-H alkylation, which is effective for coupling with unbiased primary, secondary, and tertiary alkyl fragments in high enantioselectivities. This reaction would provide a new approach for the synthesis of important molecules such as unnatural α-amino acids and late-stage functionalization of bioactive compounds, and will be useful for modern peptide synthesis and drug discovery.
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OBJECTIVE: Neuroinflammation plays a critical role in central nervous system diseases. Exosomal miRNAs released from various cells are implicated in cell-to-cell communication. Prior studies have placed substantial emphasis on the role of cytokines in mast cell-microglia interactions during neuroinflammation. However, it has never been clearly determined whether exosomal miRNAs participate in the interaction between mast cells and microglia and thus mediate neuroinflammation. METHODS: The characteristics of exosomes isolated from cell culture supernatants were confirmed by transmission electron microscopy (TEM), nanoparticle-tracking analysis (NTA) and Western blot. The transfer of PKH67-labelled exosomes and Cy3-labelled miR-409-3p was observed by fluorescence microscopy. Migration and activation of murine BV-2 microglial cells were evaluated through Transwell assays and immunofluorescence staining for Iba1 and CD68. CD86, IL-1ß, IL-6 and TNF-α were assessed via qRT-PCR and ELISA. MiR-409-3p was detected by qRT-PCR. Nr4a2 and NF-κB levels were measured by western blot. Regulatory effects were identified by luciferase reporter assays. RESULTS: Lipopolysaccharide (LPS)-stimulated murine P815 mast cells secreted exosomes that were efficiently taken up by murine BV-2 cells, which promoted murine BV-2 cell migration and activation. LPS-P815 exosomes increased the CD86, IL-1ß, IL-6 and TNF-α levels in murine BV-2 microglia. Furthermore, activated mast cells delivered exosomal miR-409-3p to murine BV-2 microglia. Upregulated miR-409-3p promoted murine BV-2 microglial migration, activation and neuroinflammation by targeting Nr4a2 to activate the NF-κB pathway. CONCLUSION: Exosomal miR-409-3p secreted from activated mast cells promotes microglial migration, activation and neuroinflammation by targeting Nr4a2 to activate the NF-κB pathway, which provides evidence that not only cytokines but also exosomal miRNAs participate in neuroinflammation. In the future, targeting exosomal miRNAs may provide new insights into neuroinflammation.
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Encefalitis/patología , Exosomas/patología , Mastocitos/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Microglía/patología , Miembro 2 del Grupo A de la Subfamilia 4 de Receptores Nucleares/genética , Animales , Línea Celular , Movimiento Celular , Células Cultivadas , Lipopolisacáridos/farmacología , Activación de Macrófagos , Ratones , FN-kappa B/efectos de los fármacos , Nanopartículas , Transducción de Señal/efectos de los fármacosRESUMEN
In this study, we explored expression and functions of circular RNA LPAR3 (circLPAR3) in esophageal squamous cell carcinoma (ESCC). The differential expression of circular RNAs (circRNAs) in 10 ESCC and corresponding paracarcinoma tissues was analyzed through circRNA microarray, then the candidate circRNAs were detected and verified through quantitative RT-PCR, and a novel circRNA was screened, which was circLPAR3. Circular RNA LPAR3 showed apparently high expression in ESCC tissues and cells, which was closely correlated with the clinical stage and lymph node metastasis of ESCC patients. Circular RNA LPAR3 was mainly located in the cytoplasm of ESCC cells, which was more stable than the baseline gene. Circular RNA LPAR3 upregulated MET gene expression through sponge adsorption of microRNA (miR)-198, activated the RAS/MAPK and the PI3K/Akt pathways, and promoted ESCC cell migration, invasion, and metastasis in vivo and in vitro. However, it had no effect on ESCC cell proliferation. Circular RNA LPAR3 can regulate the miR-198-MET signal axis to promote the migration, invasion, and metastasis of esophageal cancer cells, which can thereby serve as a potential diagnostic and therapeutic target of esophageal cancer.
