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1.
N Engl J Med ; 391(7): 585-597, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38828946

RESUMO

BACKGROUND: Osimertinib is a recommended treatment for advanced non-small-cell lung cancer (NSCLC) with an epidermal growth factor receptor (EGFR) mutation and as adjuvant treatment for resected EGFR-mutated NSCLC. EGFR tyrosine kinase inhibitors have shown preliminary efficacy in unresectable stage III EGFR-mutated NSCLC. METHODS: In this phase 3, double-blind, placebo-controlled trial, we randomly assigned patients with unresectable EGFR-mutated stage III NSCLC without progression during or after chemoradiotherapy to receive osimertinib or placebo until disease progression occurred (as assessed by blinded independent central review) or the regimen was discontinued. The primary end point was progression-free survival as assessed by blinded independent central review. RESULTS: A total of 216 patients who had undergone chemoradiotherapy were randomly assigned to receive osimertinib (143 patients) or placebo (73 patients). Osimertinib resulted in a significant progression-free survival benefit as compared with placebo: the median progression-free survival was 39.1 months with osimertinib versus 5.6 months with placebo, with a hazard ratio for disease progression or death of 0.16 (95% confidence interval [CI], 0.10 to 0.24; P<0.001). The percentage of patients who were alive and progression free at 12 months was 74% (95% CI, 65 to 80) with osimertinib and 22% (95% CI, 13 to 32) with placebo. Interim overall survival data (maturity, 20%) showed 36-month overall survival among 84% of patients with osimertinib (95% CI, 75 to 89) and 74% with placebo (95% CI, 57 to 85), with a hazard ratio for death of 0.81 (95% CI, 0.42 to 1.56; P = 0.53). The incidence of adverse events of grade 3 or higher was 35% in the osimertinib group and 12% in the placebo group; radiation pneumonitis (majority grade, 1 to 2) was reported in 48% and 38%, respectively. No new safety concerns emerged. CONCLUSIONS: Treatment with osimertinib resulted in significantly longer progression-free survival than placebo in patients with unresectable stage III EGFR-mutated NSCLC. (Funded by AstraZeneca; LAURA ClinicalTrials.gov number, NCT03521154.).


Assuntos
Acrilamidas , Compostos de Anilina , Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acrilamidas/uso terapêutico , Acrilamidas/efeitos adversos , Compostos de Anilina/uso terapêutico , Compostos de Anilina/efeitos adversos , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Método Duplo-Cego , Receptores ErbB/genética , Receptores ErbB/antagonistas & inibidores , Indóis , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Mutação , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Pirimidinas , /uso terapêutico
2.
Immunity ; 49(1): 120-133.e9, 2018 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-30005826

RESUMO

B lymphocytes can suppress immunity through interleukin (IL)-10 production in infectious, autoimmune, and malignant diseases. Here, we have identified a natural plasma cell subset that distinctively expresses the inhibitory receptor LAG-3 and mediates this function in vivo. These plasma cells also express the inhibitory receptors CD200, PD-L1, and PD-L2. They develop from various B cell subsets in a B cell receptor (BCR)-dependent manner independently of microbiota in naive mice. After challenge they upregulate IL-10 expression via a Toll-like receptor-driven mechanism within hours and without proliferating. This function is associated with a unique transcriptome and epigenome, including the lowest amount of DNA methylation at the Il10 locus compared to other B cell subsets. Their augmented accumulation in naive mutant mice with increased BCR signaling correlates with the inhibition of memory T cell formation and vaccine efficacy after challenge. These natural regulatory plasma cells may be of broad relevance for disease intervention.


