Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 200
Filtrar
1.
EClinicalMedicine ; 75: 102806, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39281099

RESUMO

Background: In the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses. Methods: This single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I-IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50 mg/m2 of paclitaxel and 25 mg/m2 of cisplatin for five cycles), concurrent radiotherapy (50.4 Gy in 28 fractions), and toripalimab (240 mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170). Findings: With a median follow-up of 44.3 months (IQR 40.8-46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9-62.8) and 35.7% (95% CI 23.8-53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR] = 13.73, 95% CI 4.43-42.54, P < 0.0001) and PFS (HR = 32.08, 95% CI 8.57-120.10, P < 0.0001). Disease recurrence occurred in 23 of 42 patients (55%), with recurrences being earlier and more frequent in the non-CR group compared to the CR group. Patients experiencing irAEs showed a significantly higher CR rate (72% vs. 39%, P = 0.082) and better PFS (HR = 0.43, 95% CI 0.19-0.93, P = 0.027) than those without irAEs. GON4L mutation was associated with a lower incidence of irAEs (P = 0.036). Interpretation: The updated survival outcomes confirmed the efficacy of toripalimab plus definitive CRT in locally advanced ESCC. Moreover, the development of irAEs may predict a more favourable prognosis. Funding: National Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Sci-Tech Project Foundation of Guangzhou.

2.
Food Funct ; 15(19): 9954-9971, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39264166

RESUMO

Background: Probiotics, prebiotics, and synbiotics have been suggested as a possible therapy for non-alcoholic fatty liver disease (NAFLD). However, their efficacy in improving blood glucose levels in NAFLD patients remains uncertain. Objective: The aim of this study was to assess the effects of supplementation with probiotics, prebiotics, or synbiotics on fasting blood glucose (FBG) levels in NAFLD patients. Methods: We searched PubMed, Web of Science, and Google Scholar for relevant trials published up to March 2024. Out of 3369 identified studies, 24 randomized controlled trials (RCTs) were included. Results: Probiotic, prebiotic, or synbiotic supplementation substantially reduced FBG (n = 23; standard mean difference (SMD) = -0.17; 95% confidence interval (CI): -0.30, -0.03; P = 0.02), fasting insulin levels (n = 12; SMD = -0.28; 95% CI: -0.49, -0.07; P = 0.01), and homeostatic model assessment for insulin resistance (HOMA-IR; n = 14; SMD = -0.28; 95% CI: -0.47, -0.09; P = 0.004). However, glycosylated hemoglobin (HbA1c; n = 3; SMD = -0.17; 95% CI: -0.48, 0.13; P = 0.27) was not significantly affected. The FBG-decreasing effect diminished as the body mass index (BMI) of volunteers increased in the baseline. Additionally, the number of probiotic strains and geographic region were shown to significantly affect FBG levels. Conclusion: This meta-analysis indicates that supplementation with probiotics, prebiotics, or synbiotics may aid in controlling glucose homeostasis in patients with NAFLD.


Assuntos
Glicemia , Hepatopatia Gordurosa não Alcoólica , Prebióticos , Probióticos , Ensaios Clínicos Controlados Aleatórios como Assunto , Simbióticos , Humanos , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Simbióticos/administração & dosagem , Probióticos/uso terapêutico , Probióticos/administração & dosagem , Glicemia/metabolismo , Homeostase , Resistência à Insulina , Feminino , Masculino , Adulto , Pessoa de Meia-Idade
4.
Sci Rep ; 14(1): 22604, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39349553

RESUMO

The stability-related asymmetry in roots, trunk, and crown is always found as a typical effect of biomechanical design under heterogeneous stimulus environment. However, it appears to be a conflict between the biomechanical principle and the source-sink distance of nutrient allocation strategies when the orientational asymmetry occurs. Adaptive growth strategies associated with biomass and nutrient allocation remain to be explored. This study used both the minirhizotron and harvest methods to test the effect of trunk inclination of camphor trees (Cinnamomum camphora) and found that the asymmetry coefficient of root biomass was - 0.29, showing more root biomass distributed on the other side of trunk inclination. This side had larger surface area and volume of fine roots, the smaller in diameter and the larger in length of the first level roots, higher leaf total nitrogen (TN) and slightly higher root TN content, higher activities of antioxidant enzymes SOD, POD, and CAT in leaves, and lower soluble sugar and protein. The biomass, morphological and physiological characteristics suggest that trees may follow both the biomechanical design and source-sink distance of nutrient allocation strategies. The research results expand the connotation of root-shoot balance in the orientational allocation of biomass and physiological responses.


