Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.984
Filtrar
1.
Food Chem ; 337: 127986, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-32920269

RESUMO

We have developed a novel approach that involves inception-resnet network (IRN) modeling based on infrared spectroscopy (IR) for rapid and specific detection of the fish allergen parvalbumin. SDS-PAGE and ELISA were used to validate the new method. Through training and learning with parvalbumin IR spectra from 16 fish species, IRN, support vector machine (SVM), and random forest (RF) models were successfully established and compared. The IRN model extracted highly representative features from the IR spectra, leading to high accuracy in recognizing parvalbumin (up to 97.3%) in a variety of seafood matrices. The proposed infrared spectroscopic IRN (IR-IRN) method was rapid (~20 min, cf. ELISA ~4 h) and required minimal expert knowledge for application. Thus, it could be extended for large-scale field screening and identification of parvalbumin or other potential allergens in complex food matrices.

2.
Neural Regen Res ; 16(1): 179-185, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32788474

RESUMO

Nogo-A is considered one of the most important inhibitors of myelin-associated axonal regeneration in the central nervous system. It is mainly expressed by oligodendrocytes. Although previous studies have found regulatory roles for Nogo-A in neurite outgrowth inhibition, neuronal homeostasis, precursor migration, plasticity, and neurodegeneration, its functions in the process of oxidative injury are largely uncharacterized. In this study, oligodendrocytes were extracted from the cerebral cortex of newborn Sprague-Dawley rats. We used hydrogen peroxide (H2O2) to induce an in vitro oligodendrocyte oxidative damage model and found that endogenously expressed Nogo-A is significantly upregulated in oligodendrocytes. After recombinant virus Ad-ZsGreen-rat Nogo-A infection of oligodendrocytes, Nogo-A expression was increased, and the infected oligodendrocytes were more susceptible to acute oxidative insults and exhibited a markedly elevated rate of cell death. Furthermore, knockdown of Nogo-A expression in oligodendrocytes by Ad-ZsGreen-shRNA-Nogo-A almost completely protected against oxidative stress induced by exogenous H2O2. Intervention with a Nogo-66 antibody, a LINGO1 blocker, or Y27632, an inhibitor in the Nogo-66-NgR/p75/LINGO-1-RhoA-ROCK pathway, did not affect the death of oligodendrocytes. Ad-ZsGreen-shRNA-Nogo-A also increased the levels of phosphorylated extracellular signal-regulated kinase 1/2 and inhibited BCL2 expression in oligodendrocytes. In conclusion, Nogo-A aggravated reactive oxygen species damage in oligodendrocytes, and phosphorylated extracellular signal-regulated kinase 1/2 and BCL2 might be involved in this process. This study was approved by the Ethics Committee of Peking University People's Hospital, China (approval No. 2018PHC081) on December 18, 2018.

3.
Exp Neurol ; : 113506, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065077

RESUMO

Overactivated microglia and neuroinflammation are considered to play a crucial role in the progression of Alzheimer's disease (AD). Triggering receptor expressed on myeloid cells-2 (TREM2), a type I transmembrane receptor, expressed uniquely by microglia in the brain, is involved in the neuroinflammatory responses of AD. In this study, to further explore the precise effects of TREM2 on neuroinflammation and the underlying mechanisms in AD, we employed a lentiviral-mediated strategy to overexpress TREM2 in the brain of APPswe/PS1dE9 (APP/PS1) transgenic mice and cultured BV2 cells. Our results showed that TREM2 overexpression rescued cognitive deficits, decreased ß-amyloid (Aß) plaques deposition, reduced synaptic and neuronal loss, as well as ameliorated neuroinflammation. The mechanistic study revealed that these protective effects were likely attributed to inhibition of neuroinflammatory responses through the JAK/STAT/SOCS signaling pathway and subsequent attenuation of pro-inflammatory cytokines. Furthermore, suppression of neuroinflammation might be ascribed to activation of the M2 microglia, as the levels of M2 phenotype markers Arg-1, IL-10 and Ym1 were markedly increased. Similarly, overexpression of TREM2 in BV2 cells also promoted M2 polarization and led to the alleviation of M1 microglial inflammatory responses through JAK/STAT/SOCS signaling pathway, suggesting that TREM2 is an important factor in shifting the microglia from M1 to M2 phenotype. Taken together, our results further provide insights into the role of TREM2 in AD pathogenesis and highlight TREM2 as a potential target against AD.

