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1.
Int J Nanomedicine ; 19: 3259-3273, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601347

RESUMO

Purpose: Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease involving synovial inflammation and joint destruction. Although therapeutic drugs for RA have some efficacy, they usually cause severe side effects and are expensive. RA is characterized by synovial hyperplasia, intra-articular hypoxia, upregulated expression of matrix metalloproteinases, and excessive accumulation of reactive oxygen species. The adverse microenvironment further aggravates activated macrophage infiltration. Therefore, controlling the microenvironment of diseased tissues and targeting the activated macrophages have become new therapeutic targets in RA patients. Methods: Here, microenvironment-targeting micelles (PVGLIG-MTX-Que-Ms) were synthesized using the thin film hydration method. In the inflammatory microenvironment, PVGLIG was cleaved by the highly expressed MMP-2, PEG5000 was eliminated, MTX was exposed, macrophage activation was targeted, and Que enrichment was enhanced. The cytotoxicity, targeting, antioxidant, and anti-inflammatory properties of drug-loaded micelles were tested in vitro. The drug-loaded micelles were used to treat CIA rats. In vivo targeting, expression of serum inflammatory factors, immunohistochemistry of the articular cartilage, and changes in immunofluorescence staining were observed. Results: The developed micelles had a particle size of (89.62 ±1.33) nm and a zeta potential of (-4.9 ±0.53) mV. The IC50 value of PVGLIG-MTX-Que-Ms (185.90 ±6.98) µmol/L was significantly lower than that of free Que (141.10 ±6.39) µmol/L. The synthesized micelles exhibited slow-release properties, low cytotoxicity, strong targeting abilities, and significant anti-inflammatory effects in vitro. In vivo, the drug-loaded micelles accumulated at the joint site for a long time. PVGLIG-MTX-Que-Ms significantly reduced joint swelling, improved bone destruction, and decreased the expression of serum inflammatory factors in CIA rats. Conclusion: The smart-targeting micelles PVGLIG-MTX-Que-Ms with strong targeting, anti-inflammatory, cartilage-protective, and other multiple positive effects are a promising new tool for RA treatment.


Assuntos
Artrite Experimental , Artrite Reumatoide , Humanos , Ratos , Animais , Metotrexato/química , Micelas , Quercetina/farmacologia , Quercetina/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Inflamação/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico
2.
Small ; : e2311076, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38279579

RESUMO

Developing active, stable, and cost-efficient electrocatalysts to replace platinum for the alkaline hydrogen evolution reaction (HER) is highly desirable yet represents a great challenge. Here, it is reported on a facile one-pot synthesis of Rux Ni layered double hydroxides (Rux Ni-LDHs) that exhibit remarkable HER activity and stability after an in-situ activation treatment, surpassing most state-of-the-art Ru-based catalysts as well as commercial Ru/C and Pt/C catalysts. The structural and chemical changes triggered by in-situ activation are systematically investigated, and the results clearly show that the pristine, less-active Rux Ni-LDHs are transformed into a highly active catalyst characterized by raft-like, defect-rich Ru° particles decorated on the surface of Rux Ni-LDHs. Density functional theory (DFT) calculations reveal that the defective Ru sites can effectively optimize the reaction pathway and lower the free energies of the elemental steps involved, leading to enhanced intrinsic activity. This work highlights the importance of the currently understudied strategy of defect engineering in boosting the HER activity of Ru-based catalysts and offers an effective approach involving in-situ electrochemical activation for the development of high-performance alkaline HER catalysts.

3.
Adv Sci (Weinh) ; 11(13): e2306792, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38288517

RESUMO

This investigation addresses the challenge of suboptimal unnatural amino acid (UAA) utilization in the site-specific suppression of nonsense mutations through genetic code expansion, which is crucial for protein restoration and precise property tailoring. A facile and economical oral liquid formulation is developed by converting UAAs into ionic liquids, significantly enhancing their bioavailability and tissue accumulation. Empirical data reveal a 10-fold increase in bioavailability and up to a 13-fold rise in focal tissue accumulation, alongside marked improvements in UAA incorporation efficiency. A 4-week oral administration in mdx mice, a model for Duchenne muscular dystrophy (DMD), demonstrates the formulation's unprecedented therapeutic potential, with up to 40% dystrophin expression restoration and 75% recovery of normal fiber functions, surpassing existing treatments and exhibiting substantial long-term safety. This study presents a potent oral dosage form that dramatically improves UAA incorporation into target proteins in vivo, offering a significant advance in the treatment of nonsense mutation-mediated disorders and holding considerable promise for clinical translation.


Assuntos
Líquidos Iônicos , Distrofia Muscular de Duchenne , Animais , Camundongos , Códon sem Sentido/genética , Camundongos Endogâmicos mdx , Líquidos Iônicos/uso terapêutico , Aminoácidos , Distrofia Muscular de Duchenne/tratamento farmacológico , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/metabolismo
4.
J Drug Target ; 31(6): 634-645, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37203195

RESUMO

The blood-brain barrier (BBB) is a barrier that maintains brain homeostasis, but it is also one of the major problems that must be overcome in the development of Alzheimer's disease (AD) drugs. To solve this problem, Salidroside (Sal) and Icariin (Ica), drugs with neuroprotective effects were loaded into liposomes, and the targeting molecule Angiopep-2 was modified on the surface of liposomes (Ang-Sal/Ica-Lip), so that the constructed nano-drug delivery system could effectively cross the BBB and exert anti-AD effects. The prepared liposomes exhibited ideal physicochemical properties. In vitro and in vivo targeting studies showed that Ang-Sal/Ica liposome could cross the BBB to increase drug accumulation in the brain, and increase the uptake of N2a cells and bEnd.3 cells. The pharmacodynamic analysis in vivo showed that Ang-Sal/Ica liposome could reverse neuronal and synaptic damage, inhibit neuroinflammation and oxidative stress and improve learning and cognitive function. Therefore, Ang-Sal/Ica liposome may be a promising therapeutic strategy for mitigating AD-related symptoms.


Assuntos
Doença de Alzheimer , Lipossomos , Camundongos , Animais , Lipossomos/química , Doença de Alzheimer/tratamento farmacológico , Células Endoteliais , Encéfalo , Barreira Hematoencefálica
5.
J Child Orthop ; 17(2): 184-190, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37034198

RESUMO

Objectives: To investigate maternal psychological status of children with congenital talipes equinovarus in different periods, and to clarify the influence on maternal psychological status of congenital talipes equinovarus treated with the Ponseti method. Methods: Sixty-seven mothers of children with congenital talipes equinovarus were investigated. Self-rating Depression Scale and Self-rating Anxiety Scale were used to evaluate the psychological stress of the mothers at different periods. Paired-samples t-test was used to analyze the results. Results: The mothers of 67 children with congenital talipes equinovarus ranged from 25 to 38 years old, with an average of 33.5 years old. Before prenatal diagnosis of congenital talipes equinovarus, the average score of Self-rating Anxiety Scale was 42.537 ± 10.476, and the average score of Self-rating Depression Scale was 47.254 ± 12.846; after prenatal diagnosis of congenital talipes equinovarus, the average score of Self-rating Anxiety Scale was 54.224 ± 13.050, and the average score of Self-rating Depression Scale was 57.403 ± 13.649 points. Before the postpartum treatment of congenital talipes equinovarus, the average score of Self-rating Anxiety Scale was 53.388 ± 12.716, the average score of Self-rating Depression Scale was 56.284 ± 13.617; after the treatment of congenital talipes equinovarus with the Ponseti method, the average score of Self-rating Anxiety Scale was 47.731 ± 12.259, and the average score of Self-rating Depression Scale was 51.910 ± 13.878 points. The above differences were statistically significant (P < 0.001). Conclusion: The prenatal diagnosis of congenital talipes equinovarus will increase the maternal psychological stress, and the maternal psychological status will be significantly improved after the deformity of congenital talipes equinovarus is corrected effectively by the Ponseti method. Level of evidence: level III, retrospective study.

6.
Sensors (Basel) ; 23(8)2023 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37112362

RESUMO

A compact and high-precision three-degrees-of-freedom (DOF; X, Y, and Z directions) grating encoder based on the quadrangular frustum pyramid (QFP) prisms is proposed in this paper to solve the insufficient installation space problem of the reading head of the multi-DOF in high-precision displacement measurement applications. The encoder is based on the grating diffraction and interference principle, and a three-DOF measurement platform is built through the self-collimation function of the miniaturized QFP prism. The overall size of the reading head is 12.3 × 7.7 × 3 cm3 and has the potential for further miniaturization. The test results show that three-DOF measurements can be realized simultaneously in the range of X-250, Y-200, and Z-100 µm due to the limitations of the measurement grating size. The measurement accuracy of the main displacement is below 500 nm on average; the minimum and maximum errors are 0.0708% and 2.8422%, respectively. This design will help further popularize the research and applications of multi-DOF grating encoders in high-precision measurements.

7.
Drug Dev Ind Pharm ; 49(2): 189-206, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36971392

RESUMO

OBJECTIVE: The aim was to develop a nanoscale drug delivery system with enzyme responsive and acid sensitive particle size and intelligent degradation aiming to research the inhibitory effect on breast cancer. SIGNIFICANCE: The delivery system addressed the problems of tissue targeting, cellular internalization, and slow drug release at the target site, which could improve the efficiency of drug delivery and provide a feasible therapeutic approach for breast cancer. METHODS: The acid sensitive functional material DSPE-PEG2000-dyn-PEG-R9 was synthesized by Michael addition reaction. Then, the berberine plus baicalin intelligent micelles were prepared by thin-film hydration. Subsequently, we characterized the physical and chemical properties of berberine plus baicalin intelligent micelles, evaluated its anti-tumor effects in vivo and in vitro. RESULTS: The target molecule was successfully synthesized, and the intelligent micelles showed excellent chemical and physical properties, delayed drug release and high encapsulation efficiency. In vitro and in vivo experiments also confirmed that the intelligent micelles could effectively target tumor sites, penetrate tumor tissues, enrich in tumor cells, inhibit tumor cell proliferation, inhibit tumor cell invasion and migration, and induce tumor cell apoptosis. CONCLUSION: Berberine plus baicalin intelligent micelles have excellent anti-tumor effects and no toxicity to normal tissues, which provides a new potential drug delivery strategy for the treatment of breast cancer.


Assuntos
Antineoplásicos , Berberina , Neoplasias da Mama , Humanos , Feminino , Micelas , Neoplasias da Mama/tratamento farmacológico , Antineoplásicos/farmacologia , Berberina/farmacologia , Berberina/química , Berberina/uso terapêutico , Tamanho da Partícula , Linhagem Celular Tumoral , Portadores de Fármacos/química
8.
STAR Protoc ; 4(1): 101950, 2023 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-36527714

RESUMO

In this protocol, we describe how to utilize the unnatural amino acid (UAA) incorporation system to read through endogenous premature termination codons in a Duchenne muscular dystrophy mouse model. We detail how to screen and optimize tRNA-enzyme pairs for efficient UAA incorporation, deliver the system intraperitoneally or intramuscularly in pathogenic mice by an adeno-associated viral (AAV) vector, and evaluate the restoration of endogenous dystrophin and increase in muscle strength after AAV injection. For complete details on the use and execution of this protocol, please refer to Shi et al. (2021).1.


Assuntos
Códon sem Sentido , Músculo Esquelético , Camundongos , Animais , Códon sem Sentido/genética , Códon sem Sentido/metabolismo , Músculo Esquelético/metabolismo , Terapia Genética/métodos , Vetores Genéticos/genética , Modelos Animais de Doenças , Dependovirus/genética , RNA de Transferência/genética , RNA de Transferência/metabolismo , Aminoácidos/metabolismo
9.
Sensors (Basel) ; 22(23)2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36501749

RESUMO

An absolute-type four-degree-of-freedom (four-DOF) grating encoder that can simultaneously measure the three-axis pose (θx, θy, θz) and one-axis out-of-plane position (Z) of an object with high accuracy is demonstrated for the first time in this research. This grating encoder is composed of a stationary reading head and a movable grating reflector. A light beam from the reading head is projected onto the grating, and three diffracted beams (0th-, +1st-, and -1st-order) are generated, collimated, and received by three separate quadrant photodetectors (QPDs). The information of θx, θy, θz, and Z is coded into spot positions of these three diffracted beams on the QPDs. Thus, the modeling and decoupling algorithms were investigated, and an independent calculation of these four-DOF absolute positions was theoretically guaranteed. A prototype was then designed, constructed, and evaluated. Experimental results verified that the proposed grating encoder could achieve the absolute measurement of four-DOF θx, θy, θz, and Z with an accuracy of sub-arcseconds and sub-micrometers. To the best of our knowledge, the proposed encoder in this research is the first one to achieve absolute simultaneous measurements of four-DOF position and pose with a large measurement range. The success of this new grating encoder can benefit various multi-DOF positioning applications, especially for large-scale synthetic aperture optics (SAO), including stitching off-axis parabolic mirrors and pulse compression grating.

