Low dose niacin and vitamin D can directly improve human microvascular endothelial cell angiogenic function under lipotoxic conditions Peters et al.,2019. Despite exerting similar benefits on ...in vitro angiogenic function, these vitamins are known to signal through independent receptors, raising the possibility that differential changes in gene expression may underlie these effects. Here we provide data collected using Affymetrix GeneChip microarrays to compare gene expression in human microvascular endothelial cells treated for 16 h with growth medium containing BSA alone, or BSA complexed with the saturated fatty acid palmitate, and supplemented with 10 μM niacin or 10 nM vitamin D (1,25-dihydroxyvitamin D3). Data sets of differential gene expression included many genes involved in cellular stress responses. Pathway analyses of genes specific to vitamin D treatment identified a robust overrepresentation of pathways related to the cell cycle and DNA replication and repair.
To determine antibiotic susceptibility of isolates of Streptococcus pneumoniae (n = 573) and Haemophilus influenzae (n = 345) collected in 2014-16 from Bulgaria, Romania, Serbia and Croatia.
MICs ...were determined by CLSI broth microdilution and susceptibility was assessed using CLSI, EUCAST and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints.
Among S. pneumoniae, susceptibility was generally lowest in Romania and Serbia and highest in Bulgaria. Rates of susceptibility to penicillin (CLSI oral or EUCAST) were 22.3% and 21.8% in Romania and Serbia respectively, 57% in Croatia and 86.6% in Bulgaria. Similarly, macrolide susceptibility using CLSI/EUCAST breakpoints was low in Romania and Serbia (∼28% and 34.5%, respectively), higher in Croatia (55.9%) and highest in Bulgaria (∼75%). Only fluoroquinolones were active against all isolates in all four countries. Susceptibility was higher and variability across countries less pronounced for H. influenzae. Susceptibility by CLSI criteria to amoxicillin/clavulanic acid, azithromycin, cefuroxime, ceftriaxone and fluoroquinolones was ≥98% in all countries. Ampicillin susceptibility ranged from 85.3% in Romania to 100% in Bulgaria. Much greater variability was seen across breakpoints. Susceptibility to azithromycin and cefuroxime using CLSI criteria was ≥98% in all four countries, but was 0%-1% by EUCAST criteria.
The variability in antimicrobial susceptibility using different breakpoints makes it difficult for clinicians to interpret antimicrobial resistance data, and efforts should be made to harmonize breakpoints. The variability found across the four neighbouring countries demonstrates the need to monitor and publish national and local resistance patterns. These findings provide information critical for the selection of appropriate antimicrobial agents for the treatment of S. pneumoniae and H. influenzae.
Background and Objectives: Periapical cystic lesions are a pathology frequently addressed to endodontic specialists. Although their therapy is still not standardized, the treatment should be as ...conservative as possible and by endodontic means, as they are lesions of endodontic origin. The present case report describes two cases of upper central incisors with large cyst-like periapical lesions, and their one-year follow up. Materials and Methods: Endodontic orthograde treatment was performed under copious irrigation with sodium hypochlorite, in association with calcium hydroxide as an intra-canal medication for both teeth. Root canal filling was achieved in a separate appointment using the continuous wave of condensation technique. A decompression procedure was used in association with endodontic therapy in the second case to reduce the pressure inside the cystic lesion and to allow its drainage, and only because the root canal could not be dried three weeks after medication. Initial cone beam computed tomography (CBCT) investigations, as well as at the one-year follow up, were used to compare the evolution of the lesion. Results: Both cases had a favorable outcome. New bone formation in the periapical region and complete resolution of the lesion was observed at the one-year control in the first case. In the second case, although the lesion was still not completely healed at 12 months, a significant reduction in its size could be observed, showing active signs of healing. Conclusions: Endodontic treatment is the first choice option in the management of teeth with pulpal necrosis and large periapical cystic-like lesions. Decompression is the only surgical procedure recommended when the canals cannot be dried and obturated. Large surgical interventions are unnecessary in cases where endodontic treatment can be performed.
The heavy-fermion metal CeCu2Si2 was the first discovered unconventional, non-phonon-mediated superconductor and, for a long time, was believed to exhibit single-band d -wave superconductivity, as ...inferred from various measurements hinting at a nodal gap structure. More recently, however, measurements using a range of techniques at low temperatures ( T ⪅ 0.1 K ) provided evidence for a fully gapped superconducting order parameter. In this Colloquium, after a historical overview the apparently conflicting results of numerous experimental studies on this compound are surveyed. The different theoretical scenarios that have been applied to understanding the particular gap structure are then addressed, including both isotropic (sign-preserving) and anisotropic two-band s -wave superconductivity, as well as an effective two-band d -wave model, where the latter can explain the currently available experimental data on CeCu2Si2. The lessons from CeCu2Si2 are expected to help uncover the Cooper-pair states in other unconventional, fully gapped superconductors with strongly correlated carriers, and, in particular, highlight the rich variety of such states enabled by orbital degrees of freedom.
Abstract Objective : Niacin (nicotinic acid) as a monotherapy can reduce vascular disease risk, but its mechanism of action remains controversial, and may not be dependent on systemic lipid modifying ...effects. Niacin has recently been shown to improve endothelial function and vascular regeneration, independent of correcting dyslipidemia, in rodent models of vascular injury and metabolic disease. As a potential biosynthetic precursor for NAD+ , niacin could elicit these vascular benefits through NAD+ -dependent, sirtuin (SIRT) mediated responses. Alternatively, niacin may act through its receptor, GPR109A, to promote endothelial function, though endothelial cells are not known to express this receptor. We hypothesized that niacin directly improves endothelial cell function during exposure to lipotoxic conditions and sought to determine the potential mechanism(s) involved. Methods and results : Angiogenic function in excess palmitate was assessed by tube formation following treatment of human microvascular endothelial cells (HMVEC) with either a relatively low concentration of niacin (10 μM), or nicotinamide mononucleotide (NMN) (1 μM), a direct NAD+ precursor. Although both niacin and NMN improved HMVEC tube formation during palmitate overload, only NMN increased cellular NAD+ and SIRT1 activity. We further observed that HMVEC express GRP109A. Activation of this receptor with either acifran or MK-1903 recapitulated niacin-induced improvements in HMVEC tube formation, while GPR109A siRNA diminished the effect of niacin. Conclusion : Niacin, at a low concentration, improves HMVEC angiogenic function under lipotoxic conditions, likely independent of NAD+ biosynthesis and SIRT1 activation, but rather through niacin receptor activation.
Since the discovery of high-temperature superconductivity in copper oxide materials
, there have been sustained efforts to both understand the origins of this phase and discover new cuprate-like ...superconducting materials
. One prime materials platform has been the rare-earth nickelates and, indeed, superconductivity was recently discovered in the doped compound Nd
Sr
NiO
(ref.
). Undoped NdNiO
belongs to a series of layered square-planar nickelates with chemical formula Nd
Ni
O
and is known as the 'infinite-layer' (n = ∞) nickelate. Here we report the synthesis of the quintuple-layer (n = 5) member of this series, Nd
Ni
O
, in which optimal cuprate-like electron filling (d
) is achieved without chemical doping. We observe a superconducting transition beginning at ~13 K. Electronic structure calculations, in tandem with magnetoresistive and spectroscopic measurements, suggest that Nd
Ni
O
interpolates between cuprate-like and infinite-layer nickelate-like behaviour. In engineering a distinct superconducting nickelate, we identify the square-planar nickelates as a new family of superconductors that can be tuned via both doping and dimensionality.
Vitamin D appears to either promote or inhibit neovascularization in a disease context-dependent manner. The effects of vitamin D, alone or in combination with niacin, on endothelial cell (EC) ...angiogenic function and on revascularization in obese animals with peripheral ischemia are unknown. Here, we report that supplementation of high palmitate medium with vitamin D, niacin or both vitamins increased EC tube formation, which relies primarily on cell migration, and also maintained tube stability over time. Transcriptomic analyses revealed that both vitamins increased stress response and anti-inflammatory gene expression. However, vitamin D decreased cell cycle gene expression and inhibited proliferation, while niacin induced stable expression of miR-126-3p and -5p and maintained cell proliferation in high palmitate. To assess vascular regeneration, diet-induced obese mice received vitamin D, niacin or both vitamins following hind limb ischemic injury. Niacin, but not vitamin D or combined treatment, improved recovery of hind limb use. Histology of tibialis anterior sections revealed no improvements in revascularization, regeneration, inflammation or fibrosis with vitamin D or combined treatment. In summary, although both vitamin D and niacin increased angiogenic function of EC cultures in high fat, only niacin improved recovery of hind limb use following ischemic injury in obese mice. It is possible that inhibition of cell proliferation by vitamin D in high-fat conditions limits vascular regeneration and recovery from peripheral ischemia in obesity.
Sex-related differences have been shown to deeply affect health-related aspects of patients. However, the lack of gender-specific analysis makes it difficult to advance personalized medicine in terms ...of a gender-based approach. The aim of the present study was to describe gender-specific features of patients diagnosed with heart failure (HF), with a focus on the clinical presentation. Data were collected from a properly designed database and referred to an Italian hospital. Patients aged ≥18 years with a primary or secondary diagnosis of HF between 1 January 2012 and 31 December 2016 were included, and their demographic and clinical characteristics were analyzed according to gender. Of the 719 HF patients included, 317 (44.1%) were male and 402 (55.9%) were female. Women tended to be older compared to men (82.4±8.8 years and 77.1±10.6 years, respectively). As for clinical presentation, 62.1% of female and 38.3% of male patients had preserved ejection fraction, and 56.1% of men and 58.2% of women suffered from atrial fibrillation. The left atrium was partially compromised in 62.4% of male and 63% of female patients, while right atrium dysfunction tended to be more frequent in male patients compared to female patients (29.1% and 25.5%, respectively). In conclusion, gender-specific features of a cohort of HF patients from a clinical setting were accurately described.
Inhibition of Microsomal Triglyceride Transfer Protein Expression and Apolipoprotein B100 Secretion by the Citrus Flavonoid
Naringenin and by Insulin Involves Activation of the Mitogen-Activated ...Protein Kinase Pathway in Hepatocytes
Emma M. Allister ,
Nica M. Borradaile ,
Jane Y. Edwards and
Murray W. Huff
From the Departments of Medicine and Biochemistry and the Robarts Research Institute, University of Western Ontario, London,
Ontario, Canada
Address correspondence and reprint requests to Dr. Murray W. Huff, Robarts Research Institute, 4-16, 100 Perth Dr., London,
Ontario, Canada, N6A 5K8. E-mail: mhuff{at}uwo.ca
Abstract
Microsomal triglyceride transfer protein (MTP) is necessary for hepatocyte assembly and secretion of apolipoprotein (apo)B100-containing
lipoproteins. The citrus flavonoid naringenin, like insulin, decreased MTP expression in HepG2 cells, resulting in inhibition
of apoB100 secretion; however, the mechanism for naringenin is independent of insulin receptor substrate-1/2. Recently, it
was reported that insulin decreased MTP expression in HepG2 cells via the mitogen-activated protein kinase (MAPK)/extracellular
signal–regulated kinase (ERK) (MAPK erk ) pathway. We hypothesized that naringenin acts via a similar mechanism. Inhibition of MAPK kinase (MEK) 1/2 in HepG2 cells
significantly attenuated the naringenin- and insulin-induced reduction in MTP expression. Both naringenin and insulin increased
ERK1/2 phosphorylation, which was completely inhibited by MEK1/2 inhibition and enhanced by inhibition of MAPK p38 , a negative regulator of MAPK erk activity. Inhibition of MEK1/2 significantly attenuated both the naringenin- and insulin-induced decrease in apoB100 secretion
demonstrating a direct link between MAPK erk activation and apoB100 secretion. Furthermore, both compounds increased MAPK p38 activation, and therefore inhibition of MAPK p38 amplified thenaringenin- and insulin-induced decrease in apoB100 secretion. We conclude that MAPK erk signaling in hepatocytes is critical for inhibition of apoB100 secretion by naringenin and insulin. Therefore, naringenin
may prove useful for activating insulin-signaling pathways important for regulation of hepatocyte lipid homeostasis.
apo, apolipoprotein
ERK, extracellular signal–regulated kinase
LDL-r, LDL receptor
LPDS, lipoprotein-deficient serum
MAPK, mitogen-activated protein kinase
MEK, MAPK kinase
MTP, microsomal triglyceride transfer protein
PI, phosphatidylinositol
SREBP, sterol regulatory element–binding protein
Footnotes
N.M.B. is currently affiliated with the Division of Cardiology, Department of Internal Medicine, Washington University School
of Medicine, St. Louis, Missouri.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Accepted March 10, 2005.
Received August 27, 2004.
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