Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 424
Filtrar
1.
Carbohydr Polym ; 337: 122171, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38710561

RESUMO

Commercially available mushroom polysaccharides have found widespread use as adjuvant tumor treatments. However, the bioactivity of polysaccharides in Lactarius hatsudake Tanaka (L. hatsudake), a mushroom with both edible and medicinal uses, remains relatively unexplored. To address this gap, five L. hatsudake polysaccharides with varying molecular weights were isolated, named LHP-1 (898 kDa), LHP-2 (677 kDa), LHP-3 (385 kDa), LHP-4 (20 kDa), and LHP-5 (4.9 kDa). Gas chromatography-mass spectrometry, nuclear magnetic resonance, and atomic force microscopy, etc., were employed to determine their structural characteristics. The results confirmed that spherical aggregates with amorphous flexible fiber chains dominated the conformation of the LHP. LHP-1 and LHP-2 were identified as glucans with α-(1,4)-Glcp as the main chain; LHP-3 and LHP-4 were classified as galactans with varying molecular weights but with α-(1,6)-Galp as the main chain; LHP-5 was a glucan with ß-(1,3)-Glcp as the main chain and ß-(1,6)-Glcp connecting to the side chains. Significant differences were observed in inhibiting tumor cell cytotoxicity and the antioxidant activity of the LHPs, with LHP-5 and LHP-4 identified as the principal bioactive components. These findings provide a theoretical foundation for the valuable use of L. hatsudake and emphasize the potential application of LHPs in therapeutic tumor treatments.


Assuntos
Antioxidantes , Glucanos , Glucanos/química , Glucanos/farmacologia , Glucanos/isolamento & purificação , Humanos , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Agaricales/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/isolamento & purificação , Peso Molecular , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificação , Linhagem Celular Tumoral , Polissacarídeos Fúngicos/química , Polissacarídeos Fúngicos/farmacologia , Polissacarídeos Fúngicos/isolamento & purificação , Basidiomycota/química , Sobrevivência Celular/efeitos dos fármacos
2.
BMC Pediatr ; 24(1): 234, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38566022

RESUMO

BACKGROUND: The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. METHODS: A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. RESULTS: After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P < 0.05), compared to the pre-COVID-19 group. Moreover, age, BMI, fever duration, leucocyte count, lymphocyte proportion, proportion of CD3+ T cells, tumor necrosis factor α (TNF-α), and IL-10 were confirmed to be independently associated with severe H1N1 infection in post-COVID-19 era. A prediction model integrating these above eight variables was established, and this model had good discrimination, accuracy, and clinical practicability. CONCLUSIONS: Pediatric H1N1 infection during post-COVID-19 era showed a higher overall disease severity than the classical H1N1 infection in pre-COVID-19 period. Meanwhile, cough and seizures were more prominent in children with H1N1 infection during post-COVID-19 era. Clinicians should be aware of these changes in such patients in clinical work. Furthermore, a simple and practical prediction model was constructed and internally validated here, which showed a good performance for predicting severe H1N1 infection in post-COVID-19 era.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Humanos , Criança , Interleucina-10 , Influenza Humana/complicações , Influenza Humana/diagnóstico , Estudos Retrospectivos , China/epidemiologia , Gravidade do Paciente , Convulsões , Tosse
3.
J Cell Mol Med ; 28(9): e18352, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38685685

RESUMO

Gliomas, the most lethal tumours in brain, have a poor prognosis despite accepting standard treatment. Limited benefits from current therapies can be attributed to genetic, epigenetic and microenvironmental cues that affect cell programming and drive tumour heterogeneity. Through the analysis of Hi-C data, we identified a potassium-chloride co-transporter SLC12A5 associated with disrupted topologically associating domain which was downregulated in tumour tissues. Multiple independent glioma cohorts were included to analyse the characterization of SLC12A5 and found it was significantly associated with pathological features, prognostic value, genomic alterations, transcriptional landscape and drug response. We constructed two SLC12A5 overexpression cell lines to verify the function of SLC12A5 that suppressed tumour cell proliferation and migration in vitro. In addition, SLC12A5 was also positively associated with GABAA receptor activity and negatively associated with pro-tumour immune signatures and immunotherapy response. Collectively, our study provides a comprehensive characterization of SLC12A5 in glioma and supports SLC12A5 as a potential suppressor of disease progression.


Assuntos
Neoplasias Encefálicas , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Glioma , Cotransportadores de K e Cl- , Simportadores , Humanos , Glioma/genética , Glioma/patologia , Glioma/metabolismo , Proliferação de Células/genética , Linhagem Celular Tumoral , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Simportadores/genética , Simportadores/metabolismo , Movimento Celular/genética , Prognóstico , Receptores de GABA-A/metabolismo , Receptores de GABA-A/genética
4.
Gut Liver ; 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38623058

RESUMO

Background/Aims: : Liver cirrhosis involves chronic inflammation and progressive fibrosis. Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: : This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: : Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions: : In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

5.
Micromachines (Basel) ; 15(4)2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38675233

RESUMO

The precise isolation of circulating tumor cells (CTCs) from blood samples is a potent tool for cancer diagnosis and clinical prognosis. However, CTCs are present in extremely low quantities in the bloodstream, posing a significant challenge to their isolation. In this study, we propose a non-contact acoustic micropillar array (AMPA) chip based on acoustic streaming for the flexible, label-free capture of cancer cells. Three shapes of micropillar array chips (circular, rhombus, and square) were fabricated. The acoustic streaming characteristics generated by the vibration of microstructures of different shapes are studied in depth by combining simulation and experiment. The critical parameters (voltage and flow rate) of the device were systematically investigated using microparticle experiments to optimize capture performance. Subsequently, the capture efficiencies of the three micropillar structures were experimentally evaluated using mouse whole blood samples containing cancer cells. The experimental results revealed that the rhombus microstructure was selected as the optimal shape, demonstrating high capture efficiency (93%) and cell activity (96%). Moreover, the reversibility of the acoustic streaming was harnessed for the flexible release and capture of cancer cells, facilitating optical detection and analysis. This work holds promise for applications in monitoring cancer metastasis, bio-detection, and beyond.

6.
J Biochem Mol Toxicol ; 38(3): e23669, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38459698

RESUMO

Paclitaxel (PTX) is a chemotherapeutic agent that is widely used for the treatment of several types of tumors. However, PTX-induced peripheral neuropathy (PIPN) is an adverse effect generally induced by long-term PTX use that significantly impairs the quality of life. Necroptosis has been implicated in various neurodegenerative disorders. Necroptosis of dorsal root ganglion neurons triggers the pathogenesis of PIPN. Therefore, the present study aims to investigate the role of spinal neuronal necroptosis in PIPN. It also explores the potential role of microglial polarization in necroptosis. We established rat models of PIPN via quartic PTX administration on alternate days (accumulated dose: 8 mg/kg). PTX induced obvious neuronal necroptosis and upregulated the expression of receptor-interacting protein kinase (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the spinal dorsal horn. These effects were inhibited with a necroptosis pathway inhibitor, necrostatin-1 (Nec-1). The effect of microglial polarization on the regulation of spinal necroptosis was elucidated by administering minocycline to inhibit PTX-induced M1 polarization of spinal microglia caused by PTX. We observed a significant inhibitory effect of minocycline on PTX-induced necroptosis in spinal cord cells, based on the downregulation of RIP3 and MLKL expression, and suppression of tumor necrosis factor-α and IL-ß synthesis. Additionally, minocycline improved hyperalgesia symptoms in PIPN rats. Overall, this study suggests that PTX-induced polarization of spinal microglia leads to RIP3/MLKL-regulated necroptosis, resulting in PIPN. These findings suggest a potential target for the prevention and treatment of neuropathic pain.


Assuntos
Neuralgia , Paclitaxel , Ratos , Animais , Paclitaxel/efeitos adversos , Microglia/patologia , Necroptose , Minociclina/efeitos adversos , Qualidade de Vida , Neuralgia/induzido quimicamente
7.
Nat Commun ; 15(1): 1029, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310101

