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1.
BMC Psychiatry ; 20(1): 544, 2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213416

RESUMO

BACKGROUND: Epidemiological studies have shown increased risk of suicide in cancer patients compared with the general population. The present study aimed to examine the association between physical symptoms and suicidal ideation in Chinese hospitalized cancer patients and test the modifying effect of health self-efficacy on the association. METHODS: A cross-sectional study was conducted with 544 hospitalized cancer patients in two general hospitals in northeast China via face-to-face interviews. Suicidal ideation was measured by using the first four items on the Yale Evaluation of Suicidality scale and then dichotomized into a positive and negative score. Multivariate logistic regression analyses were conducted to examine the impacts of physical symptoms, health self-efficacy, and their interactions on suicidal ideation. RESULTS: The suicidal ideation rate was 26.3% in the enrolled cancer patients. Logistic regression showed that insomnia (aOR = 1.84, 95% CI 1.13 to 3.00, p = 0.015) and lack of appetite (aOR = 2.14, 95% CI 1.26 to 3.64, p = 0.005) were significantly associated with suicidal ideation. Low health self-efficacy had a marginally significant exaggerating effect on the association between pain and suicidal ideation (aOR = 2.77, 95% CI 0.99 to 7.74, p = 0.053), after adjusting for significant socio-demographics, clinical characteristics, and depression. CONCLUSIONS: These findings demonstrate significant associations between physical symptoms (insomnia and/or lack of appetite) and suicidal ideation and highlight the potential modifying role of health self-efficacy in the identification and prevention of suicide among cancer patients.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33181550

RESUMO

PURPOSE: The aim of this study was to evaluate choroidal and retinal microvasculature with optical coherence tomography angiography (OCTA) after panretinal photocoagulation (PRP) for diabetic retinopathy in a primarily Hispanic and Asian population. DESIGN: Retrospective study. METHODS: Eyes were examined by OCTA in the macula (3 × 3 mm) just before PRP treatment and 1 to 3 months afterwards. Choroidal thickness (CT) and central retinal thickness (CRT) were measured. Choroidal flow signal voids (CFSV) and choriocapillaris flow signal voids (CCFSV) were acquired. Retinal microvasculature parameters, including superficial and deep vessel density, superficial and deeper perfusion density, foveal avascular zone area, perimeter and circularity, were calculated. Ocular examinations and demographic information were analyzed. RESULTS: CT at a location 1000 µm temporal to the fovea increased significantly after PRP (from 278.64 µm to 313.44 µm, P = 0.026). CCFSV increased slightly from (46.72 ±â€Š8.52)% to (47.07 ±â€Š10.77)%, but the difference was not statistically significant (P = 0.782). A similar finding was observed in CFSV (increase from 35.81% to 36.64%, P = 0.165). The change in all retinal microvasculature parameters was also not significant. Best-corrected visual acuity (BCVA) decreased from 0.218 ±â€Š0.153 to 0.262 ±â€Š0.147 (P = 0.034). Increased CRT (from 245.41 ±â€Š33.18 µm to 251.14 ±â€Š38.97 µm, P = 0.007) was observed. The change in CRT positively correlated with pre-PRP CRT (r = 0.434, P = 0.019) and BCVA reduction (r = 0.418, P = 0.024). Neither BCVA reduction nor CRT increase correlated with OCTA metrics. CONCLUSIONS: OCTA demonstrates redistribution of choroidal circulation from the periphery to the macula after PRP, with increased macular CT and stable choroidal blood flow density. Eyes with greater macular thickness are more likely to experience an increase in CRT.

3.
Technol Cancer Res Treat ; 19: 1533033820971306, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33174521

RESUMO

BACKGROUND: In the present study, we aimed to find an effective target for the treatment of tongue cancer using gene chip screening and signal pathway research. METHODS: We used microarray screening and gene expression profile analyses to find important differentially expressed genes in tongue cancer. We constructed a protein-protein interaction network, and used enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes to screen for important genes. We then silenced the genes of interest in SCC154 cells to study the relationship with the Phosphatidylinositol 3-kinase/Akt signal pathway. Western blot analyses, the 3-(4,5Dimethylthiazol-yl)-2,5Dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) test, and immunofluorescence assays were used to compare the expression levels of Phosphatidylinositol 3-kinase/Akt signal pathway-related proteins, cell viability, and cell proliferation ability in normal SCC154 cells, Si-RNA SCC154 cells, and gene-silenced SCC154 cells. The scratch test, Transwell test, and western blotting were used to determine migration, invasion, and carcinogenesis. RESULTS: Using GSE9844, GSE13601, and GSE31056 gene chips, we identified 93 upregulated genes and 76 downregulated genes in tongue cancer. Using the protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we further identified 47 differentially expressed genes. Using Kaplan-Meier plotter online tools, we also identified 3 genes (SPP1, Recombinant Human Secreted Phosphoprotein 1; PLAU, plasminogen activator urinary; and APP, amyloid precursor protein). Compared with normal SCC154 cells and Si-RNA control SCC154 cells, the expressions of Phosphatidylinositol 3-kinase/Akt pathway proteins in si-SPP1 SCC154 cells were significantly decreased (*P < 0.05), and the protein activities and proliferation abilities were also significantly decreased (*P < 0.05), while the migration ability, invasion ability, and cancer forming ability were significantly increased (*P < 0.05). CONCLUSION: Inhibition of the SPP1 gene may have a therapeutic effect on tongue cancer, and could be an effective target for the treatment of this disorder.

4.
Proc Natl Acad Sci U S A ; 117(44): 27412-27422, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33087562

RESUMO

Nuclear receptor Nur77 participates in multiple metabolic regulations and plays paradoxical roles in tumorigeneses. Herein, we demonstrated that the knockout of Nur77 stimulated mammary tumor development in two mouse models, which would be reversed by a specific reexpression of Nur77 in mammary tissues. Mechanistically, Nur77 interacted and recruited corepressors, the SWI/SNF complex, to the promoters of CD36 and FABP4 to suppress their transcriptions, which hampered the fatty acid uptake, leading to the inhibition of cell proliferation. Peroxisome proliferator-activated receptor-γ (PPARγ) played an antagonistic role in this process through binding to Nur77 to facilitate ubiquitin ligase Trim13-mediated ubiquitination and degradation of Nur77. Cocrystallographic and functional analysis revealed that Csn-B, a Nur77-targeting compound, promoted the formation of Nur77 homodimer to prevent PPARγ binding by steric hindrance, thereby strengthening the Nur77's inhibitory role in breast cancer. Therefore, our study reveals a regulatory function of Nur77 in breast cancer via impeding fatty acid uptake.

5.
J Clin Invest ; 130(11): 5782-5799, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33016927

RESUMO

Glioblastoma multiforme (GBM) heterogeneity causes a greater number of deaths than any other brain tumor, despite the availability of alkylating chemotherapy. GBM stem-like cells (GSCs) contribute to GBM complexity and chemoresistance, but it remains challenging to identify and target GSCs or factors that control their activity. Here, we identified a specific GSC subset and show that activity of these cells is positively regulated by stabilization of methyl CpG binding domain 3 (MBD3) protein. MBD3 binds to CK1A and to BTRCP E3 ubiquitin ligase, triggering MBD3 degradation, suggesting that modulating this circuit could antagonize GBM recurrence. Accordingly, xenograft mice treated with the CK1A activator pyrvinium pamoate (Pyr-Pam) showed enhanced MBD3 degradation in cells expressing high levels of O6-methylguanine-DNA methyltransferase (MGMT) and in GSCs, overcoming temozolomide chemoresistance. Pyr-Pam blocked recruitment of MBD3 and the repressive nucleosome remodeling and deacetylase (NuRD) complex to neurogenesis-associated gene loci and increased acetyl-histone H3 activity and GSC differentiation. We conclude that CK1A/BTRCP/MBD3/NuRD signaling modulates GSC activation and malignancy, and that targeting this signaling could suppress GSC proliferation and GBM recurrence.

6.
Sci Total Environ ; 755(Pt 1): 142456, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-33017760

RESUMO

Field measurements were conducted near Qingdao Port to characterize the particulate air pollutants, assess the spatial and seasonal characteristics of the pollutants, and identify the contribution from ship traffic emissions. By utilizing multiple statistical methods and data collected at two sites in Qingdao, we comprehensively explored the PM2.5 seasonal characteristics and source apportionments of different PM2.5 constituents, especially those originating from ship emissions, and identified potential source regions for samples collected in Qingdao. In this study, 118 concurrent daily PM2.5 samples were collected from August 2018 to May 2019 at a port site (QH) and a coastal background site (BG). Vanadium (V) and Nickel (Ni) are the dominant metal elements from crude oil and crude oil combustion emissions. The significant correlations between V and Ni at both sampling sites, indicating that shipping emissions have a significant impact on the port and background area. Additionally, Ni and other metals showed significant correlations at the BG site, implying Ni also emission from the land-based oil at this site. The positive matrix factorization (PMF) model identified six main sources for the PM2.5 samples in Qingdao, and they are coal combustion, industrial emissions/mineral dust, marine vessel emissions, secondary aerosols/biomass burning, sea salt/crustal emissions, and vehicle exhaust, respectively. Marine vessel emissions were the dominant contributor to PM2.5 in Qingdao during the sampling periods (25.05%). The potential source contribution function (PSCF) analysis suggested that the Yellow Sea and Jiaodong Peninsula were the major sources regions for PM2.5 in Qingdao. The Yellow Sea and Bohai Sea were the potential source regions for shipping emissions in Qingdao. Therefore, efforts to control shipping emissions should be strengthened not only at the Qingdao Port but also in surrounding ports.

7.
ISA Trans ; 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33059906

RESUMO

In the present paper, an active disturbance rejection control(ADRC) scheme via radial basis function(RBF) neural networks is designed for adaptive control of non-affine nonlinear systems facing hysteresis disturbance in which RBF neural network approximation is utilized to tackle the system uncertainties and ADRC is designed to real-time estimate and compensate disturbance with unknown backlash-like hysteresis. Combining the adaptive neural networks design with ADRC design techniques, a new dual-channel composite controller scheme is developed herein whereby adaptive neural networks are used as feed-forward inverse control and ADRC as closed-loop feedback control. Furthermore, as compared to adaptive neural networks control algorithm, the proposed RBF-ADRC dual-channel composite controller can guarantee that the desired signal can be tracked with a small domain of the origin and it is confirmed to be effective under Lyapunov stability theory and MATLAB simulations.

8.
J Mater Chem B ; 8(38): 8838-8844, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026403

RESUMO

The viscosity of lysosomes plays a significant role in modulating biological processes and reflects the status and function of this kind of organelle, e.g., locations, morphologies, and components. Herein, we constructed a novel near-infrared (NIR) lysosome-targeting viscosity probe, Lyso-cy, for monitoring viscosity changes in biological systems. The Lyso-cy probe showed very strong fluorescence emission at around 710 nm in viscous media. The fluorescence intensity of Lyso-cy increased 122-fold from when in water to when in 95% glycerol. Moreover, Lyso-cy proved to be an ideal lysosome-targeting tracer for monitoring fluctuations in the viscosity of a living cell with high spatial and temporal resolution under laser confocal microscopy.

9.
Neuroradiology ; 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32880675

RESUMO

PURPOSE: To investigate the relevant factors of unilateral pulsatile tinnitus (PT) in patients with idiopathic intracranial hypertension (IIH) using CT. METHODS: CT angiography images of IIH patients with unilateral PT (n = 19), without PT (n = 13), and controls (n = 32) were reviewed. The characteristics including transverse sinus stenosis (TSS), venous outflow laterality (VOL), sigmoid sinus wall dehiscence (SSWD), and sigmoid sinus diverticulum (SSD) were quantitatively or/and qualitatively detected. VOL was compared between the symptomatic side of IIH patients with PT and the larger side of IIH patients without PT and the controls. TSS, SSWD, and SSD were compared between the symptomatic side of IIH patients with PT, and both sides of the latter two groups. RESULTS: There was no statistical difference in body mass index or cerebrospinal fluid pressure between IIH patients with and without PT. The prevalence of TSS was significantly higher in IIH patients than that in the controls (p = 0.000), but TSS had no correlation with PT within IIH patients. The prevalence of SSWD successively decreased in IIH patients with PT, without PT, and the controls, with significant differences between each two of three groups (p = 0.000, p' = 0.000, p″ = 0.031). The proportion of VOL and the prevalence of SSD were significantly larger in IIH patients with PT than in the latter groups respectively (pVOL = 0.005, p'VOL = 0.000; pSSD = 0.040, p'SSD = 0.000). All SSDs in IIH patients with PT were accompanied with SSWD. CONCLUSION: The dominant VOL and ipsilateral SSWD with/without SSD may be correlated with the occurrence of unilateral PT in IIH patients.

10.
iScience ; 23(9): 101498, 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32916629

RESUMO

Zero- to two-dimensional nanomaterials have been incorporated into metal-matrices to improve the strength of metals, but challengingly, high-volume-fraction nanomaterials are difficult to disperse uniformly in metal matrices, severely degrading the ductility of conventionally processed metals. Here, a considerably dense uniform dispersion of in situ formed nanoscale lamellar TiC reinforcement (16.1 wt %) in Ti matrix is achieved through laser-tailored 3D printing and complete reaction of Ti powder with a small amount (1.0 wt %) of carbon nanotubes (CNTs). An enhanced tensile strength of 912 MPa and an outstanding fracture elongation of 16% are simultaneously achieved for laser-printed components, showing a maximum 350% improvement in "product of strength and elongation" compared with conventional Ti. In situ nanoscale TiC reinforcement favors the formation of ultrafine equiaxed Ti grains and metallurgically coherent interface with minimal lattice misfit between TiC lamellae and Ti matrix. Our approach hopefully provides a feasible way to broaden structural applications of CNTs in load-bearing Ti-based engineering components via laser-tailored reorganization with Ti.

11.
Epilepsy Behav ; 112: 107398, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32891888

RESUMO

Pediatric patients frequently require invasive exploration with intracranial electrodes to achieve high-resolution delineation of the epileptogenic zones (EZ). We intend to discuss the efficacy and safety of stereoelectroencephalophraphy (SEEG) monitoring in pediatric patients with difficulty to localize the EZ. We retrospectively analyzed presurgical findings, SEEG data, resections, and outcomes of a series of 72 consecutive pediatric patients (<18 yrs) who had medically refractory epilepsy and received SEEG recording between January 2015 and September 2019. There were 20 girls and 52 boys with a mean age of 10.13 ±â€¯4.11 years old (range: 1.8-18 years). Twenty-seven patients (37.5%) had nonlesional magnetic resonance imagings (MRIs). In total, 744 electrodes were implanted for an average of 10.33 ±â€¯2.53 (range: 3-18) electrodes per patient. Twenty-eight explorations were unilateral (17 left and 11 right), and 44 explorations were bilateral (12 of which was predominately one side). The average monitoring period in days for the SEEG was 8.99 ±â€¯5.79 (range: 3-25) days. The EZ could be located in 67 (94.4%) patients for the initial implantation according to SEEG monitoring. Lobectomy was performed in 12 patients (17.9%), of those anterior temporal lobectomy (ATL) was performed in 8 cases (11.9%) and insular plus was 2 cases (3.0%), multilobectomy resections in 15 cases (22.4%), tailored cortical resections in 37 cases (55.2%), and corpus callosotomy plus in 2 cases (3.0%). The average follow-up was 18.1 ±â€¯7.53 months (range: 6-54). Forty-three of 67 patients (64.2%) were Engel class I, 12 patients (17.9%) were Engel class II, 10 patients (14.9%) were Engel class III, and an additional 2 patients (3.0%) were Engel class IV. In the SEEG implantation series, no child experienced serious or permanent morbidity. One patient (1.4%) experienced symptomatic intracranial hemorrhage (ICH), and 3 patients (4.2%) experienced asymptomatic ICH. There were no postimplantation infections or other postoperative complications associated with the SEEG. Several common complications related to resection surgery were included in this series with zero mortality. Of the 6 patients in whom we performed a second surgery, 4 of them subsequently became seizure-free (66.7%) after undergoing the second resection with SEEG evaluation. Stereoelectroencephalophraphy is a safe and efficient methodology to identify the EZ in particularly complex cases of focal medically refractory epilepsy for pediatric patients, even in infancy and early childhood. Seizure outcomes of SEEG-guided resection surgery are desirable. We recommend SEEG evaluations and even a more aggressive resection in certain pediatric patients who failed initial resection with realistic chances to benefit from reoperation.

12.
Int J Biol Macromol ; 163: 2286-2294, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32961185

RESUMO

This work investigated the changes in multi-scale structure and retrogradation properties of native wheat starches (NS) modified by sodium alginate (AG) with and without fermentation. AG adhered on the surface of NS granules and fermentation promoted the adhesions. Compared with the addition of AG alone, dual modification by fermentation and AG together showed a greater effect to increase the weight-average molecular weight and reduce the relative crystallinity and double helix degree of NS. Small angle X-ray diffraction results showed a significant increase in amorphous region with dual modification compared with AG alone. Additionally, dual modification greatly slowed the increase of relative crystallinity and the enthalpy (ΔH) of NS paste during storage. The results of this study suggest that dual modification is a more effective approach to modify structures and properties of wheat starch than single AG treatment, and suggest its potential industrial application in starch-based foods.

13.
Nat Commun ; 11(1): 4765, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958780

RESUMO

Fatty acids (FAs) are essential nutrients, but how they are transported into cells remains unclear. Here, we show that FAs trigger caveolae-dependent CD36 internalization, which in turn delivers FAs into adipocytes. During the process, binding of FAs to CD36 activates its downstream kinase LYN, which phosphorylates DHHC5, the palmitoyl acyltransferase of CD36, at Tyr91 and inactivates it. CD36 then gets depalmitoylated by APT1 and recruits another tyrosine kinase SYK to phosphorylate JNK and VAVs to initiate endocytic uptake of FAs. Blocking CD36 internalization by inhibiting APT1, LYN or SYK abolishes CD36-dependent FA uptake. Restricting CD36 at either palmitoylated or depalmitoylated state eliminates its FA uptake activity, indicating an essential role of dynamic palmitoylation of CD36. Furthermore, blocking endocytosis by targeting LYN or SYK inhibits CD36-dependent lipid droplet growth in adipocytes and high-fat-diet induced weight gain in mice. Our study has uncovered a dynamic palmitoylation-regulated endocytic pathway to take up FAs.


Assuntos
Antígenos CD36/metabolismo , Endocitose/fisiologia , Ácidos Graxos/metabolismo , Lipoilação , Células 3T3-L1 , Aciltransferases/metabolismo , Adipócitos/metabolismo , Animais , Antígenos CD36/deficiência , Antígenos CD36/genética , Cavéolas/metabolismo , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Humanos , Gotículas Lipídicas/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mutação , Obesidade/tratamento farmacológico , Fosforilação , Transdução de Sinais , Quinase Syk/antagonistas & inibidores , Quinase Syk/metabolismo , Ganho de Peso/efeitos dos fármacos , Quinases da Família src/antagonistas & inibidores , Quinases da Família src/metabolismo
14.
J Med Chem ; 63(19): 10829-10854, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-32897699

RESUMO

Lesinurad, a human urate transporter 1 (URAT1) inhibitor approved as a medication for the treatment of hyperuricemia associated with gout in 2015, can cause liver and renal toxicity. Here, we modified all three structural components of lesinurad by applying scaffold hopping, bioisosterism, and substituent-decorating strategies. In a mouse model of acute hyperuricemia, 21 of the synthesized compounds showed increased serum uric acid (SUA)-reducing activity; SUA was about 4-fold lower in animals treated with 44, 54, and 83 compared with lesinurad or benzbromarone. In the URAT1 inhibition assay, 44 was over 8-fold more potent than lesinurad (IC50: 1.57 µM vs 13.21 µM). Notably, 83 also displayed potent inhibitory activity (IC50 = 31.73 µM) against GLUT9. Furthermore, we also preliminarily explored the effect of chirality on the potency of the promising derivatives 44 and 54. Compounds 44, 54, and 83 showed favorable drug-like pharmacokinetics and appear to be promising candidates for the treatment of hyperuricemia and gout.

15.
Parasit Vectors ; 13(1): 421, 2020 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807211

RESUMO

BACKGROUND: Dengue virus (DENV) is a flavivirus transmitted by mosquitoes that is prevalent in tropical and subtropical countries and has four serotypes (DENV1-4). Aedes aegypti, as the main transmission vector of DENV, exhibits strong infectivity and transmission. With the aim of obtaining a better understanding of the Ae. aegypti-DENV interaction, the transcriptome changes in DENV-2-infected Aag2 cells were studied to describe the immune responses of mosquitoes using the Ae. aegypti Aag2 cell line as a model. METHODS: RNAseq technology was used to sequence the transcripts of the Ae. aegypti Aag2 cell line before and after infection with DENV-2. A bioinformatics analysis was then performed to assess the biological functions of the differentially expressed genes, and the sequencing data were verified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). RESULTS: The transcriptome analysis generated 8866 unigenes that were found in both groups, 225 unigenes that were only found in the infection group, and 683 unigenes that only existed in the control group. A total of 1199 differentially expressed genes, including 1014 upregulated and 185 downregulated genes, were identified. The bioinformatics analysis showed that the differentially expressed genes were mainly involved in the longevity regulating pathway, circadian rhythm, DNA replication, and peroxisome, purine, pyrimidine, and drug metabolism. The qRT-PCR verification results showed the same trend, which confirmed that the expression of the differentially expressed genes had changed, and that the transcriptome sequencing data were reliable. CONCLUSIONS: This study investigated the changes in the transcriptome levels in the DENV-2-infected Ae. aegypti Aag2 cell line, which provides a faster and effective method for discovering genes related to Ae. aegypti pathogen susceptibility. The findings provide basic data and directions for further research on the complex mechanism underlying host-pathogen interactions.

16.
Breast Cancer Res Treat ; 184(2): 397-405, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32776291

RESUMO

BACKGROUND AND PURPOSE: Paclitaxel-based regimens are widely used in the neoadjuvant therapy (NAT) of breast cancer. The purpose is to analysis the efficacy and adverse events (AEs) among common paclitaxel (PTX), docetaxel and liposomal paclitaxel. At the same time, we want to analysis the axillary nodal pathologic complete response (apCR) after NAT among the three groups. METHODS: From April 2014 to 2020, 647 breast cancer patients underwent operation after NAT were included in this study. Patients received full course of anthracycline- and paclitaxel-based chemotherapy before surgery. The paclitaxel-based regimens included PTX, docetaxel and liposomal paclitaxel. The therapy efficacy and AEs of the three groups were evaluated. At the same time, the apCR was also analyzed. RESULTS: In general, 30.6% (198/647) of patients achieved breast pathologic complete response (bpCR), which was 28.6%, 28.3% and 39.3% among PTX, docetaxel and liposomal paclitaxel group, respectively (p = 0.067). The total pathologic complete response (tpCR) (achieving both bpCR and apCR) was 21.6% (140/647). The tpCR was 13.3%, 19.4% and 34.4% among PTX, docetaxel and liposomal paclitaxel group, respectively (p = 0.026). The multivariate logistic analysis result showed that clinical tumor stage and molecular subtype were significantly associated with tpCR (all p < 0.05). Among 592 clinical positive patients (cN+), the apCR was 39.0% (231/592). The multivariate logistic analysis showed that paclitaxel- based regimens and molecular subtype were indicated as independent predictors for apCR of NAT. The apCR was significantly higher in liposomal paclitaxel group (63.5%) than in PTX (24.6%) and docetaxel group (34.8%) (p < 0.001). The subgroup analysis among different molecular subtypes found that in triple negative (TN) and HER-2 positive (HER2+) subgroup, the apCR in liposomal paclitaxel group was significantly higher than those in PTX and docetaxel group (all p < 0.05). But no significant result was found in the subgroup analysis in hormone receptor positive/HER-2 negative subgroup (p = 0.050). Safety analysis indicated that the incidence of neutropenia (grade III-IV) and peripheral neurotoxicity (grade I-II) was significantly lower in the liposomal paclitaxel group than in the PTX and docetaxel group. The incidence of oral mucositis, anaphylaxis and palmar-plantar erythrodysesthesia syndrome was also much lower in liposomal paclitaxel than other two groups (all p < 0.05). And there was no significant difference in other AEs among the three groups (all p > 0.05). CONCLUSION: Liposome paclitaxel had similar tumor suppressor effect compared with PTX and docetaxel in NAT setting. Moreover, it had a better axillary lymph node (ALN) response after NAT than PTX and docetaxel. These patients who received liposome paclitaxel had more chance to avoid ALN dissection after NAT. At the same time, the application of liposome enables liposome paclitaxel could significantly reduce AEs caused by chemotherapy. Therefore, we suggested the application of liposome paclitaxel in the NAT setting, especially for cN+ patients with TN and HER2 + disease.

17.
Neurol Res ; 42(8): 703-711, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32684116

RESUMO

OBJECTIVE: Following brain injury, the neurogenic niche provides a permissive cue for iatrogenesis rather than neurogenesis; reactive astrocytes play essential roles in orchestrating this process, markedly forming a glial scar around the area of damaged brain tissue. The objective of this study was to alter the neurogenic niche at the injured cortex and study its impact on neurogenesis. METHODS: We constructed a stromal cell-derived factor 1 (SDF-1) gradient matrix to attract reactive astrocytes to the glial scar core. RESULTS: SDF-1 reacted with the astrocytes in the injured site. By changing the neurogenic niche of the injured part of the brain after traumatic brain injury (TBI), SDF-1 downregulated thrombospondin 4 (Thbs4) promoting neuronal cell regeneration and playing a beneficial role in nerve function recovery after brain injury. DISCUSSION: The matrix we created in this study could attract and interact with reactive glial cells and, thus, we called it a glial pump. Using the glial pump, we identified a new mechanism of brain injury repair and neuronal regeneration after TBI, which relied on Thbs4 downregulation after the altered neurogenic niche promoted neuronal regeneration and functional recovery.

18.
J Int Med Res ; 48(7): 300060520936903, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32687424

RESUMO

OBJECTIVES: We investigated the endoplasmic reticulum (ER) stress markers C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP) 78, as well as the inflammatory factors nuclear factor (NF)-κB and IκBα, to assess how social defeat stress induces myocardial injury. Furthermore, we evaluated the protective effects of the ER stress inhibitor 4-phenylbutyric acid (PBA) on myocardial injury in mice. METHODS: Adult mice were divided into control, control + PBA, social defeat, and social defeat + PBA groups. The social defeat and social defeat + PBA groups were exposed to social defeat stress for 10 days. Cardiac tissues from all groups were analyzed after social defeat stress. H9C2 cells were used to detect the role of the ER stress agonist thapsigargin on expression of ER stress and inflammatory markers. RESULTS: Social defeat stress promoted apoptosis of cardiomyocytes, increased CHOP, NF-κB and, phospho-NF-κB protein expression, and decreased GRP78 and IκBα protein expression. Moreover, PBA significantly reversed these changes and attenuated thapsigargin-induced increased expression of CHOP and phospho-NF-κB, and decreased IκBα expression in H9C2 cells. CONCLUSIONS: Social defeat stress initiates ER stress, promotes expression of inflammatory factors, and induces myocardial injury. Inhibiting ER stress could protect the myocardium from social defeat stress-induced myocardial injury.

19.
PLoS Negl Trop Dis ; 14(7): e0008450, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32628662

RESUMO

BACKGROUND: Zika virus (ZIKV) disease outbreaks have been occurring in South America since 2015, and has spread to North America. Because birth defects and cases of Guillain Barré have been associated with infection with ZIKV, this has drawn global attention. ZIKV is generally considered an Aedes-transmitted pathogen. The transmission of ZIKV through blood by Aedes mosquito bites has been recognized as the major transmission route. However, it is not clear whether there are other transmission routes that can cause viral infection in mosquitos. The aim of the present study is to describe the susceptibility of Armigeres subalbatus, which often develop in human waste lagoons, to ZIKV, through oral infection in adult mosquitoes and urine infection in larvae. METHODOLOGY/PRINCIPAL FINDINGS: Five-day-old female Ar. subalbatus ingested infectious blood meals containing ZIKV. After 4, 7, and 10 days of ingesting infectious blood meals, ZIKV could be detected in the midguts, salivary glands, ovaries, and collected saliva of mosquitoes. The ZIKV infection rate (IR) on day 10 reached 40% in salivary glands and 13% in saliva, indicating that these mosquitoes were able to transmit ZIKV. In addition, ZIKV infection was also discovered in mosquito ovaries, suggesting the possibility of vertical transmission of virus. Moreover, Ar. subalbatus transmitted ZIKV to infant mice bitten by infectious mosquitoes. In a second experiment, 1st-instar larvae of Ar. subalbatus were reared in water containing ZIKV and human urine. After pupation, pupae were placed in clean water and transferred to a mosquito cage for emergence. Although ZIKV RNA was detected in all of the larvae tested, ZIKV was not detected in the saliva of any adult Ar. subalbatus. Considering that there are more uncontrollable factors in nature than in the laboratory environment, the possibility that the virus is transmitted to adult mosquitoes via larvae is very small period. CONCLUSIONS/SIGNIFICANCE: Adult Ar. subalbatus could be infected with ZIKV and transmit ZIKV through mosquito bites. Therefore, in many rural areas in China and in undeveloped areas of other Asian countries, the management of human waste lagoons in the prevention and control of Zika disease should be considered. Corresponding adjustments and modifications should also be made in prevention and control strategies against ZIKV.


Assuntos
Culicidae/virologia , Mosquitos Vetores/virologia , Infecção por Zika virus/transmissão , Zika virus/fisiologia , Animais , Culicidae/crescimento & desenvolvimento , Culicidae/fisiologia , Feminino , Humanos , Larva/virologia , Camundongos , Mosquitos Vetores/crescimento & desenvolvimento , Mosquitos Vetores/fisiologia , Saliva/virologia , Zika virus/genética , Zika virus/isolamento & purificação , Infecção por Zika virus/urina , Infecção por Zika virus/virologia
20.
J Int Soc Sports Nutr ; 17(1): 41, 2020 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711519

RESUMO

BACKGROUND: Avenanthramides (AVA) are a group of di-phenolic acids found only in oats and have shown antioxidant and anti-inflammatory effects in vitro and in vivo. Eccentric muscle contraction is intimately involved in rigorous exercise that activates systemic and local inflammatory responses. The objective of the study is to evaluate whether chronic AVA supplementation could attenuate peripheral inflammatory and immunological markers in human subjects in response to an acute bout of downhill running (DR). METHODS: Eleven male and thirteen female subjects voluntarily participated in this double-blinded, randomized controlled study and were randomly divided into AVA-supplemented (AVA) or control (C) groups. All subjects conducted a DR protocol at - 10% grade with an intensity equivalent to 75% of their maximal heart rate. Blood samples were collected at rest and various time points (0-72 h) after DR (PRE). After an 8-week washout period, participants received two cookies daily containing either 206 mg/kg (AVA) or 0 mg/kg (C) AVA for 8 weeks. Following the oat supplementation regimen, the DR and blood sampling protocols were repeated (POST). Plasma inflammatory and immunological markers were measured using Multiplex immunoassay and muscle soreness was evaluated with pain rating scale. RESULTS: DR increased plasma creatine kinase (CK) activity (P < 0.01) during PRE, but the response was reduced at 24 and 48 h during POST vs. PRE regardless of AVA status (P < 0.05). Neutrophil respiratory burst (NRB) levels were elevated at 4 and 24 h (P < 0.05) during PRE but were significantly decreased at 0-48 h during POST vs. PRE (P < 0.05 or 0.01). Granulocyte-colony stimulating factor (G-CSF), the neutrophil stimulating cytokine, was also increased in response to DR but showed lower levels in AVA compared to C during POST vs. PRE (P < 0.05). Plasma interleukin-6 (IL-6) content showed an increase at 0 and 4 h during PRE and 0 h during POST (P < 0.01), whereas during POST there was a trend toward a lower IL-6 level in AVA vs. C (P = 0.082). Plasma levels of anti-inflammatory agent interleukin-1 receptor antagonist (IL-1Ra) showed an increase at 4 h during PRE, and was significantly elevated in AVA vs. C during POST. Both soluble vascular cell adhesion molecule-1 (sVCAM-1) and monocyte chemoattractant protein-1 (MCP-1) contents increased at 0 and 24 h post DR during PRE as well as POST sessions, however, sVCAM-1 content was lower in AVA vs. C during POST (P < 0.05) and MCP-1 levels were below resting level at 24, 48 and 72 h during POST (P < 0.05). DR increased muscle pain at all post-DR time points (P < 0.01), but the pain level was alleviated by oat supplementation at 48 and 72 h during POST regardless of AVA treatment (P < 0.05). CONCLUSIONS: Oat AVA supplementation reduced circulatory inflammatory cytokines and inhibited expression of chemokines and cell adhesion molecules induced by DR. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02584946 . Registered 23 October 2015.


Assuntos
Anti-Inflamatórios/administração & dosagem , Suplementos Nutricionais , Exercício Físico , Inflamação/prevenção & controle , ortoaminobenzoatos/administração & dosagem , Adulto , Creatina Quinase/sangue , Citocinas/sangue , Método Duplo-Cego , Feminino , Humanos , Masculino , Mialgia , Medição da Dor , Corrida
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