Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.925
Filtrar
1.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 494-499, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33812420

RESUMO

OBJECTIVE: To investigate the effect of long non-coding RNA-TUC338 on the proliferation and migration of lymphoma cells. METHODS: The expression of TUC338 in different lymphoma cells was detected by fluorescence quantitative PCR, cell proliferation by sulforhodamine B (SRB) assay, migration of lymphoma cells by transwell assay, and protein expression in PI3K/AKT signaling pathway by Western blot. RESULTS: The expression levels of TUC338 in lymphoma cells Daudi, U937, BC-3, and Raji significantly increased in comparison with human normal T lymphocytes H9 (t=13.277, 10.103, 16.200, and 26.687, P=0.002, 0.005, 0.001, and 0.000). Compared with NC-siRNA group, the number of cells crossing the chamber of TUC338-siRNA group was significantly reduced (t=30.508, P=0.000), the protein expression levels of p-PI3K and p-AKT significantly decreased (t=16.872 and 18.371, P=0.000 and 0.000), and OD530 absorbance values at 24 h, 48 h, and 72 h were significantly lower (P<0.05). CONCLUSION: The expression of TUC338 significantly increases in lymphoma cells, and silence of TUC338 effectively inhibits the activation of PI3K/AKT signaling pathway, thereby inhibiting the proliferation and migration of lymphoma cells, which has a potential application value in diagnosis and treatment of lymphoma.


Assuntos
RNA Longo não Codificante , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais
2.
Artigo em Inglês | MEDLINE | ID: mdl-33844875

RESUMO

The purpose of this study was to ascertain the appropriate levels of dietary sodium (Na+ ) and chloride (Cl- ) for 29- to 70-day-old goslings and to investigate the effects of different levels of Na+ and Cl- on the growth performance, water consumption, blood parameters and excreta quality of goslings to provide a reference for the healthy production of goslings. In Experiment 1, a total of 432 29-day-old male Jiangnan White goslings were randomly allotted to nine treatments according to a 3 × 3 factorial design, with six pens containing eight birds per treatment. The goslings were fed diets with three concentrations of Na+ (0.10%, 0.15% and 0.20%) and three concentrations of Cl- (0.15%, 0.20% and 0.25%). The experimental period was 42 days. In Experiment 2, a total of 24 70-day-old Jiangnan White goslings were selected for four treatments (0.10% Na+  × 0.15% Cl- ; 0.10% Na+  × 0.25% Cl- ; 0.20% Na+  × 0.15% Cl- and 0.20% Na+  × 0.25% Cl- ) and housed separately in metabolic cages. The faeces were collected for 3 consecutive days. In Experiment 1, the average daily feed intake (ADFI), average daily gain (ADG) and feed/gain (F/G) ratio of goslings were unaffected by the treatments. However, low levels of Na+ and Cl- significantly reduced the water consumption of goslings in the later growth period (p < 0.05). The average water consumption of goslings fed with 0.10% Na+  × 0.15% Cl- was significantly lower than that of the goslings fed with 0.20% Na+  × 0.25% Cl- (56 days, 1304.2 ml vs. 1471.7 ml; 63 days, 1452.8 ml vs. 1610.8 ml; 70 days, 1540.0 ml vs. 1775.4 ml; p < 0.05). The interaction between Na+ and Cl- (Na+  × Cl- ) had a significant impact on the blood haemoglobin (HGB) and haematocrit (HCT) levels in the goslings (p < 0.05). HGB increased linearly with increasing levels of Na+ . HGB and HCT first increased and then decreased with increasing levels of Cl- . In Experiment 2, Na+ and Cl- levels had significant effects on the excreta moisture content (p < 0.05). Goslings fed with 0.10% Na+  × 0.15% Cl- had a low moisture content of 5.58% compared to the goslings fed with 0.20% Na+  × 0.25% Cl- (87.51% vs. 93.09%; p < 0.05). The levels of dietary Na+ had a significant effect on the retention ratio of Na (p < 0.05), with the value for the 0.20% Na+ group being significantly higher than that for the 0.10% Na+ group (p < 0.05). In summary, different levels of Na+ and Cl- did not affect the growth of goslings. To reduce the water consumption and moisture content of excreta, the Na+ and Cl- levels in the diet can be as low as 0.10% and 0.15%, respectively.

3.
J Phys Chem Lett ; : 3786-3794, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33847498

RESUMO

Lead halide perovskite quantum dots (PQDs) are reported as a promising branch of perovskites, which have recently emerged as a field in luminescent materials research. However, before the practical applications of PQDs can be realized, the problem of poor stability has not yet been solved. Herein, we propose a trioctylphosphine (TOP)-assisted pre-protection low-temperature solvothermal synthesis of highly stable CsPbBr3/TiO2 nanocomposites. Due to the protection of branched ligands and the lower temperature of shell formation, these TOP-modified CsPbBr3 PQDs are successfully incorporated into a TiO2 monolith without a loss of fluorescence intensity. Because the excellent nature of both parent materials is preserved in CsPbBr3/TiO2 nanocomposites, it is found that the as-prepared CsPbBr3/TiO2 nanocomposites not only display excellent photocatalytic activity but also yield improved PL stability, enabling us to build highly stable white light-emitting diodes and to photodegrade rhodamine B.

4.
Langmuir ; 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33829794

RESUMO

Plasmonic Au nanoparticles (NPs) have been commonly used to enhance the photocatalytic activity of Cu2O. Till now, core-shell Au NP@Cu2O composites have been reported in previous studies. Yet, these Au@Cu2O composites only exhibit visible light response. Other special Au nanostructures, such as Au nanorods (NRs) or Au nanobipyramids (NBPs), which possess near-infrared light absorption, were rarely used to endow the near-infrared light response for Cu2O. In this work, for the first time, we used Au NPs, Au NRs, and Au NBPs and employed a handy and universal method to synthesize a series of yolk-shelled Au@Cu2O composites. The results showed that the yolk-shelled Au@Cu2O composites had much higher photocatalytic activity than their solid-shelled ones and pure Cu2O. More importantly, yolk-shelled Au NR@Cu2O and Au NBP@Cu2O composites indeed presented excellent near-infrared light-driven photocatalytic activity, which were impossible for Au NP@Cu2O and pure Cu2O. This outstanding performance for yolk-shelled Au NR@Cu2O and Au NBP@Cu2O could be attributed to the transfer of abundant hot electrons from Au NRs or Au NBPs to Cu2O, and the timely utilization of hot holes on Au through the rich pore channels on their yolk-shelled structure. Furthermore, yolk-shelled Au@Cu2O also showed better stability than pure Cu2O, owing to the migration of the oxidizing holes from Cu2O to Au driven by the built-in electric field. This work may give a guide to fabricate controllable and effective photocatalysts based on plasmonic metals and semiconductors with full solar light-driven photocatalytic activities in the future.

5.
BMJ Open ; 11(4): e043415, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795300

RESUMO

OBJECTIVES: We aimed to determine predictors of mortality within 90 days and develop a simple score for patients with mechanical thrombectomy (MT). DESIGN: Analysis of a multicentre prospective registry. SETTING: In six participating centres, patients who had an acute ischaemic stroke (AIS) treated by MT between March 2017 and May 2018 were documented prospectively. PARTICIPANTS: 224 patients with AIS were treated by MT. RESULTS: Of 224 patients, 49 (21.9%) patients died, and 87 (38.8%) were independent. Variables associated with 90-day mortality were age, previous stroke, admission National Institutes of Health Stroke Scale (NIHSS), fasting blood glucose and occlusion site. Logistic regression identified four variables independently associated with 90-day mortality: age ≥80 years (OR 3.26, 95% CI 1.45 to 7.33), previous stroke (OR 2.33, 95% CI 1.04 to 5.21), admission NIHSS ≥18 (OR 2.37, 95% CI 1.13 to 4.99) and internal carotid artery or basilar artery occlusion (OR 2.92, 95% CI 1.34 to 6.40). Using these data, we developed predicting 90-day mortality of AIS with MT (PRACTICE) score ranging from 0 to 6 points. The receiver operator curve analysis found that PRACTICE score (area under the curve (AUC)=0.744, 95% CI 0.669 to 0.820) was numerically better than iScore (AUC=0.661, 95% CI 0.577 to 0.745) and Predicting Early Mortality of Ischemic Stroke score (AUC=0.638, 95% CI 0.551 to 0.725) for predicting 90-day mortality. CONCLUSIONS: We developed a simple score to estimate the 90-day mortality of patients who had an AIS treated with MT. But the score needs to be prospectively validated. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR-OOC-17013052).

6.
J Immunother Cancer ; 9(4)2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33795385

RESUMO

BACKGROUND: Progression-free survival (PFS) exhibits suboptimal performance as the surrogate endpoint for overall survival (OS) in trials studying immune checkpoint inhibitors (ICIs). Here we propose a novel surrogate endpoint, modified PFS (mPFS), which omits the events of disease progression (but not deaths) within 3 months after randomization. METHODS: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for randomized trials studying ICIs in advanced solid tumors with available PFS and OS data up to May 2020. Individual patient-level data (IPD) for PFS and OS were reconstructed for eligible trials. A simulation-based algorithm was used to match the reconstructed, disconnected PFS and OS IPD, and 1000 independent simulated datasets of matched PFS-OS IPD were generated for each trial. mPFS durations and statuses were then measured for each of the matched PFS-OS IPD. Trial-level correlation between Cox HRs for PFS or mPFS and HRs for OS was assessed using Pearson correlation coefficient (rp) weighted by trial size; patient-level correlation between PFS or mPFS and OS was assessed using Spearman's rank correlation coefficient (rs). Findings were further validated using the original IPD from two randomized ICI trials. RESULTS: Fifty-seven ICI trials totaling 29,429 participants were included. PFS HR showed moderate correlation with OS HR (rp=0.60), and PFS was moderately correlated with OS at the patient level (median rs=0.66; range, 0.65-0.68 among the 1000 simulations). In contrast, mPFS HR achieved stronger correlation with OS HR (median rp=0.81; range, 0.77-0.84), and mPFS was more strongly correlated with OS at the patient level (median rs=0.79; range, 0.78-0.80). The superiority of mPFS over PFS remained consistent in subgroup analyses by cancer type, therapeutic regimen, and treatment setting. In both trials with the original IPD where experimental treatment significantly improved OS, mPFS successfully captured such clinical benefits whereas PFS did not. CONCLUSIONS: mPFS outperformed PFS as the surrogate endpoint for OS in ICI trials. mPFS is worthy of further investigation as a secondary endpoint in future ICI trials.

7.
Medicine (Baltimore) ; 100(9): e24887, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33655949

RESUMO

RATIONALE: Membranous glomerulonephritis (MN) is the leading cause of nephrotic syndrome in adults and is classified as primary or secondary. Secondary MN accounts for 20% to 30% of all MN cases and can arise from a number of conditions, including autoimmune diseases. Recently exostosin 1/exostosin 2 (EXT1/EXT2) have been identified as the common antigens in secondary autoimmune MN and are present in cases of pure membranous lupus nephritis (LN). The treatment of EXT1/EXT2-associated MN remains elusive. PATIENT CONCERNS: We present the case of a 15-year-old female who presented with nephrotic syndrome, positive ANA and dsDNA, and low serum complements. A renal biopsy revealed pure membranous nephritis with IgG and C3 deposition. EXT1 was found along the glomerular capillary walls and stained positive, while phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) were negative. DIAGNOSIS: The patient was diagnosed with ETX1-associated membranous LN. INTERVENTIONS: She was treated with prednisone and multiple low-dose rituximab (4 200 mg doses, approximately every 2 months, based on CD19+ cells counts). OUTCOMES: The patient had complete remission within 8 months later, and she remained in remission for the 16-month period of follow-up. LESSONS: To our knowledge, this is the first case of EXT1-associated MN that has been successfully treated by multiple low-dose rituximab. Further studies can investigate the optimal dosage and treatment protocol.


Assuntos
Autoanticorpos/imunologia , Nefrite Lúpica/tratamento farmacológico , N-Acetilglucosaminiltransferases/imunologia , Rituximab/administração & dosagem , Adolescente , Autoanticorpos/metabolismo , Biomarcadores/metabolismo , Biópsia , Relação Dose-Resposta a Droga , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Glomérulos Renais/patologia , Nefrite Lúpica/imunologia , Nefrite Lúpica/metabolismo , N-Acetilglucosaminiltransferases/metabolismo
8.
Small ; 17(13): e2006662, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33738968

RESUMO

The development of neuromorphic computation faces the appreciable challenge of implementing hardware with energy consumption on the level of a femtojoule per synaptic event to be comparable with the energy consumption of human brain. Controllable ultrathin conductive filaments are needed to achieve such extremely low energy consumption in memristive synapses but their formation is difficult to control owing to their stochastic morphology and unexpected overgrowth. Herein, a zeolite-based memristive synapse is demonstrated for the first time, in which Ag exchange in the sub-nanometer pore closely resembles synaptic Ca2+ dynamics across biomembrane channel. Particularly, the confined ultrasmall pore and low Ag ion migration barrier give the zeolite-based memristive synapse ultralow energy consumption below 10 fJ per synaptic spike, on par with the biological counterpart. Experimental results reveal that the gradual memristive effect is attributed to the dimension modulation of Ag clusters. In addition to emulating inherent cognitive functions through electrical stimulations, the experience-dependent transition of short-term plasticity to long-term plasticity using a chemical modulation method is achieved by treating the initial Ag quantity as a learning experience. The proposed memristors can be used to develop highly efficient memristive neural networks and are considered as a candidate for application in neuromorphic computation.

9.
Chem Commun (Camb) ; 57(26): 3255-3258, 2021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33647078

RESUMO

A high-performance catalyst, O-doped Sb2S3 nanosheets (SS-O NSs), is synthesized and introduced into lithium-sulfur batteries. Owing to their good conductivity, strong adsorbability/catalytic effect to polysulfides and fast Li+ diffusion, the SS-O NSs-modified cathodes can effectively mitigate the shuttle effect, thus achieving outstanding electrochemical performance.

10.
Huan Jing Ke Xue ; 42(4): 2003-2015, 2021 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-33742835

RESUMO

In order to evaluate the potential ecological risk of heavy metals in the soil-crop system in the Xiong'an New District, the heavy metal contents and forms in wheat seed and root soil samples are analyzed, and the comprehensive pollution index (IPIN), potential ecological risk index (RI), bio-enrichment coefficient (BFC), risk assessment code (RAC), principal component analysis, and correlation analysis are used to assess the potential ecological risk of heavy metals and analyze their sources. The results indicate that the average content of Cd, Cu, Pb, and Zn in the root soil is significantly higher than the soil background value in Hebei province. The IPIN ranges from 0.2 to 5.18, 94.83% of the soil samples are in the safe and pollution-free grade, and the potential ecological risks of heavy metal are slight and moderate, accounting for 64.66% and 30.17%, respectively. Cd has the greatest potential ecological harm, followed by Hg, Cr, Ni, and Zn. All the heavy metal elements besides Cd in the root soil are dominated by the residual form, which accounts for 60%, and the bioactive form (ion-exchange and water-soluble state) of Cd accounts for 33.43%, indicating relatively high bio-availability. The risk assessment code can be ranked as Cd > Ni > Hg > As > Cu > Cr > Zn > Pb, and the risk of Cd is moderate, while other elements are of low or no risk. The leading potential source of heavy metals is human activity combined with the geological background. The migration and enrichment capability of the wheat seeds is in order from strong to weak of Zn > Cu > Cd > Hg > As > Ni > Pb > Cr, and the biological effective components of As, Cd, Pb, and Zn plays an substantial role in promoting the absorption of heavy metals. The content of heavy metals in the wheat seeds has a negative correlation with the soil pH, and the physical and chemical indices, such as OM and CEC, has bi-directional influence on the biological effective state of the heavy metals.


Assuntos
Metais Pesados , Poluentes do Solo , China , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análise
11.
Infect Genet Evol ; 91: 104804, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33684569

RESUMO

OBJECTIVES: To explore if SOCS1 is regulated by plasma HDL and its subcomponents HDL2b and HDL3 to affect inflammatory reaction then to influence the severity degree and prognosis of sepsis. METHODS: One hundred sepsis patients in ICU and 85 normal control persons from October 2018 to October 2019 in our hospital were enrolled. Adult male C57BL/6 mice were used to establish sepsis model by CLP method. HDL, CRP, and WBC count of human were measured using an auto-analyzer. Plasma HDL, IL-1ß, and TNF-α proteins levels of mice were measured with ELISA. Microfluidic chip was used for plasma HDL2b and HDL3 detections. SOCS1 in liver and spleen of mice were measured by qRT-PCR. The relationship between plasma HDL//HDL2b and inflammatory indices/SOCS1 in liver/spleen was analyzed with spearman correlation coefficient method. The sepsis patients/mice were divided into non-survival and survival groups. The sepsis patients were divided into severe and mild sepsis patients based on the SOFA score or divided into high and low score groups according to the APACHE II score. The sepsis mice were divided into high and low score group based on the modified sepsis severity score criterion. RESULTS: Plasma HDL and HDL2b levels were significantly declined (P < 0.01), while HDL3 was normal in both sepsis patients and mice (P > 0.05). Plasma HDL and HDL2b were negatively associated with the serum CRP concentration and positively correlated with the prognosis and severity in sepsis patients (P < 0.05). Moreover, the downregulated plasma HDL but not HDL2b was negatively related to increased SOCS1 mRNA levels in liver and spleen of mice, which were positively connected with TNF-α and IL-1ß protein levels (P < 0.05). CONCLUSIONS: Plasma HDL is downregulated in sepsis, which may facilitate inflammatory reaction then activate the SOCS1 signaling to regulate the severity and affect prognosis of sepsis. The decline of plasma HDL2b content could aggravate the severity and poor prognosis of sepsis through facilitating inflammatory reaction. The plasma HDL3 is not involved in sepsis. The more and further explorations may be needed.

12.
Bioorg Med Chem Lett ; 40: 127901, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33705912

RESUMO

As an indicative biomarker for immunotherapy, PD-L1 plays an important role in the clinical decision-making of the immune checkpoint blockade therapy. PET imaging through radiotracer can real-timely, quantitatively, and non-invasively assess the expression of PD-L1 in tumors. Here, we reported a copper-64 radiolabeled NOTA-WL12, 64Cu-NOTA-WL12, and preliminarily evaluated its application in non-invasively detecting the PD-L1 expression.64Cu-NOTA-WL12 was produced with high radiochemical yield (>90%), radiochemical purity (>98%), and specific activity (20 MBq/nmol). 64Cu-NOTA-WL12 showed high in vitro stability and high binding affinity to the PD-L1 (KD ≈ 3.012 nM). The micro-positron emission tomography/computerized tomography (micro-PET/CT) imaging indicated that 64Cu-NOTA-WL12 was specifically accumulated in the tumor with PD-L1 expression. All results demonstrated that 64Cu-NOTA-WL12 holds great potential for noninvasive evaluation of PD-L1 expression levels.

13.
Proc Natl Acad Sci U S A ; 118(14)2021 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-33785590

RESUMO

Compelling evidence indicates that radiotherapy (RT) has a systemic inhibitory effect on nonirradiated lesions (abscopal effect) in addition to the ablation of irradiated tumors. However, this effect occurs only in rare circumstances in clinical practice, and mechanisms underlying the abscopal effect of RT are neither fully understood nor therapeutically utilized. Here we identified that intercellular adhesion molecule-1 (ICAM-1), an inducible glycoprotein of the immunoglobulin superfamily, is up-regulated in nonirradiated tumors responsive to RT. ICAM-1 expression in preclinical animal models can be noninvasively detected by optical imaging and positron emission tomography (PET) using near-infrared fluorescence dye- and 64Cu-labeled imaging probes that we synthesized, respectively. Importantly, the expression levels of ICAM-1 determined by quantitative PET imaging showed a strong negative linear correlation with the growth of nonirradiated tumors. Moreover, genetic or pharmacologic up-regulation of ICAM-1 expression by either an intratumoral injection of engineered recombinant adenovirus or systemic administration of a Toll-like receptor 7 agonist-capsulated nanodrug could induce markedly increased abscopal responses to local RT in animal models. Mechanistic investigation revealed that ICAM-1 expression can enhance both the activation and tumor infiltration of CD8+ T cells to improve the responses of the nonirradiated tumors to RT. Together, our findings suggest that noninvasive PET imaging of ICAM-1 expression could be a powerful means to predict the responses of nonirradiated tumors to RT, which could facilitate the exploration of new combination RT strategies for effective ablation of primary and disseminated lesions.

14.
Oxid Med Cell Longev ; 2021: 8873581, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33763177

RESUMO

Recent studies have recognized several risk factors for cardiopulmonary bypass- (CPB-) associated acute kidney injury (AKI). However, the lack of early biomarkers for AKI prevents practitioners from intervening in a timely manner. We reviewed the literature with the aim of improving our understanding of the risk factors for CPB-associated AKI, which may increase our ability to prevent or improve this condition. Some novel early biomarkers for AKI have been introduced. In particular, a combinational use of these biomarkers would be helpful to improve clinical outcomes. Furthermore, we discuss several interventions that are aimed at managing CPB-associated AKI, may increase the effect of renal replacement therapy (RRT), and may contribute to preventing CPB-associated AKI. Collectively, the conclusions of this paper are limited by the availability of clinical trial evidence and conflicting definitions of AKI. A guideline is urgently needed for CPB-associated AKI.

15.
Nucl Med Commun ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33741860

RESUMO

OBJECTIVE: To analyze the fluorine-18 fludeoxyglucose PET/computed tomography (18F-FDG PET/CT) findings of retroperitoneal leiomyosarcoma (RLMS) and the role of this method in differentiating between benign and malignant masses and classifying the malignant degree to improve the understanding of this rare disease. METHODS: Eight leiomyomas (A group), 13 RLMSs (B group), and 20 postoperative recurrence/metastasis RLMSs (C group) were enrolled. PET/CT features of B group were analyzed. The differences of metabolic parameters between three groups were compared, receiver operating characteristic (ROC) curve analysis was performed to group A and B, and correlation analysis was performed to subgroup B. RESULTS: (1) The RLMS patients were more likely to be female, and PET/CT showed a high degree of heterogeneous metabolism in the soft tissue mass. (2) The standardized uptake value (SUV) of RLMS were significantly higher than those of benign leiomyomas (P < 0.05). The area under the ROC curve was 0.909, the sensitivity and specificity for diagnosing RLMS were 0.923 and 0.750, respectively, The SUVmax and SUVstd of primary RLMS were moderately associated with the Ki67 index. The mean SUVmax in the G1, G2 and G3 subgroups increased successively (4.15 ± 0.35, 6.47 ± 0.83, and 10.13 ± 4.29, respectively). (3) Primary RLMS was characterized by local invasion, but hematogenous metastasis and lymph node metastasis were rare. Postoperative recurrence/metastasis of RLMS was characterized by local recurrence and hematogenous metastasis, but lymph node metastasis was rare. CONCLUSION: PET/CT has potential value in the preoperative staging, benign and malignant differentiation, malignant degree classification and postoperative follow-up of RLMS.

16.
Redox Biol ; 41: 101927, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33690107

RESUMO

The molecular events that modulate the progression of monoclonal gammopathy of undetermined significance of the immunoglobulin M class (IgM-MGUS) to Waldenstrom Macroglobulinemia (WM) are mostly unknown. We implemented comparative proteomics and metabolomics analyses on patient serum samples to identify differentially expressed molecules crucial to the progression from IgM-MGUS to WM. Our data identified altered lipid metabolism as a discriminating factor between MGUS, WM, and matched normal controls. Levels of many fatty acids, including polyunsaturated fatty acids and dicarboxylic acids, were significantly downregulated in WM sera when compared to MGUS. These reductions were associated with diminished 15-LOX and PPAR protein expression and increased 5-LOX and GPX4 expression in WM versus MGUS patients' samples. Furthermore, WM serum samples showed increased lipid peroxidation compared to MGUS. Treatment with IL-6 or TNFα, upstream regulators of differentially expressed proteins between MGUS and WM, increased lipid absorption and lipid peroxidation in WM cell lines. Knock-down of 15-LOX expression increased WM cell survival, an effect accompanied by increased 5-LOX and GPX4 expression. In summary, our data show that reduced fatty acid and lipid metabolite levels in the serum of the WM patients are associated with increased lipid peroxidation and that downregulation of 15-LOX increases the survival of WM cells. These data are highly significant in identifying the biomarkers of disease progression and designing targeted therapeutic intervention.

17.
Mol Med Rep ; 23(5)2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33760198

RESUMO

Melatonin (MT) is an indoleamine hormone that can counteract ischemia­induced organ injury through its antioxidant effects. The aim of the present study was to investigate the protective effects of exogenous MT against hemorrhagic shock (HS)­induced hepatic ischemic injury in rats, and the role of the nuclear factor (NF)­κB signaling pathway in this process. A rat model of HS­induced hepatic ischemic injury was established. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), glutamate dehydrogenase (GDH), tumor necrosis factor (TNF)­α, interferon (IFN)­Î³, interleukin (IL)­6 and IL­1ß were measured every 6 h, and the 24­h survival rate of the rats was analyzed. All surviving rats were sacrificed after 24 h. Pathological changes in the liver and the hepatocyte apoptosis rate were observed by hematoxylin and eosin staining and TUNEL assay, respectively, and the expression levels of NF­κB p65 and NF­κB inhibitor α (IκBα) were analyzed by reverse transcription­quantitative PCR analysis and western blotting. The results demonstrated that the serum levels of ALT, AST, LDH, GDH, TNF­α, IFN­Î³, IL­6 and IL­1ß gradually increased after HS compared with those in rats subjected to a sham procedure, but this increase was attenuated by MT. Furthermore, the survival rate of the MT group was significantly higher compared with that of the HS group. The degree of pathological hepatic injury, the hepatocyte apoptosis rate, and the hepatic levels of TNF­α, IFN­Î³, IL­6 and IL­1ß were significantly decreased in the MT group compared with the HS group. In addition, the mRNA expression of NF­κB p65 was significantly decreased and the mRNA expression of IκBα was significantly increased in the MT group compared with the sham group. Furthermore, the NF­κB p65 protein levels in the MT group were significantly increased in the cytosol but decreased in the nucleus, and the IκBα protein levels were increased while those of phosphorylated IκBα were decreased compared with those in the HS group. Therefore, it may be inferred that exogenous MT alleviates HS­induced hepatic ischemic injury in rats via the inhibition of NF­κB activation and IκBα phosphorylation.

18.
BMC Cardiovasc Disord ; 21(1): 152, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33765929

RESUMO

BACKGROUND: Cardiac myxomas (CMs) and thrombi are associated with high morbidity and mortality. These two conditions need totally different treatments. However, they are difficult to distinguish using naked eye. In clinical, misdiagnoses occur now and then. This study aimed to compare the characteristics of CMs and cardiac thrombi and investigate the value of a radiomics signature in distinguishing CMs from cardiac thrombi, based on cardiovascular contrast-enhanced computed tomography (CECT) images. METHODS: A total of 109 patients who had CMs (n = 59) and cardiac thrombi (n = 50) were enrolled in this retrospective study from 2009 to 2019. First, the lesion characteristics of cardiovascular CECT images were documented and compared by two radiologists. Then all patients were randomly allotted to either a primary group or a validation group according to a 7:3 ratio. Univariate analysis and the least absolute shrinkage and selection operator were used to select robust features. The best radiomics signature was constructed and validated using multivariate logistic regression. An independent clinical model was created for comparison. RESULTS: The best radiomics signature was developed using eight selected radiomics. The classification accuracies of the radiomics signature were 90.8% and 90.9%, and the area under the receiver operating characteristic curves were 0.969 and 0.926 in the training and testing cohorts, respectively. Cardiovascular CECT images showed that the two diseases had significant differences in location, surface, Hydrothorax, pericardial effusion and heart enlargement. The naked eye findings were used to create the clinical model. All metrics of the radiomics signature were higher than those of clinical model. CONCLUSIONS: Compared with clinical model, the radiomics signature based on cardiovascular CECT performed better in differentiating CMs and thrombi, suggesting that it could help improving the diagnostic efficiency.

19.
Cardiovasc Diabetol ; 20(1): 73, 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33766020

RESUMO

BACKGROUND: Essential hypertension and type 2 diabetes mellitus (T2DM) are two common chronic diseases that often coexist, and both of these diseases can cause heart damage. However, the additive effects of essential hypertension complicated with T2DM on left ventricle (LV) diastolic function have not been fully illustrated. This study aims to investigate whether T2DM affects the diastolic function of the LV in patients with essential hypertension using the volume-time curve from cardiac magnetic resonance (CMR). METHODS: A total of 124 essential hypertension patients, including 48 with T2DM [HTN(T2DM +) group] and 76 without T2DM [HTN(T2DM-) group], and 52 normal controls who underwent CMR scans were included in this study. LV volume-time curve parameters, including the peak ejection rate (PER), time to peak ejection rate (PET), peak filling rate (PFR), time to peak filling rate from end-systole (PFT), PER normalized to end-diastolic volume (PER/EDV), and PFR normalized to EDV (PFR/EDV), were measured and compared among the three groups. Multivariate linear regression analyses were performed to determine the effects of T2DM on LV diastolic dysfunction in patients with hypertension. Pearson correlation was used to analyse the correlation between the volume-time curve and myocardial strain parameters. RESULTS: PFR and PFR/EDV decreased from the control group, through HTN(T2DM -), to HTN(T2DM +) group. PFT in the HTN(T2DM-) group and HTN(T2DM +) group was significantly longer than that in the control group. The LV remodelling index in the HTN(T2DM -) and HTN(T2DM +) groups was higher than that in the normal control group, but there was no significant difference between the HTN(T2DM -) and HTN(T2DM +) groups. Multiple regression analyses controlling for covariates of systolic blood pressure, age, sex, and heart rate demonstrated that T2DM was independently associated with PFR/EDV (ß = 0.252, p < 0.05). The volume-time curve method has good repeatability, and there is a significant correlation between volume-time curve parameters (PER/EDV and PFR/EDV) and myocardial peak strain rate, especially circumferential peak strain rate, which exhibited the highest correlation (r = - 0.756 ~ 0.795). CONCLUSIONS: T2DM exacerbates LV diastolic dysfunction in patients with essential hypertension. The LV filling model changes reflected by the CMR volume-time curve could provide more information for early clinical intervention.

20.
Brief Bioinform ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33709154

RESUMO

BACKGROUND: Substructure screening is widely applied to evaluate the molecular potency and ADMET properties of compounds in drug discovery pipelines, and it can also be used to interpret QSAR models for the design of new compounds with desirable physicochemical and biological properties. With the continuous accumulation of more experimental data, data-driven computational systems which can derive representative substructures from large chemical libraries attract more attention. Therefore, the development of an integrated and convenient tool to generate and implement representative substructures is urgently needed. RESULTS: In this study, PySmash, a user-friendly and powerful tool to generate different types of representative substructures, was developed. The current version of PySmash provides both a Python package and an individual executable program, which achieves ease of operation and pipeline integration. Three types of substructure generation algorithms, including circular, path-based and functional group-based algorithms, are provided. Users can conveniently customize their own requirements for substructure size, accuracy and coverage, statistical significance and parallel computation during execution. Besides, PySmash provides the function for external data screening. CONCLUSION: PySmash, a user-friendly and integrated tool for the automatic generation and implementation of representative substructures, is presented. Three screening examples, including toxicophore derivation, privileged motif detection and the integration of substructures with machine learning (ML) models, are provided to illustrate the utility of PySmash in safety profile evaluation, therapeutic activity exploration and molecular optimization, respectively. Its executable program and Python package are available at https://github.com/kotori-y/pySmash.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...