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1.
J Formos Med Assoc ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38570237

RESUMO

In the wake of the COVID-19 pandemic, the fluctuating nurse resignation rates highlighted an understudied area in healthcare: post-pandemic challenges in clinical settings. This study, conducted from May to November 2023, employed a qualitative inquiry using focus groups to delve into these challenges. Six focus group sessions, involving 33 nurse participants recruited through snowball sampling from various hospital settings were conducted to explore their clinical experiences during and after the pandemic. Thematic analysis revealed two primary themes: the 'Invisibility of Nurses' within the healthcare system and the 'Moral Duty of Nursing Practice'. These findings illuminate a tension between the overlooked role of nurses and their ethical obligations, underscoring a critical need for policy reassessment. The study advocates for systemic changes, particularly in the undervaluation of the nursing profession and the National Health Insurance system, to address the poor working environment and mitigate long-term nursing shortages. This research deepens understanding of post-pandemic nursing workforce challenges in Taiwan, highlighting the need for policy evolution to enhance recognition and support for the nursing industry. It is suggested to provide tangible compensation to acknowledge nurses' daily care and health education for patients. A healthier working environment can be enhanced by collaborative efforts between healthcare institutions and nurses.

2.
Physiol Rep ; 12(7): e15990, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38575554

RESUMO

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are rapidly gaining ground in the treatment of heart failure (HF) with reduced ejection fraction (HFrEF) and acute myocardial infarction (AMI) by an unknown mechanism. Upregulation of Na+/H+ exchanger 1 (NHE1), SGLT1, and Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the diseased hearts was found to be attenuated by prolonged SGLT2i treatment. Unfortunately, dapagliflozin is not well understood as to how Na+/Ca2+ homeostasis is affected in cardiomyocytes. In this study, we aimed to investigate whether mechanical stretch in cardiomyocytes upregulate SGLT2, resulted to loss of Na+/Ca2+ homeostasis via ERK and eNOS signaling. AMI (+) and AMI (-) serum levels were estimated using ELISA assays of TGFß-1 or endoglin (CD105). Human cardiomyocyte cell line AC16 was subjected to different stresses: 5% mild and 25% aggressive, at 1 Hz for 24 h. Immunofluorescence assays were used to estimate troponin I, CD105, SGLT1/2, eNOSS633, and ERK1/2T202/Y204 levels was performed for 5% (mild), and 25% elongation for 24 h. AMI (+) serum showed increased TGFß1 and CD105 compared to AMI (-) patients. In consistent, troponin I, CD105, SGLT1/2, eNOSS633 and ERK1/2T202/Y204 were upregulated after 25% of 24 h cyclic stretch. Dapagliflozin addition caused SGLT2 inhibition, which significantly decreased troponin I, CD105, SGLT1/2, eNOSS633, and ERK1/2T202/Y204 under 25% cyclic stretching. In summary, SGLT2 may have sensed mechanical stretch in a way similar to cardiac overloading as in vivo. By blocking SGLT2 in stretched cardiomyocytes, the AMI biomarkers (CD105, troponin I and P-ERK) were decreased, potentially to rescue eNOS production to maintain normal cellular function. This discovery of CD105 and SGLT2 increase in mechanically stretched cardiomyocytes suggests that SGLT2 may conceive a novel role in direct or indirect sensing of mechanical stretch, prompting the possibility of an in vitro cardiac overloaded cell model, an alternative to animal heart model.


Assuntos
Compostos Benzidrílicos , Glucosídeos , Insuficiência Cardíaca , Infarto do Miocárdio , Humanos , Animais , Endoglina/metabolismo , Insuficiência Cardíaca/metabolismo , Regulação para Cima , Transportador 2 de Glucose-Sódio/metabolismo , Troponina I/metabolismo , Volume Sistólico , Miócitos Cardíacos/metabolismo
3.
J Hosp Palliat Care ; 27(1): 1-10, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38449832