10.
Ultrason Sonochem ; 89: 106136, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36055014

RESUMO

As a new and clean extraction technology, ultrasonic extraction has been demonstrated with great potential in the preparation of modified starch. In order to increase its added value, it is necessary to modify pea starch to enlarge its application. In this study, the efficiency of combining ultrasonic with alkali in the extraction of pea starch was evaluated and compared to conventional alkali extraction. Ultrasonic-assisted alkali extraction conditions were optimized using single-factor experiments and response surface methodology. The results revealed that maximum yield of pea starch (54.43 %) was achieved using ultrasound-assisted alkali extraction under the following conditions: sodium hydroxide solution with a concentration of 0.33 %, solid/alkali solution ratio of 1:6 (w/v), ultrasonic power of 240 W, temperature of 42 °C, and extraction time of 22 min. The ultrasound-assisted alkali extraction yielded 13.72 % greater pea starch than conventional alkali extraction. On the other hand, morphological, structural, and physicochemical properties of the obtained starch isolates were evaluated. The ultrasound-assisted alkali extraction resulted in pea starch with greater amylose content, water-solubility, swelling power, and viscosity compared with conventional alkali extraction. Furthermore, ultrasonication influenced the morphological properties of pea starch granules, while the molecular structure and crystal type were not affected. Moreover, the ultrasonic-assisted extraction produced starch with a slightly greater resistant starch content. Therefore, ultrasonic-assisted extraction can be suggested as a potential method for extracting pea starch with improved functional properties.


Assuntos
Amilose , Amido , Álcalis , Amilose/química , Pisum sativum/química , Amido Resistente , Hidróxido de Sódio/química , Amido/química , Ultrassom , Água/química
11.
Comput Struct Biotechnol J ; 20: 4930-4941, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147660

RESUMO

The unnatural amino acid (UAA) incorporation technique through genetic code expansion has been extensively used in protein engineering for the last two decades. Mutations into UAAs offer more dimensions to tune protein structures and functions. However, the huge library of optional UAAs and various circumstances of mutation sites on different proteins urge rational UAA incorporations guided by artificial intelligence. Here we collected existing experimental proofs of UAA-incorporated proteins in literature and established a database of known UAA substitution sites. By program designing and machine learning on the database, we showed that UAA incorporations into proteins are predictable by the observed evolutional, steric and physiochemical factors. Based on the predicted probability of successful UAA substitutions, we tested the model performance using literature-reported and freshly-designed experimental proofs, and demonstrated its potential in screening UAA-incorporated proteins. This work expands structure-based computational biology and virtual screening to UAA-incorporated proteins, and offers a useful tool to automate the rational design of proteins with any UAA.

12.
Mikrochim Acta ; 189(9): 345, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-36001198

RESUMO

A new 2D-layered nickel cobalt phosphide nanosheet confined by 3D graphene frameworks (denoted as NiCoP/GFs) is in situ controllably synthesized as a highly efficient and durable electrocatalyst, which is obtained from the transformation of corresponding NiCo layer double hydroxides and GFs. Hydrogen peroxide (H2O2) is selected as a demonstration to study the electrochemical sensing performance of the NiCoP/GFs. Benefiting from 2D morphology of NiCoP and network structure of GFs, NiCoP/GFs exhibits remarkable electroactivity toward H2O2 at a relatively low overpotential of approximately - 0.3 V (vs sat. Ag/AgCl) in 0.01 M phosphate-buffered saline solution (PBS, pH = 7.4). The NiCoP/GFs-based H2O2 electrochemical sensor achieves a high sensitivity of ∼4398 µA mM-1 cm-2, a low detection limit of 0.028 ± 0.006 µM, and desirable selectivity. In addition, the sensor can sensitively detect H2O2 from living cancer cells. This study not merely broadens the synthesis methods of transition metal phosphide-based nanocrystals but the NiCoP/GFs also has broad prospects in diverse electrochemistry fields. We have reported a controllable synthesis of 2D nickel cobalt phosphide nanosheet confined by graphene frameworks (denoted as NiCoP/GFs) as a greatly efficient and durable electrocatalyst. The NiCoP/GFs exhibits remarkable electroactivity toward detection of H2O2 at a relatively low overpotential of approximately -0.3 V. Density functional theory (DFT) calculations further prove that regulation of the electronic structure of NiCoP by GFs lowers the adsorption free energy of *OOH intermediates, and thus contributes to the greatly improved the electrocatalytic performance of NiCoP/GFs toward H2O2 reduction. The developed NiCoP/GFs can be applied as excellent electrode materials for efficient electrochemical sensing of H2O2.


Assuntos
Grafite , Nanopartículas Metálicas , Eletrodos , Grafite/química , Peróxido de Hidrogênio , Níquel/química
13.
Phytochemistry ; 203: 113389, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36007660

RESUMO

Seven undescribed sesquiterpene lactone dimers (SLDs) (carpeabrodilactones A-G), one known SLD, and six known sesquiterpenes were isolated from the fruit of Carpesium abrotanoides L. Carpeabrodilactone A was a dimeric carabrane featuring a rare C-13-C-13' linkage. Carpeabrodilactones B and C are the first two SLDs to be described possessing a carabranolide unit and a guaianolide unit connected by an O-ether linkage. The structures of the SLDs were assigned based on HRESIMS, NMR analysis, 13C NMR calculation, ECD calculation, and modified Mosher's method. Four SLDs showed potent cytotoxicity against K562 and/or A549 cells, with IC50 values below 10 µM, but none inhibited protein tyrosine phosphatases at 40 µM, including PTP1B, SHP1, CD45, and TCPTP.


Assuntos
Asteraceae , Sesquiterpenos , Asteraceae/química , Éteres , Frutas , Lactonas/química , Lactonas/farmacologia , Estrutura Molecular , Compostos Fitoquímicos , Sesquiterpenos/química , Sesquiterpenos/farmacologia
14.
Adv Biol (Weinh) ; 6(11): e2200092, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35818694

RESUMO

Site-specific incorporation of distinct noncanonical amino acids (ncAAs) into proteins via genetic code expansion in mammalian cells represents a new avenue for protein engineering. Reassigning three TAGs with the same ncAA in mammalian cells has previously been achieved using translational machinery. However, simultaneous recoding of three nonsense codons with distinct ncAAs in mammalian cells remains a challenge due to low incorporation efficiencies. Here, three optimized aaRS/tRNA pairs (i.e., the E. coli-derived tyrosyl (EcTyr)/tRNAUUA , E. coli-derived leucyl (EcLeu)/tRNACUA , and Methanosarcina mazei pyrrolysyl (MmPyl)/tRNAUCA pairs) are screened for ncAA incorporation. Furthermore, introduced combinations of eukaryotic release factor 1 (eRF1) mutants (E55R, E55D, N129D, and Y125F) significantly improve the encoding efficiency of the three premature stop codons' sites from 0.78% to 11.6%. Thus, site-specific incorporation of three distinct ncAAs into a single protein is achieved in this study. This work markedly expands the potential for multiple site-specific protein modifications within mammalian cells, thereby facilitating new in vivo applications.


Assuntos
Aminoácidos , Aminoacil-tRNA Sintetases , Animais , Aminoácidos/genética , Aminoacil-tRNA Sintetases/genética , Escherichia coli/genética , Eucariotos/genética , RNA de Transferência/genética , Mamíferos/genética
15.
Vaccines (Basel) ; 10(6)2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35746486

RESUMO

Currently, an inactivated vaccine has been widely used with encouraging results as a prophylactic agent against COVID-19 infection, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants. However, in vitro SARS-CoV-2 vaccine-specific immune features remain elusive, hindering the promotion of a third dose of the vaccine. Here, we present a detailed in vitro immune cellular response and large-scale multi-omics analysis for peripheral blood mononuclear cells (PBMCs) from participants vaccinated with CoronaVac (Sinovac Life Sciences, Beijing, China) and recovered participants from COVID-19. The mean titers of SARS-CoV-2 serum-neutralizing antibodies were significantly increased after the boosting immunization (Day 45) compared to the unimmunized state. We observed that type-1 helper T cells (Th1) tended to dominate after the first dose of vaccine, while humoral immune responses became dominant after the second dose due to the activation of type-2 helper T cell (Th2), memory B cells, and plasmablasts. T follicular helper cells (Tfh) involved in antibody production were activated after the first dose and were maintained for the observed time points. Single-cell RNA sequencing of PBMCs revealed specific changes in cell compositions and gene expression in immunized participants. Multi-omics analysis also demonstrated that CoronaVac-specific serum proteins, plasma metabolites, and plasma lipid changes were skewed to those changes in convalescent patients. Collectively, we provide a comprehensive understanding of CoronaVac-specific in vitro immune features.

16.
Nat Biomed Eng ; 6(2): 195-206, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34341535

RESUMO

Approximately 11% of monogenic diseases involve nonsense mutations that are caused by premature termination codons. These codons can in principle be read-through via the site-specific incorporation of unnatural amino acids to generate full-length proteins with minimal loss of function. Here we report that aminoacyl-tRNA-synthase-tRNA pairs specific for the desired unnatural amino acids can be used to read through a nonsense mutation in the dystrophin gene. We show partial restoration of dystrophin expression in differentiated primary myoblasts (from a mdx mouse model and a patient with Duchenne muscular dystrophy), and restoration of muscle function in two mouse models: mdx mice, via viral delivery of the engineered tRNA-synthase-tRNA pair intraperitoneally or intramuscularly and of the associated unnatural amino acid intraperitoneally; and mice produced by crossing mdx mice and transgenic mice with a chromosomally integrated pair, via intraperitoneal delivery of the unnatural amino acid. The incorporation of unnatural amino acids to restore endogenous protein expression could be explored for therapeutic use.


Assuntos
Distrofina , Distrofia Muscular de Duchenne , Aminoácidos/genética , Animais , Códon sem Sentido , Distrofina/genética , Humanos , Camundongos , Camundongos Endogâmicos mdx , Distrofia Muscular de Duchenne/genética
17.
Biomed J ; 45(6): 870-882, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-34863964

RESUMO

BACKGROUND: Hypoxia-induced apoptosis is linked to the pathogenesis of myocardial infarction. The role of apoptosis-inducing factor mitochondria associated 1 (AIFM1) in cardiomyocyte injury remains unclear. This study was aimed at probing into the role and the underlying regulatory mechanism of AIFM1 in myocardial injury. METHODS: H9c2 cardiomyocytes and C57BL/6 mice were used for myocardial hypoxic/ischemic injury and myocardial infarction animal models. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to evaluate the expression levels of AIFM1 mRNA and miR-145-5p. Western blot was used for examining the expression levels of AIFM1, caspase-3, cleaved caspase-3, p-53, and γ-H2AX. Cell viability was examined by cell counting kit-8 (CCK-8) assay and BrdU assay. Interaction between AIFM1 and miR-145-5p was determined by bioinformatics analysis, qRT-PCR, Western blot, and dual-luciferase reporter assay. RESULTS: AIFM1 expression was markedly highly elevated, while miR-145-5p expression was significantly down-regulated in the myocardial infarction animal model and H9c2 cells under hypoxia. Augmentation of AIFM1 led to a dramatic decrease of cell viability, accompanied by an increase of the secretion of the inflammatory cytokines IL-1ß, TNF-α, IL-6, and the expression of cleaved caspase-3. Furthermore, AIFM1 was identified as a target of miR-145-5p. In addition, miR-145-5p/AIFM1 axis regulated the expression of p53. CONCLUSION: AIFM1 may exacerbate myocardial ischemic injury by promoting inflammation and the injury of cardiomyocytes, and its up-regulation may be partly due to the down-regulation of miR-145-5p.


Assuntos
MicroRNAs , Infarto do Miocárdio , Camundongos , Animais , MicroRNAs/genética , Caspase 3/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fator de Indução de Apoptose/metabolismo , Hipóxia Celular/genética , Camundongos Endogâmicos C57BL , Apoptose/fisiologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Hipóxia/metabolismo , Hipóxia/patologia
18.
Ann Palliat Med ; 10(3): 3336-3342, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33849118

RESUMO

BACKGROUND: People living in plateau areas are prone to upper respiratory tract infections and secondary lung infections. The current study aimed to explore the effects of bronchoalveolar lavage under fiberoptic bronchoscope for the treatment of patients with severe pulmonary infection living in plateau areas. METHODS: 148 patients with severe lung infection admitted to the intensive care unit of Shigatse People's Hospital (Shigatse, Tibet Autonomous Region, China) between July 2019 and January 2021 were enrolled. Patients were randomly assigned to the observational group or the control group. For all patients, basic clinical data including sex, age, body mass index (BMI), blood pressure, diabetes history, stroke history, presence or absence of chronic obstructive pulmonary disease, lung infection (gram-positive bacterial infection, gram-negative bacterial infection, fungal infection, acute lung abscess), surgical history, and postoperative inhalation injury. were collected. The control group received conventional treatment, and the observational group received bronchoalveolar lavage under fiberoptic bronchoscopy. Pearson's correlation was used to analyze the correlations between bronchoalveolar lavage under fiberoptic bronchoscopy and inflammatory factors levels. Logistic regression was used to investigate the correlation between bronchoalveolar lavage under fiberoptic bronchoscopy and the effectiveness of the treatment. RESULTS: Before treatment, no significant difference existed in the basic data of the observational group and the control group. After treatment, the parameters of respiratory mechanics and inflammatory factors in the 2 groups were significantly improved compared with those before treatment (P<0.05). At the same time, in the observational group, the clinical parameters were significantly higher than those of the control group, and the levels of inflammatory factors were significantly lower than those of the control group (all P<0.05). After full adjustment for age, sex, BMI, gram-negative infection, diabetes, and acute lung abscess, compared with the control group, the therapeutic effectiveness in the observational group was increased by 23% (OR =1.23, 95% CI: 1.09-1.51, P=0.007). CONCLUSIONS: For patients with severe lung infection who are resident in high altitude areas, compared with conventional treatments, bronchoalveolar lavage under fiberoptic bronchoscopy can significantly improve chest, lung, and total dynamic compliance, as well as reduce the levels of the inflammatory factors procalcitonin (PCT) and transforming growth factor-ß, thus increasing the effectiveness of the treatment.


Assuntos
Broncoscopia , Pulmão , Lavagem Broncoalveolar , China , Humanos , Tibet
19.
Anal Methods ; 12(42): 5097-5102, 2020 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-33047756

RESUMO

Carbon dots (CDs) with blue fluorescence were synthesized using indole-3-butyric acid and l-tryptophan using a one-step hydrothermal method. The CDs were further employed as a fluorescent sensor with high selectivity for colorimetric and ratiometric detection of tetracycline (TC) in water. The limit of detection (LOD) was found to be 0.33 µM for TC with R2 = 0.98387. Besides, the CDs could be applied in practical water samples and showed good recovery.


Assuntos
Corantes Fluorescentes , Pontos Quânticos , Carbono , Colorimetria , Limite de Detecção
20.
Chem Asian J ; 14(15): 2685-2693, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31152680

RESUMO

Two trinuclear copper phosphonate complexes, [Cu3 (pda)3 (tBuPO3 )]⋅2(Et3 NH) (1) and [Cu3 (pda)3 (PhPO3 )]⋅2(Et3 NH) (2), have been synthesized and investigated by a combination of X-ray crystallography, PXRD, magneto- and electrochemistry, EPR, in situ UV-vis spectroelectrochemistry and DLS. The two complexes feature almost identical crystal structures, the anions of which are both supported by pda2- and tBuPO3 2- /PhPO3 2- groups, bridging three five-coordinated CuII atoms to form a crown-like structure. This is the first time that trinuclear copper phosphonate complexes have been isolated and characterized. Magnetic susceptibility measurements reveal that complexes 1 and 2 both display overall ferromagnetic characters, but with different exchange interactions between the metal ions within the two clusters. The electrocatalytic activity for water oxidation of the two complexes was preliminarily investigated, which reveals that both of the two complexes can carry out electrocatalytic water oxidation in a neutral system owing to the introduction of phosphonate ligands into the complexes, with a TOF of about 0.82 s-1 (1) and 0.58 s-1 (2), respectively. We propose that the presence of phosphonate ligands may affect the magnetic property and catalytic activity of the complexes.

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