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1.
Nat Commun ; 14(1): 5378, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37666848

RESUMO

Nanoparticles-based glues have recently been shown with substantial potential for hydrogel adhesion. Nevertheless, the transformative advance in hydrogel-based application places great challenges on the rapidity, robustness, and universality of achieving hydrogel adhesion, which are rarely accommodated by existing nanoparticles-based glues. Herein, we design a type of nanohesives based on the modulation of hydrogel mechanics and the surface chemical activation of nanoparticles. The nanohesives can form robust hydrogel adhesion in seconds, to the surface of arbitrary engineering solids and biological tissues without any surface pre-treatments. A representative application of hydrogel machine demonstrates the tough and compliant adhesion between dynamic tissues and sensors via nanohesives, guaranteeing accurate and stable blood flow monitoring in vivo. Combined with their biocompatibility and inherent antimicrobial properties, the nanohesives provide a promising strategy in the field of hydrogel based engineering.


Assuntos
Hidrogéis , Nanopartículas , Humanos , Engenharia , Fenômenos Físicos , Aderências Teciduais
2.
Front Immunol ; 14: 1139527, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37020543

RESUMO

Background: Radiation therapy combined with immune checkpoint inhibitors (ICIs) has recently turned into an appealing and promising approach to enhance the anti-tumor immunity and efficacy of immunological drugs in many tumors. Abscopal effect induced by radiation is a phenomenon that often leads to an efficient immunity response. In this study, we investigated whether the combination of the immunogenic effects derived from radiotherapy sequential ICIs-based therapy could increase the incidence of abscopal effects, and improve the survival rates. Case presentation: We described a clinical case regarding a 35-year-old male patient who was admitted to our hospital with a diagnosis of adenocarcinoma of the sigmoid colon and synchronous multiple liver metastases following a surgical resection. The molecular pathological examination showed immune-desert phenotype and proficient mismatch repair (pMMR). The patient was treated with adjuvant chemotherapy after surgery, however, after 7 months, multiple metastasis in the pelvic lymph nodes were diagnosed. Unfortunately, the tumor progressed despite multiple cycles of chemotherapy combined with cetuximab or bevacizumab. Within the follow-up treatment, the patient was administered with only 50Gy/25F of radiation dose to treat the anastomotic lesions. Subsequently, mono-sindilizumab was used as systemic therapy, leading to a rapid reduction of all pelvic lesions and complete clinical remission. So far, the patient survived for more than 20 months under continuous mono-sindilizumab treatment and is still in complete remission. Conclusion: A localized radiotherapy combined with a sindilizumab-based systemic therapy may overcome the immune resistance of pMMR metastatic colorectal cancer (mCRC), thus obtaining greater efficacy of the therapy. Its mechanism may be related to the abscopal effect obtained by the synergistic use of radiation and sindilizumab, which should be further investigated in the future.


Assuntos
Adenocarcinoma , Neoplasias do Colo Sigmoide , Masculino , Humanos , Bevacizumab , Terapia Combinada , Cetuximab
3.
J Biotechnol ; 366: 54-64, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36822476

RESUMO

Secretory signal peptides (SPs) can increase enhanced green fluorescent protein (eGFP) expression in cytosol. In this study, SPs Iasp (Cry1Ia), Vasp (Vip3A), and their local sequences were used as fusion tags to compare their effects on eGFP expression in Escherichia coli MC4100 and Pichia pastoris GS115. In E coli, the solubility was almost opposite between the proteins encoded by Vegfp and Iegfp. This may be because the overall hydrophobicity of the SPs differed. When the hydrophobic H-region and C-region were removed, the negative effects on eGFP solubility of the N-regions of both SPs (IaN and VN) were significantly reduced without compromise on the expression level. IaN promotes eGFP protein yield 7.1-fold more than Iasp, and using this peptide in tandem (Ia3N) further enhanced fluorescent fusion protein solubility with an efficacy similar to that of a polycationic tag. Furthermore, the GS-IaNeGFP strain produced the highest fluorescent signal intensity when these fusion proteins were expressed in P. pastoris, and the expression was higher than in other strains, including eGFP. In conclusion, we revealed the potential of the N-region of Iasp as a fusion tag in both prokaryotic and eukaryotic cells and further demonstrated the value of the N-regions of abundant SPs.