4.
Biomed Chromatogr ; : e5005, 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33067801

RESUMO

Lupeol, a phytosterol and triterpene, is widely found in edible fruits and vegetables, and has been reported to exhibit a spectrum of pharmacological activities against various disease conditions. In the present study, a derivative generated by the reaction of lupeol with p-toluenesulfonyl isocyanate (PTSI) was ionizable and fragmentable in the negative mode by electrospray ionization/tandem mass spectrometry (ESI/MS/MS). Based on this simple chemical derivatization, a liquid chromatography-electrospray ionization/tandem mass spectrometry (LC-ESI/MS/MS) method was developed and validated for the quantification of lupeol in rat plasma. The calibration curves were linear (r2 > 0.999) over concentrations from 2.5 to 250 ng/mL for lupeol. The method had an accuracy of 96.0-109.4%, and the intra- and inter-day precision (RSD%) were within ± 15%. The stability data showed no significant degradation occurred under the experimental conditions. The mean recoveries at three QC levels were within 88.7-95.7%. No significant matrix effects (105.3-109.8%) were observed in rat plasma. This method was successfully applied to the pharmacokinetic study of lupeol in rat plasma after oral administration.

5.
Cell Biochem Funct ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047358

RESUMO

MiR-140-5p is high expressed in normal fracture healing, but its specific role and mechanism in tissue-to-bone healing are rarely reported. Therefore, this study investigated the effects of miR-140-5p on tissue-to-bone healing. Clone formation experiment, flow cytometry, Alizarin Red S Staining and Oil Red O Staining were performed to investigate the biological characteristics of mouse embryonic bone marrow mesenchymal stem cells C3H10T1/2. MiR-140-5p mimic was transfected into osteogenic medium (OS)-treated C3H10T1/2 cells to investigate the effects of miR-140-5p on osteogenic differentiation. MiR-140-5p transgenic mouse model and the transgenic fracture model were established, and the effects of miR-140-5p on osteogenic differentiation, bone mineral density (BMD) and bone mass of bone tissues were detected by haematoxylin and eosin staining and computed tomography scan. The expressions of osteocalcin, differentiation-related genes (Runx2, ALP, Spp1 and Bglap3) and miR-140-5p were determined by quantitative real-time polymerase chain reaction. C3H10T1/2 cells showed the abilities of forming cloned differentiation of osteogenesis, fat cells, and its phenotypes including CD44, CD90.1 and Sca-1 but excluding CD45 haematopoietic stem cell marker. Overexpression of miR-140-5p promoted the expressions of differentiation-related genes and calcium deposition of OS-treated C3H10T1/2 cells. MiR-140-5p increased the expression of osteocalcin, BMD and bone mass and promoted bone healing of miR-140-5p-transgenic mice with fracture. MiR-140-5p promoted osteogenic differentiation of mouse embryonic bone marrow mesenchymal stem cells and post-fracture healing in mice. SIGNIFICANCE OF THE STUDY: C3H10T1/2 cells showed the abilities of forming cloned differentiation of osteogenesis, fat cells and its phenotypes including CD44, CD90.1 and Sca-1 but excluding CD45 haematopoietic stem cell marker. Overexpression of miR-140-5p promoted the expressions of differentiation-related genes and calcium deposition of osteogenic medium-treated C3H10T1/2 cells. MiR-140-5p increased the expression of osteocalcin and bone mineral density and bone mass and promoted bone healing of miR-140-5p-transgenic mice with fracture. Our results showed that miR-140-5p promoted osteogenic differentiation of mouse embryonic bone marrow mesenchymal stem cells and post-fracture healing in mice, which may be a therapeutic target for treating fractures and promoting bone healing.