RESUMO

The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Patients with N3 nasopharyngeal carcinoma have a high risk of distant metastasis, however, if the addition of immunotherapy to standard treatment could improve efficacy is unclear. In this phase II clinical trial (ChiCTR2000032317), 49 patients with stage TanyN3M0 nasopharyngeal carcinoma were enrolled and received the combination of three cycles of induction chemotherapy, camrelizumab and apatinib followed by chemoradiotherapy. Here we report on the primary outcome of distant metastasis-free survival and secondary end points of objective response rate, failure-free survival, locoregional recurrence-free survival, overall survival and toxicity profile. After induction therapy, all patients had objective response, including 13 patients (26.5%) with complete response. After a median follow-up of 28.7 months, the primary endpoint of 1-year distant metastasis-free survival was met for the cohort (1-year DMFS rate: 98%). Grade≥3 toxicity appeared in 32 (65.3%) patients, with the most common being mucositis (14[28.6%]) and nausea/vomiting (9[18.4%]). In this work, camrelizumab and apatinib in combination with induction chemotherapy show promising distant metastasis control with acceptable safety profile in patients with stage TanyN3M0 nasopharyngeal carcinoma.


Assuntos
Anticorpos Monoclonais Humanizados , Quimioterapia de Indução , Neoplasias Nasofaríngeas , Piridinas , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Quimioterapia de Indução/efeitos adversos , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Quimiorradioterapia/efeitos adversos
8.
Sci Rep ; 14(1): 4173, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378721

RESUMO

Glioblastoma is a highly aggressive and malignant type of brain cancer that originates from glial cells in the brain, with a median survival time of 15 months and a 5-year survival rate of less than 5%. Regulated cell death (RCD) is the autonomous and orderly cell death under genetic control, controlled by precise signaling pathways and molecularly defined effector mechanisms, modulated by pharmacological or genetic interventions, and plays a key role in maintaining homeostasis of the internal environment. The comprehensive and systemic landscape of the RCD in glioma is not fully investigated and explored. After collecting 18 RCD-related signatures from the opening literature, we comprehensively explored the RCD landscape, integrating the multi-omics data, including large-scale bulk data, single-cell level data, glioma cell lines, and proteome level data. We also provided a machine learning framework for screening the potentially therapeutic candidates. Here, based on bulk and single-cell sequencing samples, we explored RCD-related phenotypes, investigated the profile of the RCD, and developed an RCD gene pair scoring system, named RCD.GP signature, showing a reliable and robust performance in predicting the prognosis of glioblastoma. Using the machine learning framework consisting of Lasso, RSF, XgBoost, Enet, CoxBoost and Boruta, we identified seven RCD genes as potential therapeutic targets in glioma and verified that the SLC43A3 highly expressed in glioma grades and glioma cell lines through qRT-PCR. Our study provided comprehensive insights into the RCD roles in glioma, developed a robust RCD gene pair signature for predicting the prognosis of glioma patients, constructed a machine learning framework for screening the core candidates and identified the SLC43A3 as an oncogenic role and a prediction biomarker in glioblastoma.


Assuntos
Glioblastoma , Glioma , Morte Celular Regulada , Humanos , Glioblastoma/genética , Glioblastoma/terapia , Glioma/genética , Glioma/terapia , Prognóstico , Imunoterapia , Aprendizado de Máquina , Microambiente Tumoral , Sistemas de Transporte de Aminoácidos
9.
Quant Imaging Med Surg ; 14(2): 1971-1984, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38415120

RESUMO

Background: The solid component of subsolid nodules (SSNs) is closely associated with the invasiveness of lung adenocarcinoma, and its accurate assessment is crucial for selecting treatment method. Therefore, this study aimed to evaluate the accuracy of solid component size within SSNs measured on multiplanar volume rendering (MPVR) and compare it with the dimensions of invasive components on pathology. Methods: A pilot study was conducted using a chest phantom to determine the optimal MPVR threshold for the solid component within SSN, and then clinical validation was carried out by retrospective inclusion of patients with pathologically confirmed solitary SSN from October 2020 to October 2021. The radiological tumor size on MPVR and solid component size on MPVR (RSSm) and on lung window (RSSl) were measured. The size of the tumor and invasion were measured on the pathological section, and the invasion, fibrosis, and inflammation within SSNs were also recorded. The measurement difference between computed tomography (CT) and pathology, inter-observer and inter-measurement agreement were analyzed. Receiver operating characteristic (ROC) analysis and Bland-Altman plot were performed to evaluate the diagnostic efficiency of MPVR. Results: A total of 142 patients (mean age, 54±11 years, 39 men) were retrospectively enrolled in the clinical study, with 26 adenocarcinomas in situ, 92 minimally invasive adenocarcinomas (MIAs), and 24 invasive adenocarcinomas (IAs). The RSSl was significantly smaller than pathological invasion size with fair inter-measurement agreement [intraclass correlation coefficient (ICC) =0.562, P<0.001] and moderate interobserver agreement (ICC =0.761, P<0.001). The RSSm was significantly larger than pathological invasion size with the excellent inter-measurement agreement (ICC =0.829, P<0.001) and excellent (ICC =0.952, P<0.001) interobserver agreement. ROC analysis showed that the cutoff value of RSSm for differentiating adenocarcinoma in situ from MIA and MIA from IA was 1.85 and 6.45 mm (sensitivity: 93.8% and 95.5%, specificity: 85.7% and 88.2%, 95% confidence internal: 0.914-0.993 and 0.900-0.983), respectively. The positive predictive value-and negative predictive value of MPVR in predicting invasiveness were 92.8% and 100%, respectively. Conclusions: Using MPVR to predict the invasive degree of SSN had high accuracy and good inter-observer agreement, which is superior to lung window measurements and helpful for clinical decision-making.

