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1.
Food Chem Toxicol ; 185: 114476, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38301993

RESUMO

Indigo naturalis (IN) is a dried powder derived from plants such as Baphicacanthus cusia (Neeks) Bremek., Polygonum tinctorium Ait. and Isatis indigotica Fork. It has a historical application as a dye in ancient India, Egypt, Africa and China. Over time, it has been introduced to China and Japan for treatment of various ailments including hemoptysis, epistaxis, chest discomfort, and aphtha. Clinical and pre-clinical studies have widely demonstrated its promising effects on autoimmune diseases like psoriasis and Ulcerative colitis (UC). Despite the documented efficacy of IN in UC patients, concerns have been raised on the development of adverse effects with long term consumption, prompting a closer examination of its safety and tolerability in these contexts. This review aims to comprehensively assess the efficacy of IN in both clinical and pre-clinical settings, with a detailed exploration of the mechanisms of action involved. Additionally, it summarizes the observed potential toxicity of IN in animal and human settings was summarized. This review will deepen our understanding on the beneficial and detrimental effects of IN in UC, providing valuable insights for its future application in patients with this condition.


Assuntos
Colite Ulcerativa , Medicamentos de Ervas Chinesas , Psoríase , Animais , Humanos , Índigo Carmim/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Psoríase/induzido quimicamente , China
2.
Anal Bioanal Chem ; 416(4): 849-859, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38006441

RESUMO

Despite significant advancements in cancer research, real-time monitoring and effective treatment of cancer through non-invasive techniques remain a challenge. Herein, a novel polydopamine (PDA) nucleic acid nanoprobe has been developed for imaging signal amplification of intracellular mRNA and precise photothermal therapy guidance in cancer cells. The PDA nucleic acid nanoprobe (PDA@DNA) is constructed by assembling an aptamer hairpin (H1) labeled with the Cy5 fluorophore and another nucleic acid recognition hairpin (H2) onto PDA nanoparticles (PDA NPs), which have exceptionally high fluorescence quenching ability and excellent photothermal conversion properties. The nanoprobe could facilitate cellular uptake of DNA molecules and their protection from nuclease degradation. Upon recognition and binding to the intracellular mRNA target, a catalytic hairpin assembly (CHA) reaction occurs. The stem of H1 unfolds upon binding, allowing the exposed H1 to hybridize with H2, forming a flat and sturdy DNA double-stranded structure that detaches from the surface of PDA NPs. At the same time, the target mRNA is displaced and engages in a new cyclic reaction, resulting in the recovery and significant amplification of Cy5 fluorescence. Using thymidine kinase1 (TK1) mRNA as a model mRNA, this nanoprobe enables the analysis of TK1 mRNA with a detection limit of 9.34 pM, which is at least two orders of magnitude lower than that of a non-amplifying imaging nucleic acid probe. Moreover, with its outstanding performance for in vitro detection, this nanoprobe excels in precisely imaging tumor cells. Through live-cell TK1 mRNA imaging, it can accurately distinguish between tumor cells and normal cells. Furthermore, when exposed to 808-nm laser irradiation, the nanoprobe fully harnesses exceptional photothermal conversion properties of PDA NPs. This results in a localized temperature increase within tumor cells, which ultimately triggers apoptosis in these tumor cells. The integration of PDA@DNA presents innovative prospects for tumor diagnosis and image-guided tumor therapy, offering the potential for high-precision diagnosis and treatment of tumors.


Assuntos
Carbocianinas , Indóis , Nanopartículas , Neoplasias , Polímeros , Humanos , Fototerapia , Terapia Fototérmica , RNA Mensageiro/química , Nanopartículas/química , DNA/química , Neoplasias/patologia
3.
Endokrynol Pol ; 74(2): 168-175, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37155300