Assuntos
Antígenos CD/genética , Expressão Gênica , Interleucina-10/biossíntese , Plasmócitos/imunologia , Animais , Antígenos CD/imunologia , Subpopulações de Linfócitos B/imunologia , Epigênese Genética , Feminino , Perfilação da Expressão Gênica , Interleucina-10/genética , Ativação Linfocitária , Masculino , Camundongos , Plasmócitos/fisiologia , Receptores de Antígenos de Linfócitos B/metabolismo , Salmonelose Animal/imunologia , Transdução de Sinais , Linfócitos T/imunologia , Receptores Toll-Like/metabolismo , Regulação para Cima/genética , Vacinas/imunologia , Proteína do Gene 3 de Ativação de Linfócitos
3.
Small ; 20(2): e2305220, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37658516

RESUMO

Herein, it is found that 3D transition metal dichalcogenide (TMD)-MoS2 nanoflowers-grown on 2D tungsten oxide-anchored graphene nanosheets (MoS2 @W-G) functions as a superior catalyst for the hydrogen evolution reaction (HER) under both acidic and alkaline conditions. The optimized weight ratio of MoS2 @W-G (MoS2 :W-G/1.5:1) in 0.5 M H2 SO4 achieves a low overpotential of 78 mV at 10 mA cm-2 , a small Tafel slope of 48 mV dec-1 , and a high exchange current density (0.321 mA cm⁻2 ). Furthermore, the same MoS2 @W-G composite exhibits stable HER performance when using real seawater, with Faradaic efficiencies of 96 and 94% in acidic and alkaline media, respectively. Density functional theory calculations based on the hybrid MoS2 @W-G structure model confirm that suitable hybridization of 3D MoS2 and 2D W-G nanosheets can lower the hydrogen adsorption: Gibbs free energy (∆GH* ) from 1.89 eV for MoS2 to -0.13 eV for the MoS2 @W-G composite. The excellent HER activity of the 3D/2D hybridized MoS2 @W-G composite arises from abundance of active heterostructure interfaces, optimizing the electrical configuration, thereby accelerating the adsorption and dissociation of H2 O. These findings suggest a new approach for the rational development of alternative 3D/2D TMD/graphene electrocatalysts for HER applications using seawater.

4.
J Autoimmun ; 147: 103243, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38788537

RESUMO

OBJECTIVES: Autoreactive B cells and interferon (IFN) signature are hallmarks of primary sjögren's syndrome (pSS), but how IFN signaling pathways influence autoantibody production and clinical manifestations remain unclear. More detailed studies hold promise for improved diagnostic methodologies and personalized treatment. METHODS: We analyzed peripheral blood T and B cell subsets from 34 pSS patients and 38 healthy donors (HDs) at baseline and upon stimulation regarding their expression levels of type I and II IFN signaling molecules (STAT1/2, IRF1, IRF9). Additionally, we investigated how the levels of these molecules correlated with serological and clinical characteristics and performed ROC analysis. RESULTS: Patients showed elevated IFN pathway molecules, including STAT1, STAT2 and IRF9 among most T and B cell subsets. We found a reduced ratio of phosphorylated STAT1 and STAT2 in patients in comparison to HDs, although B cells from patients were highly responsive by increased phosphorylation upon IFN stimulation. Correlation matrices showed further interrelations between STAT1, IRF1 and IRF9 in pSS. Levels of STAT1 and IRF9 in T and B cells correlated with the IFN type I marker Siglec-1 (CD169) on monocytes. High levels of STAT1 and IRF9 within pSS B cells were significantly associated with hypergammaglobulinemia as well as anti-SSA/anti-SSB autoantibodies. Elevated STAT1 levels were found in patients with extraglandular disease and could serve as a biomarker for this subgroup (p < 0.01). Notably, IRF9 levels in T and B cells correlated with EULAR Sjögren's syndrome disease activity index (ESSDAI). CONCLUSION: Here, we provide evidence that in active pSS patients, enhanced IFN signaling incl. unphosphorylated STAT1 and STAT2 with IRFs entertain chronic T and B cell activation. Furthermore, increased STAT1 levels candidate as biomarker of extraglandular disease, while IRF9 levels can serve as biomarker for disease activity.


