Sirtuin1-p53: A potential axis for cancer therapy.

Sirtuin1 (SIRT1) is a conserved nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase that plays key roles in a range of cellular events, including the maintenance of genome stability, gene regulation, cell proliferation, and apoptosis. P53 is one of the most studied tumor suppressors and the first identified non-histone target of SIRT1. SIRT1 deacetylates p53 in a NAD+-dependent manner and inhibits its transcriptional activity, thus exerting action on a series of pathways related to tissue homeostasis and various pathological states. The SIRT1-p53 axis is thought to play a central role in tumorigenesis. Although SIRT1 was initially identified as a tumor promoter, evidence now indicates that SIRT1 may also act as a tumor suppressor. This seemingly contradictory evidence indicates that the functionality of SIRT1 may be dictated by different cell types and intracellular localization patterns. In this review, we summarize recent evidence relating to the interactions between SIRT1 and p53 and discuss the relative roles of these two molecules with regards to cancer-associated cellular events. We also provide an overview of current knowledge of SIRT1-p53 signaling in tumorigenesis. Given the vital role of the SIRT1-p53 pathway, targeting this axis may provide promising strategies for the treatment of cancer.

Comprehensive and Integrated Analysis Identifies ZEB1 as a Key Novel Gene in Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer with a poor prognosis. Therefore, it is crucial to explore molecular prognostic biomarkers for OSCC. ZEB1 (also known as δEF1) is a member of the zinc finger E-box binding protein family of transcription factors involved in various biological processes, including tumorigenesis, progression, and metastasis. Recent evidence suggests that ZEB1 has a role in the tumorigenicity of oral epithelial cells, although its mode of action needs to be investigated further. To better understand the relationship between ZEB1 and OSCC, we transfected the ZEB1-overexpressing oral squamous cell lines SCC9 and SCC25 with lentivirus and then extracted RNA from the cells for gene expression analysis. Furthermore, the GSE30784 dataset was downloaded from the Gene Expression Omnibus (GEO) database to identify potential biomarkers of OSCC and to assess the potential mechanisms. The criteria for identification of their DEGs were |logFC| > 1 and P < 0.05. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) analyses were also carried out. Integrating the data from the PPI network and survival analysis identified that ZEB1 might be an independent prognostic biomarker in OSCC. In conclusion, integrated bioinformatics and microarray analysis identified the critical gene ZEB1 linked to the overall survival (OS) of patients with OSCC. ZEB1 could be applied as a prognostic biomarker to forecast the survival of patients with OSCC and might indicate innovative therapeutic indicators for OSCC.

Effects of Solvent and Electrospinning Parameters on the Morphology and Piezoelectric Properties of PVDF Nanofibrous Membrane.

PVDF electrospun membranes were prepared by employing different mixtures of solvents and diverse electrospinning parameters. A comprehensive investigation was carried out, including morphology, nanofiber diameter, crystallinity, ß-phase fraction, and piezoelectric response under external mechanical strain. It was demonstrated that by using low-toxicity DMSO as the solvent, PVDF membranes with good morphology (bead-free, smooth surface, and uniform nanofiber) can be obtained. All the fabricated membranes showed crystallinity and ß-phase fraction above 48% and 80%, respectively; therefore, electrospinning is a good method for preparing PVDF membranes with the piezoelectric properties. Moreover, we considered a potential effect of the solvent properties and the electrospinning parameters on the final piezoelectric properties. When PVDF membranes with different ß-phase fractions and crystallinity values are applied to make the piezoelectric transducers, various piezoelectric voltage outputs can be obtained. This paper provides an effective and efficient strategy for regulating the piezoelectric properties of PVDF electrospun membranes by controlling both solvent dipole moment and process parameters. To the best of our knowledge, this is the first time that the influence of a solvent's dipole moment on the piezoelectric properties of electrospun materials has been reported.

[Effects of 40 Hz multisensory stimulation on trauma-induced anxiety-like behavior in rats].