10.
J Tradit Chin Med ; 44(1): 63-69, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38213240

RESUMO

OBJECTIVE: To explore the mechanism of the Chinese medicine Cigu Xiaozhi prescription (, CGXZ) in the treatment of the non-alcoholic fatty liver disease (NAFLD) by detoxification and phlegm-reducing, the effect of CGXZ prescription on ceramide-mediated lipid apoptosis in Hep G2 cells with NAFLD. METHODS: The experiment was randomly divided into 6 groups: normal control group, model group, CGXZ prescription medicated serum high, medium, and low dose groups, and pioglitazone positive control group. Using 500 µmol/L free fatty acid (FFA) mixture to induce Hep G2 cells to establish NAFLD cell model, respectively, with 2%, 4%, and 6% concentration of CGXZ prescription medicated serum intervention for 24 h. The changes in organelles and lipid droplet accumulation were observed under the electron microscope. Furthermore, TdT-mediated dUTP Nick-End Labeling method was used to assay hepatocyte apoptosis; Biochemical determination of glutamic-pyruvic transaminase, glutamic oxalacetic transaminase, triglycerides, and FFA levels in Hep G2 cells; the content of ceramide was determined by high-performance thin-layer chromatography. Finally, Western Blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine the protein and gene expression levels, such as inducible nitric oxide synthase (iNOS), nuclear factor κB (NF-κB), B cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). RESULTS: Under the electron microscope, the cells in the model group showed moderate-to-severe steatosis, and apoptotic bodies could be seen. The model group had greater improvements in the apoptosis rate (P < 0.01), and the levels of ceramide C2 and FFA in the cytoplasm (P < 0.01) than the normal control group. The protein expressions of NF-κB, iNOS, and Bax were significantly up-regulated (P < 0.05), while the Bcl-2 had no significant change (P > 0.05). Compared with the model group, the levels of ceramide C2 and FFA (P < 0.01), the protein expressions of NF-κB, iNOS, and Bax (P < 0.05) in the CGXZ prescription treatment group and pioglitazone positive control group were significantly decreased; Only the Bcl-2 protein was significantly up-regulated in the high-dose Chinese medicine group (P < 0.05). The down-regulation of Bax mRNA expression in each Chinese medicine treatment group was significantly better than in the pioglitazone positive control group (P < 0.01). CONCLUSIONS: The CGXZ prescription, formulated with the method of detoxification and phlegm, can inhibit lipoapoptosis in the NAFLD cell model by down-regulating the levels of ceramide C2 and FFA, which may be achieved by regulating ceramide/iNOS/NF-κB signaling pathway.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fígado , NF-kappa B/genética , NF-kappa B/metabolismo , Proteína X Associada a bcl-2/metabolismo , Ceramidas/metabolismo , Ceramidas/farmacologia , Ceramidas/uso terapêutico , Pioglitazona/metabolismo , Pioglitazona/farmacologia , Pioglitazona/uso terapêutico , Prescrições
11.
Acad Radiol ; 31(3): 833-843, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37487879