Assuntos
Escherichia coli , Saccharomycetales , Escherichia coli/genética , Escherichia coli/metabolismo , Pichia/genética , Pichia/metabolismo , Peptídeos/metabolismo , Sinais Direcionadores de Proteínas/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo
4.
Antiviral Res ; 211: 105510, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36581048

RESUMO

MicroRNA-124 (miR-124) is related to liver injury due to chronic hepatitis B (CHB) and hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). However, the mechanism whereby miR-124 regulates liver inflammation remains unknown. In this study, we show that serum miR-124 serves as a compensatory predictive factor for organ failure and the 28-day prognosis of patients with HBV-ACLF. Moreover, within a mouse model of concanavalin A-induced acute liver injury, miR-124 is highly expressed in Kupffer cells. Overexpression of miR-124 significantly decreases interleukin-6 (IL-6) secretion, and relieves pathological liver necrosis to a great extent. Mechanistically, miR-124 directly targets the 3'-untranslated region of signal transducer and activator of transcription 3 (STAT3) and inhibits IL-6/STAT3 signaling, which reduces pro-inflammatory Kupffer cell polarization. Collectively, our findings suggest that miR-124 can potentially serve as a predictive biomarker for HBV-ACLF prognosis and may represent a promising therapeutic target for relieving severe liver injury resulting from cytokine storms.


Assuntos
Hepatite B Crônica , MicroRNAs , Animais , Camundongos , Células de Kupffer/metabolismo , Células de Kupffer/patologia , Interleucina-6/metabolismo , Fator de Transcrição STAT3/metabolismo , Fígado/patologia , Vírus da Hepatite B/metabolismo
5.
Emerg Microbes Infect ; 11(1): 1586-1601, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35579924

RESUMO

The pathogenesis of liver in patients with hepatitis B virus-associated acute chronic liver failure (HBV-ACLF) remains largely unknown. We aimed to elucidate the molecular mechanism underlying the pathogenesis of liver in HBV-ACLF patients by using multiple approaches including transcriptome analysis. We performed transcriptomic sequencing analysis on the liver of HBV-ACLF patients (n = 6), chronic hepatitis B (n = 6), liver cirrhosis (n = 6) and normal control (n = 5), then explored the potential pathogenesis mechanism in liver specimen from another 48 subjects and further validated the molecular and cellular mechanisms using THP-1 cells. RNA-sequencing data analysis indicated that, among the genes up-regulated in HBV-ACLF, genes related to inflammatory response and chemotaxis accounted for a large proportion of the total DEGs. A number of key chemokines (CCL2, CCL5, CCL20, CXCL5, CXCL6, CXCL8) and NF-ĸB pathway were identified to be robust in the liver samples from HBV-ACLF patients. Interestingly, cylindromatosis (CYLD) was found to be downregulated in the liver of HBV-ACLF patients, in line with the well-established role of CYLD in regulating most of the chemokines and pro-inflammatory cytokines (CCL2, CCL5, CCL20, CXCL5, CXCL6, CXCL8, IL-6, IL-1ß) via inhibition of NF-ĸB. Indeed, the knockdown of CYLD resulted in sustained activation of NF-ĸB in macrophages and enhanced chemokines and inflammatory cytokines production, which in turn enhanced chemotactic migration of neutrophil, monocyte, T lymphocytes, and NK cell. In conclusions, down-regulated CYLD aggravated inflammatory cell chemotaxis through enhancing NF-κB activation in HBV-ACLF patients, thereby participating in the pathogenesis of HBV-ACLF injury.


Assuntos
Insuficiência Hepática Crônica Agudizada , Doença Hepática Terminal , Insuficiência Hepática Crônica Agudizada/patologia , Citocinas , Vírus da Hepatite B/genética , Vírus da Hepatite B/metabolismo , Humanos , Inflamação , NF-kappa B/genética , NF-kappa B/metabolismo
6.
Nanomaterials (Basel) ; 12(3)2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35159722

RESUMO

Gallium sulfide (GaS), with a hexagonal structure, has received extensive attention due to its graphene-like structure and derived optical properties. Here, high-quality GaS was obtained via chemical vapor synthesis and then prepared as a saturable absorber by the stamp-assisted localization-transfer technique onto fiber end face. The stability of the material and the laser damage threshold are maintained due to the optimized thickness and the cavity integration form. The potential of the GaS for nonlinear optics is explored by constructing a GaS-based Erbium-doped mode-locked fiber laser. Stable femtosecond (~448 fs) mode-locking operation of the single pulse train is achieved, and the robust mode-locked operation (>30 days) was recorded. Experimental results show the potential of GaS for multi-functional ultrafast high-power lasers and promote continuous research on graphene-like materials in nonlinear optics and photonics.

