Branched-chain amino acid (BCAA) metabolism is potentially linked with development of pancreatic ductal adenocarcinoma (PDAC)
. BCAA transaminase 2 (BCAT2) was essential for the collateral lethality ...conferred by deletion of malic enzymes in PDAC and the BCAA-BCAT metabolic pathway contributed to non-small-cell lung carcinomas (NSCLCs) other than PDAC
. However, the underlying mechanism remains undefined. Here we reveal that BCAT2 is elevated in mouse models and in human PDAC. Furthermore, pancreatic tissue-specific knockout of Bcat2 impedes progression of pancreatic intraepithelial neoplasia (PanIN) in LSL-Kras
; Pdx1-Cre (KC) mice. Functionally, BCAT2 enhances BCAA uptake to sustain BCAA catabolism and mitochondrial respiration. Notably, BCAA enhances growth of pancreatic ductal organoids from KC mice in a dose-dependent manner, whereas addition of branched-chain α-keto acid (BCKA) and nucleobases rescues growth of KC organoids that is suppressed by BCAT2 inhibitor. Moreover, KRAS stabilizes BCAT2, which is mediated by spleen tyrosine kinase (SYK) and E3 ligase tripartite-motif-containing protein 21 (TRIM21). In addition, BCAT2 inhibitor ameliorates PanIN formation in KC mice. Of note, a lower-BCAA diet also impedes PDAC development in mouse models of PDAC. Thus, BCAT2-mediated BCAA catabolism is critical for development of PDAC harbouring KRAS mutations. Targeting BCAT2 or lowering dietary BCAA may have translational significance.
The residential electricity demand in Taiwan was investigated using survey data of 7677 households between 2014 and 2017. Right-skewed regression models were employed to study key determinants ...affecting the household and appliance-specific electricity consumption. Appliances covered air conditioner, lighting, television, and refrigerator. The difference of electricity consumption between appliances with and without energy efficiency label was also studied; thus rebound effects were obtained. The estimated results indicate that household income, indoor floor area, and owning the house had positive influences on electricity consumption. Electricity consumption behavior was different among age groups and appliances. Moreover, rebound effect was large for air conditioner and refrigerator in Taiwan.
•Household electricity consumption fits the right-skewed distributions.•Finding key determinants affecting the appliance-specific electricity consumption.•Calculating actual electricity saving due to the energy efficiency label.•Rebound effect is 72% for AC, 70% for refrigerator, 11% for lighting, and 3% for TV.
Proton pump inhibitors, including omeprazole, rabeprazole, lansoprazole, and pantoprazole, achieved simultaneous enantioselective determination in the human plasma by chiral liquid ...chromatography–tandem mass spectrometry. The four corresponding stable isotope‐labeled proton pump inhibitors were adopted as the internal standards. Each enantiomer and the internal standards were extracted with acetonitrile containing 0.1% ammonia, then separated with a Chiralpak IC column (5 µm, 4.6 mm × 150 mm) within 10 min. The mobile phase was composed of acetonitrile–ammonium acetate (10 mM) containing 0.2% acetic acid (50:50, v/v). To quantify all enantiomers, an API 4000 tandem mass spectrometer was used, and multiple reaction monitoring transitions were performed on m/z 360.1→242.1, 384.1→200.1, 370.1→252.1, and 346.1→198.1, respectively. No significant matrix effect was observed for all analytes. The calibration curve for all enantiomers were linear from 1.25 to 2500 ng/mL. The precisions for intra‐ and inter‐run were < 14.2%, and the accuracy fell in the interval of –5.3 to 8.1%. Stability of samples was confirmed under the storage and processing conditions. The developed method was also suitable for separation and determination of ilaprazole enantiomers. The validated method combining the equilibrium dialysis method was applied to the protein binding ratio studies of four pairs proton pump inhibitor enantiomers in human plasma.
Adipose‐derived stem cells for wound healing Hassanshahi, Alireza; Hassanshahi, Mohammadhossein; Khabbazi, Samira ...
Journal of cellular physiology,
June 2019, Letnik:
234, Številka:
6
Journal Article
Recenzirano
Wound healing is a complex but a fine‐tuned biological process in which human skin has the ability to regenerate itself following damage. However, in particular conditions such as deep burn or ...diabetes the process of wound healing is compromised. Despite investigations on the potency of a wide variety of stem cells for wound healing, adipose‐derived stem cells (ASCs) seem to possess the least limitations for clinical applications, and literature showed that ASCs can improve the process of wound healing very likely by promoting angiogenesis and/or vascularisation, modulating immune response, and inducing epithelialization in the wound. In the present review, advantages and disadvantages of various stem cells which can be used for promoting wound healing are discussed. In addition, potential mechanisms of action by which ASCs may accelerate wound healing are summarised. Finally, clinical studies applying ASCs for wound healing and the associated limitations are reviewed.
Despite investigations on the potency of a wide variety of stem cells for wound healing, adipose‐derived stem cells (ASCs) seem to possess the least clinical limitations for clinical applications, and our review showed that ASCs can improve the process of wound healing very likely by promoting angiogenesis and/or vascularisation, modulating immune response, and inducing epithelialization in the wound.
This study examines the impact on inbound tourism caused by the presence of world heritage sites. The statistics are derived from panel data for 66 countries for the period 2006–2009. The results ...indicate that there exists a positive relationship between having such heritage sites and tourist numbers, and the relationship is stronger for natural rather than for cultural heritage sites. The evidence also indicates the presence of a U-shaped relationship between numbers of world heritage sites in a country and tourist numbers. These relationships are found to be robust even though differences in patterns are found in different regions.
•Investigate in the positive influence of world heritage sites on international tourist arrivals.•Divide the sample into several groups according to the number of WHSs to study effects of WHSs across these groups.•Explore the pooled, fixed and random effect models with panel data (66 countries, 2000–2009).•Eliminate the problem of time-invariant variables in panel data model by increasing the number of countries.
Background and Purpose
Oxidative stress is an important pathogenic factor in the development of hypertension. Resveratrol, the main antioxidant in red wine, improves NO bioavailability and prevents ...cardiovascular disease. The aim of this study was to examine whether resveratrol decreases the generation of reactive oxygen species (ROS), thereby reducing BP in rats with fructose‐induced hypertension.
Experimental Approach
Rats were fed 10% fructose with or without resveratrol (10 mg·kg−1·day−1) for 1 week or for 4 weeks with resveratrol treatment beginning at week 2; systolic BP (SBP) was measured by tail‐cuff method. Endogenous in vivo O2− production in the nucleus tractus solitarii (NTS) was determined with dihydroethidium. Real‐time PCR and immunoblotting analyses were used to quantify RNA and protein expression levels.
Key Results
In fructose‐fed rats, ROS levels in the NTS were higher, whereas the NO level was significantly decreased. Also, RNA and protein levels of NADPH oxidase subunits (p67, p22‐phox) were elevated, superoxide dismutase 2 (SOD2) reduced and AMP‐activated PK (AMPK) T172 phosphorylation levels in the NTS were lower in fructose‐fed rats. Treatment with the AMPK activator resveratrol decreased levels of NADPH oxidase subunits and ROS, and increased NO and SOD2 levels in the NTS of fructose‐fed rats. Administration of resveratrol, in combination with fructose at week 0 and later at week 2, significantly reduced the SBP of fructose‐fed rats.
Conclusions and Implications
Collectively, resveratrol decreased BP through the phosphorylation of AMPK, Akt and neuronal NOS in fructose‐fed rats. These novel findings suggest that resveratrol may be a potential pharmacological candidate for the treatment of hypertension.
Methotrexate (MTX) is a commonly used antimetabolite in cancer treatment. Its intensive use is linked with skeletal adverse effects such as reduced bone formation and bone loss, and yet little ...information is available on molecular mechanisms underlying MTX‐induced impaired bone formation. This study investigated the effects of MTX treatment at a clinical chemotherapy relevant dose on osteogenic differentiation in MC3T3E1 osteoblastic cells. To investigate the potential mechanisms, the expression of 87 genes regulating osteoblast differentiation and bone homeostasis was screened in MTX‐treated versus untreated cells by polymerase chain reaction (PCR) arrays and results illustrated significant upregulation of Notch2 and Notch target genes at both early and late stages of MC3T3E1 differentiation following MTX treatment. To confirm the roles of Notch2 pathway and its potential action mechanisms, MC3T3E1 cells were treated with MTX with an anti‐Notch2 neutralizing antibody or control IgG and effects were examined on osteogenesis and activation of the Wnt/β‐catenin pathway. Our results demonstrated that induction of Notch2 activity is associated with MTX adverse effects on osteogenic differentiation and blocking Notch2 rescues osteoblast differentiation by preserving activation of the Wnt/β‐catenin pathway.
The lithium-selenium (Li-Se) battery has attracted growing interest recently due to its high energy density and theoretical capacity. However, the shuttle effect and volume change during cycling ...severely hinder its further application. In this work, we report a metal-organic framework (MOF)-derived nitrogen-doped core-shell hierarchical porous carbon (N-CSHPC) with interconnected meso/micropores to effectively confine Se for high-performance Li-Se batteries. The micropores were located at the ZIF-8-derived core and the ZIF-67-derived shell, while mesopores appeared at the core-shell interface after the pyrolysis of the core-shell ZIF-8@ZIF-67 precursor. Such a special hierarchical porous structure effectively confined selenium and polyselenides to prevent their dissolution from the pores and also alleviated the volume change. In particular, in situ nitrogen doping, which afforded N-CSHPC, not only improved the electrical conductivity of Se but also provided strong chemical adsorption on Li2Se, as confirmed by density functional theory calculations. On the basis of dual-physical confinement and strong chemisorption, Se/N-CSHPC-II (molar ratio of Co source to Zn source of 1.0 in the core-shell ZIF-8@ZIF-67 precursor) exhibited reversible capacities of up to 555 mA h g-1 after 150 cycles at 0.2 C and 462 mA h g-1 after 200 cycles at 0.5 C and even a discharge capacity of 432 mA h g-1 after 200 cycles at 1 C. Our demonstration here suggests that the carefully designed Se/C composite can improve the reversible capacity and cycling stability of Se cathodes for Li-Se batteries.
Continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants urges the development of new vaccines. We assessed the safety and immunogenicity of SYS6006.32, a ...bivalent vaccine (XBB.1.5/BQ.1), in healthy adults who had received SARS-CoV-2 primary vaccination. In a randomised, double-blinded, active-controlled trial, 200 participants were randomised to receive one dose of SYS6006.32 (N = 100) or a prototype-based, monovalent control vaccine SYS6006 (N = 100). Adverse events (AEs) were collected through the study. Immunogenicity was assessed by live-virus neutralising antibody (Nab) and pseudovirus Nab. 61 (61.0 %) and 60 (60.0 %) participants reported AE in the SYS6006.32 and SYS6006 groups, respectively. Most AEs were grade 1 or 2. Pain and fever were the most common injection-site and systemic AEs, respectively. No serious AEs were observed. SYS6006.32 heterologous boosting induced robust Nab responses against BA.5, XBB.1.5 and EG.5 with live-virus Nab geometric mean titres (GMTs) increased by 17.1-, 34.0-, and 48.0-fold, and pseudovirus Nab GMTs increased by 12.2-, 32.0-, and 35.1-fold, respectively, 14 days after vaccination. SYS6006.32 demonstrated a superior immunogenicity to SYS6006. SYS6006.32 also induced robust pseudovirus Nab responses against XBB.1.16, XBB.2.3, and BA.2.86, with GMTs 3- to 6-fold higher than those induced by SYS6006. In conclusion, SYS6006.32 showed good safety profile and superior immunogenicity to the monovalent vaccine SYS6006.
Surface plasmon resonance (SPR) has become a well-recognized label-free technique for measuring the binding kinetics between biomolecules since the invention of the first SPR-based immunosensor in ...1980s. The most popular and traditional format for SPR analysis is to monitor the real-time optical signals when a solution containing ligand molecules is flowing over a sensor substrate functionalized with purified receptor molecules. In recent years, rapid development of several kinds of SPR imaging techniques have allowed for mapping the dynamic distribution of local mass density within single living cells with high spatial and temporal resolutions and reliable sensitivity. Such capability immediately enabled one to investigate the interaction between important biomolecules and intact cells in a label-free, quantitative, and single cell manner, leading to an exciting new trend of cell-based SPR bioanalysis. In this Trend Article, we first describe the principle and technical features of two types of SPR imaging techniques based on prism and objective, respectively. Then we survey the intact cell-based applications in both fundamental cell biology and drug discovery. We conclude the article with comments and perspectives on the future developments.
Graphical abstract
Recent developments in surface plasmon resonance (SPR) imaging techniques allow for label-free mapping the mass-distribution within single living cells, leading to great expansions in biomolecular interactions studies from homogeneous substrates functionalized with purified biomolecules to heterogeneous substrates containing individual living cells
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