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1.
Curr Top Microbiol Immunol ; 440: 71-110, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-32483657

RESUMO

mRNA vaccines have become a versatile technology for the prevention of infectious diseases and the treatment of cancers. In the vaccination process, mRNA formulation and delivery strategies facilitate effective expression and presentation of antigens, and immune stimulation. mRNA vaccines have been delivered in various formats: encapsulation by delivery carriers, such as lipid nanoparticles, polymers, peptides, free mRNA in solution, and ex vivo through dendritic cells. Appropriate delivery materials and formulation methods often boost the vaccine efficacy which is also influenced by the selection of a proper administration route. Co-delivery of multiple mRNAs enables synergistic effects and further enhances immunity in some cases. In this chapter, we overview the recent progress and existing challenges in the formulation and delivery technologies of mRNA vaccines with perspectives for future development.


Assuntos
Doenças Transmissíveis , Nanopartículas , Neoplasias , Vacinas , Humanos , Vacinas de mRNA , Vacinação , RNA Mensageiro/genética
2.
Rev Cardiovasc Med ; 24(12): 360, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39077072

RESUMO

Atrial fibrillation (AF) is one the most prevalent arrhythmias globally and is associated with a significantly higher risk of morbidity and mortality, including an up to five-fold increase in risk of stroke. While oral anticoagulation therapy remains the standard approach for stroke prevention in nonvalvular AF, left atrial appendage occlusion (LAAO) has emerged as a viable alternative for patients who are intolerant to long-term oral anticoagulation therapy. However, selecting appropriate candidates for LAAO requires a comprehensive evaluation that considers various clinical factors, although this presents a challenge in clinical practice. This review aims to provide an overview of the current recommendations for patient selection in LAAO procedures and the key factors that need to be considered both before and after the procedure, as well as the ongoing advancements in this field that may facilitate the selection of patients for LAAO.

3.
Ecotoxicol Environ Saf ; 236: 113491, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35397443

RESUMO

Since non-covalent bound character and widespread application in numerous products, people are exposed to di-n-butyl phthalate (DBP) at low levels through various ways. Epidemiological studies suggested an association between DBP exposure and atherosclerosis (AS). Still, molecular mechanisms remain unclear. This study aimed to explore the effects of DBP on monocyte recruitment, a key and initial step of AS. EA.hy926 cells were treated with DBP (10-9-10-5 M) or DMSO as control. Chemotaxis assay was applied to investigate THP-1 recruitment. Expression of mRNA /miRNAs and proteins were measured by qRT-PCR and Western blotting, respectively. Levels of monocyte chemotactic protein 1 (MCP-1) in supernatant were detected by ELISA assay. Receptor internalization assay was performed to confirm C-C chemokine receptor type 2 (CCR2) subcellular localization in THP-1 cells and the binding between CCR2 and MCP-1. Dual-luciferase reporter assay was used to analyze the combination between miR-137-3p and specificity protein 1 (SP1), as well as SP1 and MCP-1. Results showed that number of recruited THP-1 cells after EA.hy926 cells treated by DBP was significantly higher than that in the control group due to promoted MCP-1 expression. In addition, expression of MCP-1 was regulated through miR-137-3p-SP1 cascade. Besides, overexpression of miR-137-3p reversed the increased number of recruited THP-1 cells. Our results implied that DBP might promote THP-1 recruitment by targeting miR-137-3p-SP1-MCP-1 in EA.hy926 cells.


Assuntos
Aterosclerose , MicroRNAs , Aterosclerose/metabolismo , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Dibutilftalato/toxicidade , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Monócitos , Receptores de Quimiocinas , Fator de Transcrição Sp1/genética , Fator de Transcrição Sp1/metabolismo
4.
Bioorg Med Chem ; 27(11): 2187-2191, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31005367

RESUMO

Targeted drug delivery platforms can increase the concentration of drugs in specific cell populations, reduce adverse effects, and hence improve the therapeutic effect of drugs. Herein, we designed two conjugates by installing the targeting ligand GalNAc (N-acetylgalactosamine) onto atorvastatin (AT). Compared to the parent drug, these two conjugates, termed G2-AT and G2-K-AT, showed increased hepatic cellular uptake. Moreover, both conjugates were able to release atorvastatin, and consequently showed dramatic inhibition of ß-hydroxy-ß-methylglutaryl-CoA (HMG-CoA) reductase and increased LDL receptors on cell surface.


