Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 63
Filtrar
1.
Plant Biotechnol J ; 22(8): 2216-2234, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38572508

RESUMO

Climate change may result in a drier climate and increased salinization, threatening agricultural productivity worldwide. Quinoa (Chenopodium quinoa) produces highly nutritious seeds and tolerates abiotic stresses such as drought and high salinity, making it a promising future food source. However, the presence of antinutritional saponins in their seeds is an undesirable trait. We mapped genes controlling seed saponin content to a genomic region that includes TSARL1. We isolated desired genetic variation in this gene by producing a large mutant library of a commercial quinoa cultivar and screening the library for specific nucleotide substitutions using droplet digital PCR. We were able to rapidly isolate two independent tsarl1 mutants, which retained saponins in the leaves and roots for defence, but saponins were undetectable in the seed coat. We further could show that TSARL1 specifically controls seed saponin biosynthesis in the committed step after 2,3-oxidosqualene. Our work provides new important knowledge on the function of TSARL1 and represents a breakthrough for quinoa breeding.


Assuntos
Chenopodium quinoa , Genótipo , Saponinas , Sementes , Chenopodium quinoa/genética , Chenopodium quinoa/metabolismo , Saponinas/biossíntese , Saponinas/metabolismo , Sementes/genética , Sementes/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
2.
Lancet ; 400(10346): 116-125, 2022 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-35810757

RESUMO

BACKGROUND: The benefit of combined treatment with intravenous thrombolysis before endovascular thrombectomy in patients with acute ischaemic stroke caused by large vessel occlusion remains unclear. We hypothesised that the clinical outcomes of patients with stroke with large vessel occlusion treated with direct endovascular thrombectomy within 4·5 h would be non-inferior compared with the outcomes of those treated with standard bridging therapy (intravenous thrombolysis before endovascular thrombectomy). METHODS: DIRECT-SAFE was an international, multicentre, prospective, randomised, open-label, blinded-endpoint trial. Adult patients with stroke and large vessel occlusion in the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or basilar artery, confirmed by non-contrast CT and vascular imaging, and who presented within 4·5 h of stroke onset were recruited from 25 acute-care hospitals in Australia, New Zealand, China, and Vietnam. Eligible patients were randomly assigned (1:1) via a web-based, computer-generated randomisation procedure stratified by site of baseline arterial occlusion and by geographic region to direct endovascular thrombectomy or bridging therapy. Patients assigned to bridging therapy received intravenous thrombolytic (alteplase or tenecteplase) as per standard care at each site; endovascular thrombectomy was also per standard of care, using the Trevo device (Stryker Neurovascular, Fremont, CA, USA) as first-line intervention. Personnel assessing outcomes were masked to group allocation; patients and treating physicians were not. The primary efficacy endpoint was functional independence defined as modified Rankin Scale score 0-2 or return to baseline at 90 days, with a non-inferiority margin of -0·1, analysed by intention to treat (including all randomly assigned and consenting patients) and per protocol. The intention-to-treat population was included in the safety analyses. The trial is registered with ClinicalTrials.gov, NCT03494920, and is closed to new participants. FINDINGS: Between June 2, 2018, and July 8, 2021, 295 patients were randomly assigned to direct endovascular thrombectomy (n=148) or bridging therapy (n=147). Functional independence occurred in 80 (55%) of 146 patients in the direct thrombectomy group and 89 (61%) of 147 patients in the bridging therapy group (intention-to-treat risk difference -0·051, two-sided 95% CI -0·160 to 0·059; per-protocol risk difference -0·062, two-sided 95% CI -0·173 to 0·049). Safety outcomes were similar between groups, with symptomatic intracerebral haemorrhage occurring in two (1%) of 146 patients in the direct group and one (1%) of 147 patients in the bridging group (adjusted odds ratio 1·70, 95% CI 0·22-13·04) and death in 22 (15%) of 146 patients in the direct group and 24 (16%) of 147 patients in the bridging group (adjusted odds ratio 0·92, 95% CI 0·46-1·84). INTERPRETATION: We did not show non-inferiority of direct endovascular thrombectomy compared with bridging therapy. The additional information from our study should inform guidelines to recommend bridging therapy as standard treatment. FUNDING: Australian National Health and Medical Research Council and Stryker USA.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Adulto , Austrália , Isquemia Encefálica/tratamento farmacológico , Procedimentos Endovasculares/métodos , Fibrinolíticos/efeitos adversos , Humanos , Estudos Prospectivos , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Resultado do Tratamento
3.
J Stroke Cerebrovasc Dis ; 32(8): 107203, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37441912

