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1.
Small Methods ; : e2400697, 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38824667

RESUMO

Small molecule-based photothermal agents (PTAs) hold promising future for photothermal therapy; however, unexpected inactivation exerts negative impacts on their application clinically. Herein, a self-regenerating PTA strategy is proposed by integrating 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS•+) with a thermodynamic agent (TDA) 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH). Under NIR laser, the photothermal effect of ABTS•+ accelerates the production of alkyl radicals by AIPH, which activates the regeneration of ABTS•+, thus creating a continuous positive feedback loop between photothermal and thermodynamic effects. The combination of ABTS•+ regeneration and alkyl radical production leads to the tandem photothermal and thermodynamic tumor therapy. In vitro and in vivo experiments confirm that the synergistic action of thermal ablation, radical damage, and oxidative stress effectively realizes tumor suppression. This work offers a promising approach to address the unwanted inactivation of PTAs and provides valuable insights for optimizing combination therapy.

2.
Exploration (Beijing) ; 4(2): 20230105, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38855612

RESUMO

The tumour-targeting efficiency of systemically delivered chemodrugs largely dictates the therapeutic outcome of anticancer treatment. Major challenges lie in the complexity of diverse biological barriers that drug delivery systems must hierarchically overcome to reach their cellular/subcellular targets. Herein, an "all-in-one" red blood cell (RBC)-derived microrobot that can hierarchically adapt to five critical stages during systemic drug delivery, that is, circulation, accumulation, release, extravasation, and penetration, is developed. The microrobots behave like natural RBCs in blood circulation, due to their almost identical surface properties, but can be magnetically manipulated to accumulate at regions of interest such as tumours. Next, the microrobots are "immolated" under laser irradiation to release their therapeutic cargoes and, by generating heat, to enhance drug extravasation through vascular barriers. As a coloaded agent, pirfenidone (PFD) can inhibit the formation of extracellular matrix and increase the penetration depth of chemodrugs in the solid tumour. It is demonstrated that this system effectively suppresses both primary and metastatic tumours in mouse models without evident side effects, and may represent a new class of intelligent biomimicking robots for biomedical applications.

3.
Curr Probl Cardiol ; 49(9): 102673, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38782197

RESUMO

Right heart catheterization (RHC) stands as a unique tool for both diagnosing and managing a broad spectrum of cardiovascular diseases. Though its origins trace back to the 18th century, the most substantial progress was achieved in the 20th century. The focus of this review is on pulmonary hypertension (PH), where RHC is recognized as the diagnostic gold standard. Parameters derived from this procedure are crucial for classifying PH into various subgroups, assessing the risk of adverse events or mortality, and informing treatment strategies. The European Society of Cardiology guidelines define PH as an increase in mean pulmonary artery pressure (PAPm) greater than 25 mmHg. The differentiation between pre- and post-capillary PH is based on the levels of pulmonary artery wedge pressure (PAWP). Furthermore, right atrial pressure (RAP), cardiac index (CI), and mixed venous oxygen saturation (SvO2) are the sole parameters recommended for prognostic assessment, specifically in patients with pulmonary arterial hypertension (PAH). Patients presenting with RAP exceeding 14 mmHg, CI less than 2.0 L/min/m2, and SvO2 below 60% are considered to be at a high risk (greater than 10%) of death within the subsequent year. A primary goal in the management of PAH is the early diagnosis to facilitate the swift initiation of treatment. This aims to minimize symptom burden, optimize the patient's biochemical, hemodynamic, and functional profile, and curtail adverse events. To achieve these objectives, clinicians must remain informed about emerging risk factors and be familiar with the revised hemodynamic definition for PAH.

4.
Curr Probl Cardiol ; 49(7): 102581, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38653444

RESUMO

Out-of-hospital cardiac arrest (OHCA) is a major cause of mortality worldwide, with a high incidence and low survival rate. Prompt cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) use are major contributors in the "chain of survival" for OHCA. the response of a community plays a key role in determining the outcomes in OHCA. The outcomes of OHCA are affected by health inequalities in bystander CPR and AED use, due to factors such as differences in sex, ethnicity, and socioeconomic status amongst others. Literature shows patients from lower socio-economic backgrounds are more likely to have risk factors for a cardiac arrest and are therefore more likely to have OHCA. Studies have also reported lower rates of bystander AED use in females compared to males. Targeting deprived areas with tailored training and access to AEDs can be beneficial in improving CPR outcomes in communities. Due to the physical nature of CPR maneuvers, age and frailty of the patient can both impact the outcome of the resuscitation. Environmental factors affecting AED use include availability, visibility, accessibility, support, extra equipment, training materials, staffing, and awareness. Education should focus on areas such as conducting BLS on both male and female patients, recognizing cardiac arrest, tailoring BLS to difference ages as well as provision for training in different languages, including sign language. Like some other countries, CPR training is now being implemented in the school curriculum.


Assuntos
Reanimação Cardiopulmonar , Desfibriladores , Disparidades em Assistência à Saúde , Parada Cardíaca Extra-Hospitalar , Humanos , Reanimação Cardiopulmonar/métodos , Desfibriladores/estatística & dados numéricos , Cardioversão Elétrica/estatística & dados numéricos , Cardioversão Elétrica/instrumentação , Cardioversão Elétrica/métodos , Serviços Médicos de Emergência/estatística & dados numéricos , Serviços Médicos de Emergência/métodos , Saúde Global , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/estatística & dados numéricos , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/epidemiologia , Fatores de Risco , Fatores Socioeconômicos
5.
Curr Probl Cardiol ; 49(7): 102582, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38657722

RESUMO

Left ventricular noncompaction (LVNC) is a rare genetic and congenital disorder characterized by the excessive formation of blood-filled trabeculae and intertrabecular recesses in the uncompressed inner endocardial wall associated with a thin, compact wall, the mesocardium. Although LVNC was described for the first time as long ago as 1984, our understanding of the disease with regard to its genetic pattern, diagnosis, clinical presentation, and treatment is still scanty. LVNC can be present as an isolated condition or associated with congenital heart disease, genetic syndromes, or neuromuscular disease. This suggests that LVNC is not a distinct form of cardiomyopathy, but rather a morphological expression of different diseases. Recognition of the disease is of fundamental importance because its clinical manifestations are variable, ranging from the absence of any symptom to congestive heart failure, lethal arrhythmias, and thromboembolic events. The main cardiac symptoms associated with LVNC are related to HF, occurring in up to half of the patients. Atrial fibrillation can affect 25 % of adult patients and ventricular tachyarrhythmias up to around 50 %. There is a possible association between bradycardia and Wolff-Parkinson-White syndrome in pediatric patients with LVNC. Other frequent manifestations are related to thromboembolic events, such as stroke, pulmonary embolism, and mesenteric ischemia. In asymptomatic patients, LVNC is identified by echocardiography or when the patient is subjected to family screening. However, when the disease is identified during the fetal period, the presence of systemic diseases, such as mitochondrial alterations and metabolic disorders, is frequently reported.


Assuntos
Miocárdio Ventricular não Compactado Isolado , Humanos , Adulto , Miocárdio Ventricular não Compactado Isolado/diagnóstico , Miocárdio Ventricular não Compactado Isolado/terapia , Miocárdio Ventricular não Compactado Isolado/fisiopatologia , Ecocardiografia/métodos , Gerenciamento Clínico
6.
Adv Mater ; 36(23): e2312153, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38444205

RESUMO

The presence of bacteria in tumor results in chemotherapeutic drug resistance and weakens the immune response in colorectal cancer. To overcome bacterium-induced chemotherapeutic drug resistance and potentiate antitumor immunity, herein a novel molecule Biotin-Lys(SA-Cip-OH)-Lys(SA-CPT)-Phe-Phe-Nap (Biotin-Cip-CPT-Nap) is rationally designed containing four functional motifs (i.e., a biotin motif for targeting, Phe-Phe(-Nap) motif for self-assembly, ciprofloxacin derivative (Cip-OH) motif for antibacterial effect, and camptothecin (CPT) motif for chemotherapy). Using the designed molecule, a novel strategy of intracellular enzymatic nanofiber formation and synergistic antibacterium-enhanced chemotherapy and immunotherapy is achieved. Under endocytosis mediated by highly expressed biotin receptor in colorectal cancer cell membrane and the catalysis of highly expressed carboxylesterase in the cytoplasm, this novel molecule can be transformed into Biotin-Nap, which self-assembled into nanofibers. Meanwhile, antibiotic Cip-OH and chemotherapeutic drug CPT are released, overcoming bacterium-induced drug resistance and enhancing the therapeutic efficacy of immunotherapy towards colorectal cancer. This work offers a feasible strategy for the design of novel multifunctional prodrugs to improve the efficiency of colorectal cancer treatment.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Pró-Fármacos , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Humanos , Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Animais , Imunoterapia , Peptídeos/química , Peptídeos/farmacologia , Camptotecina/farmacologia , Camptotecina/química , Antibacterianos/farmacologia , Antibacterianos/química , Camundongos , Nanofibras/química , Ciprofloxacina/farmacologia , Ciprofloxacina/química , Liberação Controlada de Fármacos , Biotina/química
7.
Anim Nutr ; 15: 332-340, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38053804

RESUMO

This study aimed to investigate the feeding effect of wheat silage on growth performance, nutrient digestibility, rumen fermentation, and microbiota composition in feedlot lambs. Sixty-four male crossbred Chinese Han lambs (BW = 27.8 ± 0.67 kg, 3 months of age) were randomly assigned to four ration groups with wheat silage replacing 0% (WS0), 36% (WS36), 64% (WS64), and 100% (WS100) of oaten hay on forage dry matter basis. The concentrate-to-forage ratio was 80:20 and the feeding trial lasted 52 d. Increasing wheat silage inclusion linearly decreased dry matter intake by 4% to 27% (P < 0.01). However, increasing the wheat silage replacement of oaten hay by no more than 64% improved the feed efficiency by 14% as noted by the feed-to-gain ratio (P = 0.04). Apparent digestibility of organic matter (P < 0.01), neutral detergent fibre (P = 0.04) and acid detergent fibre (P < 0.01) quadratically increased. Ammonia nitrogen (P = 0.01) decreased while microbial protein production (P < 0.01) increased with the increase of wheat silage inclusion. Total volatile fatty acids concentration increased quadratically with the increase of wheat silage inclusion (P < 0.01), and the highest occurred in WS64. The molar proportion of acetate (P < 0.01) and acetate-to-propionate ratio (P = 0.04) decreased while butyrate (P < 0.01) and isovalerate (P = 0.04) increased. Increasing wheat silage inclusion increased the Firmicutes-to-Bacteroidota ratio by 226% to 357%, resulting in Firmicutes instead of Bacteroidota being the most abundant phylum. The relative abundance of cellulolytic Ruminococcus numerically increased but that of amylolytic Prevotella (P < 0.01) decreased as increasing wheat silage inclusion. Taken together, increasing wheat silage replacement of oaten hay by no more than 64% exhibited greater feed efficiency and fibre digestion despite low feed intake by feedlot lambs due to the change of Firmicutes-to-Bacteroidota ratio in the rumen.

8.
J Nanobiotechnology ; 21(1): 401, 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37907987

RESUMO

Anti-tumor M1-like and pro-tumor M2-like tumor-associated macrophages (TAMs) coexist in tumor microenvironments (TME). The adverse effects of these M1/M2 subsets on tumors directly affect the current strategies to improve anti-tumor immune response. Therefore, it has attracted great attention to change the tumor immunosuppressive microenvironment by reprogramming TAMs. In this paper, we constructed biomimetic nanoparticles (HMMDN-Met@PM) targeting M2-like TAMs for macrophage re-polarization. In detail, the core of the biomimetic nanoparticles is metformin-loaded hollow mesoporous manganese dioxide nanoparticles (HMMDN-Met). Benefited from the hollow and porous structure of HMMDN, metformin, the regulator of M1/M2 adopted in this work, can be easily and widely loaded into HMMDN. Moreover, macrophage membranes were utilized for HMMDN-Met coating (HMMDN-Met@MM) to prevent the premature drug leakage and provide specific molecular recognition/TME targeting. In addition, M2 macrophage targeting peptide (M2pep) was modified on the surface of macrophage membrane to specifically deliver the drug to M2-like TAMs to promote the polarization of M2 to M1 macrophages. Through in vitro and in vivo studies, we found that the expression of surface markers and inflammatory factors CD206, Arg-1 and IL-10 of type M2 macrophages decreased, while the surface markers of type M1 macrophages and the expression of inflammatory factors CD80, TNF-α and iNOS increased, indicating the successful re-polarization of M2 macrophages and finally realizing the inhibition of tumor growth. At the same time, under the acidic and GSH conditions of tumor, HMMDN was decomposed into Mn2+, which is a contrast agent for magnetic resonance imaging, thus realizing the tracking of tumor. This work practices biomimetic nanosystem in targeted imaging and immunotherapy, paving the way for strategy designing for tumor inhibition.


Assuntos
Metformina , Nanopartículas , Neoplasias , Humanos , Macrófagos Associados a Tumor , Biomimética , Neoplasias/tratamento farmacológico , Nanopartículas/química , Imunoterapia , Imageamento por Ressonância Magnética , Metformina/farmacologia , Microambiente Tumoral
9.
Antioxidants (Basel) ; 12(3)2023 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-36979020

RESUMO

Guanidine acetic acid (GAA) has been reported to improve growth performance, nutrient utilization, and meat quality in livestock. This study aimed to investigate whether coated GAA (CGAA) in comparison with uncoated GAA (UGAA) could have different effects on rumen fermentation, antioxidant capacity, and microflora composition in the rumen. Seventy-two lambs were randomly arranged in a 2 × 3 factorial experiment design with two diets of different forage type (OH: oaten hay; OHWS: oaten hay plus wheat silage) and three GAA treatments within each diet (control, diet without GAA addition; UGAA, uncoated GAA; CGAA, coated GAA). The whole feeding trial lasted for 120 days. The lambs in the OH group presented lower total volatile fatty acid (VFA), alpha diversity, Firmicutes, NK4A214_group, and Lachnospiraceae_NK3A20_group than those on the OHWS diet in the last 60 days of the feeding stage (p < 0.05). Regardless of what GAA form was added, dietary GAA supplementation increased the total VFA, microbial crude protein (MCP), adenosine triphosphate (ATP), and antioxidant capacity in rumen during lamb feedlotting (p < 0.05). However, molar propionate proportion, acetate:propionate ratio (A:P), and relative Succiniclasticum abundance decreased with GAA addition in the first 60 days of the growing stage, while the molar butyrate proportion and NK4A214_group (p < 0.05) in response to GAA addition increased in the last 60 days of feeding. These findings indicated that dietary GAA enhanced antioxidant capacity and fermentation characteristics in the rumen, but the addition of uncoated GAA in diets might cause some dysbacteriosis of the rumen microbiota.

10.
Foods ; 12(3)2023 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-36766172

RESUMO

The aim of this study was to investigate whether guanidine acetic acid (GAA) yields a response in rapid-growing lambs depending on forage type. In this study, seventy-two small-tailed Han lambs (initial body weights = 12 ± 1.6 kg) were used in a 120-d feeding experiment after a 7-d adaptation period. A 2 × 3 factorial experimental feeding design was applied to the lambs, which were fed a total mixed ration with two forage types (OH: oaten hay; OHWS: oaten hay plus wheat silage) and three forms of additional GAA (GAA: 0 g/kg; UGAA: Uncoated GAA, 1 g/kg; CGAA: Coated GAA, 1 g/kg). The OH diet had a greater dry matter intake, average daily gain, and hot carcass weight than the OHWS diet. The GAA supplementation increased the final body weight, hot carcass weight, dressing percentage, and ribeye area in the longissimus lumborum. Meanwhile, it decreased backfat thickness and serum triglycerides. Dietary GAA decreased the acidity of the meat and elevated the water-holding capacity in mutton. In addition, the crude protein content in mutton increased with GAA addition. Dietary GAA (UGAA or CGAA) might be an effective additive in lamb fed by different forage types, as it has potential to improve growth performance and meat quality.

12.
Nat Commun ; 13(1): 6534, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319625

RESUMO

Cancer vaccine, which can promote tumor-specific immunostimulation, is one of the most important immunotherapeutic strategies and holds tremendous potential for cancer treatment/prevention. Here, we prepare a series of nanoparticles composed of doxorubicin- and tyrosine kinase inhibitor-loaded and hyaluronic acid-coated dendritic polymers (termed HDDT nanoparticles) and find that the HDDT nanoparticles can convert various cancer cells to micrometer-sized vesicles (1.6-3.2 µm; termed HMVs) with ~100% cell-to-HMV conversion efficiency. We confirm in two tumor-bearing mouse models that the nanoparticles can restrain tumor growth, induce robust immunogenic cell death, and convert the primary tumor into an antigen depot by producing HMVs in situ to serve as personalized vaccines for cancer immunotherapy. Furthermore, the HDDT-healed mice show a strong immune memory effect and the HDDT treatment can realize long-term protection against tumor rechallenge. Collectively, the present work provides a general strategy for the preparation of tumor-associated antigen-containing vesicles and the development of personalized cancer vaccines.


Assuntos
Vacinas Anticâncer , Nanopartículas , Neoplasias , Camundongos , Animais , Células Dendríticas , Imunoterapia , Antígenos de Neoplasias , Neoplasias/tratamento farmacológico , Imunidade
13.
Front Vet Sci ; 9: 954675, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990281

RESUMO

Guanidine acetic acid (GAA) is increasingly considered as a nutritional growth promoter in monogastric animals. Whether or not such response would exist in rapid-growing lambs is unclear yet. The objective of this study was to investigate whether dietary supplementation with uncoated GAA (UGAA) and coated GAA (CGAA) could alter growth performance, nutrient digestion, serum metabolites, and antioxidant capacity in lambs. Seventy-two small-tailed Han lambs initially weighed 12 ± 1.6 kg were randomly allocated into six groups in a 2 × 3 factorial experimental design including two forage-type rations [Oaten hay (OH) vs. its combination with wheat silage (OHWS)] and three GAA treatment per ration: no GAA, 1 g UGAA, and 1 g CGAA per kg dry matter. The whole experiment was completed in two consecutive growing stages (stage 1, 13-30 kg; stage 2, 30-50 kg). Under high-concentrate feeding pattern (Stage 1, 25: 75; Stage 2, 20: 80), UGAA or CGAA supplementation in young lambs presented greater dry matter intake (DMI) in stage 1 and average daily gain (ADG) in the whole experimental period; lambs in OH group had higher ADG and DMI than that in OHWS group in stage 1 and whole experimental period, but this phenomenon was not observed in stage 2. Both UCGA and CGAA addition increased dietary DM, organic matter (OM), neutral detergent fiber (NDF), and acid detergent fiber (ADF) digestion in both stages. In blood metabolism, UCGA and CGAA addition resulted in a greater total protein (TP) and insulin-like growth factor 1(IGF-1) levels, as well as antioxidant capacity; at the same time, UCGA and CGAA addition increased GAA metabolism-creatine kinase and decreased guanidinoacetate N-methyltransferase (GAMT) and L-Arginine glycine amidine transferase catalyzes (AGAT) activity. In a brief, the results obtained in the present study suggested that GAA (UGAA and CGAA; 1 g/kg DM) could be applied to improve growth performance in younger (13-30 kg) instead of older (30-50 kg) lambs in high-concentrate feedlotting practice.

14.
Biosens Bioelectron ; 216: 114613, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35973274

RESUMO

Since atherosclerosis, a disease characterized by abnormal arterial lipid deposition, may lead to fatal cardiovascular diseases, imaging of atherosclerotic plaques is of great value for their pathological assessment. In this study, we propose a lipid droplet (LD)-hitchhiking strategy to in situ create Trojan foam cells for fluorescence/photoacoustic imaging of atherosclerotic plaques via homologous targeting effect. In our design, functional liposomes (DCP liposomes) composed of phospholipid dioleoylphosphatidylserine (DOPS), a novel LD inducer we found, and Cypate-PC, a synthesized lipid-like molecular probe, have demonstrated great capability of inducing LDs in monocytes/macrophages while being enveloped into the resulting Trojan foam cells. Taking advantage of homologous targeting effect, the imaging probe hitchhikes on the LDs in Trojan foam cells for targeted transport to the plaque sites. Moreover, the confinement in highly hydrophobic LDs endows the imaging probe with high efficiency in light absorption, enabling greatly intensified fluorescence/photoacoustic signals. The DCP liposomes have shown great potency in inducing the generation of Trojan foam cells, and eventually ex vivo fluorescence imaging and in vivo photoacoustic imaging of atherosclerotic plaques. The proposed strategy provides more insights into the design of targeted imaging methodologies, and also an effective avenue to facilitate the evaluation and subsequent treatment of atherosclerotic plaques.


Assuntos
Aterosclerose , Técnicas Biossensoriais , Técnicas Fotoacústicas , Placa Aterosclerótica , Aterosclerose/patologia , Células Espumosas/patologia , Humanos , Gotículas Lipídicas/patologia , Lipossomos , Sondas Moleculares , Imagem Óptica , Fosfolipídeos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/patologia
15.
Chem Sci ; 13(22): 6573-6582, 2022 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-35756512

RESUMO

Surface-enhanced Raman scattering (SERS) based on chemical mechanism (CM) has great potential for superior stability and selectivity. Moreover, a bioinspired CM-Raman substrate-Raman reporter system with charge separation and electron transport nature provides thylakoid-mimicking potential for multifunctional applications. Herein, hollow carbon nitride nanospheres hierarchically assembled with a well-oriented copper(ii) phthalocyanine layer and hyaluronic acid (HCNs@CuPc@HA) were designed as a light-harvesting nanocomposite and photosynthesis-mimicking nanoscaffold that enhance both CM-SERS and photoredox catalysis. Remarkable SERS enhancement was achieved due to the strengthened short-range substrate-molecule interaction, enriched CuPc molecule loading and enhanced light-mater interactions. Meanwhile, the uniform CuPc molecule film mimics a photo-pigment to accelerate the near infrared (NIR)-oxygen generation and photodynamic catalysis of photosynthetic membrane-like HCNs. The experimental findings were further validated by numerical theory analysis. The greatly enhanced SERS signal and photosynthetic-mimicking properties of the heterostructure (denoted as HCNCHs) were successfully employed for circulating tumor cell (CTC) diagnosis and SERS imaging-guided cancer catalytic therapy in tumor xenograft models.

16.
J Am Chem Soc ; 144(26): 11897-11910, 2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35731698

RESUMO

Metastasis-induced high mortality of cancers urgently demands new approaches to simultaneously inhibit primary tumor metastasis and distant tumor growth. Herein, by rational design of a trident molecule Nap-Phe-Phe-Lys(SA-CPT)-Lys(SA-HCQ)-Tyr(H2PO3)-OH (Nap-CPT-HCQ-Yp) with three functional "spears" (i.e., a phosphotyrosine motif for enzymatic self-assembly, camptothecin (CPT) motif for chemotherapy, and hydroxychloroquine (HCQ) motif for autophagy inhibition) and nanobrush-nanoparticle-nanofiber transition property, we propose a novel strategy of intracellular enzymatic nanofiber formation and synergistic autophagy inhibition-enhanced chemotherapy and immunotherapy for spatial suppression of tumor metastasis. Under sequential alkaline phosphatase catalysis and carboxylesterase hydrolysis, Nap-CPT-HCQ-Yp undergoes nanobrush-nanoparticle-nanofiber transition, accompanied by the releases of CPT and HCQ. The formed intracellular nanofibers effectively inhibit the metastasis and invasion behaviors of cancer cells. Meanwhile, the released CPT and HCQ synergistically induce a prominent therapeutic effect through autophagy inhibition-enhanced chemotherapy. Furthermore, chemotherapy of Nap-CPT-HCQ-Yp enhances immunogenic cell death, resulting in the activation of toxic T-cells. Finally, a combination of checkpoint blockade therapy and Nap-CPT-HCQ-Yp-mediated chemotherapy elicits systemic antitumor immunity, thereby achieving efficient inhibitions of primary tumors as well as distant tumors in a breast tumor model. Our work offers a simple and feasible strategy for the design of "smart" multifunctional prodrugs to spatially suppress tumor metastasis.


Assuntos
Neoplasias da Mama , Nanofibras , Nanopartículas , Pró-Fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Camptotecina/farmacologia , Camptotecina/uso terapêutico , Linhagem Celular Tumoral , Feminino , Humanos , Hidroxicloroquina/farmacologia , Hidroxicloroquina/uso terapêutico , Pró-Fármacos/uso terapêutico
17.
Anal Chem ; 94(10): 4243-4251, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35235297

RESUMO

The discrimination between dead and live cells is crucial for cell viability evaluation. Carbon dots (CDs), with advantages like simple and cost-effective synthesis, excellent biocompatibility, and high photostability, have shown potential for realizing selective live/dead cell staining. However, most of the developed CDs with the live/dead cell discrimination capacity usually have low photoluminescence quantum yields (PLQYs) and excitation wavelength-dependent fluorescence emission (which can cause fluorescence overlap with other fluorescent probes and make dual-color live/dead staining impossible), and hence, developing ultrabright CDs with excitation wavelength-independent fluorescence emission property for live/dead cell discrimination becomes an important task. Here, using a one-pot hydrothermal method, we prepared ultrasmall (∼1.6 nm), ultrabright (PLQY: ∼78%), and excitation wavelength-independent sulfur-doped carbon dots (termed S-CDs) using rose bengal and 1,4-dimercaptobenzene as raw materials and demonstrated that the S-CDs could rapidly (∼5 min) and accurately distinguish dead cells from live ones for almost all the cell types including bacterial, fungal, and animal cells in a wash-free manner. We confirmed that the S-CDs could rapidly pass through the dead cell surfaces to enter the interior of the dead cells, thus visualizing these dead cells. In contrast, the S-CDs could not enter the interior of live cells and thus could not stain these live cells. We further verified that the S-CDs presented better biocompatibility and higher photostability than the commercial live/dead staining dye propidium iodide, ensuring its bright application prospect in cell imaging and cell viability assessment. Overall, this work develops a type of CDs capable of realizing the live/dead cell discrimination of almost all the cell types (bacterial, fungal, and animal cells), which has seldom been achieved by other fluorescent nanoprobes.


Assuntos
Carbono , Pontos Quânticos , Animais , Corantes Fluorescentes , Nitrogênio , Pontos Quânticos/toxicidade , Rosa Bengala , Enxofre
18.
Front Psychiatry ; 12: 566990, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34194341

RESUMO

Chinese emergency department (ED) staff encountered significant mental stress while fighting the coronavirus disease 2019 (COVID-19) pandemic. We sought to investigate the prevalence and associated factors for depressive symptoms among ED staff (including physicians, nurses, allied health, and auxiliary ED staff). A cross-sectional national survey of ED staff who were on duty and participated in combating the COVID-19 pandemic was conducted March 1-15, 2020. A total of 6,588 emergency medical personnel from 1,060 hospitals responded to this survey. A majority of respondents scored above 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. Those aged 31-45, those working in the COVID-19 isolation unit, and those with relatives ≤ 16 or ≥70 years old at home all had statistically significant associations with scoring >10 points. Depressive symptoms among Chinese emergency medical staff were likely quite common during the response to the COVID-19 pandemic and reinforce the importance of targeted ED staff support during future outbreaks.

19.
J Mater Chem B ; 9(21): 4303-4308, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-33908594

RESUMO

Plasma membrane (PM), a fundamental building component of a cell, is responsible for a variety of cell functions and biological processes. However, it is still challenging to acquire its morphology and morphological variation information via an effective approach. Herein, we report a PM imaging study regarding an aggregation-induced emission luminogen (AIEgen) called tetraphenylethylene-naphthalimide+ (TPE-NIM+), which is derived from our previously reported tetraphenylethylene-naphthalimide (TPE-NIM). The designed AIEgen (TPE-NIM+) shows significant characteristics of ultrafast staining, high photostability, wash-free property, and long retention time at the PM, which can structurally be correlated with its positively charged quaternary amine and hydrophobic moiety. TPE-NIM+ is further applied for staining of different cell lines, proving its universal PM imaging capability. Most importantly, we demonstrate that TPE-NIM+ can clearly delineate the contours of densely packed living cells with high cytocompatibility. Therefore, TPE-NIM+ as a PM imaging reagent superior to currently available commercial PM dyes shall find a number of applications in the biological/biomedical fields and even beyond.


Assuntos
Membrana Celular/química , Sondas Moleculares/química , Coloração e Rotulagem , Linhagem Celular , Humanos , Interações Hidrofóbicas e Hidrofílicas , Análise Espectral/métodos , Estilbenos/química
20.
Langmuir ; 36(39): 11637-11644, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32902987

RESUMO

Many noble metal-based nanoparticles have emerged for applications in cancer radiotherapy in recent years, but few investigations have been carried out for palladium nanoparticles. Herein, palladium nanosheets (Pd NSs), which possess a sheetlike morphology with a diameter of ∼14 nm and a thickness of ∼2 nm, were utilized as a sensitizer to improve the performance of radiotherapy. It was found that Pd NSs alone did not decrease the cell viability after treatment for as long as 130 h, suggesting the excellent cytocompatibility of the nanoagents. However, the viability of cancer cells treated with X-ray irradiation became lower, and the viability became even lower if the cells were co-treated with X-ray and Pd NSs, indicating the radiosensitization effect of Pd NSs. Additionally, compared with X-ray irradiation, the combined treatment of Pd NSs and X-ray irradiation induced the generation of more DNA double-stranded breaks and reactive oxygen species within cancer cells, which eventually caused elevated cell apoptosis. Moreover, in vivo experiments also verified the radiosensitization effect and the favorable biocompatibility of Pd NSs, indicating their potential for acquiring satisfactory in vivo radiotherapeutic effect at lower X-ray doses. It is believed that the present research will open new avenues for the application of noble metal-based nanoparticles in radiosensitization.


Assuntos
Nanopartículas Metálicas , Radiossensibilizantes , Apoptose , Sobrevivência Celular , Nanopartículas Metálicas/toxicidade , Paládio , Radiossensibilizantes/toxicidade
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