Traditional Chinese medicine treatment of diseases has been recognized, but the material basis and mechanisms are not clear. In this study, target prediction of the antigastric cancer (GC) effect of ...Guiqi Baizhu (GQBZP) and the analysis of potential key compounds, key targets, and key pathways for the therapeutic effects against GC were carried out based on the method of network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment. There were 33 proteins shared between GQBZP and GC, and 131 compounds of GQBZP had a high correlation with these proteins, indicating that the PI3K‐AKT signaling pathway might play a key role in GC. From these studies, we selected human epidermal growth factor receptor 2 (HER2) and programmed cell death 1‐ligand 1 (PD‐L1) for docking; the results showed that 385 and 189 compounds had high docking scores with HER2 and PD‐L1, respectively. Six compounds were selected for microscale thermophoresis (MST). Daidzein/quercetin and isorhamnetin/formononetin had the highest binding affinity for HER2 and PD‐L1, with Kd values of 3.7 μmol/L and 490, 667, and 355 nmol/L, respectively. Molecular dynamics simulation studies based on the docking complex structures as the initial conformation yielded the binding free energy between daidzein/quercetin with HER2 and isorhamnetin/formononetin with PD‐L1, calculated by molecular mechanics Poisson‐Boltzmann surface area, of −26.55, −14.18, −19.41, and −11.86 kcal/mol, respectively, and were consistent with the MST results. In vitro experiments showed that quercetin, daidzein, and isorhamnetin had potential antiproliferative effects in MKN‐45 cells. Enzyme activity assays showed that quercetin could inhibit the activity of HER2 with an IC50 of 570.07 nmol/L. Our study provides a systematic investigation to explain the material basis and molecular mechanism of traditional Chinese medicine in treating diseases.
We are committed to establishing a systematic research method based on network pharmacology, multitarget molecular docking, molecular dynamics simulation, and protein and experimental verification in vitro and in vivo, to establish a systematic analysis method for traditional Chinese medicine (TCM) treatment of diseases. We aim to provide a possible theoretical and experimental basis for the standardization and internationalization of TCM.
Sensor networks play an important role in structural health monitoring and tactile sensors. General sensor networks require different types and a large number of sensors. This article proposes a ...shape memory alloy (SMA) sensor interwoven network. Without the need for additional force or displacement sensors, the position of one external force acting on the sensor network can be estimated, and the magnitude of the force and the corresponding deformation of the sensor network can be determined, only by measuring the resistance of the SMA wires. This article not only proposes a theoretical analytical model to solve the force position and its magnitude, and even the entire deformation of the SMA sensor network, but also designs a sensor network and its test bench for loading experiments. The experimental results confirm the feasibility of the theoretical model. The SMA sensor interwoven network has important application value under the condition that it is not convenient to directly observe the position of the external force and monitor the force size, such as an intelligent self-sensing badminton racket at least.
Adult neurogenesis and synaptic remodeling persist as a unique form of structural and functional plasticity in the hippocampal dentate gyrus (DG) and subventricular zone (SVZ) of the lateral ...ventricles due to the existence of neural stem cells (NSCs). Transplantation of NSCs may represent a promising approach for the recovery of neural circuits. Here, we aimed to examine effects of highly neuronal differentiation of NSCs transplantation on hippocampal neurogenesis, metabolic changes and synaptic formation in APP/PS1 mice. 12‐month‐old APP/PS1 mice were used for behavioral tests, immunohistochemistry, western blot, transmission electron microscopy and proton magnetic resonance spectroscopy (1H‐MRS). The results showed that N‐acetylaspartate (NAA) and Glutamate (Glu) levels were increased in the Tg‐NSC mice compared with the Tg‐PBS and Tg‐AD mice 10 weeks after NSCs transplantation. NSC‐induced an increase in expression of synaptophysin and postsynaptic protein‐95, and the number of neurons with normal synapses was significantly increased in Tg‐NSC mice. More doublecortin‐, BrdU/NeuN‐ and Nestin‐positive neurons were observed in the hippocampal DG and SVZ of the Tg‐NSC mice. This is the first demonstration that engrafted NSCs with a high differentiation rate to neurons can enhance neurogenesis in a mouse model of AD and can be detected by 1H‐MRS in vivo. It is suggested that engraft of NSCs can restore memory and promote endogenous neurogenesis and synaptic remodeling, moreover, 1H‐MRS can detect metabolite changes in AD mice in vivo. The observed changes in NAA/creatine (Cr) and glutamate (Glu)/Cr may be correlated with newborn neurons and new synapse formation.
Background
Although stratifying individuals with respect to nasopharyngeal carcinoma (NPC) risk with Epstein‐Barr virus–based markers is possible, the performance of diagnostic methods for detecting ...lesions among screen‐positive individuals is poorly understood.
Methods
The authors prospectively evaluated 882 participants aged 30 to 70 years who were enrolled between October 2014 and November 2018 in an ongoing, population‐based NPC screening program and had an elevated NPC risk. Participants were offered endoscopy and magnetic resonance imaging (MRI), and lesions were identified either by biopsy at a follow‐up endoscopy or further contact and linkage to the local cancer registry through December 31, 2019. The diagnostic performance characteristics of endoscopy and MRI for NPC detection were investigated.
Results
Eighteen of 28 identified NPC cases were detected by both methods, 1 was detected by endoscopy alone, and 9 were detected by MRI alone. MRI had significantly higher sensitivity than endoscopy for NPC detection overall (96.4% vs 67.9%; Pdifference = .021) and for early‐stage NPC (95.2% vs 57.1%; P = .021). The sensitivity of endoscopy was suggestively lower among participants who had previously been screened in comparison with those undergoing an initial screening (50.0% vs 81.2%; P = .11). The authors observed a higher overall referral rate by MRI versus endoscopy (17.3% vs 9.1%; P < .001). Cases missed by endoscopy had early‐stage disease and were more commonly observed for tumors originating from the pharyngeal recess.
Conclusions
MRI was more sensitive than endoscopy for NPC detection in the context of population screening but required the referral of a higher proportion of screen‐positive individuals. The sensitivity of endoscopy was particularly low for individuals who had previously been screened.
This prospective study of people at high risk of nasopharyngeal carcinoma (NPC) shows that magnetic resonance imaging (MRI) screening is significantly more sensitive than endoscopy for detecting NPC and early‐stage NPC. There is also a higher overall rate of referral by MRI versus endoscopy, and this leads to a slightly lower positive predictive value for MRI versus endoscopy.
Neuregulin-4 (Nrg4) is a newly discovered adipokine that is synthesized in many tissues and plays an important role in modulating systemic energy metabolism and in the development of metabolic ...disorders. However, little is known about the relationship between Nrg4 and coronary artery disease (CAD). In this study, we investigated the association between Nrg4 and the presence and severity of CAD.We enrolled 73 patients diagnosed by coronary angiography (CAG) as having CAD and 32 controls. The CAD group was divided into two subgroups according to their SYNTAX score. Plasma levels of Nrg4 were measured in all participants and compared among different groups. The relationship between Nrg4 and CAD was analyzed. Receiver operating characteristic (ROC) analysis was conducted to evaluate the usefulness Nrg4 in assessing the presence and severity of CAD.Nrg4 levels were negatively associated with the SYNTAX score (r = −0.401, P = 0.000). The patients with a higher SYNTAX score had significantly lower Nrg4 levels as compared with the low SYNTAX score subgroup and the controls (P < 0.05). The Nrg4 levels of the low SYNTAX score subgroup were much lower than controls (P < 0.05). Furthermore, an association between Nrg4 and CAD (odds ratio, 0.279; 95% confidence interval, 0.088-0.882) was observed. Nrg4 had 43.8% sensitivity and 96.9% specificity for identifying CAD, and 73.1% sensitivity and 87.3% specificity for identifying patients who had severe coronary artery lesions.Nrg4 levels were found to be inversely associated with the presence and severity of CAD.
Research on the association of physical activity and sedentary time with dementia is accumulating, though elusive, and the interaction effects of the two remain unclear. We analysed the joint ...associations of accelerometer-measured physical activity and sedentary time with risk of incident dementia (all-cause dementia, Alzheimer's disease and vascular dementia).
A total of 90,320 individuals from the UK Biobank were included. Accelerometer-measured total volume of physical activity (TPA) and sedentary time were measured at baseline and dichotomised by median (low TPA < 27 milli-gravity (milli-g), high TPA ≥ 27 milli-g; low sedentary time < 10.7 h/day, high sedentary time ≥ 10.7 h/day). Cox proportional hazards models were used to evaluate the joint associations with incident dementia on both additive and multiplicative scales.
During a median follow-up of 6.9 years, 501 cases of all-cause dementia were identified. Higher TPA was associated with a lower risk of all-cause dementia, Alzheimer's disease and vascular dementia; the multivariate adjusted hazard ratios (HRs) (95% CI) per 10 milli-g increase were 0.63 (0.55-0.71), 0.74 (0.60-0.90) and 0.69 (0.51-0.93), respectively. Sedentary time was only found to be linked to all-cause dementia, and the HR for high sedentary time was 1.03 (1.01-1.06) compared with that for low sedentary time. No additive and multiplicative relationship of TPA and sedentary time to incident dementia was found (all P values > 0.05).
Higher TPA level was related to a lower risk of incident dementia irrespective of sedentary time, which highlighted the implication of promoting physical activity participation to counteract the potential detrimental effect of sedentary time on dementia.
Two new copper( ii ) complexes of sparfloxacin (sf), Cu(Hsf)(HPB)(H 2 O)(ClO 4 ) 2 (1) and Cu(Hsf)(PBT)(H 2 O)(ClO 4 ) 2 (2) (where HPB = 2-(2′-pyridyl)benzimidazole and PBT = 2-(4′-pyridyl) ...benzothiazole), have been synthesized and characterized by physicochemical and spectroscopic techniques. The oil–water partition coefficient (log P ) values of complexes 1 and 2 were 1.47 and 1.71, respectively. By studying the interaction between the complexes and DNA, it was found that the complexes could bind to DNA through an intercalation mode. Moreover, both complexes were evaluated for antitumor activity, revealing that the complexes displayed good inhibitory activity toward the tested cancer cell lines (human lung carcinoma A549 cells, human hepatocellular carcinoma Bel-7402 cells and human esophageal carcinoma Eca-109 cells), but showed relatively low toxicity against normal human hepatic LO2 cells. In particular, the antitumor mechanism of the complexes on Eca-109 cells was investigated by morphological analysis, apoptosis analysis and determination of cell cycle arrest, mitochondrial membrane potential, reactive oxygen species (ROS) levels, and release of cytochrome c and Ca 2+ . The results demonstrated that the complexes could induce loss of intracellular mitochondrial functions and increase of ROS levels, which led to an increase of Ca 2+ levels and the release of cytochrome c into the cytoplasm. In addition, the cell cycle was arrested in the G2/M phase, and western blot analysis showed that the caspase family was activated. These results fully proved that the complexes could induce apoptosis through DNA damage and loss of mitochondrial functions, accompanied by the regulation of endogenous proteins.
Banxia Houpu decoction (BXHPD) has been used to treat depression in clinical practice for centuries. However, the pharmacological mechanisms of BXHPD still remain unclear. Network Pharmacology (NP) ...approach was used to explore the potential molecular mechanisms of BXHPD in treating depression. Potential active compounds of BXHPD were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform Database. STRING database was used to build a interaction network between the active compounds and target genes associated with depression. The topological features of nodes were visualized and calculated. Significant pathways and biological functions were identified using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. A total of 44 active compounds were obtained from BXHPD, and 121 potential target genes were considered to be therapeutically relevant. Pathway analysis indicated that MAPK signaling pathway, ErbB signaling pathway, HIF-1 signaling pathway and PI3K-Akt pathway were significant pathways in depression. They were mainly involved in promoting nerve growth and nutrition and alleviating neuroinflammatory conditions. The result provided some potential ways for modern medicine in the treatment of depression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Interconnected hollow carbon nanospheres (HCNSs) were prepared by pressure‐assisted reduction and graphitization of sucrose in autoclaves without template. The obtained HCNSs with a large surface ...area, very thin graphitic shells, and an interconnected structure exhibit excellent performances as the electrode material for lithium ion batteries.
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