Assuntos
Biomassa , Cinnamomum camphora , Folhas de Planta , Raízes de Plantas , Cinnamomum camphora/metabolismo , Cinnamomum camphora/crescimento & desenvolvimento , Raízes de Plantas/crescimento & desenvolvimento , Raízes de Plantas/metabolismo , Raízes de Plantas/anatomia & histologia , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Nitrogênio/metabolismo , Adaptação Fisiológica , Árvores/crescimento & desenvolvimento
5.
Int J Biol Macromol ; 276(Pt 2): 133940, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39025179

RESUMO

In this work, the hydroxypropyl-ß-cyclodextrin (HP-ß-CD)/Epicatechin (EC) clathrate compounds were rapidly prepared based on an ultrasound-mediated method, and Polycaprolactone (PCL)/Locust bean gum (LBG) nanofibers loaded clathrate compounds were fabricated by electrostatic spinning (ELS) for fruit packaging. The results of infrared spectrum and crystal type analysis proved that clathrate compounds were successfully prepared. With the addition of clathrate compounds, the diameter of fibers increased from 553.43 to 1273.47 nm, and hydrogen bonds were formed between clathrate compounds and fibrous membranes, which improved the thermal stability, reduced the crystallinity, and enhanced the hydrophilicity and gas permeability of fibrous membranes. The fibrous membranes indicated sustained release of EC for 240 h, retaining the activity of EC and demonstrating good bacteriostatic ability in vitro and in vivo. The test results showed that the antibacterial fibrous membranes prepared in this work have a positive application prospect for fruit packaging.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina , Embalagem de Alimentos , Frutas , Galactanos , Mananas , Nanofibras , Gomas Vegetais , Poliésteres , Gomas Vegetais/química , Galactanos/química , Embalagem de Alimentos/métodos , Nanofibras/química , Poliésteres/química , Frutas/química , Mananas/química , 2-Hidroxipropil-beta-Ciclodextrina/química , Antibacterianos/farmacologia , Antibacterianos/química , Interações Hidrofóbicas e Hidrofílicas
6.
Anal Chim Acta ; 1315: 342822, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38879216

RESUMO

In this study, a novel electrochemiluminescence (ECL) biosensor was developed to detect microRNA-21 (miRNA-21) with high sensitivity by leveraging the combined mechanisms of resonance energy transfer (RET) and surface plasmon coupling (SPC). Initially, the glassy carbon electrode (GCE) were coated with Cu-Zn-In-S quantum dots (CZIS QDs), known for their defect-related emission suitable for ECL sensing. Subsequently, a hairpin DNA H3 with gold nanoparticles (Au NPs) attached at the end was modified over the surface of the quantum dots. The Au NPs could effectively quench the ECL signals of CZIS QDs via RET. Further, a significant amount of report DNA was generated through the action of a 3D DNA walker. When the report DNA opened H3-Au NPs, the hairpin structure experienced a conformational change to a linear shape, increasing the gap between the CZIS QDs and the Au NPs. Consequently, the localized surface plasmon resonance ECL (LSPR-ECL) effect replaced ECL resonance energy transfer (ECL-RET). Moreover, the report DNA was released following the addition of H4-Au NPs, resulting in the formation of Au dimers and a surface plasma-coupled ECL (SPC-ECL) effect that enhanced the ECL intensity to 6.97-fold. The integration of new ECL-RET and SPC-ECL biosensor accurately quantified miRNA-21 concentrations from 10-8 M to 10-16 M with a limit of detection (LOD) of 0.08 fM, as well as successfully applied to validate human serum samples.


