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ABSTRACT: Serial cardiovascular magnetic resonance evaluation of children and young adults with SCD who underwent hematopoietic cell transplantation showed mean ECV, representing diffuse myocardial fibrosis, decreased 3.4% from baseline to 12 months posttransplantation. This trial was registered at www.clinicaltrials.gov as #NCT04362293.
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Anemia Falciforme , Fibrose , Transplante de Células-Tronco Hematopoéticas , Humanos , Anemia Falciforme/terapia , Anemia Falciforme/patologia , Anemia Falciforme/complicações , Masculino , Feminino , Adolescente , Criança , Adulto Jovem , Cardiomiopatias/etiologia , Cardiomiopatias/terapia , Cardiomiopatias/patologia , Adulto , Miocárdio/patologia , Imageamento por Ressonância Magnética , Pré-EscolarRESUMO
Attention is one of the basic cognitive functions sensitive to high altitude, and most studies have focussed on exposure times of approximately 3 years; however, it is unclear how attention changes in migrants who have lived and worked at high altitude for nearly 20 years. We explored the dynamics of attentional networks and neurophysiological mechanisms in migrants over 3-20 years using the Attentional Network Test combined with Electrocardiograph and Electroencephalography and found a consistent quadratic correlation between exposure and executive control efficiency, P3 amplitude and heart rate variability (HRV), with a decrease followed by an increase/relative stability, with approximately 10 years being the breakpoint. However, neither linear nor quadratic trajectories were observed for the alerting and orienting network. Mediation analysis revealed that the P3 amplitude mediated the decrease and increase in executive control efficiency with exposure time depends on the breakpoint. Correlations between HRV and executive control efficiency and P3 amplitude suggest that U-shaped changes in executive control in migrants may be related to body homeostasis maintained by the autonomic nervous system, and that P3 amplitude may serve as a neurophysiological marker of migrants' adaptation/recovery from high-altitude exposure.
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PURPOSE: Despite BAFF's (B cell activating factor, BAFF) known influence on B cell survival and proliferation, its specific effects within the tumor microenvironment remain unclear. We aimed to elucidate how BAFF overexpression in breast cancer cells impacts tumor growth and the functions of T and B cells in the tumor microenvironment. METHODS: BAFF was overexpressed in the 4T1 mouse triple-negative breast cancer cell line, and tumor growth, immune cell infiltration, and activity were assessed in vitro and in vivo using flow cytometry, co-culture assays, and mouse tumor models with B cell depletion. RESULTS: BAFF overexpression in 4T1 cells promoted tumor growth in vivo, suppressed CD8+ T cell activity, and increased IL-10-secreting CD5+ regulatory B cells in tumors. 4T1/BAFF cells directly enhanced IL-10 production in CD5+ B cells via BAFF/BAFF-receptor interactions, and IL-10 from CD5+ B cells inhibited IFN-γ secretion by T cells. B cell depletion partially reversed the tumor-promoting effects of BAFF overexpression. Our study reveals a novel mechanism by which BAFF can foster tumor progression, with the induction of IL-10-secreting regulatory B cells that suppress anti-tumor T cell responses appearing to be a key component of BAFF's tumor-promoting activity. CONCLUSION: These findings underscore the complex immunomodulatory effects that BAFF exerts in the tumor microenvironment and point to BAFF-induced regulatory B cells as a potential new therapeutic target in breast cancer that warrants further investigation.
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Mucosal bile acid (BA) profile is still unestablished in diarrhea-predominant irritable bowel syndrome (IBS-D). The aim of this study was to explore colonic mucosal BAs and their associations with mucosal mast cell (MMC)-derived nerve growth factor (NGF) and bowel symptoms in IBS-D. Colonic mucosal biopsies from 36 IBS-D patients and 35 healthy controls (HCs) were obtained for targeted BA profiling. MMC count and the expression of NGF and tight junction proteins (TJPs) were examined. We found that colonic mucosal BA profile was altered in the IBS-D cohort. The proportion of primary BAs was significantly higher and that of secondary BAs was lower in IBS-D patients. According to the 90th percentile of total mucosal BA content of HCs, IBS-D patients were divided into BA-H (nâ =â 7, 19.4%) and BA-L (nâ =â 29, 80.6%) subgroups. BA-H patients showed significantly higher total mucosal BA content compared to BA-L subgroup and HCs. The mucosal content of 11 BA metabolites significantly increased in BA-H subgroup, e.g. cholic acid (CA) and taurocholic acid (TCA). Moreover, BA-H patients displayed significantly elevated MMC count and NGF expression, with decreased expression of TJPs (claudin-1, junctional adhesion molecule-A and zonula occludens-1). Correlation analyses revealed that mucosal TCA content positively correlated with MMC count, MMC-derived NGF levels, and abdominal pain while negatively correlated with TJP expression. In conclusion, IBS-D patients showed an altered BA profile in the colonic mucosa. Approximately 20% of them exhibit elevated mucosal BA content, which may be associated with MMC-derived NGF signaling and bowel symptoms.
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MOTIVATION: Primer design is a routine practice for modern molecular biology labs. Bioinformatics tools like primer3 and primer-blast have standardized the primer design for a specific region. However, large-scale primer design, especially for genome-wide screening, is still a labor-intensive job for most wet-lab researchers using these pipelines. RESULTS: Here, we present the primerdiffer pipeline, which can be used to batch design primers that differentiate haplotypes on a large scale with precise false priming checking. This command-line interface (CLI) pipeline includes greedy primer search, local and global in silico PCR-based false priming checking, and automated best primer selection. The local CLI application provides flexibility to design primers with the user's own genome sequences and specific parameters. Some species-specific primers designed to genotype the hybrid introgression strains from Caenorhabditis briggsae and Caenorhabditis nigoni have been validated using single-worm PCR. This pipeline provides the first CLI-based large-scale primer design tool to differentiate haplotypes in any targeted region. AVAILABILITY AND IMPLEMENTATION: The open-source python modules are available at github (https://github.com/runsheng/primerdiffer, https://github.com/runsheng/primervcf) and Python package index (https://pypi.org/project/primerdiffer/, https://pypi.org/project/primervcf/).
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Biologia Computacional , Software , Haplótipos , Genótipo , Reação em Cadeia da PolimeraseRESUMO
PURPOSE: The potential efficacy of metformin in breast cancer (BC) has been hotly discussed but never conclusive. This genetics-based study aimed to evaluate the relationships between metformin targets and BC risk. METHODS: Metformin targets from DrugBank and genome-wide association study (GWAS) data from IEU OpenGWAS and FinnGen were used to investigate the breast cancer (BC)-metformin causal link with various Mendelian Randomization (MR) methods (e.g., inverse-variance-weighting). The genetic association between type 2 diabetes (T2D) and the drug target of metformin was also analyzed as a positive control. Sensitivity and pleiotropic tests ensured reliability. RESULTS: The primary targets of metformin are PRKAB1, ETFDH and GPD1L. We found a causal association between PRKAB1 and T2D (odds ratio [OR] 0.959, P = 0.002), but no causal relationship was observed between metformin targets and overall BC risk (PRKAB1: OR 0.990, P = 0.530; ETFDH: OR 0.986, P = 0.592; GPD1L: OR 1.002, P = 0.806). A noteworthy causal relationship was observed between ETFDH and estrogen receptor (ER)-positive BC (OR 0.867, P = 0.018), and between GPD1L and human epidermal growth factor receptor 2 (HER2)-negative BC (OR 0.966, P = 0.040). Other group analyses did not yield positive results. CONCLUSION: The star target of metformin, PRKAB1, does not exhibit a substantial causal association with the risk of BC. Conversely, metformin, acting as an inhibitor of ETFDH and GPD1L, may potentially elevate the likelihood of developing ER-positive BC and HER2-negative BC. Consequently, it is not advisable to employ metformin as a standard supplementary therapy for BC patients without T2D.
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Neoplasias da Mama , Diabetes Mellitus Tipo 2 , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Metformina , Humanos , Metformina/uso terapêutico , Metformina/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Feminino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicações , Quimioterapia Adjuvante/métodos , Hipoglicemiantes/uso terapêutico , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Since the snare traction-assisted ESD has been proven effective in treating flat lesions of the digestive tract, we modified and innovated the process and path of the traditional snare entering the digestive tract, aiming to investigate the efficacy and safety of using the per-nasal "GTS partner" assisted traction technology in gastric ESD. METHODS: Patients with superficial gastric neoplasms were prospectively enrolled between November 2022 and May 2024 and randomly assigned to a conventional ESD (C-ESD) group or per-nasal "GTS partner" traction-assisted ESD (GTS-ESD) group. The primary outcomes were procedure time and dissection speed. RESULTS: The GTS-ESD and C-ESD groups included 40 patients each, and all the enrolled patients underwent the assigned treatment. The median procedure time in the GTS-ESD group was shorter than that in the C-ESD group (38 min vs. 48 min; P < 0.001), and the mean resection speed of the GTS-ESD group was faster than that of the C-ESD group (17.95 mm2/min vs. 11.86 mm2/min; P = 0.033). The median resection speed of lesions ≥ 20 mm was faster by GTS-ESD than by C-ESD (21.21 mm2/min vs. 12.83 mm2/min, P = 0.002). The en bloc resection rate (100% vs 100%) and R0 resection rate (100% vs. 97.5%) were similar between the two groups. There were no adverse events related to the per-nasal "GTS partner" assisted traction technology, and the traction technology had little interference with the endoscopist. CONCLUSIONS: The per-nasal "GTS partner" assisted traction technique can significantly shorten the gastric ESD procedure time and has the advantages of no damage to normal mucosa and adjustable traction direction, especially in the lower 1/3 of the stomach or lesions with a diameter of ≥ 20 mm.
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A meta-analysis was conducted to evaluate the effects of loose combined cutting seton surgery on wound healing and pain in patients with high anal fistula, aiming to provide evidence-based medical evidence for surgical method selection for these patients. A comprehensive computerized search of PubMed, Cochrane Library, EMBASE, Wanfang and China National Knowledge Infrastructure databases was conducted to collect all relevant studies published up to November 2023, evaluating the effects of loose combined cutting seton surgery in treating patients with high anal fistulas. Two researchers independently screened, extracted data, and assessed the quality of the identified studies. RevMan 5.4 software was employed for data analysis. Overall, 16 articles were included, comprising 1124 patients, with 567 undergoing loose combined cutting seton surgery and 557 undergoing simple cutting seton surgery. The analysis revealed patients undergoing loose combined cutting seton surgery had a higher rate of postoperative wound healing (97.44% vs. 81.69%, odds ratio [OR]: 7.49, 95% confidence interval [CI]: 4.29-13.10, p < 0.00001), shorter wound healing time (standardized mean differences [SMD]: -1.48, 95% CI: -1.89 to -1.08, p < 0.00001), lower postoperative wound pain scores (SMD: -2.51, 95% CI: -3.51 to -1.51, p < 0.00001), and a lower rate of postoperative complications (3.43% vs. 20.83%, OR: 0.13, 95% CI: 0.05-0.31, p < 0.00001). The current evidence suggests that compared to simple cutting seton surgery, loose combined cutting seton surgery in treating high anal fistulas can promote postoperative wound healing, shorten wound healing time, alleviate pain, and reduce the incidence of postoperative complications, making it a worthy clinical practice for widespread application.
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Dor Pós-Operatória , Fístula Retal , Cicatrização , Humanos , Fístula Retal/cirurgia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Resultado do TratamentoRESUMO
Pomegranate peel-derived extracellular nanovesicles(PPENs) were isolated and purified by ultra-high speed centrifugation and sucrose density gradient centrifugation. Their morphology and structure were characterized. In vitro α-glucosidase inhibition assay and model test of insulin resistance(IR) in HepG2 cells showed that PPENs had good anti-diabetic activity. The IC_(50) value of α-glucosidase inhibition was(35.3±1.1) µg·mL~(-1), significantly better than the positive drug acarbose. At a concentration of 100 µg·mL~(-1), PPENs could increase the glucose absorption of IR cells significantly. Lipidome, proteome, and metabolite analysis of PPENs were performed using chromatography-mass spectrometry. MicroRNA(miRNA) sequences were identified, and target genes of miRNA were predicted. The analysis results indicated that PPENs contained abundant lipids and transport proteins, providing a material basis for the transportation and distribution of PPENs in tissue. Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis suggested that lipids and miRNAs may be the key components of PPENs to exert anti-diabetic activity.
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Hipoglicemiantes , Punica granatum , Punica granatum/química , Humanos , Células Hep G2 , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Vesículas Extracelulares/química , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , MicroRNAs/genética , alfa-Glucosidases/genética , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo , Frutas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Nanopartículas/químicaRESUMO
The construction of the SCF3-containing 1,1-diaryl tertiary carbon stereocenters with high enantioselectivities is reported via a nickel-catalyzed asymmetric C-C coupling strategy. This method demonstrates simple operations, mild conditions and excellent functional group tolerance, with newly designed SCF3-containing synthon, which can be easily obtained from commercially available benzyl bromide and trifluoromethylthio anion in a two-step manner. Further substrate exploration indicated that the reaction system could be extended to diverse perfluoroalkyl sulfide (SC2F5, SC3F7, SC4F9, SCF2CO2Et)-substituted 1,1-diaryl compounds with excellent enantioselectivities. The synthetic utility of this transformation was further demonstrated by convenient derivatization to optical SCF3-containing analogues of bioactive compounds without an apparent decrease in enantioselectivity.
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Massively parallel sequencing of the polyadenylated RNAs has played a key role in delineating transcriptome complexity, including alternative use of an exon, promoter, 5' or 3' splice site or polyadenylation site, and RNA modification. However, reads derived from the current RNA-seq technologies are usually short and deprived of information on modification, compromising their potential in defining transcriptome complexity. Here, we applied a direct RNA sequencing method with ultralong reads using Oxford Nanopore Technologies to study the transcriptome complexity in Caenorhabditis elegans We generated approximately six million reads using native poly(A)-tailed mRNAs from three developmental stages, with average read lengths ranging from 900 to 1100 nt. Around half of the reads represent full-length transcripts. To utilize the full-length transcripts in defining transcriptome complexity, we devised a method to classify the long reads as the same as existing transcripts or as a novel transcript using sequence mapping tracks rather than existing intron/exon structures, which allowed us to identify roughly 57,000 novel isoforms and recover at least 26,000 out of the 33,500 existing isoforms. The sets of genes with differential expression versus differential isoform usage over development are largely different, implying a fine-tuned regulation at isoform level. We also observed an unexpected increase in putative RNA modification in all bases in the coding region relative to the UTR, suggesting their possible roles in translation. The RNA reads and the method for read classification are expected to deliver new insights into RNA processing and modification and their underlying biology in the future.
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Caenorhabditis elegans/genética , RNA Mensageiro/genética , RNA/genética , Transcriptoma/genética , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Éxons/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento/genética , Análise de Sequência de RNARESUMO
BACKGROUND AIMS: The current approach for preventing hemolysis of red blood cells (RBCs) in major ABO-incompatible bone marrow (BM) grafts after infusion is to deplete RBCs from BM products before transplantation. Traditionally, manual density separation (MDS) using Ficoll-Hypaque (Cytiva Sweden AB, Uppsala, Sweden has been used to accomplish RBC depletion. This process yields good CD34+ cell recovery, but it requires open manipulation and is labor-intensive and time-consuming. We hypothesized that an alternative automated method using Haemonetics Cell Saver 5+ (Haemonetics Corporation, Boston, MA, USA) would offer equivalent RBC depletion and CD34+ cell recovery. Small marrow volumes from pediatric donors can be processed using Cell Saver (CS) without adding the third-party RBCs necessary for other automated methods. METHODS: This retrospective analysis comprised data from 58 allogeneic BM grafts. RBC depletion and CD34+ cell recovery from BM using MDS (35 grafts) were compared with CS (14 grafts). Nine products underwent RBC depletion using CS with Ficoll (CS-F) when RBC volume was less than 125 mL. RESULTS: Linear regression analysis of log transformation of CD34+ cell recovery adjusted for log transformation of both baseline CD34+ cell content and baseline total volume showed no significant difference between MDS and CS (estimated coefficient, -0.121, P = 0.096). All products contained an RBC volume of less than 0.25 mL/kg post-processing. CD34+ cell recovery with CS-F was comparable to MDS and CS and suitable for pediatric recipients of allogeneic hematopoietic cell transplantation. CONCLUSIONS: We provide evidence that an automated method using Haemonetics Cell Saver 5+ achieves RBC depletion and CD34+ cell recovery comparable to MDS when adjusting for baseline factors.
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Transplante de Medula Óssea , Medula Óssea , Criança , Humanos , Células da Medula Óssea , Transplante de Medula Óssea/métodos , Separação Celular/métodos , Eritrócitos , Ficoll , Estudos RetrospectivosRESUMO
Calcineurin inhibitors (CNI), cyclosporine and tacrolimus, are commonly used for pharmacologic prophylaxis of graft-versus-host disease after allogeneic hematopoietic cell transplantation (HCT). Unfortunately, their use is associated with significant toxicities. While intolerance to CNI is well defined, there is very little information on how they impact outcomes after HCT in children. Our retrospective study in a cohort of 82 children shows a high intolerance rate of 39% in this population associated with lower event-free survival and a higher transplant-related mortality.
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BACKGROUND: Fibroblast growth factors (FGFs) are key factors affecting diabetic wound healing. However, the FGF family's expression patterns in skin and wounds influenced by both diabetes and sex are still unknown. METHODS AND RESULTS: In this study, normal and Streptozotocin (STZ)-induced type 1 diabetic C57BL/6J male and female mice were used to study the FGF family's expression in non-wound skin and wounds. We found that the expression patterns of Fgfs were affected by sex in both normal and diabetic animals during wound healing. In normal control mice, sex difference had a limited effect on basal skin Fgf expressions. However, it significantly influenced Fgf expressions in wounds. Type 1 diabetes reduced basal and wound-induced skin Fgf expressions. Female mice had far lower wound-induced skin Fgf expressions in diabetic mice. In addition, sex differently influenced Fibroblast growth factors receptor (Fgfr) expression patterns of non-wound skin and wounds in both normal and diabetic mice. Moreover, female mice had a lower relative level of Fibronectin leucine-rich repeat transmembrane protein 2 (FLRT2) - a FGFR activation marker gene - in wound and blood plasma. Correspondingly, the wound areas of female animals were larger than that of male animals in the early stage of wound healing (less than 3-day injury). CONCLUSION: Our research shows that the FGF family have different expression patterns in normal and diabetic wound healing in mice of different sex. Additionally, we also provide the signatures of individual FGFs in diabetic wound healing, which deserve further investigation.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Camundongos , Feminino , Masculino , Animais , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Estreptozocina/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Caracteres Sexuais , Camundongos Endogâmicos C57BL , Pele/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/genética , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Glicoproteínas de Membrana/metabolismoRESUMO
PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.
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Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Frutas , Estudos Prospectivos , Incidência , Glucose , Fatores de RiscoRESUMO
Diffuse large B cell lymphoma (DLBCL) is a B cell neoplasm characterized by high PIM1 expression, which is responsible for poor prognosis. Activation-induced cytidine deaminase (AID) is closely linked to PIM1 hypermutation in DLBCL. Here, we found that the DNA methyltransferase 1 (DNMT1) level decreased with AID depletion in the DLBCL cell line SU-DHL-4, and increased significantly when AID was highly expressed. The double ablation of AID and DNMT1 contributed to increased PIM1 expression, which initiated faster DLBCL cell proliferation, whereas ten-eleven translocation family member 2 (TET2) decreased with AID deficiency and increased with AID overexpression in DLBCL cell line OCI-LY7. The double depletion of AID and TET2 was associated with decreased PIM1 levels and showed slower cell division. We suggest an alternative role of AID as a co-factor of DNA methylation cooperated with DNMT1, or of DNA demethylation associated with TET2 in modulating PIM1 expression. Our findings demonstrate that AID interacts with either DNMT1 or TET2 to form a complex to bind with a PIM1 promoter and thus is responsible for the modulation of PIM1 expression. These results provide insights into an alternative role of AID to DLBCL-associated genes.
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Citidina Desaminase , Linfoma Difuso de Grandes Células B , Proteínas Proto-Oncogênicas c-pim-1 , Humanos , Linhagem Celular , Citidina Desaminase/genética , Citidina Desaminase/metabolismo , Linfoma Difuso de Grandes Células B/genética , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-pim-1/genética , Proteínas Proto-Oncogênicas c-pim-1/metabolismoRESUMO
Pulmonary fibrosis (PF) is a chronic interstitial lung disease with no effective therapies. Galectin-3 (Gal-3), a marker of oxidative stress, plays a key role in the pathogenesis of PF. Fibroblast-myofibroblast differentiation (FMD) is an important source of fibrotic cells in PF. Previous studies showed that melatonin (MT) exerted anti-fibrotic effect in many diseases including PF through its antioxidant activity. In the present study we investigated the relationships among Gal-3, NRF2, ROS in FMD and their regulation by MT. We established an in vitro model of FMD in TGF-ß1-treated human fetal lung fibroblast1 (HFL1) cells and a PF mouse model via bleomycin (BLM) intratracheal instillation. We found that Gal-3 expression was significantly increased both in vitro and in vivo. Knockdown of Gal-3 in HFL1 cells markedly attenuated TGF-ß1-induced FMD process and ROS accumulation. In TGF-ß1-treated HFL1 cells, pretreatment with NRF2-specific inhibitor ML385 (5 µM) significantly increased the levels of Gal-3, α-SMA and ROS, suggesting that the expression of Gal-3 was regulated by NRF2. Treatment with NRF2-activator MT (250 µM) blocked α-SMA and ROS accumulation accompanied by reduced Gal-3 expression. In BLM-induced PF model, administration of MT (5 mg·kg-1·d-1, ip for 14 or 28 days) significantly attenuated the progression of lung fibrosis through up-regulating NRF2 and down-regulating Gal-3 expression in lung tissues. These results suggest that Gal-3 regulates TGF-ß1-induced pro-fibrogenic responses and ROS production in FMD, and MT activates NRF2 to block FMD process by down-regulating Gal-3 expression. This study provides a useful clue for a clinical strategy to prevent PF. Graphic abstract of the mechanisms. MT attenuated BLM-induced PF via activating NRF2 and inhibiting Gal-3 expression.
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Melatonina , Fibrose Pulmonar , Animais , Humanos , Camundongos , Bleomicina/efeitos adversos , Fibroblastos , Galectina 3/efeitos dos fármacos , Galectina 3/metabolismo , Pulmão/patologia , Melatonina/farmacologia , Melatonina/uso terapêutico , Fator 2 Relacionado a NF-E2/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Fibrose Pulmonar/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Crescimento Transformador beta1/metabolismoRESUMO
BACKGROUND: We aimed to evaluate the added value of inversion imaging in differentiating between benign and malignant breast masses when combined with the Breast Imaging Reporting and Data System (BI-RADS). METHODS: A total of 364 patients with 367 breast masses (151 benign and 216 malignant) who underwent conventional ultrasound and inversion imaging prior to breast surgery were included. A 5-point inversion score (IS) scale was proposed based on the masses' internal echogenicity and distribution characteristics in the inversion images. The combination of IS and BI-RADS was compared with BI-RADS alone to evaluate the value of inversion imaging for breast mass diagnosis. The diagnostic performance of the BI-RADS and its combination with IS for breast masses were analyzed using area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: The IS for malignant breast masses (3.96 ± 0.77) was significantly higher than benign masses (2.58 ± 0.98) (P < 0.001). The sensitivity, specificity, accuracy, PPV, and NPV of BI-RADS were 86.1%, 81.5%, 84.2%, 86.9%, and 80.4%, respectively, and an AUC was 0.909. By compared with BI-RADS, 72 breast masses were downgraded from suspected malignancy to benign, and 6 masses were upgraded from benign to suspected malignancy. Thus, the specificity was increased from 81.5 to 84.8%, it allows 72 benign masses avoid biopsy. CONCLUSION: The combination of inversion imaging with BI-RADS can effectively improve the diagnostic efficacy of breast masses, and inversion imaging could help benign masses avoid biopsy.
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Neoplasias da Mama , Neoplasias , Feminino , Humanos , Ultrassonografia Mamária/métodos , Mama/diagnóstico por imagem , Mama/patologia , Ultrassonografia , Valor Preditivo dos Testes , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Sensibilidade e EspecificidadeRESUMO
As a flexible and compact nanophotonic device, the metasurface exhibits excellent potential in holographic display and optical information encryption. However, most metasurfaces are passive devices due to the limitations of fixed material properties and structural components. Magneto-optical metasurface is a hybrid device that integrates tunable functional material with elaborately designed nanostructures. It can realize dynamic modulation of the properties of light since the permittivity tensor for the magneto-optical material can be changed by applying an external magnetic field. Here, we propose a tunable metasurface composing metallic nanohole arrays with a bismuth-substituted yttrium iron garnet interleave layer and a metallic film underlayer placed on a glass substrate. The magneto-optical metasurface can achieve dynamic switchable holographic display in different polarization channels via magnetic field control based on the optical rotation of magnetic material and the complex amplitude modulation of the elaborately designed nanoholes. This feature provides a novel approach for the construction of an active tunable metasurface, which can improve the information storage capacity and security of the device. This concept is expected to be applied to various dynamic modulation fields, such as magnetically tunable lens, beam shaping, and optical information encryption.
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Influenza A virus is globally widespread, causing a large number of infections and deaths due to acute lung injury (ALI) every year. The destruction and impairment of alveolar epithelial and microvascular endothelial cell barrier functions are the key inducers of ALI and acute respiratory distress syndrome caused by influenza virus infection. Although noncoding ribonucleic acids (ncRNAs) do not encode proteins in host cells, they possess the ability of protein regulation and signal transduction. Moreover, studies have shown that ncRNAs are significantly and differentially expressed following influenza virus infection, and these ncRNAs play vital roles in the pathogenesis of influenza virus infection. By analyzing the recently published literature, we found that ncRNA could regulate alveolar epithelial and microvascular endothelial cell barrier functions in different ways, which include influencing the innate and acquired immune responses of host cells, affecting apoptosis and autophagy, regulating tight and adherent junctions, etc. In the present paper, we reviewed the roles and regulatory mechanisms of these ncRNAs and discussed the effects of these ncRNAs on pulmonary epithelial and endothelial cell barriers. Further, by sorting and analyzing available research data, we proposed the possibility of applying these ncRNAs for treating ALI in influenza cases, thereby alleviating the permeability of pulmonary epithelial and endothelial cell barriers. Moreover, we discussed future research and development prospects. Our review suggests that targeted therapy and drug research based on ncRNAs would provide an important direction for the molecular therapy of influenza-induced ALI.