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This review provides an overview of growth factor alterations in the context of diabetes and peripheral artery disease, as well as a description of the role of phosphatases in the regulation of angiogenic pathways followed by an analysis of the effects of hyperglycemia on the modulation of protein tyrosine phosphatase expression and activity. Knowledge of the role of phosphatases in diabetic peripheral artery disease will help the development of future therapeutics to locally regulate phosphatases and improve angiogenesis.Aim The present study aims to identify those microRNAs (miRNAs) in patients with univentricular heart (UVH) disease with and without Fontan palliation that may be associated with advanced liver fibrosis/cirrhosis. Materials and Methods SurePrint™ 8 × 60K Human v21 miRNA arrays were used to determine the miRNA abundance profiles in the blood of 48 UVH patients with and without Fontan palliation and 32 matched healthy controls. The abundance levels of selected miRNAs have been validated by quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Results According to microarray analysis, 50 miRNAs were found to be significantly abundant in UVH patients of which miR-29b-3p and miR-29c-3p were significantly related to the model of end-stage liver disease (MELD)-Albumin and albumin-bilirubin (ALBI) score representing advanced liver fibrosis/cirrhosis. Relative expression levels of both miRNAs were significantly higher in patients with a higher collapsibility index representing venous hepatic congestion, a higher MELD-Albumin or ALBI score and incomplete or no Fontan palliation. In the logistic regression analysis, a MELD-Albumin score ≥ 11 or ALBI score > -2.6 were best predicted by total bilirubin (OR 6.630, P = 0.016), albumin (OR 0.424, P = 0.026), and miR-29c-3p (OR 33.060, P = 0.047). After adjustment to the status of Fontan palliation, however, no statistical significance of these parameters was found thus underlining the importance of palliation status on progression of liver fibrosis/ cirrhosis in UVH patients. Conclusions In UVH patients with and without Fontan palliation, miR-29b-3p and miR-29c-3p seem to be markers of advanced liver fibrosis/cirrhosis and thus may be used in the risk assessment of these patients.The activities of adhesion and signaling receptors in platelets are controlled by several mechanisms. An important way of regulation is provided by proteolytic cleavage of several of these receptors, leading to either a gain or a loss of platelet function. The proteases involved are of different origins and types (i) present as precursor in plasma, (ii) secreted into the plasma by activated platelets or other blood cells, or (iii) intracellularly activated and cleaving cytosolic receptor domains. We provide a comprehensive overview of the proteases acting on the platelet membrane. We describe how these are activated, which are their target proteins, and how their proteolytic activity modulates platelet functions. The review focuses on coagulation-related proteases, plasmin, matrix metalloproteinases, ADAM(TS) isoforms, cathepsins, caspases, and calpains. We also describe how the proteolytic activities are determined by different platelet populations in a thrombus and conversely how proteolysis contributes to the formation of such populations.
Acute kidney injury (AKI) is a common clinical condition with high morbidity and mortality. Early risk stratification by identifying patients at risk for death or dialysis requirement has important therapeutic implications for timely interventions.
The aim of this study was to examine the association of routine blood test parameters, specifically red blood cell distribution width (RDW) and neutrophil-to-lymphocyte ratio (NLR), with the AKI patient outcomes.
All adult patients hospitalized from January 1, 2016, to June 30, 2016, in the Second Xiangya Hospital of Central South University were surveyed. Demographic characteristics, laboratory measurements, comorbidities, and outcomes of a total of 1,188 adult AKI patients were analyzed.
The incidence of AKI was 1.8% (1,188/65,329). The all-cause mortality was 16.0% (190/1,188). The multivariable relative risk of AKI mortality comparing high RDW with low RDW was 1.84 and the risk comparing high NLR with low NLR was 2.54. RDW and NLR combination showed additive values in stratifying high-risk patients, and the predictive power was comparable to the use of serum creatinine for staging AKI. In subgroup analyses, high RDW predicted prerenal AKI mortality better than intrinsic AKI. High RDW and NLR also independently predicted renal replacement therapy (RRT) requirement in AKI patients. In contrast, WBC count and platelet-to-lymphocyte ratio did not show obvious correlations with death and RRT requirement in AKI patients.
The results support the potential usefulness of RDW and NLR in risk stratification of AKI patients, providing additional prognostic information for treatment and supportive care.
The results support the potential usefulness of RDW and NLR in risk stratification of AKI patients, providing additional prognostic information for treatment and supportive care.
The impact of achieving hemodialysis laboratory and hemodynamic quality metrics on patient-reported outcomes (PROs) is unknown.
To determine if meeting dialysis laboratory quality of care measures is associated with improved PROs.
In this cross-sectional study, we measured the relationship between dialysis patients' Patient Reported Outcome Measurement Information System (PROMIS) scores and commonly used dialysis quality of care measures.
PROMIS surveys were administered to 92 dialysis patients. The mean ± SD scores demonstrated higher fatigue (55.0 ± 9.8) and lower physical function (37.9 ± 7.9) but similar cognition (50.3 ± 10.9) compared to general population normative scores of 50 ± 10. Dialysis patients meeting Kt/V goals had no better scores than those who did not. Meeting the hemoglobin (Hgb) value of ≥10 g/dL was associated with a lower fatigue score, but no difference in cognitive or physical function scores. Meeting the serum albumin goal of ≥4.0 mg/dL was associated with a higher physical function score but made no difference for cognitive function or fatigue score. As a continuous variable, a higher Hgb was associated with lower reported fatigue (HR -1.74 95%, CI [-3.09, -0.39]), but no other measures were associated with PRO scores when adjusted for demographics and comorbidities.
We found little association between measures currently used to assess the quality of dialysis care and PROs. Encouraging improved utilization of PROs and incorporating PROs into quality measurements might give a more robust assessment of quality of care. Future studies should assess the benefits of this approach.
We found little association between measures currently used to assess the quality of dialysis care and PROs. Encouraging improved utilization of PROs and incorporating PROs into quality measurements might give a more robust assessment of quality of care. Future studies should assess the benefits of this approach.
Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE). Asymmetric dimethylarginine (ADMA) has been associated with cardiovascular events in SLE patients and is a strong predictor of the progression of chronic kidney disease. However, whether ADMA can provide a predictive value for the diagnosis and treatment of LN patients remains unclear. This study evaluated the clinical significance of ADMA in LN patients.
Blood samples of 114 patients with LN, 52 patients with primary glomerular disease, and 20 healthy people were collected. Plasma ADMA was measured via enzyme-linked immunosorbent assay. The relationship between plasma ADMA levels and pathological types and renal function and efficacy in LN patients were further analyzed.
There was no significant difference in plasma ADMA levels between LN and primary glomerular disease, but both were significantly higher than the values in healthy people (
< 0.05). Plasma ADMA levels in LN patients were negatively lophosphamide as induction therapy (OR = 0.978; 95% CI 0.961-0.996;
< 0.05).
High plasma ADMA levels in combination with eGFR and complement C3 may be useful to diagnose diffuse proliferative LN. Low plasma ADMA may help to predict complete remission in proliferative LN patients treated with cyclophosphamide as induction therapy. Plasma ADMA may be a new biomarker to determine the pathological type of LN and predict the therapeutic effect.
High plasma ADMA levels in combination with eGFR and complement C3 may be useful to diagnose diffuse proliferative LN. Low plasma ADMA may help to predict complete remission in proliferative LN patients treated with cyclophosphamide as induction therapy. Plasma ADMA may be a new biomarker to determine the pathological type of LN and predict the therapeutic effect.
Chronic kidney disease (CKD) with known valve calcification (VC) places individuals at high risk of cardiovascular disease. selleck screening library The study of VC in CKD is challenging due to the lack of a suitable research model. Here, we established a rat model of multivalve calcification induced by subtotal nephrectomy and a high-phosphate (HP) diet and analyzed the valve characteristics.
We established a CKD model in Sprague-Dawley rats by performing 5/6 nephrectomy (5/6Nx) followed by feeding with chow containing different phosphate concentrations for 8, 12, or 16 weeks. The rats were divided into 4 groups sham+normal phosphate (NP, 0.9% P), sham+high phosphate (HP, 2.0% P), 5/6Nx+NP, and 5/6Nx+HP. Serum creatinine (Scr), blood urea nitrogen (BUN), parathyroid hormone (PTH), calcium, phosphorus, and 24-h urine protein levels were investigated. Pathological examinations included histological characterization, safranin staining, Alcian blue staining, and von Kossa staining at different time points. Using nanoanalytical electicles mainly composed of phosphorus and calcium were observed in both the aortic and mitral valves by transmission electron microscopy and scanning electron microscopy (SEM). The main mineral component of the calcified aortic valve particles was hydroxyapatite [Ca
(PO
)
(OH)], as shown by X-ray diffraction. However, there were no obvious differences in heart function between rats in the 5/6Nx+HP and sham+HP groups.
Our findings demonstrate that multivalve calcification is involved in CKD following 16-week HP and that hydroxyapatite [Ca
(PO
)
(OH)] is the main component of the calcified aortic valve particles of rats in the 5/6Nx+HP group.
Our findings demonstrate that multivalve calcification is involved in CKD following 16-week HP and that hydroxyapatite [Ca5(PO4)3(OH)] is the main component of the calcified aortic valve particles of rats in the 5/6Nx+HP group.
Membranous nephropathy (MN), a major cause of nephrotic syndrome, has attracted people's attention in recent years for its growing prevalence. It is the second or third leading cause of ESRD in patients with primary glomerulonephritis and is the leading glomerulopathy that recurs after kidney transplantation.
MN can be classified as idiopathic membranous nephropathy (IMN) and secondary MN. The discovery of the M-type phospholipase A2 receptor (PLA2R) and thrombospondin type-1 domain-containing 7A (THSD7A) provides the new diagnostic methods and treatment strategies for IMN on the molecular level. The study on single nucleotide polymorphism of IMN genes, such as the single M-type phospholipase A2 receptor 1 (
) gene and human leukocyte antigen (
) gene, explains the pathogenesis of the disease from the perspective of genetics and conforms to the trend of the era of precision medicine.
This review focuses on advances in the pathogenesis of IMN, including molecular and genetic pathogenesis, as well as discussing the diagnostic and treatment guiding value brought by these new discoveries.
My Website: https://www.selleckchem.com/
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