RESUMO

BACKGROUND: Stroke recurrence and disability are important challenges to overcome in patients with minor ischemic stroke. The aim of our study was to determine the factors associated with unfavorable outcomes in patients with minor ischemic stroke. METHODS: This was a prospective cohort study including patients with minor ischemic stroke with a National Institutes of Health Stroke Scale (NIHSS) score ≤ 4 who were treated at the Bach Mai Hospital stroke center from June 15, 2021, to September 15, 2022. Unfavorable outcome was defined as mRS 2-6 at 90 days. Multivariable logistic regression analysis was conducted to assess risk factors related to clinical outcomes. RESULTS: Of 678 patients presenting with minor ischemic stroke, there were 90 (13.3%, 90/678) patients with no intracranial artery imaging. Hence, 588 were patients analyzed, of whom 6.0% received thrombolytic therapy, 8.5% developed NIHSS > 4 in 24 hours, and 30.4% had intracranial stenosis > 50%. Compared with the group of unfavorable outcomes, the favorable outcome group had more NIHSS 0-1 (29.9% vs.8.7%, P<0.001), lower cardioembolic (3.2% vs.7.9%, P=0.021), low IV-tPA ratio (4.8% vs.10.3%, P=0.019), lower NIHSS progression > 4 in the first 24 hours (3.9% vs.25.4%, P<0.001), and lower ICAS rate (28.1% vs.38.9%, P=0.02). Multivariable regression analysis of factors affecting unfavorable outcomes included baseline NIHSS 2-4 (OR, 3.85; 95% CI, 1.97-7.52), NIHSS progression > 4 (OR, 7.57; 95% CI, 3.80-15.10), and ICAS (OR 1.68; 95%CI, 1.07-2.64). CONCLUSIONS: In patients with minor ischemic stroke, unfavorable outcomes were associated with baseline NIHSS 2-4, NIHSS progression > 4 points in 24 hours, and ICAS. These factors may identify a patient population in need of close monitoring and at higher risk of adverse outcomes.

4.
Plant Cell Physiol ; 63(11): 1624-1640, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-35583202

RESUMO

Sustainable agriculture in the future will depend on crops that are tolerant to biotic and abiotic stresses, require minimal input of water and nutrients and can be cultivated with a minimal carbon footprint. Wild plants that fulfill these requirements abound in nature but are typically low yielding. Thus, replacing current high-yielding crops with less productive but resilient species will require the intractable trade-off of increasing land area under cultivation to produce the same yield. Cultivating more land reduces natural resources, reduces biodiversity and increases our carbon footprint. Sustainable intensification can be achieved by increasing the yield of underutilized or wild plant species that are already resilient, but achieving this goal by conventional breeding programs may be a long-term prospect. De novo domestication of orphan or crop wild relatives using mutagenesis is an alternative and fast approach to achieve resilient crops with high yields. With new precise molecular techniques, it should be possible to reach economically sustainable yields in a much shorter period of time than ever before in the history of agriculture.