RESUMO

INTRODUCTION: The study aimed to explore the efficacy and safety of low-dose (LD) and regular-dose (RD) prednisone (PDN) for the treatment of subacute thyroiditis (SAT). MATERIAL AND METHODS: Patients were randomly allocated using the block randomization method to the 2 groups. The primary outcome was the time required for PDN treatment. Secondary outcomes included percentages of relapse, mean score for the Morisky Medication Adherence Scale-8© (MMAS-8), time required for symptoms to resolve, cumulative PDN dose (mg), and mean erythrocyte sedimentation rate (ESR) at 2 weeks and at baseline. RESULTS: The study cohort included 77 patients, randomized 74 participants, and 68 completed the study. There was no significant difference in the treatment duration between the LD and RD groups (55.31 ± 14.05 vs. 61.25 ± 19.95 days, p = 0.053). The mean difference in the time required for PDN treatment between the LD and RD groups was -1.86 [95% confidence interval (CI) = -10.64 to 6.92] days, which was within the non-inferiority margin of 7 days. There was a significant difference in the mean score for MMAS-8 between the LD and RD groups (5.84 ± 0.88 vs. 5.33 ± 1.12, p = 0.031). Also, there was a significant difference in the cumulative PDN dose between the LD and RD groups (504.22 ± 236.86 vs. 1002.28 ± 309.86, p = 0.046). The ESR at 2 weeks was statistically significant compared to baseline values in both groups, with pre-treatment and post-treatment ESRs of 49.91 ± 24.95 and 17.91 ± 12.60/mm/h, (p < 0.0001) in the LD group and 65.08 ± 21.77 and 17.23 ± 13.61/mm/h (p < 0.0001) in the RD group. CONCLUSION: Low-dose PDN therapy may be sufficient to achieve complete recovery and better outcomes for SAT. This study is registered with the Chinese Clinical Trial Registry (02/10/2021 ChiCTR2100051762).


Assuntos
Tireoidite Subaguda , Humanos , Prednisona/uso terapêutico , Tireoidite Subaguda/tratamento farmacológico , Estudos Prospectivos , Resultado do Tratamento , Recidiva Local de Neoplasia
4.
Differentiation ; 132: 15-23, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37055300

RESUMO

BACKGROUND: Aging and regeneration are heavily linked processes. While it is generally accepted that regenerative capacity declines with age, some vertebrates, such as newts, can bypass the deleterious effects of aging and successfully regenerate a lens throughout their lifetime. RESULTS: Here, we used Spectral-Domain Optical Coherence Tomography (SD-OCT) to monitor the lens regeneration process of larvae, juvenile, and adult newts. While all three life stages were able to regenerate a lens through transdifferentiation of the dorsal iris pigment epithelial cells (iPECs), an age-related change in the kinetics of the regeneration process was observed. Consistent with these findings, iPECs from older animals exhibited a delay in cell cycle re-entry. Furthermore, it was observed that clearance of the extracellular matrix (ECM) was delayed in older organisms. CONCLUSIONS: Collectively, our results suggest that although lens regeneration capacity does not decline throughout the lifespan of newts, the intrinsic and extrinsic cellular changes associated with aging alter the kinetics of this process. By understanding how these changes affect lens regeneration in newts, we can gain important insights for restoring the age-related regeneration decline observed in most vertebrates.


Assuntos
Cristalino , Pleurodeles , Animais , Salamandridae , Matriz Extracelular , Divisão Celular
5.
J Chromatogr A ; 1685: 463622, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36375215

RESUMO

Efficient extraction is a vital step in mercury speciation. In this context, using 4-vinylbenzeneboronic acid and 9-vinylanthracene as functional monomers, a new magnetic adsorbent was fabricated according to one-pot hydrothermal approach. Various characterization results prove the as-prepared adsorbent presented abundant functional groups and saturation magnetism. Combining with magnetic solid phase extraction (MSPE), the adsorbent exhibited satisfactory entrapment performance towards different mercury species which had been pre-coordinated with dithizone to form metal-organic coordination. A series of parameters influencing the extraction performance were inspected in detail. Under the most beneficial conditions, sensitive and reliable approach to quantify trace methylmercury, ethylmercury, phenylmercury and inorganic mercury in aqueous samples was developed by the combination of HPLC/DAD. Limits of detection and precision located in the ranges of 0.012-0.074 µg/L and 2.5-9.8%, respectively. Recoveries with low, medium and high fortified contents in actual waters varied from 79.8 to 119%. Confirmatory experiments were performed to evidence the accuracy and reliability of established approach. In addition, a possible mechanism was suggested based on the chemical nature of analytes, extraction conditions and characterization results.