OBJECTIVE: To investigate the effects of 40 Hz acousto-optical stimulation on anxiety like symptoms of post-traumatic stress disorder (PTSD), with emphasis on the possible molecular mechanism stimulation. METHODS: Thirty SD rats were randomly divided into three groups: Control group, PTSD group and PTSD+40 Hz group,ten rats in each group. The SPS&S model was established in the rats of the PTSD group and PTSD+40 Hz group and, then PTSD+40 Hz group rats were stimulated with 40 Hz acousto-optical stimulation for 7 days. The behavior of anxiety was tested by elevated plus maze (EPM) and open field test (OFT). The expressions of brain-derived neurotrophic factor (BDNF), tyrosine kinase receptor B (TrkB), synapsinⅠand postsynaptic density protein 95 (PSD95) in the rat prefrontal cortex (PFC) and hippocampus (HIP) were detected by Western blot. The mRNA transcription level of BDNF genes in the PFC and HIP was verified by real-time quantitative PCR (RT-PCR) and the distribution of BDNF in the PFC and HIP was determined by immunofluorescence. RESULTS: Compared with the Control group, in the OFT the total distance and the time spending in the center, and in the EPM the total distance were decreased significantly (P＜0.05), the number of entering into the open arm as a percentage of the total number of entering in two arms was decreased,and the expression levels of BDNF, TrkB, PSD95, Synapsin I protein in HIP and PFC, and the mRNA expression level of BDNF were reduced significantly (P＜0.01), the immunofluorescence expression of BDNF was reduced in CA1, DG and PFC in the PTSD group rats; Compared with the PTSD group, the total distance and the time spending in the center in OFT (P＜0.05), the total distance and the number of entering into the open arm as a percentage of the total number were increased significantly (P＜0.05), the protein expression levels of BDNF, TrkB, PSD95, SynapsinⅠin the PFC and HIP, the mRNA expression level of BDNF were increased significantly (P＜0.05), and the immunofluorescence expression of BDNF was increased significantly in CA1, DG and PFC in the PTSD+40 Hz group rats. CONCLUSION: 40 Hz acousto-optical stimulation improves the formation of anxiety-like symptoms in rats with PTSD, which may be related to the synaptic plasticity influenced by BDNF-TrkB signaling pathway.

Structure-guided discovery of antioxidant peptides bounded to the Keap1 receptor as hunter for potential dietary antioxidants.

Human health can be damaged by free radicals, and antioxidant peptides are excellent radical scavengers. Antioxidant tripeptides data set based on 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulofnic acid) (ABTS) assay was created, 9 types of descriptors were integrated and 4 quantitative structure-activity relationship (QSAR) models were constructed in this study. Several structural factors influencing the activity of antioxidant tripeptides and the dominant amino acids at each position of tripeptides were revealed by the optimal model. Ten food-derived tripeptides with higher activity were selected for synthesis and activity determination. Molecular docking results demonstrated that these tripeptides were stably bound to the Keap1 receptor, further elucidating the antioxidant mechanism. It was known from the simulation of gastrointestinal digestion experiments that the model results possessed a guiding effect on the selection of proteins with high antioxidant activity. The performance of the model was proved to be robust after validation.

Combining experimental techniques with molecular dynamics to investigate the impact of different enzymatic hydrolysis of ß-lactoglobulin on the antigenicity reduction.

ß-Lactoglobulin (ß-LG) is one of the major food allergens. Enzymatic hydrolysis is a promising strategy to reduce the antigenicity of ß-LG in industrial production. The relationship between the cleavage sites of ß-LG by protease and its antigenic active sites were explored in this study. Molecular docking and molecular dynamics (MD) were used to analyze the active sites and interaction force of ß-LG and IgG antibody. Whey protein was hydrolyzed by four specific enzymes and the antigenicity of the hydrolysates were determined by ELISA. The results of MD showed that the amino acid residue Gln155 (-4.48 kcal mol-1) played the most important roles in the process of binding. Hydrolysates produced by AY-10, which was the only one with specificity towards cleavage sites next to a Gln, had the lowest antigenicity at the same hydrolysis degree. Antigenicity decrease was related to the energy contribution of the cleavage site in the active sites.

Various machine learning approaches coupled with molecule simulation in the screening of natural compounds with xanthine oxidase inhibitory activity.

Gout is a common inflammatory arthritis associated with various comorbidities, such as cardiovascular disease and metabolic syndrome. Xanthine oxidase inhibitors (XOIs) have emerged as effective substances to control gout. Much attention has been given to the search for natural XOIs. In this study, a molecular database of natural XOIs was created for modeling purposes. Quantitative structure-activity relationship models were developed by combining various machine learning approaches and three descriptor pools. The models revealed several features of XOIs, including hydrophobicity and steric molecular structures. Experimental results showed the xanthine oxidase (XO) inhibitory activity of predicted compounds. Vanillic acid was identified as a promising new XOI candidate, with an IC50 of 0.593 µg mL-1. The functions of hydrogen bonds and hydrophobic interactions in XO activity inhibition were confirmed by molecular docking. This study fills knowledge gaps pertaining to the discovery of natural XOIs and to the interaction mechanisms between XOIs and XO.

FTIR spectroscopy coupled with machine learning approaches as a rapid tool for identification and quantification of artificial sweeteners.

Fourier transform infrared (FTIR) spectroscopy calibrations were developed to simultaneously determine the multianalytes of five artificial sweeteners, including sodium cyclamate, sucralose, sodium saccharin, acesulfame-K and aspartame. By combining the pretreatment of the spectrum and principal component analysis, 131 feature wavenumbers were extracted from the full spectral range for modelling to qualitative and quantitative analysis. Compared to random forest, k nearest neighbour and linear discriminant analysis, support vector machine model had better predictivity, indicating the most effective identification performance. Furthermore, multivariate calibration models based on partial least squares regression were constructed for quantifying any combinations of the five artificial sweeteners, and validated by prediction data sets. As shown by the good agreement between the proposed method and the reference HPLC for the determination of the sweeteners in beverage samples, a promising and rapid tool based on FTIR spectroscopy, coupled with chemometrics, has been performed to identify and objectively quantify artificial sweeteners.

Agmatinase promotes the lung adenocarcinoma tumorigenesis by activating the NO-MAPKs-PI3K/Akt pathway.

Lung adenocarcinoma (LUAD) is one of the leading causes of cancer-related death worldwide. There is an urgent need to uncover the pathogenic mechanism to develop new treatments. Agmatinase (AGMAT) expression and its association with clinicopathological characteristics were analyzed via GEO, Oncomine, and TCGA databases, and IHC staining in human LUAD specimens. An EdU cell proliferation kit, propidiumiodide staining, colony formation, cell migration, and invasion assays, and a xenograft tumor model were used to detect the biological function of AGMAT in LUAD. Furthermore, the expression level of nitric oxide (NO) was detected using a DAF-FMDA fluorescent probe or nitrite assay kit, and further validated with Carboxy-PTIO (a NO scavenger). The roles of three isoforms of nitric oxide synthases (nNOS, eNOS, and iNOS) were validated using L-NAME (eNOS inhibitor), SMT (iNOS inhibitor), and spermidine (nNOS inhibitor). AGMAT expression was up-regulated in LUAD tissues. LUAD patients with high AGMAT levels were associated with poorer prognoses. AGMAT promoted LUAD tumorigenesis in NO released by iNOS both in vitro and in vivo. Importantly, NO signaling up-regulated the expression of cyclin D1 via activating the MAPK and PI3K/Akt-dependent c-myc activity, ultimately promoting the malignant proliferation of tumor cells. On the whole, AGMAT promoted NO release via up-regulating the expression of iNOS. High levels of NO drove LUAD tumorigenesis via activating MAPK and PI3K/Akt cascades. AGMAT might be a potential diagnostic and therapeutic target for LUAD patients.

Facile Fabrication of Hierarchical rGO/PANI@PtNi Nanocomposite via Microwave-Assisted Treatment for Non-Enzymatic Detection of Hydrogen Peroxide.

A hierarchical composite based on the modified reduced graphene oxide with platinum-nickel decorated polyaniline nano-spheres (rGO/PANI@PtNi) was facilely prepared via microwave-assisted self-reduction for an application in nonenzymatic hydrogen peroxide (H2O2) detection. Compared to the pristine rGO, the composite exhibited a much tougher surface due to the stacking of conductive PANI nano-spheres on rGO sheets, leading to good dispersion of PtNi nanoparticles and a large active area. Furthermore, the multi-valance Ni2+/3+ in the PtNi particles effectively promoted the catalytic property of Pt sites and facilitated a superior electrochemical performance of PtNi alloy than that of neat Pt. Owing to the synergistic effect of the improved electrical conductivity and the promoted electrocatalytical property, the modified glassy carbon electrode (GCE) with rGO/PANI@PtNi nanocomposite displayed an outstanding electrochemical sensitivity towards H2O2 with a fast response time (<2 s), a wide linear range (0.1-126.4 mM), a low detection limit (0.5 µM), as well as a long-life stability for one week without obvious degradation. This novel strategy opens a novel and promising approach to design high performance sensors for H2O2 detection.

Impact of enzymatic hydrolysis followed by transglutaminase-induced cross-linking on decreasing antigenicity and reserving partial interfacial properties of whey protein isolate.

Whey protein isolate (WPI) was hydrolyzed by alcalase and trypsin for three hydrolysis degrees (DHs), followed by transglutaminase (TGase) induced cross-linking. The prepared products were measured for surface hydrophobicity and emulsifying and foaming properties, as well as in vitro antigenicity for α-lactalbumin and ß-lactoglobulin. The results indicated that enzymatic hydrolysis of WPI mostly resulted in WPI hydrolysates with significantly decreased antigenicity of α-lactalbumin and ß-lactoglobulin, especially in the case of a higher DH value. Moreover, the TGase-induced cross-linking led to a further antigenicity decrease for these prepared products. Alcalase was always more potent than trypsin to decrease antigenicity. In comparison with WPI, the conducted enzymatic hydrolysis also brought losses to surface hydrophobicity and emulsifying and foaming properties. On the other hand, the conducted cross-linking could partially rescue these properties. It is thus concluded that the assessed enzymatic hydrolysis coupled with TGase-induced cross-linking might be an applicable process for WPI to decrease its potential antigenicity but reserve partial interfacial properties.