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1.
Sci Rep ; 14(1): 7278, 2024 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-38538674

RESUMO

Brucella, a gram-negative intracellular bacterium, causing Brucellosis, a zoonotic disease with a range of clinical manifestations, from asymptomatic to fever, fatigue, loss of appetite, joint and muscle pain, and back pain, severe patients have developed serious diseases affecting various organs. The mRNA vaccine is an innovative type of vaccine that is anticipated to supplant traditional vaccines. It is widely utilized for preventing viral infections and for tumor immunotherapy. However, research regarding its effectiveness in preventing bacterial infections is limited. In this study, we analyzed the epitopes of two proteins of brucella, the TonB-dependent outer membrane receptor BtuB and the LPS assembly protein LptD, which is involved in nutrient transport and LPS synthesis in Brucella. In order to effectively stimulate cellular and humoral immunity, we utilize a range of immunoinformatics tools such as VaxiJen, AllergenFPv.1.0 and SignalP 5.0 to design proteins. Finally, five cytotoxic T lymphocyte (CTL) cell epitopes, ten helper T lymphocyte (HTL) cell epitopes, and eight B cell epitopes were selected to construct the vaccine. Computer simulations are also used to verify the immune response of the vaccine. The codon optimization, in silico cloning showed that the vaccine can efficiently transcript and translate in E. coli. The secondary structure of mRNA vaccines and the secondary and tertiary structures of vaccine peptides were predicted and then docked with TLR-4. Finally, the stability of the developed vaccine was confirmed through molecular dynamics simulation. These analyses showed that the design the multi-epitope mRNA vaccine could potentially target extracellular protein of prevalent Brucella, which provided novel strategies for developing the vaccine.


Assuntos
Brucella , Proteínas de Escherichia coli , Vacinas , Humanos , Brucella/genética , Vacinas de mRNA , Escherichia coli , Lipopolissacarídeos , Epitopos de Linfócito T , Epitopos de Linfócito B , Linfócitos T Citotóxicos , Simulação de Dinâmica Molecular , Vacinas de Subunidades , Biologia Computacional , Simulação de Acoplamento Molecular , Proteínas da Membrana Bacteriana Externa/genética
2.
Adv Healthc Mater ; : e2303374, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38366905

RESUMO

Orthopedic prostheses are the ultimate therapeutic solution for various end-stage orthopedic conditions. However, aseptic loosening and pyogenic infections remain as primary complications associated with these devices. In this study, a hierarchical titanium dioxide (TiO2 ) nanotube drug delivery system loaded with cinnamaldehyde for the surface modification of titanium implants, is constructed. These specially designed dual-layer TiO2 nanotubes enhance material reactivity and provide an extensive drug-loading platform within a short time. The introduction of cinnamaldehyde enhances the bone integration performance of the scaffold (simultaneously promoting bone formation and inhibiting bone resorption), anti-inflammatory capacity, and antibacterial properties. In vitro experiments have demonstrated that this system promoted osteogenesis by upregulating both Wnt/ß-catenin and MAPK signaling pathways. Furthermore, it inhibits osteoclast formation, suppresses macrophage-mediated inflammatory responses, and impedes the proliferation of Staphylococcus aureus and Escherichia coli. In vivo experiments shows that this material enhances bone integration in a rat model of femoral defects. In addition, it effectively enhances the antibacterial and anti-inflammatory properties in a subcutaneous implant in a rat model. This study provides a straightforward and highly effective surface modification strategy for orthopedic Ti implants.

3.
Cell Commun Signal ; 22(1): 81, 2024 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291404

RESUMO

BACKGROUND: Previous research has revealed that the 18 glycoside hydrolase gene family (GH18) member Chitinase 3-like 1 (Chi3l1) can regulate osteoclast differentiation and bone resorption. However, its downstream receptors and molecular mechanisms during osteoclastogenesis have yet to be elucidated. METHODS: Initially, we conducted a comprehensive investigation to evaluate the effects of recombinant Chi3l1 protein or Chi3l1 siRNA on osteoclast differentiation and the RANKL-induced MAPK/AKT signaling pathways. Moreover, we used immunofluorescence and immunoprecipitation assays to identify IL13Rα2 as the downstream receptor of Chi3l1. Subsequently, we investigated the impact of IL13Rα2 recombinant protein or IL13Rα2-siRNA on osteoclast differentiation and the associated signaling pathways. Finally, we performed in vivo experiments to examine the effect of recombinant IL13Rα2 protein in an LPS-induced mouse model of cranial osteolysis. RESULTS: Our findings highlight that the administration of recombinant Chi3l1 protein increased the formation of osteoclasts and bolstered the expression of several osteoclast-specific genes (TRAP, NFATC1, CTR, CTSK, V-ATPase d2, and Dc-STAMP). Additionally, Chi3l1 significantly promoted the RANKL-induced MAPK (ERK/P38/JNK) and AKT pathway activation, whereas Chi3l1 silencing inhibited this process. Next, using immunofluorescence and co-immunoprecipitation assays, we identified IL13Rα2 as the binding partner of Chi3l1 during osteoclastogenesis. IL13Rα2 recombinant protein or IL13Rα2-siRNA also inhibited osteoclast differentiation, and IL13Rα2-siRNA attenuated the RANKL-induced activation of the MAPK (ERK/P38/JNK) and AKT pathways, similar to the effects observed upon silencing of Chi3l1. Moreover, the promoting effect of recombinant Chi3l1 protein on osteoclastogenesis and the activation of the MAPK and AKT pathways was reversed by IL13Rα2 siRNA. Finally, recombinant LI13Rα2 protein significantly attenuated the LPS-induced cranial osteolysis and the number of osteoclasts in vivo. CONCLUSIONS: Our findings suggested that IL13Rα2 served as a crucial receptor for Chi3l1, enhancing RANKL-induced MAPK and AKT activation to promote osteoclast differentiation. These findings provide valuable insights into the molecular mechanisms of Chi3l1 in osteoclastogenesis, with potential therapeutic implications for osteoclast-related diseases. Video Abstract.


Assuntos
Reabsorção Óssea , Subunidade alfa2 de Receptor de Interleucina-13 , Osteólise , Animais , Camundongos , Reabsorção Óssea/tratamento farmacológico , Diferenciação Celular , Proteína 1 Semelhante à Quitinase-3/metabolismo , Subunidade alfa2 de Receptor de Interleucina-13/metabolismo , Subunidade alfa2 de Receptor de Interleucina-13/uso terapêutico , Lipopolissacarídeos/farmacologia , Fatores de Transcrição NFATC/metabolismo , Osteoclastos , Osteólise/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ligante RANK/metabolismo , Proteínas Recombinantes/farmacologia , RNA Interferente Pequeno/metabolismo
4.
PLoS One ; 18(8): e0286358, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37561685

RESUMO

Brucellosis is a common zoonosis, which is caused by Brucella infection, and Brucella often infects livestock, leading to abortion and infertility. At present, human brucellosis remains one of the major public health problems in China. According to previous research, most areas in northwest China, including Xinjiang, Tibet, and other regions, are severely affected by Brucella. Although there are vaccines against animal Brucellosis, the effect is often poor. In addition, there is no corresponding vaccine for human Brucellosis infection. Therefore, a new strategy for early prevention and treatment of Brucella is needed. A multi-epitope vaccine should be developed. In this study, we identified the antigenic epitopes of the Brucella type IV secretion system VirB8 and Virb10 using an immunoinformatics approach, and screened out 2 cytotoxic T lymphocyte (CTL) epitopes, 9 helper T lymphocyte (HTL) epitopes, 6 linear B cell epitopes, and 6 conformational B cell epitopes. These advantageous epitopes are spliced together through different linkers to construct a multi-epitope vaccine. The silico tests showed that the multi-epitope vaccine was non-allergenic and had a strong interaction with TLR4 molecular docking. In immune simulation results, the vaccine construct may be useful in helping brucellosis patients to initiate cellular and humoral immunity. Overall, our findings indicated that the multi-epitope vaccine construct has a high-quality structure and suitable characteristics, which may provide a theoretical basis for the development of a Brucella vaccine.


Assuntos
Brucella , Brucelose , Vacinas , Animais , Humanos , Sistemas de Secreção Tipo IV , Epitopos de Linfócito B , Simulação de Acoplamento Molecular , Epitopos de Linfócito T , Brucelose/prevenção & controle , Biologia Computacional/métodos , Vacinas de Subunidades
5.
Biochem Pharmacol ; 215: 115704, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37536474

RESUMO

Inbonemetabolism,osteoclastsare the only cellscapableofresorbingbone. Hyperactivity of osteoclasts may lead to osteolytic disease like osteoporosis and arthritis. Although there are several drugs for the treatment of osteolytic diseases, they have limitations and a variety of side effects. An inhibitor of Janus kinase (JAK), XL019, has shown promising results in the treatment of myelofibrosis and other cancers. But whether it can functionally impact osteoclast activity has not been proven. In this study, the effects of XL019 on osteoclastogenesis and the mechanism pathway were investigated in vitro. It was found that XL019 could impair osteoclasts formation, interfere with bone resorption ability and downregulate the osteoclast-specific genes and proteins expression. Furthermore, Western blot and molecular docking studies demonstrated that XL019 inhibited RANKL-induced osteoclastogenesis by suppressing MAPK signaling. A molecular docking analysis explained how XL019 binds to MAPK pathway factors. In addition, titanium particles induced calvarial osteolysis in mice further confirming its beneficial effect on bone homeostasis in vivo. In conclusion, this study demonstrates that Osteoclastactivity canbeeffectivelyinhibitedby XL019viaMAPK signalingpathway,making it a promising alternative pharmacologicaltreatmentfor bone metabolicdisorders.


Assuntos
Reabsorção Óssea , Inibidores de Janus Quinases , Osteólise , Animais , Camundongos , Osteoclastos , Inibidores de Janus Quinases/farmacologia , Simulação de Acoplamento Molecular , Transdução de Sinais , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/metabolismo , Osteogênese , Osteólise/metabolismo , Ligante RANK/farmacologia , Diferenciação Celular , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo
6.
Acta Biomater ; 168: 159-173, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37467837

RESUMO

Matrix mechanics regulate essential cell behaviors through mechanotransduction, and as one of its most important elements, substrate stiffness was reported to regulate cell functions such as viability, communication, migration, and differentiation. Neutrophils (Neus) predominate the early inflammatory response and initiate regeneration. The activation of Neus can be regulated by physical cues; however, the functional alterations of Neus by substrate stiffness remain unknown, which is critical in determining the outcomes of engineered tissue mimics. Herein, a three-dimensional (3D) culture system made of hydrogels was developed to explore the effects of varying stiffnesses (1.5, 2.6, and 5.7 kPa) on the states of Neus. Neus showed better cell integrity and viability in the 3D system. Moreover, it was shown that the stiffer matrix tended to induce Neus toward an anti-inflammatory phenotype (N2) with less adhesion molecule expression, less reactive oxygen species (ROS) production, and more anti-inflammatory cytokine secretion. Additionally, the aortic ring assay indicated that Neus cultured in a stiffer matrix significantly increased vascular sprouting. RNA sequencing showed that a stiffer matrix could significantly activate JAK1/STAT3 signaling in Neus and the inhibition of JAK1 ablated the stiffness-dependent increase in the expression of CD182 (an N2 marker). Taken together, these results demonstrate that a stiffer matrix promotes Neus to shift to the N2 phenotype, which was regulated by JAK1/STAT3 pathway. This study lays the groundwork for further research on fabricating engineered tissue mimics, which may provide more treatment options for ischemic diseases and bone defects. STATEMENT OF SIGNIFICANCE.


Assuntos
Medula Óssea , Neutrófilos , Mecanotransdução Celular , Hidrogéis/farmacologia , Hidrogéis/química , Diferenciação Celular
7.
J Environ Manage ; 344: 118646, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37481916

RESUMO

Mining activities induce some social problems, such as polluted environments, the destruction of aquatic live, which have long been debated by scholars and practitioners. To mitigate this problem, underpinning dynamic capability view, our study explores whether the digital transformation (DT) affects corporate social responsibility (CSR) by using 1308 Chinese mining A-shared listed firms from 2010 to 2021, and how the potential relationship is moderated by environmental uncertainty (EU) and supply chain concentration (SCC). Applying fixed effects regressions, we find that DT fosters CSR in the mining industry, but CSR performance is weakened when DT processed at higher EU and SCC respectively. Our findings enrich the literature on CSR of mining industry and highlight that DT is an important driver that shapes CSR practice.


Assuntos
Tecnologia Digital , Mineração , Responsabilidade Social , Desenvolvimento Sustentável , China
8.
Anticancer Agents Med Chem ; 23(13): 1506-1518, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37026490

RESUMO

Gastric cancer is a severe malignant tumor with high morbidity and mortality, which seriously affects people's health. At present, the most common treatment for gastric cancer is chemotherapy. However, chemotherapy is very harmful to the human body, and some of the injuries caused by chemotherapy are irreversible. Natural products have low toxicity and anti-cancer activity, so they are currently widely studied at present. Natural products are a large variety of compounds naturally found in fruits, vegetables, spices, and medicinal plants. It is reported that natural products have different anti-cancer properties. This review has summarized the study of natural products in inducing gastric cancer cell apoptosis, inhibiting gastric cancer cell metastasis, and inhibiting gastric cancer cell proliferation. The relevant references on gastric cancer and natural products were obtained from scientific databases, including Pub- Med, Web of Science, and Science Direct. This paper records dozens of natural products with anti-gastric tumor activity and describes the potential living anti-cancer chemical compounds, their element targets, and their underlying mechanism. This review may lay the foundation for future researchers to treat gastric cancer.


Assuntos
Produtos Biológicos , Plantas Medicinais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Produtos Biológicos/farmacologia , Produtos Biológicos/uso terapêutico , Frutas/química , Apoptose
9.
Oxid Med Cell Longev ; 2023: 1952348, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36756301

RESUMO

As a degenerative disease in joints, temporomandibular joint osteoarthritis (TMJOA) is characterized by progressive cartilage degradation, subchondral bone remodeling, and chronic synovitis, severely undermining functions and quality of life in patients. NADPH oxidase 4 (NOX4) contributes to reactive oxygen species (ROS) production and inflammatory pathway activation in osteoarthritis, which has attracted increasing attention in research in recent years. GLX351322 (GLX), a novel NOX4 inhibitor, exerts a protective effect on chondrocytes. However, whether it has a therapeutic effect on ROS production and inflammatory responses in synovial macrophages remains to be evaluated. In this study, we examined the effect of GLX on LPS-induced ROS production and inflammatory responses in vitro and on complete Freund's adjuvant (CFA)-induced TMJ inflammation in vivo. We found that GLX could depress LPS-induced intracellular ROS production and inflammatory response without cytotoxicity by inhibiting the ROS/MAPK/NF-κB signaling pathways. In line with in vitro observations, GLX markedly attenuated the synovial inflammatory reaction in the TMJ, thus protecting the condylar structure from severe damage. Taken together, our results suggest that GLX intervention or NOX4 inhibition is a promising curative strategy for TMJOA and other inflammatory diseases.


Assuntos
NADPH Oxidase 4 , NF-kappa B , Osteoartrite , Humanos , Inflamação/metabolismo , Lipopolissacarídeos , NADPH Oxidase 4/antagonistas & inibidores , NF-kappa B/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Qualidade de Vida , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Articulação Temporomandibular/metabolismo , Articulação Temporomandibular/fisiopatologia
10.
J Med Chem ; 66(3): 1852-1872, 2023 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-36715603

RESUMO

Exploring multi-targeting chemotherapeutants with advantages over single-targeting agents and drug combinations is of great significance in drug discovery. Herein, we employed phytogenic evodiamine (EVO) and conventional Pt(II) drugs to design and synthesize multi-target EVO-Pt(IV) anticancer prodrugs (4-14). Among them, compound 10 exhibited a 118-fold enhancement in the IC50 value compared to cisplatin and low toxicity to normal cells. Further studies proved that 10 significantly enhanced intracellular Pt accumulation and DNA damage, perturbed mitochondrial membrane potential, inhibited cell migration and invasion, upregulated reactive oxygen species levels, and induced apoptosis and autophagic cell death. Molecular docking assay revealed that 10 fits perfectly into the extracellular signal-regulated protein kinase (ERK)-1 pocket, which was verified to produce profound ERK suppression. Most strikingly, compound 10 exhibited superior in vivo antitumor efficiency and effectively attenuated systemic toxicity. Our results emphasize that functionalizing platinum drugs with the multi-target EVO could generate synergistically excellent anticancer activity with low toxicity and decreased resistance, which may represent a brand-new cancer therapy modality.


Assuntos
Antineoplásicos , Pró-Fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Pró-Fármacos/farmacologia , Pró-Fármacos/uso terapêutico , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Cisplatino/farmacologia , MAP Quinases Reguladas por Sinal Extracelular , Apoptose , Dano ao DNA , Autofagia
11.
Microbiol Spectr ; 11(1): e0201722, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36515504

RESUMO

Clavulanic acid (CA) is the preferred clinical drug for the treatment of infections by ß-lactam antibiotic-resistant bacteria. CA is produced by Streptomyces clavuligerus, and although there have been many reports on the effects of carbon and nitrogen sources on CA production, the mechanisms involved remain unclear. In this study, we found that CA accumulation in S. clavuligerus F613-1 was increased significantly in MH medium, which is rich in organic nitrogen, compared with that in ML medium, which contains half the amount of organic nitrogen present in MH medium. Transcriptome analysis revealed that genes involved in CA biosynthesis, such as ceas1, ceas2, bls1, bls2, cas2, pah2, gcaS, and cad, and arginine biosynthesis, such as argB, argC, argD, argG, argH, argJ, and argR, were upregulated under rich organic nitrogen. Metabolome data revealed notable differences between cultures of F613-1 grown in MH and ML media with regard to levels of key intracellular metabolites, most of which are involved in arginine metabolic pathways, including arginine, glutamine, and glutamic acid. Additionally, supplementation of ML medium with arginine, glutamine, or glutamic acid resulted in increased CA production by S. clavuligerus F613-1. Our results indicate that rich organic nitrogen mainly affects CA biosynthesis by increasing the levels of amino acids associated with the arginine metabolic pathway and activating the expression of the CA biosynthetic gene cluster. These findings provide important insights for improving medium optimization and engineering of S. clavuligerus F613-1 for high-yield production of CA. IMPORTANCE The bacterium Streptomyces clavuligerus is used for the industrial production of the broad-spectrum ß-lactamase inhibitor clavulanic acid (CA). However, much remains unknown about the factors which affect CA yields. We investigated the effects of different levels of organic nitrogen on CA production. Our analyses indicate that higher organic nitrogen levels were associated with increased CA yields and increased levels of arginine biosynthesis. Further analyses supported the relationship between arginine metabolism and CA production and demonstrated that increasing the levels of arginine or associated amino acids could boost CA yields. These findings suggest approaches for improving the production of this clinically important antibiotic.


Assuntos
Arginina , Glutamina , Arginina/metabolismo , Glutamina/metabolismo , Nitrogênio , Ácido Clavulânico/química , Antibacterianos , Aminoácidos/metabolismo , Redes e Vias Metabólicas , Glutamatos/metabolismo
12.
Sci Rep ; 12(1): 10146, 2022 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-35710873

RESUMO

Brucella is a typical facultative intracellular bacterium that can cause zoonotic infections. For Brucella, it is difficult to eliminate with current medical treatment. Therefore, a multi-epitope vaccine (MEV) should be designed to prevent Brucella infection. For this purpose, we applied the reverse vaccinology approach from Omp10, Omp25, Omp31 and BtpB. Finally, we obtained 13 cytotoxic T lymphocyte (CTL) epitopes, 17 helper T lymphocyte (HTL) epitopes, 9 linear B cell epitopes, and 2 conformational B cell epitopes for further study. To keep the protein folded normally, we linked AAY, GPGPG, and KK to CTL epitopes, HTL epitopes, and B cell epitopes, respectively. The N-terminal of the vaccine peptide is supplemented with appropriate adjuvants to enhance immunogenicity. To evaluate its immunogenicity, stability, safety, and feasibility, a final MEV containing 806 amino acids was constructed by linking linkers and adjuvants. In addition, molecular docking and molecular dynamics simulations were performed to verify the affinity and stability of the MEV-TLR4. Then, codon adaptation and in silico cloning studies were carried out to identify the possible codons for expressing the MEV. In animal experiments, the results demonstrated that the MEV had high immunogenicity. Collectively, this study provided a theoretical basis for the development of a Brucella vaccine.


Assuntos
Brucella melitensis , Animais , Biologia Computacional/métodos , Epitopos de Linfócito B , Epitopos de Linfócito T , Simulação de Acoplamento Molecular , Vacinas de Subunidades
13.
J Craniomaxillofac Surg ; 49(10): 929-934, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34210564

RESUMO

To confirm the effectiveness and stability of an improved anchoring nail through a prospective study using clinical evaluation and magnetic resonance imaging (MRI). Patients undergoing TMJ disc reduction and fixation were followed up for 1 year.Visual analog scale (VAS) pain scores and TMJ range of motion (maximum interincisal opening, protrusive excursion, lateral excursion) data were gathered pre- and postoperatively, and patient satisfaction was recorded. Four time points were investigated: before surgery (T0), 1 month post-surgery (T1), 6 months post-surgery (T2), and 1 year post-surgery (T3). Twenty-five patients (50 joints) participated in the study. The overall success rates of the improved and traditional anchoring nails were 88% and 92%, respectively. One year post-surgery, the patients' TMJ motion improved significantly (p < 0.001), and their pain was significantly alleviated (p < 0.001). Condyle height did not change significantly within 6 months (p = 0.801), but had increased by approximately 1.35 mm (p < 0.001) at 1 year post-surgery. The MRI scans also confirmed that new bone mass growth was present 1 year post-surgery. Compared with the traditional anchoring nail, the improved anchoring nail had a similar success rate and was associated with fewer foreign body sensations and less pain. Its clinical application should be further tested in studies with longer follow-up times and larger sample sizes.


Assuntos
Disco da Articulação Temporomandibular , Transtornos da Articulação Temporomandibular , Humanos , Unhas , Estudos Prospectivos , Amplitude de Movimento Articular , Disco da Articulação Temporomandibular/diagnóstico por imagem , Disco da Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/cirurgia
14.
Medicine (Baltimore) ; 100(18): e25753, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950960

RESUMO

BACKGROUNDS: Due to difficulty in early diagnosis of chronic pancreatitis (CP), it is urgent to find novel biomarkers to detect CP. Exosomal microRNAs (Exo-miRNAs) located in the serum may be potential diagnostic and therapeutic targets for CP. OBJECTIVE: To identify differentially expressed Exo-miRNAs (DE-Exo-miRNAs) in the serum of CP patients, we performed a bioinformatics analysis. METHODS: The dataset GSE128508 was downloaded from the Gene Expression Omnibus (GEO) database. The analysis was carried out using BRB-ArrayTools and significance analysis of microarrays (SAM). The target genes of DE-S-Exo-miRNAs were predicted by miRWalk databases. Further gene ontology (GO) term and Kyoto Encyclopedia of Genomes (KEGG) pathway analyses were performed with plug-in ClueGO in Cytoscape software 3.7.0. Subsequently, the interaction regulatory network between encoded proteins of target genes was performed with the Search Tool for the Retrieval of Interacting Genes (STRING) database and analyzed using plug-in Molecular Complex Detection (MCODE) and cytoHubba in Cytoscape software 3.7.0. RESULTS: We identified 227 DE-Exo-miRNAs in the serum. Further analysis using the miRWalk database identified 5164 target genes of these miRNAs. The protein-protein interaction (PPI) regulatory network of 1912 potential target genes for hub 10 up-regulated miRNAs with high degrees and one down-regulated miRNAs were constructed using the STRING database and Cytoscape software. The functional analysis using Cytoscape software tool highlighted that target genes involved in pancreatic cancer. Acinar-ductal metaplasia (ADM) in the inflammatory environment of CP is a precursor of pancreatic cancer. Subsequently, we constructed a network of target genes associated with ADM and their miRNAs. CONCLUSIONS: Exo-miRNAs in the serum as well as their target genes may be promising targets for the early diagnosis and treatment of CP. In addition, we identified potential Exo-miRNAs involved in ADM that is a precursor of pancreatic cancer associated with CP.


Assuntos
MicroRNAs/sangue , Pâncreas/patologia , Neoplasias Pancreáticas/genética , Pancreatite Crônica/patologia , Lesões Pré-Cancerosas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Biologia Computacional , Conjuntos de Dados como Assunto , Exossomos/metabolismo , Feminino , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Metaplasia , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Pancreatite Crônica/sangue , Pancreatite Crônica/imunologia , Lesões Pré-Cancerosas/sangue , Lesões Pré-Cancerosas/genética , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/genética
15.
Dig Dis Sci ; 66(2): 541-546, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32193861

RESUMO

BACKGROUND: Pain associated with colonoscopies is a major barrier to patients participating in colorectal cancer screenings. While sedation and analgesia are used to reduce pain during the procedure, they are associated with increased complications and costs. Thus, it is necessary to identity novel techniques to relieve pain in a safe and cost-effective way. AIMS: To test whether watching real-time videos of colonoscopies while receiving detailed interpretations of the procedures reduces pain and anxiety and increases a patient's satisfaction. METHODS: Patients were randomized into three groups including a group who watched real-time videos of their colonoscopies (Group A), a group who watched real-time videos of their colonoscopies while receiving detailed interpretations of the procedures from the endoscopists (Group B), and a group who did not receive either method (Group C). RESULTS: Pain and anxiety scores were significantly (Group A vs. Group C, [Formula: see text]; Group B vs. Group C, [Formula: see text]) lower in Groups A and B compared to Group C. Additionally, significantly (Group A vs. Group C, [Formula: see text]; Group B vs. Group C, [Formula: see text]) increased satisfaction was observed in Groups A and B compared to Group C. There were no statistically significant differences observed in the pain and anxiety scores when comparing Groups A and B. However, the overall satisfaction score was significantly ([Formula: see text]) higher in Group B compared to Group A. CONCLUSIONS: Real-time videos of colonoscopies as well as videos along with detailed interpretations of the procedures decrease pain and anxiety while improving satisfaction in patients undergoing colonoscopies without sedation. Videos combined with interpretations lead to a greater increase in patient satisfaction.


Assuntos
Ansiedade/psicologia , Colonoscopia/psicologia , Dor/psicologia , Educação de Pacientes como Assunto/métodos , Satisfação do Paciente , Gravação em Vídeo/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/prevenção & controle , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dor/prevenção & controle , Manejo da Dor/métodos , Manejo da Dor/psicologia , Estudos Prospectivos , Adulto Jovem
16.
Int J Nanomedicine ; 15: 6761-6777, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32982232

RESUMO

PURPOSE: Guided bone regeneration (GBR) therapy, which is a widely used technique in clinical practice and is effective in improving the repair of alveolar bone defects or bone mass deficiency regeneration, requires the use of membrane materials with good biocompatibility, barrier function, rigidity matching the space maintenance ability, economic benefits and excellent clinical applicability. The aim of this study was to develop an electrospun attapulgite (ATT)-doped poly (lactic-co-glycolic acid) (PLGA) scaffold (PLGA/ATT scaffold) as a novel material for GBR applications. METHODS AND RESULTS: Scanning electron microscopy (SEM) and X-ray diffraction (XRD) were used to determine the morphology and the crystalline structure of the PLGA/ATT scaffolds, respectively. Porosity and contact-angle measurements were also carried out to further characterize the physical properties of the PLGA/ATT scaffolds. The results of in vitro studies showed that bone marrow mesenchymal stem cells (BMSCs) attached more readily to and spread better over the PLGA/ATT scaffolds than the Bio-Gide membrane. Furthermore, in the in vitro osteoinductive experiments with BMSCs, the PLGA/ATT scaffolds were found to enhance the activity of alkaline phosphatase (ALP), promote the formation of mineralized bone nodules, and up-regulate the expression of several osteogenic markers-namely, runt-related transcription factor 2, alkaline phosphatase, osteopontin, and osteocalcin-which are similar to the effects of the Bio-Gide membrane. Further, in in vivo studies, the results of sequential fluorescent labeling, micro-computed tomography, and histological analysis suggest that using the PLGA/ATT scaffolds for repairing V-shaped buccal dehiscence on a dog's tooth root improved bone regeneration, which is not only similar to the result obtained using the Bio-Gide membrane but also much better than that obtained using PLGA scaffolds and the negative control. CONCLUSION: To achieve satisfactory therapeutic results and to lower the cost of GBR treatment, this study provided a promising alternative material of bio-degradable membrane in clinical treatment.


Assuntos
Perda do Osso Alveolar/terapia , Regeneração Óssea/fisiologia , Compostos de Magnésio/farmacologia , Compostos de Silício/farmacologia , Tecidos Suporte/química , Animais , Regeneração Óssea/efeitos dos fármacos , Calcificação Fisiológica , Colágeno , Cães , Expressão Gênica , Gengiva/citologia , Humanos , Compostos de Magnésio/química , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Osteogênese/efeitos dos fármacos , Osteogênese/genética , Osteogênese/fisiologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Porosidade , Ratos Sprague-Dawley , Compostos de Silício/química , Raiz Dentária/diagnóstico por imagem , Microtomografia por Raio-X
17.
World J Clin Cases ; 8(11): 2364-2373, 2020 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-32548169

RESUMO

BACKGROUND: Haemophagocytic syndrome (HPS) is rarely seen in patients with acute pancreatitis (AP). HPS as a complication of AP in patients without any previous history has not been elucidated. CASE SUMMARY: A 46-year-old man was admitted for symptom of persistent abdominal pain, nausea, and vomiting for 2 d after heavy drinking. During hospital stay, he suddenly developed skin rash and a secondary fever. The laboratory findings revealed progressive pancytopenia, abnormal hepatic tests, and elevation of serum triglyceride, ferritin, and lactate dehydrogenase levels. However, apparent bacterial or viral infections were not detected. He was also possibly related to autoimmune diseases because of positive expression of various autoimmune antibodies and no remarkable past history. Finally, the bone marrow examination showed a histiocytic reactive growth and prominent hemophagocytosis, which resulted in a diagnosis of HPS. Unexpectedly, the patient responded well to the immunosuppressive therapy. CONCLUSION: HPS is a very rare extrapancreatic manifestation of AP. The diagnosis relies on bone marrow examination and immunosuppressive therapy is effective. For AP with skin changes, the possibility of HPS should be considered during clinical work.

18.
Appl Opt ; 58(9): 2183-2189, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-31044916

RESUMO

Traditional microscopes do not meet a wide field of view and high resolution at the same time. We propose a method for image restoration and color fusion of digital microscopes. It combines a single high-resolution gray scale hologram with a low-resolution color image to obtain a high-resolution color image. Specifically, the high-resolution gray scale image is obtained by reconstructing three different height holograms using a wavelet-based method, and the color information is obtained using a portable cell phone microscope. The subsequent calibration and blending of colors ultimately results in a high-resolution, wide-field color map that can be of great help in the study of pathology or biomedicine. This method breaks the rule that the large field of view and high resolution of a traditional microscope cannot be simultaneously satisfied, which can realize a more comprehensive observation of the shape and details of the slice.

19.
Sensors (Basel) ; 18(8)2018 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-30081474

RESUMO

Learning variable impedance control is a powerful method to improve the performance of force control. However, current methods typically require too many interactions to achieve good performance. Data-inefficiency has limited these methods to learn force-sensitive tasks in real systems. In order to improve the sampling efficiency and decrease the required interactions during the learning process, this paper develops a data-efficient learning variable impedance control method that enables the industrial robots automatically learn to control the contact force in the unstructured environment. To this end, a Gaussian process model is learned as a faithful proxy of the system, which is then used to predict long-term state evolution for internal simulation, allowing for efficient strategy updates. The effects of model bias are reduced effectively by incorporating model uncertainty into long-term planning. Then the impedance profiles are regulated online according to the learned humanlike impedance strategy. In this way, the flexibility and adaptivity of the system could be enhanced. Both simulated and experimental tests have been performed on an industrial manipulator to verify the performance of the proposed method.

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