7.
Cancer Med ; 9(10): 3437-3444, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32207253

RESUMO

There were no ideal markers to predict the development of radiation pneumonitis (RP). We want to investigate the value of variations of lymphocytes and T lymphocyte subsets in predicting RP after radiotherapy (RT) of lung cancer based on previous clinical findings. A total of 182 lung cancer patients who received RT were retrospectively analyzed. Circulating lymphocytes and T lymphocyte subsets were measured before, during, and after RT. Patients were evaluated from the start of RT to 6 months post-RT. A mice model with acute radiation-induced lung injury was established and circulating lymphocytes were measured weekly until 8 weeks after irradiation. Univariate and multivariate analyses were adopted to identify risk factors of RP. Lymphocyte levels significantly decreased (P < .001) in patients before RP symptoms developed that also was able to be seen in the mice model and the values recovered during remission of symptoms. The decrease in lymphocyte count reflected the severity of RP. Meanwhile, CD4+  T lymphocyte count was significantly lower during the occurrence of symptoms in patients with RP than in those without RP (P < .001), and it improved along with RP recovery. Levels of lymphocytes and CD4+  T lymphocyte subsets proved as independent predictors of RP. Here we showed that lower peripheral blood levels of lymphocytes and CD4+  T lymphocyte were associated with an increased risk of RP, which was validated by this mice model, and thus are associated with differences in radiation-induced lung toxicity among individuals and help identify those who are susceptible to developing RP after RT.


Assuntos
Adenocarcinoma de Pulmão/radioterapia , Carcinoma de Células Escamosas/radioterapia , Neoplasias Pulmonares/radioterapia , Pulmão/efeitos da radiação , Pneumonite por Radiação/sangue , Radioterapia de Intensidade Modulada/efeitos adversos , Carcinoma de Pequenas Células do Pulmão/radioterapia , Subpopulações de Linfócitos T , Linfócitos T , Adenocarcinoma de Pulmão/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Contagem de Linfócito CD4 , Carcinoma de Células Escamosas/patologia , Feminino , Humanos , Contagem de Leucócitos , Neoplasias Pulmonares/patologia , Contagem de Linfócitos , Masculino , Camundongos , Pessoa de Meia-Idade , Neutrófilos , Estudos Retrospectivos , Carcinoma de Pequenas Células do Pulmão/patologia
8.
Front Immunol ; 11: 594212, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33552051

RESUMO

Background and Purpose: To directly reveal the change in genome mutation, RNA transcript of tumor cells, and tumor microenvironment (TME) after stereotactic body radiotherapy (SBRT) in paired human lung tumor specimens. Materials and Methods: Paired tumor samples were collected from 10 patients with non-small cell lung cancer (NSCLC) or lung metastatic carcinoma within a week before and after SBRT. DNA and RNA of tumor tissues was extracted from the paired samples. Whole-exome and RNA sequencing assays were performed by next-generation sequencing. Gene mutation, genomic expression, T-cell receptor (TCR) repertoire, and profiling of tumor-infiltrating immune cells were analyzed through bioinformatics analysis in paired tumor samples. CD8+ T-cell infiltration and PD-L1 expressions were detected by immunostaining in tumor tissues. Results: The diversity of TCR repertoire and PD-L1 expression increased significantly in the TME, and the most enriched term of the gene ontology analysis was the immune response gene after receiving SBRT. SBRT induced neo-mutation of genes in tumor cells but did not increase tumor mutation burden in tumor tissues. TME displayed complex immune cell changes and infiltration and expression of immune-regulating factors such as C-X-C motif chemokine (CXCL) 10, CXCL16, interferons (IFNs), and IFN receptors. CD8+ T-cells in tumor tissues did not improve significantly after SBRT while the infiltrating TH1 and TH2 cells decreased remarkably. Conclusion: SBRT improved the TCR repertoire diversity and PD-L1 expression in the TME and induced neo-mutation of genes in tumor cells but did not increase CD8+ T-cell infiltration and IFN expression in the tumor tissue within a week.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/etiologia , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/radioterapia , Radiocirurgia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Microambiente Tumoral/efeitos da radiação , Adulto , Idoso , Antígeno B7-H1/genética , Biomarcadores Tumorais , Biópsia , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Genômica/métodos , Humanos , Neoplasias Pulmonares/patologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Radiocirurgia/métodos , Receptores de Antígenos de Linfócitos T/metabolismo , Análise de Sequência de RNA , Sequenciamento do Exoma
9.
Radiat Oncol ; 14(1): 104, 2019 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31196126

RESUMO

PURPOSE: Despite recent advances in multimodal treatments, the prognosis of patients with glioblastoma multiforme (GBM) remains poor. The aim of this study was to evaluate the efficacy of moderately hypofractionated simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT) combined with temozolomide (TMZ) for the postoperative treatment of GBM. MATERIALS AND METHODS: From February 2012 to February 2018, 80 patients with newly diagnosed and histologically confirmed GBM in our institute were reviewed retrospectively. All patients underwent complete resection or partial resection surgery and then received hypofractionated SIB-IMRT with concomitant TMZ followed by adjuvant TMZ. A total dose of 64 Gy over 27 fractions was delivered to the gross tumor volume (GTV), clinical target volume 1 (CTV1) received 60 Gy over 27 fractions, and CTV2 received 54 Gy over 27 fractions. The progression-free survival (PFS) and overall survival (OS) rates and the toxicities were evaluated. Prognostic factors were analyzed using univariate and multivariate Cox models. RESULTS: The median follow-up was 16 months (range, 5~72 months). The median PFS was 15 months, and the 1-, 2-, and 3-year PFS rates were 56.0, 27.6, and 19.5%, respectively. The median OS was 21 months, and the 1-, 2-, 3-, and 5-year OS rates were 77.6, 41.6, 32.8, and 13.4%, respectively. The toxicities were mild and acceptable. Age, KPS scores and the total number of TMZ cycles were significant factors influencing patient survival. CONCLUSION: Moderately hypofractionated SIB-IMRT combined with TMZ is a feasible and safe treatment option with mild toxicity and good PFS and OS.


Assuntos
Neoplasias Encefálicas/terapia , Quimiorradioterapia/métodos , Glioblastoma/terapia , Cuidados Pós-Operatórios , Radioterapia de Intensidade Modulada/métodos , Temozolomida/uso terapêutico , Adulto , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/patologia , Feminino , Glioblastoma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Hipofracionamento da Dose de Radiação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
10.
Cell Prolif ; 52(3): e12592, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30848009

RESUMO

OBJECTIVES: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) has significant therapeutic efficacy in non-small-cell lung cancer (NSCLC) patients. However, acquired resistance is inevitable and limits the long-term efficacy of EGFR-TKI. Our study aimed to investigate the role of ras-associated binding protein 25 (Rab25) in mediating EGFR-TKI resistance in NSCLC. MATERIALS AND METHODS: Rab25 expression in NSCLC patients was measured by immunohistochemical staining. Western blotting was used to analyse the expression of molecules in the Rab25, EGFR and Wnt signalling pathways. Lentiviral vectors were constructed to knock in and knock out Rab25. The biological function of Rab25 was demonstrated by cell-counting kit-8 and flow cytometry. The interaction between Rab25 and ß1 integrin was confirmed by co-immunoprecipitation. RESULTS: Rab25 overexpression induced erlotinib resistance, whereas Rab25 knockdown reversed this refractoriness in vitro and in vivo. Moreover, Rab25 interacts with ß1 integrin and promotes its trafficking to the cytoplasmic membrane. The membrane-ß1 integrin induced protein kinase B (AKT) phosphorylation and subsequently activated the Wnt/ß-catenin signalling pathway, promoting cell proliferation. Furthermore, high Rab25 expression was associated with poor response to EGFR-TKI treatment in NSCLC patients. CONCLUSIONS: Rab25 mediates erlotinib resistance by activating the ß1 integrin/AKT/ß-catenin signalling pathway. Rab25 may be a predictive biomarker and has potential therapeutic value in NSCLC patients with acquired resistance to EGFR-TKI.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Cloridrato de Erlotinib/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Proteínas rab de Ligação ao GTP/metabolismo , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/metabolismo , Animais , Resistencia a Medicamentos Antineoplásicos , Técnicas de Silenciamento de Genes , Humanos , Integrina beta1/metabolismo , Masculino , Camundongos , Camundongos Nus , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , beta Catenina/metabolismo , Proteínas rab de Ligação ao GTP/antagonistas & inibidores , Proteínas rab de Ligação ao GTP/genética
11.
Hepatol Res ; 48(3): E133-E145, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28707778

RESUMO

AIM: Chronic hepatitis B (CHB) patients with normal alanine aminotransferase (ALT) levels are not free from significant hepatic lesions. Recently, there has been an improved understanding of the clinical significance of quantitative hepatitis B core antibody levels (qAnti-HBc) during CHB management. In this cross-sectional study, we evaluated the utility of qAnti-HBc in identifying significant liver inflammation in CHB patients. METHODS: A total of 469 patients (training set, n = 363; validation set, n = 106) who underwent liver biopsy (LB) were included. The qAnti-HBc levels were quantified and the relationship between histology and serum markers was systematically analyzed. RESULTS: In the training set, qAnti-HBc levels were found to have significant diagnostic value for moderate to severe liver inflammation (≥G2) in all patients (area under the receiver operating characteristic curve [AUROC] = 0.768; 95% confidence interval [CI], 0.721-0.810; P < 0.001) and in patients with normal or near-normal ALT levels (AUROC = 0.767; 95% CI, 0.697-0.828; P < 0.001). Our novel index (AC index) for the identification of ≥G2 inflammation, which combined the qAnti-HBc and ALT levels, significantly improved diagnostic performance (AUROC = 0.813; 95% CI, 0.768-0.852) compared to the use of ALT alone (AUROC = 0.779; 95% CI, 0.732-0.821) in all patients. In the validation set, the AC index showed an improved AUROC of 0.890 (95% CI, 0.814-0.942) and 0.867 (95% CI, 0.749-0.943) in all patients and patients with normal ALT levels, respectively. CONCLUSIONS: The qAnti-HBc level predicts significant liver inflammation well, even in patients with normal or near-normal ALT levels. Compared with the conventional ALT level, the AC index is a more reliable non-invasive biomarker for significant liver inflammation in CHB patients.

12.
J Exp Clin Cancer Res ; 36(1): 186, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29246166

RESUMO

BACKGROUND: Gliomas are the most common primary tumors in central nervous system. The prognosis of the patients with glioma is poor regardless of the development of therapeutic strategies. Its aggressive behavior mainly depends on the potent ability of proliferation. The transcription factor EGR1 (early growth response 1) is a member of a zinc finger transcription factor family which plays an essential role in cell growth and proliferation. METHODS: EGR1 expression levels in 39 glioma tissues and 10 normal brain tissues were tested by RT-qPCR and Western-blotting. The effects of EGR1 on U251 cells, U251 stem-like cells (GSCs), and U87 cells proliferation were assessed using in vitro and in vivo cell proliferation assays. The specific binding between EGR1 and CCND1 promoter was confirmed by CHIP assay. EGF was used to improve EGR1 expression in this assay. RESULTS: EGR1 expression levels in human gliomas are decreased compared with normal brain tissues, however, the patients with low EGR1 expression level showed significantly enhanced patient survival in all glioma patients. EGR1 silencing inhibited proliferation and induced G1 phase arrest in glioma cells. EGR1 contributed to proliferation by directly raising CCND1. Meanwhile, EGR1 overexpression induced by EGF was able to promote the proliferation of glioma cells. CONCLUSIONS: Our results show that stable knockdown EGR1 would inhibit glioma proliferation. The results suggest EGR1 showing lower expression in cancer tissues compared with normal tissues maybe still play an important role in tumor proliferation.


Assuntos
Neoplasias Encefálicas/patologia , Ciclina D1/metabolismo , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Regulação Neoplásica da Expressão Gênica/fisiologia , Glioma/patologia , Animais , Proliferação de Células/fisiologia , Ciclina D1/genética , Humanos , Camundongos , Camundongos SCID , Regiões Promotoras Genéticas/genética
13.
Opt Express ; 24(23): 26722-26731, 2016 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-27857403

RESUMO

We demonstrate a high power dual-frequency linear-polarization fiber laser that carries radio frequency signal. Such fiber laser is based on an all-fiber master oscillator power amplifier configuration that consists of a dual-frequency seed laser and three-stage amplifiers. The dual-frequency seed laser is constructed by recombining two beams that are split from a single-frequency linearly-polarized laser. One beam has initial frequency and the other beam is modulated by an acoustic-optical modulator to have a frequency shift of 150 MHz. Then the radio frequency signal of 150 MHz is carried on the laser due to the beat frequency of these two beams. In the main amplifier, a piece of polarization maintaining large-mode-area fiber with short length is used to combine the SBS suppression with high power amplification. As a result, the dual-frequency laser is amplified to 434 W without the occurrence of SBS. The slope efficiency is 81.3%. The polarization degree of the laser and the modulation depth of the optically carried radio frequency signal are both well maintained during the amplification process. Besides, a high signal-noise-ratio of above 75 dB is realized, which demonstrates the low-noise property of the optically carried radio frequency signal. To the best of our knowledge, this is the highest reported output power of the optically carried radio frequency signal.

14.
Mol Med Rep ; 13(3): 1999-2006, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26794964

RESUMO

To investigate the molecular pathogenesis of the canonical Wnt/ß-catenin pathway in exercise-induced osteoarthritis (OA), 30 male healthy Sprague Dawley rats were divided into three groups (control, normal exercise­induced OA and injured exercise­induced OA groups) in order to establish the exercise­induced OA rat model. The mRNA and protein expression levels of Runx­2, BMP­2, Ctnnb1, Sox­9, collagen Ⅱ, Mmp­13, Wnt­3a and ß­catenin in chondrocytes were detected by reverse transcription­quantitative polymerase chain reaction, western blotting and immunohistochemical staining. The mRNA levels of Runx­2, BMP­2 and Ctnnb1 were upregulated in the normal exercise­induced OA and injured exercise­induced OA groups; while Runx­2 and BMP­2 were upregulated in the injured exercise­induced OA group when compared with the normal exercise­induced OA group. The protein levels of Mmp­13, Wnt­3a and ß­catenin were increased and collagen Ⅱ was reduced in the normal exercise­induced OA and injured exercise­induced OA groups. Ctnnb1, Wnt­3a and ß­catenin, which are key genes and proteins in the canonical Wnt/ß­catenin pathway, were abnormally expressed in chondrocytes of the exercise­induced OA rat model. Ctnnb1, ß­catenin and Wnt­3a were suggested to participate in the pathogenesis of exercise­induced OA by abnormally activating the Wnt/ß­catenin pathway during physical exercise due to excessive pressure. The results of the present study may provide an improved understanding of the pathogenesis of exercise-induced OA.


Assuntos
Cartilagem Articular/patologia , Regulação da Expressão Gênica , Osteoartrite/etiologia , Osteoartrite/genética , Condicionamento Físico Animal/efeitos adversos , Via de Sinalização Wnt/genética , beta Catenina/metabolismo , Animais , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/metabolismo , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Condrócitos/patologia , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Subunidade alfa 1 de Fator de Ligação ao Core/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Modelos Animais de Doenças , Immunoblotting , Imuno-Histoquímica , Masculino , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , beta Catenina/genética
15.
J Sports Med Phys Fitness ; 56(11): 1346-1351, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26333792

RESUMO

BACKGROUND: In this study, we aimed to investigate the college students' injury patterns caused by sport activities in anterior cruciate ligament (ACL) reconstruction stage, and to estimate the association between activities at the time of injury and the odds of simplex ACL injuries. METHODS: A cohort of 2548 college students with primary ACL reconstruction was recruited from Hebei Province, China. Football, basketball, sprint, table tennis and badminton had been chosen as the most prevalent sports activities causing injuries in colleges. The concurrent injury patterns at the time of ACL reconstruction were simplex ACL, meniscus, cartilage, and multi-ligament injuries. RESULTS: Compared with football, college students playing basketball were 4.95 (95% confidence interval [CI], 2.61-8.76) times more likely to have simplex ACL tear, 2.31 (95% CI, 1.73-3.05) times more inclined to have lateral meniscus injury, 2.53 (95% CI, 1.22-3.67) times more likely to have a cartilage injury, and 1.93 (95% CI, 1.22-3.04) times more likely to have a medial meniscus injury. Students playing sprint were 2.04 (95% CI, 1.78-3.38) times more likely to have cartilage injury. CONCLUSIONS: Injury patterns are associated with certain sports. Compared with football, basketball has a greater possibility of leading to simplex ACL tear, as well as medial meniscus, lateral meniscus and cartilage injuries. Additionally, injury patterns observed during surgery may reflect the forces applied to the knee by the given sports performed.


Assuntos
Lesões do Ligamento Cruzado Anterior/epidemiologia , Lesões do Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior , Traumatismos em Atletas/epidemiologia , Traumatismos em Atletas/cirurgia , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Fatores de Risco , Lesões do Menisco Tibial/epidemiologia , Lesões do Menisco Tibial/cirurgia , Adulto Jovem
16.
Emerg Microbes Infect ; 4(7): e38, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26251828

RESUMO

Limited research has been conducted on healthcare-associated infective endocarditis (HAIE), although it is of increasing importance. The aim of this study is to compare the epidemiology, clinical characteristics, and prognosis of community-acquired IE (CA-IE) with HAIE and non-nosocomial healthcare-associated IE (NNHCA-IE). A retrospective, consecutive case-series analysis was organized and performed during the 20-year study period in Huashan Hospital, Shanghai, China. A total of 154 patients were enrolled, including 126 (81.8%) who had CA-IE and 28 (18.2%) who had HAIE, among whom 20 (71.4%) had non-nosocomial IE. Patients with HAIE compared to patients with CA-IE had poorer clinical conditions (Charlson comorbidity index ≥2: 35.7% vs. 15.1%, P = 0.012; immunosuppressive therapy: 21.4% vs. 4.0%, P = 0.005), underwent more prosthetic valve replacement (35.7% vs. 7.1%, P <0.001), had less streptococcus infection (16.7% vs. 51.1%, P = 0.007) but more atypical bacterial infection (50.0% vs. 21.1%, P = 0.017) and poorer outcomes (17.9% vs. 4.0%, P = 0.019). It is noteworthy that the results were quite similar between the comparison of patients with NNHCA-IE and those with CA-IE. Overall, in-hospital mortality was 6.5%. The IE acquisition site and low serum albumin levels (odds ratio (OR): 0.8; P = 0.04) were significantly associated with an increased risk of mortality. Nosocomial IE patients had an 8.3-fold and NNHCA-IE patients had 6.5-fold increase in the risk of mortality compared to CA-IE patients. In conclusion, HAIE and NNHCA-IE have important epidemiological and prognostic implications. Because NNHCA-IE usually occurs in patients residing in the community, it is suggested that these patients should be identified and treated by the community primary care clinical staff as early as possible.


Assuntos
Infecções Comunitárias Adquiridas/epidemiologia , Infecção Hospitalar/epidemiologia , Endocardite/epidemiologia , Adulto , Envelhecimento/patologia , Bacteriemia/microbiologia , Causalidade , China/epidemiologia , Infecções Comunitárias Adquiridas/diagnóstico por imagem , Infecções Comunitárias Adquiridas/etiologia , Infecção Hospitalar/diagnóstico por imagem , Infecção Hospitalar/etiologia , Complicações do Diabetes , Endocardite/diagnóstico por imagem , Endocardite/etiologia , Feminino , Cardiopatias Congênitas/complicações , Próteses Valvulares Cardíacas/efeitos adversos , Mortalidade Hospitalar , Humanos , Terapia de Imunossupressão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Prognóstico , Estudos Retrospectivos , Cardiopatia Reumática/complicações , Fatores de Risco , Ultrassonografia
17.
ScientificWorldJournal ; 2014: 682189, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25133251

RESUMO

BACKGROUND: Ex vivo culture of intact embryonic kidney has become a powerful system for studying renal development. However, few methods have been available for gene manipulation and have impeded the identification and investigation of genes in this developmental process. RESULTS: Here we systemically compared eight different serotypes of pseudotyped self-complementary adenoassociated viruses (scAAVs) transduction in cultured embryonic kidney with a modified culture procedure. We demonstrated that scAAV was highly effective in delivering genes into and expressing in compacted tissues. scAAV serotypes 2 and 8 exhibited higher efficiency of transduction compared to others. Expression kinetics assay revealed that scAAV can be used for gene manipulation at the study of UB branching and nephrogenesis. Repressing WT1 in cultured kidney using shRNA impairs tubule formation. We for the first time employed and validated scAAV as a gene delivery tool in cultured kidney. CONCLUSIONS: These findings are expected to expedite the use of the ex vivo embryonic kidney cultures for kidney development research. For other ex vivo cultured organ models, scAAV could also be a promising tool for organogenesis study.


Assuntos
Dependovirus/genética , Rim/metabolismo , Transdução Genética/métodos , Animais , Células HEK293 , Humanos , Rim/crescimento & desenvolvimento , Camundongos , Camundongos Endogâmicos C57BL , Técnicas de Cultura de Órgãos/métodos
18.
Jpn J Clin Oncol ; 42(9): 856-60, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22701036

RESUMO

The recurrence and progression of brain metastases after brain irradiation are a major cause of mortality and morbidity in patients with cancer. The risk of radiation-induced neurotoxicity and efficacy probably leads oncologists to not consider re-irradiation. We report the case of a 48-year-old Asian male diagnosed with squamous cell lung cancer and multiple brain metastases initially treated with 40 Gy whole-brain radiotherapy and 20 Gy partial brain boost. Fourteen gray stereotactic radiosurgery as salvage for brain metastases in the left occipital lobe was performed after initial irradiation. The recurrence of brain metastases in the left occipital lobe was demonstrated on magnetic resonance imaging at 9 months after initial radiotherapy. He received the second course of 28 Gy stereotactic radiosurgery for the recurrent brain metastases in the left occipital lobe. The third relapse of brain metastases was demonstrated by a magnetic resonance imaging scan at 7 months after the second radiotherapy. The third course of irradiation was performed because he refused to undergo surgical resection of the recurrent brain metastases. The third course of irradiation used a pulsed reduced dose-rate radiotherapy technique. It was delivered in a series of 0.2 Gy pulses separated by 3-min intervals. The recurrent brain metastases were treated with a dose of 60 Gy using 30 daily fractions of 2 Gy. Despite the brain metastases receiving 162 Gy irradiation, this patient had no apparent acute or late neurologic toxicities and showed clinical improvement. This is the first report of the pulsed reduced dose-rate radiotherapy technique being used as the third course of radiotherapy for recurrent brain metastases.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/secundário , Irradiação Craniana , Neoplasias Pulmonares/patologia , Meios de Contraste , Fracionamento da Dose de Radiação , Gadolínio , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
19.
Nan Fang Yi Ke Da Xue Xue Bao ; 26(6): 828-30, 2006 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-16793612

RESUMO

OBJECTIVE: To evaluate the effects of acute normovolemic hemodilution (ANH) combined with controlled hypotension on reducing heterogeneous transfusion and safety during liver tumorectomy. METHODS: Thirty patients undergoing elective liver tumorectomy were randomly divided into 3 groups (10 each), namely ANH group (group A), ANH combined with controlled hypotension group (group B) and control group (group C). All the patients were anesthetized via endotracheal intubation. Before the operation, ANH was performed in groups A and B after anesthesia induction, and controlled hypotension was initiated in group B during tumorectomy. Blood transfusion and fluid infusion were carried out routinely in group C. Hb and Hct were measured before operation, after ANH, and immediately, 1 day and 7 days after the operation. The difference in intraoperative blood loss and heterogeneous blood transfusion volume in the 3 groups was observed. RESULTS: In group A, heterogeneous blood transfusion was avoided in 6 cases and but given in the other cases for an average of 400 ml. In group C, every patient received heterogeneous blood transfusion (664.8-/+248.1 ml), but none of the patients received heterogeneous blood in group B. The difference in transfusion volume between the 3 groups was significant (P<0.01). Hemodynamics was basically stable during operation in the 3 groups. CONCLUSION: ANH combined with controlled hypotension is safe and effective for decreasing and even avoiding homologous blood transfusion in liver tumorectomy.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Hemodiluição/métodos , Hepatectomia/métodos , Hipotensão Controlada/métodos , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Transfusão de Sangue/estatística & dados numéricos , Terapia Combinada , Feminino , Humanos , Soluções Isotônicas , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Resultado do Tratamento
20.
Ecotoxicology ; 15(5): 461-7, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16703454

RESUMO

Hybrid willows (Salix matsudana Koidz x Salix alba L.), weeping willows (Salix babylonica L.) and hankow willows (Salix matsudana Koidz) were exposed to potassium ferrocyanide to determine the potential of these plants to extract, transport and metabolize this iron cyanide complex. Young rooted cuttings were grown in hydroponic solution at 24.0 +/- 0.5 degrees C for 144 h. Ferrocyanide in solution, air, and aerial tissues of plants was analyzed spectrophotometrically. Uptake of ferrocyanide from the aqueous solution by plants was evident for all treatments and varied with plant species, ranging from 8.64 to 15.67% of initial mass. The uptake processes observed from hydroponic solution showed exponential disappearance kinetics. Very little amounts of the applied ferrocyanide were detected in all parts of plant materials, confirming passage of ferrocyanide through the plants. No ferrocyanide in air was found due to plant transpiration. Mass balance analysis showed that a large fraction of the reduction of initial mass in hydroponic solution was metabolized during transport within the plant materials. The difference in the metabolic rate of ferrocyanide between the three plant species was comparably small, indicating transport of ferrocyanide from hydroponic solution to plant materials and further transport within plant materials was a limiting step for assimilating this iron cyanide complex. In conclusion, phytoremediation of ferrocyanide by the plants tested in this study has potential field application.


Assuntos
Ferrocianetos/farmacocinética , Salix/metabolismo , Poluentes do Solo/farmacocinética , Biodegradação Ambiental , Ferrocianetos/química , Humanos , Folhas de Planta , Raízes de Plantas , Caules de Planta , Poluentes do Solo/química
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