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1.
J Diabetes Investig ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020731

RESUMO

AIMS: This secondary analysis of the 24-week SMART study examined the efficacy of add-on saxagliptin or acarbose to metformin across different patient subgroups with type 2 diabetes mellitus (T2DM), based on baseline characteristics. METHODS: Randomized patients (N=481) were classified into subgroups based on their baseline age (<65, ≥65 years), body mass index (BMI; <24, 24-<28, ≥28Kg/m2 ), glycated hemoglobin (HbA1c; <8%, 8-<9%, 9-<10%, ≥10%), and renal function (creatinine clearance 50-<80, ≥80mL/min). Treatment effects on primary outcome (HbA1c) and key secondary outcomes of fasting plasma glucose (FPG), 2-hour postprandial glucose (2h-PPG), and homeostatic model assessment of ß-cell function were assessed across patient subgroups. RESULTS: For saxagliptin, reductions in HbA1c from baseline to Week 24 were consistent across different subgroups regardless of baseline age, BMI, HbA1c, and renal function (range -0.66 to -1.16%). ` Saxagliptin was associated with consistent reductions in FPG (-0.60 to -1.33 mmol/L) and 2h-PPG (-0.48 to -1.95 mmol/L) across the majority of subgroups studied. Efficacy of acarbose on FPG attenuated progressively with increasing baseline HbA1c (+0.86 to -1.43 mmol/L); an increase from baseline FPG was observed in patients with HbA1c >9%. The effect of acarbose on PPG was also variable (+0.23 to -3.38 mmol/L). CONCLUSIONS: As add-on to metformin, both saxagliptin and acarbose reduced HbA1c regardless of baseline HbA1c, age, BMI, and renal function; however, only saxagliptin was effective at a stable glycemic control (FPG and PPG). The efficacy of acarbose on FPG and PPG was significantly attenuated in patients with higher baseline HbA1c (≥8%).

2.
Biomater Sci ; 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31899467

RESUMO

Primary central nervous system lymphoma (PCNSL) is a rare brain tumor. Its therapeutic efficacy is much lower than that of traditional lymphoma, largely due to the presence of the blood-brain barrier (BBB), which hinders the effective drug delivery and deposition on the disease site. Angiopep-2 (ANG) can target low-density lipoprotein receptor-related protein (LRP) on the surface of brain capillary endothelial cells (BCECs) and exhibits high BBB transport capability. In this study, we designed an ANG conjugated poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) (APP) nanoparticle to deliver doxorubicin (DOX) for the treatment of PCNSL. Our data indicated that the targeted APP nanoparticles showed significantly increased cellular uptake by BCECs compared with the control nanoparticles. In the intracranial SU-DHL-2-LUC lymphoma xenograft mice model, APP enhanced drug deposition in tumor tissues, and DOX-loaded APP (APP@DOX) exhibited a better therapeutic effect than free DOX and nontargeted PP@DOX, which significantly prolonged the survival time of mice.

3.
J Diabetes Complications ; 34(2): 107464, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31771933

RESUMO

AIMS: Our aim was to search for clinical predictors of good glycemic control in patients starting or intensifying oral hypoglycemic pharmacological therapy. METHODS: A multicenter, prospective cohort of 499 diabetic subjects was enrolled in this study: patients with newly diagnosed diabetes (NDM group) or poor glycemic control with oral antidiabetic drugs (OADs) (PDM group). All subjects then started or intensified OADs therapy and followed up for 91 days. Glycemic control was determined according to HbA1c at day 91 with HbA1c <7% considered good. RESULTS: The proportions of patients with good glycemic control after follow up for 91 days were 66.9% and 34.8% in NDM group and PDM group respectively. Logistic regression analysis showed that the change in GA at 28 days was the only predictor of good glycemic control in NDM patients (OR = 1.630, 95% CI 1.300-2.044, P < 0.001). In PDM patients, changes in GA at 28 days, CPI, baseline HbA1c, diabetic duration, and BMI were all independent predictors of good glycemic control (All P < 0.05). CONCLUSIONS: GA decline is a good predictor of future success in newly diagnosed patients. In patients intensifying therapy, beside GA decline, other individualized clinical characteristics should also be considered.

4.
Bioresour Technol ; 297: 122345, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31706892

RESUMO

The aim of this study was to investigate the syntrophic methanogenesis from the perspective of energy transfer and competition. Effects of redox materials and redox potential on direct interspecies electron transfer (DIET) were examined through thermodynamic analysis based on the energy distribution principle. Types of redox materials could affect the efficiency of DIET via changing the total energy supply of the syntrophic methanogenesis. Decreasing system redox potential could facilitate DIET through increasing the total available energy. The competition between hydrogenotrophic methanogens and DIET methanogens might be the reason for the low proportion of the DIET pathway in the syntrophic methanogenesis. A facilitation mechanism of DIET was proposed based on the energy distribution. Providing sufficient electrons, inhibiting hydrogenotrophic methanogens and adding more competitive redox couples to avoid hydrogen generation might be beneficial for the facilitation of DIET.


Assuntos
Elétrons , Metano , Transporte de Elétrons , Oxirredução , Termodinâmica
5.
World Neurosurg ; 133: e275-e280, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31518747

RESUMO

BACKGROUND: The acellular dermal matrix (ADM) and turbinate flap (TF) have been widely used in the reconstruction of skull base defects. However, owing to the lack of reported data, the therapeutic effects have been controversial. The purpose of the present study was to compare the effect of the ADM and TF on cerebrospinal fluid (CSF) rhinorrhea after nasal endoscopic resection of a skull base tumor. METHODS: The data from 46 patients who had undergone nasal endoscopic resection of a skull base tumor and repair of CSF rhinorrhea were retrospectively analyzed. The patients were divided into ADM and TF groups according to the difference in repair materials used. We compared and analyzed the intraoperative information and postoperative outcomes. RESULTS: The operation time, blood loss, defect area, and need for blood transfusion were not significantly different between the ALT and TF groups. The postoperative length of hospital stay (14.33 ± 3.66 vs. 16.76 ± 5.51 days; P = 0.669) and the incidence of complications, including wound infection (1 vs. 0; P = 0.270), intracranial infection (1 vs. 1; P = 0.900), hemorrhage (2 vs. 3; P = 0.788), 15-day CSF leak (1 vs. 2; P = 0.658), and respiratory infection (2 vs. 1; P = 0.450) were comparable between the 2 groups. The 6-month (0 vs. 0; P = 1.000) and 12-month (0 vs. 0; P = 1.000) incidence of recurrence also showed no significant differences. CONCLUSION: The use of the ADM for patients with CSF rhinorrhea showed comparable results in terms of postoperative outcomes compared with the use of TF. ADM could serve as a safe and feasible alternative for endoscopic repair of CSF rhinorrhea after nasal endoscopic resection of skull base tumors.

6.
Eur J Med Chem ; 185: 111827, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31732256

RESUMO

Human African trypanosomiasis (HAT), caused by the parasitic protozoa Trypanosoma brucei, is one of the fatal diseases in tropical areas and current medicines are insufficient. Thus, development of new drugs for HAT is urgently needed. Leucyl-tRNA synthetase (LeuRS), a recently clinically validated antimicrobial target, is an attractive target for development of antitrypanosomal drugs. In this work, we report a series of α-phenoxy-N-sulfonylphenyl acetamides as T. brucei LeuRS inhibitors. The most potent compound 28g showed an IC50 of 0.70 µM which was 250-fold more potent than the starting hit compound 1. The structure-activity relationship was also discussed. These acetamides provided a new scaffold and lead compounds for the further development of clinically useful antitrypanosomal agents.

7.
Cancer Manag Res ; 11: 9733-9741, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814768

RESUMO

Objective: This study explored the effectiveness of a new inflammatory prognostic system, using preoperative neutrophil to lymphocyte ratio (NLR) to predict the postoperative survival rate of patients with sinonasal squamous cell carcinoma (SSCC). Methods: Patients diagnosed with SSCC who undergone surgically treated without neoadjuvant therapy were included in the study between May 2008 and October 2017. Preoperative NLR is defined as: preoperative neutrophil/postoperative lymphocyte ratio. The prognostic value was uncovered by univariate and multivariate Cox hazards analysis. Results: A total of 147 patients were included in this study. Through the multivariate analysis, pathological T stage (hazard ratio [HR] 1.719, confidence interval [CI] 1.277-3.642, p<0.001), pathological N stage (HR 1.344, 95% CI 1.015-2.776, p<0.001), and preoperative NLR (HR 1.579, 95% CI 1.217-3.092, p=0.002) were independent risk factor for overall survival (OS). Pathological T stage (HR 1.835, 95% CI 1.141-3.132, <0.001), pathological N stage (HR 1.281, 95% CI 1.169-2.476, p<0.001), and preoperative NLR (HR 1.688, 95% CI 1.162-3.363, p p<0.001) were also independently associated with disease-free survival (DFS). Pathological T stage (HR p<0.001, 95% CI 1.537-3.021, p<0.001), pathological N stage (HR1.571, 95% CI 1.157-2.258, p<0.001), and preoperative NLR (HR 1.509, 95% CI 1.153-3.104, p=0.001) were independent risk factors for disease-specific survival (DSS). Conclusion: The preoperative NLR is considered to be a useful predictor of postoperative survival in SSCC patients.

8.
PLoS One ; 14(12): e0226383, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31805159

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0210033.].

9.
Medicine (Baltimore) ; 98(50): e18213, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852078

RESUMO

We aimed to investigate the association between excess body mass index (BMI) and papillary thyroid cancer (PTC) in an operative population, and the impact of higher BMI on clinicopathological aggressiveness of PTC.Charts of 10,844 consecutive patients with thyroid nodules undergoing partial or total thyroidectomy between 1993 and 2015 were reviewed. Patients diagnosed with PTC were stratified in 4 groups: BMI < 18.5 (underweight), 18.5 ≤ BMI < 24 (normal-weight), 24 ≤ BMI < 28 (overweight) and BMI ≥ 28(obese). The impacts of high BMI on prevalence and clinicopathological parameters of PTC were retrospectively analyzed in both univariate and multivariate binary logistic regression analysis.For every 5-unit increase in body mass, the odds of risk-adjusted malignance increased by 36.6%. The individuals who were obese and overweight were associated with high risk of thyroid cancer [odds ratio (OR)= 1.982, P < .001; OR= 1.377, P < .001; respectively] compared to normal weight patients, and this positive association was found in both genders. Obesity was independent predictors for tumors larger than 1 cm (OR = 1.562, P < .001) and multifocality (OR = 1.616, P < .001). However, there was no difference in cervical lymph node (LN) metastasis among BMI groups. Crude analysis showed BMI was associated with advanced tumor-node-metastasis (TNM) stage (relative risk, approximately 1.23 per 5 BMI units, P < .001), but this association disappeared after adjusting for confounding factors.Obesity was significantly associated with the risk of PTC in a large, operative population. Higher BMI was significantly associated with larger tumor size and multifocal tumor.


Assuntos
Índice de Massa Corporal , Obesidade/complicações , Câncer Papilífero da Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Tireoidectomia/métodos , Estudos de Casos e Controles , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Estudos Retrospectivos , Câncer Papilífero da Tireoide/etiologia , Câncer Papilífero da Tireoide/cirurgia , Neoplasias da Glândula Tireoide/etiologia , Neoplasias da Glândula Tireoide/cirurgia
11.
Oxid Med Cell Longev ; 2019: 8690746, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772713

RESUMO

Background: Hyper-free fatty acidemia (HFFA) impairs cardiac capillaries, as well as type 2 diabetes mellitus (T2DM). Perilipin 5 (Plin5) maintains metabolic balance of free fatty acids (FFAs) in high oxidative tissues via the states of nonphosphorylation and phosphorylation. However, when facing to T2DM-HFFA, Plin5's role in cardiac microvascular endothelial cells (CMECs) is not defined. Methods: In mice of WT or Plin5-/-, T2DM models were rendered by high-fat diet combined with intraperitoneal injection of streptozocin. CMECs isolated from left ventricles were incubated with high glucose (HG) and high FFAs (HFFAs). Plin5 phosphorylation was stimulated by isoproterenol. Plin5 expression was knocked down by small interfering RNA (siRNA). We determined cardiac function by small animal ultrasound, apoptotic rate by flow cytometry, microvessel quantity by immunohistochemistry, microvascular integrity by scanning electron microscopy, intracellular FFAs by spectrophotometry, lipid droplets (LDs) by Nile red staining, mRNAs by quantitative real-time polymerase chain reaction, proteins by western blots, nitric oxide (NO) and reactive oxygen species (ROS) by fluorescent dye staining and enzyme-linked immunosorbent assay kits. Results: In CMECs, HFFAs aggravated cell injury induced by HG and activated Plin5 expression. In mice with T2DM-HFFA, Plin5 deficiency reduced number of cardiac capillaries, worsened structural incompleteness, and enhanced diastolic dysfunction. Moreover, in CMECs treated with HG-HFFAs, both ablation and phosphorylation of Plin5 reduced LDs content, increased intracellular FFAs, stimulated mitochondrial ß-oxidation, added ROS generation, and reduced the expression and activity of endothelial nitric oxide synthase (eNOS), eventually leading to increased apoptotic rate and decreased NO content, all of which were reversed by N-acetyl-L-cysteine. Conclusion: Plin5 preserves lipid balance and cell survival in diabetic CMECs by regulating FFAs metabolism bidirectionally via the states of nonphosphorylation and phosphorylation.

12.
Nano Lett ; 19(12): 8947-8955, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31694380

RESUMO

In recent years, small nanoparticles (NPs) with a diameter of less than 10 nm have aroused considerable interest in biomedical applications. However, their intratumor performance, as well as the antitumor efficacy, has not been well understood due to their size-dependent pharmacokinetics, which presents a formidable challenge for delivering a comparable amount of different small NPs to tumor tissues. Utilizing the multistage delivery strategy, we construct G3-, G5-, and G7-iCluster delivery systems by using poly(amidoamine) (PAMAM) dendrimers of different generations (G3-, G5-, and G7-PAMAM) as building blocks. The iCluster nanoparticles showed comparable pharmacokinetics and similar initial tumor deposition due to their similarity in size and surface chemistry. After accumulating at a tumor site, individual small dendrimers were released, and thus, their intratumor performance was comparatively investigated. Our results indicated that a subtle change in generation markedly affects their intratumor activities. G5-iCluster outperformed G3-iCluster and G7-iCluster in the treatment efficacy in an orthotopic pancreatic tumor model. The mechanistic study revealed that G3-PAMAM showed reduced particle retention in tumor tissue due to its small size and weak cell internalization, while G7-PAMAM was much less penetrative because of its relatively large size and strong particle-cell interaction. In contrast, G5-PAMAM exhibited balanced tumor penetration, cell internalization, and tumor retention. Our finding highlights the huge influence of the subtle difference of small NPs in their intratumor performance.

13.
Med Sci Monit ; 25: 6775-6781, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31496537

RESUMO

BACKGROUND High-intensity focused ultrasound (HIFU) and plasma radiofrequency ablation (PRA) have been used to treat recurrent allergic rhinitis (AR); however, there is a lack of literature comparing the efficacy of these 2 methods. We assessed and compared the therapeutic effects of HIFU and PRA on recurrent AR. MATERIAL AND METHODS We enrolled 66 patients with recurrent AR at West China Hospital of Sichuan University. Visual analogue score (VAS), pain score, rhinoconjunctivitis quality of life questionnaire (RQLQ), and nasal endoscopy were performed to evaluate the therapeutic effect. RESULTS Nasal endoscopy showed that HIFU and PAR reduced the volume of the inferior turbinate, whereas HIFU reduced the amount of nasal secretions in patients. VAS scores showed that HIFU and PRA nasal congestion symptoms were significantly reduced (P<0.05). The preoperative VAS scores for nasal fluid and sneezing were significantly lower in patients receiving HIFU (P<0.05) than in those receiving PRA (P>0.05). HIFU-treated patients had significantly lower postoperative pain scores than those in the PRA group (P<0.05). RQLQ showed activity, sleep, and non-nasal or ocular symptoms, and both HIFU and PRA patients had significantly lower scores (P<0.05). Nasal symptom scores, actual problems, and mood in the HIFU group were significantly worse than those in the PRA group (P<0.05). However, neither treatment had a significant effect on ocular symptoms (P>0.05). CONCLUSIONS Compared with PRA, HIFU can significantly reduce the nasal symptoms of AR patients, improve the quality of life, and can be used as an adjuvant therapy with better therapeutic effect.

14.
ACS Nano ; 13(8): 8648-8658, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31328920

RESUMO

Lymph nodes (LNs) are normally the primary site of tumor metastasis, and effective delivery of chemotherapeutics into LNs through systemic administration is critical for metastatic cancer treatment. Here, we uncovered that improved perfusion in a primary tumor facilitates nanoparticle translocation to LNs for inhibiting tumor metastasis. On the basis of our finding that an iCluster platform, which undergoes size reduction from ∼100 nm to ∼5 nm at the tumor site, markedly improved particle perfusion in the interstitium of the primary tumor, we further revealed in the current study that such tumor-specific size transition promoted particle intravasation into tumor lymphatics and migration into LNs. Quantitative analysis indicated that the drug deposition in LNs after iCluster treatment was significantly higher in the presence of a primary tumor in comparison with that after primary tumor resection. Early intervention of metastatic 4T1 tumors with iCluster chemotherapy and subsequent surgical resection of the primary tumor resulted in significantly extending animal survival, with 4 out of the 10 mice remaining completely tumor-free for 110 days. Additionally, in the more clinical relevant late metastatic model, iCluster inhibited the metastatic colonies to the lungs and extended animal survival time. This finding provides insights into the design of more effective nanomedicines for treating metastatic cancer.

15.
Medicine (Baltimore) ; 98(27): e16261, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277148

RESUMO

BACKGROUND: Nowadays most of the intensive care units (ICUs) operate as a closed format in comparison to an open format. The new concept of a closed ICU is where patients are admitted under the full responsibility of a trained intensivist, whereas an open ICU is where patients are admitted under the care of another attending physician and intensivists are just available for consultation. In this analysis, we aimed to systematically compare mortality rate and other clinical features observed in open vs closed ICU formats. METHODS: Biomedical and pharmacological bibliographic database Excerpta Medica database (EMBASE), Medical Literature Analysis and Retrieval System Online (MEDLINE), the Cochrane Central and www.ClinicalTrials.gov were searched for required English publications. Mortality, the frequency of patients requiring mechanical ventilation, central line, arterial line and pulmonary arterial catheter were assessed respectively. Statistical analysis was carried out by the RevMan software. Odds ratios (OR) with 95% confidence intervals (CIs) were used to represent the data following analysis. RESULTS: Five studies with a total number of 6160 participants enrolled between years 1992 to 2007 were included. Results of this analysis showed that mortality rate was significantly higher in the open format ICU (OR: 1.31, 95% CI: 1.17-1.48; P = .00001) (using a fixed effect model) and (OR: 1.31, 95% CI: 1.09-1.59; P = .005) (using a random effect model). Closed format ICUs were associated with significantly higher number of patients that required central line (OR: 0.56, 95% CI: 0.34-0.92; P = .02). Patients requiring mechanical ventilation (OR: 1.08, 95% CI: 0.65-1.78; P = .77), patients requiring arterial line (OR: 1.05, 95% CI: 0.49-2.29; P = .89) and patients requiring pulmonary arterial catheter (OR: 0.86, 95% CI: 0.40-1.87; P = .71) were similar in the open vs the closed setting. CONCLUSION: This analysis showed that mortality rate was significantly higher in an open as compared to a closed format ICU. However, the frequency of patients requiring mechanical ventilation, arterial line and pulmonary arterial catheter was similarly observed. Larger trials are expected to further confirm those hypotheses.


Assuntos
Estado Terminal/mortalidade , Unidades de Terapia Intensiva/estatística & dados numéricos , Inovação Organizacional , Saúde Global , Mortalidade Hospitalar/tendências , Humanos , Tempo de Internação/tendências , Taxa de Sobrevida/tendências
16.
Nano Lett ; 19(8): 5356-5365, 2019 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-31286779

RESUMO

Certain chemotherapeutics (e.g., oxaliplatin, OXA) can evoke effective antitumor immunity responses by inducing immunogenic cell death (ICD). Unfortunately, tumors always develop multiple immunosuppressive mechanisms, such as the upregulation of immunosuppressive factors, to counteract the effects of immunogenic chemotherapy. Indoleamine 2,3-dioxygenase-1 (IDO1), a tryptophan catabolic enzyme overexpressed in tumor-draining lymph nodes (TDLNs) and tumor tissues, plays a pivotal role in the generation of the immunosuppressive microenvironment. Reversing IDO1-mediated immunosuppression may strengthen the ICD-induced immune response. Herein, we developed a nanoenabled approach for IDO1 pathway interference, which is accomplished by delivering IDO1 siRNA to both TDLNs and tumor tissues with the help of cationic lipid-assisted nanoparticles (CLANs). We demonstrated that the contemporaneous administration of OXA and CLANsiIDO1 could achieve synergetic antitumor effects via promoting dendritic cell maturation, increasing tumor-infiltrating T lymphocytes and decreasing the number of regulatory T cells in a subcutaneous colorectal tumor model. We further proved that this therapeutic strategy is applicable for the treatment of orthotopic pancreatic tumors and offers a strong immunological memory effect, which can provide protection against tumor rechallenge.

17.
Eur Arch Otorhinolaryngol ; 276(10): 2819-2826, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31332548

RESUMO

BACKGROUND: The discomfort and complications have always been problems for nasal packing materials. This study provided a new nasal packing material called high expansion degradable cotton (HEDC). METHODS: Nasal endoscopic surgery was used to establish a dog model of nasal bleeding, and wound surfaces were filled with Merocel, Nasopore and HEDC, respectively. Intraoperative and postoperative bleeding of 24 h was calculated. We evaluate the absorbability score, adhesion score, infection sore and nasal mucosal epithelium in postoperative 3, 7, 14 and 28 days. HE staining and electron microscopy were used to evaluate the recovery of nasal mucosa. RESULTS: There was no significant difference in nasal bleeding between HEDC, Merocel and Nasopore. Nasal endoscopic examination revealed HEDC absorbability of score, adhesion score, infection score were significantly lower than Merocel and Nasopore. The epithelialization time of HEDC was significantly shorter than that of Merocel and Nasopore. HE staining showed that HEDC and Nasopore could significantly reduce scar hyperplasia on the wound surface. The results of electron microscopy suggested that HEDC could protect the edge cilia of the wound. CONCLUSION: HEDC could be used as new choice for hemostasis after nasal endoscopic surgery, which could reduce nasal epithelialization time, and protect wound edge cilia.


Assuntos
Epistaxe/terapia , Formaldeído/administração & dosagem , Procedimentos Cirúrgicos Nasais/efeitos adversos , Cirurgia Endoscópica por Orifício Natural/efeitos adversos , Álcool de Polivinil/administração & dosagem , Hemorragia Pós-Operatória/terapia , Animais , Cães , Técnicas Hemostáticas , Hemostáticos/administração & dosagem , Humanos , Modelos Animais , Procedimentos Cirúrgicos Nasais/métodos , Cirurgia Endoscópica por Orifício Natural/métodos , Aderências Teciduais , Resultado do Tratamento
18.
Onco Targets Ther ; 12: 4631-4641, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31354296

RESUMO

Background: The chemokine family plays an important role in the growth, invasion, and metastasis of tumors. However, most studies have only focused on a few genes or a few gene loci, and thus could not reveal the associations between functional polymorphisms of chemokine family members and tumor progression. This study aimed to determine the associations between single nucleotide polymorphisms (SNPs) of chemokine family members and the prognosis of esophageal cancer (EC). Methods: The Cox risk proportional model and log-rank test were used to analyze the associations of 16 potentially functional SNPs in 13 genes from the chemokine family with the survival of 729 Chinese patients with EC. Results: Prognostic analysis on the 16 SNPs showed that different genotypes of 5 SNPs were associated with patients' survival and the risk of death. Multivariate Cox regression analysis showed that the risk of death was higher in CCL26rs2302009 genotype A/C carriers than in A/A carriers and it was also higher in CX3CL1rs2239352 genotype T/T carriers than in C/C carriers. Stepwise Cox regression analysis showed that CCL26rs2302009 genotype A/C was an independent prognostic factor of EC, and its association with increased risk of death was stronger in patients who were ≤60 years old, female, with tumors located in the middle part of esophagus, with undifferentiated or poorly differentiated tumors, with early-stage pathologic type disease, with the longest diameter of tumor ≤5cm than in their counterparts. Conclusion: These findings suggest that CCL26rs2302009 may be a candidate biomarker for EC and its effect on death risk are associated with the histological grade, pathologic type, and the longest diameter of tumor.

19.
Nat Commun ; 10(1): 2367, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31147539

RESUMO

Nocturnin (NOCT) is a rhythmically expressed protein that regulates metabolism under the control of circadian clock. It has been proposed that NOCT deadenylates and regulates metabolic enzyme mRNAs. However, in contrast to other deadenylases, purified NOCT lacks the deadenylase activity. To identify the substrate of NOCT, we conducted a mass spectrometry screen and report that NOCT specifically and directly converts the dinucleotide NADP+ into NAD+ and NADPH into NADH. Further, we demonstrate that the Drosophila NOCT ortholog, Curled, has the same enzymatic activity. We obtained the 2.7 Šcrystal structure of the human NOCT•NADPH complex, which revealed that NOCT recognizes the chemically unique ribose-phosphate backbone of the metabolite, placing the 2'-terminal phosphate productively for removal. We provide evidence for NOCT targeting to mitochondria and propose that NADP(H) regulation, which takes place at least in part in mitochondria, establishes the molecular link between circadian clock and metabolism.

20.
Bioresour Technol ; 286: 121380, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31048264

RESUMO

A comparative study of rhamnolipid congener synthesis was performed using the neotype Pseudomonas aeruginosa ATCC 10145 and two marine isolates (1A01151 and 1A00364). Compared with the neotype, 1A01151 and 1A00364 showed increased production of rhamnolipids containing higher proportion of congeners with longer fatty acid chains (C10-C12 and C10-C12:1) and/or di-rhamnose moiety. These could reduce surface tension of water to lower minimum values of 21.3 mN m-1 and 25.7 mN m-1. The comparative profile of rhamnolipid congener composition, fatty acid content and gene expression suggested that elevated expression of rhlAB and rhlC throughout the fermentation process and enhanced accumulation of dTDP-l-rhamnose and fatty acid precursors (C12 and C12:1) at the onset of rhamnolipid accumulation were related to improved rhamnolipid production and surface-active property. This work provides insights into the metabolic relationship between rhamnolipids and related precursor biosynthesis, and could therefore be beneficial for process optimization for efficient rhamnolipid congener production.


Assuntos
Proteínas de Bactérias , Pseudomonas aeruginosa , Glicolipídeos , Ramnose
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