Assuntos
Mercúrio , Mercúrio/análise , Cromatografia Líquida de Alta Pressão/métodos , Reprodutibilidade dos Testes , Extração em Fase Sólida/métodos , Água/química , Indicadores e Reagentes/análise , Fenômenos Magnéticos
6.
Sensors (Basel) ; 22(17)2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36081038

RESUMO

Path planning is a very important step for mobile smart vehicles in complex environments. Sampling based planners such as the Probabilistic Roadmap Method (PRM) have been widely used for smart vehicle applications. However, there exist some shortcomings, such as low efficiency, low reuse rate of the roadmap, and a lack of guidance in the selection of sampling points. To solve the above problems, we designed a pseudo-random sampling strategy with the main spatial axis as the reference axis. We optimized the generation of sampling points, removed redundant sampling points, set the distance threshold between road points, adopted a two-way incremental method for collision detections, and optimized the number of collision detection calls to improve the construction efficiency of the roadmap. The key road points of the planned path were extracted as discrete control points of the Bessel curve, and the paths were smoothed to make the generated paths more consistent with the driving conditions of vehicles. The correctness of the modified PRM was verified and analyzed using MATLAB and ROS to build a test platform. Compared with the basic PRM algorithm, the modified PRM algorithm has advantages related to speed in constructing the roadmap, path planning, and path length.


Assuntos
Algoritmos , Projetos de Pesquisa
7.
Front Endocrinol (Lausanne) ; 13: 865436, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35464064

RESUMO

Chemotherapy is a critical treatment for endocrine-related cancers; however, chemoresistance and disease recurrence remain a challenge. The interplay between cancer cells and the tumor microenvironment via cell adhesion molecules (CAMs) promotes drug resistance, known as cell adhesion-mediated drug resistance (CAM-DR). CAMs are cell surface molecules that facilitate cell-to-cell or cell-to-extracellular matrix binding. CAMs exert an adhesion effect and trigger intracellular signaling that regulates cancer cell stemness maintenance, survival, proliferation, metastasis, epithelial-mesenchymal transition, and drug resistance. To understand these mechanisms, this review focuses on the role of CD44, cadherins, selectins, and integrins in CAM-DR in endocrine-related cancers.


Assuntos
Moléculas de Adesão Celular , Neoplasias , Caderinas/metabolismo , Caderinas/farmacologia , Adesão Celular , Moléculas de Adesão Celular/metabolismo , Humanos , Integrinas/metabolismo , Microambiente Tumoral
8.
J Neurosci Methods ; 367: 109436, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34890697

RESUMO

BACKGROUND: The temporal precision in neural spike train data is critically important for understanding functional mechanism in the nervous systems. However, the timing variability of spiking activity can be highly nonlinear in practical observations due to behavioral variability or unobserved/unobservable cognitive states. NEW METHOD: In this study, we propose to adopt a powerful nonlinear method, referred to as the Fisher-Rao Registration (FRR), to remove such nonlinear phase variability in discrete neuronal spike trains. We also develop a smoothing procedure on the discrete spike train data in order to use the FRR framework. COMPARISON WITH EXISTING METHODS: We systematically compare the FRR with the state-of-the-art linear and nonlinear methods in terms of model efficiency and effectiveness. RESULTS: We show that the FRR has superior performance and the advantages are well illustrated with simulation and real experimental data. CONCLUSIONS: It is found the FRR framework provides more appropriate alignment performance to understand the temporal variability in neuronal spike trains.


Assuntos
Modelos Neurológicos , Neurônios , Potenciais de Ação/fisiologia , Simulação por Computador , Neurônios/fisiologia
9.
J Immunother Cancer ; 9(10)2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34697216

RESUMO

BACKGROUND: Combination therapy has been explored for advanced head and neck squamous cell carcinoma (HNSCC) owing to the limited efficacy of anti-epidermal growth factor receptor (EGFR) therapy. Increased expression and glycosylation of immune checkpoint molecules in tumors are responsible for cetuximab therapy refractoriness. The role of programmed death ligand 2 (PD-L2), a ligand of PD-1, in the immune function is unclear. Here, we examined the regulatory mechanism of PD-L2 glycosylation and its role in antitumor immunity and cetuximab therapy. METHODS: Single-cell RNA sequencing and immunohistochemical staining were used to investigate PD-L2 expression in cetuximab-resistant/sensitive HNSCC tissues. The mechanism of PD-L2 glycosylation regulation was explored in vitro. The effects of PD-L2 glycosylation on immune evasion and cetuximab efficacy were verified in vitro and using mice bearing orthotopic SCC7 tumors. RESULTS: The PD-L2 levels were elevated and N-glycosylated in patients with cetuximab-resistant HNSCC. Glycosylated PD-L2 formed a complex with EGFR, which resulted in the activation of EGFR/signal transducer and activator of transcription 3 (STAT3) signaling and decreased the cetuximab binding affinity to EGFR. The N-glycosyltransferase fucosyltransferase (FUT8), a transcriptional target of STAT3, was required for PD-L2 glycosylation. Moreover, glycosylation modification stabilized PD-L2 by blocking ubiquitin-dependent lysosomal degradation, which consequently promoted its binding to PD-1 and immune evasion. Inhibition of PD-L2 glycosylation using Stattic, a specific STAT3 inhibitor, or PD-L2 mutation blocking its binding to FUT8, increased cytotoxic T lymphocyte activity and augmented response to cetuximab. CONCLUSIONS: Increased expression and glycosylation of PD-L2 in tumors are an important mechanism for cetuximab therapy refractoriness. Thus, the combination of PD-L2 glycosylation inhibition and cetuximab is a potential therapeutic strategy for cancer.


Assuntos
Antígeno B7-H1/metabolismo , Receptores ErbB/antagonistas & inibidores , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Animais , Antineoplásicos Imunológicos/farmacologia , Antígeno B7-H1/imunologia , Cetuximab/farmacologia , Receptores ErbB/imunologia , Feminino , Glicosilação , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Nus , Proteína 2 Ligante de Morte Celular Programada 1/imunologia , Análise de Sequência de RNA , Análise de Célula Única , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Evasão Tumoral/imunologia
10.
Front Oncol ; 11: 709255, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34527582

RESUMO

Plasma circulating extracellular vesicle (EV) has emerged as a promising biomarker for diagnosis and prognosis of various epithelial tumors. However, fast and efficient capture of EVs with microfluidic chip in sarcoma remains to be established. Herein, we reported a ZnO-nanorods integrated (ZNI) microfluidic chip, where EV capture antibody was uniformly grafted to the surface of the ZnO-nanorods of the chip to enhance the plasma turbulence formation and the capture efficiency at the micro-scale. Based on osteosarcoma (OS) cell line, we demonstrated that a combination of CD81 and CD63 antibody on ZNI chip yielded the greatest amount of total EVs, with an extra sensitive limit of detection (LOD) of ~104 particles mL-1. Furthermore, the addition of fluorescent labeling of Vimentin (VIM), a previously reported sarcoma cell surface biomarker, could enabled the dual visualization of total plasma EVs and VIM-positive EVs from OS patients' plasma. Based on our ZNI chip, we found that the amount of plasma total EVs was significantly different between OS and healthy donors (1562 a.u. versus 639 a.u., p< 0.05), but not between metastatic and nonmetastatic OS (p> 0.05). Interestingly, patients with metastatic disease had a significantly greater amount of VIM-positive EVs (1411 a.u. versus 231 a.u.., p< 0.05) and increased VIM-positive/total EVs ratio (0.943 versus 0.211, p< 0.05) in comparison with the nonmetastatic counterpart. Therefore, our ZNI microfluidic chip has great potential for the fast quantification of plasma EVs, and the microfluidic-based quantification of total and VIM-positive EVs might serve as a promising biomarker for the diagnosis and surveillance in OS patients.

11.
Oncoimmunology ; 10(1): 1947569, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34377590

RESUMO

PD-L2 expression is an important predictor of anti-PD-1 therapy efficacy in patients with head and neck squamous cell carcinoma (HNSCC). However, whether the PD-L2-based immune signature can serve as a prognostic biomarker for patients with HNSCC remains unclear. Here, we reported that PD-L2 was positively stained in 62.7% of tumors, which was more than twice as that of PD-L1, and in 61.4% of patients with PD-L1-negative tumors. Survival tree analysis (STA) revealed that PD-L2high was an independent predictor of poor overall survival (OS). Six patterns were generated from STA, demonstrating that patients with PD-L2lowCD3high were associated with an improved median OS of 72 months and prognostic index (PI) of -3.95 (95% CI, -5.14 to -2.76), whereas patients with PD-L2highCD3lowCD8low to a median OS of 10 months and PI of 1.43 (95% CI, 0.56 to 2.30). Analysis of single-cell RNA sequencing showed that PD-L2 expression was associated with IL-6 expression. We confirmed that IL-6 augments PD-L2 expression in HNSCC cell lines. The PD-L2-based immune signature can serve as an effective biomarker for anti-PD-1 therapy. In addition, PD-L2 may serve as a potential immunotherapeutic target, and we propose anti-IL6 therapy in the adjuvant setting for patients with HNSCC with high PD-L2 expression.


Assuntos
Neoplasias de Cabeça e Pescoço , Biomarcadores Tumorais/genética , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico
12.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 46(6): 666-672, 2021 Jun 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34275937

RESUMO

The precise etiology of oral lichen planus (OLP) is still unclear, but the existing evidence suggests that drug intake, virus infection, fungal infection, psychological disorders, and immunodeficiency are closely associated with the pathogenesis of OLP. We report a case of OLP accompanied with candidiasis induced by long-term use of antimicrobials for recurrent aphthous ulcer (RAU) and update the literature, to discuss the possible association between OLP and misuse of antimicrobials, and to inform general dentists and pharmacists the importance for practice with optimal antimicrobial stewardship. In this case, a 42-year-old man presented to Xiangya Stomatological Hospital with white reticular patterns spreading in the oral cavity for almost 1 year. He was diagnosed with OLP via histopathological examination. He had a 5-year history of RAU which occurred every 1-2 months, and he was given antimicrobials ingested or injected whenever the ulcers came up. Satisfactory treatment results were obtained by stopping the abuse of antimicrobials and local antifungal therapy. Meanwhile, the exacerbation and alleviation of OLP was closely related to the administration of antimicrobials. Combined with literature review, antimicrobial might contribute to the development of OLP by inducing candidiasis, a common side-effect of misuse of antimicrobials. Considering the seriousness of antimicrobial resistance and opportunistic infection, dentists should prescribe antimicrobials judiciously according to guidelines and evidence-based indications. Appropriate prescribing of antimicrobials is a professional responsibility to all dentists.


Assuntos
Líquen Plano Bucal , Micoses , Estomatite Aftosa , Viroses , Adulto , Antifúngicos , Humanos , Líquen Plano Bucal/induzido quimicamente , Líquen Plano Bucal/tratamento farmacológico , Masculino , Estomatite Aftosa/induzido quimicamente , Estomatite Aftosa/tratamento farmacológico
13.
Front Cell Dev Biol ; 9: 666376, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34178990

RESUMO

Soft-tissue sarcoma (STS) is represented by a heterogeneous group of rare malignancies with various molecular oncogenesis. Therapies targeting DNA repair pathways in STS have achieved minimal progress, potentially due to the lack of molecular biomarker(s) beyond the histology subtype. In this report, we comprehensively analyzed the expression profiles of 100 liposarcomas (LPSs), the most common STS subtype, in comparison with 21 adipose tissues from multiple GEO datasets to identify the potential prognostic and therapeutic biomarker for LPS. Furthermore, we investigated TCGA database, our archived tumor samples, and patient-derived tumor cell cultures (PTCCs) as a validation. We identified a total of 69 common differentially expressed genes (DEGs) among public datasets, with mini-chromosome maintenance protein 4 (MCM4) identified as a novel biomarker correlated with patients' clinical staging and survival outcome. MCM4-high expression LPS was characterized by MCM4 copy number increase, genomic instability, and BRCAness phenotype compared with the MCM4-low expression counterpart. In contrast, the mutational and the immune landscape were minimally different between the two groups. Interestingly, the association of MCM4-high expression with genomic instability and BRCAness were not only validated in LPS samples from our institution (n = 66) but also could be expanded to the pan-sarcoma cohort from TCGA database (n = 263). Surprisingly, based on four sarcoma cell lines and eight PTCCs (three LPS and five other sarcoma), we demonstrated that MCM4 overexpression tumors were therapeutically sensitive to PARP inhibitor (PARPi) and platinum chemotherapy, independent of the histology subtypes. Our study, for the first time, suggested that MCM4 might be a novel prognostic biomarker, associated with dysregulated DNA repair pathways and potential therapeutic vulnerability in STS.

14.
Front Cell Dev Biol ; 9: 633607, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33816483

RESUMO

BACKGROUND: Increasing evidence has shown that hypoxia microenvironment relates to tumor initiation and progression. However, no studies focus on the application of hypoxia-associated genes in predicting osteosarcoma patients' prognosis. This research aims to identify the hypoxia-associated genes related to osteosarcoma metastasis and construct a gene signature to predict osteosarcoma prognosis. METHODS: The differentially expressed messenger RNAs (DEmRNAs) related to osteosarcoma metastasis were identified from Therapeutically Applicable Research to Generate Effective Treatments (Target) database. Univariate and multivariate cox regression analyses were performed to develop the hypoxia-associated prognostic signature. The Kaplan-Meier (KM) survival analyses of patients with high and low hypoxia risk scores were conducted. The nomogram was constructed and the gene signature was validated in the external Gene Expression Omnibus (GEO) cohort. Single-sample gene set enrichment analysis (ssGSEA) was conducted to investigate the relationships between immune infiltration and gene signature. RESULTS: Two genes, including decorin (DCN) and prolyl 4-hydroxylase subunit alpha 1 (P4HA1), were involved in the hypoxia-associated gene signature. In training and testing datasets, patients with high-risk scores showed lower survival rates and the gene signature was identified as the independent prognostic factor. Receiver operating characteristic (ROC) curves demonstrated the robustness of signature. Functional analyses of DEmRNAs among high- and low-risk groups revealed that immune-associated functions and pathways were significantly enriched. Furthermore, ssGSEA showed that five immune cells (DCs, macrophages, neutrophils, pDCs, and TIL) and three immune features (CCR, APC co inhibition, and Check-point) were down-regulated in the high-risk group. CONCLUSION: The current study established and validated a novel hypoxia-associated gene signature in osteosarcoma. It could act as a prognostic biomarker and serve as therapeutic guidance in clinical applications.

15.
J Musculoskelet Neuronal Interact ; 21(1): 149-156, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33657766

RESUMO

OBJECTIVES: To investigate the effects of bone morphogenetic protein-2 (BMP-2) compound with fibrin on osteoporotic vertebral fracture healing in rats. METHODS: For the present study 160 Specific-Pathogen Free 32-week-old female Sprague-Dawley rats were used. 120 rats were randomly divided in three groups (experimental, model and sham operation group- n=40 per group) and were ovariectomized to establish the osteoporosis model. 40 rats served as a control group without treatment. The expression of BMP-2 in the fracture zone at the 4th, 6th, 8th, and 12th weeks was detected by qRT-PCR. The expression of BALP and CTX-I in serum at the 12th week was detected by Elisa. RESULTS: At week 8, the morphology of the sham operation group was the same and the fracture healing occurred more slowly than in the other groups. At week 12, the expression of BMP-2 in the model group was significantly higher than that in the other three groups (p<0.05). At week 12, the maximum load, maximum strain, and elastic modulus of model group were significantly lower than those of the other three groups. CONCLUSIONS: BMP-2 compound with fibrin can enhance the timing and quality of bone fracture healing in rats.


Assuntos
Proteína Morfogenética Óssea 2/administração & dosagem , Fibrina/administração & dosagem , Consolidação da Fratura/efeitos dos fármacos , Fraturas por Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/metabolismo , Animais , Proteína Morfogenética Óssea 2/biossíntese , Quimioterapia Combinada , Feminino , Consolidação da Fratura/fisiologia , Ovariectomia/efeitos adversos , Ratos , Ratos Sprague-Dawley
16.
Hereditas ; 158(1): 9, 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33593435

RESUMO

BACKGROUND: Osteosarcoma is the primary bone malignant neoplasm that often develops metastasis. Increasing evidences have shown that non-coding RNAs (ncRNAs) relate to the progression of osteosarcoma. However, the ncRNAs' roles in osteosarcoma metastasis are still unknown. METHODS: Differentially expressed (DE) RNAs were identified from Gene Expression Omnibus (GEO) database. Protein-protein interaction (PPI) of DE messenger RNAs (DEmRNAs) was built through STRING database. The target mRNAs and long ncRNAs (lncRNAs) of microRNAs (miRNA) were predicted through miRDB, Targetscan and Genecode databases, which then cross-checked with previously obtained DERNAs to construct competing endogenous RNA (ceRNA) network. All networks were visualized via Cytoscape and the hub RNAs were screened out through Cytoscape plug-in Cytohubba. The gene functional and pathway analyses were performed through DAVID and MirPath databases. The survival analyses of hub RNAs were obtained through Kaplan-Meier (KM) survival curves. RESULTS: Five hundred sixty-four DEmRNAs, 16 DElncRNAs and 22 DEmiRNAs were screened out. GO functional and KEGG pathway analyses showed that DERNAs were significantly associated with tumor metastasis. The ceRNA network including 6 lncRNAs, 55 mRNAs and 20 miRNAs were constructed and the top 10 hub RNAs were obtained. Above all, PI3K/AKT signaling pathway was identified as the most important osteosarcoma metastasis-associated pathway and its hub ceRNA module was constructed. The survival analyses showed that the RNAs in hub ceRNA module closely related to osteosarcoma patients' prognosis. CONCLUSIONS: The current study provided a new perspective on osteosarcoma metastasis. More importantly, the RNAs in hub ceRNA module might act as the novel therapeutic targets and prognostic factors for osteosarcoma patients.


Assuntos
Metástase Neoplásica/genética , Osteossarcoma/genética , RNA Longo não Codificante/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , MicroRNAs/genética , Prognóstico , Mapas de Interação de Proteínas , RNA Mensageiro/genética
17.
J Musculoskelet Neuronal Interact ; 20(4): 556-562, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33265084

RESUMO

OBJECTIVE: To investigate the clinical effects of dynamic hip screw (DHS) and proximal femoral nail anti-rotation (PFNA) on senile osteoporosis patients and their effects on the expression level of bone-specific alkaline phosphatase (BALP). METHODS: 116 elderly patients with osteoporotic fracture were divided into DHS group (n=67) and PFNA group (n=49). BALP values were measured by ELISA before operation and 30 days after operation. RESULTS: The operation time, the bleeding volume, and the weight-bearing time of PFNA group was shorter than DHS group (p<0.05); the dominant blood loss and occult blood loss in PFNA group were less than those in DHS group (p<0.05); the healing time and detumescence time, the complications of PFNA group was fewer than the DHS group (p<0.05). The ten-meter walking speed and the five sitting tests in PFNA group were shorter than that in DHS group (p<0.05); the excellent and good rate and Harris score in PFNA group were higher than those in DHS group (p<0.05). The expression of BALP in PFNA group was lower than that in DHS group (p<0.05). CONCLUSION: PFNA surgery has less trauma, fewer complications, more optimistic postoperative healing and recovery degree, and is more conducive to the reduction of BALP expression level.


Assuntos
Fosfatase Alcalina/sangue , Fixação Interna de Fraturas/métodos , Fraturas do Quadril/cirurgia , Fraturas por Osteoporose/cirurgia , Idoso , Pinos Ortopédicos , Parafusos Ósseos , Feminino , Fixação Interna de Fraturas/efeitos adversos , Humanos , Masculino , Complicações Pós-Operatórias/epidemiologia , Recuperação de Função Fisiológica , Estudos Retrospectivos , Resultado do Tratamento
18.
Physiol Rep ; 8(22): e14646, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33230976

RESUMO

Effective communication between the mammalian hippocampus and neocortex is essential to certain cognitive-behavioral tasks critical to survival in a changing environment. Notably, functional synchrony between local field potentials (LFPs) of the ventral hippocampus (vHPC) and the medial prefrontal cortex (mPFC) within the theta band (4-12 Hz) underlies innate avoidance behavior during approach-avoidance conflict tasks in male rodents. However, the physiology of vHPC-mPFC communications in females remains unestablished. Furthermore, little is known about how mPFC subdivisions functionally interact in the theta band with hippocampal subdivisions in both sexes in the absence of task demand. Given the established roles of biological sex and gonadal hormone status on innate avoidance behaviors and neuronal excitability, here, we characterize the effects of biological sex and female estrous stage on hippocampal-prefrontal (HPC-mPFC) theta signaling in freely moving female and male rats. LFPs from vHPC, dorsal hippocampus (dHPC), mPFC-prelimbic (PrL), and mPFC-infralimbic (IL) were simultaneously recorded during spontaneous exploration of a familiar arena. Data suggest that theta phase and power in vHPC preferentially synchronize with PrL; conversely, dHPC and IL preferentially synchronize. Males displayed greater vHPC-PrL theta synchrony than females, despite similar regional frequency band power and inter-regional coherence. Additionally, several significant estrous-linked changes in HPC-mPFC theta dynamics were observed. These findings support the hypothesis that HPC-mPFC theta signaling is sensitive to both biological sex and female estrous stage. These findings establish novel research avenues concerning sex as a biological variable and effects of gonadal hormone status on HPC-mPFC network activity as it pertains to threat evaluation biomarkers.


Assuntos
Ciclo Estral/fisiologia , Hipocampo/fisiologia , Córtex Pré-Frontal/fisiologia , Ritmo Teta , Animais , Aprendizagem da Esquiva , Comportamento Exploratório , Feminino , Masculino , Ratos , Ratos Sprague-Dawley , Fatores Sexuais
19.
AMIA Annu Symp Proc ; 2020: 243-252, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33936396

RESUMO

Dietary supplements (DSs) have been widely used in the U.S. and evaluated in clinical trials as potential interventions for various diseases. However, many clinical trials face challenges in recruiting enough eligible patients in a timely fashion, causing delays or even early termination. Using electronic health records to find eligible patients who meet clinical trial eligibility criteria has been shown as a promising way to assess recruitment feasibility and accelerate the recruitment process. In this study, we analyzed the eligibility criteria of 100 randomly selected DS clinical trials and identified both computable and non-computable criteria. We mapped annotated entities to OMOP Common Data Model (CDM) with novel entities (e.g., DS). We also evaluated a deep learning model (Bi-LSTM-CRF) for extracting these entities on CLAMP platform, with an average F1 measure of 0.601. This study shows the feasibility of automatic parsing of the eligibility criteria following OMOP CDM for future cohort identification.


Assuntos
Ensaios Clínicos como Assunto , Aprendizado Profundo , Suplementos Nutricionais , Registros Eletrônicos de Saúde , Seleção de Pacientes , Bases de Dados Factuais , Estudos de Viabilidade , Humanos , Modelos Teóricos , Processamento de Linguagem Natural , Prática Associada
20.
Chem Commun (Camb) ; 55(99): 14910-14913, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31769458

RESUMO

Pd-[Bmim][Cl] phase was immobilized onto Al2O3 to neutralize the excessive hydrogen in the gas phase to prevent the over-hydrogenation of acetylene, thereby achieving a high selectivity for ethylene.

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