Assuntos
Biomarcadores , Fator Gênico 3 Estimulado por Interferon, Subunidade gama , Fator de Transcrição STAT1 , Síndrome de Sjogren , Humanos , Síndrome de Sjogren/imunologia , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/metabolismo , Fator de Transcrição STAT1/metabolismo , Feminino , Fosforilação , Pessoa de Meia-Idade , Masculino , Fator Gênico 3 Estimulado por Interferon, Subunidade gama/metabolismo , Idoso , Adulto , Linfócitos B/imunologia , Linfócitos B/metabolismo , Autoanticorpos/imunologia , Autoanticorpos/sangue , Transdução de Sinais , Subpopulações de Linfócitos B/imunologia , Subpopulações de Linfócitos B/metabolismo , Lectina 1 Semelhante a Ig de Ligação ao Ácido Siálico/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismo
5.
BMC Cancer ; 24(1): 176, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317094

RESUMO

BACKGROUND: This study aimed to evaluate the efficacy and side effects of first-line afatinib treatment in a real-world setting in Vietnam. METHODS: This retrospective study was conducted across nine hospitals in Vietnam. Advanced epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) patients who received afatinib as first-line therapy between April 2018 and June 2022 were included, and patient medical records were reviewed. Key outcomes were overall response rate (ORR), time-to-treatment failure (TTF), and tolerability. RESULTS: A total of 343 patients on first-line afatinib were eligible for the study. EGFR exon 19 deletion (Del19) alone was detected in 46.9% of patients, L858R mutation alone in 26.3%, and other uncommon EGFR mutations, including compound mutations, in 26.8%. Patients with brain metastases at baseline were 25.4%. Patients who received 40 mg, 30 mg, and 20 mg as starting doses of afatinib were 58.6%, 39.9%, and 1.5%, respectively. The ORR was 78.1% in the overall population, 82.6% in the Del19 mutation subgroup, 73.3% in the L858R mutation subgroup, and 75.0% in the uncommon mutation subgroup (p > 0.05). The univariate and multivariate analyses indicate that the ORR increased when the starting dose was 40 mg compared to starting doses below 40 mg (83.9% vs. 74.3%, p = 0.034). The median TTF (mTTF) was 16.7 months (CI 95%: 14.8-18.5) in all patients, with a median follow-up time of 26.2 months. The mTTF was longer in patients in the common EGFR mutation subgroup (Del19/L858R) than in those in the uncommon mutation subgroup (17.5 vs. 13.8 months, p = 0.045) and in those without versus with brain metastases at baseline (17.5 vs. 15.1 months, p = 0.049). There were no significant differences in the mTTF between subgroups based on the starting dose of 40 mg and < 40 mg (16.7 vs. 16.9 months, p > 0.05). The most common treatment-related adverse events (any grade/grade ≥ 3) were diarrhea (55.4%/3.5%), rash (51.9%/3.2%), paronychia (35.3%/5.0%), and stomatitis (22.2%/1.2%). CONCLUSIONS: Afatinib demonstrated clinical effectiveness and good tolerability in Vietnamese EGFR-mutant NSCLC patients. In our real-world setting, administering a starting dose below 40 mg might result in a reduction in ORR; however, it might not have a significant impact on TTF.


Assuntos
Afatinib , Neoplasias Encefálicas , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Afatinib/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/secundário , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Estudos de Coortes , Receptores ErbB/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Vietnã/epidemiologia
6.
Langmuir ; 40(11): 6051-6064, 2024 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-38437236

RESUMO

Preconcentration of biomolecules based on ion concentration polarization (ICP) has been splendidly applied to various biomedical and chemical processes. However, in many circumstances, biomolecule preconcentration could not occur due to the lack of full studies on the preconcentration mechanism, especially on the effect of microchannel dimensions. In this work, we provide analytical studies on the critical dimensions (minimum and maximum) of microchannels for the preconcentration of biomolecules. These formulas are verified with the numerical results by fully solving the coupled governing equations: Poisson-Nernst-Planck and Navier-Stokes experiments with appropriate boundary conditions and assumptions. In addition, we examine the impact of operational parameters, such as electric potentials and critical external pressures, on the formation of the preconcentration. Moreover, two important results are provided for the first time, including the position of the preconcentrated biomolecule region and the concentration enhancement factor of the biomolecules. These analytical and numerical results are consistent with experimental observations and, therefore, could provide sharp insight into the mechanism of biomolecule preconcentration and give useful guidelines to better design and optimize ICP-based microfluidic preconcentration devices.


Assuntos
Dispositivos Lab-On-A-Chip
7.
Analyst ; 149(8): 2252-2271, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38470814

RESUMO

A convergent sector in microfluidic devices utilizing ion concentration polarization (ICP) can help increase the preconcentration rate and the concentration enhancement factor (CEF) of biomolecules. In this work, we present a detailed study of the nozzle-like-squeeze effect of a convergent channel on the preconcentration of biomolecules. By numerically solving coupled Nernst-Planck-Poisson-Navier-Stokes governing equations for the 2D channel model, we report the first study on the critical width of a convergent region in the channel to retain the advantage of the nozzle-like-squeeze effect in speeding up preconcentration and augmenting CEF. In addition, we investigated the impact of the location and the dimensions of a convergent sector on the mechanism of biomolecule preconcentration. The location of an ion-selective membrane was also determined to ensure that biomolecules are focused on the convergent region of the channel. Moreover, we introduce analytical studies to compare and verify simulation findings. Specifically, the formulas for the critical dimensions of a convergent channel, location of a preconcentrated biomolecule plug, and position of an ion-selective membrane are presented. Furthermore, important working parameters, including electric potentials and hydrostatic pressures, were examined to scrutinize their effect on convergent concentrators. These detailed analytical solutions and numerical simulation results are consistent with experimental observations, providing deep insights into the ICP phenomenon and the preconcentration mechanism of biomolecules in convergent microfluidic concentration devices.


Assuntos
Técnicas Analíticas Microfluídicas , Técnicas Analíticas Microfluídicas/métodos , Dispositivos Lab-On-A-Chip
8.
J Fluoresc ; 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280054

RESUMO

SiO2@Ag nanocomposite (NC) has been synthesized by the chemical reduction and StÓ§ber method for Metal-enhanced fluorescence (MEF) of Rhodmine 6G (R6G) and Surface-enhanced Raman spectroscopy (SERS) of Malachite green (MG). As-synthesized SiO2@Ag NC indicated SiO2 nanosphere (NS) and Ag nanoparticle (NP) morphologies. The SiO2@Ag NC was high quality with a well-defined crystallite phase with average sizes of 24 nm and 132 nm for Ag NP and SiO2 NC, respectively. By using SiO2@Ag NC, the photoluminescence (PL) intensity of the R6G (at 59.17 ppm) was increased approximately 133 times. The SERS of the MG (at 1.0 ppm) with SiO2@Ag NC as substrate clearly observed vibrational modes in MG dye at 798, 916, 1172, 1394, and 1616 cm-1. As a result, the SERS enhancement factor (EFSERS) at 1172 cm-1 obtained 6.3 × 106. This initial study points to the potential of SiO2@Ag NC as a promising material for MEF and SERS substrates to detect dyes at low concentrations.

9.
Proc Natl Acad Sci U S A ; 118(50)2021 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-34876527

RESUMO

Pancreatic cancer is usually asymptomatic in the early stages; the 5-y survival rate is around 9%; and there is a lack of effective treatment. Here we show that SSEA-4 is more expressed in all pancreatic cancer cell lines examined but not detectable in normal pancreatic cells; and high expression of SSEA-4 or the key enzymes B3GALT5 + ST3GAL2 associated with SSEA-4 biosynthesis significantly lowers the overall survival rate. To evaluate potential new treatments for pancreatic cancer, homogeneous antibodies with a well-defined Fc glycan for optimal effector functions and CAR-T cells with scFv construct designed to target SSEA-4 were shown highly effective against pancreatic cancer in vitro and in vivo. This was further supported by the finding that a subpopulation of natural killer (NK) cells isolated by the homogeneous antibody exhibited enhancement in cancer-cell killing activity compared to the unseparated NK cells. These results indicate that targeting SSEA-4 by homologous antibodies or CAR-T strategies can effectively inhibit cancer growth, suggesting SSEA-4 as a potential immunotherapy target for treating pancreatic disease.


Assuntos
Anticorpos/imunologia , Neoplasias Pancreáticas/tratamento farmacológico , Antígenos Embrionários Estágio-Específicos/imunologia , Animais , Linhagem Celular Tumoral , Terapia Baseada em Transplante de Células e Tecidos , Regulação da Expressão Gênica , Humanos , Imunoterapia , Imunoterapia Adotiva , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Chem Biodivers ; 21(5): e202400380, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38498616

RESUMO

The chemical investigation of the stems of Knema globularia led to the isolation of two new benzoquinones derivatives, embenones A and B (1 and 2), along with three known compounds (3-5). The structures of the isolated compounds were determined using spectroscopic techniques, including HRESIMS, 1D and 2D NMR, in conjunction with comparison to existing literature data. Compounds 1 and 2 represent new carbon skeletons in nature. Furthermore, all isolated compounds were evaluated for their α-glucosidase inhibitory activity, with compounds 1-3 exhibiting superior potency relative to the positive control (acarbose, IC50 331 µM). Their IC50 values ranged from 1.40 to 96.1 µM.


Assuntos
Benzoquinonas , Myristicaceae , Caules de Planta , alfa-Glucosidases/metabolismo , Benzoquinonas/química , Benzoquinonas/isolamento & purificação , Benzoquinonas/farmacologia , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Conformação Molecular , Estrutura Molecular , Caules de Planta/química , Relação Estrutura-Atividade , Vietnã , Myristicaceae/química
11.
Anticancer Drugs ; 34(10): 1122-1131, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37067993

RESUMO

Histone lysine demethylase 4 (KDM4) is an epigenetic regulator that facilitates the transition between transcriptionally silent and active chromatin states by catalyzing the removal of methyl groups on histones H3K9, H3K36, and H1.4K26. KDM4 overamplification or dysregulation has been reported in various cancers and has been shown to drive key processes linked to tumorigenesis, such as replicative immortality, evasion of apoptosis, metastasis, DNA repair deficiency, and genomic instability. KDM4 also plays a role in epigenetic regulation of cancer stem cell renewal and has been linked to more aggressive disease and poorer clinical outcomes. The KDM4 family is composed of four main isoforms (KDM4A-D) that demonstrate functional redundancy and cross-activity; thus, selective inhibition of one isoform appears to be ineffective and pan-inhibition targeting multiple KDM4 isoforms is required. Here, we describe TACH101, a novel, small-molecule pan-inhibitor of KDM4 that selectively targets KDM4A-D with no effect on other KDM families. TACH101 demonstrated potent antiproliferative activity in cancer cell lines and organoid models derived from various histologies, including colorectal, esophageal, gastric, breast, pancreatic, and hematological malignancies. In vivo , potent inhibition of KDM4 led to efficient tumor growth inhibition and regression in several xenograft models. A reduction in the population of tumor-initiating cells was observed following TACH101 treatment. Overall, these observations demonstrate the broad applicability of TACH101 as a potential anticancer agent and support its advancement into clinical trials.


Assuntos
Histona Desmetilases , Neoplasias , Humanos , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Histona Desmetilases/uso terapêutico , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , Epigênese Genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/uso terapêutico
12.
World J Urol ; 41(12): 3789-3794, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37897515

RESUMO

PURPOSE: Cut-off time to avoid orchiectomy relies on small series of patients. The objective was to determine the cut-off time to avoid orchiectomy in torsion of the spermatic cord in a large cohort. METHODS: We performed a retrospective multicenter study (TORSAFUF cohort) of patients with suspected spermatic cord torsion between 2005 and 2019. All patients aged > 12 years who were suspected of having a torsion of the spermatic cord in 14 University Hospitals in France were included (n = 2986). Patients for whom data on pain duration were not available (n = 923) or for whom the final diagnosis was not torsion of the spermatic cord (n = 807) were excluded. The primary outcome was orchiectomy. The secondary outcomes were testicular survival time and the prediction of orchiectomy with the duration of pain. RESULTS: 1266 patients were included with an orchiectomy rate of 12% (150 patients). The mean age was 21.5 years old in the salvage group and 23.7 years old in the orchiectomy group (p = 0.01), respectively. The median time from the onset of pain to surgery was 5.5 (IQR = 5) hours in the salvage group and 51.1 (IQR = 70) hours in the orchiectomy group (p < 0.0001). The risk of orchiectomy increased after a time cut-off of 6 h 30. A delay of 15 h 30 in pain duration was found to predict orchiectomy (sensitivity: 0.81; specificity: 0.87). CONCLUSIONS: Pain duration can predict the probability of salvaging the testicles and performing orchiectomy. Rapid intervention should be recommended, regardless of the time elapsed from the onset of pain.


Assuntos
Orquiectomia , Torção do Cordão Espermático , Adulto , Humanos , Masculino , Adulto Jovem , Orquidopexia , Dor , Estudos Retrospectivos , Torção do Cordão Espermático/diagnóstico , Torção do Cordão Espermático/cirurgia , Torção do Cordão Espermático/complicações , Adolescente
13.
Org Biomol Chem ; 21(44): 8813-8818, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37889185

RESUMO

In four simple steps, a series of 5H-thiazolo[2',3':2,3]imidazo[4,5-b]indole and 11H-benzo[4',5']thiazolo[2',3':2,3]imidazo[4,5-b]indole derivatives were prepared with high yields. The key step in this procedure was demonstrated to be two-fold Cu-catalysed C-N coupling reactions of 5-bromo-6-(2-bromophenyl)imidazo[2,1-b]thiazole and 3-bromo-2-(2-bromophenyl)benzo[d]imidazo[2,1-b]thiazole with various amines.

14.
Chem Biodivers ; 20(4): e202201096, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36891669

RESUMO

The objective of this study was to evaluate the antioxidant, anti-skin-aging, anti-inflammatory, and anti-acetylcholinesterase activities of the hexane (n-hex), AcOEt, BuOH, MeOH, and aqueous extracts from R. oligophlebia roots. The total phenolic and flavonoid contents (TPC and TFC) were determined using Folin-Ciocalteu and AlCl3 colorimetric assays. The antioxidant capacity was examined by reducing power (RP), ferric reducing antioxidant power (FRAP), ABTS⋅+ , and DPPH⋅+ radical cation assays. All extracts potentially exhibited antioxidant activity with IC50 values ranging from 2.93 to 5.73 µg/mL for ABTS⋅+ and from 5.69 to 7.65 µg/mL for DPPH⋅+ except the n-hex extract. The BuOH, MeOH, and aqueous extract possess promising anti-skin-aging activities, as observed by an attenuation of UV-A toxicity on human keratinocytes. We proposed that these anti-skin-aging properties are possibly due to direct scavenging activity against reactive oxygen species and upregulate cellular antioxidant machinery. Moreover, we found that the antioxidant capacity was well correlated with anti-inflammatory capacity against nitric oxide (NO) production in terms of the n-hex, AcOEt, and BuOH extracts with IC50 values from 23.21 to 47.1 µg/mL. In contrast, these activities were found to be poorly correlated with AchE activity. To the best of our knowledge, this is the first report of the antioxidant, anti-skin-aging, anti-inflammatory, and anti-acetylcholinesterase activities of the extracts of R. oligophlebia roots. These findings indicated that this species could be a potential source of natural antioxidant, anti-aging, and anti-inflammatory agents. Consequently, it may be suggested as a medicinal plant that prevents diseases related to oxidative stress and inflammatory responses.


Assuntos
Anti-Inflamatórios , Inibidores da Colinesterase , Connaraceae , Humanos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Connaraceae/química , Flavonoides/química , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Fenóis/química , Fenóis/farmacologia
15.
Sensors (Basel) ; 23(9)2023 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-37177402

RESUMO

Health is gold, and good health is a matter of survival for humanity. The development of the healthcare industry aligns with the development of humans throughout history. Nowadays, along with the strong growth of science and technology, the medical domain in general and the healthcare industry have achieved many breakthroughs, such as remote medical examination and treatment applications, pandemic prediction, and remote patient health monitoring. The advent of 5th generation communication networks in the early 2020s led to the Internet of Things concept. Moreover, the 6th generation communication networks (so-called 6G) expected to launch in 2030 will be the next revolution of the IoT era, and will include autonomous IoT systems and form a series of endogenous intelligent applications that serve humanity. One of the domains that receives the most attention is smart healthcare. In this study, we conduct a comprehensive survey of IoT-based technologies and solutions in the medical field. Then, we propose an all-in-one computing architecture for real-time IoHT applications and present possible solutions to achieving the proposed architecture. Finally, we discuss challenges, open issues, and future research directions. We hope that the results of this study will serve as essential guidelines for further research in the human healthcare domain.


Assuntos
Internet das Coisas , Humanos , Internet , Ouro , Inteligência , Atenção à Saúde
16.
J Environ Manage ; 335: 117537, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36842358

RESUMO

The length of global coastline is about 356 thousand kilometers with various dynamic natural and anthropogenic. Although the number of studies on coastal landscape categorization has been increasing, it is still difficult to distinguish precisely them because the used methods commonly are traditional qualitative ones. With the leverage of remote sensing data and GIS tools, it helps categorize and identify a variety of features on land and water based on multi-source data. The aim of study is using different natural - social profile data obtained from ALOS, NOAA, and multi-temporal Landsat satellite images as input data of the convolutional-neural-network (CvNet) models for coastal landscape classification. Studies used 900 cut-line samples which represent coastal landscapes in Vietnam for training and optimizing CvNet models. As a result, nine coastal landscapes were identified including: deltas, alluvial, mature and young sand dunes, cliff, lagoon, tectonic, karst, and transitional landscapes. Three CvNet models using three different optimizer types classified the landscapes of other 1150 cut-lines in Vietnam with the accuracies about 98% and low loss function value. Excepting dalmatian, karst and delta coastal landscapes, five others distribute heterogeneous along the coasts in Vietnam. Therefore, the evaluation of additional natural components is necessary and CvNet model have ability to update new landscape types in variety of tropical nation as a step toward coastal landscape classification at both national and global scales.


Assuntos
Monitoramento Ambiental , Tecnologia de Sensoriamento Remoto , Vietnã , Monitoramento Ambiental/métodos , Redes Neurais de Computação , Meio Ambiente
17.
Chem Biodivers ; 19(4): e202100882, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35146904

RESUMO

Four compounds, luteolin (1), 6-γ,γ-dimethylallylquercetin 7-O-ß-D-glucopyranoside (2), 6-γ,γ-dimethylallylkaempferol 7-O-ß-D-glucopyranoside (3), and 6-γ,γ-dimethylallyldihydrokaempferol 7-O-ß-D-glucoside (4), were isolated for the first time from AcOEt extract of the O. integerrima flower. We then evaluated the antioxidant effects of AcOEt, butanol, and MeOH extracts and their effects on H2 O2 against oxidative stress in HaCaT keratinocyte cell lines. Furthermore, 2,2-diphenyl-1-picrylhydrazyl hydrate (DPPH⋅) radical scavenging activities of 1-4 were determined and their mechanisms of action on tyrosinase were predicted by in silico studies. The results revealed that the AcOEt extract and 1-3 exhibited good DPPH⋅ radical scavenging activity. Furthermore, this extract also had a significant protective effect against H2 O2 -induced oxidative stress in HaCaT cells. In silico studies indicated that the activity of 1-3 may be due to tyrosinase inhibition with MM-GBSA free binding energies of -78.9, -70.1, and -71.1 kcal mol-1 , respectively, compared to 4 with an energy -56.9 kcal mol-1 .


Assuntos
Antioxidantes , Ochnaceae , Antioxidantes/química , Antioxidantes/farmacologia , Flores , Queratinócitos , Monofenol Mono-Oxigenase , Extratos Vegetais/química , Extratos Vegetais/farmacologia
18.
J Asian Nat Prod Res ; 24(6): 596-602, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34292109

RESUMO

One new cycloartane-type triterpenoid, named macrobidoupoic acid A (as an C-24 epimeric mixture, 4a, 4 b), together with three known ones (1-3), were clarified by different chromatography from the M. bidoupensis whole plants. Triterpenoids (1, 3 & 4) were detected for the first time from the Macrosolen genus. Chemical structures of them were illuminated using HR-ESI-MS, and NMR (1 D & 2 D) assessments. The cytotoxic properties of triterpenoids (3 & 4) were examined against two human cancer cell lines (A549, and RD) by MTT assay. As results shown, triterpenoids (3 & 4) possessed moderate cytotoxic activity against A549 and RD cancer cells (IC50 ranged from 5.44 to 39.52 µM).


Assuntos
Triterpenos , Estrutura Molecular , Triterpenos/química , Triterpenos/farmacologia
19.
J Environ Manage ; 320: 115732, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-35930878

RESUMO

Identifying and monitoring coastlines and shorelines play an important role in coastal erosion assessment around the world. The application of deep learning models was used in this study to detect coastlines and shorelines in Vietnam using high-resolution satellite images and different object segmentation methods. The aims are to (1) propose indicators to identify coastlines and shorelines; (2) build deep learning (DL) models to automatically interpret coastlines and shorelines from high-resolution remote sensing images; and (3) apply DL-trained models to monitor coastal erosion in Vietnam. Eight DL models were trained based on four artificial-intelligent-network structures, including U-Net, U2-Net, U-Net3+, and DexiNed. The high-resolution images collected from Google Earth Pro software were used as input data for training all models. As a result, the U-Net using an input-image size of 512 × 512 provides the highest performance of 98% with a loss function of 0.16. The interpretation results of this model were used effectively for the coastline and shoreline identification in assessing coastal erosion in Vietnam due to sea-level rise in storm events over 20 years. The outcomes proved that while the shoreline is ideal for observing seasonal tidal changes or the immediate motions of current waves, the coastline is suitable to assess coastal erosion caused by the influence of sea-level rise during storms. This paper has provided a broad scope of how the U-Net model can be used to predict the coastal changes over vietnam and the world.


Assuntos
Aprendizado Profundo , Vietnã
20.
J Urol ; 206(6): 1461-1468, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34398666

RESUMO

PURPOSE: We evaluate the safety of immediate contralateral orchiopexy (ICLO) at the time of scrotal exploration for testicular torsion suspicion. MATERIALS AND METHODS: Patient data were retrieved from the TORSAFUF cohort project, which is a multicenter national study conducted at 14 academic French hospitals between 2005 and 2019. Each patient who underwent surgical exploration for testicular torsion suspicion was included. The primary study outcome was the safety of ICLO compared to ipsilateral scrotal exploration alone. The primary outcome of interest was the complication rate within 90 days of surgery. The end point was planned before data collection. RESULTS: Overall, 2,775 patients were included, of whom 1,554 (56%) underwent ICLO. After propensity score matching and multivariable analysis, ICLO was associated with a higher complication rate (OR 1.51, 95% CI 1.1-2.1, p=0.01), especially a higher rate of hematoma (OR 2.9, 95% CI 1.3-6.6, p=0.01), and delayed wound healing (OR 3.0, 95% CI 1.8-5.2, p <0.001). CONCLUSIONS: At the time of scrotal exploration for acute scrotum, ICLO was associated with an increased postoperative complication rate, with a particular increase in hematoma, and delayed wound healing. ICLO should not be performed systematically.


Assuntos
Orquidopexia/métodos , Exame Físico , Torção do Cordão Espermático/diagnóstico , Torção do Cordão Espermático/cirurgia , Adolescente , Adulto , Estudos de Coortes , França , Humanos , Masculino , Pontuação de Propensão , Escroto , Fatores de Tempo , Adulto Jovem
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