Long COVID is characterized by persistent symptoms beyond 3-months of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection that last for at least 2 months and cannot be explained by ...an alternative diagnosis. Autonomic, immunologic, endothelial, and hypercoagulation are implicated as possible mechanisms of long COVID symptoms. Despite recognition of the public health challenges posed by long COVID, the current understanding of the pathophysiological underpinnings is still evolving. In this narrative review, we explore the long-term effects of SARS-CoV-2 infection on T cell activation such as autoimmune disorders and endothelial cell dysfunction involving vascular impairments within pulmonary and renal architecture. We have described how endothelial dysfunction and vascular abnormalities may underscore findings of exercise intolerance by way of impaired peripheral oxygen extraction in individuals with long COVID.
Endothelial Progenitor cells (EPCs) has been shown to be dysfunctional in both type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) leading to poor regeneration of endothelium and renal ...perfusion. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. Cellular mechanisms of DPP4 inhibitors such as linagliptin (LG) on CVD risk, in patients with T2DM with established CKD has not been established. Linagliptin, a DPP4 inhibitor when added to insulin, metformin or both may improve endothelial dysfunction in a diabetic kidney disease (DKD) population.
31 subjects taking metformin and/or Insulin were enrolled in this 12 weeks, double blind, randomized placebo matched trial, with 5 mg LG compared to placebo. Type 2 diabetes subjects (30-70 years old), HbA1c of 6.5-10%, CKD Stage 1-3 were included. CD34+ cell number, migratory function, gene expression along with vascular parameters such as arterial stiffness, biochemistry, resting energy expenditure and body composition were measured. Data were collected at week 0, 6 and 12. A mixed model regression analysis was done with p value < 0.05 considered significant.
A double positive CD34/CD184 cell count had a statistically significant increase (p < 0.02) as determined by flow cytometry in LG group where CD184 is SDF1a cell surface receptor. Though mRNA differences in CD34+ve was more pronounced CD34- cell mRNA analysis showed increase in antioxidants (superoxide dismutase 2 or SOD2, Catalase and Glutathione Peroxidase or GPX) and prominent endothelial markers (PECAM1, VEGF-A, vWF and NOS3). Arterial stiffness measures such as augmentation Index (AI) (p < 0.04) and pulse wave analysis (PWV) were improved (reduced in stiffness) in LG group. A reduction in LDL: HDL ratio was noted in treatment group (p < 0.04). Urinary exosome protein examining podocyte health (podocalyxin, Wilms tumor and nephrin) showed reduction or improvement.
In DKD subjects, Linagliptin promotes an increase in CXCR4 expression on CD34 + progenitor cells with a concomitant improvement in vascular and renal parameters at 12 weeks. Trial Registration Number NCT02467478 Date of Registration: 06/08/2015.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The oxygen speciation in (Na2O)x(GeO2)100-x glasses with 4 ≤ x ≤ 28 is studied using high-resolution 17O NMR spectroscopy at ultra-high field (35.2 T). The structure of glasses with x ≤ 18 consists ...of oxygen atoms bridging either two four-coordinated GeIV atoms (O44) or a GeIV and another six-coordinated GeVI atom (O46). The O46: O44 ratio monotonically increases with increasing Na2O content in this composition range. Further addition of Na2O results in a lowering of O46 and in a concomitant rise in the concentration of non-bridging oxygen (NBO) atoms. The resulting compositional variation in the average coordination number of Ge atoms is associated with the non-monotonic evolution of density and the germanate anomaly in these glasses. On the other hand, increasing fictive temperature results in a net conversion of GeVI → GeIV + NBO in these glasses, which is argued to be a source of temperature dependent configurational entropy in germanate liquids.
•Oxygen speciation in sodium germanate glasses is studied using ultra-high field 17O NMR.•Initial addition of Na2O to GeO2 results in GeIV -to- GeVI conversion.•Further addition of Na2O results in a rise in the concentration of NBO atoms.•Average GeO network connectivity is linked to the germanate anomaly.•Temperature dependent Ge speciation in these glasses is linked to fragility.
Despite its chemical simplicity, a definitive description of the structure of TeO2 glass has remained elusive due to the complexity of the Te-O coordination environment. In this work we probe the ...Te-O coordination environment in glassy TeO2 using 2D 125Te isotropic-anisotropic chemical shift correlation nuclear magnetic resonance (NMR) spectroscopy. The NMR results are consistent with the presence of two Te-O environments in this glass, characterized by their distinct set of 125Te chemical shift parameters. The dominant environment (~89%) is a distorted trigonal bipyramidal TeO4 unit, reminiscent of that observed in crystalline γ-TeO2. A second, minor (~11%) component can be assigned, on the basis of its chemical shift parameters, to a TeO3 unit. The resulting average coordination number, nTeO, measured by 125Te NMR (nTeO ≈ 3.9) is higher than its previously reported value obtained using neutron diffraction (nTeO ≈ 3.7).
•Structure of TeO2 glass is studied using 2D 125Te NMR spectroscopy.•The presence of two distinct Te-O coordination environments can be detected.•Relative fractions of TeO3 and TeO4 environments are ~11% and ~89%, respectively.•Average Te-O coordination number of TeO2 glass is ~3.9.
Consumption of non-nutritive sweeteners (NNS) has been consistently associated with obesity and cardiometabolic disease in epidemiologic studies. Herein, we investigated effects of sucralose, a ...widely used NNS, at a cellular level. We wanted to investigate effect of sucralose on reactive oxygen species accumulation and adipogenesis in a human adipocyte tissue-derived mesenchymal stromal cells (MSCs) in a controlled fashion. Methods In vitro experiments were conducted on commercially available MSCs obtained from human adipose tissue. hMSCs were exposed with sucralose at 0.2 mM (a concentration which could plausibly be observed in the circulatory system of high NNS consumers) up to 1.0 mM (supra-physiologic concentration) in the presence of both normal and high glucose media to detect a dose response based on the outcome measures. Reactive oxygen species (ROS) were detected using Mitosox Red staining and further analyzed by ImageJ and gene expression analysis. Effect of sucralose on adipogenic differentiation was observed in different concentrations of sucralose followed by gene expression analysis and Oil Red O staining. Results Increased ROS accumulation was observed within 72 h of exposure. Increased adipogenesis was also noted when exposed to higher dose of sucralose. Conclusion Sucralose promotes ROS accumulation and adipogenesis in human adipose tissue derived mesenchymal stromal cells. Keywords: Non-nutritive sweeteners, Mesenchymal stromal cells, Adipogenesis, Obesity, Diabetes, Reactive oxygen species
We present a computational study of the magnetic and electronic transport properties of cumulene-based monocobaltocene and dicobaltocene complexes. We show that the odd cumulene-based dicobaltocene ...complexes are a potential candidate for the ferromagnetic material. The calculation of the zero-field splitting (ZFS) parameter D confirms that the odd cumulene-based dicobaltocene complexes can be used as potential single-molecule magnets. The monocobaltocene-based complexes are found to be a good spin filter, as demonstrated by the calculation of the transmission and current versus voltage curve. The orthogonal SOMOs of the dicobaltocene complexes make them weak or a nonspin filter despite having a high spin ground state.
Background Diabetic kidney disease is associated with glomerulosclerosis and poor renal perfusion. Increased capillary formation and improved perfusion may help to halt or reverse the injury. ...Transplanting apoptosis-resistant p53-silenced endothelial progenitor cells (p53sh-EPCs) may help improve vascularization and renal perfusion and could be more beneficial than another stem cell such as the mouse mesenchymal stromal cell (mMSC). Methods and Results Hyperglycemia and proteinuria were confirmed at 8 to 10 weeks in streptozotocin-induced type1 diabetic C57Bl/6 mice, followed by transplantation of 0.3 million p53sh-EPCs, Null-EPCs (control), or mMSC under each kidney capsule. Urine was collected weekly for creatinine and protein levels. Blood pressure was measured by direct arterial cannulation and renal perfusion was measured by renal ultrasound. The kidneys were harvested for histology and mRNA expression. Reduction of protein/creatinine (AUC) was observed in p53sh-EPC-transplanted mice more than null-EPC (1.8-fold,
=0.03) or null-mMSC (1.6-fold,
=0.04, n=4) transplanted mice. Markers for angiogenesis, such as endothelial nitric oxide synthase (1.7-fold,
=0.06), were upregulated post p53sh-EPC transplantation compared with null EPC. However, vascular endothelial growth factor-A expression was reduced (7-fold,
=0.0004) in mMSC-transplanted mice, compared with p53sh-EPC-transplanted mice. Isolectin-B4 staining of kidney section showed improvement of glomerular sclerosis when p53sh-EPC was transplanted, compared with null-EPC or mMSC. In addition, mean and peak renal blood velocity (1.3-fold,
=0.01, 1.4-fold,
=0.001, respectively) were increased in p53sh-EPC-transplanted mice, relative to null-EPC transplanted mice. Conclusions Apoptosis-resistant p53sh EPC transplantation could be beneficial in the treatment of diabetic kidney disease by decreasing proteinuria, and improving renal perfusion and glomerular architecture.
A fundamental understanding of glass relaxation behavior is vital to the glass and polymer science communities. While prior work has focused on relaxation of first-order thermodynamic properties such ...as enthalpy and density, we present theoretical and experimental results showing that fluctuations in enthalpy and density relax nonmonotonically. These results provide direct evidence for dynamical heterogeneities and their close association with density fluctuations. Our results imply that density fluctuations, and hence light scattering, can be minimized through design of thermal history.
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