RESUMO

This article underscores the importance of integrating comprehensive palliative care for noncancer patients who are undergoing hemodialysis, with an emphasis on the aging populations in Asian nations such as Taiwan, Japan, the Republic of Korea, and China. As the global demographic landscape shifts towards an aging society and healthcare continues to advance, a marked increase has been observed in patients undergoing hemodialysis who require palliative care. This necessitates an immediate paradigm shift to incorporate this care, addressing the intricate physical, psychosocial, and spiritual challenges faced by these individuals and their families. Numerous challenges impede the provision of effective palliative care, including difficulties in prognosis, delayed referrals, cultural misconceptions, lack of clinician confidence, and insufficient collaboration among healthcare professionals. The article proposes potential solutions, such as targeted training for clinicians, the use of telemedicine to facilitate shared decision-making, and the introduction of time-limited trials for dialysis to overcome these obstacles. The integration of palliative care into routine renal treatment and the promotion of transparent communication among healthcare professionals represent key strategies to enhance the quality of life and end-of-life care for people on hemodialysis. By embracing innovative strategies and fostering collaboration, healthcare providers can deliver more patient-centered, holistic care that meets the complex needs of seriously ill patients within an aging population undergoing hemodialysis.

4.
Molecules ; 29(6)2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38542969

RESUMO

Although much promising synthetic progress in conjugated polymer-based organic solar cells (OSCs) has resulted in significant improvement in power conversion efficiencies (PCEs) of from over 15 to >19.0% in the last five years, the sophisticated and complex reactions from at least two families' monomers with remarkably different electron push-pull effects could still pose an unavoidable material burden for the commercialization of OSCs in the coming future. Therefore, the method of preparing a homopolymer from a sole monomer would significantly reduce the synthetic steps and costs in order to pave the way for the large-scale production of OSC materials. Therefore, alkylthio-thiophenyl-substituted benzo[1,2-b;4,5-b']dithiophene (BDTTS) as the sole and key structural moiety with dihalogen and distannyl functional groups was designed and synthesized, respectively, in this study, for facile monomer syntheses and polymerizations to achieve three wide-bandgap homopolymer donors of BDTTS-alt-BDTT-Cl (P13), BDTTS-alt-BDTT (P15), and BDTTS (P14), respectively. The structural symmetry dependency on their physical, electrochemical, and optical properties, thin-film morphologies, and photovoltaic (PV) performance was investigated in detail. As a result, OSCs based on the asymmetric polymer P15, paired with BTP-eC9 as the electron acceptor, presented the best PV performance, with a PCE of 11.5%, a fill factor (FF) of 65.87%, and a short-circuit current (JSC) of 22.04 mA·cm-2, respectively. This PCE value is among the highest ones reported for BDT-type homopolymer donor-based OPVs, providing us with knowledge for obtaining promising PV performance from devices made of P15-like materials.

5.
Environ Pollut ; 347: 123674, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38458517

RESUMO

Fine particulate matter (PM2.5) has been linked to increased severity and incidence of airway diseases, especially chronic obstructive pulmonary disease (COPD) and asthma. Airway remodeling is an important event in both COPD and asthma, and airway smooth muscle cells (ASMCs) are key cells which directly involved in airway remodeling. However, it was unclear how PM2.5 affected ASMCs. This study investigates the effects of PM2.5 on airway smooth muscle and its mechanism. We first showed that inhaled particulate matter was distributed in the airway smooth muscle bundle, combined with increased airway smooth muscle bundle and collagen deposition in vivo. Then, we demonstrated that PM2.5 induced up-regulation of collagen-I and alpha-smooth muscle actin (α-SMA) expression in rat and human ASMCs in vitro. Next, we found PM2.5 led to rat and human ASMCs senescence and exhibited senescence-associated secretory phenotype (SASP) by autophagy-induced GATA4/TRAF6/NF-κB signaling, which contributed to collagen-I and α-SMA synthesis as well as airway smooth muscle remodeling. Together, our results provided evidence that SASP induced by PM2.5 in airway smooth muscle cells prompted airway remodeling.


Assuntos
Asma , Doença Pulmonar Obstrutiva Crônica , Humanos , Ratos , Animais , Remodelação das Vias Aéreas , Fenótipo Secretor Associado à Senescência , Miócitos de Músculo Liso , Asma/metabolismo , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/metabolismo , Colágeno Tipo I , Proliferação de Células , Material Particulado/metabolismo , Células Cultivadas
6.
Hu Li Za Zhi ; 71(2): 26-33, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38532672

RESUMO

As populations age, average life expectancy increases and the complexity of diseases rises, leading to nursing care and healthcare systems facing severe challenges related to inadequate resources. Artificial intelligence (AI), including elements such as investigation, integration, learning, prediction, and decision-making, holds significant potential for application in clinical care not only to enhance care quality but also to help guide the future direction of healthcare. AI applications are already being increasingly utilized to improve the quality of clinical care and to streamline workflows. However, because nursing education has lagged behind in terms of adopting AI, greater attention must be given to training up nursing students with AI-related knowledge and application skills. AI technologies should be integrated into nursing curricula and clinical internships to adapt to the rapidly changing high-tech healthcare environment, enabling the more-effective use of AI technology in providing high-quality and safe nursing care.


Assuntos
Inteligência Artificial , Educação em Enfermagem , Humanos , Aprendizagem , Currículo , Conhecimento
7.
Adv Mater ; : e2400521, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38477468

RESUMO

Large-area printing fabrication is a distinctive feature of organic solar cells (OSCs). However, the advance of upscalable fabrication is challenged by the thickness of organic active layers considering the importance of both exciton dissociation and charge collection. In this work, a bulk-heterojunction-buried (buried-BHJ) structure is introduced by sequential deposition to realize efficient exciton dissociation and charge collection, thereby contributing to efficient OSCs with 500 nm thick active layers. The buried-BHJ distributes donor and acceptor phases in the vertical direction as charge transport channels, while numerous BHJ interfaces are buried in each phase to facilitate exciton dissociation simultaneously. It is found that buried-BHJ configurations possess efficient exciton dissociation and rapid charge transport, resulting in reduced recombination losses. In comparison with traditional structures, the buried-BHJ structure displays a decent tolerance to film thickness. In particular, a power conversion efficiency of 16.0% is achieved with active layers at a thickness of 500 nm. To the best of the authors' knowledge, this represents the champion efficiency of thick film OSCs.

8.
J Med Ethics ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38527787

RESUMO

Respect for patient autonomy is paramount in resolving ethical tensions in end-of-life care. The concept of relational autonomy has contributed to this debate; however, scholars often use this concept in a fragmented manner. This leads to partial answers on ascertaining patients' true wishes, meaningfully engaging patients' significant others, balancing interests among patients and significant others, and determining clinicians' obligations to change patients' unconventional convictions to enhance patient autonomy. A satisfactory solution based on relational autonomy must incorporate patients' competence (apart from decisional capacity), authenticity (their true desires or beliefs) and the involvement level of their significant others. To that end, we argue that John Christman's procedural approach to relational autonomy provides critical insights, such as the diachronic or socio-historical personhood, sustained critical reflection and his recent explication of the nature of asymmetrical relationships and helpful interlocutors. This study reviews Christman's account, proposes minor modifications and advocates for an integrated three-dimensional model for medical decision-making. Clarifying the relationship among the three elements promotes an ethical framework with a coherent understanding of relational autonomy. This model not only provides a descriptive and normative framework for end-of-life care practice but also reconsiders the nature of the clinician-patient relationship and its normative implications. We further present a case study to illustrate the merits of our proposed model. Altogether, our proposal will help navigate complex medical decision-making, foster trust and negotiate shared values between patients and their significant others, particularly in end-of-life care.

9.
Nat Commun ; 15(1): 1946, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431627

RESUMO

All-small-molecule organic solar cells with good batch-to-batch reproducibility combined with non-halogen solvent processing show great potential for commercialization. However, non-halogen solvent processing of all-small-molecule organic solar cells are rarely reported and its power conversion efficiencies are very difficult to improve. Herein, we designed and synthesized a small molecule donor BM-ClEH that can take advantage of strong aggregation property induced by intramolecular chlorine-sulfur non-covalent interaction to improve molecular pre-aggregation in tetrahydrofuran and corresponding micromorphology after film formation. Tetrahydrofuran-fabricated all-small-molecule organic solar cells based on BM-ClEH:BO-4Cl achieved high power conversion efficiencies of 15.0% in binary device and 16.1% in ternary device under thermal annealing treatment. In contrast, weakly aggregated BM-HEH without chlorine-sulfur non-covalent bond is almost inefficient under same processing conditions due to poor pre-aggregation induced disordered π-π stacking, indistinct phase separation and exciton dissociation. This work promotes the development of non-halogen solvent processing of all-small-molecule organic solar cells and provides further guidance.

10.
Hum Gene Ther ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38420654

RESUMO

Liver injury with concomitant loss of therapeutic transgene expression can be a clinical sequela of systemic administration of recombinant adeno-associated virus (rAAV) when used for gene therapy, and a significant barrier to treatment efficacy. Despite this, it has been difficult to replicate this phenotype in preclinical models, thereby limiting the field's ability to systematically investigate underlying biological mechanisms and develop interventions. Prior animal models have focused on capsid and transgene-related immunogenicity, but the impact of concurrently present nontransgene or vector antigens on therapeutic efficacy, such as those derived from contaminating nucleic acids within rAAV preps, has yet to be investigated. In this study, using Ad5-CMV_GFP-immunized immunocompetent BALB/cJ mice, and a coagulation factor VIII expressing rAAV preparation that contains green flourescent protein (GFP) cDNA packaged as P5-associated contaminants, we establish a model to induce transaminitis and observe concomitant therapeutic efficacy reduction after rAAV administration. We observed strong epitope-specific anti-GFP responses in splenic CD8+ T cells when GFP cDNA was delivered as a P5-associated contaminant of rAAV, which coincided and correlated with alanine and aspartate aminotransferase elevations. Furthermore, we report a significant reduction in detectable circulating FVIII protein, as compared with control mice. Lastly, we observed an elevation in the detection of AAV8 capsid-specific T cells when GFP was delivered either as a contaminant or transgene to Ad5-CMV_GFP-immunized mice. We present this model as a potential tool to study the underlying biology of post-AAV hepatotoxicity and demonstrate the potential for T cell responses against proteins produced from AAV encapsidated nontherapeutic nucleic acids, to interfere with efficacious gene transfer.

11.
Langmuir ; 40(4): 2369-2376, 2024 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-38230676

RESUMO

Urinary tract infections (UTIs) have greatly affected human health in recent years. Accurate and rapid diagnosis of UTIs can enable a more effective treatment. Herein, we developed a multichannel sensor array for efficient identification of bacteria based on three antimicrobial agents (vancomycin, lysozyme, and bacitracin) functional gold nanoclusters (AuNCs). In this sensor, the fluorescence intensity of the three AuNCs was quenched to varying degrees by the bacterial species, providing a unique fingerprint for different bacteria. With this sensing platform, seven pathogenic bacteria, different concentrations of the same bacteria, and even bacterial mixtures were successfully differentiated. Furthermore, UTIs can be accurately identified with our sensors in ∼30 min with 100% classification accuracy. The proposed sensing systems offer a rapid, high-throughput, and reliable sensing platform for the diagnosis of UTIs.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Humanos , Ouro , Vancomicina , Bactérias , Espectrometria de Fluorescência
12.
Am J Hosp Palliat Care ; 41(4): 431-441, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37386881

RESUMO

Background: Surprise questions (SQs) are used as screening tools in palliative care. Probabilistic questions (PQs) are more accurate than temporal predictions. However, no study has examined the usefulness of SQs and PQs assessed by nurses. Objectives: To examine the accuracy of nurses' SQ and PQ assessments in patients with advanced cancer receiving home palliative care. Design: A prospective single-center cohort study. Setting/Subjects: Adult patients with advanced cancer who received palliative care at home in South Korea between 2019 and 2020. Measurements: Palliative care specialized nurses were asked the SQ, "Would you be surprised if the patient died in a specific timeframe?" and PQ, "What is the probability that this patient will be alive (0 to 100%) within a specific timeframe?" at the 1-, 2-, 4-, and 6-week timeframes at enrollment. We calculated the sensitivities and specificities of the SQs and PQs. Results: 81 patients were recruited with 47 days of median survival. The sensitivity, specificity, and overall accuracy (OA) of the 1-week SQ were 50.0, 93.2, and 88.9%, respectively. The accuracies for the 1-week PQ were 12.5, 100.0, and 91.3%, respectively. The 6-week SQ showed sensitivity, specificity, and OA of 84.6, 42.9, and 62.9%, respectively; the accuracies for the 6-week PQ were 59.0, 66.7, and 63.0%, respectively.Conclusion: The SQ and PQ showed acceptable accuracy in home palliative care patients. Interestingly, PQ showed higher specificity than SQ at all timeframes. The SQ and PQ assessed by nurses may be useful in providing additional prognostic information for home palliative care.


Assuntos
Neoplasias , Cuidados Paliativos , Adulto , Humanos , Estudos Prospectivos , Estudos de Coortes , Morte , Prognóstico , Neoplasias/terapia
13.
Adv Sci (Weinh) ; 11(4): e2305442, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38009491

RESUMO

Neuroinflammation is associated with poor outcomes in patients with spinal cord injury (SCI). Recent studies have demonstrated that stimulator of interferon genes (Sting) plays a key role in inflammatory diseases. However, the role of Sting in SCI remains unclear. In the present study, it is found that increased Sting expression is mainly derived from activated microglia after SCI. Interestingly, knockout of Sting in microglia can improve the recovery of neurological function after SCI. Microglial Sting knockout restrains the polarization of microglia toward the M1 phenotype and alleviates neuronal death. Furthermore, it is found that the downregulation of mitofusin 2 (Mfn2) expression in microglial cells leads to an imbalance in mitochondrial fusion and division, inducing the release of mitochondrial DNA (mtDNA), which mediates the activation of the cGas-Sting signaling pathway and aggravates inflammatory response damage after SCI. A biomimetic microglial nanoparticle strategy to deliver MASM7 (named MSNs-MASM7@MI) is established. In vitro, MSNs-MASM7@MI showed no biological toxicity and effectively delivered MASM7. In vivo, MSNs-MASM7@MI improves nerve function after SCI. The study provides evidence that cGas-Sting signaling senses Mfn2-dependent mtDNA release and that its activation may play a key role in SCI. These findings provide new perspectives and potential therapeutic targets for SCI treatment.


Assuntos
Microglia , Traumatismos da Medula Espinal , Humanos , Microglia/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Regulação para Baixo , Inflamação/metabolismo , Traumatismos da Medula Espinal/metabolismo , Nucleotidiltransferases/metabolismo
14.
Biochem Biophys Res Commun ; 692: 149360, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38081108

RESUMO

BACKGROUND: Myocardial infarction (MI) dramatically changes the mechanical stress, which is intensified by the fibrotic remodeling. Integrins, especially the αV subunit, mediate mechanical signal and mechanoparacrine of transforming growth factor ß1 (TGF-ß1) in various organ fibrosis by activating CFs into myofibroblasts (MFBs). We investigated a possible role of integrin αV mediated mechanoparacrine of TGF-ß1 in MFBs activation for fibrous reparation in mice with MI. METHODS: Heart samples from MI, sham, or MI plus cilengitide (14 mg/kg, specific integrin αV inhibitor) treated mice, underwent functional and morphological assessments by echocardiography, and histochemistry on 7, 14 and 28 days post-surgery. The mechanical and ultrastructural changes of the fibrous scar were further evaluated by atomic mechanics microscope (AFM), immunofluorescence, second harmonic generation (SHG) imaging, polarized light and scanning electron microscope, respectively. Hydroxyproline assay was used for total collagen content, and western blot for protein expression profile examination. Fibroblast bioactivities, including cell shape, number, Smad2/3 signal and expression of extracellular matrix (ECM) related proteins, were further evaluated by microscopic observation and immunofluorescence in polyacrylamide (PA) hydrogel with adjustable stiffness, which was re-explored in fibroblast cultured on stiff matrix after silencing of integrin αV. The content of total and free TGF-ß1 was tested by enzyme-linked immunosorbent assay (ELISA) in both infarcted tissue and cell samples. RESULT: Increased stiffness with heterogeneity synchronized with integrin αV and alpha smooth muscle actin (α-SMA) positive MFBs accumulation in those less mature fibrous areas. Cilengitide abruptly reduced collagen content and disrupted collagen alignment, which also decreased TGF-ß1 bioavailability, Smad2/3 phosphorylation, and α-SMA expression in the fibrous area. Accordingly, fibroblast on stiff but not soft matrix exhibited obvious MFB phenotype, as evidenced by enlarged cell, hyperproliferation, well-developed α-SMA fibers, and elevated ECM related proteins, while silencing of integrin αV almost abolished this switch via attenuating paracrine of TGF-ß1 and nuclear translocation of Smad2/3. CONCLUSION: This study illustrated that increased tissue stiffness activates CFs into MFBs by integrin αV mediated mechanoparacrine of TGF-ß1, especially in immature scar area, which ultimately promotes fibrous scar maturation.


Assuntos
Infarto do Miocárdio , Miofibroblastos , Animais , Camundongos , Actinas/metabolismo , Cicatriz/metabolismo , Colágeno/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Fibrose , Integrina alfaV/metabolismo , Infarto do Miocárdio/patologia , Miofibroblastos/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
16.
Eur J Pharmacol ; 962: 176171, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37996009

RESUMO

Our previous study reported that the heterodimer of Angiotensin II Type I Receptor (AT1R) and Mu-Opioid Receptor 1 (MOR1) involves Nitric Oxide (NO) reduction which leads to elevation of blood pressure. Secondly, we showed that Toll-like Receptor 4 (TLR4) may be involved in the heterodimerization of AT1R and MOR1 in the brainstem Nucleus Tractus Solitarii (NTS), which regulates systemic blood pressure and gastric nitric oxide through the insulin pathway. Here, we investigated the role of microglial activation and TLR4 in the heterodimerization of AT1R and MOR1. Hypertensive rats were established after four weeks of fructose consumption. SBP of rats was measured using non-invasive blood pressure method. PLA technique was utilized to determine protein-protein interaction in the nucleus tractus solitarii. Results showed that the level of MOR-1 and AT1R was induced significantly in the fructose group compared with control. PLA signal potentially showed that AT1R and MOR1 were formed in the nucleus tractus solitarii after fructose consumption. Meanwhile, the innate immune cell in the CNS microglia was observed in the nucleus tractus solitarii using biomarkers and was activated. TLR4 inhibitor CLI-095, was administered to animals to suppress the neuroinflammation and microglial activation. CLI-095 treatment reduced the heterodimer formation of AT1R and MOR1 and restored nitric oxide production in the nucleus tractus solitarii. These findings imply that TLR4-primed neuroinflammation involves formation of heterodimers AT1R and MOR1 in the nucleus tractus solitarii which leads to increase in systemic blood pressure.


Assuntos
Angiotensina II , Hipertensão , Ratos , Animais , Angiotensina II/farmacologia , Microglia/metabolismo , Receptor 4 Toll-Like/metabolismo , Óxido Nítrico/metabolismo , Receptores Opioides/metabolismo , Frutose , Doenças Neuroinflamatórias , Pressão Sanguínea , Receptor Tipo 1 de Angiotensina/metabolismo , Poliésteres , Núcleo Solitário
17.
Macromol Biosci ; 24(4): e2300362, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38150293

RESUMO

RNA interference (RNAi) technology has been a promising treatment strategy for combating intractable diseases. However, the applications of RNAi in clinical are hampered by extracellular and intracellular barriers. To overcome these barriers, various siRNA delivery systems have been developed in the past two decades. The first approved RNAi therapeutic, Patisiran (ONPATTRO) using lipids as the carrier, for the treatment of amyloidosis is one of the most important milestones. This has greatly encouraged researchers to work on creating new functional siRNA carriers. In this review, the recent advances in siRNA carriers consisting of lipids, polymers, and polymer-modified inorganic particles for cancer therapy are summarized. Representative examples are presented to show the structural design of the carriers in order to overcome the delivery hurdles associated with RNAi therapies. Finally, the existing challenges and future perspective for developing RNAi as a clinical modality will be discussed and proposed. It is believed that the addressed contributions in this review will promote the development of siRNA delivery systems for future clinical applications.


Assuntos
Portadores de Fármacos , Nanopartículas , RNA Interferente Pequeno/química , Interferência de RNA , Portadores de Fármacos/química , Terapia Genética , Polímeros/química , Lipídeos/química , Nanopartículas/química
18.
J Biomed Sci ; 30(1): 96, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110940

RESUMO

BACKGROUND: Human enteroviruses A71 (EV-A71) and D68 (EV-D68) are the suspected causative agents of hand-foot-and-mouth disease, aseptic meningitis, encephalitis, acute flaccid myelitis, and acute flaccid paralysis in children. Until now, no cure nor mucosal vaccine existed for EV-A71 and EV-D68. Novel mucosal bivalent vaccines are highly important for preventing EV-A71 and EV-D68 infections. METHODS: In this study, formalin-inactivated EV-A71 and EV-D68 were used as antigens, while PS-G, a polysaccharide from Ganoderma lucidum, was used as an adjuvant. Natural polysaccharides have the characteristics of intrinsic immunomodulation, biocompatibility, low toxicity, and safety. Mice were immunized intranasally with PBS, EV-A71, EV-D68, or EV-A71 + EV-D68, with or without PS-G as an adjuvant. RESULTS: The EV-A71 + EV-D68 bivalent vaccine generated considerable EV-A71- and EV-D68-specific IgG and IgA titres in the sera, nasal washes, saliva, bronchoalveolar lavage fluid, and feces. These antibodies neutralized EV-D68 and EV-A71 infectivity. They also cross-neutralized infections by different EV-D68 and EV-A71 sub-genotypes. Furthermore, compared with the PBS group, EV-A71 + EV-D68 + PS-G-vaccinated mice exhibited an increased number of EV-D68- and EV-A71-specific IgA- and IgG-producing cells. In addition, T-cell proliferative responses, and IFN-γ and IL-17 secretion in the spleen were substantially induced when PS-G was used as an adjuvant with EV-A71 + EV-D68. Finally, in vivo challenge experiments demonstrated that the immune sera induced by EV-A71 + EV-D68 + PS-G conferred protection in neonate mice against lethal EV-A71 and EV-D68 challenges as indicated by the increased survival rate and decreased clinical score and viral RNA tissue expression. Taken together, all EV-A71/EV-D68 + PS-G-immunized mice developed potent specific humoral, mucosal, and cellular immune responses to EV-D68 and EV-A71 and were protected against them. CONCLUSIONS: These findings demonstrated that PS-G can be used as a potential adjuvant for EV-A71 and EV-D68 bivalent mucosal vaccines. Our results provide useful information for the further preclinical and clinical development of a mucosal bivalent enterovirus vaccine against both EV-A71 and EV-D68 infections.


Assuntos
Enterovirus Humano A , Enterovirus Humano D , Infecções por Enterovirus , Enterovirus , Reishi , Criança , Animais , Humanos , Camundongos , Enterovirus Humano D/genética , Enterovirus Humano A/genética , Vacinas Combinadas , Antígenos Virais , Imunoglobulina A , Imunoglobulina G
19.
Inorg Chem ; 62(49): 20202-20208, 2023 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-37993990

RESUMO

Single-emission luminescence sensors are less than satisfactory for complex systems due to their susceptibility to environmental disturbances. Lanthanum-based metal-organic frameworks (Ln-MOFs) with highly stable ratiometric dual-emission are regarded as promising luminescence probes owing to their fascinating ligand-to-metal energy transfer behaviors (also known as the antenna effect). Herein, we report the synthesis of a pair of isostructural europium-based MOFs (termed JNU-219 and JNU-220) by utilizing two X-shaped tetracarboxylate linkers, 4,4',4″,4‴-benzene-2,3,5,6-tetrayl-tetrabenzoate (BTEB) and 4,4',4″,4‴-pyrazine-2,3,5,6-tetrayl-tetrabenzoate (BTTB). Both JNU-219 and JNU-220 present the characteristic red luminescence of Eu3+, yet the pyrazine functionalization of the BTTB linker renders JNU-220 with significantly increased luminescence emission, almost 30 times that of JNU-219. As a result, the detection limit of JNU-220 for the ratiometric luminescence sensing of PO43- was determined to be as low as 0.22 µM, which is far superior to those of other reported MOF materials. Additionally, we demonstrate the excellent stability and reusability of JNU-220, further verifying its potential as a robust ratiometric luminescence probe.

20.
Palliat Support Care ; : 1-7, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37859416

RESUMO

OBJECTIVES: Advance care planning (ACP) interventions are supposed to affect patients' autonomy and family health-care outcomes positively. However, the clinical benefits of ACP actualization and associated contextual factors merit questioning. Therefore, this study explores the critical contextual and procedural factors related to ACP decision-making based on the actual situation of older patients with cancer encountering end-of-life care in Taiwan. METHODS: This retrospective qualitative secondary analysis used the Kipling method (5W1H) to explore further the critical contextual and procedural factors related to ACP decision-making processes. We applied thematic analysis and dual coding for 35 narratives, including 10 patients with cancer, 10 family caregivers, and 15 health-care staff, derived from a preliminary qualitative study regarding palliative care decision-making among patients with advanced cancer, their families, and health-care staff. RESULTS: We identified 6 domains detailing the contextual factors for ACP decision-making: (1) WHO (decision makers); (2) WHAT (discussion content); (3) WHEN (care plan for which disease stage); (4) WHERE (patient's situational location); (5) WHY (reasons underpinning the decisions); and (6) HOW (the way to form the decisions). SIGNIFICANCE OF RESULTS: Using the Kipling method to elaborate the contextual factors for ACP decision-making among older patients with cancer strengthens the understanding of complicated end-of-life care decision-making procedure. This study also demonstrates the dynamic and cultural complexity and the various factors considered during end-of-life care and future ACP discussion.

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