Antibiotics taken within the first year of life are linked to infant gut microbiome disruption and elevated atopic dermatitis risk.

BACKGROUND: Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in both pediatric and adult populations. The development of AD has been linked to antibiotic usage, which causes perturbation of the microbiome and has been associated with abnormal immune system function. However, imbalances in the gut microbiome itself associated with antibiotic usage have been inconsistently linked to AD. OBJECTIVES: This study aimed to elucidate the timing and specific factors mediating the relationship between systemic (oral or intravenous) antibiotic usage and AD. METHODS: We used statistical modeling and differential analysis to link CHILD Cohort Study participants' history of antibiotic usage and early-life gut microbiome alterations to AD. RESULTS: Here we report that systemic antibiotics during the first year of life, as compared to later, are associated with AD risk (adjusted odds ratio [aOR] = 1.81; 95% CI: 1.28-2.57; P < .001), with an increased number of antibiotic courses corresponding to a dose response-like increased risk of AD risk (1 course: aOR: 1.67; 95% CI: 1.17-2.38; 2 or more courses: aOR: 2.16; 95% CI: 1.30-3.59). Further, we demonstrate that microbiome alterations associated with both AD and systemic antibiotic usage fully mediate the effect of antibiotic usage on the development of AD (ßindirect = 0.072; P < .001). Alterations in the 1-year infant gut microbiome of participants who would later develop AD included increased Tyzzerella nexilis, increased monosaccharide utilization, and parallel decreased Bifidobacterium and Eubacterium spp, and fermentative pathways. CONCLUSIONS: These findings indicate that early-life antibiotic usage, especially in the first year of life, modulates key gut microbiome components that may be used as markers to predict and possibly prevent the development of AD.

CO2 hydrogenation over functional nanoporous polymers and metal-organic frameworks.

CO2 is one of the major environmental pollutants and its mitigation is attracting huge attention over the years due to continuous increase in this greenhouse gas emission in the atmosphere. Being environmentally hazardous and plentiful presence in nature, CO2 utilization as C1 resource into fuels and feedstock is very demanding from the green chemistry perspectives. To accomplish this CO2 utilization issue, functional organic materials like porous organic polymers (POPs), covalent organic frameworks (COFs) as well as organic-inorganic hybrid materials like metal-organic frameworks (MOFs), having characteristics of large surface area, high thermal stability and tunability in the porous nanostructures play significant role in designing the suitable catalyst for the CO2 hydrogenation reactions. Although CO2 hydrogenation is a widely studied and emerging area of research, till date review exclusively focused on designing POPs, COFs and MOFs bearing reactive functional groups is very limited. A thorough literature review on this matter will enrich our knowledge over the CO2 hydrogenation processes and the catalytic sites responsible for carrying out these chemical transformations. We emphasize recent state-of-the art developments in POPs/COFs/MOFs having unique functionalities and topologies in stabilizing metallic NPs and molecular complexes for the CO2 reduction reactions. The major differences between MOFs and porous organics are critically summarized in the outlook section with the aim of the future benefit in mitigating CO2 emission from ambient air.

Loss of endothelial cell-specific autophagy-related protein 7 exacerbates doxorubicin-induced cardiotoxicity.

Doxorubicin (DOX) is an effective, broad-spectrum antineoplastic agent with serious cardiotoxic side effects, which may lead to the development of heart failure. Current strategies to diagnose, prevent, and treat DOX-induced cardiotoxicity (DIC) are inadequate. Recent evidence has linked the dysregulation and destruction of the vascular endothelium to the development of DIC. Autophagy is a conserved pro-survival mechanism that recycles and removes damaged sub-cellular components. Autophagy-related protein 7 (ATG7) catalyzes autophagosome formation, a critical step in autophagy. In this study, we used endothelial cell-specific Atg7 knockout (EC-Atg7 -/- ) mice to characterize the role of endothelial cell-specific autophagy in DIC. DOX-treated EC-Atg7 -/- mice showed reduced survival and a greater decline in cardiac function compared to wild-type controls. Histological assessments revealed increased cardiac fibrosis in DOX-treated EC-Atg7 -/- mice. Furthermore, DOX-treated EC-Atg7 -/- mice had elevated serum levels of creatine kinase-myocardial band, a biomarker for cardiac damage. Thus, the lack of EC-specific autophagy exacerbated DIC. Future studies on the relationship between EC-specific autophagy and DIC could establish the importance of endothelium protection in preventing DIC.

Empagliflozin Reduces Myocardial Extracellular Volume in Patients With Type 2 Diabetes and Coronary Artery Disease.

OBJECTIVES: This study sought to evaluate the effects of empagliflozin on extracellular volume (ECV) in individuals with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). BACKGROUND: Empagliflozin has been shown to reduce left ventricular mass index (LVMi) in patients with T2DM and CAD. The effects on myocardial ECV are unknown. METHODS: This was a prespecified substudy of the EMPA-HEART (Effects of Empagliflozin on Cardiac Structure in Patients with Type 2 Diabetes) CardioLink-6 trial in which 97 participants were randomized to receive empagliflozin 10 mg daily or placebo for 6 months. Data from 74 participants were included: 39 from the empagliflozin group and 35 from the placebo group. The main outcome was change in left ventricular ECV from baseline to 6 months determined by cardiac magnetic resonance (CMR). Other outcomes included change in LVMi, indexed intracellular compartment volume (iICV) and indexed extracellular compartment volume (iECV), and the fibrosis biomarkers soluble suppressor of tumorgenicity (sST2) and matrix metalloproteinase (MMP)-2. RESULTS: Baseline ECV was elevated in the empagliflozin group (29.6 ± 4.6%) and placebo group (30.6 ± 4.8%). Six months of empagliflozin therapy reduced ECV compared with placebo (adjusted difference: -1.40%; 95% confidence interval [CI]: -2.60 to -0.14%; p = 0.03). Empagliflozin therapy reduced iECV (adjusted difference: -1.5 ml/m2; 95% CI: -2.6 to -0.5 ml/m2; p = 0.006), with a trend toward reduction in iICV (adjusted difference: -1.7 ml/m2; 95% CI: -3.8 to 0.3 ml/m2; p = 0.09). Empagliflozin had no impact on MMP-2 or sST2. CONCLUSIONS: In individuals with T2DM and CAD, 6 months of empagliflozin reduced ECV, iECV, and LVMi. No changes in MMP-2 and sST2 were seen. Further investigation into the mechanisms by which empagliflozin causes reverse remodeling is required. (Effects of Empagliflozin on Cardiac Structure in Patients With Type 2 Diabetes [EMPA-HEART]; NCT02998970).

Disruption of endothelial cell intraflagellar transport protein 88 exacerbates doxorubicin-induced cardiotoxicity.

AIMS: Doxorubicin (DOX) is a potent anticancer drug with severe dose-dependent cardiotoxicity. To address this issue, previous research primarily focused on DOX-induced toxicity on cardiomyocytes. However, more recent research has looked into the endothelium as a therapeutic target due to the emerging role of endothelial cells in the support of cardiomyocyte survival and function. MAIN METHODS: We investigated a novel role of endothelial cell (EC) primary cilia in the prevention of DOX-mediated cardiotoxicity. Mice lacking EC primary cilia, via the deletion of EC-specific intraflagellar protein 88 (IFT88) expression, were administered DOX (20 mg/kg i.p.), and assessed for survival, cardiac function, cardiac structure changes, and indices of cardiomyocyte injury. KEY FINDINGS: DOX-treatment resulted in reduced survival and cardiac function (ejection fraction and fractional shortening) in EC-IFT88-/- mice vs. their similarly treated wild-type littermates. Cardiomyocyte vacuolization, cardiac fibrosis, and serum CK-MB levels were also increased in DOX-treated mice compared to saline-treated controls. However, these parameters were not significantly different when comparing WT and EC-IFT88-/- mice after DOX treatment. SIGNIFICANCE: The loss of EC primary cilia accelerated DOX-mediated mortality and reduced cardiac function, suggesting pathways downstream of ciliary-mediated signal transduction as potential targets to promote EC support of cardiomyocyte function during DOX treatment.

The SGLT2 inhibitor empagliflozin reduces mortality and prevents progression in experimental pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a rare, but progressive and devastating vascular disease with few treatment options to prevent the advancement to right ventricular dysfunction hypertrophy and failure. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, enhances urinary glucose excretion as well as reduces cardiovascular events and mortality in individuals with type 2 diabetes. While empagliflozin has been reported to lower systemic hypertension due to increased diuresis, the effect of empagliflozin on PAH is unknown. We used monocrotaline (MCT)-treated Sprague-Dawley rats to determine if empagliflozin alters PAH-associated outcomes. Compared to vehicle control, daily empagliflozin administration significantly improved survival in rats with severe MCT-induced PAH. Hemodynamic assessments showed that empagliflozin treatment significantly reduced mean pulmonary artery pressure, right ventricular systolic pressure, and increased pulmonary acceleration time. Empagliflozin treatment resulted in reduced right ventricular hypertrophy and fibrosis. Histological and molecular assessments of lung vasculature revealed significantly reduced medial wall thickening and decreased muscularization of pulmonary arterioles after empagliflozin treatment compared to vehicle-treated rats. In summary, SGLT2 inhibition with empagliflozin lowered mortality, reduced right ventricle systolic pressure, and attenuated maladaptive pulmonary remodeling in MCT-induced PAH. Clinical studies evaluating the efficacy of SGLT-2 inhibition should be considered for patients with PAH.

Recyclable Au/SiO2-Shell/Fe3O4-Core Catalyst for the Reduction of Nitro Aromatic Compounds in Aqueous Solution.

Highly stable gold nanoparticles immobilized on the surface of amine-functionalized nanocomposite microspheres possessing a magnetite (Fe3O4) nanoparticle core and a silica (SiO2) shell (Au/SiO2-shell/Fe3O4-core) were prepared. These gold nanocomposite catalysts were tested for 4-nitrophenol (4-NP) and 2-nitroaniline (2-NA) reduction in aqueous solution in the temperature range 293-323 K and in the presence of aqueous NaBH4 reducing agent. The magnetically recyclable gold catalyst showed high stability (∼3 months), efficient recyclability (up to 10 cycles), and high activity (∼100% conversion within 225 s, ∼700 ppm 4-NP or 2-NA). The pseudo-first-order apparent reaction rate constants (k) of 4-NP and 2-NA reduction were 7.5 × 10-3 and 4.1 × 10-3 s-1, respectively, and with an apparent catalytic activity of 4.48 × 10-8 kmol/(m3 s).

A novel role of endothelial autophagy as a regulator of myocardial fatty acid oxidation.

BACKGROUND: We sought to determine if endothelial autophagy affects myocardial energy metabolism. METHODS: We used isolated working mouse hearts to compare cardiac function, energy metabolism, and ischemic response of hearts from endothelial cell-specific ATG7 knockout (EC-ATG7-/-) mice to hearts from their wild-type littermates. We also conducted gene analyses on human umbilical vein endothelial cells incubated with scrambled small interfering RNA or small interfering ATG7. RESULTS: In the presence of insulin, working hearts from EC-ATG7-/- mice, relative to those from wild-type littermates, exhibited greater reductions in insulin-associated palmitate oxidation indicating a diminished reliance on fatty acids as a fuel source. Likewise, palmitate oxidation was markedly lower in the hearts of EC-ATG7-/- mice versus wild-type mice during reperfusion of ischemic hearts. Although hearts from EC-ATG7-/- mice revealed significantly lower triacylglycerol content compared with those from wild-type mice, ATG7-silenced human umbilical vein endothelial cells demonstrated appreciably lower fatty acid binding protein 4 and 5 expression relative to those treated with scrambled small interfering RNA. CONCLUSIONS: Disruption of endothelial autophagy reduces cardiac fatty acid storage and dampens reliance on fatty acid oxidation as a cardiac fuel source. The autophagy network represents a novel target for designing new strategies aimed at resetting perturbed myocardial bioenergetics.

Role of endothelial primary cilia as fluid mechanosensors on vascular health.

Primary cilia are microtubule-based organelles that protrude from the cell surface of many mammalian cell types, including endothelial and epithelial cells, osteoblasts, and neurons. These antennal-like projections enable cells to detect extracellular stimuli and elicit responses via intracellular signaling mechanisms. Primary cilia on endothelial cells lining blood vessels function as calcium-dependent mechanosensors that sense blood flow. In doing so, they facilitate the regulation of hemodynamic parameters within the vascular system. Defects in endothelial primary cilia result in inappropriate blood flow-induced responses and contribute to the development of vascular dysfunctions, including atherosclerosis, hypertension, and aneurysms. This review examines the current understanding of vascular endothelial cilia structure and function and their role in the vascular system. Future directions for primary cilia research and treatments for ciliary-based pathologies are discussed.

Role of Endothelium in Doxorubicin-Induced Cardiomyopathy.

The clinical use of doxorubicin in cancer is limited by cardiotoxic effects that can lead to heart failure. Whereas earlier work focused on the direct impact of doxorubicin on cardiomyocytes, recent studies have turned to the endothelium, because doxorubicin-damaged endothelial cells can trigger the development and progression of cardiomyopathy by decreasing the release and activity of key endothelial factors and inducing endothelial cell death. Thus, the endothelium represents a novel target for improving the detection, management, and prevention of doxorubicin-induced cardiomyopathy.

Novel APC gene mutations associated with protein alteration in diffuse type gastric cancer.

BACKGROUND: The role of adenomatous polyposis coli (APC) gene in mitosis might be critical for regulation of genomic stability and chromosome segregation. APC gene mutations have been associated to have a role in colon cancer and since gastric and colon tumors share some common genetic lesions, it is relevant to investigate the role of APC tumor suppressor gene in gastric cancer. METHODS: We investigated for somatic mutations in the Exons 14 and 15 of APC gene from 40 diffuse type gastric cancersamples. Rabbit polyclonal anti-APC antibody was used, which detects the wild-type APC protein and was recommended for detection of the respective protein in human tissues. Cell cycle analysis was done from tumor and adjacent normal tissue. RESULTS: APC immunoreactivity showed positive expression of the protein in stages I, II, III and negative expression in Stages III and IV. Two novel deleterious variations (g.127576C > A, g.127583C > T) in exon 14 sequence were found to generate stop codon (Y622* and Q625*)in the tumor samples. Due to the generation of stop codon, the APC protein might be truncated and all the regulatory features could be lost which has led to the down-regulation of protein expression. Our results indicate that aneuploidy might occurdue to the codon 622 and 625 APC-driven gastric tumorigenesis, in agreement with our cell cycle analysis. The APC gene function in mitosis and chromosomal stability might be lost and G1 might be arrested with high quantity of DNA in the S phase. Six missense somatic mutations in tumor samples were detected in exon 15 A-B, twoof which showed pathological and disease causing effects based on SIFT, Polyphen2 and SNPs & GO score and were not previously reported in the literature or the public mutation databases. CONCLUSION: The two novel pathological somatic mutations (g.127576C > A, g.127583C > T) in exon 14 might be altering the protein expression leading to development of gastric cancer in the study population. Our study showed that mutations in the APC gene alter the protein expression and cell cycle regulation in diffuse type gastric adenocarcinoma.

Hyaluronidase 2 Deficiency Causes Increased Mesenchymal Cells, Congenital Heart Defects, and Heart Failure.

BACKGROUND: Hyaluronan (HA) is required for endothelial-to-mesenchymal transition and normal heart development in the mouse. Heart abnormalities in hyaluronidase 2 (HYAL2)-deficient (Hyal2-/- ) mice and humans suggested removal of HA is also important for normal heart development. We have performed longitudinal studies of heart structure and function in Hyal2-/- mice to determine when, and how, HYAL2 deficiency leads to these abnormalities. METHODS AND RESULTS: Echocardiography revealed atrial enlargement, atrial tissue masses, and valvular thickening at 4 weeks of age, as well as diastolic dysfunction that progressed with age, in Hyal2-/- mice. These abnormalities were associated with increased HA, vimentin-positive cells, and fibrosis in Hyal2-/- compared with control mice. Based on the severity of heart dysfunction, acute and chronic groups of Hyal2-/- mice that died at an average of 12 and 25 weeks respectively, were defined. Increased HA levels and mesenchymal cells, but not vascular endothelial growth factor in Hyal2-/- embryonic hearts, suggest that HYAL2 is important to inhibit endothelial-to-mesenchymal transition. Consistent with this, in wild-type embryos, HYAL2 and HA were readily detected, and HA levels decreased with age. CONCLUSIONS: These data demonstrate that disruption of normal HA catabolism in Hyal2-/- mice causes increased HA, which may promote endothelial-to-mesenchymal transition and proliferation of mesenchymal cells. Excess endothelial-to-mesenchymal transition, resulting in increased mesenchymal cells, is the likely cause of morphological heart abnormalities in both humans and mice. In mice, these abnormalities result in progressive and severe diastolic dysfunction, culminating in heart failure.

Mutations in HYAL2, Encoding Hyaluronidase 2, Cause a Syndrome of Orofacial Clefting and Cor Triatriatum Sinister in Humans and Mice.

Orofacial clefting is amongst the most common of birth defects, with both genetic and environmental components. Although numerous studies have been undertaken to investigate the complexities of the genetic etiology of this heterogeneous condition, this factor remains incompletely understood. Here, we describe mutations in the HYAL2 gene as a cause of syndromic orofacial clefting. HYAL2, encoding hyaluronidase 2, degrades extracellular hyaluronan, a critical component of the developing heart and palatal shelf matrix. Transfection assays demonstrated that the gene mutations destabilize the molecule, dramatically reducing HYAL2 protein levels. Consistent with the clinical presentation in affected individuals, investigations of Hyal2-/- mice revealed craniofacial abnormalities, including submucosal cleft palate. In addition, cor triatriatum sinister and hearing loss, identified in a proportion of Hyal2-/- mice, were also found as incompletely penetrant features in affected humans. Taken together our findings identify a new genetic cause of orofacial clefting in humans and mice, and define the first molecular cause of human cor triatriatum sinister, illustrating the fundamental importance of HYAL2 and hyaluronan turnover for normal human and mouse development.

Hyaluronidase 2 (HYAL2) is expressed in endothelial cells, as well as some specialized epithelial cells, and is required for normal hyaluronan catabolism.

Hyaluronidase 2 (HYAL2) is a membrane-anchored protein that is proposed to initiate the degradation of hyaluronan (HA) in the extracellular matrix. The distribution of HYAL2 in tissues, and of HA in tissues lacking HYAL2, is largely unexplored despite the importance of HA metabolism in several disease processes. Herein, we use immunoblot and histochemical analyses to detect HYAL2 and HA in mouse tissues, as well as agarose gel electrophoresis to examine the size of HA. HYAL2 was detected in all tissues that were examined, including the brain. It was localized to the surface and cytoplasm of endothelial cells, as well as specialized epithelial cells in several tissues, including the skin. Accumulated HA, often of higher molecular mass than that in control tissues, was detected in tissues from Hyal2 (-/-) mice. The accumulating HA was located near to where HYAL2 is normally found, although in some tissues, it was distant from the site of HYAL2 localization. Overall, HYAL2 was highest in tissues that remove HA from the circulation (liver, lymph node and spleen), but the levels of HA accumulation in Hyal2 (-/-) mice were highest in tissues that catabolize locally synthesized HA. Our results support HYAL2's role as an extracellular enzyme that initiates HA breakdown in somatic tissues. However, our findings also suggest that HYAL2 contributes to HA degradation through other routes, perhaps as a soluble or secreted form.

Ligand centered radical pathway in catechol oxidase activity with a trinuclear zinc-based model: synthesis, structural characterization and luminescence properties.

A new trinuclear zinc(II) complex, [Zn3(L)(NCS)2](NO3)2·CH3OH·H2O (1), of a (N,O)-donor compartmental Schiff base ligand (H2L=N,N'-bis(3-methoxysalicylidene)-1,3-diamino-2-propanol), has been synthesized in crystalline phase. The zinc(II) complex has been characterized by elemental analysis, IR spectroscopy, UV-Vis spectroscopy, powder X-ray diffraction study (PXRD), (1)H NMR, EI mass spectrometry and thermogravimetric analysis. PXRD revealed that 1 crystallizes in P-1 space group with a=9.218 Å, b=10.849 Å, c=18.339 Å, with unit cell volume is 2179.713(Å)(3). Fluorescence spectra in methanolic solution reflect that intensity of emission for 1 is much higher compared to H2L and both the compounds exhibit good fluorescence properties. The complex 1 exhibits significant catalytic activities of biological relevance, viz. catechol oxidase. In methanol, it efficiently catalyzes the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) to corresponding quinone via formation of a dinuclear species as [Zn2(L)(3,5-DTBC)]. Electron Paramagnetic Resonance (EPR) experiment suggests generation of radicals in the presence of 3,5-DTBC and it may be proposed that the radical pathway is probably responsible for conversion of 3,5-DTBC to 3,5-DTBQ promoted by complex of redox-innocent Zn(II) ion.

Growth arrest in the ribosomopathy, Bowen-Conradi syndrome, is due to dramatically reduced cell proliferation and a defect in mitotic progression.

Bowen-Conradi syndrome (BCS) is a ribosomopathy characterized by severe developmental delay and growth failure that typically leads to death by one year of age. It is caused by a c.257A>G, p.D86G substitution in the ribosomal biogenesis protein, Essential for Mitotic Growth 1 (EMG1). We generated a knock-in of the D86G substitution in mice to characterize the effects of EMG1 deficiency, particularly in the brain, where EMG1 expression is high. Embryos homozygous for the mutation in Emg1 were small for gestational age with neural tube defects, and died between embryonic days 8.5 and 12.5. These embryos exhibited dramatically reduced cell proliferation, which we also detected in autopsy brain tissue and bone marrow of BCS patients, consistent with a requirement for high levels of EMG1 in tissues with rapid cell proliferation. In fibroblasts derived from the BCS mouse embryos, we detected a high proportion of binucleated cells, indicating that a mitotic defect underlies the growth arrest in BCS. These studies add to growing evidence of a link between ribosome biogenesis, mitotic progression, and brain development that is currently unexplored.

Long-term correction of Sandhoff disease following intravenous delivery of rAAV9 to mouse neonates.

G(M2) gangliosidoses are severe neurodegenerative disorders resulting from a deficiency in ß-hexosaminidase A activity and lacking effective therapies. Using a Sandhoff disease (SD) mouse model (Hexb(-/-)) of the G(M2) gangliosidoses, we tested the potential of systemically delivered adeno-associated virus 9 (AAV9) expressing Hexb cDNA to correct the neurological phenotype. Neonatal or adult SD and normal mice were intravenously injected with AAV9-HexB or -LacZ and monitored for serum ß-hexosaminidase activity, motor function, and survival. Brain G(M2) ganglioside, ß-hexosaminidase activity, and inflammation were assessed at experimental week 43, or an earlier humane end point. SD mice injected with AAV9-LacZ died by 17 weeks of age, whereas all neonatal AAV9-HexB-treated SD mice survived until 43 weeks (P < 0.0001) with only three exhibiting neurological dysfunction. SD mice treated as adults with AAV9-HexB died between 17 and 35 weeks. Neonatal SD-HexB-treated mice had a significant increase in brain ß-hexosaminidase activity, and a reduction in G(M2) ganglioside storage and neuroinflammation compared to adult SD-HexB- and SD-LacZ-treated groups. However, at 43 weeks, 8 of 10 neonatal-HexB injected control and SD mice exhibited liver or lung tumors. This study demonstrates the potential for long-term correction of SD and other G(M2) gangliosidoses through early rAAV9 based systemic gene therapy.

Murine hyaluronidase 2 deficiency results in extracellular hyaluronan accumulation and severe cardiopulmonary dysfunction.

Hyaluronidase (HYAL) 2 is a membrane-anchored protein that is proposed to hydrolyze hyaluronan (HA) to smaller fragments that are internalized for breakdown. Initial studies of a Hyal2 knock-out (KO) mouse revealed a mild phenotype with high serum HA, supporting a role for HYAL2 in HA breakdown. We now describe a severe cardiac phenotype, deemed acute, in 54% of Hyal2 KO mice on an outbred background; Hyal2 KO mice without the severe cardiac phenotype were designated non-acute. Histological studies of the heart revealed that the valves of all Hyal2 KO mice were expanded and the extracellular matrix was disorganized. HA was detected throughout the expanded valves, and electron microscopy confirmed that the accumulating material, presumed to be HA, was extracellular. Both acute and non-acute Hyal2 KO mice also exhibited increased HA in the interstitial extracellular matrix of atrial cardiomyocytes compared with control mice. Consistent with the changes in heart structure, upper ventricular cardiomyocytes in acute Hyal2 KO mice demonstrated significant hypertrophy compared with non-acute KO and control mice. When the lungs were examined, evidence of severe fibrosis was detected in acute Hyal2 KO mice but not in non-acute Hyal2 KO or control mice. Total serum and heart HA levels, as well as size, were increased in acute and non-acute Hyal2 KO mice compared with control mice. These findings indicate that HYAL2 is essential for the breakdown of extracellular HA. In its absence, extracellular HA accumulates and, in some cases, can lead to cardiopulmonary dysfunction. Alterations in HYAL2 function should be considered as a potential contributor to cardiac pathologies in humans.

In situ UV-vis and EPR study on the formation of hydroperoxide species during direct gas phase propylene epoxidation over Au/Ti-SiO(2) catalyst.

In recent years, there have been great experimental and theoretical advances in the understanding of the epoxidation of propylene by O(2) and H(2) over Au supported on titanium-containing oxidic supports; however, thus far spectroscopic evidence of reacting species for proposed mechanisms has been lacking. Hydroperoxide species have been postulated as an intermediate responsible for the epoxidation of propylene with O(2) and H(2). In order to obtain direct evidence for the different type of active oxygen species, in situ UV-vis and EPR measurements were carried out during the epoxidation of propylene with O(2) and H(2) over a Au/Ti-SiO(2) (Ti/Si = 3:100) catalyst. It was determined that the adsorbed species of oxygen (O(2)(-)) resided on Au, more likely at a perimeter site, and it led to the formation of titanium hydroperoxo species. These results support the possible mechanism of formation of these hydroperoxo species via H(2)O(2) produced from O(2) and H(2) adsorbed on the Au surfaces.