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1.
Small ; 20(13): e2308167, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37953455

RESUMO

Intervertebral disc degeneration (IVDD) is a significant contributor to low back pain, characterized by excessive reactive oxygen species generation and inflammation-induced pyroptosis. Unfortunately, there are currently no specific molecules or materials available to effectively delay IVDD. This study develops a multifunctional full name of PG@Cu nanoparticle network (PG@Cu). A designed pentapeptide, bonded on PG@Cu nanoparticles via a Schiff base bond, imparts multifunctionality to the metal polyphenol particles (PG@Cu-FP). PG@Cu-FP exhibits enhanced escape from lysosomal capture, enabling efficient targeting of mitochondria to scavenge excess reactive oxygen species. The scavenging activity against reactive oxygen species originates from the polyphenol-based structures within the nanoparticles. Furthermore, Pyroptosis is effectively blocked by inhibiting Gasdermin mediated pore formation and membrane rupture. PG@Cu-FP successfully reduces the activation of the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome by inhibiting Gasdermin protein family (Gasdermin D, GSDMD) oligomerization, leading to reduced expression of Nod-like receptors. This multifaceted approach demonstrates higher efficiency in inhibiting Pyroptosis. Experimental results confirm that PG@Cu-FP preserves disc height, retains water content, and preserves tissue structure. These findings highlight the potential of PG@Cu-FP in improving IVDD and provide novel insights for future research in IVDD treatments.


Assuntos
Degeneração do Disco Intervertebral , Nanopartículas , Humanos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Gasderminas , Inflamassomos/metabolismo , Mitocôndrias/metabolismo , Polifenóis/farmacologia
2.
Int J Mol Sci ; 25(3)2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38339180

RESUMO

To investigate the mechanism of aquatic pathogens in quorum sensing (QS) and decode the signal transmission of aquatic Gram-negative pathogens, this paper proposes a novel method for the intelligent matching identification of eight quorum signaling molecules (N-acyl-homoserine lactones, AHLs) with similar molecular structures, using terahertz (THz) spectroscopy combined with molecular dynamics simulation and spectral similarity calculation. The THz fingerprint absorption spectral peaks of the eight AHLs were identified, attributed, and resolved using the density functional theory (DFT) for molecular dynamics simulation. To reduce the computational complexity of matching recognition, spectra with high peak matching values with the target were preliminarily selected, based on the peak position features of AHL samples. A comprehensive similarity calculation (CSC) method using a weighted improved Jaccard similarity algorithm (IJS) and discrete Fréchet distance algorithm (DFD) is proposed to calculate the similarity between the selected spectra and the targets, as well as to return the matching result with the highest accuracy. The results show that all AHL molecular types can be correctly identified, and the average quantization accuracy of CSC is 98.48%. This study provides a theoretical and data-supported foundation for the identification of AHLs, based on THz spectroscopy, and offers a new method for the high-throughput and automatic identification of AHLs.


Assuntos
Acil-Butirolactonas , Espectroscopia Terahertz , Acil-Butirolactonas/química , Simulação de Dinâmica Molecular , Percepção de Quorum , Estrutura Molecular , Lactonas
3.
J Med Virol ; 95(7): e28953, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37461287

RESUMO

As the understanding of the mechanisms of SARS-CoV-2 infection continues to grow, researchers have come to realize that ACE2 and TMPRSS2 receptors are not the only way for the virus to invade the host, and that there are many molecules that may serve as potential receptors or cofactors. The functionality of these numerous receptors, proposed by different research groups, demands a fast, simple, and accurate validation method. To address this issue, we here established a DnaE intein-based cell-cell fusion system, a key result of our study, which enables rapid simulation of SARS-CoV-2 host cell infection. This system allowed us to validate that proteins such as AXL function as SARS-CoV-2 spike protein receptors and synergize with ACE2 for cell invasion, and that proteins like NRP1 act as cofactors, facilitating ACE2-mediated syncytium formation. Our results also suggest that mutations in the NTD of the SARS-CoV-2 Delta variant spike protein show a preferential selection for Spike-AXL interaction over Spike-LDLRAD3. In summary, our system serves as a crucial tool for the rapid and comprehensive verification of potential receptors, screening of SARS-CoV-2-neutralizing antibodies, or targeted drugs, bearing substantial implications for translational clinical applications.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Anticorpos Antivirais , Fusão Celular , Inteínas , Peptidil Dipeptidase A/metabolismo , Glicoproteína da Espícula de Coronavírus
4.
BMC Pulm Med ; 23(1): 461, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37993830

RESUMO

BACKGROUND: Numerous studies have reported the association between tea intake and lung diseases. However, the probable relationship between tea consumption on lung diseases still remain controversial and it is unclear whether these findings are due to reverse causality or confounding factor. METHODS: In order to systematically investigate the causal connection between tea intake on respiratory system disorders, we employed a two-sample Mendelian randomized (MR) study. Genetic instruments for tea intake were identified from a genome-wide association study (GWAS) involving 447,385 individuals. Data on lung diseases were collected from a variety of publicly available genome-wide association studies. The main method used for MR analysis is the inverse variance weighting (IVW) method. To ensure the accuracy of the findings, further sensitivity analysis was conducted. RESULTS: The IVW method in our MR analysis revealed no evidence to support a causal relationship between tea intake and lung diseases (IPF: OR = 0.997, 95% CI = 0.994-1.000, p = 0.065; Lung cancer: OR = 1.003, 95% CI = 0.998-1.008, P = 0.261; COPD: OR = 1.001, 95% CI = 0.993-1.006, p = 0.552; acute bronchitis: OR = 0.919, 95% CI = 0.536-1.576, p = 0.759; tuberculosis: OR = 1.002, 95% CI = 0.998-1.008, p = 0.301; pneumonia: OR = 0.789, 95% CI = 0.583-1.068, p = 0.125). The reliability of the results was further demonstrated by four additional MR analysis techniques and additional sensitivity testing. CONCLUSION: We found no evidence of a link between tea intake on lung diseases in our MR results based on genetic information.


Assuntos
Estudo de Associação Genômica Ampla , Neoplasias Pulmonares , Humanos , Análise da Randomização Mendeliana , Reprodutibilidade dos Testes , Neoplasias Pulmonares/genética , Chá
5.
BMC Musculoskelet Disord ; 24(1): 667, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612739

RESUMO

PURPOSE: This study aims to evaluate complications, clinical outcomes, and radiographic results following Coflex implantation. METHODS: We retrospectively studied 66 patients who had decompressive surgery combined with Coflex implantation to treat lumbar spinal stenosis. All imaging data were collected and examined for imaging changes. Clinical outcomes, included Oswestry Disability Index (ODI), back and leg visual analog scale (VAS) scores, were evaluated before surgery, six months after surgery and at the last follow-up. The number of complications occurring after five years of follow-up was counted. All reoperation cases were meticulously recorded. RESULTS: 66 patients were followed up for 5-14 years. The VAS and ODI scores were significantly improved compared with baseline. Heterotopic Ossification (HO) was detectable in 59 (89.4%). 26 (39.4%) patients had osteolysis at the contact site of Coflex with the spinous process. Coflex loosening was detected in 39 (60%) patients. Spinous process anastomosis was found in 34 (51.5%) patients. There was a statistically significant difference in the VAS score of back pain between patients with and without spinous process anastomosis. Nine cases of lumbar spinal restenosis were observed, and prosthesis fracture was observed in one case. CONCLUSION: Our study identified various imaging changes after Coflex implantation, and majority of them did not affect clinical outcomes. The majority of patients had HO, but osteolysis and Coflex loosening were relatively rare. The VAS score for back pain of these patients was higher if they have spinous process anastomosis. After five-year follow-up, we found lumbar spinal restenosis and prosthesis fracture cases.


Assuntos
Fraturas Ósseas , Osteólise , Humanos , Seguimentos , Estudos Retrospectivos , Implantação de Prótese , Reoperação
6.
Cell Biol Int ; 46(5): 840-848, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35143103

RESUMO

Although many previous studies have found that the mitotic arrest deficient 2-like 1 (MAD2L1) protein contributes to the proliferation of colorectal cancer (CRC) cells, but the upstream mechanism of MAD2L1 is still largely elusive. This study aimed to explore the microRNAs (miRNAs) upstream of MAD2L1 to improve our understanding of the mechanism of the MAD2L1 gene in CRC. The upstream target miRNAs (miR-515-5p) of MAD2L1 were predicted by the online databases miRWalk, miRDIP, and TargetScan. Quantitative real-time PCR (qRT-PCR) was used to detect the expression level of miR-515-5p in human CRC tissues. The targeting relationship between miR-515-5p and MAD2L1 was tested by dual luciferase reporter gene assays. The effects of miR-515-5p on the biological behaviors of CRC cells by regulating MAD2L1 expression were verified by qRT-PCR, western blot, Cell Counting Kit-8, and flow cytometry. The results showed that miR-515-5p was a highly reliable upstream miRNA of the MAD2L1 gene. As an upstream target miRNA of MAD2L1, miR-515-5p was lowly expression in CRC tissues. The overexpression of miR-515-5p could inhibit the proliferation of CRC cells and induce cell cycle arrest at the G1 phase leading to cell apoptosis. However, MAD2L1 gene overexpression could reverse the effects of miR-515-5p overexpression on the biological behaviors of CRC cells above. This study illustrated that miR-515-5p can inhibit proliferation and induce G1 phase arrest leading to apoptosis in CRC cells. The mechanism underlying this phenomenon may be related to the negative targeted regulation of MAD2L1.


Assuntos
Neoplasias Colorretais , MicroRNAs , Apoptose/genética , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Mad2/genética , Proteínas Mad2/metabolismo , Proteínas Mad2/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo
7.
J Chem Phys ; 156(20): 204301, 2022 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-35649828

RESUMO

The adsorption and self-assembly structures of melamine molecules on an Ag(111) surface are studied by low temperature scanning tunneling microscopy (STM) combined with tip-enhanced Raman spectroscopy (TERS). Two ordered self-assembly phases of melamine molecules on Ag(111) were studied by STM and TERS, combining with first-principles simulations. The α-phase consists of flat-lying melamine molecules, while the ß-phase consists of mixed up-standing/tilted melamine molecules. Moreover, dehydrogenation of melamine can be controlled by annealing the sample as well as by a tip-enhanced photo-catalytic effect. Our work demonstrates TERS as a powerful tool not only for investigating the configuration and vibration properties of molecules on a metal surface with high spatial resolution but also for manipulating the chemical reactions with tip and photo-induced effects.

8.
Int J Mol Sci ; 23(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36077369

RESUMO

Fruit shape, an important agronomic trait of cucumber (Cucumis sativus L.), is tightly controlled by a series of genes such as CsSUN, a homologue of SlSUN that is responsible for the tomato (Solanum lycopersicum) fruit shape via the modulation of cell division. However, the direct genetic evidence about the CsSUN-mediated regulation of fruit shape is still scarce, limiting our mechanistic understanding of the biological functions of CsSUN. Here, we introduced CsSUN into the round-fruited tomato inbred line 'SN1' (wild type, WT) via the Agrobacterium tumefaciens-mediated method. The high and constitutive expression of CsSUN was revealed by real-time PCR in all the tested tissues of the transgenic plants, especially in the fruits and ovaries. Phenotypic analyses showed that the ectopic expression of CsSUN increased fruit length while it decreased fruit diameter, thus leading to the enhanced fruit shape index in the transgenic tomato lines relative to the WT. Additionally, the reduction in the seed size and seed-setting rate and the stimulation of seed germination were observed in the CsSUN-expressed tomato. A histological survey demonstrated that the elongated fruits were mainly derived from the significant increasing of the longitudinal cell number, which compensated for the negative effects of decreased cell area in the central columellae. These observations are different from action mode of SlSUN, thus shedding new insights into the SUN-mediated regulation of fruit shape.


Assuntos
Cucumis sativus , Solanum lycopersicum , Divisão Celular/genética , Cucumis sativus/genética , Expressão Ectópica do Gene , Frutas/metabolismo , Regulação da Expressão Gênica de Plantas , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
9.
Int J Mol Sci ; 23(10)2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35628653

RESUMO

Cucumber (Cucumis sativus L.) is an economically important vegetable crop with the unique growth habit and typical trailing shoot architecture of Cucurbitaceae. Elucidating the regulatory mechanisms of growth and development is significant for improving quality and productivity in cucumber. Here we isolated a spontaneous cucumber mutant organ development defective 1 (odd1) with multiple morphological changes including root, plant stature, stem, leaf, male and female flowers, as well as fruit. Anatomical and cytological analyses demonstrated that both cell size and number decreased, and the shoot apical meristem (SAM) was smaller in odd1 compared with WT. Pollen vigor and germination assays and cross tests revealed that odd1 is female sterile, which may be caused by the absence of ovules. Genetic analysis showed that odd1 is a recessive single gene mutant. Using the MutMap strategy, the odd1 gene was found to be located on chromosome 5. Integrated profiling of transcriptome and proteome indicated that the different expression genes related to hormones and SAM maintenance might be the reason for the phenotypic changes of odd1. These results expanded the insight into the molecular regulation of organ growth and development and provided a comprehensive reference map for further studies in cucumber.


Assuntos
Cucumis sativus , Cucumis sativus/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteoma/genética , Proteoma/metabolismo , Transcriptoma
10.
Molecules ; 27(3)2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35164100

RESUMO

We report a Raman characterization of the α borophene polymorph by scanning tunneling microscopy combined with tip-enhanced Raman spectroscopy. A series of Raman peaks were discovered, which can be well related with the phonon modes calculated based on an asymmetric buckled α structure. The unusual enhancement of high-frequency Raman peaks in TERS spectra of α borophene is found and associated with its unique buckling when landed on the Ag(111) surface. Our paper demonstrates the advantages of TERS, namely high spatial resolution and selective enhancement rule, in studying the local vibrational properties of materials in nanoscale.

11.
Entropy (Basel) ; 24(2)2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35205569

RESUMO

In recent years, the identification of the essential nodes in complex networks has attracted significant attention because of their theoretical and practical significance in many applications, such as preventing and controlling epidemic diseases and discovering essential proteins. Several importance measures have been proposed from diverse perspectives to identify crucial nodes more accurately. In this paper, we propose a novel importance metric called node propagation entropy, which uses a combination of the clustering coefficients of nodes and the influence of the first- and second-order neighbor numbers on node importance to identify essential nodes from an entropy perspective while considering the local and global information of the network. Furthermore, the susceptible-infected-removed and susceptible-infected-removed-susceptible epidemic models along with the Kendall coefficient are used to reveal the relevant correlations among the various importance measures. The results of experiments conducted on several real networks from different domains show that the proposed metric is more accurate and stable in identifying significant nodes than many existing techniques, including degree centrality, betweenness centrality, closeness centrality, eigenvector centrality, and H-index.

12.
J Autoimmun ; 116: 102562, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33168359

RESUMO

Adult-onset Still's disease (AOSD) is a rare autoinflammatory disease with systemic involvement, and its pathophysiology remains unclear. Genome-wide association studies (GWAS) in the Chinese population have revealed an association between AOSD and the major histocompatibility complex (MHC) locus; however, causal variants in the MHC remain undetermined. In the present study, we identified independent amino-acid polymorphisms in human leukocyte antigen (HLA) molecules that are associated with Han Chinese patients with AOSD by fine-mapping the MHC locus. Through conditional analyses, we identified position 34 in HLA-DQα1 (p = 1.44 × 10-14) and Asn in HLA-DRß1 position 37 (p = 5.12 × 10-11) as the major determinants for AOSD. Moreover, we identified the associations for three main HLA class II alleles: HLA-DQB1*06:02 (OR = 2.70, p = 3.02 × 10-14), HLA-DRB1*15:01 (OR = 2.44, p = 3.66 × 10-13), and HLA-DQA1*01:02 (OR = 1.97, p = 1.09 × 10-9). This study reveals the relationship between functional variations in the class II HLA region and AOSD, implicating the MHC locus in the pathogenesis of AOSD.


Assuntos
Aminoácidos/genética , Predisposição Genética para Doença/genética , Cadeias alfa de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Polimorfismo de Nucleotídeo Único , Doença de Still de Início Tardio/genética , Adulto , Alelos , Povo Asiático/genética , China , Frequência do Gene , Predisposição Genética para Doença/etnologia , Estudo de Associação Genômica Ampla/métodos , Genótipo , Cadeias alfa de HLA-DQ/química , Cadeias HLA-DRB1/química , Haplótipos , Humanos , Desequilíbrio de Ligação , Modelos Moleculares , Conformação Proteica , Doença de Still de Início Tardio/etnologia
13.
Appl Microbiol Biotechnol ; 105(11): 4415-4425, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34037843

RESUMO

The pathogenesis of gut microbiota in humans can be indicated due to the wide application of techniques, such as 16S rRNA sequencing. Presently, several studies have found a significant difference in fecal flora between normal individuals and patients with gastric cancer. Although clinical research on the feedback mechanism of gastric flora and gut microbiota is lacking, clarifying the relationship between gut microbiota and the characteristics of cancer is significant for the early diagnosis of gastric cancer. This study was conducted to review the results of several studies in the past 5 years and analyze the intestinal bacteria in patients with gastric cancer and compare them with those in patients with esophageal and small intestine cancers. It was found that the gut microbiota in patients with gastric cancer was similar to that in patients with esophageal cancer. However, making an analysis and comparing the gut microbiota in patients with small intestine and gastric cancers was impossible due to the low incidence of small intestinal cancer. Our review summarized the research progress on using the gut microbiota for early screening for gastric cancer, and the results of this study will provide a further direction in this field. KEY POINTS: • We reviewed several relative mechanisms of the gut microbiota related to gastric cancer. • The gut microbiota in gastric, esophageal, and small intestine cancers are significantly different in types and quantity, and we have provided some tips for further research. • A prospective review of sequencing methods and study results on the gut microbiota in gastric, esophageal, and small intestine cancers was described.


Assuntos
Neoplasias Esofágicas , Microbioma Gastrointestinal , Neoplasias Gástricas , Humanos , Intestino Delgado , Estudos Prospectivos , RNA Ribossômico 16S/genética
14.
Clin Immunol ; 198: 89-99, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30502542

RESUMO

BACKGROUND: Programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1)-targeted therapies have enhanced T-cell response and demonstrated efficacy in the treatment of multiple cancers. However, the role and clinical significance of PD-L1 expression on CD19+ B-cells and their subsets, with particular reference to systemic lupus erythematosus (SLE), have not yet been studied in detail. OBJECTIVE: The present study aimed to investigate PD-L1 expression on CD19+ B-cells and their subsets, in addition to exploring its possible role in Tfh-cell activation and B-cell differentiation in SLE. METHODS: Frequencies of CD19+ B-cells, their subsets, PD-L1 and Tfh cells in the peripheral blood of SLE patients and healthy controls (HCs) were determined using cytometry. The clinical data of SLE patients were recorded in detail, and the correlation between their laboratory parameters, clinical parameters and disease activity indices was statistically analyzed. CD19+PD-L1+B-cells and CD19+PD-L1- B-cells were sorted and cultured with a stimulant, following which the supernatants were collected for immunoglobulin G and anti-double stranded DNA detection via enzyme-linked immunosorbent assay. RESULTS: In SLE patients, CD19+B-cells and partial subgroups were enriched in peripheral blood. Also, the observed increase in the frequency of CD19+PD-L1+B-cells was significantly associated with a higher disease activity index. An in vitro culture test demonstrated that the amounts of anti-dsDNA and immunoglobulin G secreted by the CD19+PD-L1+B-cells of SLE patients and HCs were vastly different. In addition, a strong correlation existed between the frequencies of CD19+PD-L1+B-cells and defined Tfh cells of SLE patients. CONCLUSION: This study demonstrated that the expression of CD19+PD-L1+B-cells in the peripheral blood of SLE patients was abnormal, and that disease-related laboratory parameters and clinical indicators were correlated. CD19+PD-L1+B-cells were enriched and played a critical role in activating the pathogenic T-cell and B-cell responses in patients with SLE.


Assuntos
Antígenos CD19/análise , Linfócitos B/imunologia , Antígeno B7-H1/fisiologia , Lúpus Eritematoso Sistêmico/imunologia , Adulto , DNA/imunologia , Feminino , Humanos , Imunoglobulina G/biossíntese , Masculino , Pessoa de Meia-Idade , Linfócitos T Auxiliares-Indutores/imunologia
15.
Clin Exp Rheumatol ; 37 Suppl 121(6): 52-57, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31573475

RESUMO

OBJECTIVES: As a rare systemic autoinflammatory disease, adult-onset Still's disease (AOSD) has heterogeneous clinical manifestations, response to treatment and outcome. This study tried to assess the clinical characteristics, laboratory tests, and treatments of Chinese AOSD patients, and make a retrospective analysis. METHODS: We collected from 7 hospitals in China a total of 517 Chinese patients with AOSD who satisfied the Yamaguchi criteria. We retrospectively evaluated their clinical features, laboratory tests, treatments and compared them with published data from different studies. All the data in this study were from medical records and further statistic analyses. RESULTS: We evaluated a total of 517 AOSD patients, 72% female, average age of onset was 37.7; spiking fever, rash and arthralgia occurred in 472 (91.3%), 413 (79.9%), 378 (73.1%) cases, respectively. There were 439/513 (85.6%) cases with leukocytosis and 456/476 (95.8%) cases with raised serum ferritin. The highest frequently used medications and regimens for remission were glucocorticoids (498/517, 96.3%), methotrexate (273/517, 52.8%) and hydroxychloroquine (174/517, 33.7%). 84.4%. 357/423 of AOSD cases were able to achieve initial remission with different regimens, mostly including glucocorticoids, methotrexate or hydroxychloroquine. 47.2% of them (244/517) received 30

Assuntos
Glucocorticoides/uso terapêutico , Prednisona/uso terapêutico , Doença de Still de Início Tardio , Adulto , China , Feminino , Humanos , Masculino , Indução de Remissão , Estudos Retrospectivos , Doença de Still de Início Tardio/diagnóstico , Doença de Still de Início Tardio/tratamento farmacológico , Doença de Still de Início Tardio/patologia , Inquéritos e Questionários
16.
Health Care Manag Sci ; 22(2): 304-317, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29497913

RESUMO

Unit-dose drug distribution systems provide optimal choices in terms of medication security and efficiency for organizing the drug-use process in large hospitals. As small hospitals have to share such automatic systems for economic reasons, the structure of their logistic organization becomes a very sensitive issue. In the research reported here, we develop a generalized multi-level optimization method - multi-level particle swarm optimization (MLPSO) - to design a shared unit-dose drug distribution network. Structurally, the problem studied can be considered as a type of capacitated location-routing problem (CLRP) with new constraints related to specific production planning. This kind of problem implies that a multi-level optimization should be performed in order to minimize logistic operating costs. Our results show that with the proposed algorithm, a more suitable modeling framework, as well as computational time savings and better optimization performance are obtained than that reported in the literature on this subject.


Assuntos
Sistemas de Medicação no Hospital/organização & administração , Serviço de Farmácia Hospitalar/organização & administração , Algoritmos , Automação , França , Humanos , Sistemas de Medicação no Hospital/economia , Modelos Teóricos
17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(3): 394-398, 2018 May.
Artigo em Chinês | MEDLINE | ID: mdl-30014641

RESUMO

OBJECTIVE: To investigate the protective effects of paeoniflorin on the lung injury in systemic lupus erythematosus with mouse model. METHODS: Ten wild type mice and 40 MRL/lpr mice were used in this study. MRL/lpr mice were randomly assigned to MRL/lpr group,MRL/lpr + dexamethasone (1.5 mg/kg) group,MRL/lpr + paeoniflorin (20 mg/kg) group,and MRL/lpr + paeoniflorin (40 mg/kg). The levels of malondialdehyde (MDA) , superoxide dismutase (SOD) ,catalase (CAT) ,glutathione peroxidase (GSH-Px) in serum were detected. The serum levesl of inflammatory cytokines were measured. Lung pathological changes were determined by HE staining. The protein level of phospho-phosphatidylinositol-3 kinase (P-PI3K),phospho-serine-threonine kinase B(P-Akt) ,phospho-nuclear factor kappa B (P-NF-κB),phospho-inhibitor of nuclear factor kappa Bα (P-IκBα) were detected by Western blot. RESULTS: Paeoniflorin decreased serum level of MDA and increased the levels of SOD,CAT,GSH-PX,and decreased the levels of inflammatory cytokines. Paeoniflorin improved lung pathological changes and inhibited the protein levels of P-PI3K,P-Akt,P-NF-κBp65,and P-IκBα in the lung tissue of MRL/lpr mice. CONCLUSION: Paeoniflorin may be beneficial for the prevention of lung injury in systemic lupus erythematosus.


Assuntos
Glucosídeos/farmacologia , Lesão Pulmonar/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Monoterpenos/farmacologia , Animais , Lesão Pulmonar/complicações , Lúpus Eritematoso Sistêmico/complicações , Camundongos , Camundongos Endogâmicos MRL lpr
18.
BMC Cancer ; 17(1): 179, 2017 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-28270124

RESUMO

BACKGROUND: Virtually all prostate cancer deaths occur due to obtaining the castration-resistant phenotype after prostate cancer cells escaped from apoptosis and/or growth suppression initially induced by androgen receptor blockade. TNF-related apoptosis-inducing ligand (TRAIL) was an attractive cancer therapeutic agent due to its minimal toxicity to normal cells and remarkable apoptotic activity in tumor cells. However, most localized cancers including prostate cancer are resistant to TRAIL-induced apoptosis, thereby creating a therapeutic challenge of inducing TRAIL sensitivity in cancer cells. Herein the effects of cyproterone acetate, an antiandrogen steroid, on the TRAIL-induced apoptosis of androgen receptor-negative prostate cancer cells are reported. METHODS: Cell apoptosis was assessed by both annexin V/propidium iodide labeling and poly (ADP-ribose) polymerase cleavage assays. Gene and protein expression changes were determined by quantitative real-time PCR and western blot assays. The effect of cyproterone acetate on gene promoter activity was determined by luciferase reporter assay. RESULTS: Cyproterone acetate but not AR antagonist bicalutamide dramatically increased the susceptibility of androgen receptor-negative human prostate cancer PC-3 and DU145 cells to TRAIL-induced apoptosis but no effects on immortalized human prostate stromal PS30 cells and human embryonic kidney HEK293 cells. Further investigation of the TRAIL-induced apoptosis pathway revealed that cyproterone acetate exerted its effect by selectively increasing death receptor 5 (DR5) mRNA and protein expression. Cyproterone acetate treatment also increased DR5 gene promoter activity, which could be abolished by mutation of a consensus binding domain of transcription factor CCAAT-enhancer-binding protein homologous protein (CHOP) in the DR5 gene promoter. Cyproterone acetate increases CHOP expression in a concentration and time-dependent manner and endoplasmic reticulum stress reducer 4-phenylbutyrate could block cyproterone acetate-induced CHOP and DR5 up-regulation. More importantly, siRNA silencing of CHOP significantly reduced cyproterone acetate-induced DR5 up-regulation and TRAIL sensitivity in prostate cancer cells. CONCLUSIONS: Our study shows a novel effect of cyproterone acetate on apoptosis pathways in prostate cancer cells and raises the possibility that a combination of TRAIL with cyproterone acetate could be a promising strategy for treating castration-resistant prostate cancer.


Assuntos
Acetato de Ciproterona/administração & dosagem , Neoplasias da Próstata/tratamento farmacológico , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Ligante Indutor de Apoptose Relacionado a TNF/genética , Fator de Transcrição CHOP/genética , Androgênios/genética , Apoptose/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Regiões Promotoras Genéticas/efeitos dos fármacos , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , RNA Interferente Pequeno , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Fator de Transcrição CHOP/antagonistas & inibidores
19.
Nanomedicine ; 13(2): 363-370, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27562212

RESUMO

This study aims to explore a therapeutic tool that kills pathogens by using mechanical force other than temperature. We fabricated a device that generates a swing magnetic field (sMF) with low-heat production and then evaluated the killing effect of magnetotactic bacteria MO-1 on Staphylococcus aureus (S. aureus) under the sMF. S. aureus was only killed under the sMF when attached to MO-1 cells. The killing efficiency increased with increasing attachment ratio of MO-1 cells to S. aureus. Treatment with antibody-coated MO-1 cells under the sMF improved the healing of S. aureus-infected wound. The theoretical analysis demonstrated that MO-1 cells generated a mechanical force of approximately 8kPa under the sMF, thereby exerting on S. aureus and inducing cell death. The proposed platform, which uses magnetotactic bacteria under the sMF to generate mechanical force, provides a basis for development of therapeutic tools to treat infectious diseases.


Assuntos
Magnetismo/métodos , Infecções Estafilocócicas/terapia , Staphylococcus aureus , Animais , Bactérias Gram-Negativas , Campos Magnéticos , Camundongos , Infecção dos Ferimentos
20.
J Cancer Educ ; 32(4): 790-798, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27476073

RESUMO

The development of supportive care for cancer patients has been shown to have a positive impact on both mortality rates and many aspects of life after cancer, particularly in young women. Meanwhile, there are still numerous inequalities in terms of cancer mortalities and quality of life among cancer survivors in France. The processes leading to unequal access to supportive care services, and the impact this has on the post-treatment period, have been poorly documented, however. The goal of this study was to understand the barriers to using supportive care services among young women breast cancer survivors under the age of 50 and to find out how this can contribute to inequalities. Thirty-six young breast cancer survivors, one third of which deemed socially deprived, were interviewed using a qualitative, inductive approach at two comprehensive care centres in France. Our findings primarily show that there are still a number of barriers to accessing supportive care for a large number of patients. The way information about supportive services is delivered is a major cause of inequalities in the use of these services. The guidance provided does not take into account either the patients' needs or their capacity to integrate the information and anticipate problems. Certain specific post-treatment issues have yet to be addressed. Some systemic barriers could be lifted by changing the way information on supportive care services is currently organised and thereby prevent the survivorship plans now being implemented in cancer care settings from reinforcing health inequalities.


Assuntos
Neoplasias da Mama/psicologia , Neoplasias da Mama/reabilitação , Sobreviventes de Câncer/psicologia , Continuidade da Assistência ao Paciente , Acessibilidade aos Serviços de Saúde , Fatores Socioeconômicos , Adulto , Fatores Etários , Comunicação , Feminino , França , Humanos , Entrevistas como Assunto , Pessoa de Meia-Idade , Pesquisa Qualitativa , Qualidade de Vida
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