6.
Plant J ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33048399

RESUMO

Heat stress occurring at reproductive stages can result in significant and permanent damage to crop yields. However, previous genetic studies in understanding heat stress response and signaling were performed mostly on seedling and plants at early vegetative stages. Here we identify, using a developmentally defined, gain-of-function genetic screen with ~18,000 Arabidopsis thaliana activation-tagged lines, a mutant that maintained productive seed set post severe heat stress at flowering. Genome walking indicated this phenotype was caused by the insertion of 35S enhancers adjacent to a nuclear localized transcription factor AtMYB68. Subsequent overexpression analysis confirmed that AtMYB68, was responsible for the reproductive heat tolerance of the mutant. Furthermore, these transgenic Arabidopsis plants exhibited enhanced ABA sensitivity at and post germination, reduced transpirational water loss during a drought treatment, and enhanced seed yield under combined heat and drought stress at flowering. Ectopic expression of AtMYB68 in Brassica napus driven either by 35S or a heat inducible promoter recapitulated the enhanced reproductive heat stress and drought tolerance phenotypes observed in the transgenic Arabidopsis. The improvement to heat stress is likely due to enhanced pollen viability observed in the transgenic plants. More importantly, the transgenic canola showed significant yield advantages over the non-transgenic controls in multiple location, multiple season field trials under various drought and heat stress conditions. Together these results suggest that AtMYB68 regulate plant stress tolerance at the most important yield determining stage of plant development, and is an effective target for crop yield protection under the current global climate volatility.

8.
J Vet Sci ; 21(5): e78, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33016023

RESUMO

BACKGROUND: Enteritis is one of the most frequently reported symptoms in piglets infected with porcine circovirus type 2 (PCV2), but the immunopathogenesis has not been reported. OBJECTIVES: This study examined the effect of a PCV2 infection on the intestinal mucosal immune function through morphological observations and immune-related molecular detection. METHODS: Morphological changes within the ileum of piglets during a PCV2 infection were observed. The expression of the related-molecules was analyzed using a gene chip. The immunocyte subsets were analyzed by flow cytometry. The secretory immunoglobulin A (SIgA) content was analyzed by enzyme-linked immunosorbent assay. RESULTS: The PCV2 infection caused ileal villus damage, intestinal epithelial cells exfoliation, and an increase in lymphocytes in the lamina propria at 21 days post-infection. Differentially expressed genes occurred in the defense response, inflammatory response, and the complement and coagulation cascade reactions. Most of them were downregulated significantly at the induction site and upregulated at the effector site. The genes associated with SIgA production were downregulated significantly at the induction site. In contrast, the expression of the Toll-like receptor-related genes was upregulated significantly at the effector site. The frequencies of dendritic cells, B cells, and CD8⁺T cells were upregulated at the 2 sites. The SIgA content decreased significantly in the ileal mucosa. CONCLUSIONS: PCV2 infections can cause damage to the ileum that is associated with changes in immune-related gene expression, immune-related cell subsets, and SIgA production. These findings elucidated the molecular changes in the ileum after a PCV2 infection from the perspective of intestinal mucosal immunity, which provides insights into a further study for PCV2-induced enteritis.

