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1.
Artif Cells Nanomed Biotechnol ; 48(1): 143-158, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32207347

RESUMO

Surgical resection remains the preferred approach for some patients with glioblastoma (GBM), and eradication of the residual tumour niche after surgical resection is very helpful for prolonging patient survival. However, complete surgical resection of invasive GBM is difficult because of its ambiguous boundary. Herein, a novel targeting material, c(RGDyk)-poloxamer-188, was synthesized by modifying carboxyl-terminated poloxamer-188 with a glioma-targeting cyclopeptide, c(RGDyk). Quantum dots (QDs) as fluorescent probe were encapsulated into the self-assembled c(RGDyk)-poloxamer-188 polymer nanoparticles (NPs) to construct glioma-targeted QDs-c(RGDyk)NP for imaging-guided surgical resection of GBM. QDs-c(RGDyk)NP exhibited a moderate hydrodynamic diameter of 212.4 nm, a negative zeta potential of -10.1 mV and good stability. QDs-c(RGDyk)NP exhibited significantly lower toxicity against PC12 and C6 cells and HUVECs than free QDs. Moreover, in vitro cellular uptake experiments demonstrated that QDs-c(RGDyk)NP specifically targeted C6 cells, making them display strong fluorescence. Combined with ultrasound-targeted microbubble destruction (UTMD), QDs-c(RGDyk)NP specifically accumulated in glioma tissue in orthotropic tumour rats after intravenous administration, evidenced by ex vivo NIR fluorescence imaging of bulk brain and glioma tissue sections. Furthermore, fluorescence imaging with QDs-c(RGDyk)NP guided accurate surgical resection of glioma. Finally, the safety of QDs-c(RGDyk)NP was verified using pathological HE staining. In conclusion, QDs-c(RGDyk)NP may be a potential imaging probe for imaging-guided surgery.

2.
Hum Reprod ; 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32154563

RESUMO

STUDY QUESTION: Could in vitro maturation (IVM) following transvaginal oocyte retrieval during gynaecological surgery (IVM-surgery) be an effective and safe strategy for fertility preservation? SUMMARY ANSWER: IVM-surgery on unstimulated ovaries is a novel option that can be considered for fertility preservation for women requiring gynaecological surgery, but more research is needed to identify appropriate patients who may benefit and to determine the cost-effectiveness of such an approach. WHAT IS KNOWN ALREADY: IVM followed by oocyte/embryo cryopreservation has been useful as a safe reproductive strategy for some infertile women. STUDY DESIGN, SIZE, DURATION: This prospective cohort study comprised 158 consecutive women with polycystic ovary syndrome (PCOS) who underwent laparoscopy or hysteroscopy for other reasons and had concomitant transvaginal oocyte retrieval followed by IVM between 2014 and 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 158 women with anovulatory PCOS who underwent IVM-surgery in our infertility centre were recruited for this study. Matured IVM oocytes obtained from these women were either freshly fertilized and subsequently frozen at the blastocyst stage (fresh oocyte group, n = 46) or the oocytes were frozen (frozen oocyte group, n = 112) for fertility preservation followed by later thawing for insemination and cleavage embryo transfer (ET) (n = 33). The following outcomes were then evaluated: embryological data, clinical pregnancy rate, live birth rate (LBR), neonatal outcomes, post-operative complications and post-operative ovarian function. MAIN RESULTS AND THE ROLE OF CHANCE: Among all the women who underwent IVM-surgery, the clinical pregnancy rate and LBR per initiated IVM cycle were 9.5% (15/158) and 6.9% (11/158), respectively. Women (40.6%, 20/33) who underwent the procedure with frozen-thawed oocytes (oocyte survival rate, 83.0%) obtained a high quality of cleaved embryos. In the fresh oocyte group, the clinical pregnancy rate and LBR per ET cycle were 69.2 and 53.8%, respectively. In the frozen oocyte group, the clinical pregnancy rate and LBR per ET cycle were 28.6 and 19.1%, respectively. No adverse neonatal outcomes were recorded. IVM-surgery was not associated with post-operative complications, a longer hospital stay, or impaired ovarian function. LIMITATIONS, REASONS FOR CAUTION: Because of the small sample size and the low utilization rate and cost-effectiveness per retrieval, the present findings should be interpreted with caution, and further studies are needed for the long-term follow-up of live births. WIDER IMPLICATIONS OF THE FINDINGS: This strategy can also help patients with normal ovulation to obtain available oocytes and embryos for cryopreservation and subsequent use. STUDY FUNDING/COMPETING INTEREST(S): This research was supported by the Joint Research Fund for Overseas Natural Science of China (No. 31429004), the National Key Research and Development Program of China (No. 2017YFC1002000, 2017YFC1001504, 2016YFC1000302), the Ministry of Science and Technology of China Grants (No. 2014CB943203), the Chinese Society of Reproductive Medicine Fund (No. 16020400656) and the National Natural Science Foundation of China (No. 81300456). All the authors have nothing to disclose in terms of conflicts of interest. TRIAL REGISTRATION NUMBER: chictr-ONC-17011861.

3.
Biotechnol Bioeng ; 2020 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-32096553

RESUMO

Mechanism-based inactivation of l-aspartate-α-decarboxylase (PanD), which leads to irreversible modification of active site, is a major challenge in the efficient production of ß-alanine from L-aspartic acid. In this study, a semi-rational strategy that combined conformational dynamics and structural alignment was applied to increase the catalytic stability of Bacillus subtilis PanD (BsPanD). Using site-saturation and C-terminal deletion, the variant Q5 (BsPanDI46V/I88M/K104S/I126* ) was generated. The catalytic half-life and the total turnover number (TTN) of Q5 were 3.48-fold and 2.52-fold higher, respectively, compared with that of the parent Q0. The reasons for the differences were the prolonged distance d1 between the phenolic group of Tyr58 and pyruvoyl group of Ser25 (4.9 Å in Q0 vs. 5.5 Å in Q5), an increased difficulty for incorrect protonation to occur, and the decreased flexibility of residues in regions A, B, and C, thereby enhancing the probability of correct protonation. Variant Q5, coupled with l-aspartase (AspA) in a 15-L bioreactor, generated a linear cascade system using fumaric acid as a substrate, yielding 118.6 g/L ß-alanine with a product/catalyst (P/C) ratio of 5.9 g/g and a conversion > 99%. These results showed that reshaping the protonation conformation of PanD can efficiently relieve mechanism-based inactivation and boost catalytic stability.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31712074

RESUMO

BACKGROUND & AIMS: The EncephalApp Stroop test is a high-sensitivity but low-specificity test that has been used to identify patients with covert hepatic encephalopathy (CHE). We aimed to develop a new strategy to detect CHE, combining EncephalApp Stroop test score with scores from subtests of the psychometric hepatic encephalopathy scoring system (PHES). METHODS: We performed a survey of 569 adult volunteers (229 men) in 9 communities in Shanghai, China, administering the EncephalApp Stroop test to determine the range of scores in the general population. Data from the standard PHES, including the number connection test-A, number connection test-B (NCT-B), line tracing test, serial dotting test (SDT), and digit symbol test, were used as the reference standard for diagnosis of CHE. A combination of the EncephalApp Stroop with subtests of the PHES was used to establish a new strategy for CHE diagnosis. We validated our findings using data from 160 patients with cirrhosis from 5 centers China. RESULTS: We determined the range of EncephalApp Stroop test scores for the volunteers of different decades of age, education levels, and sexes. Age, education level, and sex were independently associated with EncephalApp Stroop test scores. A combination of scores from the EncephalApp Stroop test, the NCT-B, and the SDT identified patients with CHE with the highest level of accuracy, when the standard PHES was used as the reference standard. A combination of scores of 187 sec for the EncephalApp Stroop test and below -1 for the NCT-B or below -1 for the SDT identified patients with CHE with an area under the curve (AUC) of 0.86, 81.0% sensitivity, and 91.9% specificity, and 87.5% accuracy. In the validation cohort, these cutoff scores identified patients with CHE with an AUC of 0.88, 97.1% sensitivity, 79.3% specificity, and 86.9% accuracy. The average time to calculate this score was 374±140 sec, compared 424±115 sec for the entire PHES. CONCLUSION: Scores from the EncephalApp Stroop test, NCT-B, and SDT identify patients with CHE with approximately 87% accuracy, and in a much shorter time than the standard PHES. This score combination could be a valid and convenient method for identifying patients with CHE. chictr.org.cn number, ChiCTR-EDC-17012007, ChiCTR1800019954.

5.
BMC Health Serv Res ; 19(1): 873, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31752845

RESUMO

BACKGROUND: The statement format of the Decisional Conflict Scale (sf-DCS) is designed and widely used to assess patients' state of uncertainty during health related decision making. As yet no Mandarin version of the sf-DCS has been produced. This study aims to produce the first Mandarin version of the sf-DCS and test its validity and reliability in mainland China. METHODS: The translation and cross-cultural adaptation of the original English version of the sf-DCS into Mandarin was carried out in accordance with previously published guidelines. The psychometric properties of sf-DCS were assessed in two hypothesized decision-making contexts through online surveys. RESULTS: In the online survey designed to test scale validity and reliability, 437 people responded to the influenza immunization survey and 238 responded to the breast cancer screening survey. The results confirm that the Mandarin version of sf-DCS has good criteria validity and the exploratory factor analysis suggested a fitted revised five factors model by removing three items. Respondents who were "unsure" about their decisions/intentions, had read less information, and reported lower self-perceived prior knowledge level scored higher on sf-DCS. The Cronbach's alpha for the sf-DCS total score was 0.963 and that for each subscale ranged from 0.784 to 0.937 in both decision making contexts, and the test-retest correlation coefficient was 0.528. CONCLUSIONS: The Mandarin version of sf-DCS has good criteria validity and its internal consistency is satisfactory. Our analysis suggests a refinement of the original sf-DCS's factor structure is needed.


Assuntos
Atitude Frente a Saúde , Tomada de Decisões , Psicometria , Inquéritos e Questionários , Adulto , Neoplasias da Mama , China , Cultura , Análise Fatorial , Feminino , Humanos , Vacinas contra Influenza , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Traduções , Incerteza
6.
World J Gastroenterol ; 25(36): 5505-5514, 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31576096

RESUMO

BACKGROUND: Bilioenteric Roux-en-Y anastomosis is one of the most complicated approaches for reconstructing the gastrointestinal tract, and endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging in patients after bilioenteric Roux-en-Y anastomosis. The optimal endoscopic strategies for such cases remain unknown. AIM: To explore the feasibility and effectiveness of single balloon enteroscopy-assisted (SBE-assisted) therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis based on multi-disciplinary collaboration between endoscopists and surgeons as well as report the experience from China. METHODS: This is a single center retrospective study. All of the SBE-assisted therapeutic ERCP procedures were performed by the collaboration between endoscopists and surgeons. The operation time, success rate, and complication rate were calculated. RESULTS: Forty-six patients received a total of 64 SBE-assisted therapeutic ERCP procedures, with successful scope intubation in 60 (93.8%) cases and successful diagnosis in 59 (92.2%). All successfully diagnosed cases received successful therapy. None of the cases had perforation or bleeding during or after operation, and no post-ERCP pancreatitis occurred. CONCLUSION: Based on multi-disciplinary collaboration, SBE-assisted therapeutic ERCP in patients after bilioenteric Roux-en-Y anastomosis is relatively safe and effective and has a high success rate.


Assuntos
Anastomose em-Y de Roux/efeitos adversos , Doenças Biliares/cirurgia , Colangiopancreatografia Retrógrada Endoscópica/métodos , Pancreatopatias/cirurgia , Reoperação/métodos , Enteroscopia de Balão Único/métodos , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Equipe de Assistência ao Paciente , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Reoperação/efeitos adversos , Estudos Retrospectivos , Enteroscopia de Balão Único/efeitos adversos
7.
Ying Yong Sheng Tai Xue Bao ; 30(10): 3509-3517, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31621238

RESUMO

Rehmannia glutinosa, a perennial herbaceous species, belongs to the family Scrophularia-ceae. As a staple medicinal material, its tuberous roots are highly valued in traditional Chinese medicine. However, R. glutinosa suffers from serious consecutive monoculture problems in production, which leads to a decline in both productivity and quality. Phyllosphere bacteria, the most abundant component of phyllosphere microorganisms, play crucial roles in plant growth and health. Characterization of phyllosphere bacteria could provide new insights into the mechanisms of consecutive monoculture problems and their control measures. Meanwhile, the varied taxa could be served as an important indicator of consecutive monoculture problems. The barcoded pyrosequencing of 16S rDNA genes combined with a culture-dependent approach was applied to characterize the shifts of bacterial community structure and diversity in the phyllosphere under consecutive monoculture of R. glutinosa. The results showed that consecutive monoculture clearly affected bacterial community structure in the phyllosphere. The phyllosphere bacterial communities of the two-year monocultured (TY) and the diseased plants (DP) were more similar, and different from the one-year monocultured (OY). The evenness, Shannon and Simpson diversity indices were significantly lower in TY and DP than in OY. Species annotation showed that bacterial community in R. glutinosa phyllosphere mainly consisted of Proteobacteria (91.2%), Firmicutes (5.1%) and Actinobacteria (3.7%). There was no significant difference in the number of detected bacterial taxa. However, Proteobacteria was significantly increased while Firmicutes and Actinobacteria were significantly decreased under consecutive monoculture. At the genus level, the relative abundances of genera Exiguobacterium, Bacillus and Arthrobacter, potentially beneficial microorganisms, were significantly higher in OY than that in TY and DP, but it was opposite for the genus Pseudomonas. The results from the culture-dependent approach and pathogenicity test showed that Pseudomonas plecoglossicida D9, widely isolated from the diseased leaves, was highly pathogenic to leaves. In conclusion, R. glutinosa monoculture resulted in distinct phyllosphere bacterial community variation with the accumulation of pathogen loads at the expense of beneficial microorganisms, which could contribute to the occurrence of leaf disease symptoms,and aggravate R. glutinosa replant disease in a monoculture regime.


Assuntos
Rehmannia , Bactérias , DNA Ribossômico , Raízes de Plantas , Pseudomonas
8.
J Pain Res ; 12: 2009-2026, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31308730

RESUMO

Background: Preoperative anxiety is associated with postoperative hyperalgesia; however, few studies have investigated the mechanism underlying this association in female surgical patients. Research has suggested that ON cells in the rostral ventromedial medulla (RVM) receive nerve impulses via cholecystokinin 2 (CCK2) receptors, facilitating hyperalgesia. Additionally, the downstream serotonergic projection system from the RVM to the spinal cord has a dual regulating effect on pain responses, and the 5-hydoxytryptophan 2B (5-HT2B) receptor in spinal dorsal horn neurons is critically involved in mechanical allodynia. Methods: Ovariectomized rats were treated with estrogen replacement, single prolonged stress (SPS), and plantar incision. Various receptor agonists and antagonists were then administered into the RVM and spinal cord to study the mechanism underlying postoperative hyperalgesia caused by preoperative anxiety in female rats. Results: Behavioral testing revealed that preoperative SPS induced postoperative hyperalgesia, as well as the expression of the CCK2 receptor in the RVM and the expression of the 5-HT2B receptor, protein kinase Cγ (PKCγ), and phosphorylation of the N-methyl-d-aspartate receptor1 (p-NR1) in the spinal cord increased confirmed by Western blot. RVM microinjection of the CCK2 receptor agonist CCK-8 and intrathecal injection of the 5-HT2B receptor agonist BW723C86 both produced hyperalgesia in female rats after plantar incision, whereas the CCK2 receptor antagonist YM022, the 5-HT2B receptor antagonist RS127445, and the PKCγ inhibitor C37H65N9O13 decreased the rats' sensitivity to the same stimulus. Additionally, electrophysiological analysis suggested that activation of the 5-HT2B receptor increased the whole-cell current (IBa) in superficial dorsal horn neurons through the PKCγ pathway. Conclusion: Our study demonstrated that preoperative anxiety-induced postoperative hyperalgesia in female rats is associated with descending pain pathways. The CCK2 receptor in the RVM and spinal 5-HT2B receptor may play a role in this hyperalgesic effect.

9.
Reprod Biol Endocrinol ; 17(1): 49, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234873

RESUMO

BACKGROUND: Superovulation treatment had some adverse effects on maturity and development of oocytes. Can superovulation dose of gonadotropins (Gns) affect the transcriptome of granulosa cells and follicular fluid (FF) hormone levels? METHODS: One leading pre-ovulatory follicle per subject was used from three natural-cycle and four Gn-stimulated patients. Granulosa cells and FF samples were collected from the same leading follicle of each patient. RNA was extracted from granulosa cells and subjected to deep sequencing and analysis. Follicle-stimulating hormone (FSH), estradiol (E2), androstenedione (AND), testosterone (T), luteinizing hormone (LH), and progesterone (P4) levels in FF were measured by immunoassays. Student's t test was used for statistical analysis. RESULTS: A total of 715 genes were up-regulated, and 287 genes were down-regulated, in the Gn-stimulated group relative to the control group. Gene Ontology analysis revealed that the down-regulated genes were enriched in cell cycle and meiosis pathways, primarily those associated with follicle or oocyte maturation and quality. On the other hand, the up-regulated genes were enriched in functions related to immunity and cytokine-cytokine receptor interactions. Compared to the follicles of natural cycle, the E2 and LH concentrations were significantly reduced (P < 0.001), the P4 concentration was significantly increased (P = 0.003), and the concentrations of FSH, T and AND had no difference in the follicles of Gn-stimulated cycle. CONCLUSIONS: Cell cycle- and meiosis-associated genes were down-regulated by Gns stimulation, whereas immune- and cytokine-associated genes were up-regulated. Hormone levels were also affected by Gns stimulation. Compared with natural-cycle follicles,putative markers associated with oocyte quality and follicle maturation were significantly different from those in Gn-stimulated follicles. Hormone levels in follicles were compatible with the steroidogenic patterns of granulosa cell, which reflects the follicle maturation and oocyte quality.


Assuntos
Líquido Folicular/metabolismo , Gonadotropinas/farmacologia , Células da Granulosa/metabolismo , Hormônios Hipofisários/metabolismo , Transcriptoma/efeitos dos fármacos , Androstenodiona/metabolismo , Estradiol/metabolismo , Feminino , Fertilização In Vitro , Hormônio Foliculoestimulante/metabolismo , Ontologia Genética , Humanos , Hormônio Luteinizante/metabolismo , Transdução de Sinais/genética , Testosterona/metabolismo
10.
Pathol Res Pract ; 215(6): 152386, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30935762

RESUMO

AIM: To elucidate whether the interaction between Anxa2 and Stat3 could promote the progression of hepatocellular carcinoma (HCC) and that high co-expression of Anxa2 and Stat3 could predict poor prognosis in HCC patients. METHODS: We investigated Anxa2 and Stat3 expression using Western blot analysis in 4 HCC and adjacent nontumor tissues and using immunohistochemistry in 100 patients' paraffin sections. Then we assessed the expression of Stat3, Anxa2 and co-expression of Stat3 and Anxa2 with relevant clinical pathological parameters and their prognostic value in HCC patients. The recurrence and overall survival rates were estimated using the Kaplan-Meier method and compared with the log-rank test. The prognostic analysis was carried out with univariate and multivariate Cox regressions models. RESULTS: The incidence of high Stat3 expression in HCC tissues (35%) was significantly higher than that in non-HCC tissues (8%) (P < 0.001). The same result was observed in Anxa2 (P < 0.001). Also, the overexpression of Stat3 or Anxa2 showed a significant relationship with the recurrence of the 100 HCC patients (P = 0.012; P = 0.003). Additionally, tumor size >3 cm in diameter, multiple tumor number, and the presence of microvascular tumor thrombus were also significantly associated with recurrence in 100 patients. Then, all enrolled patients were divided into four groups according to IHC score of Stat3 and Anxa2, and the results indicated a significant difference in recurrence time between the subgroups (P < 0.001). What's more, co-highexpression of Stat3 and Anxa2 was related to the presence of microvascular tumor thrombus (P = 0.003) and poor tumor differentiation (P < 0.001), but not relevant with other clinical features (All P > 0.05). CONCLUSION: The expression of Stat3, Anxa2, or co-high-expression of the two proteins was associated with HCC recurrence and survival.


Assuntos
Anexina A2/biossíntese , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Fator de Transcrição STAT3/biossíntese , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico
11.
Jpn J Clin Oncol ; 49(7): 646-655, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30968933

RESUMO

BACKGROUND AND AIM: The impact of transarterial chemoembolization (TACE) and preventive antiviral therapy on the occurrence of hepatitis B virus (HBV) reactivation and subsequent hepatitis remains controversial. This meta-analysis aimed to evaluate the effect of TACE and preventive antiviral therapy on the risk of HBV reactivation and subsequent hepatitis. Meanwhile, we explored the role of HBeAg status in HBV reactivation after TACE. METHODS: We performed this meta-analysis with 11 included studies to assess the effect of TACE and preventive antiviral therapy on predicting clinical outcomes in HBV-related hepatocellular carcinoma (HCC). The pooled odds ratios (OR) were calculated using a random or fixed effects model. PUBMED, MEDLINE, EMBASE and the Cochrane Central Register of Controlled were searched for the included articles (from 2000 to December 2017). RESULTS: Our results showed that TACE significantly increased the risk of HBV reactivation (OR: 3.70; 95% CI 1.45-9.42; P < 0.01) and subsequent hepatitis (OR: 4.30; 95% CI 2.28-8.13; P < 0.01) in HCC patients. There was no significant difference in HBV reactivation after TACE between HBeAg positive and negative patients (OR: 1.28; 95% CI 0.31-5.34; P = 0.73). Preventive antiviral therapy could statistically reduce the rate of HBV reactivation (OR: 0.08; 95% CI 0.02-0.32; P < 0.01) and hepatitis (OR: 0.22; 95% CI 0.06-0.80; P = 0.02) in those with TACE treatment. CONCLUSIONS: The present study suggested that TACE was associated with a higher possibility of HBV reactivation and subsequent hepatitis. Preventive antiviral therapy is significantly in favor of a protective effect.


Assuntos
Antivirais/farmacologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/virologia , Quimioembolização Terapêutica , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/prevenção & controle , Neoplasias Hepáticas/terapia , Ativação Viral/efeitos dos fármacos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Viés de Publicação , Fatores de Risco
12.
Pain Res Manag ; 2019: 9017931, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30863475

RESUMO

Chronic postsurgical pain (CPSP) is a chronic pain state that is difficult to be treated clinically. A series of complicated changes have been produced from nociceptive stimulation to the occurrence and development of postsurgical pain. Many mechanisms remain unclear. In order to study the role of intercellular gap junctions in inducing inflammatory microenvironment at the beginning of nociceptor after operation, the model of skin/muscle incision and retraction (SMIR) was established. We observed the changes of the expression of exchange proteins directly activated by cAMP-1 (Epac1) and p120 catenin (p120), the quantities of macrophages and endothelial cells, vascular endothelial permeability, and mechanical withdrawal threshold (MWT). It was found that macrophages and endothelial cells were functionally coupled through Epac1-p120. Adhesive linkage disorder remodeled the chronic, inflammatory, and eutrophic microenvironment at the beginning of nociceptor after operation through macrophages, endothelial cells, and endothelial paracellular pathways. It might be an early event and a key step in peripheral sensitization of CPSP. The expression of p120 in muscle tissue around the incision might become a prognostic marker for the conversion of acute postsurgical pain into CPSP. Targeted intervention of Epac1-p120 might be a clinical strategy for inhibiting the conversion of acute postsurgical pain into CPSP.


Assuntos
Cateninas/metabolismo , Dor Crônica/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Dor Pós-Operatória/metabolismo , Animais , Masculino , Ratos , Ratos Sprague-Dawley
13.
Mol Cell Biochem ; 450(1-2): 53-64, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29922945

RESUMO

S100A11 as a S100 protein family member has been documented to play dual-direction regulation over cancer cell proliferation. We explored the role of S100A11 in the proliferation and apoptosis of pancreatic cancer cell line PANC-1 and the potential mechanisms involving the TGF-ß1/SMAD4/p21 pathway. S100A11 and TGF-ß1 protein expressions in 30 paraffin-embedded specimens were evaluated by immunohistochemistry. S100A11 and TGF-ß1 expression in PANC-1 cell line was suppressed using small interfering RNA (siRNA), respectively. Subsequently, pancreatic cancer cell apoptosis was measured by Cell Counting Kit-8 and flow cytometry, and S100A11 and TGF-ß1/SMAD4/p21 pathway proteins and genes were detected with Western blotting and quantitative polymerase chain reaction (qPCR). S100A11 cytoplasmic/nuclear protein translocation was examined using NE-PER® cytoplasm/nuclear protein extraction in cells interfered with TGF-ß1 siRNA. Our results showed that S100A11 expression was positively correlated with TGF-ß1 expression in pancreatic cancerous tissue. Silencing TGF-ß1 down-regulated intracellular P21WAF1 expression by 90%, blocked S100A11 from cytoplasm entering nucleus, and enhanced cell proliferation. Silencing S100A11 down-regulated intracellular P21 expression and promoted cell apoptosis without significantly changing TGF-ß1 and SMAD4 expression. Our findings revealed that S100A11 and TGF-ß1/SMAD4 signaling pathway were related but mutually independent in regulating PANC-1 cells proliferation and apoptosis. Other independent mechanisms might be involved in S100A11's regulation of pancreatic cell growth. S100A11 could be a potential gene therapy target for pancreatic cancer.


Assuntos
Apoptose , Proliferação de Células , Proteínas de Neoplasias/metabolismo , Neoplasias Pancreáticas/metabolismo , Proteínas S100/metabolismo , Transdução de Sinais , Proteína Smad4/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p21 , Feminino , Humanos , Masculino , Proteínas de Neoplasias/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteínas S100/genética , Proteína Smad4/genética , Fator de Crescimento Transformador beta1/genética
14.
Pathol Res Pract ; 215(2): 235-242, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30396755

RESUMO

Apoptosis in intestinal epithelial cells (IECs) promotes the development of ulcerative colitis (UC), a type of inflammatory bowel disease (IBD). Efficient clearance of apoptotic cells is essential for tissue homeostasis in metazoans. Actin related protein 3 (ARP3) promotes endothelial dysfunction. The expression and function of ARP3 in UC remains unclear. In this study, the expression of apoptotic markers as p53, Bax, Cleaved-Caspease9 and Cleaved-Caspease3 were proved to be increased in the intestinal epithelial cells (IECs) of UC patients and in a mouse disuccinimidyl suberate(DSS)-induced colitis model; meanwhile, ARP3 expression was elevated. ARP3 expression levels and the severity of symptoms in patients with UC were positively correlated. By knocking down ARP3 in a TNF-α-treated NCM-460 cell colitis model, the apoptotic markers described above were all decreased. In conclusion, our data indicates that ARP3 might promote the apoptosis of IECs in UC, revealing a potential molecular target for treating UC.


Assuntos
Proteína 3 Relacionada a Actina/metabolismo , Apoptose/fisiologia , Colite Ulcerativa/metabolismo , Mucosa Intestinal/metabolismo , Animais , Linhagem Celular , Colite Ulcerativa/patologia , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Mucosa Intestinal/patologia , Camundongos , Camundongos Endogâmicos C57BL
15.
J Cell Biochem ; 120(1): 988-999, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30160795

RESUMO

Pancreatic cancer (PC) is one of the most lethal cancers known worldwide, and its prognosis is poor in most patients. Exosomes are nanosized extracellular vesicles, which are released from various cell types. They are involved in cellular communication. The diagnosis and treatment of PC were improved substantially with exosomes. In this study, we isolated PC-derived exosomes and investigated their proteomic profile. Then, we conducted bioinformatic analysis on proteomic data. Differential ultracentrifugation was performed to isolate exosomes from human serum samples and four PC cell lines. Transmission electron microscopy and Western blot analysis were used to characterize the isolated exosomes. Liquid chromatography coupled with tandem mass spectrometry was conducted to identify the proteome of serum exosomes. Proteomic analysis demonstrated that all the serum exosomes were derived from three cohorts of human subjects; these serum exosomes contained a total of 655 proteins, out of which 315 proteins overlapped with ExoCarta database. Gene oncology and kyoto encyclopedia of genes and genomes analyses provided the functional annotation of the proteome. Interestingly, 18 or 14 proteins were upregulated and 11 or 14 proteins were downregulated in serum exosomes derived from patients with PC as compared with in serum exosomes derived from healthy volunteers or from pancreatitis patients respectively. Annexin A11, a calcium-dependent phospholipid-binding protein, was expressed in a PC cell line (CFPAC-1)-derived exosomes and in tumor tissues of patients with PC, respectively. Our data provided a basic foundation for further studies on the protein composition of PC-derived exosomes and its involvement in PC biology.


Assuntos
Exossomos/metabolismo , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/patologia , Proteoma/metabolismo , Algoritmos , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Cromatografia Líquida , Estudos de Coortes , Bases de Dados de Proteínas , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Microscopia Eletrônica de Transmissão , Transdução de Sinais/genética , Espectrometria de Massas em Tandem
16.
Mol Biol Rep ; 45(6): 1863-1871, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30306507

RESUMO

Psychological stress has been recognized as a well-documented risk factor associated with ß2-adrenergic receptor (ß2-AR) in the development of pancreatic cancer. Aldo-keto reductase 1 member B1 (AKR1B1) is a potential interacting partner of ß2-AR, but the effect of their interaction on pancreatic cancer cells is not known at present. We found a positive correlation between AKR1B1 and ß2-AR expression in pancreatic cancer tissue samples, and co-localization of these proteins in the human pancreatic cancer BXPC-3 cell line. Compared to the controls, the CFPAC-1 and PANC-1 pancreatic cancer cells overexpressing ß2-AR and AKR1B1 respectively showed significantly higher proliferation rates, which is attributed to higher proportion of cells in the S phase and decreased percentage of early apoptotic cells. Furthermore, overexpression of ß2-AR led to a significant increase in the expression of AKR1B1 and phosphorylated extracellular signal-regulated kinase (p-ERK1/2). Overexpression of AKR1B1 significantly decreased ß2-AR levels and increased that of p-ERK1/2. Taken together, ß2-AR directly interacted with and up-regulated AKR1B1 in pancreatic cancer cells, and promoted their proliferation and inhibited apoptosis via the ERK1/2 pathway. Our findings also highlight the ß2-AR-AKR1B1 axis as a potential therapeutic target for pancreatic cancer.


Assuntos
Aldeído Redutase/genética , Neoplasias Pancreáticas/genética , Receptores Adrenérgicos beta 2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Aldeído Redutase/metabolismo , Aldo-Ceto Redutases , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Masculino , Pessoa de Meia-Idade , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Pâncreas/metabolismo , Neoplasias Pancreáticas/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Adrenérgicos beta 2/genética , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima
17.
Biomed Res Int ; 2018: 3634563, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30148165

RESUMO

Exosomes are discrete populations of small (40-200 nm in diameter) membranous vesicles that are released into the extracellular space by most cell types, eventually accumulating in the circulation. As molecular messengers, exosomes exert a broad array of vital physiologic functions by transporting information between different cell types. Because of these functional properties, they may have potential as biomarker sources for prognostic and diagnostic disease. Recent research has found that exosomes have potential to be utilized as drug delivery agents for therapeutic targets. However, basic researches on exosomes and researches on their therapeutic potential both require the existence of effective and rapid methods for their separation from human samples. In the current absence of a standardized method, there are several methods available for the separation of exosomes, but very few studies have previously compared the efficiency and suitability of these different methods. This review summarized and compared the available traditional and novel methods for the extraction of exosomes from human samples and considered their advantages and disadvantages for use in clinical laboratories and point-of-care settings.


Assuntos
Exossomos , Manejo de Espécimes , Transporte Biológico , Biomarcadores , Humanos , Prognóstico , Proteínas
18.
Oncotarget ; 9(14): 11767-11782, 2018 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-29589596

RESUMO

Nephropathy is one of the most severe complications of diabetic patients. The therapeutic strategies for diabetic patients should not only focus on the control of blood glucose but also pay attention to the occurrence of diabetic nephropathy (DN). Coenzyme Q10 (CoQ10) has great therapeutic potential for DN. However, the clinical application of CoQ10 has been limited because of its low water-solubility and non-specific distribution. Liposomes were supposed to be an effective way for delivering CoQ10 to kidney. CoQ10 was effectively encapsulated into the liposome (CoQ10-LIP) with a high entrapment efficiency of 86.15 %. The CoQ10-LIP exhibited a small hydrodynamic diameter (180 ± 2.1 nm) and negative zeta potential (-18.20 mV). Moreover, CoQ10-LIP was combined with ultrasound-mediated microbubble destruction (UTMD) to enhance specific distribution of CoQ10 in kidney. In early stage of diabetic mellitus (DM), rats were administrated with CoQ10-LIP followed by UTMD (CoQ10-LIP+UTMD) to prevent occurrence of DN. Results revealed that CoQ10-LIP+UTMD effectively prevented the renal morphology and function of diabetics rats from damage. The protective mechanism of CoQ10-LIP was highly associated with protecting podocyte, promoting vascular repair and inhibiting cell apoptosis. Conclusively, CoQ10-LIP in combination with UTMD might be a potential strategy to prevent occurrence of DN.

19.
Int J Nanomedicine ; 13: 681-694, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29440894

RESUMO

Introduction: The short lifetime of protein-based therapies has largely limited their therapeutic efficacy in injured nervous post-spinal cord injury (post-SCI). Methods: In this study, an affinity-based hydrogel delivery system provided sustained-release of proteins, thereby extending the efficacy of such therapies. The affinity-based hydrogel was constructed using a novel polymer, heparin-poloxamer (HP), as a temperature-sensitive bulk matrix and decellular spinal cord extracellular matrix (dscECM) as an affinity depot of drug. By tuning the concentration of HP in formulation, the cold ternary fibroblast growth factor-2 (FGF2)-dscECM-HP solution could rapidly gelatinize into a hydrogel at body temperature. Due to the strong affinity for FGF2, hybrid FGF2-dscECM-HP hydrogel enabled sustained-release of encapsulated FGF2 over an extended period in vitro. Results: Compared to free FGF2, it was observed that both neuron functions and tissue morphology after SCI were clearly recovered in rats treated with FGF2-dscECM-HP hydrogel. Moreover, the expression of neurofilament protein and the density of axons were increased after treatment with hybrid FGF2-dscECM-HP. In addition, the neuroprotective effects of FGF2-dscECM-HP were related to inhibition of chronic endoplasmic reticulum stress-induced apoptosis. Conclusion: The results revealed that a hybrid hydrogel system may be a potential carrier to deliver macromolecular proteins to the injured site and enhance the therapeutic effects of proteins.


Assuntos
Matriz Extracelular/química , Fator 2 de Crescimento de Fibroblastos/farmacologia , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Fármacos Neuroprotetores/farmacologia , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Axônios/efeitos dos fármacos , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Feminino , Fator 2 de Crescimento de Fibroblastos/farmacocinética , Heparina/química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacocinética , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacocinética , Células PC12 , Poloxâmero/química , Ratos , Ratos Sprague-Dawley , Medula Espinal/citologia , Traumatismos da Medula Espinal/patologia , Temperatura Ambiente
20.
J Clin Nurs ; 27(5-6): e1013-e1021, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29076204

RESUMO

AIMS AND OBJECTIVES: To reveal nurses' self-reported practice of managing chest tubes and to define decision-makers for these practices. BACKGROUND: No consensus exists regarding ideal chest-tube management strategy, and there are wide variations of practice based on local policies and individual preferences, rather than standardised evidence-based protocols. DESIGN: This article describes a cross-sectional study. METHODS: Questionnaires were emailed to 31 hospitals in Tianjin, and the sample consisted of 296 clinical nurses whose work included nursing management of chest drains. The questionnaire, which was prepared by the authors of this research, consisted of three sections, including a total of 22 questions that asked for demographic information, answers regarding nursing management that reflected the practice they actually performed and who the decision-makers were regarding eight chest-drain management procedures. McNemar's test was used to analyse the data. RESULTS: The results indicated that most respondents thought that it was necessary to manipulate chest tubes to remove clots impeding unobstructed drainage (91.2%). Most respondents indicated that dressings would be changed when the dressing was dysfunctional. At the same time, more than half of respondents approved of changing dressings routinely, and the frequency of changing dressings varied. When drainage was employed for pleural effusion and for a pneumothorax, 64.6% and 94.5% of respondents, respectively, considered that underwater seal-drainage bottles should be changed routinely, and the frequency of changing bottles both varied. The results indicated that nurses were the primary decision-makers in the replacement of chest tubes, manipulation of chest tubes and monitoring of drainage fluid. CONCLUSIONS: There was considerable variation in respondents' self-reported clinical nursing practice regarding management of chest drains. The rationale on which respondents' practices were based also varied greatly. This study indicated that nurses were the primary decision-makers for three of eight procedures regarding management of chest drains, which reflects that clinical nurses' decision-making power regarding management of chest drains was weak. RELEVANCE TO CLINICAL PRACTICE: This study describes the nurse-reported practices of Chinese nurses from Tianjin, including changing and selecting dressing types, manipulating chest tubes, clamping drains and replacing drainage bottles, and the study defines who the decision-makers were for these interventions. By focusing on nurses' self-report of behaviours in managing chest drains (actual nursing practice vs. nursing knowledge), this article also relates the literature to the research findings and denotes the gaps in knowledge for future research.


Assuntos
Tubos Torácicos/normas , Drenagem/enfermagem , Padrões de Prática em Enfermagem , Adulto , Bandagens , China , Tomada de Decisão Clínica , Consenso , Estudos Transversais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Autorrelato
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