Assuntos
Domesticação , Melhoramento Vegetal , Produtos Agrícolas/genética , Agricultura , Biodiversidade
5.
New Phytol ; 236(4): 1409-1421, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35927949

RESUMO

Halophytes tolerate high salinity levels that would kill conventional crops. Understanding salt tolerance mechanisms will provide clues for breeding salt-tolerant plants. Many halophytes, such as quinoa (Chenopodium quinoa), are covered by a layer of epidermal bladder cells (EBCs) that are thought to mediate salt tolerance by serving as salt dumps. We isolated an epidermal bladder cell-free (ebcf) quinoa mutant that completely lacked EBCs and was mutated in REBC and REBC-like1. This mutant showed no loss of salt stress tolerance. When wild-type quinoa plants were exposed to saline soil, EBCs accumulated potassium (K+ ) as the major cation, in quantities far exceeding those of sodium (Na+ ). Emerging leaves densely packed with EBCs had the lowest Na+ content, whereas old leaves with deflated EBCs served as Na+ sinks. When the leaves expanded, K+ was recycled from EBCs, resulting in turgor loss that led to a progressive deflation of EBCs. Our findings suggest that EBCs in young leaves serve as a K+ -powered hydrodynamic system that functions as a water sink for solute storage. Sodium ions accumulate within old leaves that subsequently wilt and are shed. This mechanism improves the survival of quinoa under high salinity conditions.


Assuntos
Chenopodium quinoa , Plantas Tolerantes a Sal , Plantas Tolerantes a Sal/genética , Tolerância ao Sal/genética , Chenopodium quinoa/genética , Bexiga Urinária , Melhoramento Vegetal , Salinidade , Sódio , Potássio , Íons , Solo , Água
6.
J Stroke Cerebrovasc Dis ; 31(11): 106804, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36206608

RESUMO

INTRODUCTION: Uncertainty remains on the optimal management of basilar artery occlusion (BAO). Two large randomized controlled trials (RCTs) in 2019 and 2021 demonstrated neutral results with respect to the use of endovascular therapy (EVT) for BAO. This study aimed to understand regional variation in physicians' perceptions towards the treatment of BAO as stratified by physician respondents from China versus outside China, prior to the publication of studies demonstrating a benefit of EVT for BAO. METHODS: An international online survey was conducted of stroke neurologists and neurointerventionalists from January to March 2022. Survey questions evaluated physician opinions toward the use of EVT in BAO, as well as the clinical and imaging features underlying treatment decisions. Respondents were dichotomized as either from China or from other countries and differences between groups were analyzed. RESULTS: There were 1245 physician respondents across 73 countries of which 295 (23.7%) were from China. Compared to respondents from the rest of the world, respondents from China were more likely to be interventionalists (71.5% vs 35.0%; p < 0.0001). Overall, more than 95% of respondents believed that EVT was superior to medical therapy under certain circumstances. Chinese respondents were more likely to believe that further RCTs were necessary than respondents from other countries (93.6% vs 76.2%; p < 0.0001). Chinese respondents were more likely to use advanced imaging in later time windows and use a premorbid mRS threshold of ≤2 for BAO selection to EVT. CONCLUSION: Most stroke physicians believe EVT is beneficial in selected patients with BAO. Clinical and imaging modality differences were observed in the selection criteria used for EVT. There was greater inclination to enroll all trial eligible patients in a BAO RCT by respondents from China as compared to other parts of the world.


Assuntos
Arteriopatias Oclusivas , Artéria Basilar , Procedimentos Endovasculares , Humanos , Arteriopatias Oclusivas/terapia , Artéria Basilar/cirurgia , Procedimentos Endovasculares/métodos , Estudos Retrospectivos , Acidente Vascular Cerebral/terapia , Inquéritos e Questionários , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como Assunto
7.
Molecules ; 25(15)2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32717858

RESUMO

The synthesis of three water-soluble lactose-modified 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based photosensitizers with tumor-targeting capabilities is reported, including an investigation into their photodynamic therapeutic activity on three distinct cancer cell lines (human hepatoma Huh7, cervical cancer HeLa, and breast cancer MCF-7 cell lines). The halogenated BODIPY dyes exhibited a decreased fluorescence quantum yield compared to their non-halogenated counterpart, and facilitated the efficient generation of singlet oxygen species. The synthesized dyes exhibited low cytotoxicities in the dark and high photodynamic therapeutic capabilities against the treated cancer cell lines following irradiation at 530 nm. Moreover, the incorporation of lactose moieties led to an enhanced cellular uptake of the BODIPY dyes. Collectively, the results presented herein provide promising insights for the development of photodynamic therapeutic agents for cancer treatment.


Assuntos
Compostos de Boro/síntese química , Lactose/química , Neoplasias/metabolismo , Fármacos Fotossensibilizantes/síntese química , Compostos de Boro/química , Compostos de Boro/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Química Click , Células HeLa , Humanos , Células MCF-7 , Neoplasias/terapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Pontos Quânticos , Oxigênio Singlete/metabolismo
8.
Plant Cell Physiol ; 60(12): 2660-2671, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31665522

RESUMO

Plants convert solar energy into chemical energy through photosynthesis, which supports almost all life activities on earth. Because the intensity and quality of sunlight can change dramatically throughout the day, various regulatory mechanisms help plants adjust their photosynthetic output accordingly, including the regulation of light energy accumulation to prevent the generation of damaging reactive oxygen species. Non-photochemical quenching (NPQ) is a regulatory mechanism that dissipates excess light energy, but how it is regulated is not fully elucidated. In this study, we report a new NPQ-regulatory protein named Day-Length-dependent Delayed-Greening1 (DLDG1). The Arabidopsis DLDG1 associates with the chloroplast envelope membrane, and the dldg1 mutant had a large NPQ value compared with wild type. The mutant also had a pale-green phenotype in developing leaves but only under continuous light; this phenotype was not observed when dldg1 was cultured in the dark for ≥8 h/d. DLDG1 is a homolog of the plasma membrane-localizing cyanobacterial proton-extrusion-protein A that is required for light-induced H+ extrusion and also shows similarity in its amino-acid sequence to that of Ycf10 encoded in the plastid genome. Arabidopsis DLDG1 enhances the growth-retardation phenotype of the Escherichia coli K+/H+ antiporter mutant, and the everted membrane vesicles of the E. coli expressing DLDG1 show the K+/H+ antiport activity. Our findings suggest that DLDG1 functionally interacts with Ycf10 to control H+ homeostasis in chloroplasts, which is important for the light-acclimation response, by optimizing the extent of NPQ.


Assuntos
Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Membrana Celular/metabolismo , Cianobactérias/metabolismo , Proteínas de Escherichia coli/metabolismo , Fotossíntese/fisiologia , Prótons
9.
Photosynth Res ; 139(1-3): 413-424, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30390180

RESUMO

Precise control of the proton concentration gradient across thylakoid membranes (ΔpH) is essential for photosynthesis and its regulation because the gradient contributes to the generation of the proton motive force used for ATP synthesis and also for the fast and reversible induction of non-photochemical quenching (NPQ) to avoid photoinhibition and photodamage. However, the regulatory mechanism(s) controlling ΔpH in response to fluctuating light has not been fully elucidated. We previously described a new NPQ-regulatory chloroplastic protein, Fluctuating-Light-Acclimation Protein1 (FLAP1), which is important for plant growth and modulation of ΔpH under fluctuating light conditions. For this report, we further characterized FLAP1 activity by individually crossing an Arabidopsis flap1 mutant with npq4 and pgr5 plants; npq4 is defective in PsbS-dependent NPQ, and pgr5 is defective in induction of steady-state proton motive force (pmf) and energy-dependent quenching (qE). Both npq4 and npq4 flap1 exhibited similar NPQ kinetics and other photosynthetic parameters under constant or fluctuating actinic light. Conversely, pgr5 flap1 had recovered NPQ, photosystem II quantum yield and growth under fluctuating light, each of which was impaired in pgr5. Together with other data, we propose that FLAP1 activity controls proton homeostasis under steady-state photosynthesis to manipulate luminal acidification levels appropriately to balance photoprotection and photochemical processes.


Assuntos
Cloroplastos/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Homeostase/genética , Homeostase/fisiologia , Mutação/genética , Fotossíntese/genética , Fotossíntese/fisiologia , Prótons
10.
Photosynth Res ; 139(1-3): 359-365, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29916043

RESUMO

The proton motive force (PMF) across the chloroplast thylakoid membrane that is generated by electron transport during photosynthesis is the driving force for ATP synthesis in plants. The PMF mainly arises from the oxidation of water in photosystem II and from electron transfer within the cytochrome b6f complex. There are two electron transfer pathways related to PMF formation: linear electron flow and cyclic electron flow. Proton gradient regulation 5 (PGR5) is a major component of the cyclic electron flow pathway, and the Arabidopsis pgr5 mutant shows a substantial reduction in the PMF. How the PGR5-dependent cyclic electron flow contributes to ATP synthesis has not, however, been fully delineated. In this study, we monitored in vivo ATP levels in Arabidopsis chloroplasts in real time using a genetically encoded bioluminescence-based ATP indicator, Nano-lantern(ATP1). The increase in ATP in the chloroplast stroma of pgr5 leaves upon illumination with actinic light was significantly slower than in wild type, and the decrease in ATP levels when this illumination stopped was significantly faster in pgr5 leaves than in wild type. These results indicated that PGR5-dependent cyclic electron flow around photosystem I helps to sustain the rate of ATP synthesis, which is important for growth under fluctuating light conditions.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Cloroplastos/metabolismo , Trifosfato de Adenosina/metabolismo , Proteínas de Arabidopsis/genética , Transporte de Elétrons/genética , Transporte de Elétrons/fisiologia , Fotossíntese/genética , Fotossíntese/fisiologia , Complexo de Proteínas do Centro de Reação Fotossintética/genética , Complexo de Proteínas do Centro de Reação Fotossintética/metabolismo
11.
J Org Chem ; 84(18): 12131-12137, 2019 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-31448604

RESUMO

Herein we report the development of radical benzylation reactions of quinones using Selectfluor and catalytic Ag(I) initiators. The reaction is believed to proceed via a C-H abstraction mechanism after Ag(I)-mediated reduction of Selectfluor. This reaction occurs under mild conditions and is effective for a variety of quinones and radical precursors bearing primary benzylic carbons. The use of preformed Ag(4-OMePy)2NO3 as a catalyst proved effective in improving the reaction efficiency by reducing unwanted degradation pathways available to Selectfluor.

12.
PLoS Pathog ; 12(1): e1005375, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26795118

RESUMO

Most West Nile virus (WNV) infections are asymptomatic, but some lead to neuroinvasive disease with symptoms ranging from disorientation to paralysis and death. Evidence from animal models suggests that neuroinvasive infections may arise as a consequence of impaired immune protection. However, other data suggest that neurologic symptoms may arise as a consequence of immune mediated damage. We demonstrate that elevated immune responses are present in neuroinvasive disease by directly characterizing WNV-specific T cells in subjects with laboratory documented infections using human histocompatibility leukocyte antigen (HLA) class II tetramers. Subjects with neuroinvasive infections had higher overall numbers of WNV-specific T cells than those with asymptomatic infections. Independent of this, we also observed age related increases in WNV-specific T cell responses. Further analysis revealed that WNV-specific T cell responses included a population of atypically polarized CXCR3+CCR4+CCR6- T cells, whose presence was highly correlated with neuroinvasive disease. Moreover, a higher proportion of WNV-specific T cells in these subjects co-produced interferon-γ and interleukin 4 than those from asymptomatic subjects. More globally, subjects with neuroinvasive infections had reduced numbers of CD4+FoxP3+ Tregs that were CTLA4 positive and exhibited a distinct upregulated transcript profile that was absent in subjects with asymptomatic infections. Thus, subjects with neuroinvasive WNV infections exhibited elevated, dysregulated, and atypically polarized responses, suggesting that immune mediated damage may indeed contribute to pathogenic outcomes.


Assuntos
Subpopulações de Linfócitos T/imunologia , Linfócitos T/imunologia , Febre do Nilo Ocidental/imunologia , Adulto , Idoso , Epitopos de Linfócito T/imunologia , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
13.
J Immunol ; 197(8): 3214-3224, 2016 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-27591323

RESUMO

Rhinovirus (RV) is a major cause of common cold and an important trigger of acute episodes of chronic lung diseases. Antigenic variation across the numerous RV strains results in frequent infections and a lack of durable cross-protection. Because the nature of human CD4+ T cells that target RV is largely unknown, T cell epitopes of RV capsid proteins were analyzed, and cognate T cells were characterized in healthy subjects and those infected by intranasal challenge. Peptide epitopes of the RV-A16 capsid proteins VP1 and VP2 were identified by peptide/MHC class II tetramer-guided epitope mapping, validated by direct ex vivo enumeration, and interrogated using a variety of in silico methods. Among noninfected subjects, those circulating RV-A16-specific CD4+ T cells detected at the highest frequencies targeted 10 unique epitopes that bound to diverse HLA-DR molecules. T cell epitopes localized to conserved molecular regions of biological significance to the virus were enriched for HLA class I and II binding motifs, and constituted both species-specific (RV-A) and pan-species (RV-A, -B, and -C) varieties. Circulating epitope-specific T cells comprised both memory Th1 and T follicular helper cells, and were rapidly expanded and activated after intranasal challenge with RV-A16. Cross-reactivity was evidenced by identification of a common *0401-restricted epitope for RV-A16 and RV-A39 by tetramer-guided epitope mapping and the ability for RV-A16-specific Th1 cells to proliferate in response to their RV-A39 peptide counterpart. The preferential persistence of high-frequency RV-specific memory Th1 cells that recognize a limited set of conserved epitopes likely arises from iterative priming by previous exposures to different RV strains.


Assuntos
Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/imunologia , Proteínas do Capsídeo/imunologia , Epitopos de Linfócito T/imunologia , Memória Imunológica , Infecções por Picornaviridae/imunologia , Rhinovirus/imunologia , Adolescente , Adulto , Mapeamento de Epitopos , Humanos , Pessoa de Meia-Idade , Adulto Jovem
14.
J Virol ; 87(23): 12794-804, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24049183

RESUMO

Yellow fever virus (YFV) can induce acute, life-threatening disease that is a significant health burden in areas where yellow fever is endemic, but it is preventable through vaccination. The live attenuated 17D YFV strain induces responses characterized by neutralizing antibodies and strong T cell responses. This vaccine provides an excellent model for studying human immunity. While several studies have characterized YFV-specific antibody and CD8(+) T cell responses, less is known about YFV-specific CD4(+) T cells. Here we characterize the epitope specificity, functional attributes, and dynamics of YFV-specific T cell responses in vaccinated subjects by investigating peripheral blood mononuclear cells by using HLA-DR tetramers. A total of 112 epitopes restricted by seven common HLA-DRB1 alleles were identified. Epitopes were present within all YFV proteins, but the capsid, envelope, NS2a, and NS3 proteins had the highest epitope density. Antibody blocking demonstrated that the majority of YFV-specific T cells were HLA-DR restricted. Therefore, CD4(+) T cell responses could be effectively characterized with HLA-DR tetramers. Ex vivo tetramer analysis revealed that YFV-specific T cells persisted at frequencies ranging from 0 to 100 cells per million that are detectable years after vaccination. Longitudinal analysis indicated that YFV-specific CD4(+) T cells reached peak frequencies, often exceeding 250 cells per million, approximately 2 weeks after vaccination. As frequencies subsequently declined, YFV-specific cells regained CCR7 expression, indicating a shift from effector to central memory. Cells were typically CXCR3 positive, suggesting Th1 polarization, and produced gamma interferon and other cytokines after reactivation in vitro. Therefore, YFV elicits robust early effector CD4(+) T cell responses that contract, forming a detectable memory population.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Proteínas não Estruturais Virais/imunologia , Proteínas Estruturais Virais/imunologia , Vacina contra Febre Amarela/imunologia , Febre Amarela/imunologia , Vírus da Febre Amarela/imunologia , Adulto , Idoso , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Citocinas/imunologia , Epitopos de Linfócito T/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Febre Amarela/prevenção & controle , Febre Amarela/virologia , Vacina contra Febre Amarela/administração & dosagem , Vírus da Febre Amarela/fisiologia , Adulto Jovem
15.
Biomater Sci ; 12(6): 1536-1548, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38299265

RESUMO

Imaging-guided diagnosis and treatment of cancer hold potential to significantly improve therapeutic accuracies and efficacies. Central to this theragnostic approach has been the use of multicomponent-based multimodal nanoparticles (NPs). Apart from this conventional approach, here we propose a design strategy for the simple and straightforward formulation of NPs based on boron dipyrromethene (BODIPY) derivatives, LaB-X (X = H, Et, and Br). Specifically, the conjugation of lactose to the inherently hydrophobic BODIPY promoted the formation of LaB-X NPs in water. Furthermore, the BODIPY backbone was subjected to distyrylation, dibromination, and diethylation to tailor the optical window and the balance between fluorescence and singlet oxygen generation capabilities. We demonstrate that while the photoinduced anticancer activities of LaB-H and LaB-Et NPs were trivial, LaB-Br NPs effectively induced the apoptotic death of hepatocellular carcinoma cells under red light irradiation while allowing fluorescence cell imaging in the phototherapeutic window. This dual fluorescence photosensitizing activity of LaB-Br NPs could be switched off and on, so that both fluorescence and singlet oxygen generation were paused during NP formation in an aqueous solution, while both processes resumed after cellular uptake, likely due to NP disassembly.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Oxigênio Singlete , Fotoquimioterapia/métodos , Compostos de Boro/química , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Corantes , Nanopartículas/química , Fármacos Fotossensibilizantes/química
16.
Nanoscale ; 16(19): 9462-9475, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38639449

RESUMO

The dimerization of boron dipyrromethene (BODIPY) moieties is an appealing molecular design approach for developing heavy-atom-free triplet photosensitizers (PSs). However, BODIPY dimer-based PSs generally lack target specificity, which limits their clinical use for photodynamic therapy. This study reports the synthesis of two mitochondria-targeting triphenylphosphonium (TPP)-functionalized meso-ß directly linked BODIPY dimers (BTPP and BeTPP). Both BODIPY dimers exhibited solvent-polarity-dependent singlet oxygen (1O2) quantum yields, with maximum values of 0.84 and 0.55 for BTPP and BeTPP, respectively, in tetrahydrofuran. The compact orthogonal geometry of the BODIPY dimers facilitated the generation of triplet excited states via photoinduced charge separation (CS) and subsequent spin-orbit charge-transfer intersystem crossing (SOCT-ISC) processes and their rates were dependent on the energetic configuration between the frontier molecular orbitals of the two BODIPY subunits. The as-synthesized compounds were amphiphilic and hence formed stable nanoparticles (∼36 nm in diameter) in aqueous solutions, with a zeta potential of ∼33 mV beneficial for mitochondrial targeting. In vitro experiments with MCF-7 and HeLa cancer cells indicated the effective localization of BTPP and BeTPP within cancer-cell mitochondria. Under light irradiation, BTPP and BeTPP exhibited robust photo-induced therapeutic effects in both cell lines, with half-maximal inhibitory concentration (IC50) values of ∼30 and ∼55 nM, respectively.


Assuntos
Compostos de Boro , Mitocôndrias , Nanopartículas , Compostos Organofosforados , Fotoquimioterapia , Fármacos Fotossensibilizantes , Oxigênio Singlete , Humanos , Compostos de Boro/química , Compostos de Boro/farmacologia , Compostos Organofosforados/química , Compostos Organofosforados/farmacologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Nanopartículas/química , Oxigênio Singlete/metabolismo , Oxigênio Singlete/química , Células MCF-7 , Sobrevivência Celular/efeitos dos fármacos , Células HeLa , Dimerização
17.
Radiol Case Rep ; 19(8): 3349-3353, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38832340

RESUMO

Portal cavernoma cholangiopathy (PCC) refers to morphological changes in the intrahepatic, extrahepatic biliary system, along with the gallbladder (GB), induced by portal cavernoma (PC). Acute acalculous cholecystitis (AAC) represents an infrequent clinical manifestation of PCC. Given the inadequacy of documentation within medical literature, AAC may go undiagnosed among patients with PC presenting symptoms of right upper quadrant pain. The current study aims to report a case of acute acalculous cholecystitis secondary to portal cavernoma, focusing on radiological findings, with a brief review of literature.

18.
J Cardiovasc Dev Dis ; 11(9)2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39330327

RESUMO

(1) Background: Atrial fibrillation (AF) poses a growing cardiovascular challenge globally, with significant implications in Vietnam. This study aimed to investigate the impact of AF on ischemic stroke/transient ischemic attack (TIA) and clinical outcomes, as well as the utilization of oral anticoagulation (OAC) therapy in Vietnam. (2) Methods: Data from the Registry of Stroke Care Quality (RES-Q) across 66 hospitals in Vietnam between 2017 and 2023 were utilized. Patients diagnosed with ischemic stroke or TIA were included, and clinical characteristics, pre- and post-hospitalization medication, and hospitalized outcomes were examined. (3) Results: Of 94,144 patients, 15.1% had AF. Patients with AF were older and had a higher prevalence of heart failure and more severe strokes. AF was associated with increased mortality during hospitalization and a poorer prognosis. In AF patients, anticoagulation therapy utilization increased from 15.8% pre-hospitalization to 82.4% at discharge, with a preference for direct oral anticoagulants. (4) Conclusions: AF significantly impacts ischemic stroke/TIA outcomes in Vietnam. Pre-hospitalization and anticoagulation therapy utilization were low but improved at discharge. These findings emphasize the need for improved AF management and stroke prevention strategies in developing countries.

19.
Heliyon ; 10(9): e30647, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38765090

RESUMO

Lifestyle, diet, socioeconomic status and genetics all contribute to heterogeneity in immune responses. Vietnam is plagued with a variety of health problems, but there are no available data on immune system values in the Vietnamese population. This study aimed to establish reference intervals for immune cell parameters specific to the healthy Vietnamese population by utilizing multi-color flow cytometry (MCFC). We provide a comprehensive analysis of total leukocyte count, quantitative and qualitative shifts within lymphocyte subsets, serum and cytokine and chemokine levels and functional attributes of key immune cells including B cells, T cells, natural killer (NK) cells and their respective subpopulations. By establishing these reference values for the Vietnamese population, these data contribute significantly to our understanding of the human immune system variations across diverse populations. These data will be of substantial comparative value and be instrumental in developing personalized medical approaches and optimizing diagnostic strategies for individuals based on their unique immune profiles.

20.
Sci Total Environ ; 926: 171793, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38513854

RESUMO

Due to global demand, millions of tons of plastics have been widely consumed, resulting in the widespread entry of vast amounts of microplastic particles into the environment. The presence of microplastics (MPs) in water supplies, including bottled water, has undergone systematic review, assessing the potential impacts of MPs on humans through exposure assessment. The main challenges associated with current technologies lie in their ability to effectively treat and completely remove MPs from drinking and supply water. While the risks posed by MPs upon entering the human body have not yet been fully revealed, there is a predicted certainty of negative impacts. This review encompasses a range of current technologies, spanning from basic to advanced treatments and varying in scale. However, given the frequent detection of MPs in drinking and bottled water, it becomes imperative to implement comprehensive management strategies to address this issue effectively. Consequently, integrating current technologies with management options such as life-cycle assessment, circular economy principles, and machine learning is crucial to eliminating this pervasive problem.


Assuntos
Microplásticos , Poluentes Químicos da Água , Purificação da Água , Abastecimento de Água , Microplásticos/análise , Poluentes Químicos da Água/análise , Purificação da Água/métodos , Monitoramento Ambiental/métodos , Água Potável/química , Plásticos/análise
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA