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This study aimed to compare the effects of various dietary selenium (Se) sources (0.5 mg/kg) on performance, meat quality, and antioxidant capacity in broilers as well as essential trace elements concentrations in their blood and tissues. A total of 360 one-day-old male yellow-feathered chickens (37.00 ± 0.17 g) were randomly allocated to 5 diet treatments: the basal diet (CON) and 4 diets supplemented with sodium selenite (SS), selenomethionine (SM), selenium-enriched yeast (SY), and nano-selenium (NS) for 56 d, respectively, with 6 replicates per treatment and 12 chickens per replicate. Dietary Se supplementation did not affect growth performance and carcass characteristics in broilers (P > 0.05). Supplemental SM enhanced the redness in the pectoral muscle compared to CON and NS (P < 0.05). Supplementation of SY and NS improved the concentrations of Se, copper, manganese, and zinc in the serum (P < 0.05). Supplemental SS also elevated the zinc content in the serum (P < 0.05). Broilers fed the SY diet showed increased Se content in the liver and pectoral muscle compared to those fed CON, SM, and NS diets (P < 0.05). Also, SY improved the pectoral muscle Se concentration compared to SS (P < 0.05). Besides, dietary Se supplementation increased the Se content in the thigh muscle (P < 0.05), with SY showing highest Se deposition. Dietary supplementation with SS, SM, and NS improved the activities of total superoxide dismutase and total antioxidant capacity (T-AOC) in the serum (P < 0.05). Supplemental SY also elevated the T-AOC in the serum (P < 0.05). Additionally, SS and SM enhanced the T-AOC in the liver (P < 0.05). In conclusion, supplemental SM affected meat color. Supplementing diets with various Se sources increased antioxidant capacity and Se content in the thigh muscle of broilers, with SY showing a more pronounced deposition efficiency. Besides, diets supplemented with different Se sources had variable effects on the concentrations of essential trace elements in the serum and tissues of broilers.
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Ração Animal , Antioxidantes , Galinhas , Dieta , Suplementos Nutricionais , Carne , Selênio , Oligoelementos , Animais , Galinhas/crescimento & desenvolvimento , Ração Animal/análise , Antioxidantes/metabolismo , Dieta/veterinária , Carne/análise , Suplementos Nutricionais/análise , Oligoelementos/metabolismo , Oligoelementos/administração & dosagem , Selênio/administração & dosagem , Masculino , Distribuição Aleatória , Selenometionina/administração & dosagem , Selenito de Sódio/administração & dosagem , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacosRESUMO
Bone malunion or nonunion leads to functional and esthetic problems and is a major healthcare burden. Activation of bone marrow mesenchymal stem cells (BMSCs) and subsequent induction of osteogenic differentiation by local metabolites are crucial steps for bone healing, which has not yet been completely investigated. Here, we found that lactate levels are rapidly increased at the local injury site during the early phase of bone defect healing, which facilitates the healing process by enhancing BMSCs regenerative capacity. Mechanistically, lactate serves as a ligand for the Olfr1440 olfactory receptor, to trigger an intracellular calcium influx that in turn activates osteogenic phenotype transition of BMSCs. Conversely, ablation of Olfr1440 delays skeletal repair and remodelling, as evidenced by thinner cortical bone and less woven bone formation in vivo. Administration of lactate in the defect area enhanced bone regeneration. These findings thus revealed the key roles of lactate in the osteogenic differentiation of BMSCs, which deepened our understanding of the bone healing process, as well as provided cues for a potential therapeutic option that might greatly improve bone defect treatment.
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Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells (BMSCs) and vascular endothelial cells (ECs). However, there are apparent limitations in stem cell-based therapy which hinder its clinic translation. Hence, we investigated the potential of alternative stem cell substitutes for facilitating bone regeneration. In this study, we successfully prepared cell membrane vesicles (CMVs) from BMSCs and ECs. The results showed that BMSC-derived cell membrane vesicles (BMSC-CMVs) possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental cells. EC-derived cell membrane vesicles (EC-CMVs) also contained BMP2 and VEGF derived from their parental cells. BMSC-CMVs enhanced tube formation and migration ability of hUVECs, while EC-CMVs promoted the osteogenic differentiation of hBMSCs in vitro. Using a rat skull defect model, we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in vivo. Therefore, our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.
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Células Endoteliais , Osteogênese , Ratos , Animais , Regeneração Óssea , Osso e Ossos , Membrana CelularRESUMO
BACKGROUND: Active case finding (ACF) is a potentially promising approach for the early identification and treatment of tuberculosis patients. However, evidence on its cost-effectiveness, particularly in low- and middle-income countries, remains limited. This study evaluates the cost-effectiveness of a community-based ACF practice in Shenzhen, China. METHODS: We employed a Markov model-based decision analytic method to assess the costs and effectiveness of 3 tuberculosis detection strategies: passive case finding (PCF), basic ACF, and advanced ACF. The analysis was conducted from a societal perspective on a dynamic cohort over a 20-year horizon, focusing on active tuberculosis (ATB) prevalence and the incremental cost-effectiveness ratio (ICER). RESULTS: Compared to the PCF strategy, the basic and advanced ACF strategies effectively reduced ATB cases by 6.8 and 10.2 per 100 000 population, respectively, by the final year of this 20-year period. The ICER for the basic and advanced ACF strategies were ¥14 757 and ¥8217 per quality-adjusted life-year, respectively. Both values fell below the cost-effectiveness threshold. CONCLUSIONS: Our findings indicate that the community-based ACF screening strategy, which targets individuals exhibiting tuberculosis symptoms, is cost-effective. This underscores the potential benefits of adopting similar community-based ACF strategies for symptomatic populations in tuberculosis-endemic areas.
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Análise Custo-Benefício , Cadeias de Markov , Tuberculose , Humanos , China/epidemiologia , Tuberculose/diagnóstico , Tuberculose/economia , Tuberculose/epidemiologia , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , PrevalênciaRESUMO
Optic neuropathies, characterized by injury of retinal ganglion cell (RGC) axons of the optic nerve, cause incurable blindness worldwide. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) represent a promising "cell-free" therapy for regenerative medicine; however, the therapeutic effect on neural restoration fluctuates, and the underlying mechanism is poorly understood. Here, we illustrated that intraocular administration of MSC-sEVs promoted both RGC survival and axon regeneration in an optic nerve crush mouse model. Mechanistically, MSC-sEVs primarily targeted retinal mural cells to release high levels of colony-stimulating factor 3 (G-CSF) that recruited a neural restorative population of Ly6Clow monocytes/monocyte-derived macrophages (Mo/MΦ). Intravitreal administration of G-CSF, a clinically proven agent for treating neutropenia, or donor Ly6Clow Mo/MΦ markedly improved neurological outcomes in vivo. Together, our data define a unique mechanism of MSC-sEV-induced G-CSF-to-Ly6Clow Mo/MΦ signaling in repairing optic nerve injury and highlight local delivery of MSC-sEVs, G-CSF, and Ly6Clow Mo/MΦ as therapeutic paradigms for the treatment of optic neuropathies.
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Vesículas Extracelulares , Células-Tronco Mesenquimais , Traumatismos do Nervo Óptico , Camundongos , Animais , Axônios/metabolismo , Fator Estimulador de Colônias de Granulócitos/metabolismo , Regeneração Nervosa/fisiologia , Traumatismos do Nervo Óptico/terapia , Traumatismos do Nervo Óptico/metabolismo , Células Ganglionares da Retina/fisiologia , Células-Tronco Mesenquimais/metabolismo , Vesículas Extracelulares/metabolismo , Macrófagos/metabolismoRESUMO
Pancreatic cancer is among the most malignant cancers, and thus early intervention is the key to better survival outcomes. However, no methods have been derived that can reliably identify early precursors of development into malignancy. Therefore, it is urgent to discover early molecular changes during pancreatic tumorigenesis. As aberrant glycosylation is closely associated with cancer progression, numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis; however, detailed glycoproteomic information, especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment, needs to be further explored. Herein, we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans, glycosites, and intact glycopeptides in pancreatic cancer cells and patient sera. The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells, whereas human sera, which contain many secreted glycoproteins, had significant changes of glycans at their specific glycosites. These results indicated the potential role for tumor-specific glycosylation as disease biomarkers. We also found that AMG-510, a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutation, profoundly reduced the glycosylation level in MIA PaCa-2 cells, suggesting that KRAS plays a role in the cellular glycosylation process, and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Glicosilação , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Glicoproteínas , Espectrometria de Massas , Biomarcadores/metabolismo , PolissacarídeosRESUMO
BACKGROUND: Benign prostatic hyperplasia (BPH) is a common condition that affects the quality of life of older men. Specific micronutrients, including retinol, retinyl esters, carotenoids, vitamin E, and vitamin C, have antioxidant and anti-inflammatory properties. However, the correlation between serum concentrations of these micronutrients and BPH is unclear. METHODS: We used data from the National Health and Nutrition Examination Survey (NHANES), which included 2067 representative US men. BPH was assessed using the self-reported questionnaire. This association was explored by adjusting for confounders using multivariate logistic regression. RESULTS: After fully adjusting for confounders, for every 0.01 µmol/L increase in serum retinyl esters, the risk of BPH increased by 2% (OR = 1.02; 95% CI: 1.01-1.03; p = 0.006). Based on the Bonferroni-corrected p-value, we found this correlation to be significant. One µmol/L increase in total carotenoids was associated with a 22% increase in BPH risk (OR = 1.22; 95% CI: 1.03-1.46; p = 0.025). By analyzing the correlation between different types of carotenoids and BPH, we also found that ß-carotenoids (OR = 1.43; 95% CI: 1.03-1.99; p = 0.036) was also positively correlated with BPH. The subgroup analysis revealed a positive correlation between serum vitamin E (OR = 1.02; 95% CI: 1.00-1.04; p = 0.018) and BPH in men under 60 years of age. Serum retinyl ester (OR = 1.02; 95% CI: 1.01-1.04; p = 0.008) and carotenoid (OR = 1.52; 95% CI: 1.22-1.87; p < 0.001) concentrations were positively correlated with BPH in men over 60 years of age. CONCLUSION: Our study suggests that excessive serum retinyl esters, total carotenoids, and especially ß-carotenoids are potential risk factors for BPH, and this association should be further investigated.
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Hiperplasia Prostática , Masculino , Humanos , Pessoa de Meia-Idade , Idoso , Hiperplasia Prostática/epidemiologia , Inquéritos Nutricionais , Qualidade de Vida , Micronutrientes , Ésteres de Retinil , Carotenoides , Vitamina ERESUMO
Background: The risk of visceral obesity on erectile function has recently attracted much attention. The visceral adiposity index (VAI) is a brief and reliable indicator of visceral obesity measurement. Nevertheless, the association between VAI and erectile dysfunction (ED) is not completely clarified. Methods: Data from NHANES 2001-2004 were enrolled in this study. Erectile function was assessed by a database-self-administered questionnaire. VAI was calculated with body mass index (BMI), waist circumference (WC), triglyceride (TG), and high-density lipoprotein (HDL) cholesterol. The weighted logistic regression model was performed to evaluate the association between VAI and ED. Results: Ultimately, 3380 participants were enrolled in the study, including 900 with ED and 2480 without ED. Compared to participants without ED, those with ED generally had higher levels of VAI (1.76 vs. 1.53). The weighted logistic regression analyses demonstrated increased odds of developing ED in participants within the 4th quartile (Q4) of VAI compared to the 1st quartile (Q1) of VAI (OR = 2.023; 95% CI, 1.534-2.669; P < 0.001). Similar results were still obtained after adjusting for the relevant covariates (OR = 1.404; 95% CI, 1.008-1.954; P = 0.044). In subgroup analyses grouped by smoking status, higher VAI was associated with increased odds of developing ED only in the current smoking group (OR = 1.092; 95% CI, 1.021-1.167; P = 0.010). Conclusion: This study indicated that higher VAI is independently related to ED risk and that early intervention is necessary to reduce the progression of ED with high VAI levels.
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Disfunção Erétil , Masculino , Adulto , Humanos , Disfunção Erétil/epidemiologia , Disfunção Erétil/etiologia , Obesidade Abdominal/complicações , Estudos Transversais , Adiposidade , Inquéritos Nutricionais , HDL-ColesterolRESUMO
Lung adenocarcinoma (LUAD) remains a leading cause of cancer-related morbidity and mortality globally. While DDX52, an ATP-dependent RNA helicase, plays a role in several biological processes, its specific involvement in LUAD is yet to be elucidated. We utilized ROC curves to determine DDX52's predictive potential for LUAD. Kaplan-Meier survival curves, along with univariate and multivariate Cox analyses, assessed the prognostic implications of DDX52 in LUAD. We constructed nomogram models to further delineate DDX52's influence on prognosis, employed GSEA for functional analysis, and used qRT-PCR to examine DDX52 expression in LUAD tissues. DDX52 expression was notably higher in LUAD tissues, suggesting its potential as a negative prognostic marker. We observed a direct relationship between DDX52 expression and advanced T and N stages, as well as higher grading and staging in LUAD patients. Cox analyses further underscored DDX52's role as an independent prognostic determinant for LUAD. GSEA insights indicated DDX52's influence on LUAD progression via multiple signaling pathways. Our nomogram, founded on DDX52 expression, effectively projected LUAD patient survival, as validated by calibration curves. Elevated DDX52 expression in LUAD tissues signals its potential as a poor prognostic marker. Our findings emphasize DDX52's role not only as an independent prognostic factor for LUAD but also as a significant influencer in its progression through diverse signaling pathways. The constructed nomogram also underscores the feasibility of predicting LUAD patient survival based on DDX52 expression.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Pulmonares , Humanos , Prognóstico , RNA Helicases , DNA Helicases , Expressão Gênica , BiomarcadoresRESUMO
BACKGROUND: The relationship between uric acid (UA) and benign prostatic hyperplasia (BPH) is controversial and has rarely been studied in American populations. METHODS: Data from two cycles of the National Health and Nutrition Examination Surveys, comprising data from 2005 to 2008, were used. The majority of BPH were identified by self-report. We investigated the relationship between UA and BPH using univariate and multivariate logistic regression analyses. RESULTS: 2,845 participants were enrolled in the study, including 531 participants with BPH and 2,314 controls. After fully adjusting for all confounders, the risk of developing BPH was reduced by 18% for every 100 µmol/L increase in UA (OR = 0.82, 95% CI: 0.69-0.97, p = 0.023). Participants in the highest quartile of UA were found to have a reduced likelihood of developing BPH (ORQ4vs1 = 0.61, 95% CI: 0.41-0.91) in comparison to those in the lowest quartile of UA. Subgroup analyses found that among those younger than 60 years, non-Hispanic whites, former smokers, heavy drinkers, those without diabetes, or those with hypertension, high UA remained negatively associated with BPH. CONCLUSIONS: The above results suggest that UA may be a potential protective factor for BPH, but the mechanism needs to be further explored.
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Hipertensão , Hiperplasia Prostática , Masculino , Humanos , Estados Unidos/epidemiologia , Hiperplasia Prostática/epidemiologia , Ácido Úrico , Fatores de Risco , Inquéritos NutricionaisRESUMO
Human organic anion transporting polypeptide 2B1 (OATP2B1) is a membrane transporter widely expressed in organs crucial for drug absorption and disposition such as the intestine, liver, and kidney. Evidence indicates that OATP2B1 is a glycoprotein. However, the sites of glycosylation and their contribution to the function and expression of OATP2B1 are largely unknown. In this study, by site-directed mutagenesis, we determined that two of four potential N-glycosylation sites in OATP2B1, N176 and N538, are indeed glycosylated. Functional studies revealed that the transport activities of mutants N176Q and N538Q were greatly reduced as compared to that of wild-type OATP2B1. However, the reduced activity was not due to the impairment of transport function per se but due to the decreased surface expression as the Km and normalized Vmax values of N176Q and N538Q were comparable to those of OATP2B1. Quantitative polymerase chain reaction (PCR) revealed that N176Q and N538Q mutations did not affect the expression of OATP2B1 at a transcriptional level. Immunofluorescence analysis showed that deglycosylated OATP2B1 was largely retained in the endoplasmic reticulum, which may activate the endoplasmic reticulum-associated degradation pathway, and the ubiquitin-proteasome system played a major role in the degradation of OATP2B1. Taken together, OATP2B1 is N-glycosylated, and N-glycosylation is essential for the surface expression of OATP2B1 but not critical for the transport function of OATP2B1 per se.
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Myasthenia gravis (MG) is a classic autoimmune neuromuscular disease with strong clinical heterogeneity. The concept of subgroup classification was proposed to guide the precise treatment of MG. Subgroups based on serum antibodies and clinical features include ocular MG, early-onset MG with AchR antibodies, late-onset MG with AchR antibodies, thymoma-associated MG, MuSK-associated MG, LRP4-associated MG, and seronegative MG. However, reliable objective biomarkers are still needed to reflect the individualized response to therapy. MicroRNAs (miRNAs) are small non-coding RNA molecules which can specifically bind to target genes and regulate gene expression at the post-transcriptional level, and then influence celluar biological processes. MiRNAs play an important role in the pathogenesis of autoimmune diseases, including MG. Several studies on circulating miRNAs in MG have been reported. However, there is rare systematic review to summarize the differences of these miRNAs in different subgroups of MG. Here, we summarize the potential role of circulating miRNAs in different subgroups of MG to promote personalized medicine.
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MicroRNA Circulante , MicroRNAs , Miastenia Gravis , Neoplasias do Timo , Humanos , Receptores Colinérgicos , MicroRNA Circulante/genética , Medicina de Precisão , Autoanticorpos , Receptores Proteína Tirosina Quinases , MicroRNAs/genéticaRESUMO
Background: COVID-19, a serious respiratory disease that has the potential to affect numerous organs, is a serious threat to the health of people around the world. The objective of this article is to investigate the potential biological targets and mechanisms by which SARS-CoV-2 affects benign prostatic hyperplasia (BPH) and related symptoms. Methods: We downloaded the COVID-19 datasets (GSE157103 and GSE166253) and the BPH datasets (GSE7307 and GSE132714) from the Gene Expression Omnibus (GEO) database. In GSE157103 and GSE7307, differentially expressed genes (DEGs) were found using the "Limma" package, and the intersection was utilized to obtain common DEGs. Further analyses followed, including those using Protein-Protein Interaction (PPI), Gene Ontology (GO) function enrichment analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Potential hub genes were screened using three machine learning methods, and they were later verified using GSE132714 and GSE166253. The CIBERSORT analysis and the identification of transcription factors, miRNAs, and drugs as candidates were among the subsequent analyses. Results: We identified 97 common DEGs from GSE157103 and GSE7307. According to the GO and KEGG analyses, the primary gene enrichment pathways were immune-related pathways. Machine learning methods were used to identify five hub genes (BIRC5, DNAJC4, DTL, LILRB2, and NDC80). They had good diagnostic properties in the training sets and were validated in the validation sets. According to CIBERSORT analysis, hub genes were closely related to CD4 memory activated of T cells, T cells regulatory and NK cells activated. The top 10 drug candidates (lucanthone, phytoestrogens, etoposide, dasatinib, piroxicam, pyrvinium, rapamycin, niclosamide, genistein, and testosterone) will also be evaluated by the P value, which is expected to be helpful for the treatment of COVID-19-infected patients with BPH. Conclusion: Our findings reveal common signaling pathways, possible biological targets, and promising small molecule drugs for BPH and COVID-19. This is crucial to understand the potential common pathogenic and susceptibility pathways between them.
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COVID-19 , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/genética , COVID-19/genética , SARS-CoV-2 , Genes cdc , AlgoritmosRESUMO
PURPOSE: Intracavitary chemotherapy is one of the current treatment options for kidney-sparing treatment of upper tract urothelial carcinoma (UTUC). The purpose of this meta-analysis was to assess the efficacy and safety of intracavitary perfusion. METHODS: We carefully selected publications for study from four databases (Embase, PubMed, Web of Science, and Scopus) up to January 2023. The R 4.0.4 software was used to calculate the pooled ratio and its 95% confidence intervals (95% CIs). The I2 score was used to test heterogeneity, and the funnel plot was used to estimate the publication bias. RESULTS: Thirty-four studies with a total of 788 patients were included in this study. The overall survival at a median follow-up of 26.3 months was 87.2% (95% CI 0.80-0.93). The cancer-specific survival at a median follow-up of 30 months was 94.1% (95% CI 0.89-0.98). At a median follow-up of 30 months, the recurrence rate of UTUC was 27.5% (95% CI 0.21-0.34). By subgroup analysis, we found that the recurrence rate in patients with T1 / Ta stage was 35.1% and CIS stage 29.0%. The recurrence rates of BCG, Mitomycin C, and Mitomycin Gel (UGN101) were 31.2%, 41.3% and 12.9%, respectively. The recurrence rates for anterograde and retrograde perfusion were 28.5% and 21.8%, respectively. CONCLUSION: With the advent of new drugs, including UGN101, patients with UTUC have a better prognosis. Therefore, kidney preservation therapy for patients with UTUC would be promising.
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Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias Ureterais , Neoplasias da Bexiga Urinária , Humanos , Carcinoma de Células de Transição/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Quimioterapia Adjuvante , Rim/patologia , Neoplasias Renais/patologia , Mitomicina/uso terapêutico , Neoplasias Ureterais/tratamento farmacológico , Neoplasias Ureterais/patologiaRESUMO
Myasthenia gravis (MG) is an antibody-mediated autoimmune disorder characterized by fluctuation of fatigue and weakness of muscle. Due to the heterogeneity of the course of MG, available biomarkers for prognostic prediction are urgently needed. Ceramide (Cer) was reported to participate in immune regulation and many autoimmune diseases, but its effects on MG remain undefined. This study aimed to investigate the ceramides expression levels in MG patients and their potential as novel biomarkers of disease severity. Levels of plasma ceramides were determined by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Severity of disease was assessed by quantitative MG scores (QMGs), MG-specific activities of daily living scale (MG-ADLs) and 15-item MG quality of Life (MG-QOL15). The concentrations of serum interleukin-1ß (IL-1ß), IL-6, IL-17A, and IL-21 were determined by enzyme-linked immunosorbent assay (ELISA), and the proportions of circulating memory B cells and plasmablasts were detected by flow-cytometry assay. Four plasma ceramides levels we studied were detected higher in MG patients. And three of them (C16:0-Cer, C18:0-Cer, and C24:0-Cer) were positively associated with QMGs. In addition, receiver operating characteristic (ROC) analysis suggested that plasma ceramides have a good ability of differentiating MG from HCs. Importantly, only C18:0-Cer was shown to be positively associated with the concentration of serum IL and circulating memory B cells, and the decrease in plasma C18:0-Cer paralleled the clinical improvement of patients with MG. All together, our data suggest that ceramides may play an important role in the immunopathological mechanism of MG, and C18:0-Cer has the potential to be a novel biomarker for disease severity in MG.
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Ceramidas , Miastenia Gravis , Humanos , Ceramidas/metabolismo , Cromatografia Líquida , Atividades Cotidianas , Qualidade de Vida , Espectrometria de Massas em Tandem , Biomarcadores , Miastenia Gravis/diagnóstico , Gravidade do PacienteRESUMO
Background: Prostate cancer (PCa) is the second most common type of cancer and the fifth leading cause of cancer-related death in men. Androgen deprivation therapy (ADT) has become the first-line therapy for inhibiting PCa progression; however, nearly all patients receiving ADT eventually progress to castrate-resistant prostate cancer. Therefore, this study aimed to identify hub genes related to bicalutamide resistance in PCa and provide new insights into endocrine therapy resistance. Methods: The data were obtained from public databases. Weighted correlation network analysis was used to identify the gene modules related to bicalutamide resistance, and the relationship between the samples and disease-free survival was analyzed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed, and hub genes were identified. The LASSO algorithm was used to develop a bicalutamide resistance prognostic model in patients with PCa, which was then verified. Finally, we analyzed the tumor mutational heterogeneity and immune microenvironment in both groups. Results: Two drug resistance gene modules were identified. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that both modules are involved in RNA splicing. The protein-protein interaction network identified 10 hub genes in the brown module LUC7L3, SNRNP70, PRPF3, LUC7L, CLASRP, CLK1, CLK2, U2AF1L4, NXF1, and THOC1) and 13 in the yellow module (PNN, PPWD1, SRRM2, DHX35, DMTF1, SALL4, MTA1, HDAC7, PHC1, ACIN1, HNRNPH1, DDX17, and HDAC6). The prognostic model composed of RNF207, REC8, DFNB59, HOXA2, EPOR, PILRB, LSMEM1, TCIRG1, ABTB1, ZNF276, ZNF540, and DPY19L2 could effectively predict patient prognosis. Genomic analysis revealed that the high- and low-risk groups had different mutation maps. Immune infiltration analysis showed a statistically significant difference in immune infiltration between the high- and low-risk groups, and that the high-risk group may benefit from immunotherapy. Conclusion: In this study, bicalutamide resistance genes and hub genes were identified in PCa, a risk model for predicting the prognosis of patients with PCa was constructed, and the tumor mutation heterogeneity and immune infiltration in high- and low-risk groups were analyzed. These findings offer new insights into ADT resistance targets and prognostic prediction in patients with PCa.
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Neoplasias da Próstata , ATPases Vacuolares Próton-Translocadoras , Masculino , Humanos , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Antagonistas de Androgênios/uso terapêutico , Prognóstico , Anilidas/farmacologia , Anilidas/uso terapêutico , Microambiente Tumoral , Proteínas Repressoras , Transativadores , Proteínas NuclearesRESUMO
In the oil industry, oil spills occur due to offshore rig explosions, ship collisions, and other reasons. It is crucial to accurately and rapidly identify oil spills to protect marine ecosystems. Synthetic aperture radar (SAR) can all-weather and all-time work and provide a wealth of polarization information for identification of oil spills based on semantic segmentation model. However, the performance of classifiers in the semantic segmentation model has become a significant challenge to improving recognition ability. To solve this problem, an improved semantic segmentation model named DRSNet was proposed, which uses ResNet-50 as the backbone in DeepLabv3+ and support vector machines (SVM) as the classifier. The experiment was conducted using ten polarimetric features from SAR images and results demonstrate that the DRSNet performs best compared to other semantic segmentation models. Current work provides a valuable tool to enhance maritime emergency management capabilities.
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Poluição por Petróleo , Poluentes Químicos da Água , Máquina de Vetores de Suporte , Poluentes Químicos da Água/análise , Radar , Ecossistema , Semântica , Monitoramento Ambiental/métodosRESUMO
Senile osteoporosis is characterized by age-related bone loss and bone microarchitecture deterioration. However, little is known to date about the mechanism that maintains bone homeostasis during aging. In this study, we identify adenosine monophosphate-activated protein kinase alpha 1 (AMPKα1) as a critical factor regulating the senescence and lineage commitment of mesenchymal stem cells (MSCs). A phospho-mutant mouse model shows that constitutive AMPKα1 activation prevents age-related bone loss and promoted MSC osteogenic commitment with increased bone-derived insulin-like growth factor 1 (IGF-1) secretion. Mechanistically, upregulation of IGF-1 signalling by AMPKα1 depends on cAMP-response element binding protein (CREB)-mediated transcriptional regulation. Furthermore, the essential role of the AMPKα1/IGF-1/CREB axis in promoting aged MSC osteogenic potential is confirmed using three-dimensional (3D) culture systems. Taken together, these results can provide mechanistic insight into the protective effect of AMPKα1 against skeletal aging by promoting bone-derived IGF-1 secretion.
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Fator de Crescimento Insulin-Like I , Osteoporose , Camundongos , Animais , Fator de Crescimento Insulin-Like I/metabolismo , Osso e Ossos/metabolismo , Envelhecimento/metabolismo , Osteogênese , Osteoporose/prevenção & controleRESUMO
Background: The prostate, as an endocrine and reproductive organ, undergoes complex hormonal and metabolic changes. Recent studies have shown a potential relationship between metabolic syndrome and the progression and recurrence of prostate cancer (PCa). This study aimed to construct a metabolic syndrome-related prognostic index (MSRPI) to predict biochemical recurrence-free survival (BFS) in patients with PCa and to identify cold and hot tumors to improve individualized treatment for patients with PCa. Methods: The Cancer Genome Atlas database provided training and test data, and the Gene Expression Omnibus database provided validation data. We extracted prognostic differentially expressed metabolic syndrome-related genes (DEMSRGs) related to BFS using univariate Cox analysis and identified potential tumor subtypes by consensus clustering. The least absolute shrinkage and selection operator (LASSO) algorithm and multivariate Cox regression were used to construct the MSRPI. We further validated the predictive power of the MSRPI using KaplanMeier survival analysis and receiver operating characteristic (ROC) curves, both internally and externally. Drug sensitivity was predicted using the half-maximal inhibitory concentration (IC50). Finally, we explored the landscape of somatic mutations in the risk groups. Results: Forty-six prognostic DEMSRGs and two metabolic syndrome-associated molecular clusters were identified. Cluster 2 was more immunogenic. Seven metabolic syndrome-related genes (CSF3R, TMEM132A, STAB1, VIM, DUOXA1, PILRB, and SLC2A4) were used to construct risk equations. The high-risk index was significantly associated with a poor BFS, which was also validated in the validation cohort. The area under the ROC curve (AUC) for BFS at 1-, 3-, and 5- year in the entire cohort was 0.819, 0.785, and 0.772, respectively, demonstrating the excellent predictive power of the MSRPI. Additionally, the MSRPI was found to be an independent prognostic factor for BFS in PCa. More importantly, MSRPI helped differentiate between cold and hot tumors. Hot tumors were associated with the high-risk group. Multiple drugs demonstrated significantly lower IC50 values in the high-risk group, offering the prospect of precision therapy for patients with PCa. Conclusion: The MSRPI developed in this study was able to predict biochemical recurrence in patients with PCa and identify cold and hot tumors. MSRPI has the potential to improve personalized precision treatment.
Assuntos
Síndrome Metabólica , Neoplasias da Próstata , Masculino , Humanos , Prognóstico , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/genética , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/genética , Próstata , AlgoritmosRESUMO
Introduction: Second-generation androgen receptor inhibitors (SGARIs), namely enzalutamide, apalutamide, and darolutamide, are good for improving survival outcomes in prostate cancer patients, but some researchers have shown that using SGARIs increases side effects, which complicates clinicians' choice of. Therefore, we performed this network meta-analysis to assess the efficacy and toxicity of several SGARIs in the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC), non-metastatic castration-resistant prostate cancer (nmCRPC), and metastatic castration-resistant prostate cancer (mCRPC). Methods: We searched PubMed, EMBASE and Cochrane Library databases from January 2000 to December 2022 to identify randomized controlled studies associated with SGARIs. We use Stata 16.0 and R 4.4.2 for data analysis, hazard ratio (HR) with 95% confidence intervals (CI) were used to assess the results. Results: This meta-analysis included 7 studies with a total of 9488 patients. In mHSPC, enzalutamide and darolutamide had a positive effect on overall survival (OS) (HR, 0.70; 95% CI, 0.59-0.82), but we did not find a difference in their efficacy to improve OS (HR, 1.19; 95% CI, 0.75-1.89). Also in nmCRPC, enzalutamide, apalutamide and darolutamide were beneficial for metastasis-free survival (MFS) (HR, 0.32; 95% CI, 0.25-0.41). Compared to darolutamide, enzalutamide (HR, 0.71; 95% CI, 0.54-0.93) and apalutamide (HR, 0.68; 95% CI, 0.51-0.91) prolonged MFS, but there was no difference in efficacy between enzalutamide and apalutamide (HR, 0.97; 95% CI, 0.73-1.28). Finally in mCRPC, there was no significant difference in indirect effects on OS between pre- and post-chemotherapy enzalutamide (HR, 0.89; 95% CI, 0.70-1.13). However, using enzalutamide before chemotherapy to improve radiographic progression-free survival (rPFS) was a better option (HR, 2.11; 95% CI, 1.62-2.73). Conclusion: The SGARIs used in each trial were beneficial for the primary endpoint in the study. Firstly there was no significant difference in the effect of enzalutamide and darolutamide in improving OS in patients with mHSPC. Secondly improving MFS in patients with nmCRPC was best achieved with enzalutamide and apalutamide. In addition both pre- and post-chemotherapy use of enzalutamide was beneficial for OS in mCRPC patients, but for improving rPFS pre-chemotherapy use of enzalutamide should be preferred.The INPLASY registration number of this systematic review is INPLASY202310084.