RESUMO

RATIONALE AND OBJECTIVES: The effectiveness and safety of hepatic arterial infusion chemotherapy (HAIC) or transarterial chemoembolization (TACE) for cases with single pseudo-capsuled hepatocellular carcinoma (pHCC), as well as their survival outcomes, were investigated. MATERIALS AND METHODS: A total of 196 cases with single pHCC (diameter >5 cm) receiving initial HAIC (n = 92) and TACE (n = 104) were enrolled. The propensity score match (PSM) approach based on Cox models was employed to tune any possible imbalance in treatment assignment. The overall survival (OS), objective response rate (ORR), progression-free survival (PFS), and partial response rate (PRR) of the subjects were investigated using the log-rank test. The independent risk factors for outcomes were investigated by univariate and multivariate analyses, and the results were analyzed using the Cox regression model. RESULTS: The median follow-up of the subjects was 22.3 months. After PSM, no significant difference was found in the OS of the HAIC and TACE groups (OS, 12.0 vs. 16.8 months; P = .267), while the median PFS of the TACE group was prolonged compared with the HAIC group (PFS, 5.7 vs. 2.8 months; P = .003). Moreover, PRR and ORR of the TACE group were prolonged compared with the HAIC group (PRR, 34.6% vs. 21.7%; P = .046; ORR, 35.6% vs. 21.7%; P = .033). The nomogram model showed high predictive accuracy and significant discrimination. CONCLUSION: TACE therapy could delay tumor progression compared with HAIC for cases with a single pHCC.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Quimioembolização Terapêutica/métodos , Resultado do Tratamento , Artéria Hepática/diagnóstico por imagem , Estudos Retrospectivos
12.
J Gene Med ; 26(1): e3572, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37525871

RESUMO

BACKGROUND: The physiological and immunological characteristics of the tumor microenvironment (TME) have a profound impact on the effectiveness of immunotherapy. The present study aimed to define the TME subtype of osteosarcoma according to the signatures representing the global TME of the tumor, as well as create a new prognostic assessment tool to monitor the prognosis, TME activity and immunotherapy response of patients with osteosarcoma. METHODS: The enrichment scores of 29 functional gene expression signatures in osteosarcoma samples were calculated by single sample gene set enrichment analysis (ssGSEA). TME classification of osteosarcoma was performed and a prognostic assessment tool was created based on 29 ssGSEA scores to comprehensively correlate them with TME components, immunotherapy efficacy and prognosis of osteosarcoma. RESULTS: Three TME subtypes were generated that differed in survival, TME activity and immunotherapeutic response. Four differentially expressed genes between TME subtypes were involved in the development of prognostic assessment tools. The established prognosis assessment tool had strong performance in both training and verification cohorts, could be effectively applied to the survival prediction of samples of different ages, genders and transfer states, and could well distinguish the TME status of different samples. CONCLUSIONS: The present study describes three different TME phenotypes in osteosarcoma, provides a risk stratification tool for osteosarcoma prognosis and TME status assessment, and provides additional information for clinical decision-making of immunotherapy.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Feminino , Masculino , Prognóstico , Microambiente Tumoral/genética , Osteossarcoma/diagnóstico , Osteossarcoma/genética , Osteossarcoma/terapia , Fenótipo , Imunoterapia , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/genética , Neoplasias Ósseas/terapia
13.
Biomed Pharmacother ; 170: 115954, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38039753

RESUMO

The potential of Ferrimagnetic vortex iron oxide nanoring-mediated mild magnetic hyperthermia (FVIO-MHT) in solid tumor therapy has been demonstrated. However, the impact of FVIO-MHT on the tumor microenvironment (TME) remains unclear. This study utilized single-cell transcriptome sequencing to examine the alterations in the TME in response to FVIO-MHT in breast cancer. The results revealed the cellular composition within the tumor microenvironment (TME) was primarily modified due to a decrease in tumor cells and an increased infiltration of myeloid cells. Subsequently, an enhancement in active oxygen (ROS) metabolism was observed, indicating oxidative damage to tumor cells. Interestingly, FVIO-MHT reprogrammed the macrophages' phenotypes, as evidenced by alterations in the transcriptome characteristics associated with both classic and alternative activated phenotypes. And an elevated level of ROS generation and oxidative phosphorylation suggested that activated phagocytosis and inflammation occurred in macrophages. Additionally, cell-cell communication analysis revealed that FVIO-MHT attenuated the suppression between tumor cells and macrophages by inhibiting phagocytic checkpoint and macrophage migration inhibitory factor signaling pathways. Inhibition of B2m, an anti-phagocytosis checkpoint, could promote macrophage-mediated phagocytosis and significantly inhibit tumor growth. These data emphasize FVIO-MHT may promote the antitumor capabilities of macrophages by alleviating the suppression between tumor cells and macrophages.


Assuntos
Neoplasias da Mama , Hipertermia Induzida , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Espécies Reativas de Oxigênio/farmacologia , Macrófagos , Fenômenos Magnéticos , Perfilação da Expressão Gênica , Microambiente Tumoral
14.
Anal Chem ; 95(51): 18760-18766, 2023 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-38078811

RESUMO

In separation science, precise control and regulation of the MOF stationary phase are crucial for achieving a high separation performance. We supposed that increasing the mass transfer resistance of MOFs with excessive porosity to achieve a moderate mass transfer resistance of the analytes is the key to conducting the MOF stationary phase with a high resolution. Three-dimensional UiO-67 (UiO-67-3D) and two-dimensional UiO-67 (UiO-67-2D) were chosen to validate this strategy. Compared with UiO-67-3D with overfast mass transfer and low retention, the reduced porosity of UiO-67-2D increased the mass transfer resistance of analytes in reverse, resulting in improved separation performance. Kinetic diffusion experiments were conducted to verify the difference in mass transfer resistance of the analytes between UiO-67-3D and UiO-67-2D. In addition, the optimization of the UiO-67-2D thickness for separation revealed that a moderate diffusion length of the analytes is more advantageous in achieving the equilibrium of absorption and desorption.

15.
Rev. latinoam. enferm. (Online) ; 31: e3926, ene.-dic. 2023. tab
Artigo em Espanhol | LILACS, BDENF | ID: biblio-1441996

RESUMO

Objetivo: examinar la relación entre éxito en la carrera y ambiente de trabajo con enfermeras actuantes en tecnología de reproducción asistida (TRA), e identificar factores que afectan su éxito en la carrera. Método: estudio transversal realizado en 53 centros de fertilidad de 26 provincias en la China Continental. Datos recolectados utilizando cuestionario de datos demográficos, un Cuestionario de Competencias de TRA para Enfermeras Especializadas, la Career-Success Scale (Escala de éxito profesional) y la Nursing Work Environment Scale (Escala del entorno de trabajo de enfermería). Se aplicó estadística inferencial y descriptiva. Resultados: 597 enfermeras actuantes en TRA participaron en nuestra encuesta, entregando 555 cuestionarios válidos. Los puntajes generales promedio de éxito en la carrera y ambiente de trabajo fueron 3,75 (desviación estándar, [DE]=1,01) y 3,42 (DE=0,77) respectivamente. Se observó fuerte correlación positiva entre éxito en la carrera y ambiente de trabajo (r=0,742; p<0,01). La regresión múltiple mostró que la concurrencia a conferencias académicas, atención psicológica, desarrollo profesional, apoyo y cuidado, salario y bienestar constituyeron factores significantes con influencia en el éxito en la carrera. Conclusión: la concurrencia a conferencias académicas, atención psicológica y ambiente de trabajo guardan relación positiva con el éxito en la carrera. Los gestores deberían considerar formas de abordar tales factores.


Objective: to examine the relationship between career success and work environment of nurses who practice in assisted reproductive technology and to identify factors that affect career success. Method: a cross-sectional study conducted in 53 fertility centres in 26 provinces in mainland China. Data were collected using a demographic data questionnaire, a specialised nursing competence questionnaire, the Career-Success Scale, and the Nursing Work Environment Scale. Descriptive and inferential statistics were applied. Results: 597 assisted reproductive technology nurses participated in our survey, and 555 valid questionnaires were collected. Theoverall mean scores for career success and work environment were 3.75 [standard deviation (SD) = 1.01] and 3.42 (SD = 0.77) respectively. There was a strong positive correlation between career success and work environment (r = 0.742, p < 0.01). Multiple regression showed that attending academic conferences, psychological care, professional development, support and care, salary, and welfare were significant factors that influence career success. Conclusion: attending academic conferences, psychological care, and work environment are positively related to career success. Administrators should consider ways to address these factors.


Objetivo: examinar a relação entre o sucesso profissional e o ambiente de trabalho de enfermeiros da área de tecnologia de reprodução assistida e identificar os fatores que afetaram tal sucesso. Método: estudo transversal conduzido em 53 centros de fertilidade em 26 províncias da China Continental. Os dados foram coletados por meio de um questionário demográfico, um questionário sobre competências de enfermagem especializada em tecnologias de reprodução assistida, da Career-Success Scale (Escala de Sucesso Profissional) e da Nursing Work Environment Scale (Escala do Ambiente de Trabalho na Enfermagem). Aplicaram-se análises de estatística descritiva e inferencial. Resultados: participaram do estudo 597 enfermeiros da área de tecnologia de reprodução assistida, e 555 questionários válidos foram coletados. As pontuações globais médias para o sucesso profissional e o ambiente de trabalho foram 3,75 [desvio padrão (DP) = 1,01] e 3,42 (DP = 0,77), respectivamente. Verificou-se forte correlação positiva entre o sucesso profissional e o ambiente de trabalho (r = 0,742; p < 0,01). A análise de regressão múltipla mostrou que a participação em eventos acadêmicos, a assistência psicológica, o desenvolvimento profissional, o apoio e os cuidados, e o salário e o bem-estar foram fatores que influenciaram significativamente o sucesso profissional. Conclusão: a participação em eventos acadêmicos, a assistência psicológica e o ambiente de trabalho mostraram correlação positiva com o sucesso profissional. Os gestores deveriam considerar formas de abordar esses fatores.


Assuntos
Humanos , China , Estudos Transversais , Técnicas de Reprodução Assistida , Satisfação no Emprego , Enfermeiras e Enfermeiros
16.
Urolithiasis ; 52(1): 1, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37966550

RESUMO

To compare the safety and the efficacy of simultaneous bilateral surgery in the oblique overriding position versus staging surgery in the treatment of bilateral renal calculi. A total of 46 patients with bilateral renal stones from May 2019 to January 2022 in our center were retrospectively analyzed, including 29 males and 17 females, with a mean age of 48 ± 13.6 years, body mass index of 24.6 ± 2.3 kg/m2, and uneven size of bilateral renal stones, with a mean diameter of 29.5 ± 9.1 mm on the side with the larger kidney stones (PCNL) and a mean diameter of 13.1 ± 3.2 mm on the side with the smaller kidney stones. The patients were divided into two groups for simultaneous and stepwise bilateral endoscopic surgery, and the operative time, anesthesia time, postoperative hemoglobin, blood creatinine, postoperative VAS pain score, Clavien complication rating, average hospital stay, and stone removal rate at one month after surgery were evaluated in both groups. The simultaneous group outperformed the other group in anesthesia time, operative time, VAS score, and mean number of days in the hospital, and there were no significant differences between the two groups in postoperative hemoglobin drop values, hematocrit elevation values, Clavien complication ratings, and stone clearance rate at one month. Both simultaneous surgery and staging surgery were safe and effective. Simultaneous surgery can effectively shorten the operation and anesthesia time, and reduce the postoperative pain and hospital days of patients while ensuring similar stone clearance rates.


Assuntos
Anestesia , Cálculos Renais , Feminino , Masculino , Humanos , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Cálculos Renais/cirurgia , Dor Pós-Operatória , Hemoglobinas
17.
Materials (Basel) ; 16(21)2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37959561

RESUMO

In order to study the torsional performance of steel tube concrete after reinforcement with a carbon-fiber-reinforced polymer (CFRP), the mechanical properties of 18 specimens were studied from both experimental and finite element perspectives. The T-θ curve and τ-γ curve of the specimen were measured in the experiment, and the failure mode of the specimen was analyzed. Subsequently, a reasonable finite element model was established using ABAQUS software, and the variation in various parameters surrounding the performance of the specimen was analyzed. Based on the experimental and finite element results, a formula for calculating the bearing capacity of the specimen was established. According to both the experimental and numerical results, the torsional bearing capacity of C-CF-CFRP-ST, defined as the torque endured by the specimen with maximum shear strain, was determined to be 15,000 µÎµ, together with its corresponding calculation formula. After the test, it was demonstrated that the main components of the concrete-filled CFRP-steel tube composite material-the steel tube and the concrete-could be used as reusable resources.

18.
Polymers (Basel) ; 15(22)2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38006175

RESUMO

Temperature-sensitive carboxylated cellulose nanocrystals/N-isopropyl acrylamide aerogels (CCNC-NIPAMs) were developed as novel pesticide-controlled release formulas. Ammonium persulfate (APS) one-step oxidation was used to prepare bagasse-based CCNCs, and then the monomer N-isopropyl acrylamide (NIPAM) was successfully introduced and constructed into the temperature-sensitive CCNC-NIPAMs through polymerization. The results of the zeta potential measurement and Fourier infrared transform spectrum (FTIR) show that the average particle size of the CCNCs was 120.9 nm, the average surface potential of the CCNCs was -34.8 mV, and the crystallinity was 62.8%. The primary hydroxyl group on the surface of the CCNCs was replaced by the carboxyl group during oxidation. The morphology and structure of CCNC-NIPAMs were characterized via electron microscopy, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), compression performance, porosity analysis, and thermogravimetric (TG) analysis. The results demonstrate that CCNC-NIPAM has a high porosity and low density, as well as good thermal stability, which is conducive to loading and releasing pesticides. In the swelling, drug loading, and controlled release process, the CCNC-NIPAM exhibited significant temperature sensitivity. Under the same NIPAM reaction amount, the equilibrium swelling rate of the CCNC-NIPAM first increased and then decreased with increasing temperature, and the cumulative drug release ratio of the CCNC-NIPAM at 39 °C was significantly higher than that at 25 °C. The loading efficiency of the CCNC-NIPAM on the model drug thiamethoxam (TXM) was up to 23 wt%, and the first-order model and Korsmyer-Peppas model could be well-fitted in the drug release curves. The study provides a new method for the effective utilization of biomass and pesticides.

19.
Front Pediatr ; 11: 1236239, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37830057

RESUMO

DGUOK deficiency has primarily been associated with lethal hepatic failure with or without hypotonia, nystagmus, and psychomotor retardation, features typical of mitochondrial disease. A study in 3 Turkish children identified homozygosity for a variant in DGUOK as associated with idiopathic non-cirrhotic portal hypertension (INCPH). However, no further instances of INCPH associated with DGUOK variants have been reported. We here describe a fourth patient with DGUOK variants and childhood-onset INCPH, a 12-year-old Han Chinese boy, reporting clinical manifestations, histopathologic findings, and results of genetic studies. The child presented with hepatosplenomegaly; portal hypertension and hypersplenism were found. Vascular changes with hepatic fibrosis (Scheuer score 3) were observed on liver biopsy. Whole-exome sequencing and family analyses revealed compound heterozygosity for the DGUOK (NM_080916.3) variants c.778_781dup, (p.Thr261Serfs*28) and c.831_832del, (p.*278Thrfs*9) in the proband. These observations support ascription of instances of INCPH in children to variation in DGUOK.

20.
J Med Chem ; 66(20): 14221-14240, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37820326

RESUMO

Invasive fungal infections (IFIs) such as cryptococcal meningitis (CM) remain a serious health issue worldwide due to drug resistance closely related to biofilm formation. Unfortunately, available antifungal drugs with ideal safety and promising potency are still lacking; thus, the research of new candidate and therapeutic approach is urgently needed. As an important gas messenger molecule, nitric oxide (NO) shows vital inhibition on various microorganism biofilms. Hence, three series of novel NO-donating azole derivatives were designed and synthesized, and the in vitro antifungal activity as well as the mechanism of action was investigated. Among them, 3a and 3e displayed excellent antifungal activity against Cryptococcus neoformans and biofilm depending on the release of NO. Moreover, a more stable analogue 3h of 3a demonstrated markedly anti-CM effects via intranasal dropping, avoiding the first-pass effects and possessing a better brain permeability bypass blood-brain barrier. These results present a promising antifungal candidate and intranasal dropping approach for the treatment of CM, warranting further studies.


Assuntos
Criptococose , Cryptococcus neoformans , Meningite Criptocócica , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Doadores de Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/uso terapêutico , Azóis/farmacologia , Criptococose/tratamento farmacológico , Meningite Criptocócica/tratamento farmacológico , Testes de Sensibilidade Microbiana
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA