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The 3MLCTppz state was generated upon excitation at 290 nm, and the intensity of the TA band related to the 3MLCTppz state decreased as the time delay increased. Concurrently, the TA band related to the 3MLCTLX state intensified. On the other hand, no further changes in the TA spectra were observed upon direct excitation of the 3MLCTLX state at 420 nm. In contrast with other Ir(ppz)2(LX) complexes, Ir(ppz)2(picOH) produced long-lived TA species, attributed to excited-state intramolecular proton transfer of the picOH ligand in the excited singlet state.
Operative mortality for type A aortic dissection is still 10-20% at centers of excellence. Additionally, 10-20% are not considered as viable candidates for open surgical repair and not offered life-saving emergency surgery. ARISE is a multicenter investigation evaluating the novel GORE® Ascending Stent Graft (ASG; Flagstaff, AZ).
The purpose of this study is to assess early feasibility of using these investigational devices to treat ascending aortic dissection.
This a prospective, multicenter, non-randomized, single-arm study that enrolls patients at high surgical risk with appropriate anatomical requirements based on computed tomography imaging at 7 of 9 US sites. Devices are delivered transfemorally under fluoroscopic guidance. Primary endpoint is all-cause mortality at 30 days. Secondary endpoints include major adverse cardiovascular and cerebrovascular events (MACCE) at 30 days, 6 months, and 12 months.
Nineteen patients were enrolled with a mean age of 75.7 years (range 47-91) and 11 (57.9%) were female. Ten (52.6%) had DeBakey type I disease, and the rest were type II. Sixteen (84.2%) of the patients were acute. Patients were treated with safe access, (7/19 (36.8%) percutaneous, 10/19 (52.6%) transfemoral, 2/19 (10.5%) iliac conduit), delivery, and deployment completed in all cases. Median procedure time was 154 mins (range 52-392) and median contrast used was 111 mL (range 75-200). MACCE at 30 days occurred in 5 patients including mortality 3/19 (15.8%), disabling stroke in 1/19 (5.3%), and myocardial infarction in 1/19 (5.3%).
Results from the ARISE early feasibility study of a specific ascending stent graft device to treat ascending aortic dissection are promising.
Results from the ARISE early feasibility study of a specific ascending stent graft device to treat ascending aortic dissection are promising.Smooth muscle cells and endothelial cells have a remarkable level of plasticity in vascular pathologies. In thoracic and abdominal aortic aneurysms, smooth muscle cells have been suggested to undergo phenotypic switching and to contribute to degradation of the aortic wall structure in response to, for example, inflammatory mediators, dysregulation of growth factor signaling or oxidative stress. Recently, endothelial-to-mesenchymal transition, and a clonal expansion of degradative smooth muscle cells and immune cells, as well as mesenchymal stem-like cells have been suggested to contribute to the progression of aortic aneurysms. What are the factors driving the aortic cell phenotype changes and how vascular flow, known to affect aortic wall structure and to be altered in aortic aneurysms, could affect aortic cell remodeling? In this review, we summarize the current literature on aortic cell heterogeneity and phenotypic switching in relation to changes in vascular flow and aortic wall structure in aortic aneurysms in clinical samples with special focus on smooth muscle and endothelial cells. SQ22536 datasheet The differences between thoracic and abdominal aortic aneurysms are discussed.
HDL (high-density lipoprotein) and its major protein component, apoA-I (apolipoprotein A-I), play a unique role in cholesterol homeostasis and immunity. ApoA-I deficiency in hyperlipidemic, atheroprone mice was shown to drive cholesterol accumulation and inflammatory cell activation/proliferation. The present study was aimed at investigating the impact of apoA-I deficiency on lipid deposition and local/systemic inflammation in normolipidemic conditions.
ApoE deficient mice, apoE/apoA-I double deficient (DKO) mice, DKO mice overexpressing human apoA-I, and C57Bl/6J control mice were fed normal laboratory diet until 30 weeks of age. Plasma lipids were quantified, atherosclerosis development at the aortic sinus and coronary arteries was measured, skin ultrastructure was evaluated by electron microscopy. Blood and lymphoid organs were characterized through histological, immunocytofluorimetric, and whole transcriptome analyses.
DKO were characterized by almost complete HDL deficiency and by plasma total cholesterol levels comparable to control mice. Only DKO showed xanthoma formation and severe inflammation in the skin-draining lymph nodes, whose transcriptome analysis revealed a dramatic impairment in energy metabolism and fatty acid oxidation pathways. An increased presence of CD4
T effector memory cells was detected in blood, spleen, and skin-draining lymph nodes of DKO. A worsening of atherosclerosis at the aortic sinus and coronary arteries was also observed in DKO versus apoE deficient. Human apoA-I overexpression in the DKO background was able to rescue the skin phenotype and halt atherosclerosis development.
HDL deficiency, in the absence of hyperlipidemia, is associated with severe alterations of skin morphology, aortic and coronary atherosclerosis, local and systemic inflammation.
HDL deficiency, in the absence of hyperlipidemia, is associated with severe alterations of skin morphology, aortic and coronary atherosclerosis, local and systemic inflammation.Covering up to 2022Gossypol is a polyphenolic compound isolated from cottonseed. There are two optical enantiomers of gossypol, (-)-gossypol and (+)-gossypol. Gossypol exists as three different tautomers, aldehyde, ketone and lactol. Gossypol is toxic and provides a protective mechanism for cotton plants against pests. Gossypol was used as a male contraceptive in China in the 1970s. It was eventually abandoned due to noticeable side effects, disruption of potassium uptake and incomplete reversibility. Gossypol has gained considerable research interest due to its attractive biological activities, especially antitumor and antivirus. Gossypol derivatives are prepared by a structural modification to reduce toxicity and improve their therapeutic effect. This review depicts the bioactivity and regulation mechanisms of gossypol and its derivatives as drug lead compounds, with emphasis on its antitumor mechanism. The design and synthesis of pharmacologically active derivatives based on the structure of gossypol, such as gossypol Schiff bases, apogossypol, gossypolone, are thoroughly discussed. This review aims to serve as a reference for gossypol-based drug discovery and drug design.Zoledronic acid (ZA), a third-generation bisphosphonate, has been extensively used to treat osteoporosis and cancer bone metastasis and demonstrated to suppress proliferation of varied cancer cells and selectively kill tumor-associated microphages (TAMs). However, the clinical applications of ZA in extraskeletal tumor treatment are largely restricted due to its rapid renal clearance and binding to bones. In this study, to promote intracellular delivery of ZA for amplified antitumor efficacy, tumor acidity-responsive polymeric nanoparticles with high ZA payload (ca. 12.3 wt%) and low premature ZA leakage were designed. As a pivotal material for surface coating, the acidity-sensitive and amphiphilic methoxy poly(ethylene glycol) (mPEG)-benzoic imine-octadecane (C18) (mPEG-b-C18) was synthesized by conjugation of mPEG-CHO with 1-octadecylamine upon Schiff base reaction. Through tailor-made co-assembly of the hydrophobic poly(lactic-co-glycolic acid) (PLGA), amphiphilic tocopheryl polyethylene glycol succinate (Tn vivo and inhibited tumor growth, thereby increasing the survival rate of the treated mice. The collective data suggest the great promise of tumor acidity-sensitive ZA-carrying hybrid nanoparticles in the treatment of extraskeletal solid tumors.The excitatory-inhibitory imbalance hypothesis postulates dysregulation of the gamma-aminobutyric acid (GABA) and glutamate (Glu) neurotransmitter systems as a common underlying deficit in individuals with autism spectrum disorders (ASD). Previous studies suggest an important role of these systems in the pathophysiology of ASD, including a study of our group reporting decreased glutamate concentrations in the pregenual anterior cingulate cortex (ACC) of adults with ASD. The aim of this study was to replicate our previous findings of impaired glutamate metabolism in ASD in a new sample and to additionally quantify GABA in the ACC and dorsolateral prefrontal cortex (dlPFC). Concentrations of GABA and glutamate-glutamine (Glx; combined glutamate and glutamine signal) were quantified in the ACC and dlPFC of 43 adults with ASD and 43 neurotypical controls (NTC) by magnetic resonance spectroscopy (MRS). The ASD group showed increased absolute GABA concentrations and elevated GABA/creatine ratios in the left dlPFC compared to NTC, while no group differences were detected in the pregenual and dorsal ACC. Previous findings of altered Glx concentration in the pregenual ACC of the ASD group could not be replicated. Regarding Glx concentrations and Glx/creatine ratios, there were no significant differences in the dlPFC and ACC either. The study supports the hypothesis of an altered GABA and glutamate equilibrium, indicating an imbalance between excitatory and inhibitory metabolism in ASD patients. However, inconsistent results across studies and brain regions suggest a complex underlying phenomenon. LAY SUMMARY Adults of the autism spectrum exhibit elevated levels of the inhibitory neurotransmitter GABA in the left dorsolateral prefrontal cortex. This finding supports the hypothesis of an imbalance between excitatory and inhibitory equilibrium in patients with autism spectrum disorders.The majority of binary chalcogen fluorides are fiercely reactive and extremely difficult to handle. Here, we show that access to crystalline donor-acceptor complexes between chalcogen difluorides (sulfur, selenium) and tetrafluorides (selenium, tellurium) with the N-heterocyclic carbene (NHC) 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene (IPr) is possible conveniently and safely without the need to generate the highly unstable EF2 (E=S, Se) or the very toxic and corrosive SeF4 .
The global health burden of stroke is significant and few therapeutic treatment options currently exist for patients. Pre-clinical research relies heavily on rodent stroke models but the limitations associated with using these systems alone has meant translation of drug compounds to the clinic has not been greatly successful to date. Zebrafish disease modeling offers a potentially complementary platform for pre-clinical compound screening to aid the drug discovery process for translational stroke research.
In this review, the authors introduce stroke and describe the issues associated with the current pre-clinical drug development pipeline and the advantages that zebrafish disease modeling can offer. Existing zebrafish models of ischemic and hemorrhagic stroke are reviewed. Examples of how zebrafish models have been utilized for drug discovery in other disease disciplines are also discussed.
Zebrafish disease modeling holds the capacity and potential to significantly enhance the stroke drug development pipeline.
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