Assuntos
Acetilgalactosamina/análogos & derivados , Acetilgalactosamina/farmacologia , Receptor de Asialoglicoproteína/metabolismo , Atorvastatina/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Acetilgalactosamina/metabolismo , Animais , Atorvastatina/síntese química , Atorvastatina/metabolismo , Linhagem Celular Tumoral , Hepatócitos/metabolismo , Humanos , Hidroximetilglutaril-CoA Redutases/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/síntese química , Inibidores de Hidroximetilglutaril-CoA Redutases/metabolismo , Ligantes , Receptores de LDL/metabolismo , Suínos
5.
Bioorg Med Chem ; 27(3): 479-482, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30594452

RESUMO

Daratumumab, an FDA approved antibody drug, displays specific targeting ability to abnormal white blood cells overexpressing CD38 and provides efficacious therapy for multiple myeloma. Here, in order to achieve enhanced remission of multiple myeloma, we designed Dara-DM4, antibody drug conjugates (ADCs) by conjugating Daratumumab and DM4 via a disulfide linker. Dara-DM4 showed significantly higher cellular uptake and inhibitory efficacy on MM1S cells that overexpressing CD38 with an IC50 of 0.88 µg/mL post 72 hr treatment. These results support a promising ADCs strategy for multiple myeloma treatment.


Assuntos
Anticorpos Monoclonais/metabolismo , Desenho de Fármacos , Imunoconjugados/farmacologia , Maitansina/farmacologia , Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Imunoconjugados/química , Maitansina/química , Estrutura Molecular , Relação Estrutura-Atividade
6.
Molecules ; 21(1): E46, 2015 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-26729079

RESUMO

This study was aimed to investigate whether vitamin A deficiency could alter P-GP expression and function in tissues of rats and whether such effects affected the drug distribution in vivo of vitamin A-deficient rats. We induced vitamin A-deficient rats by giving them a vitamin A-free diet for 12 weeks. Then, Abcb1/P-GP expression was evaluated by qRT-PCR and Western blot. qRT-PCR analysis revealed that Abcb1a mRNA levels were increased in hippocampus and liver. In kidney, it only showed an upward trend. Abcb1b mRNA levels were increased in hippocampus, but decreased in cerebral cortex, liver and kidney. Western blot results were in good accordance with the alterations of Abcb1b mRNA levels. P-GP function was investigated through tissue distribution and body fluid excretion of rhodamine 123 (Rho123), and the results proclaimed that P-GP activities were also in good accordance with P-GP expression in cerebral cortex, liver and kidney. The change of drug distribution was also investigated through the tissue distribution of vincristine, and the results showed a significantly upward trend in all indicated tissues of vitamin A-deficient rats. In conclusion, vitamin A deficiency may alter Abcb1/P-GP expression and function in rat tissues, and the alterations may increase drug activity/toxicity through the increase of tissue accumulation.


Assuntos
Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Vincristina/toxicidade , Deficiência de Vitamina A/induzido quimicamente , Animais , Córtex Cerebral/metabolismo , Modelos Animais de Doenças , Hipocampo/metabolismo , Rim/metabolismo , Fígado/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Vincristina/farmacocinética , Deficiência de Vitamina A/genética , Deficiência de Vitamina A/metabolismo
7.
Water Res ; 257: 121755, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38739979

RESUMO

Algal bloom (AB) risk assessment is critical for maintaining ecosystem health and human sustainability. Previous AB risk assessments have focused on the potential occurrence of ABs and related factors in the growing season, whereas their hazards, especially in the pre-growing season, have attracted less attention. Here, we performed a comprehensive AB risk assessment, including water trophic levels, phytoplankton biomass, functional trait-based assemblages, and related environmental factors, in the pre-growing season in Dongting Lake, China. Although mesotrophic water and low phytoplankton biomass suggested low AB potential, toxic taxa, which constituted 13.28% of the phytoplankton biomass, indicated non-negligible AB hazards. NH4+ and water temperature were key factors affecting phytoplankton motility and toxicity. Our study establishes a new paradigm for quantitative AB risk assessment, including both potential AB occurrence and hazards. We emphasize the importance of phytoplankton functional traits for early AB warning and NH4+ reduction for AB control in the pre-growing season.


Assuntos
Biomassa , Eutrofização , Lagos , Fitoplâncton , Estações do Ano , Medição de Risco , China , Monitoramento Ambiental/métodos , Ecossistema
8.
Anal Chim Acta ; 1279: 341763, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-37827664

RESUMO

In a qualitative analysis of near-infrared spectroscopy (NIRS), when the samples to be analyzed are difficult to obtain or there are few counterexamples, the robustness of the models is poor, resulting in the decline of the generalization ability of the models. In this case, the effective method is to construct virtual samples to achieve the balance of categories. In this contribution, three virtual spectrum construction strategies including Synthetic Minority Oversampling Technique (SMOTE), Adaptive Synthetic Sampling (ADASYN), and Deep Convolutional Generative Adversarial Network (DCGAN) were explored to deal with the problem of insufficient or imbalanced sample numbers in NIRS analysis. The strategies were tested with the melamine and Yali pears two spectral datasets. The PLS-DA and Correct Recognition Rate (CRR) were used for discriminant model construction and accuracy evaluation, respectively. The results show that SMOTE, ADASYN, and DCGAN processing strategies can all improve the global CRR (CRRglob). The SMOTE and ADASYN can improve the CRR for majority class sample (CRRmaj), but the CRR for minority class sample (CRRmin) has decreased. For the DCGAN method, the CRRglob, CRRmaj, and CRRmin were all improved. The standard deviation of the results of the multiple parallel calculations demonstrates the robustness of DCGAN generation method. Therefore, the DCGAN method has good reliability and practicability, and can increase the robustness and generalization ability of the NIRS model.

9.
Biosensors (Basel) ; 13(2)2023 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-36831969

RESUMO

Browning is the most common physiological disease of Yali pears during storage. At the initial stage, browning only occurs in the tissues near the fruit core and cannot be detected from the appearance. The disease, if not identified and removed in time, will seriously undermine the quality and sale of the whole batch of fruit. Therefore, there is an urgent need to explore a method for early diagnosis of the browning in Yali pears. In order to realize the dynamic and online real-time detection of the browning in Yali pears, this paper conducted online discriminant analysis on healthy Yali pears and those with different degrees of browning using visible-near infrared (Vis-NIR) spectroscopy. The experimental results show that the prediction accuracy of the original spectrum combined with a 1D-CNN deep learning model reached 100% for the test sets of browned pears and healthy pears. Features extracted by the 1D-CNN method were converted into images by Gramian angular field (GAF) for PCA visual analysis, showing that deep learning had good performance in extracting features. In conclusion, Vis-NIR spectroscopy combined with the 1D-CNN discriminant model can realize online detection of browning in Yali pears.


Assuntos
Pyrus , Pyrus/química , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Frutas/química
10.
J Sci Food Agric ; 92(7): 1504-10, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22189958

RESUMO

BACKGROUND: Populations of Coilia nasus, an anadromous fish, have declined dramatically in the Yangtze River estuary and its associated lakes owing to excessive fishing and changes in aquatic ecology. Recently, the success of artificial breeding programmes and advanced methods of propagation have allowed great increases in production of this species. Thus, to gain a better understanding of the flesh quality of C. nasus, muscle cellularity and quality parameters of the flesh were studied in wild and farmed specimens. RESULTS: Muscle cellularity was different between wild and farmed fish. Muscle fibre density was significantly higher in farmed specimens, while muscle fibre diameter was higher in wild specimens. Farmed fish had higher moisture, hydroxyproline and collagen contents and a lower fat content compared with wild fish. No significant differences in textural parameters were found between the two groups. Saturated (SFA), polyunsaturated (PUFA) and total n-6 fatty acid contents were significantly higher in farmed fish, but monounsaturated fatty acid (MUPA) content was higher in wild fish. CONCLUSION: The variation in the studied parameters determined significant differences in the flesh quality of wild and farmed C. nasus. Depending on muscle cellularity and fatty acid composition, farmed fish could be more suitable for human consumption than wild fish.


Assuntos
Animais Selvagens/metabolismo , Aquicultura , Ácidos Graxos/metabolismo , Peixes , Células Musculares/citologia , Músculo Esquelético , Alimentos Marinhos/análise , Animais , Colágeno/metabolismo , Dieta , Gorduras na Dieta/metabolismo , Abastecimento de Alimentos/métodos , Humanos , Hidroxiprolina/metabolismo , Músculo Esquelético/citologia , Músculo Esquelético/metabolismo , Água/metabolismo
11.
Front Nutr ; 9: 1026730, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36352901

RESUMO

Insect-affected pests, as an important indicator in inspection and quarantine, must be inspected in the imports and exports of fruits like "Yali" pears (a kind of duck head-shaped pear). Therefore, the insect-affected pests in Yali pears should be previously detected in an online, real-time, and accurate manner during the commercial sorting process, thus improving the import and export trade competitiveness of Yali pears. This paper intends to establish a model of online and real-time discrimination for recessive insect-affected pests in Yali pears during commercial sorting. The visible-near-infrared (Vis-NIR) spectra of Yali samples were pretreated to reduce noise interference and improve the spectral signal-to-noise ratio (SNR). The Competitive Adaptive Reweighted Sampling (CARS) method was adopted for the selection of feature modeling variables, while Partial Least Squares Discriminant Analysis (PLS-DA), Support Vector Machine (SVM), and Convolutional Block Attention Module-Convolutional Neural Networks (CBAM-CNN) were used to establish online discriminant models. T-distributed Stochastic Neighbor Embedding (T-SNE) and Gradient-weighted Class Activation Mapping (Grad-CAM) were used for the clustering and attention distribution display of spectral features of deep learning models. The results show that the online discriminant model obtained by SGS pretreatment combined with the CBAM-CNN deep learning method exhibits the best performance, with 96.88 and 92.71% accuracy on the calibration set and validation set, respectively. The prediction time of a single pear is 0.032 s, which meets the online sorting requirements.

12.
Front Nutr ; 9: 1042868, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330143

RESUMO

Visible-near infrared (Vis-NIR) spectra analysis method is widely used in the quality grading of bulk fruits with its rapid, non-destructive, diverse detection modes and flexible modular integration scheme. However, during the online grading of fruits, the random mechanized way of dropping fruit onto the conveyor belt method and the open detection environment led to more spectral abnormal samples, which affect the accuracy of the detection. In this paper, the soluble solids content (SSC) of snow peach is quantitatively analyzed by static and online detection methods. Several spectral preprocessing methods including Norris-Williams Smoothing (NWS), Savitzky-Golay Smoothing (SGS), Continuous Wavelet Derivative (CWD), Multivariate Scattering Correction (MSC), and Variable Sorting for Normalization (VSN) are adopted to eliminate spectral rotation and translation errors and improve the signal-to-noise ratio. Monte Carlo Uninformative Variable Elimination (MCUVE) method is used for the selection of optimal characteristic modeling variables. Partial Least Squares Regression (PLSR) is used to model and analyze the preprocessed spectra and the spectral variables optimized by MCUVE, and the effectiveness of the method is evaluated. Sparse Partial Least Squares Regression (SPLSR) and Sparse Partial Robust M Regression (SPRMR) are used for the construction of robust models. The results showed that the SGS preprocessing method can effectively improve the analysis accuracy of static and online models. The MCUVE method can realize the extraction of stable characteristic variables. The SPRMR model based on SGS preprocessing method and the effective variables has the optimal analysis results. The analysis accuracy of snow peach static model is slightly better than that of online analytical model. Through the test results of the PLSR, SPLSR and SPRMR models by the artificially adding noise test method, it can be seen that the SPRMR method eliminates the influence of abnormal samples on the model during the modeling process, which can effectively improve the anti-noise ability and detection reliability.

13.
Toxicology ; 477: 153279, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35926758

RESUMO

Di-n-butyl phthalate (DBP) is ubiquitous in environment and has been detected in almost all human bodies. Few data could be found about the effects of DBP on cardiovascular system, though its reproductive toxicities have been studied extensively. This study aimed to explore effects of DBP on phenotypic switching of vascular smooth muscle cells (VSMCs), an essential step during the formation of atherosclerosis (AS). A7r5 cells were employed and exposed to various levels of DBP (10-9, 10-8, 10-7, 10-6, and 10-5 M) or DMSO as control. CCK-8 assay was used to detect the effects of DBP on cell viability. Expressions of mRNA/miRNAs and proteins were measured by qRT-PCR and western blotting, respectively. Bioinformatic analysis and dual-luciferase reporter assay were used to analyze the combination between miR-139-5p and Myocardin (MYOCD). Results revealed that DBP at 10-7 M prompted phenotypic switching from contractile to synthetic of VSMCs by inhibiting contractile VSMCs marker genes via suppressing the expression of MYOCD. Moreover, miR-139c-5p directly targeted MYOCD 3'UTR and modulated MYOCD expression. Besides, DBP inhibited the expression of MYOCD and VSMCs marker genes by upregulating miR-139-5p. Collectively, these data suggested that DBP could promote the phenotypic switching from contractile to synthetic of VSMCs in A7r5 cells through miR-139-5p-MYOCD.


Assuntos
MicroRNAs , Músculo Liso Vascular , Proliferação de Células , Células Cultivadas , Dibutilftalato/toxicidade , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso , Proteínas Nucleares , Transativadores
14.
Environ Pollut ; 313: 120242, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36162564

RESUMO

Eutrophication transforms clear water into turbid water in shallow lakes. Current restoration techniques focus on re-establishing the clear-water state rather than on its maintenance. We investigated the response of submerged macrophytes to temporary grass carp (Ctenopharyngodon idella) and scraping snail (Bellamya aeruginosa) introductions. We also explored the impacts of herbivores on underwater light conditions to identify their long- and short-term potential to halt regime shift from clear to turbid after clear-water state reestablishment. Herbivores reduced both the biomass of submerged macrophytes and accumulated nutrients in the tissue of submerged macrophytes. This potentially avoided the pulse of endogenous nutrient release which would have exceeded the threshold required for the regime shift from clear to turbid. However, herbivores had a non-significant impact on submerged macrophyte-reduced light attenuation coefficient, which has a positive linear relationship with water chlorophyll a. Further, grass carp and snails enhanced the inhibition ratio of submerged macrophytes to phytoplankton by 3.96 and 2.13 times, respectively. Our study provides novel findings on the potential of herbivore introduction as an indirect biomanipulation tool for halting the regime shift of shallow lakes from clear to turbid after the restoration of submerged macrophytes.


Assuntos
Carpas , Herbivoria , Animais , Clorofila A , Ecossistema , Eutrofização , Lagos , Fósforo , Fitoplâncton , Água
15.
Nutrients ; 14(24)2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36558392

RESUMO

Magnesium is one of the most abundant essential minerals in the body. Magnesium supplements mostly have low bioavailability, except magnesium L-threonate. In 2010, a novel magnesium compound, magnesium L-threonate (Magtein®) was identified and was shown to raise the magnesium levels in the brain and neurons effectively. In this double-blind, placebo-controlled study, Magtein®PS, a magnesium L-threonate (Magtein®)- and phosphatidylserine-based formulation additionally containing vitamins C and D, was tested for its cognitive benefits in 109 healthy Chinese adults aged 18-65 years. Subjects were randomly assigned to receive either Magtein®PS or placebo (starch) capsules, at a dose of 2 g/day. "The Clinical Memory Test", the standard test commonly used in Chinese hospitals and academic institutes for cognitive evaluation, was administered before and 30 days after subjects received the supplement. Subjects receiving Magtein®PS showed significant improvements over the control group in all five subcategories of "The Clinical Memory Test" as well as the overall memory quotient scores. The older participants showed more improvement than younger participants. Results indicated significant benefits of Magtein®PS in improving memory and cognition in healthy Chinese adults.


Assuntos
População do Leste Asiático , Magnésio , Humanos , Adulto , Magnésio/farmacologia , Encéfalo , Cognição , Suplementos Nutricionais , Método Duplo-Cego
16.
Front Plant Sci ; 13: 959784, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35937355

RESUMO

Yields of wheat crops that succeed rice paddy crops are generally low. To date, it has been unclear whether such low yields were due to rice paddies altering soil physical or mineral characteristics, or both. To investigate this quandary, we conducted field experiments in the Jianghan Plain to analyze differences in the spatial distribution of wheat roots between rice-wheat rotation (RW) and dryland-wheat rotations (DW) using a range of nitrogen treatments. Dryland wheat crops were preceded by either dryland soybean or corn in the prior summer. Biomass of wheat crops in RW systems was significantly lower than that of DW for all N fertilizer treatments, although optimal nitrogen management resulted in comparable wheat yields in both DW and RW. Soil saturated water capacity and non-capillary porosity were higher in DW than RW, whereas soil bulk density was higher in RW. Soil available nitrogen and organic matter were higher in DW than RW irrespective of N application, while soil available P and K were higher under RW both at anthesis and post-harvest stages. At anthesis, root length percentage (RLP) was more concentrated in surface layers (0-20 cm) in RW, whereas at 20-40 cm and 40-60 cm, RLP was higher in DW than RW for all N treatments. At maturity, RLP were ranked 0-20 > 20-40 > 40-60 cm under both cropping systems irrespective of N fertilization. Root length percentage and soil chemical properties at 0-20 cm were positively correlated (r = 0.79 at anthesis, r = 0.68 at post-harvest) with soil available P, while available N (r = -0.59) and soil organic matter (r = -0.39) were negatively correlated with RLP at anthesis. Nitrogen applied at 180 kg ha-1 in three unform amounts of 60 kg N ha-1 at sowing, wintering and jointing resulted in higher yields than other treatments for both cropping systems. Overall, our results suggest that flooding of rice paddies increased bulk density and reduced available nitrogen, inhibiting the growth and yield of subsequent wheat crops relative to rainfed corn or soybean crops.

17.
Front Cardiovasc Med ; 9: 1013979, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36211575

RESUMO

Objective: This study aimed to analyze the characteristics of patients with pericardial effusion requiring pericardiocentesis and to evaluate the safety of pericardiocentesis without discontinuation of anticoagulant or antiplatelet drugs. Methods: We performed a retrospective study of patients undergoing pericardiocentesis in our hospital between 2012 and 2022. Patients were categorized into the Antithrombotic Group if they had used any antiplatelet or anticoagulant drugs on the day of pericardiocentesis; otherwise they were categorized into the Non-antithrombotic Group. All procedures were performed by experienced cardiologists with echocardiographic guidance. Bleeding events were defined using the National Institutes of Health scale of adverse events. Results: A total of 501 consecutive patients were identified and 70 cases were under antithrombotic drugs (Antithrombotic Group). Patients in Antithrombotic Group were older, had more comorbidities, presented with lower platelet counts and prolonged activated partial thromboplastin time (all p < 0.05). Malignancy was the most common etiology for pericardial effusion in both groups (28.6% in Antithrombotic Group and 54.7% in Non-antithrombotic Group) and tuberculosis was the second etiology in the Non-antithrombotic Group (21.9%), while procedure-related effusion (17.1%) accounted for the second cause in the Antithrombotic Group. Two patients in the Antithrombotic Group had mild oozing at the puncture site that resolved without interventions (2.9 vs. 0%, p = 0.019), and no bleeding events higher than Grade 1 occurred in either group. Conclusion: Although antiplatelet or anticoagulant drugs may put patients undergoing pericardiocentesis at theoretically higher risk of bleeding, our study demonstrated that they are not associated with increased major bleeding complications.

18.
J Control Release ; 345: 306-313, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35301053

RESUMO

Cytokines are important immunotherapeutics with approved drugs for the treatment of human cancers. However, systemic administration of cytokines often fails to achieve adequate concentrations to immune cells in tumors due to dose-limiting toxicity. Thus, developing localized therapy that directly delivers immune-stimulatory cytokines to tumors may improve the therapeutic efficacy. In this study, we generated novel lipid nanoparticles (LNPs) encapsulated with mRNAs encoding cytokines including IL-12, IL-27 and GM-CSF, and tested their anti-tumor activity. We first synthesized ionizable lipid materials containing di-amino groups with various head groups (DALs). The novel DAL4-LNP effectively delivered different mRNAs in vitro to tumor cells and in vivo to tumors. Intratumoral injection of DAL4-LNP loaded with IL-12 mRNA was most potent in inhibiting B16F10 melanoma tumor growth compared to IL-27 or GM-CSF mRNAs in monotherapy. Furthermore, intratumoral injection of dual DAL4-LNP-IL-12 mRNA and IL-27 mRNA showed a synergistic effect in suppressing tumor growth without causing systematic toxicity. Most importantly, intratumoral delivery of IL-12 and IL-27 mRNAs induced robust infiltration of immune effector cells, including IFN-γ and TNF-α producing NK and CD8+ T cells into tumors. Thus, intratumoral administration of DAL-LNP loaded with IL-12 and IL-27 mRNA provides a new treatment strategy for cancer.


Assuntos
Interleucina-27 , Nanopartículas , Neoplasias , Linfócitos T CD8-Positivos , Citocinas , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Humanos , Imunoterapia , Interleucina-12/genética , Lipossomos , Neoplasias/tratamento farmacológico , RNA Mensageiro/genética , RNA Mensageiro/uso terapêutico
19.
Adv Mater ; 34(47): e2207486, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36121735

RESUMO

Toll-like receptors (TLRs) and CD40-related signaling pathways represent critical bridges between innate and adaptive immune responses. Here, an immunotherapy regimen that enables co-stimulation of TLR7/8- and CD40-mediated pathways is developed. TLR7/8 agonist resiquimod (R848) derived amino lipids, RAL1 and RAL2, are synthesized and formulated into RAL-derived lipid nanoparticles (RAL-LNPs). The RAL2-LNPs show efficient CD40 mRNA delivery to DCs both in vitro (90.8 ± 2.7%) and in vivo (61.3 ± 16.4%). When combined with agonistic anti-CD40 antibody, this approach can produce effective antitumor activities in mouse melanoma tumor models, thereby suppressing tumor growth, prolonging mouse survival, and establishing antitumor memory immunity. Overall, RAL2-LNPs provide a novel platform toward cancer immunotherapy by integrating innate and adaptive immunity.


Assuntos
Melanoma , Nanopartículas , Receptor 7 Toll-Like , Animais , Camundongos , Adjuvantes Imunológicos , Antígenos CD40 , Imunoterapia , Camundongos Endogâmicos C57BL , Receptor 7 Toll-Like/agonistas , Receptores Toll-Like , Melanoma/tratamento farmacológico
20.
Artigo em Zh | MEDLINE | ID: mdl-21315004

RESUMO

OBJECTIVE: To investigate the value of determination of serum myoglobin (MYO) in estimation of the degree of illness and prognosis of patients with sepsis in Xining area. METHODS: Serum MYO was measured and acute physiological and chronic health estimationII (APACHEII) score was evaluated in 30 cases with sepsis within 24 hours of admission to emergency intensive care unit (EICU), and their correlation was analyzed. The patients were divided into two groups, survival group and death group according to the result within 28 days. The MYO and APACHEII score were analyzed in both groups. All cases were divided into three groups: namely <500 (n=10), 500-1 000 (n=14), >1 000 µg/L (n=6) groups, according to serum MYO value, and APACHEII score and dead case were compared among three groups. RESULTS: Sixteen patients survived, and 14 patients died. The level of serum MYO and APACHEII score were significantly lower in survival group than death group [MYO (µg/L): 607.85±499.40 vs. 976.21±370.10, APACHEII score: 15.50±4.43 vs. 18.93±3.63, t(1)=2.28, t(2)=2.29, both P<0.05]. With the elevation of serum MYO, the dead case was increased in sepsis patients (the dead case in MYO<500, 500-1 000, >1 000 µg/L groups was 2, 7, 5 cases, respectively,χ(2)=5.94, P<0.05), but there was no difference in APACHEII score among three groups. There was significant positive correlation between serum MYO and APACHEII score (r=0.407, P<0.05). CONCLUSION: Determination of serum MYO can reflect degree of illness and prognosis of sepsis patients in Xining area.


Assuntos
Mioglobina/sangue , Sepse/sangue , Sepse/diagnóstico , APACHE , Adolescente , Adulto , Idoso , China , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Prognóstico , Adulto Jovem
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