9.
J Pineal Res ; : e12698, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33016468

RESUMO

Targeting mitochondrial quality control with melatonin has been found promising for attenuating diabetic cardiomyopathy (DCM), although the underlying mechanisms remain largely undefined. Activation of SIRT6 and melatonin membrane receptors exerts cardioprotective effects while little is known about their roles during DCM. Using high-fat diet-streptozotocin-induced diabetic rat model, we found that prolonged diabetes significantly decreased nocturnal circulatory melatonin and heart melatonin levels, reduced the expressions of cardiac melatonin membrane receptors, decreased myocardial SIRT6 and AMPK-PGC-1α-AKT signaling. 16 weeks of melatonin treatment inhibited the progression of DCM and the following myocardial ischemia-reperfusion (MI/R) injury by reducing mitochondrial fission, enhancing mitochondrial biogenesis and mitophagy via re-activating SIRT6 and AMPK-PGC-1α-AKT signaling. After the induction of diabetes, adeno-associated virus carrying SIRT6-specific small hairpin RNA or luzindole was delivered to the animals. We showed that SIRT6 knockdown or antagonizing melatonin receptors abolished the protective effects of melatonin against mitochondrial dysfunction as evidenced by aggravated mitochondrial fission and reduced mitochondrial biogenesis and mitophagy. Additionally, SIRT6 shRNA or luzindole inhibited melatonin-induced AMPK-PGC-1α-AKT activation as well as its cardioprotective actions. Collectively, we demonstrated that long-term melatonin treatment attenuated the progression of DCM and reduced myocardial vulnerability to MI/R injury through preserving mitochondrial quality control. Melatonin membrane receptors-mediated SIRT6-AMPK-PGC-1α-AKT axis played a key role in this process. Targeting SIRT6 with melatonin treatment may be a promising strategy for attenuating DCM and reducing myocardial vulnerability to ischemia-reperfusion injury in diabetic patients.

10.
Curr Drug Metab ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33038908

RESUMO

BACKGROUND: With significant clinical effects, traditional Chinese medicine (TCM) has been attracting increasing interest of the world's scientific community. However, TCM contains immense amounts of chemical components. It is a great challenge to objectively evaluate of the correlation between the in vivo process and the therapeutic effect of TCM. The purpose of this systematic review was to summarize the recent investigation (from 2017 to 2019) on preclinical pharmacokinetics (PK) of TCM via liquid chromatography coupled with mass spectrometry (LC-MS/MS). METHOD: We reviewed the published articles regarding the PK of TCM by LC-MS/MS. In addition, we summarized information on PK parameter of bioactive components, single herb and traditional Chinese medicine prescriptions. RESULTS: The vast majority of literatures on preclinical PK of TCM use single oral administration, the biological matrix is mostly rat plasma, and the main PK parameters include AUC, Cmax, Tmax and T1/2, etc. Conclusion: Although LC-MS/MS can be used for high-throughput analysis, the characterization of in vivo processes of TCM is still has a long way. With the advantages of high sensitivity, high specificity and simple operation, the increasingly mature LC-MS/MS technology will play an important role in the PK of TCM.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33040244

RESUMO

OBJECTIVES: It is imperative to understand the influence of second-generation cryoballoon (CB-2) and contact-force sensing radiofrequency ablation (CF-RF) on clinical outcomes in atrial fibrillation (AF). This updated meta-analysis of randomized controlled trials (RCTs) examined the efficacy and safety of CB-2 vs. CF-RF in patients with AF. METHODS: RCTs on the use of CB-2 vs. CF-RF in patients with AF were included. The primary outcome was the recurrence of AF, and the key secondary outcomes included serious complications, acute pulmonary vein isolation (PVI), procedure duration, and fluoroscopy time. RESULTS: A total of 261 articles were identified, and five studies with a total of 845 participants were included in the study. A total of 93% of participants had paroxysmal AF, 7% of participants had persistent AF, and none of participants had permanent AF. There were 499 participants in the CB-2 arm and 346 in the CF-RF arm. AF recurrence was comparable in the CB-2 group (30.3%) and the CF-RF group (29.2%) (OR = 0.93; 95%CI = 0.56-1.54; P = 0.79; I2 = 48%). There were no statistical differences in acute PVI (P = 0.92; I2 = 0%) and serious complications (P = 0.87; I2 = 47%) between the two groups. The procedure duration was shorter in the CB-2 group than in the CF-RF group (MD = - 13.39; 95%CI = - 15.58, - 7.19; P < 0.0001; I2 = 59%). CONCLUSION: Our study demonstrated that CB-2 and CF-RF had comparable recurrences of AF and similar incidences of serious complications in AF patients during the ablation process.

12.
Psychophysiology ; : e13700, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33040366

RESUMO

Numerous investigators have tested contentions that angry faces capture early attention more completely than happy faces do in the context of other faces. However, syntheses of studies on early event-related potentials related to the anger superiority hypothesis have yet to be conducted, particularly in relation to the N200 posterior-contralateral (N2pc) component which provides a reliable electrophysiological index related to orienting of attention suitable for testing this hypothesis. Fifteen samples (N = 534) from 13 studies featuring the assessment of N2pc amplitudes during exposure to angry-neutral and/or happy-neutral facial expression arrays were included for meta-analysis. Moderating effects of study design features and sample characteristics on effect size variability were also assessed. N2pc amplitudes elicited by affectively valenced expressions (angry and happy) were significantly more pronounced than those elicited by neutral expressions. However, the mean effect size difference between angry and happy expressions was ns. N2pc effect sizes were moderated by sample age, number of trials, and nature of facial images used (schematic vs. real) with larger effect sizes observed when samples were comparatively younger, more task trials were presented and schematic face arrays were used. N2pc results did not support anger superiority hypothesis. Instead, attentional resources allocated to angry versus happy facial expressions were similar in early stages of processing. As such, possible adaptive advantages of biases in orienting toward both anger and happy expressions warrant consideration in revisions of related theory.

13.
Vaccine ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33041102

RESUMO

Mucosal surfaces of the gastrointestinal tract play an important role in immune homeostasis and defense and may be compromised by enteric disorders or infection. Therapeutic intervention using monoclonal antibody (mAb) offers the potential for treatment with minimal off-target effects as well as the possibility of limited systemic exposure when administered orally. Critically, to achieve efficacy at luminal surfaces, mAb must remain stable and functionally active in the gastrointestinal environment. To better understand the impact of isotype, class, and molecular structure on the intestinal stability of recombinant antibodies, we used an in vitro simulated intestinal fluid (SIF) assay to evaluate a panel of antibody candidates for enteric mAb-based therapeutics. Recombinant IgG1 was the least stable following SIF incubation, while the stability of IgA generally increased upon polymerization, with subtle differences between subclasses. Notably, patterns of variability within and between mAbs suggest that variable regions contribute to mAb stability and potentially mediate mAb susceptibility to proteases. Despite relatively rapid degradation in SIF, mAbs targeting Enterotoxigenic Escherichia coli (ETEC) displayed functional activity following SIF treatment, with SIgA1 showing improved function compared to SIgA2. The results of this study have implications for the design of enteric therapeutics and subsequent selection of lead candidates based upon in vitro intestinal stability assessments.

15.
Adv Mater ; : e2005353, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33043512

RESUMO

Power consumption is one of the most challenging bottlenecks for complementary metal-oxide-semiconductor integration. Negative-capacitance field-effect transistors (NC-FETs) offer a promising platform to break the thermionic limit defined by the Boltzmann tyranny and architect energy-efficient devices. However, it is a great challenge to achieving ultralow-subthreshold-swing (SS) (10 mV dec-1 ) and small-hysteresis NC-FETs simultaneously at room temperature, which has only been reported using the hafnium zirconium oxide system. Here, based on a ferroelectric LiNbO3 thin film with great spontaneous polarization, an ultralow-SS NC-FET with small hysteresis is designed. The LiNbO3 NC-FET platform exhibits a record-low SS of 4.97 mV dec-1 with great repeatability due to the superior capacitance matching characteristic as evidenced by the negative differential resistance phenomenon. By modulating the structure and operating parameters (such as channel length (Lch ), drain-sourse bias (Vds ), and gate bias (Vg )) of devices, an optimized SS from ≈40 to ≈10 mV dec-1 and hysteresis from ≈900 to ≈60 mV are achieved simultaneously. The results provide a new potential method for future highly integrated electronic and optical integrated energy-efficient devices.

16.
Artigo em Inglês | MEDLINE | ID: mdl-33044585

RESUMO

PURPOSE: Vein graft failure (VGF) is an important limitation for coronary artery bypass graft (CABG) surgery. Inhibition of the excessive proliferation and migration of venous smooth muscle cells (SMCs) is an effective strategy to alleviate VGF during the CABG perioperative period. In the present study, we aimed to explore the role and potential mechanism of all-trans retinoic acid (ATRA) on preventing vein grafts stenosis. METHODS: The autogenous vein grafts model was established in the right jugular artery of rabbits. Immunohistochemistry staining and western blot assays were used to detected the protein expression, while real-time PCR assay was applied for mRNAs expression detection. The interaction between proteins was identified by co-immunoprecipitation assay. The Cell Counting Kit-8 and wound-healing assays were used to investigate the role of ATRA on human umbilical vein smooth muscle cells (HUVSMCs) function. Cell cycle progression was identified by flow cytometry assay. RESULTS: Vein graft stenosis and SMCs hyperproliferation were confirmed in vein grafts by histological and Ki-67 immunohistochemistry assays. Treatment of ATRA (10 mg/kg/day) significantly mitigated the stenosis extent of vein grafts, demonstrated by the decreased thickness of intima-media, and decreased Ki-67 expression. ATRA could repress the PDGF-bb-induced excessive proliferation and migration of HUVSMCs, which was mediated by Rb-E2F dependent cell cycle inhibition. Meanwhile, ATRA could reduce the interaction between KLF5 and RARα, thereby inhibiting the function of cis-elements of KLF5. KLF5-induced inducible nitric oxide synthase (iNOS) expression activation could be significantly inhibited by ATRA. CONCLUSIONS: These results suggested that ATRA treatment may represent an effective prevention and therapy avenue for VGF.

17.
J Infect Dev Ctries ; 14(9): 963-967, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-33031081

RESUMO

INTRODUCTION: COVID-19 has become a global health security issue, it has caused more than half a million deaths worldwide so far, the treatment strategies are the most concerned issues for clinicians. In this study, the treatments and outcomes in 40 pediatric patients diagnosed with COVID-19 and treated with different drugs were evaluated. METHODOLOGY: All cases were diagnosed with COVID-19 nucleic acid positive by using RT-PCR or clinical manifestations, imaging specific characteristics and epidemiological clinical diagnosis. The biological information and first symptom of all cases were collect. A variety of treatments were employed and the outcomes were evaluated by Cox regression analysis. Multivariable analysis was performed to evaluate cure rate at 14 days with different drug treatment. RESULTS: The average length of hospital stay was 10.4 days. The cure rate was increased with the treatment time extended and 90% of pediatric patients were cured and discharged after 14 days' treatment. And multivariable analysis results proved that none of the covariates were related to the cure rate at 14 days with different drug treatment since p values were over 0.05. CONCLUSIONS: Multivariable analysis suggested that the present drug treatments cannot significantly shorten the clinical cure time and improve the cure rate of children with COVID-19.

18.
J Hypertens ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33031177

RESUMO

OBJECTIVE: To investigate the associations of sodium excretion with blood pressure, mortality and cardiovascular diseases in Chinese population. METHODS: We studied 39 366 individuals aged 35-70 years from 115 urban and rural communities in 12 centers across mainland China. Trained research staff conducted face-to-face interview to record baseline information of all participants based on questionnaires, and collected their morning fasting urine samples to estimate 24-h sodium excretion (24hUNaE). Multivariable frailty Cox regression accounting for clustering by centre was performed to examine the association between estimated 24hUNaE and the primary composite outcome of death and major cardiovascular events in a Chinese population. RESULTS: Mean 24hUNaE was 5.68 (SD 1.69) g/day. After a median follow-up of 8.8 years, the composite outcome occurred in 3080 (7.8%) participants, of which 1426 (3.5%) died and 2192 (5.4%) suffered from cardiovascular events. 24hUNaE was positively associated with increased SBP and DBP. Using the 24hUNaE level of 4-4.99 g/day as the reference group, a 24hUNaE of either lower (<3 g/day) or higher (≥7 g/day) was associated with an increased risk of the composite outcome with a hazard ratio of 1.22 (95% confidence interval: 1.01-1.49) and 1.15 (95% confidence interval: 1.01-1.30), respectively. A similar trend was observed between 24hUNaE level and risk of death or major cardiovascular events. CONCLUSION: These findings support a positive association between estimated urinary sodium excretion and blood pressure, and a possible J-shaped pattern of association between sodium excretion and clinical outcomes, with the lowest risk in participants with sodium excretion between 3 and 5 g/day.

19.
Thorac Cancer ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33034409

RESUMO

BACKGROUND: The aim of this study was to explore whether the ratio between negative and positive lymph nodes (RNP ) could predict the overall survival (OS) of esophageal cancer (EC) patients with lymph node metastasis following esophagectomy. METHODS: We utilized the Surveillance, Epidemiology and End Results (SEER) database to include the records of 2374 patients with lymph node metastases post-surgery. All patients were randomly assigned into the training cohort (n = 1424) and validation cohort (n = 950). Multivariate Cox regression analyses were performed to identify independent prognostic factors. A novel RNP -based TRNP M staging system was proposed. The prognostic value of N, RNP , TNM and TRNP M staging system was evaluated using the linear trend χ2 test, likelihood ratio χ2 test, and Akaike information criterion (AIC) to determine the potential superiorities. We constructed nomograms to predict survival in both cohorts, and the calibration curves confirmed the predictive ability. RESULTS: Univariate analyses showed that N and RNP stage significantly influenced the OS of patients. Multivariate analyses revealed that RNP was an independent prognostic predictor in both the training and validation cohorts. For the stratification analysis in the two cohorts, we found significant differences in the prognosis of patients in different RNP groups on the basis of the different N stages and the number of dissected lymph nodes. In addition, the lower AIC value of RNP stage and TRNP M staging system represented superior predictive accuracy for OS than the N stage and TNM staging system, respectively. Furthermore, the calibration curves for the probability of three- and five-year survival showed good consistency between nomogram predictive abilities and actual observation. CONCLUSIONS: We demonstrated that compared to the classical pathological lymph nodal staging system, the RNP stage showed superior predictive accuracy for OS and can serve as a more effective prognostic guidance for lymph node positive EC patients.

20.
Sci Rep ; 10(1): 16754, 2020 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028909

RESUMO

L-arginine/NOS/NO signaling pathway plays a critical role in controlling variety of vascular diseases. However, whether NOS inhibition by L-NAME suppresses late embryonic development is undefined. The aim of this study is to determine whether NOS inhibition by L-NAME is critical for late embryonic rat hind limb development. The pregnant rat at E13.5 administrated L-NAME by consecutive intraperitoneal injection. The embryos been harvested from E16.5 to E 20.5. Hematoxylin and Eosin Staining, Immunofluorescence and Immunohistochemistry performed to determine hind limb Vasculogenesis, HUVEC culture, Adenoviral PFKFB3 infection, Real time PCR and western blot were performed to determine whether L-arginine/NOS/NO pathway controlling late embryonic hind limb development through PFKFB3 mediated angiogenetic pathway. NOS inhibition by L-NAME resulting in late embryonic hind limb developmental defects characterized by severe hemorrhage. The in vivo studies showed that NOS inhibition strongly suppressed hind limb angiogenetic remodeling by impairing differentiation of endothelial cells and smooth muscle cells, and extracellular matrix synthesis. For underlie mechanism, our studies indicated that L-NAME treatment dramatically suppresses PFKFB3 expression in hematopoietic progenitor cells, tubulogenetic endothelial cells and smooth muscle cells. Knockdown of PFKFB3 dramatically inhibits the expression of angiogenetic genes, as well as tubulogenesis and extracellular matrix related genes. Taken together, our data in this study demonstrated that L-arginine-eNOS-NO pathway is important for rat hind limb development during late embryonic stage. This could be both a useful animal model and a promising therapeutic treatment for defects of late embryonic developmental hind limbs.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA