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1.
Oxid Med Cell Longev ; 2020: 9268083, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014280

RESUMO

Accumulating evidence has demonstrated that oxidative stress is associated with depression. Our present study aimed at investigating the antidepressant effect and the possible mechanisms of curcumin (CUR) in chronic unpredictable mild stress- (CUMS-) induced depression model in rats. After exposure to CUMS for four weeks, the rats showed depressive-like behavior, and the depressive-like behaviors in CUMS-treated rats were successfully corrected after administration of CUR. In addition, CUR could effectively decrease protein expression of oxidative stress markers (Nox2, 4-HNE, and MDA) and increase the activity of CAT. CUR treatment also reversed CUMS-induced inhibition of Nrf2-ARE signaling pathway, along with increasing the mRNA expression of NQO-1 and HO-1. Furthermore, the supplementation of CUR also increased the ratio of pCREB/CREB and synaptic-related protein (BDNF, PSD-95, and synaptophysin). In addition, CUR could effectively reverse CUMS-induced reduction of spine density and total dendritic length. In conclusion, the study revealed that CUR relieves depressive-like state through the mitigation of oxidative stress and the activation of Nrf2-ARE signaling pathway.

2.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5188-5191, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33019154

RESUMO

A miniaturized intracerebral potential recorder for long-term local field potential (LFP) of deep brain signals is proposed. LFP can be recorded by deep brain electrodes. The abnormal beta-band oscillation of LFP in subthalamic nucleus and internal globus pallidus in patients with Parkinson's disease (PD) are associated with the severity of the symptoms. The LFP signal from patients who have been implanted with deep brain electrode can be monitored by our system for at least 24 hours in real time. Graphical user interface has also been developed for use by medical personnel. Imitation experiments and in vivo experiments were performed to successfully verify that our system can measure LFP signals. With 24-hour intracerebral signals, researchers can analyze what is happened in the brain in daily life. In the future, more effective PD treatment can be developed, such as intelligent closed-loop deep brain stimulation.

3.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5208-5211, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33019158

RESUMO

The "diving reflex" (DR) is a very powerful autonomic reflex that facilitates survival in hypoxic/anoxic conditions and could trigger multifaceted physiologic effects for the treatment of various diseases by modulating the cardiovascular, respiratory, and nervous systems. The DR can be induced by cold water or noxious gases applied to the anterior nasal mucosa and paranasal regions, which can stimulate trigeminal thermo- or chemo-receptors to send afferent signals to medullary nuclei which mediate the sympathetic and parasympathetic nervous systems. Although promising, these approaches have yet to be adopted in routine clinical practice due to the inability to precisely control exposure-response relationships, lack of reproducibility, and difficulty implementing in a clinical setting. In this study, we present the ability of electrical Trigeminal (Infraorbital) Nerve Stimulation (eTINS) to induce the DR in a dose-controllable manner. We found that eTINS not only triggered specific physiological changes compatible with the pattern of "classic" DR observed in animals/humans, but also controlled the induced-DR at varying levels. This study demonstrates, for the first time, that the intensity of the DR is controllable by dose and opens possibility to investigate its protective mechanism against various pathologies in well-controlled research settings.

4.
J Biol Chem ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037073

RESUMO

The adipocyte-derived hormone leptin increases trafficking of KATP and Kv2.1 channels to the pancreatic ß-cell surface, resulting in membrane hyperpolarization and suppression of insulin secretion. We have previously shown that this effect of leptin is mediated by the NMDA subtype of glutamate receptors (NMDARs). It does so by potentiating NMDAR activity, thus enhancing Ca2+ influx and the ensuing downstream signaling events that drive channel trafficking to the cell surface. However, the molecular mechanism by which leptin potentiates NMDARs in ß-cells remains unknown. Here we report that leptin augments NMDAR function via Src kinase-mediated phosphorylation of the GluN2A subunit. Leptin-induced membrane hyperpolarization diminished upon pharmacological inhibition of GluN2A but not GluN2B, indicating involvement of GluN2A-containing NMDARs. GluN2A harbors tyrosine residues which when phosphorylated by Src family kinases potentiate NMDAR activity. We found that leptin increases phosphorylation of Y418 in Src, an indicator of kinase activation. Pharmacological inhibition of Src or overexpression of a kinase-dead Src mutant prevented the effect of leptin, while a Src kinase activator peptide mimicked it. Using mutant GluN2A overexpression, we show that Y1292 and Y1387 but not Y1325 are responsible for the effect of leptin. Importantly, ß-cells from db/db mice, a type 2 diabetes mouse model lacking functional leptin receptors, or from obese diabetic human donors failed to respond to leptin but hyperpolarized in response to NMDA. Our study reveals a signaling pathway wherein leptin modulates NMDARs via Src to regulate ß-cell excitability and suggests NMDARs as a potential target to overcome leptin resistance.

5.
Gene Ther ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046836

RESUMO

Recent studies have revealed that YKL-40 is involved in the pathogenesis of asthma. However, its specific mechanism remains unclear. The present study aims to investigate the effect of adenovirus vector-mediated YKL-40 short hairpin RNA (shRNA) on regulation of airway inflammation in a murine asthmatic model. Mice were assessed for airway hyperresponsiveness (AHR), total leukocytes and the percentage of eosinophil cells in bronchoalveolar lavage fluid (BALF). YKL-40 mRNA and protein expression levels were detected using quantitative real-time PCR and western blot assays. Enzyme-linked immunosorbent assay (ELISA) was used to detect YKL-40 and eosinophil-related chemokine expression levels in BALF and serum. Lung histology analyses were performed to evaluate the degree of inflammatory cell infiltration around the airway and airway mucus secretion.YKL-40 shRNA significantly inhibited the YKL-40 gene expression in asthmatic mice. In addition, YKL-40 shRNA alleviated eosinophilic airway inflammation, AHR, airway mucus secretion and decreased the levels of YKL-40 in BALF and serum in a murine asthmatic model. The levels and mRNA expression of IL-5, IL-13 in asthmatic mice lung tissues, eotaxin, and GM-CSF in BALF and serum significantly decreased. Bone marrow signaling molecules including IL-5, eotaxin, and GM-CSF were correlated with decreased levels of YKL-40. The study reveals that YKL-40 could be involved in asthma inflammation by altering bone marrow signaling molecules. YKL-40 gene RNA interference could provide new therapeutic strategies for asthma.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33055031

RESUMO

Correlation filters combined with deep features have delivered impressive results in visual tracking task. However, existing approaches treat deep features produced by different network layers independently, limiting their representation power. To address this issue, this paper proposes a multi-task deep dual correlation filters (MDDCF) based method for robust visual tracking. First, a new multi-task learning scheme is designed to take full advantage of the multi-level features of deep networks, where target representation with individual features is regarded as a single task. As such, the interdependencies between different levels of features can be better explored. Second, we reformulate the objective function of the dual correlation filters and propose a new alternating optimization method, allowing joint training of the correlation filters and network parameters. Third, we design an effective object template update scheme which can well capture the target appearance variations. Extensive experimental evaluations on seven benchmark datasets show that the proposed MDDCF tracker performs favorably against state-ofthe-art methods.

8.
J Nat Prod ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026809

RESUMO

Excessive eIF4E phosphorylation by mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (MNK1 and MNK2; collectively, MNKs) has been associated with oncogenesis. The overexpression of eIF4E in acute myeloid leukemia (AML) is related to cancer cell growth and survival. Thus, the inhibition of MNKs and eIF4E phosphorylation are potential therapeutic strategies for AML. Herein, a structure-based virtual screening approach was performed to identify potential MNK inhibitors from natural products. Three flavonoids, apigenin, hispidulin, and luteolin, showed MNK2 inhibitory activity with IC50 values of 308, 252, and 579 nM, respectively. A structure-activity relationship analysis was performed to disclose the molecular interactions. Furthermore, luteolin exhibited substantial inhibitory efficacy against MNK1 (IC50 = 179 nM). Experimental results from cellular assays showed that hispidulin and luteolin inhibited the growth of MOLM-13 and MV4-11 AML cells by downregulating eIF4E phosphorylation and arresting the cell cycle at the G0/G1 phase. Therefore, hispidulin and luteolin showed promising results as lead compounds for the potential treatment for AML.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33031042

RESUMO

Visual tracking is one of the fundamental tasks in computer vision with many challenges, and it is mainly due to the changes in the target's appearance in temporal and spatial domains. Recently, numerous trackers model the appearance of the targets in the spatial domain well by utilizing deep convolutional features. However, most of these CNN-based trackers only take the appearance variations between two consecutive frames in a video sequence into consideration. Besides, some trackers model the appearance of the targets in the long term by applying RNN, but the decay of the target's features degrades the tracking performance. In this article, we propose the antidecay long short-term memory (AD-LSTM) for the Siamese tracking. Especially, we extend the architecture of the standard LSTM in two aspects for the visual tracking task. First, we replace all of the fully connected layers with convolutional layers to extract the features with spatial structure. Second, we improve the architecture of the cell unit. In this way, the information of the target appearance can flow through the AD-LSTM without decay as long as possible in the temporal domain. Meanwhile, since there is no ground truth for the feature maps generated by the AD-LSTM, we propose an adversarial learning algorithm to optimize the AD-LSTM. With the help of adversarial learning, the Siamese network can generate the response maps more accurately, and the AD-LSTM can generate the feature maps of the target more robustly. The experimental results show that our tracker performs favorably against the state-of-the-art trackers on six challenging benchmarks: OTB-100, TC-128, VOT2016, VOT2017, GOT-10k, and TrackingNet.

10.
Cell Death Dis ; 11(10): 854, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33056980

RESUMO

Radiotherapy for head and neck cancer is associated with impairment of salivary gland function and consequent xerostomia, which has a devastating effect on the quality of life of the patients. The mechanism of radiation-induced salivary gland damage is not completely understood. Cellular senescence is a permanent state of cell cycle arrest accompanied by a secretory phenotype which contributes to inflammation and tissue deterioration. Genotoxic stresses, including radiation-induced DNA damage, are known to induce a senescence response. Here, we show that radiation induces cellular senescence preferentially in the salivary gland stem/progenitor cell niche of mouse models and patients. Similarly, salivary gland-derived organoids show increased expression of senescence markers and pro-inflammatory senescence-associated secretory phenotype (SASP) factors after radiation exposure. Clearance of senescent cells by selective removal of p16Ink4a-positive cells by the drug ganciclovir or the senolytic drug ABT263 lead to increased stem cell self-renewal capacity as measured by organoid formation efficiency. Additionally, pharmacological treatment with ABT263 in mice irradiated to the salivary glands mitigates tissue degeneration, thus preserving salivation. Our data suggest that senescence in the salivary gland stem/progenitor cell niche contributes to radiation-induced hyposalivation. Pharmacological targeting of senescent cells may represent a therapeutic strategy to prevent radiotherapy-induced xerostomia.

11.
Invest New Drugs ; 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33052556

RESUMO

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are recommended first-line treatments in EGFR-mutated (EGFRm) non-small-cell lung cancer (NSCLC). However, acquired resistance (e.g. MET amplification) is frequently observed. Savolitinib (volitinib, HMPL-504, AZD6094) is an oral, potent, and highly selective MET-TKI. In this phase Ib, open-label, multicenter study, we enrolled Chinese patients with EGFRm advanced NSCLC, whose disease progressed following prior EGFR-TKI treatment. In the safety run-in, patients received savolitinib 600 or 800 mg plus gefitinib 250 mg orally once daily, and dose-limiting toxicities were recorded. In the expansion phase, patients with MET amplification received savolitinib plus gefitinib. The primary endpoint was safety/tolerability. Secondary endpoints included antitumor activity. Thirteen patients were enrolled in the safety phase (median age 52 years, 46% female) and 51 enrolled in the expansion phase (median age 61 years, 67% female). No dose-limiting toxicities were reported in either dose group during the safety run-in. Adverse events of grade ≥ 3 in the safety run-in and expansion phases (n = 57) were reported in 21 (37%) patients. The most frequently reported adverse events (all grades) were: vomiting (n = 26, 46%), nausea (n = 23, 40%), increased aspartate aminotransferase (n = 22, 39%). Of four deaths, none were treatment-related. The objective response rates in EGFR T790M-negative, -positive, and -unknown patients were 52% (12/23), 9% (2/23), and 40% (2/5), respectively. Savolitinib 600 mg plus gefitinib 250 mg once daily had an acceptable safety profile and demonstrated promising antitumor activity in EGFRm, MET-amplified advanced NSCLC patients who had disease progression on EGFR-TKIs. NCT02374645, Date of registration: March 2nd 2015.

12.
Cell Prolif ; : e12924, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33078469

RESUMO

OBJECTIVES: Chemoresistance induced by cisplatin has become the major impediment to lung cancer chemotherapy. This study explored the potential chemoresistant genes and underlying mechanisms of chemoresistance in NSCLC. MATERIALS AND METHODS: Gene expression profile was integrated with DNA methylation profile to screen the candidate chemoresistant genes. Bioinformatic analysis and immunohistochemistry were used to analyse the association of a candidate gene with the characteristics of NSCLC patients. Recombinant lentivirus vectors were utilized to overexpress or silence candidate gene. Microarrays and immunoblotting were applied to explore the downstream targets of candidate gene. Xenograft models were established to validate the findings in vitro. RESULTS: An increased ZNF300 expression was detected in three chemoresistant cell lines of NSCLC, and the higher expression of ZNF300 was associated with poor OS of NSCLC patients. Cells with upregulated ZNF300 presented chemoresistance and enhanced aggressive growth compared to cells with downregulated ZNF300. ZNF300 inhibited MAPK/ERK pathways and activated CDK1 through inhibiting WEE1 and MYT1 and modulating MYC/AURKA/BORA/PLK1 axis. ICA and ATRA improved the anti-tumour effect of cisplatin on chemoresistant cells by inducing differentiation. CONCLUSIONS: ZNF300 promotes chemoresistance and aggressive behaviour of NSCLC through regulation of proliferation and differentiation by downregulating MAPK/ERK pathways and regulation of slow-cycling phenotype via activating CDK1 by inhibiting WEE1/MYT1 and modulating MYC/AURKA/BORA/PLK1 axis. Cisplatin, combined with ATRA and ICA, might be beneficial in chemoresistant cases of NSCLC.

13.
Eur Radiol ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33068187

RESUMO

OBJECTIVES: To evaluate carotid stiffening in participants without conventional cardiovascular risk factors (CVRFs) by using ultrafast pulse wave velocity (ufPWV). METHODS: The present study enrolled 517 participants without conventional CVRFs (CVRF-Free total population). Subjects in this population were defined as current non-smokers with untreated blood pressure < 140/90 mmHg, fasting blood glucose (FBG) < 7.0 mmol/L, total cholesterol (TC) < 6.2 mmol/L, low-density lipoprotein cholesterol < 4.1 mmol/L, and high-density lipoprotein cholesterol ≥ 1.0 mmol/L. Participants in the subgroup with optimal CVRFs (CVRF-Optimal subgroup; n = 188) were defined as having blood pressure < 120/80 mmHg, TC < 5.2 mmol/L, and FBG < 5.6 mmol/L. Clinical interviews, physical examinations, serum draw, carotid intima-media thickness (cIMT), and ufPWV were evaluated. Adjusted odds ratios (ORs) with 95% confidence intervals and ordinal logistic regression models were used. RESULTS: Carotid stiffening was present in 46.2-54.5% of CVRF-Free subjects. Age, male sex, and body mass index (BMI) were independently associated with carotid stiffening in both the CVRF-Free total population and CVRF-Optimal subgroup (OR for age = 1.10-1.11, OR for male sex = 2.65-7.19, OR for BMI = 1.34-1.62; p < 0.05). Carotid stiffening was associated with TC only in the CVRF-Free total population (OR for TC = 1.84; p = 0.034). CONCLUSIONS: Many CVRF-Free individuals have carotid stiffening. ufPWV for atherosclerotic stiffening aids the assessment of early atherogenesis and may further clarify the true status of healthy adults without CVRFs. KEY POINTS: • CVRF-Optimal individuals have a lower carotid stiffness than CVRF-Free populations. • ufPWV is a quantitative predictor for the early assessment of AS. • Absent major CVRFs cannot be considered low risk for carotid stiffening and atherosclerosis.

14.
JAMA Intern Med ; 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33031502

RESUMO

Importance: Professional guidelines recommend noninvasive cardiac testing (NIT) within 72 hours of an emergency department (ED) evaluation for suspected acute coronary syndrome. However, there is inexact evidence that this strategy reduces the risk of future death or acute myocardial infarction (MI). Objective: To evaluate the effectiveness of early NIT in reducing the risk of death or acute MI within 30 days. Design, Setting, and Participants: This retrospective, multicenter cohort study within the Kaiser Permanente Southern California integrated health care delivery system compared the effectiveness of early noninvasive cardiac testing vs no testing in patients with chest pain and in whom acute MI was ruled out who presented to an ED from January 2015 to December 2017. Patients were followed up for up to 30 days after emergency department discharge. Exposures: Noninvasive cardiac testing performed within 3 days of an ED evaluation for suspected acute coronary syndrome. Main Outcomes and Measures: The primary outcome was composite risk of death or acute MI, within 30 days of an ED discharge. Results: A total of 79 040 patients were evaluated in this study, of whom 57.7% were female. The mean (SD) age of the cohort was 57 (16) years, and 16 164 patients (21%) had completed early NIT. The absolute risk of death or MI within 30 days was low (<1%). Early NIT had the minor benefit of reducing the absolute composite risk of death or MI (0.4% [95% CI, -0.6% to -0.3%]), and, separately, of death (0.2% [95% CI, -0.2% to -0.1%]), MI (-0.3% [95% CI, -0.5% to -0.1%]), and major adverse cardiac event (-0.5% [95% CI, -0.7% to -0.3%]). The number needed to treat was 250 to avoid 1 death or MI, 500 to avoid 1 death, 333 to avoid 1 MI, and 200 to avoid 1 major adverse cardiovascular event within 30 days. Subgroup analysis revealed a number needed to treat of 14 to avoid 1 death or MI in the subset of patients with elevated troponin. Conclusions and Relevance: Early NIT was associated with a small decrease in the risk of death or MI in patients admitted to the ED with suspected acute coronary syndrome, but this clinical strategy may not be optimal for most patients given the large number needed to treat.

15.
Food Chem ; 341(Pt 2): 128265, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33031957

RESUMO

A series of 1,2,4-triazole hydrazones (1-16) were synthesized, and their inhibitory activities and mechanisms on tyrosinase were investigated by ultraviolet spectrophotometry, fluorescence quenching, molecular docking study, etc. Most of compounds possessed potent tyrosinase inhibitory activity. Thereinto, compound 9 presented the superior activity with IC50 of 0.9 µM, which was markedly lower than the standard kojic acid (IC50 = 64.1 µM). Compound 9 not only interacted with copper ions in the active center of the enzyme but also bound to the enzyme-substrate complex, indicating that it was a competitive-noncompetitive mixed inhibitor. Additionally, it also displayed potent DPPH scavenging activity. Antibrowning test showed that compound 9 effectively reduced the enzymatic browning of fresh-cut potatoes. Furthermore, compound 9 exhibited low cytotoxic activity against human normal cell line with IC50 of 49.9 µM. Overall, the present study suggests that these compounds may serve as lead molecules for developing novel antibrowning agents in food industry.

16.
Spectrochim Acta A Mol Biomol Spectrosc ; 246: 119004, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33070014

RESUMO

A novel ratiometric fluorescent sensor based on Förster resonance energy transfer (FRET) platform was designed for riboflavin (RF) detection. The graphitic carbon nitrides quantum dots - Zn-MOF composite (g-CNQDs@Zn-MOF) was used as the fluorescent probe. In the FRET system, g-CNQDs@Zn-MOF and RF acted as donor and acceptor, respectively. The probe exhibited high sensitivity and good selectivity to RF, and had been successfully used for the detection of RF in milk and vitamin B2 tablets. The detection limit of the sensor was 15 nM. The strategy expanded the application of MOF in sensing filed and provided a new method for the detection of RF.

17.
Chest ; 158(4): e153-e157, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33036111

RESUMO

CASE PRESENTATION: A 52-year-old man was referred to our hospital for cough, fever, chest pain, and progressive dyspnea. He has worked as a full-time security staff at a community center and was in a normal state of health until 11 months prior to referral when he began experiencing cough, expectoration, a high-grade fever (up to 39.7°C), chills, and left chest pain. He visited the local hospital several times with suspected lung cancer. Bronchoscopy showed chronic inflammatory changes in his bronchi. He was given a course of antibiotics, but his fever had not subsided. The patient had visited a bamboo rat farm and consumed bamboo rat meat one year previously. He had never smoked.

18.
J Food Biochem ; : e13515, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33043487

RESUMO

Grifola frondosa is a basidiomycete polypore fungus. Polysaccharides from G. frondosa (PGF) has recently attracted attention for its various physiological activities including antioxidant, antitumor, and anti-fatigue effects. In this study, hypoglycemic activity of PGF and its preventive effect against the progression of kidney fibrosis in Diabetic nephropathy (DN) rats were investigated. The results showed that PGF led to a significant decrease in fasting blood glucose levels and an increase in body weight in the treatment group compared with those of model group. Serum biochemical indexes including N-acetyl-ß-D-glucosaminidase (NAG), blood urea nitrogen (BUN), serum creatinine (SCr), and urine microalbumin (u-mAlb) levels of PGF-treated group were significantly lower than those of model group. Inflammatory cytokines and renal fibrosis indexes of PGF group were also decreased compared to the model group. The whole results demonstrated the renal-protective effects of PGF via reducing the inflammatory factor content and preventing renal fibrosis. PRACTICAL APPLICATIONS: G. frondosa constitutes a rich source of polysaccharides, steroid, and phenolic compounds. The results obtained revealed that the purified PGF have the effect of reducing inflammation cytokines and renal fibrosis indexes. These two factors are associated with the development and progression of diabetic nephropathy. Therefore, PGF may produce both hypoglycemic and renal-protective effects, and potentially be of use as a functional food for the treatment or prevention of diabetic nephropathy.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33044117

RESUMO

INTRODUCTION: Non-small cell lung cancer (NSCLC) accounts for most lung cancers worldwide and has a poor prognosis at later stages; programmed cell death protein-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have provided promising new treatment approaches for these patients. Tislelizumab, an anti-PD-1 monoclonal antibody, was engineered to minimize binding to FcγR on macrophages to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy. Tislelizumab has demonstrated clinical activity and is approved in China for treatment of previously treated classical Hodgkin lymphoma and previously treated metastatic PD-L1-high urothelial carcinoma. AREAS COVERED: This review summarizes the clinical efficacy, safety, and tolerability of tislelizumab in patients with NSCLC and examines the mechanism of action, pharmacokinetic, and pharmacodynamic profiles of tislelizumab. EXPERT OPINION: Tislelizumab has higher affinity to PD-1 than pembrolizumab and nivolumab, potentially due to its differential PD­1 binding orientation. Tislelizumab demonstrated encouraging efficacy results, long duration of response, and a manageable safety profile across multiple clinical trials in advanced NSCLC. Ongoing trials of drug combinations (eg, tislelizumab plus angiogenesis inhibitors, immune checkpoint inhibitors, or immune agonists) and examining efficacy across the severity of disease will provide opportunities to understand and feature tislelizumab in clinical practice.

20.
Food Chem ; 340: 128108, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-33010643

RESUMO

α-Dicarbonyl compounds are generated in large amounts during heat treatment in food production. This work compared the influence of glycation by α-dicarbonyl on the hydrothermal aggregation of bovine serum albumin (BSA) and of ß-casein (ß-CN). Glycation by α-dicarbonyl compounds was found to be more efficient than glycation by glucose in reducing the free amino groups, surface hydrophobicity and isoelectric point of BSA, thus greatly inhibited the hydrothermal aggregation of BSA. In addition, glycation by α-dicarbonyl greatly transformed the rigid BSA aggregates into flexible structures, based on analysis by fluorescence spectrum, transmission electron microscope and small-angle X-ray scattering. In contrast, both the aggregation process and aggregates conformation of ß-CN were found to be minimally affected by glycation, possibly due to the intrinsic disorder of ß-CN. This work highlights the substantial influences of α-dicarbonyl on dietary proteins during heat treatment depending on the protein structural characteristics.

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