Assuntos
Técnicas Biossensoriais , DNA , Técnicas Eletroquímicas , Medições Luminescentes , MicroRNAs , Pontos Quânticos , Ressonância de Plasmônio de Superfície , MicroRNAs/análise , MicroRNAs/sangue , Humanos , Técnicas Eletroquímicas/métodos , Técnicas Biossensoriais/métodos , DNA/química , Pontos Quânticos/química , Ressonância de Plasmônio de Superfície/métodos , Medições Luminescentes/métodos , Ouro/química , Limite de Detecção , Transferência de Energia , Nanopartículas Metálicas/química
7.
J Pharm Biomed Anal ; 248: 116269, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-38906072

RESUMO

Corrections to the article based on comments published by Dr Acree, various models, including the modified Apelblat model, the λh model, the Jouyban-Acree model, the SUN model and the CNIBS/R-K model, recalculated, obtained new parameters and relative absolute percentage deviations.


Assuntos
Solubilidade , Solventes , Termodinâmica , Solventes/química , Modelos Químicos , Fosforilcolina/análogos & derivados , Fosforilcolina/química
8.
Br J Cancer ; 131(4): 709-717, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38937623

RESUMO

BACKGROUND: A phase II trial (EC-CRT-001) demonstrated the promising efficacy of combining toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) for locally advanced oesophageal squamous cell carcinoma (ESCC). Biomarkers are key to identifying patients who may benefit from this therapeutic approach. METHODS: Of the 42 patients with ESCC who received toripalimab combined with definitive CRT, 37 were included in this analysis. Baseline assessments included PET/CT metabolic parameters (SUVmax, SUVmean, SUVpeak, MTV, and TLG), RNA sequencing of tumour biopsies to quantify the tissue mutational burden (TMB), and multiplex immunofluorescence staining to estimate immune cell infiltration in the tumour microenvironment (TME). Frozen neoplastic samples were procured for RNA sequencing to further explore the immune-related TME. RESULTS: Among the 37 patients, high baseline SUVmax (≥12.0; OR = 6.5, 95% CI 1.4-48.2, p = 0.032) and TLG (≥121.8; OR = 6.8, 95% CI 1.6-33.5, p = 0.012) were significantly correlated with lower complete response rates. All five PET/CT parameters were notably associated with overall survival; only SUVmax and TLG were associated with a significantly worse progression-free survival. A trend towards an inverse correlation was observed between SUVmax and TMB (R = -0.33, p = 0.062). PD-1 + CD8 + T cell infiltration was negatively correlated with MTV (R = -0.355, p = 0.034) and TLG (R = -0.385, p = 0.021). Moreover, RNA sequencing revealed that the high TLG subgroup exhibited low immune cell infiltration, indicating an immunosuppressive landscape. CONCLUSIONS: High baseline SUVmax and TLG might predict poorer treatment response and worse survival in patients with ESCC undergoing immunotherapy combined with CRT. In addition, high PET/CT metabolic parameters, particularly TLG, were correlated with an immunosuppressive TME, which warrants further exploration.


Assuntos
Quimiorradioterapia , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Imunoterapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Microambiente Tumoral , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/imunologia , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/patologia , Masculino , Feminino , Quimiorradioterapia/métodos , Pessoa de Meia-Idade , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/imunologia , Idoso , Prognóstico , Imunoterapia/métodos , Anticorpos Monoclonais Humanizados/uso terapêutico , Adulto
9.
Proc Natl Acad Sci U S A ; 121(24): e2319679121, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38830106

RESUMO

Whole-genome duplication (WGD; i.e., polyploidy) and chromosomal rearrangement (i.e., genome shuffling) significantly influence genome structure and organization. Many polyploids show extensive genome shuffling relative to their pre-WGD ancestors. No reference genome is currently available for Platanaceae (Proteales), one of the sister groups to the core eudicots. Moreover, Platanus × acerifolia (London planetree; Platanaceae) is a widely used street tree. Given the pivotal phylogenetic position of Platanus and its 2-y flowering transition, understanding its flowering-time regulatory mechanism has significant evolutionary implications; however, the impact of Platanus genome evolution on flowering-time genes remains unknown. Here, we assembled a high-quality, chromosome-level reference genome for P. × acerifolia using a phylogeny-based subgenome phasing method. Comparative genomic analyses revealed that P. × acerifolia (2n = 42) is an ancient hexaploid with three subgenomes resulting from two sequential WGD events; Platanus does not seem to share any WGD with other Proteales or with core eudicots. Each P. × acerifolia subgenome is highly similar in structure and content to the reconstructed pre-WGD ancestral eudicot genome without chromosomal rearrangements. The P. × acerifolia genome exhibits karyotypic stasis and gene sub-/neo-functionalization and lacks subgenome dominance. The copy number of flowering-time genes in P. × acerifolia has undergone an expansion compared to other noncore eudicots, mainly via the WGD events. Sub-/neo-functionalization of duplicated genes provided the genetic basis underlying the unique flowering-time regulation in P. × acerifolia. The P. × acerifolia reference genome will greatly expand understanding of the evolution of genome organization, genetic diversity, and flowering-time regulation in angiosperms.


Assuntos
Evolução Molecular , Genoma de Planta , Filogenia , Poliploidia , Cromossomos de Plantas/genética , Duplicação Gênica
10.
Biosens Bioelectron ; 261: 116495, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38878699

RESUMO

In this study, we have for the first time constructed a ratiometric ECL biosensor for the ultrasensitive detection of microRNAs (miRNAs) using gold nanoparticles (Au NPs) to trigger both the low-potential emission from conjugated polymer poly(9,9-dioctylfluorene-2,7-diyl) dots (PFO Pdots) and the LSPR-ECL effect with sulfur-doped boron nitride quantum dots (S-BN QDs). PFO Pdots were first applied to the Au NPs-modified electrode, followed by covalent binding to capture the hairpin H1. Immediately thereafter, a small amount of miRNA-141 was able to generate a large amount of output DNA (OP) by traversing the target cycle. OP, H3-S-BN QDs, and H4-glucose oxidase (H4-GOD) were then added sequentially to the Au NPs-modified electrode surface, and the hybridization chain reaction (HCR) was initiated. This resulted in the introduction of a large amount of GOD into the system, which catalyzed the in situ formation of the co-reactant hydrogen peroxide (H2O2) from the substrate glucose. Due to the electron transfer effect, the production of H2O2 led to the ECL quenching of PFO Pdots. Meanwhile, H2O2 served as a co-reactant of S-BN QDs, resulting in strong ECL emission of S-BN QDs at the cathode. Furthermore, the cathodic ECL intensity of S-BN QDs was further enhanced by an LSPR-ECL mechanism between Au NPs and S-BN QDs. By measuring the ratio of ECL intensities at two excitation potentials, this approach could provide sensitive and reliable detection of miRNA-141 in the range of 0.1 fM ∼10 nM, with a detection limit of 0.1 fM.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Ouro , Limite de Detecção , Medições Luminescentes , Nanopartículas Metálicas , MicroRNAs , Pontos Quânticos , Técnicas Biossensoriais/métodos , Ouro/química , MicroRNAs/análise , Nanopartículas Metálicas/química , Pontos Quânticos/química , Técnicas Eletroquímicas/métodos , Humanos , Medições Luminescentes/métodos , Fluorenos/química , Glucose Oxidase/química , Peróxido de Hidrogênio/química
11.
Spectrochim Acta A Mol Biomol Spectrosc ; 317: 124404, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38723465

RESUMO

Peroxynitrite is one of the important reactive oxygen species in the human body and is closely related to the physiological and pathological processes of many diseases. Therefore, the development of probes to detect peroxynitrite is important for diagnostic and pathologic studies of many diseases. In this work, a ratiometric probe was designed using benzopyran as the recognition site, and the sensitivity and selectivity of the probe were tuned by modification of substituents on benzopyran. Upon reaction with peroxynitrite, the color of the solution changes to the naked eye (from blue to yellow), and the fluorescence changes from red to blue. The probe SJ has the advantages of large Stokes shift (237 nm), fast response (≤10 s), wide linear range, good selectivity, low detection line (21.3 nm), and low cytotoxicity. Probe SJ has been successfully used for bioimaging of endogenous and exogenous peroxynitrite.


Assuntos
Corantes Fluorescentes , Ácido Peroxinitroso , Espectrometria de Fluorescência , Ácido Peroxinitroso/análise , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Humanos , Animais , Benzopiranos/química , Camundongos , Limite de Detecção
12.
J Clin Nurs ; 2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38798026

RESUMO

AIM: To synthesize available evidence about core competencies for nurses engaged in palliative care. DESIGN: A scoping review conducted according to the framework from Joanna Briggs Institute. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist was adopted to report this scoping review. The PubMed, Web of Science, Embase, ScienceDriect, CNKI, WangFang, VIP and Sinomed databases were used to systematically search for published studies from their inception to December 2023. Two researchers independently screened and selected relevant studies and performed the data charting. RESULTS: Twenty-six studies were included in this scoping review. Among these, 14 studies identified core competency assessment instruments among nurses engaged in palliative care, with the Palliative Care Core Competence Questionnaire was used most frequently; 13 studies investigated the status of core competencies of nurses engaged in palliative care, the majority of included studies indicated that nurse's core competencies were at moderate levels; 11 studies explored the factors influencing the core competencies of the nurses engaged in palliative care, which were classified as sociodemographic-related factors, palliative care education-related factors, death attitude, palliative care practice-related experience and others. CONCLUSION: This scoping review offers a comprehensive overview of the current landscape of core competencies among nurses in palliative care. Findings suggested that the clinical nursing leaders need to develop tailored strategies and interventions to address specific factors and promote the continuous development of nurses' competencies in palliative care. RELEVANCE TO CLINICAL PRACTICE: Core competency assessment instruments equip nurses and healthcare organizations with a range of validated tools for evaluating their proficiency in palliative care. Targeted core competency enhancement programmes need to be developed to foster a nursing workforce better equipped to improve the quality of life of end-of-life patients and their families. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

13.
Anal Chem ; 96(15): 5852-5859, 2024 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-38556977

RESUMO

A multicolor electrochemiluminescence (ECL) biosensor based on a closed bipolar electrode (BPE) array was proposed for the rapid and intuitive analysis of three prostate cancer staging indicators. First, [Irpic-OMe], [Ir(ppy)2(acac)], and [Ru(bpy)3]2+ were applied as blue, green, and red ECL emitters, respectively, whose mixed ECL emission colors covered the whole visible region by varying the applied voltages. Afterward, we designed a simple Mg2+-dependent DNAzyme (MNAzyme)-driven tripedal DNA walker (TD walker) to release three output DNAs. Immediately after, three output DNAs were added to the cathodic reservoirs of the BPE for incubation. After that, we found that the emission colors from the anode of the BPE changed as a driving voltage of 8.0 V was applied, mainly due to changes in the interfacial potential and faradaic currents at the two poles of the BPE. Via optimization of the experimental parameters, cutoff values of such three indicators at different clinical stages could be identified instantly with the naked eye, and standard precision swatches with multiple indicators could be prepared. Finally, in order to precisely determine the prostate cancer stage, the multicolor ECL device was used for clinical analysis, and the resulting images were then compared with standard swatches, laying the way for accurate prostate cancer therapy.


Assuntos
Técnicas Biossensoriais , Neoplasias da Próstata , Masculino , Humanos , Medições Luminescentes/métodos , Fotometria , Neoplasias da Próstata/diagnóstico , Antígeno Prostático Específico , DNA , Técnicas Biossensoriais/métodos , Eletrodos , Técnicas Eletroquímicas/métodos
14.
Theranostics ; 14(6): 2379-2395, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646644

RESUMO

Background: It is poorly understood what cellular types participate in ductular reaction (DR) and whether DR facilitates recovery from injury or accelerates hepatic fibrosis. The aim of this study is to gain insights into the role of hepatic progenitor cell (HPC)-originated DR during fibrotic progression. Methods: DR in liver specimens of PBC, chronic HBV infection (CHB) or NAFLD, and four rodent fibrotic models by different pathogenic processes was evaluated. Gli1 expression was inhibited in rodent models or cell culture and organoid models by AAV-shGli1 or treating with GANT61. Results: Severity of liver fibrosis was positively correlated with DR extent in patients with PBC, CHB or NAFLD. HPCs were activated, expanded, differentiated into reactive cholangiocytes and constituted "HPC-originated DR", accompanying with exacerbated fibrosis in rodent models of HPC activation & proliferation (CCl4/2-AAF-treated), Μdr2-/- spontaneous PSC, BDL-cholestatic fibrosis or WD-fed/CCl4-treated NASH-fibrosis. Gli1 expression was significantly increased in enriched pathways in vivo and in vitro. Enhanced Gli1 expression was identified in KRT19+-reactive cholangiocytes. Suppressing Gli1 expression by administration of AAV-shGli1 or GANT61 ameliorated HPC-originated DR and fibrotic extent. KRT19 expression was reduced after GANT61 treatment in sodium butyrate-stimulated WB-F344 cells or organoids or in cells transduced with Gli1 knockdown lentiviral vectors. In contrast, KRT19 expression was elevated after transducing Gli1 overexpression lentiviral vectors in these cells. Conclusions: During various modes of chronic injury, Gli1 acted as an important mediator of HPC activation, expansion, differentiation into reactive cholangiocytes that formed DR, and subsequently provoked hepatic fibrogenesis.


Assuntos
Proteínas Hedgehog , Cirrose Hepática , Transdução de Sinais , Células-Tronco , Proteína GLI1 em Dedos de Zinco , Animais , Feminino , Humanos , Masculino , Camundongos , Ratos , Diferenciação Celular , Modelos Animais de Doenças , Proteínas Hedgehog/metabolismo , Hepatite B Crônica/metabolismo , Hepatite B Crônica/patologia , Hepatite B Crônica/complicações , Fígado/patologia , Fígado/metabolismo , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Camundongos Endogâmicos C57BL , Piridinas/farmacologia , Pirimidinas/farmacologia , Células-Tronco/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteína GLI1 em Dedos de Zinco/genética
15.
Int J Biol Macromol ; 268(Pt 2): 131787, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38657939

RESUMO

Chitin oligosaccharides (CTOS) possess potential applications in food, medicine, and agriculture. However, lower mass transfer and catalytic efficiency are the main kinetic limitations for the production of CTOS from shrimp shell waste (SSW) and crystalline chitin. Chemical or physical methods are usually used for pretreatment to improve chitinase hydrolysis efficiency, but this is not eco-friendly and cost-effective. To address this challenge, a chitinase nanoreactor with the liquid-solid system (BcChiA1@ZIF-8) was manufactured to boost the one-step degradation of SSW and crystalline chitin. Compared with free enzyme, the catalytic efficiency of BcChiA1@ZIF-8 on colloidal chitin was significantly improved to 142 %. SSW and crystalline chitin can be directly degraded by BcChiA1@ZIF-8 without any pretreatments. The yield of N, N'-diacetylchitobiose [(GlcNAc)2] from SSW and N-acetyl-D-glucosamine (GlcNAc) from crystalline chitin was 2 times and 3.1 times than that of free enzyme, respectively. The reason was that BcChiA1@ZIF-8 with a liquid-solid system enlarged the interface area, increased the collision frequency between enzyme and substrate, and improved the large-substrates binding activity of chitinase. Moreover, the biphasic system exhibited excellent stability, and the design showed universal applicability. This strategy provided novel guidance for other polysaccharide biosynthesis and the conversion of environmental waste into carbohydrates.


Assuntos
Exoesqueleto , Quitina , Quitinases , Oligossacarídeos , Quitina/química , Quitina/metabolismo , Animais , Quitinases/metabolismo , Quitinases/química , Oligossacarídeos/química , Exoesqueleto/química , Hidrólise , Reatores Biológicos , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Crustáceos , Cinética , Resíduos , Penaeidae/enzimologia
16.
Biosens Bioelectron ; 253: 116162, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437748

RESUMO

An electrochemiluminescence (ECL) biosensor with a pair of new ECL emitters and a novel sensing mechanism was designed for the high-sensitivity detection of microRNA-141 (miRNA-141). Sulfur-doped boron nitrogen quantum dots (S-BN QDs) were initially employed to modify the cathode of the bipolar electrode (BPE), while the anode reservoir was [Ir(dfppy)2(bpy)]PF6/TPrA system. The next step involved attaching H1-bound ultra-small WO3-x nanodots (WO3-x NDs) to the S-BN QDs-modified BPE cathode via DNA hybridization. A strong surface plasmon coupling (SPC) effect was observed between S-BN QDs and WO3-x NDs, which allowed for the enhancement of the red and visible ECL emission from S-BN QDs. After target-induced cyclic amplification to produce abundant Zn2+ and Au NPs-DNA3-Au NPs (Au NPs-S3-Au NPs), Zn2+ could cleave DNA at a nucleotide sequence-specific recognition site to release the WO3-x NDs, resulting in the first diminution of cathode ECL signal and the first enhancement of anode ECL signal. Moreover, the ECL signal at cathode decreased for the second time and the emission of [Ir(dfppy)2(bpy)]PF6 was continuously enhanced after the introduction of Au nanoparticles-S3-Au nanoparticles on the cathode surface. Our sensing mode with a dual "on-off" signal conversion strategy shows a good detection capability for miRNAs ranging from 10-17 to 10-10 M, with a limit of detection (LOD) as low as 10-17 M, which has great application potential in biomedical research and clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , MicroRNAs , Ouro , Boro , Transferência de Energia , Nitrogênio , Enxofre , DNA
17.
Nat Commun ; 15(1): 1919, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429311

RESUMO

The combination of toripalimab (an anti-PD-1 antibody) with definitive chemoradiotherapy (CRT) demonstrated encouraging efficacy against locally advanced esophageal squamous cell carcinoma (ESCC) in the EC-CRT-001 phase II trial (NCT04005170). The primary endpoint of this trial was the clinical complete response rate (cCR), and the secondary endpoints included overall survival (OS), progression-free survival (PFS), duration of response, and quality of life. The exploratory analyses of EC-CRT-001 include exploring the role of circulating tumor DNA (ctDNA) and blood-based tumor mutational burden (bTMB) in predicting the response and survival. In total, 118 blood and 35 tissue samples from 42 enrolled patients were included in the analyses. We found that ctDNA-negative patients achieved a higher cCR compared to those with detectable ctDNA during CRT (83%, 19/23 vs. 39%, 7/18; p = 0.008) or post-CRT (78%, 21/27 vs. 30%, 3/10; p = 0.017). Patients with detectable ctDNA during CRT had shorter PFS (p = 0.014). Similarly, patients with post-CRT detectable ctDNA had a significantly shorter PFS (p = 0.012) and worse OS (p = 0.004). Moreover, patients with high bTMB levels during CRT had prolonged OS (p = 0.027). In conclusion, ctDNA and bTMB have the potential to predict treatment efficacy and survival in ESCC treated with CRT and immunotherapy.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/terapia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Qualidade de Vida , Quimiorradioterapia
18.
J Pharm Biomed Anal ; 241: 115998, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38330784

RESUMO

L-α-glyceryl phosphorylcholine, also referred to as choline ethanol phosphate and phosphocholine glycerophosphate, is a naturally occurring metabolite of water-soluble phospholipids in animals. This molecular property is important for informing the crystallization and purification of drugs. The solubility of L-α-glyceryl phosphorylcholine was determined in ten pure solvents and three mixed solvents under atmospheric pressure. The experimental results indicate that L-α-glyceryl phosphorylcholine is most soluble in methanol and least soluble in acetone. Additionally, the solubility of L-α-glyceryl phosphorylcholine was found to increase with temperature within the experimental range. Furthermore, the solubility of L-α-glyceryl phosphorylcholine in binary solvents is dependent on the proportion of positive solvent and temperature. The solubility of L-α-glyceryl phosphorylcholine increases with the proportion of positive solvent. XRD and DSC results indicate that the crystal form of L-α-glyceryl phosphorylcholine remains unchanged before and after dissolution in the reagent, and its melting point temperature is 413.15 K. Various models, including the modified Apelblat model, λh model, Jouyban-Acree model, SUN model, and CNIBS/R-K model, were used to fit the solubility data of L-α-glyceryl phosphorylcholine in different solvents. The study found that the modified Apelblat model and CNIBS/R-K model were the most appropriate for fitting the data. The KAT-LSER model was used to analyze the molecular interactions between solvents and solutes, revealing that the solvent step method with non-specific polarity/polarization interaction had the greatest impact on solubility.


Assuntos
Glicerilfosforilcolina , Fosforilcolina , Solubilidade , Solventes/química , Termodinâmica , Água/química
19.
J Environ Manage ; 353: 120199, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38316072

RESUMO

Nanofibers were prepared by electrospinning a mixture of polycaprolactone and silica, and modified to improve the hydrophilicity and stability of the material and to degrade nitrogenous wastewater by adsorbing heterotrophic nitrifying aerobic denitrifying (Ochrobactrum anthropic). The immobilized bacteria showed highly efficient simultaneous nitrification-denitrification ability, which could convert nearly 90 % of the initial nitrogen into gaseous nitrogen under aerobic conditions, and the average TN removal rate reached 5.59 mg/L/h. The average ammonia oxidation rate of bacteria immobilized by modified nanofibers was 7.36 mg/L/h, compared with 6.3 mg/L/h for free bacteria and only 4.23 mg/L/h for unmodified nanofiber-immobilized bacteria. Kinetic studies showed that modified nanofiber-immobilized bacteria complied with first-order degradation kinetics, and the effects of extreme pH, temperature, and salinity on immobilized bacteria were significantly reduced, while the degradation rate of free bacteria produced larger fluctuations. In addition, the immobilized bacterial nanofibers were reused five times, and the degradation rate remained stable at more than 80 %. At the same time, the degradation rate can still reach 50 % after 6 months of storage at 4 °C. It also demonstrated good nitrogen removal in practical wastewater treatment.


Assuntos
Nanofibras , Águas Residuárias , Desnitrificação , Nitritos/metabolismo , Nitrogênio/metabolismo , Cinética , Aerobiose , Nitrificação , Bactérias/metabolismo , Processos Heterotróficos
20.
Food Funct ; 15(5): 2485-2496, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38334682

RESUMO

Hypertension-induced kidney injury is considered a vital consequence of long-term and uncontrolled hypertension, which is commonly associated with an excessive accumulation of angiotensin II (Ang II) from hyperactivated RAS. Antihypertensive peptides have a significant effect on blood pressure regulation, but few studies have focused on the ameliorative function of antihypertensive peptides on renal injury. This study explored the effects of soybean protein-derived hydrolysate (SPH) on SHR and Ang II-induced HK-2 cells. SPH significantly attenuated blood pressure and alleviated renal pathological injury in SHRs after oral gavage administration. According to the pathological results, the kidneys of SHRs showed inflammation and SPH attenuated inflammatory cell infiltration in the kidneys of SHRs. Immunohistochemical analysis further revealed that SPH inhibited MCP-1 expression and increased Nrf2 expression in the kidneys. An in vitro HK-2 cell model demonstrated that SPH exhibited optimal activity for reducing Ang II-induced inflammatory cytokines and ROS overproduction. Mechanistically, SPH was observed to regulate MAPK/JNK and NF-κB signaling pathways. These findings indicate that potent antihypertensive SPH significantly ameliorates hypertension-induced kidney damage.


Assuntos
Hipertensão , NF-kappa B , NF-kappa B/genética , NF-kappa B/metabolismo , Anti-Hipertensivos/farmacologia , Angiotensina II/metabolismo , Glycine max , Rim , Transdução de Sinais , Hipertensão/induzido quimicamente , Hipertensão/tratamento farmacológico , Hipertensão/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA