Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 542
Filtrar
1.
Neural Regen Res ; 20(2): 587-597, 2025 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38819069

RESUMO

JOURNAL/nrgr/04.03/01300535-202502000-00034/figure1/v/2024-05-28T214302Z/r/image-tiff Several studies have found that transplantation of neural progenitor cells (NPCs) promotes the survival of injured neurons. However, a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application. Small extracellular vesicles (sEVs) contain bioactive molecules for neuronal protection and regeneration. Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases. In this study, we intravitreally transplanted sEVs derived from human induced pluripotent stem cells (hiPSCs) and hiPSCs-differentiated NPCs (hiPSC-NPC) in a mouse model of optic nerve crush. Our results show that these intravitreally injected sEVs were ingested by retinal cells, especially those localized in the ganglion cell layer. Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration, and regulated the retinal microenvironment by inhibiting excessive activation of microglia. Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells, which had protective effects on RGCs after optic nerve injury. These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

2.
J Hazard Mater ; 476: 135111, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38981231

RESUMO

Covalent organic frameworks (COFs) are attractive materials for sample pretreatment due to their tunable structures and functions. However, the precise recognition of contaminant in complex environmental matrices by COFs remains challenging owing to their insufficient specific active sites. Herein, we report Co2+ coordination-assisted molecularly imprinted flexible COF (MI-COF@Co2+) for selective recognition of ochratoxin A (OTA). The MI-COF@Co2+ was prepared via one-step polymerization of 3,3-dihydroxybenzidine, 2,4,6-tris(4-formylphenoxy)- 1,3,5-triazine, Co2+ and template. The flexible units endowed COFs with the self-adaptable ability to regulate the molecular conformation and coordinate with Co2+ to locate the imprinted cavities. The coordination interaction greatly improved the adsorption capacity and selectivity of MI-COF@Co2+ for OTA. The prepared MI-COF@Co2+ was used as solid phase extraction adsorbent for high-performance liquid chromatography determination of OTA with the detection limit of 0.03 ng mL-1 and the relative standard deviation of < 2.5 %. In addition, this method permitted interference-free determination of OTA in real samples with recovery from 89.5 % to 102.8 %. This work provides a simple way to improve the selectivity of COFs for the determination of hazardous compounds in complex environments.

3.
J Med Chem ; 67(13): 10967-10985, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38943600

RESUMO

Antibody-based targeted therapy in cancer faces a challenge due to uneven antibody distribution in solid tumors, hindering effective drug delivery. We addressed this by developing peptide mimetics with nanomolar-range affinity for Receptor Tyrosine Kinase-Like Orphan Receptor 1 (ROR1) using computational methods. These peptides showed both specific targeting and deep penetration in vitro and in vivo. Additionally, we created peptide-drug conjugates (PDCs) by linking targeting peptides to toxin drugs via various linkers and enhancing their in vivo half-life with fatty side chains for albumin binding. The antitumor candidate II-3 displayed exceptional affinity (KD = 1.72 × 10-9 M), internalization efficiency, anticancer potency (IC50 = 0.015 ± 0.002 µM), and pharmacokinetics (t1/2 = 2.6 h), showcasing a rational approach for designing PDCs with favorable tissue distribution and strong tumor penetration.


Assuntos
Peptídeos , Humanos , Animais , Peptídeos/química , Peptídeos/farmacologia , Camundongos , Linhagem Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Imunoconjugados/química , Imunoconjugados/farmacologia , Imunoconjugados/farmacocinética , Imunoconjugados/uso terapêutico , Neoplasias/tratamento farmacológico , Feminino , Camundongos Endogâmicos BALB C
4.
Adv Sci (Weinh) ; : e2309307, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38923329

RESUMO

Glaucoma is a leading cause of irreversible blindness worldwide and is characterized by progressive retinal ganglion cell (RGC) degeneration and vision loss. Since irreversible neurodegeneration occurs before diagnosable, early diagnosis and effective neuroprotection are critical for glaucoma management. Small extracellular vesicles (sEVs) are demonstrated to be potential novel biomarkers and therapeutics for a variety of diseases. In this study, it is found that intravitreal injection of circulating plasma-derived sEVs (PDEV) from glaucoma patients ameliorated retinal degeneration in chronic ocular hypertension (COH) mice. Moreover, it is found that PDEV-miR-29s are significantly upregulated in glaucoma patients and are associated with visual field defects in progressed glaucoma. Subsequently, in vivo and in vitro experiments are conducted to investigate the possible function of miR-29s in RGC pathophysiology. It is showed that the overexpression of miR-29b-3p effectively prevents RGC degeneration in COH mice and promotes the neuronal differentiation of human induced pluripotent stem cells (hiPSCs). Interestingly, engineered sEVs with sufficient miR-29b-3p delivery exhibit more effective RGC protection and neuronal differentiation efficiency. Thus, elevated PDEV-miR-29s may imply systemic regulation to prevent RGC degeneration in glaucoma patients. This study provides new insights into PDEV-based glaucoma diagnosis and therapeutic strategies for neurodegenerative diseases.

5.
Bioorg Med Chem ; 107: 117750, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38776567

RESUMO

Analgesia and blood sugar control are considered as two main unmet clinical needs for diabetes related neuropathic pain patients. Transient receptor potential vanilloid type-1 (TRPV1) channel is a highly validated target for pain perception, while no TRPV1 antagonists have been approved due to hyperthermia side effects. Herein, two series of new TRPV1 antagonists with flavonoid skeleton were designed by the structure-based drug design (SBDD) strategy. After comprehensive evaluation, compound CX-3 was identified as a promising TRPV1 antagonist. CX-3 exhibited equivalent TRPV1 antagonistic activity with classical TRPV1 antagonist BCTC in vitro, and exerted better analgesic activity in vivo than that of BCTC in the formalin induced inflammatory pain model without hyperthermia risk. Moreover, CX-3 exhibited robust glucose-lowering effects and showed high selectivity over other ion channels. Overall, these findings identified a first-in-class highly selective TRPV1 antagonist CX-3, which is a promising candidate to target the pathogenesis of diabetes related neuropathic pain.


Assuntos
Analgésicos , Hipoglicemiantes , Canais de Cátion TRPV , Animais , Humanos , Masculino , Camundongos , Ratos , Analgésicos/farmacologia , Analgésicos/química , Analgésicos/síntese química , Relação Dose-Resposta a Droga , Descoberta de Drogas , Hipoglicemiantes/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/síntese química , Estrutura Molecular , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/metabolismo
6.
Bioorg Chem ; 147: 107405, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38696843

RESUMO

The prolonged intravitreal administration of anti-vascular endothelial growth factor (VEGF) drugs is prone to inducing aberrant retinal vascular development and causing damage to retinal neurons. Hence, we have taken an alternative approach by designing and synthesizing a series of cyclic peptides targeting CC motif chemokine receptor 3 (CCR3). Based on the binding mode of the N-terminal region in CCR3 protein to CCL11, we used computer-aided identification of key amino acid sequence, conformational restriction through different cyclization methods, designed and synthesized a series of target cyclic peptides, and screened the preferred compound IB-2 through affinity. IB-2 exhibits excellent anti-angiogenic activity in HRECs. The apoptosis level of 661W cells demonstrated a significant decrease with the escalating concentration of IB-2. This suggests that IB-2 may have a protective effect on photoreceptor cells. In vivo experiments have shown that IB-2 significantly reduces retinal vascular leakage and choroidal neovascularization (CNV) area in a laser-induced mouse model of CNV. These findings indicate the potential of IB-2 as a safe and effective therapeutic agent for AMD, warranting further development.


Assuntos
Degeneração Macular , Peptídeos Cíclicos , Receptores CCR3 , Animais , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/síntese química , Degeneração Macular/tratamento farmacológico , Degeneração Macular/patologia , Camundongos , Receptores CCR3/antagonistas & inibidores , Receptores CCR3/metabolismo , Humanos , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/química , Estrutura Molecular , Relação Estrutura-Atividade , Camundongos Endogâmicos C57BL , Relação Dose-Resposta a Droga , Apoptose/efeitos dos fármacos , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/patologia , Neovascularização de Coroide/metabolismo , Células Fotorreceptoras de Vertebrados/efeitos dos fármacos , Células Fotorreceptoras de Vertebrados/patologia , Angiogênese
7.
Food Chem ; 451: 139427, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38692237

RESUMO

Here, we report a monomer planarity modulation strategy for room-temperature constructing molecularly imprinted-covalent organic frameworks (MI-COFs) for selective extraction of ochratoxin A (OTA). 2,4,6-triformylphloroglucinol (Tp) was used as basic building block, while three amino monomers with different planarity were employed as modulators to explore the effect of planarity on the selectivity of MI-COFs. The MI-TpTapa constructed from Tp and the lowest planarity of monomer Tapa gave the highest selectivity for OTA, and was further used as the adsorbent for dispersed-solid phase extraction (DSPE) of OTA in alcohol samples. Coupling MI-TpTapa based DSPE with high-performance liquid chromatography allowed the matrix-effect free determination of OTA in alcohol samples with the limit of detection of 0.023 µg kg-1 and the recoveries of 91.4-97.6%. The relative standard deviation (RSD, n = 6) of intra and inter day was <3.2%. This work provides a new way to construct MI-COFs for selective extraction of hazardous targets.


Assuntos
Contaminação de Alimentos , Impressão Molecular , Ocratoxinas , Extração em Fase Sólida , Ocratoxinas/análise , Ocratoxinas/isolamento & purificação , Ocratoxinas/química , Extração em Fase Sólida/métodos , Extração em Fase Sólida/instrumentação , Cromatografia Líquida de Alta Pressão , Contaminação de Alimentos/análise , Adsorção , Álcoois/química , Álcoois/isolamento & purificação , Estruturas Metalorgânicas/química
8.
J Hazard Mater ; 472: 134469, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38691995

RESUMO

The scarcity of selective adsorbents for efficient extraction and removal of microcystins (MCs) from complex samples greatly limits the precise detection and effective control of MCs. Three-dimensional covalent organic frameworks (3D COFs), characterized by their large specific surface areas and highly ordered rigid structure, are promising candidates, but suffer from lack of specific recognition. Herein, we design to engineer molecularly imprinted cavities within 3D COFs via molecularly imprinted technology, creating a novel adsorbent with exceptional selectivity, kinetics and capacity for the efficient extraction and removal of MCs. As proof-of-concept, a new CC bond-containing 3D COF, designated JNU-7, is designed and prepared for copolymerization with methacrylic acid, the pseudo template L-arginine and ethylene dimethacrylate to yield the JNU-7 based molecularly imprinted polymer (JNU-7-MIP). The JNU-7-MIP exhibits a great adsorption capacity (156 mg g-1) for L-arginine. Subsequently, the JNU-7-MIP based solid-phase extraction coupled with high performance liquid chromatography-mass spectrometry achieves low detection limit of 0.008 ng mL-1, wide linear range of 0.025-100 ng mL-1, high enrichment factor of 186, rapid extraction of 10 min, and good recoveries of 92.4%-106.5% for MC-LR. Moreover, the JNU-7-MIP can rapidly remove the MC-LR from 1 mg L-1 to levels (0.26-0.35 µg L-1) lower than the WHO recommended limit for drinking water (1 µg L-1). This work reveals the considerable potential of 3D COF based MIPs as promising adsorbents for the extraction and removal of contaminants in complex real samples.


Assuntos
Microcistinas , Impressão Molecular , Extração em Fase Sólida , Poluentes Químicos da Água , Microcistinas/isolamento & purificação , Microcistinas/química , Microcistinas/análise , Adsorção , Extração em Fase Sólida/métodos , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Poluentes Químicos da Água/análise , Estruturas Metalorgânicas/química , Arginina/química , Polímeros Molecularmente Impressos/química , Cromatografia Líquida de Alta Pressão , Limite de Detecção
9.
Int J Pharm ; 656: 124114, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38615804

RESUMO

Personalized medicine aims to effectively and efficiently provide customized drugs that cater to diverse populations, which is a significant yet challenging task. Recently, the integration of artificial intelligence (AI) and three-dimensional (3D) printing technology has transformed the medical field, and was expected to facilitate the efficient design and development of customized drugs through the synergy of their respective advantages. In this study, we present an innovative method that combines AI and 3D printing technology to design and fabricate customized capsules. Initially, we discretized and encoded the geometry of the capsule, simulated the dissolution process of the capsule with classical drug dissolution model, and verified it by experiments. Subsequently, we employed a genetic algorithm to explore the capsule geometric structure space and generate a complex multi-layer structure that satisfies the target drug release profiles, including stepwise release and zero-order release. Finally, Two model drugs, isoniazid and acetaminophen, were selected and fused deposition modeling (FDM) 3D printing technology was utilized to precisely print the AI-designed capsule. The reliability of the method was verified by comparing the in vitro release curve of the printed capsules with the target curve, and the f2 value was more than 50. Notably, accurate and autonomous design of the drug release curve was achieved mainly by changing the geometry of the capsule. This approach is expected to be applied to different drug needs and facilitate the development of customized oral dosage forms.


Assuntos
Inteligência Artificial , Cápsulas , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Medicina de Precisão , Impressão Tridimensional , Medicina de Precisão/métodos , Preparações de Ação Retardada/química , Acetaminofen/química , Acetaminofen/administração & dosagem , Isoniazida/química , Isoniazida/administração & dosagem , Tecnologia Farmacêutica/métodos , Composição de Medicamentos/métodos , Algoritmos
10.
J Clin Gastroenterol ; 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38652022

RESUMO

BACKGROUND: There is a lack of sufficient evidence on whether mixed-type differentiated predominant early gastric cancer (MD-EGC) can be treated endoscopically by referring to the criteria for differentiated-type early gastric cancer (EGC). This study aims to evaluate the efficacy of endoscopic submucosal dissection (ESD) in MD-EGC. METHODS: Patients with differentiated-type EGC treated with ESD first from January 2015 to June 2021 were reviewed, including MD-EGC and pure differentiated-type EGC (PD-EGC). Clinical data, including the clinicopathological characteristics, resection outcomes of ESD, and recurrence and survival time, were collected, and the difference between MD-EGC and PD-EGC was tested. RESULTS: A total of 48 patients (48 lesions) with MD-EGC and 850 patients (890 lesions) with PD-EGC were included. Compared with PD-EGC, MD-EGC had a higher submucosal invasion rate (37.5% vs. 13.7%, P<0.001) and lymphatic invasion rate (10.4% vs. 0.4%, P<0.001). The rates of complete resection (70.8% vs. 92.5%, P<0.001) and curative resection (54.2% vs. 87.4%, P<0.001) in MD-EGC were lower than those of PD-EGC. Multivariate analysis revealed that MD-EGC (OR 4.26, 95% CI, 2.22-8.17, P<0.001) was an independent risk factor for noncurative resection. However, when curative resection was achieved, there was no significant difference in the rates of recurrence (P=0.424) between the 2 groups, whether local or metachronous recurrence. Similarly, the rates of survival(P=0.168) were no significant difference. CONCLUSIONS: Despite the greater malignancy and lower endoscopic curative resection rate of MD-EGC, patients who met curative resection had a favorable long-term prognosis.

11.
Bioorg Chem ; 147: 107371, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38643564

RESUMO

Due to the strong selectivity and permeability of tumor tissue, anti-cancer peptide-drug conjugates (PDCs) can accumulate high concentration of toxic payloads at the target, effectively killing tumor cells. This approach holds great promise for tumor-targeted treatment. In our previous study, we identified the optimal peptide P1 (NPNWGRSWYNQRFK) targeting HER2 from pertuzumab, a monoclonal antibody that blocks the HER2 signaling pathway. Here, a series of PDCs were constructed through connecting P1 and CPT with different linkers. Among these, Z8 emerged as the optimal compound, demonstrating good antitumor activity and targeting ability in biological activity tests. Z8 exhibited IC50 values of 1.04 ± 0.24 µM and 1.91 ± 0.71 µM against HER2-positive SK-BR-3 and NCI-N87 cells, respectively. Moreover, superior antitumor activity and higher biosafety of Z8 were observed compared to the positive control CPT in vivo, suggesting a novel idea for the construction of PDCs.


Assuntos
Antineoplásicos , Camptotecina , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Peptídeos , Receptor ErbB-2 , Humanos , Receptor ErbB-2/metabolismo , Receptor ErbB-2/antagonistas & inibidores , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Camptotecina/farmacologia , Camptotecina/química , Relação Estrutura-Atividade , Animais , Proliferação de Células/efeitos dos fármacos , Peptídeos/química , Peptídeos/farmacologia , Peptídeos/síntese química , Estrutura Molecular , Relação Dose-Resposta a Droga , Camundongos , Descoberta de Drogas , Linhagem Celular Tumoral , Feminino , Camundongos Endogâmicos BALB C , Camundongos Nus
12.
Int J Surg ; 110(6): 3723-3733, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38498393

RESUMO

Numerous studies have demonstrated a robust correlation between metabolic syndrome (MetS) and colorectal cancer (CRC). Nonetheless, no systematic analysis or visualization of relevant publications has been conducted via bibliometrics. This research, centred on 616 publications obtainable through the Web of Science Core Collection (WoSCC), employed CiteSpace software and VOSviewer software for correlation analyses of authors, journals, institutions, countries, keywords, and citations. The findings indicate that the Public Library of Science had the highest number of publications, while the United States, China, and South Korea were the most contributory nations. Recent years have seen the mechanisms linking Metabolic Syndrome with Colorectal Cancer, including diet, obesity, insulin resistance, and intestinal flora, remain a burgeoning research area. Furthermore, bariatric surgery appears to be a promising new area of study. This paper presents the initial bibliometric and visualization analysis of research literature concerning CRC and MetS which examines research trends and hotspots.


Assuntos
Bibliometria , Neoplasias Colorretais , Síndrome Metabólica , Síndrome Metabólica/epidemiologia , Humanos , Pesquisa Biomédica/tendências , Pesquisa Biomédica/estatística & dados numéricos , Saúde Global
13.
Anal Chem ; 96(14): 5608-5614, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38534147

RESUMO

Understanding the individual fluorescence response mechanism of covalent organic frameworks (COFs) at a single-crystal level is of great significance for the rational design of COF-based microsensors but unreachable because all previous COF-based sensors are performed with average fluorescence response behavior of various sized polycrystalline COFs. Herein, we design to explore the fluorescence response of a monodisperse single-crystal COF and further reveal the individual heterogeneity of the response mechanism. Three-dimensional single-crystal COF-301 (SCOF-301) with an intramolecular H-bond-induced excited-state intramolecular proton-transfer effect is selected as a proof-of-concept SCOF. With ethanol, benzene, and ammonia as model analytes, three different deformation and competition H-bond site-induced fluorescence response mechanisms related to crystal size are revealed. Small single particles of SCOF-301 (SSCOF-301) exhibit a more flexible structure, leading to the dominant role of deformation in the fluorescence response of small-sized SSCOF-301. The decreasing flexibility of SSCOF-301 with the increase of crystal size results in involvement of competition of the H-bond site to the fluorescence response besides deformation. Further increase of the crystal size makes the large-sized SSCOF-301 difficult to deform; thus, the competition of the H-bond site dominates the fluorescence response. This work provides a deep understanding of the individual fluorescence response mechanism of COFs to guide the design of a functional COF sensor with suitable size and mechanism for different structural analytes.

14.
Int J Nanomedicine ; 19: 2553-2571, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38505171

RESUMO

Purpose: Accumulating evidence indicates that mesenchymal stem cells (MSCs)-derived exosomes hold significant potential for the treatment of atherosclerosis. However, large-scale production and organ-specific targeting of exosomes are still challenges for further clinical applications. This study aims to explore the targeted efficiency and therapeutic potential of biomimetic platelet membrane-coated exosome-mimetic nanovesicles (P-ENVs) in atherosclerosis. Methods: To produce exosome-mimetic nanovesicles (ENVs), MSCs were successively extruded through polycarbonate porous membranes. P-ENVs were engineered by fusing MSC-derived ENVs with platelet membranes and characterized using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blot. The stability and safety of P-ENVs were also assessed. The targeted efficacy of P-ENVs was evaluated using an in vivo imaging system (IVIS) spectrum imaging system and immunofluorescence. Histological analyses, Oil Red O (ORO) staining, and Western blot were used to investigate the anti-atherosclerotic effectiveness of P-ENVs. Results: Both ENVs and P-ENVs exhibited similar characteristics to exosomes. Subsequent miRNA sequencing of P-ENVs revealed their potential to mitigate atherosclerosis by influencing biological processes related to cholesterol metabolism. In an ApoE-/- mice model, the intravenous administration of P-ENVs exhibited enhanced targeting of atherosclerotic plaques, resulting in a significant reduction in lipid deposition and necrotic core area. Our in vitro experiments showed that P-ENVs promoted cholesterol efflux and reduced total cholesterol content in foam cells. Further analysis revealed that P-ENVs attenuated intracellular cholesterol accumulation by upregulating the expression of the critical cholesterol transporters ABCA1 and ABCG1. Conclusion: This study highlighted the potential of P-ENVs as a novel nano-drug delivery platform for enhancing drug delivery efficiency while concurrently mitigating adverse reactions in atherosclerotic therapy.


Assuntos
Aterosclerose , Exossomos , Células-Tronco Mesenquimais , Camundongos , Animais , Exossomos/metabolismo , Biomimética , Fusão de Membrana , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Colesterol/metabolismo , Células-Tronco Mesenquimais/metabolismo
15.
Heliyon ; 10(5): e27166, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449604

RESUMO

Platelets play a pivotal role in many physiological and pathological processes, with their special targeting/adhering properties towards infarcted myocardium, injured or dysfunctional endothelium, and growing thrombus. Leveraging the site-targeting/adhering property, a variety of platelet-inspired targeting delivery(PITD)designs have been developed, the majority of which are reached by hitchhiking live platelets, cloaking nanoparticles with platelet membranes and mimicking platelet functions. With PITD, drugs or regenerative cells can directly reach targeted sites with minimized systematical distribution thus being of great clinical benefits. Coronary heart disease (CHD) is a major health burden worldwide. Plenty of PITD designs have shown promising outcomes for the treatment of CHD in preclinical models, especially in thrombolysis and post-percutaneous coronary intervention (post-PCI) anti-restenosis. Besides, PITD applications in cardiac protection and atherosclerotic plaque imaging are also under investigation. What's more, the potential benefits of PITD in the field of cell-based therapy are also attracting growing attention since it may resolve the problem of low arriving and retention efficiency, which are also particularly discussed in this review. In brief, our focus is putting on PITD strategies designed for the treatment of CHD, which hopefully can facilitate further optimization of this direction.

16.
J Inflamm Res ; 17: 1789-1804, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38528993

RESUMO

Aim: This study aims to explore the effect of different doses of antibiotics on rats in order to observe alterations in their fecal microbiota, inflammatory changes in the colonic mucosa and four types of inflammatory markers in blood serum. Methods: Our methodology involved separating 84 female Sprague Dawley rats into groups A-G, with each group consisting of 12 rats. We collected the rat feces for analysis, using a distinct medium for bacterial cultivation and counting colonies under a microscope. On the 11th and 15th days of the experiment, half of the rats from each group were euthanized and 5 mL of abdominal aortic blood and colon tissues were collected. Inflammations changes of colon were observed and assessed by pathological Hematoxylin Eosin (HE) staining. Enzyme-linked immune sorbent assay (ELISA) was adopted for detecting C-reactive protein (CRP), IL-6, IL1-ß and TNF-α. Results: Our findings revealed that the initial average weight of the rats did not differ between groups (p>0.05); but significant differences were observed between stool samples, water intake, food intake and weight (p=0.009, <0.001, 0.016 and 0.04, respectively) within two hours after the experiment. Additionally, there were notable differences among the groups in nine tested microbiota before and after weighting methods (all p<0.001). There were no difference in nine microbiota at day 1 (all p>0.05); at day 4 A/B (p=0.044), A/D (p<0.001), A/E (p=0.029); at day 8, all p<0.01, at day 11, only A/F exist significant difference (p<0.001); at day 14 only A/D has difference (p=0.045). Inflammation changes of colon were observed between groups A-G at days 11 and 15. Significant differences between all groups can be observed for CRP, IL-6, IL1-ß and TNF-α (p<0.001). Conclusion: This study suggests that antibiotics administration can disrupt the balance of bacteria in the rat gut ecosystem, resulting in an inflammatory response in their bloodstream and inducing inflammation changes of colon.

17.
Anal Chem ; 96(8): 3561-3568, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38372135

RESUMO

Covalent organic frameworks (COFs) are attractive adsorbents for sample pretreatment due to their unique structure and properties. However, the selectivity of COFs for the extraction of hazardous compounds is still limited due to the lack of specific interactions between COFs and targets. Herein, we report a pore size adjustment strategy for room-temperature synthesis of molecularly imprinted COF (MICOF) for selective extraction of zearalenone (ZEN) in complex food samples. The three-dimensional building block tetra(4-aminophenyl) methane was used as a functional monomer, while dialdehyde monomers with different numbers of benzene ring were used to adjust the pore size of MICOF to match with the size of ZEN molecules. The prepared MICOF gave the largest adsorption capacity of 177.2 mg g-1 and the highest imprinting factor of 10.1 for ZEN so far. MICOF was used as the adsorbent for dispersed solid-phase extraction in combination with high-performance liquid chromatography for the determination of trace ZEN in cereals. The high selectivity of the developed method allows simple aqueous standard calibration for the matrix effect-free determination of ZEN in food samples. The limit of detection and the recoveries of the developed method were 0.21 µg kg-1 and 93.7-101.4%, respectively. The precision for the determination of ZEN was less than 3.8% (RSD, n = 6). The developed method is promising for the selective determination of ZEN in complex matrices.


Assuntos
Estruturas Metalorgânicas , Nanosferas , Zearalenona , Estruturas Metalorgânicas/química , Zearalenona/análise , Grão Comestível/química , Temperatura , Cromatografia Líquida de Alta Pressão/métodos , Extração em Fase Sólida/métodos , Adsorção
18.
PLoS One ; 19(2): e0298789, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38394225

RESUMO

A key metric to determine the performance of a stock in a market is its return over different investment horizons (τ). Several works have observed heavy-tailed behavior in the distributions of returns in different markets, which are observable indicators of underlying complex dynamics. Such prior works study return distributions that are marginalized across the individual stocks in the market, and do not track statistics about the joint distributions of returns conditioned on different stocks, which would be useful for optimizing inter-stock asset allocation strategies. As a step towards this goal, we study emergent phenomena in the distributions of returns as captured by their pairwise correlations. In particular, we consider the pairwise (between stocks i, j) partial correlations of returns with respect to the market mode, ci,j(τ), (thus, correcting for the baseline return behavior of the market), over different time horizons (τ), and discover two novel emergent phenomena: (i) the standardized distributions of the ci,j(τ)'s are observed to be invariant of τ ranging from from 1000min (2.5 days) to 30000min (2.5 months); (ii) the scaling of the standard deviation of ci,j(τ)'s with τ admits good fits to simple model classes such as a power-law τ-λ or stretched exponential function [Formula: see text] (λ, ß > 0). Moreover, the parameters governing these fits provide a summary view of market health: for instance, in years marked by unprecedented financial crises-for example 2008 and 2020-values of λ (scaling exponent) are substantially lower. Finally, we demonstrate that the observed emergent behavior cannot be adequately supported by existing generative frameworks such as single- and multi-factor models. We introduce a promising agent-based Vicsek model that closes this gap.


Assuntos
Investimentos em Saúde , Modelos Econômicos , Humanos , Alimentos Formulados , Hospitalização , Idioma
19.
J Hazard Mater ; 467: 133755, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38359765

RESUMO

Covalent organic frameworks (COFs) are promising adsorbents for extraction, but their selectivity for molecular recognition remains a challenging issue due to the very limited structural design with rigid structure. Herein, we report an elegant strategy for the design and synthesis of molecularly imprinted flexible COFs (MI-FCOFs) via one-pot reaction between the flexible building block of 2,4,6-tris(4-formylphenoxy)- 1,3,5-triazine and linear 4-phenylenediamine for selective extraction of aflatoxins. The flexible chain structure enabled the developed MI-FCOF to adjust the shape and conformation of frameworks to suit the template molecule, giving high selectivity for aflatoxins recognition. Moreover, MI-FCOF with abundant imprinted sites and function groups exhibited an exceptional adsorption capacity of 258.4 mg g-1 for dummy template which is 3 times that of no-imprinted FCOF (NI-FCOF). Coupling MI-FCOF based solid-phase extraction with high-performance liquid chromatography gave low detection limits of 0.003-0.09 ng mL-1 and good precision with relative standard deviations ≤ 6.7% for the determination of aflatoxins. Recoveries for the spiked rice, corn, wheat and peanut samples were in the range of 85.4%- 105.4%. The high selectivity of the developed MI-FCOF allows matrix-free determination of AFTs in food samples. This work offers a new way to the design of MI-FCOF for selective molecular recognition.


Assuntos
Aflatoxinas , Estruturas Metalorgânicas , Impressão Molecular , Adsorção , Arachis
20.
Eur J Med Chem ; 267: 116208, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38325006

RESUMO

Dual-acting drugs that simultaneously inhibit fatty acid amide hydrolase (FAAH) and antagonize the transient receptor potential vanilloid 1 (TRPV1) is a promising stronger therapeutic approach for pain management without side effects associated with single-target agents. Here, several series of dual FAAH/TRPV1 blockers were designed and synthesized through rational molecular hybridization between the pharmacophore of classical TRPV1 antagonists and FAAH inhibitors. The studies resulted in compound 2r, which exhibited strong dual FAAH/TRPV1 inhibition/antagonism in vitro, exerted powerful analgesic effects in formalin-induced pain test (phase II, in mice), desirable anti-inflammatory activity in carrageenan-induced paw edema in rats, no TRPV1-related hyperthermia side effect, and favorable pharmacokinetic properties. Meanwhile, the contributions of TRPV1 and FAAH to its antinociceptive effects were verified by target engagement and molecular docking studies. Overall, compound 2r can serve as a new scaffold for developing FAAH/TRPV1 dual-activie ligands to counteract pain.


Assuntos
Antineoplásicos , Manejo da Dor , Ratos , Camundongos , Animais , Simulação de Acoplamento Molecular , Canais de Cátion TRPV , Ácidos Araquidônicos , Dor/tratamento farmacológico , Amidoidrolases/metabolismo , Antineoplásicos/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...