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Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas de Esófago/genética , Neoplasias Pulmonares/genética , MicroARNs/metabolismo , ARN Circular/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/secundario , Carcinoma de Células Escamosas de Esófago/cirugía , Esofagectomía , Esófago/patología , Esófago/cirugía , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Pulmón/patología , Neoplasias Pulmonares/secundario , Metástasis Linfática/genética , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas Proto-Oncogénicas c-met/genética , ARN Circular/genética , Receptores del Ácido Lisofosfatídico/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND & AIMS: Previous genome-wide association studies (GWAS) have identified multiple susceptible variants associated with persistent hepatitis B virus (HBV) infection. However, most of these variants are located in the noncoding regions, which make it difficult to determine the effective genes underlying these associations. We performed a two-stage study, in the first stage we integrated RNA sequencing data of liver tissues and high-density genotyping data from the Genotype-Tissue Expression (GTEx) project with our previous GWAS data to conduct a transcriptome-wide association study (TWAS) on HBV infection. Firstly, the cis-heritable genes were screened by a genetic relatedness matrix of genome-wide complex trait analysis (GCTA) from GTEx data. Then, the genetic expression of 2587 cis-heritable genes was predicted by restricted maximum likelihood (REML) of genome-wide efficient mixed-model association (GEMMA) in our GWAS data with 951 HBV carrier cases and 937 HBV cleared controls. Next, we investigated the associations between predictive expression levels and persistent HBV infection risk. Gene set enrichment analysis (GSEA) was applied to infer the function of the identified genes. To identify the causal single nucleotide polymorphisms (SNPs) of HBV infection risk, we conducted the expression quantitative trait loci (eQTL)-based stepwise logistic regression analysis in the regions around 1 Mb of these genes and validated the association between 994 health controls and 994 HBV-persistent infection cases by genotyping experiment. In the second stage, 1538 HBV-related hepatocellular carcinoma (HCC) cases and 1465 persistent HBV infection controls were collected to determine the effect of these variants on HBV-related HCC as well, which were examined by the additive model in logistic regression analysis. We identified seven genes associated with HBV infection. In the classic human leukocyte antigen (HLA) region, three novel genes BAK1, HLA-DOB and C4A (Z range from -3.95 to -3.64, P range from 7.84 × 10-5 to 2.00 × 10-4 ), as well as two genes (HLA-DPA1 and HLA-DPB1) were reported by previous GWAS. In the non-HLA region, immune related at newly identified loci, PARP9 (Z = 3.69, P = 2.20 × 10-4 ) at 3q21.1. At 22q11.21, we identified TMEM191A (Z = 3.55, P = 3.80 × 10-4 ) as a target gene in addition to the reported non-cis-heritable gene UBE2L3. After further stepwise logistic regression analysis and validation, we identified eight variants independently associated with persistent HBV infection. Among those variants, the additive model showed that two SNPs associated with HBV-related HCC risk (rs9272714 and rs9394194, OR range from 1.20 to 1.25, P range from 1.19 × 10-4 to 3.97 × 10-4 ). By integrating transcriptome data, our study not only identified new susceptibility loci of persistent HBV infection but also determined the potential target genes at reported loci, which provided insight into the genetic aetiology of persistent HBV infection and related HCC.
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Carcinoma Hepatocelular , Hepatitis B Crónica , Hepatitis B , Neoplasias Hepáticas , Carcinoma Hepatocelular/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Hepatitis B/genética , Virus de la Hepatitis B/genética , Hepatitis B Crónica/genética , Humanos , Neoplasias Hepáticas/genética , Polimorfismo de Nucleótido Simple , TranscriptomaRESUMEN
Many studies have shown that there were similarity between tumorigenesis and gametogenesis. Our previous work found that cancer-testis (CT) genes could serve as a novel source of candidate of cancer. Here, by analysing The Cancer Genome Atlas (TCGA) database, we characterized a CT gene, SPANXC, which is expressed only in testis. The SPANXC was reactivated in lung adenocarcinoma (LUAD) tissues. And the expression of SPANXC was associated with prognosis of LUAD. We also found that the activation of SPANXC was due to the promoter hypomethylation of SPANXC. Moreover, SPANXC could modulate cell metastasis both in vitro and in vivo. Mechanistically, we found that SPANXC could bind to ROCK1, a metastasis-related gene, and thus SPANXC may regulate cell metastasis partly through interaction with ROCK1 in LUAD. Together, our results demonstrated that the CT expression pattern of SPANXC served as a crucial role in metastasis of LUAD. And these data further corroborated the resemblance between processes of germ cell development and tumorigenesis, including migration and invasion.
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Adenocarcinoma del Pulmón/secundario , Biomarcadores de Tumor/metabolismo , Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/patología , Proteínas de Neoplasias/metabolismo , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Proliferación Celular , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Masculino , Ratones , Ratones Desnudos , Proteínas de Neoplasias/genética , Pronóstico , Regiones Promotoras Genéticas , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto , Quinasas Asociadas a rhoRESUMEN
Rheumatoid arthritis (RA) is a chronic autoimmune disease which is characterized by synovial inflammation and cartilage damage for which causes articular dysfunction. Activation of fibroblast-like synoviocytes (FLS) is a critical step that promotes disease progression. In this study, we aimed to explore the effect of interleukin-34 (IL-34) on RA FLS as a proinflammatory factor and IL-34-stimulated FLS on the production of Th17. We found that serum IL-34 levels were increased compared to those of the healthy controls and had positive correlations with C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and anticyclic citrullinated peptide (CCP) antibody accordingly. CSF-1R was also highly expressed on RA FLS. The interaction of IL-34 and CSF-1R promoted a dramatic production of IL-6 by FLS through JNK/P38/NF-κB signaling pathway. Further, the IL-34-stimulated IL-6 secretion by RA FLS was found to upregulate the number of Th17. The treatment of IL-6R antagonist could attenuate the production of Th17 mediated by IL-34-stimulated RA FLS. Our results suggest that the increased IL-34 levels were closely related to the disease activity of RA. Additionally, the overexpression of IL-6 in the IL-34-stimulated FLS promoted the generation of Th17. Therefore, IL-34 was supposed to be involved in the pathogenesis of RA. The inhibition of IL-34 might provide a novel target for therapies of RA.
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Interleucina-6/metabolismo , Interleucinas/sangre , Interleucinas/metabolismo , Sinoviocitos/metabolismo , Artritis Reumatoide/metabolismo , Proteína C-Reactiva/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Células Cultivadas , Femenino , Humanos , Interleucina-17/metabolismo , Interleucinas/genética , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Membrana Sinovial/citología , Membrana Sinovial/metabolismoRESUMEN
TNF-like protein 1A (TL1A), a member of tumor necrosis factor family, recognized as a ligand of death receptor 3 (DR3) and decoy receptor 3 (DcR3). The interaction of TL1A and DR3 may participate in the pathogenesis of some autoimmune diseases including rheumatoid arthritis (RA). Our previous results showed that high concentrations of TL1A could be found in synovial and serum in RA patients, and it was correlated with disease severity. In addition, TL1A could promote Th17 differentiation induced by TGF-ß and IL-6 and increased the production of IL-17A. In the present study, we found that TL1A could promote the expression of IL-6 on fibroblast-like synoviocytes (FLS) of RA patients via NF-κB and JNK signaling pathway. TL1A-stimulated FLS increased the percentage of Th17 of peripheral blood mononuclear cells (PBMC) in RA via the production of IL-6, a critical cytokine involved in the differentiation of Th17. Moreover, the blocking of tumor necrosis factor receptor 2 (TNFR2) decreased TL1A-stimulated IL-6 production by RA FLS. Our results suggest that TL1A was capable of acting on RA FLS to elevate IL-6 expression, which promoted the production of Th17. More importantly, we showed that TL1A could influence RA FLS through binding to TNFR2 rather than DR3 on FLS, which indicated that the treatment of TNF inhibitors not only blocked the TNF but also suppressed the TL1A in RA patients.
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Artritis Reumatoide/metabolismo , Interleucina-6/metabolismo , Receptores Tipo II del Factor de Necrosis Tumoral/metabolismo , Sinoviocitos/metabolismo , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo , Artritis Reumatoide/patología , Femenino , Humanos , Interleucina-17/metabolismo , Masculino , Sinoviocitos/patología , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
BACKGROUND AND OBJECTIVE: Rupture of small intracranial aneurysm (IA) often leads to the development of highly fatal clinical syndromes such as subarachnoid hemorrhage. Due to the patient specificity of small IA, there are many difficulties in evaluating the rupture risk of small IA such as multiple influencing factors, high clinical experience requirements and poor reusability. METHODS: In this study, clinical methods such as transcranial doppler (TCD) and magnetic resonance imaging (MRI) are used to obtain patient-specific parameters, and the fluid-structure interaction method (FSI) is used to model and evaluate the biomechanics and hemodynamics of patient-specific small IA. RESULTS: The results show that a spiral vortex stably exists in the patient-specific small IA. Due to the small size of the patient-specific small IA, the blood flow velocity still maintains a high value with maximum reaching 3 m/s. The inertial impact of blood flow and vortex convection have certain influence on hemodynamic and biomechanics parameters. They cause three high value areas of WSSM on the patient-specific small IA with maximum of 180 Pa, 130 Pa and 110 Pa, respectively. They also cause two types of WSS concentration points, positive normal stress peak value areas and negative normal stress peak value areas to appear. CONCLUSION: This paper found that the factors affecting hemodynamic parameters and biomechanical parameters are different. Unlike hemodynamic parameters, biomechanical parameters are also affected by blood pressure in addition to blood flow velocity. This study reveals the relationship between the flow field distribution and changes of patient-specific small IA, biomechanics and hemodynamics.
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Aneurisma Intracraneal , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Fenómenos Biomecánicos , Hemodinámica/fisiología , Velocidad del Flujo Sanguíneo , Presión Sanguínea , Rotura , Modelación Específica para el Paciente , Estrés MecánicoRESUMEN
Point cloud registration is challenging in the presence of heavy outlier correspondences. This paper focuses on addressing the robust correspondence-based registration problem with gravity prior that often arises in practice. The gravity directions are typically obtained by inertial measurement units (IMUs) and can reduce the degree of freedom (DOF) of rotation from 3 to 1. We propose a novel transformation decoupling strategy by leveraging the screw theory. This strategy decomposes the original 4-DOF problem into three sub-problems with 1-DOF, 2-DOF, and 1-DOF, respectively, enhancing computation efficiency. Specifically, the first 1-DOF represents the translation along the rotation axis, and we propose an interval stabbing-based method to solve it. The second 2-DOF represents the pole which is an auxiliary variable in screw theory, and we utilize a branch-and-bound method to solve it. The last 1-DOF represents the rotation angle, and we propose a global voting method for its estimation. The proposed method solves three consensus maximization sub-problems sequentially, leading to efficient and deterministic registration. In particular, it can even handle the correspondence-free registration problem due to its significant robustness. Extensive experiments on both synthetic and real-world datasets demonstrate that our method is more efficient and robust than state-of-the-art methods, even when dealing with outlier rates exceeding 99%.
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OBJECTIVE: To investigate the effects of electromagnetic radiation on the physiological indices and immune function of operators. METHODS: The general conditions and electromagnetic radiation awareness rate of 205 operators under electromagnetic radiation were evaluated using a self-designed questionnaire. Physical examination, electrocardiography, and routine urine test were performed in these operators. Peripheral blood was collected from the operators under electromagnetic radiation for blood cell counting and biochemical testing, and their peripheral blood lymphocytes were cultured for determination of chromosomal aberrant frequency and micronucleus frequency. The data from these operators (exposure group) were compared with those of 95 ordinary individuals (control group). RESULTS: The chief complaint of giddiness, tiredness, dizziness, and amnesia showed significant differences between the exposure group and control group (P < 0.01), and the difference in headache became larger with an increase in working years. The awareness rate of electromagnetic radiation damage was significantly higher in the exposure group than in the control group. The difference in bradycardia was significant between the two groups (P <0.01), and the incidence was higher with longer working years. Significant differences between the two groups were also found in the numbers of individuals with elevated alanine aminotransferase, total bilirubin, and direct bilirubin (P < 0.01), populations with increased lymphocyte ratio and decreased neutrophil ratio (P < 0.01), populations with positive occult blood, urobilinogen, and bilirubin tests, and the number of individuals with increased micronucleus frequency of cultured peripheral blood lymphocytes (P < 0.01). In addition, the exposure group had significantly increased complement C3 and C4 (P < 0.01), significantly increased IgG (P < 0.05), and significantly decreased IgM (P < 0.01), as compared with the control group. CONCLUSION: Electromagnetic radiation may lead to the changes in physiological indices, genetic effects, and immune function and affect the health and immune function in operators. The adverse effects are increased as the working years increase. So it is important to strengthen occupational protection of operators under electromagnetic radiation.