ABSTRACT
The maintenance of appropriate arterial tone is critically important for normal physiological arterial function. However, the cellular and molecular mechanisms remain poorly defined. Here, we have shown that in the mouse aorta, resident macrophages prevented arterial stiffness and collagen deposition in the steady state. Using phenotyping, transcriptional profiling, and targeted deletion of Csf1r, we have demonstrated that these macrophages-which are a feature of blood vessels invested with smooth muscle cells (SMCs) in both mouse and human tissues-expressed the hyaluronan (HA) receptor LYVE-l. Furthermore, we have shown they possessed the unique ability to modulate collagen expression in SMCs by matrix metalloproteinase MMP-9-dependent proteolysis through engagement of LYVE-1 with the HA pericellular matrix of SMCs. Our study has unveiled a hitherto unknown homeostatic contribution of arterial LYVE-1+ macrophages through the control of collagen production by SMCs and has identified a function of LYVE-1 in leukocytes.
Subject(s)
Collagen/metabolism , Glycoproteins/metabolism , Hyaluronan Receptors/metabolism , Macrophages/metabolism , Muscle, Smooth, Vascular/cytology , Myocytes, Smooth Muscle/metabolism , Vascular Stiffness/physiology , Animals , Aorta/physiology , Female , Glycoproteins/genetics , Humans , Hyaluronic Acid/metabolism , Male , Matrix Metalloproteinase 9/metabolism , Membrane Transport Proteins , Mice , Mice, Inbred C57BL , Mice, Knockout , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/geneticsABSTRACT
Intermolecular alkylations of electron-deficient arenes proceed with good para selectivity. Palladium catalysts were used to generate nucleophilic alkyl radicals from alkyl halides, which then directly add onto the arenes. The arene scope and the site of alkylation are opposite to those of classical Friedel-Crafts alkylations, which prefer electron-rich systems.
ABSTRACT
An asymmetric reductive amination of ketones using both arylamines and benzhydrazide in the presence of nickel catalysts was developed. A one-pot synthesis of tetrahydroquinoxalines was also developed starting directly from α-ketoaldehydes and 1,2-diaminobenzene. Formic acid was used as a safe and economic surrogate for high-pressure hydrogen gas. Strongly σ-donating bis(alkylphosphine)s are crucial ancillary ligands for both stereoselective hydride insertion and decarboxylation of the formate.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/therapeutic use , Dexamethasone/therapeutic use , Multiple Myeloma/drug therapy , Oligopeptides/therapeutic use , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cyclophosphamide/adverse effects , Dexamethasone/adverse effects , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Multiple Myeloma/epidemiology , Oligopeptides/adverse effects , Treatment OutcomeABSTRACT
BACKGROUND: Smoking is a learnt behavior during adolescence and understanding the factor/s associated with smoking will assist in identifying suitable measures in combating the rising prevalence of smoking among adolescents. This research aimed to identify the factor/s associated with smoking among form four students in Kota Tinggi, Johor. Multistage sampling was used to select a representative sample of students in 2008 and data were collected using a self-administered validated questionnaire. This study revealed that the overall smoking prevalence was 19.0% with a significantly higher proportion of male smokers (35.8%) as compared to females (3.15%). Adolescents who were male (aOR 6.6, 95%CI 2.61-16.4), those who had peer/s who smoked (aOR 4.03, 95% CI 1.31-12.4), and those who studied in rural areas and Felda Settlements ( aOR 4.59, 95 CI 1.11-18.0; aOR 9.42, 95%CI 3.91-29.1) were more likely to smoke in the past one week. On the other hand, adolescents with better knowledge on the hazards of smoking and negative attitudes towards smoking were less likely to smoke (aOR 0.51, 95%CI 0.37-0.72; aOR 0.67, 95%CI 0.46-0.99). Future promotional and interventional programmes on smoking should be considered and the above identified risk factors integrated to reduce smoking prevalence among students of school-going ages in Kota Tinggi. Johor.
Subject(s)
Adolescent Behavior , Health Knowledge, Attitudes, Practice , Smoking/epidemiology , Smoking/psychology , Students/psychology , Tobacco Use Disorder/psychology , Adolescent , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Longitudinal Studies , Malaysia/epidemiology , Male , Prevalence , Prognosis , Risk Factors , Schools , Surveys and Questionnaires , Tobacco Use Disorder/etiologyABSTRACT
The structure and stability of emulsions formed in the presence of nanoparticles of poly(lactic-co-glycolic acid) (PLGA) were characterised. From oil-water contact angles on PLGA films, it was deduced that particle surface hydrophobicity is linked to the oil phase polarity. Incorporation of polyvinyl alcohol molecules into the nanoparticle surfaces reduces the particle hydrophobicity sufficiently for oil-in-water emulsions to be preferentially stabilised. PLGA nanoparticles enhance the stability of emulsions formed from a wide range of oils of different polarities. The nanoparticle concentration was found to be a key parameter controlling the average size and coalescence stability of the emulsion drops. Visualisation of the interfacial structure by electron microscopy indicated that PLGA nanoparticles were located at the drop surfaces, evidence of the capacity of these particles to stabilise Pickering-type emulsions. These results provide insights into the mechanism of PLGA nanoparticle stabilisation of emulsions.
Subject(s)
Drug Carriers/chemical synthesis , Emulsifying Agents/chemistry , Lactic Acid/chemistry , Nanoparticles/chemistry , Polyglycolic Acid/chemistry , Emulsions , Hydrogen-Ion Concentration , Hydrophobic and Hydrophilic Interactions , Microscopy, Electron, Transmission , Oils/chemistry , Particle Size , Polylactic Acid-Polyglycolic Acid Copolymer , Polyvinyl Alcohol/chemistry , Water/chemistryABSTRACT
This study reports on the physicochemical characterisation and in vitro investigations of macro-porous silica-lipid hybrid (SLH) microcapsules when formulated using various lipids: long-chain triglycerides (LCT), medium-chain triglycerides (MCT), medium-chain mono-, diglycerides (MCMDG); and emulsifiers: anionic lecithin and cationic oleylamine. For the lipophilic compound coumarin 102 (logP=4.09), a complete and immediate in vitro release was attained for the SLH microcapsules under simulated intestinal sink conditions. The in vitro digestion study of various types of SLH microcapsules demonstrates: (i) reduced variability and enhanced lipid digestibility for the MCMDG-based microcapsules (i.e. 90-100% lipolysis) in comparison with an equivalent lipid solution and emulsion (50-90% lipolysis); and (ii) more controllable digestion kinetics for the LCT-based microcapsules which produce a lipolysis rate higher than that of a lipid solution but lower than that of a lipid emulsion. The drug phase partition results show approximately 5- to 17-fold increase in the drug solubilisation degree resulting from the digestion of MCT and MCMDG-based microcapsules (116 µg/mL), and LCT-based microcapsules (416 µg/mL) in comparison with the blank micellar medium (24 µg/mL). In conclusion, the SLH microcapsules could be tailored to manipulate the digestion patterns of both medium- and long-chain lipids in order to maximise the drug solubilisation capacity.