41 research outputs found
Elimination of Endogenous Toxin, Creatinine from Blood Plasma Depends on Albumin Conformation: Site Specific Uremic Toxicity & Impaired Drug Binding
Uremic syndrome results from malfunctioning of various organ systems due to the retention of uremic toxins which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. The aim of this study was to elucidate the mechanisms underlying the renal elimination of uremic toxin creatinine that accumulate in chronic renal failure. Quantitative investigation of the plausible correlations was performed by spectroscopy, calorimetry, molecular docking and accessibility of surface area. Alkalinization of normal plasma from pH 7.0 to 9.0 modifies the distribution of toxin in the body and therefore may affect both the accumulation and the rate of toxin elimination. The ligand loading of HSA with uremic toxin predicts several key side chain interactions of site I that presumably have the potential to impact the specificity and impaired drug binding. These findings provide useful information for elucidating the complicated mechanism of toxin disposition in renal disease state
Enhancing adherence in trials promoting change in diet and physical activity in individuals with a diagnosis of colorectal adenoma; a systematic review of behavioural intervention approaches
Anti-cancer drug validation: the contribution of tissue engineered models
Abstract Drug toxicity frequently goes concealed until clinical trials stage, which is the most challenging, dangerous and expensive stage of drug development. Both the cultures of cancer cells in traditional 2D assays and animal studies have limitations that cannot ever be unraveled by improvements in drug-testing protocols. A new generation of bioengineered tumors is now emerging in response to these limitations, with potential to transform drug screening by providing predictive models of tumors within their tissue context, for studies of drug safety and efficacy. Considering the NCI60, a panel of 60 cancer cell lines representative of 9 different cancer types: leukemia, lung, colorectal, central nervous system (CNS), melanoma, ovarian, renal, prostate and breast, we propose to review current Bstate of art^ on the 9 cancer types specifically addressing the 3D tissue models that have been developed and used in drug discovery processes as an alternative to complement their studyThis article is a result of the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This article was also supported by the EU Framework Programme for Research and Innovation HORIZON 2020 (H2020) under grant agreement n° 668983 — FoReCaST. FCT distinction attributed to Joaquim M. Oliveira (IF/00423/2012) and Vitor M. Correlo (IF/01214/2014) under the Investigator FCT program is also greatly acknowledged.info:eu-repo/semantics/publishedVersio
Plasma Cholesteryl Ester Transfer Protein (CETP) in Relation to Human Pathophysiology
Plasma CETP was initially isolated as a highly purified 74 kD protein. The human CETP gene is located at chromosome 16q13, near the locus of the lecithin cholesterol acyltransferase (LCAT) gene. The CETP gene consists of 16 exons, spanning 25 kb. The CETP mRNA encodes 476 amino acids. The mature CETP contains four N-linked sugars with a variable glycosylation site of 341Asn. CETP mRNA is expressed in various tissues, but liver cells, adipocytes, and macrophages are abundant sources. One of the determinants of high density lipoprotein (HDL) neutral lipid composition is plasma CETP. In incubated human plasma, transfer and equilibration of (LCAT)-generated cholesteryl ester (CE) is found. Humans, hamsters, guinea pigs, and chickens belong to a group with intermediate CETP activity. Plasma CETP binds neutral lipids CE or triglyceride (TG), and phospholipid (PL) on HDL3, but CETP selectively promotes an exchange of CE and TG among lipoproteins. On the one hand, HDL-TG can be hydrolyzed by hepatic lipase, and on the other hand, plasma CETP decreases HDL particle size via CE/TG exchange between chylomicron/VLDL and HDL. Thus, CETP thereby accelerates the catabolic rate of HDL apolipoproteins. CETP enhances HDL remodeling from large HDL to small subclasses including pre-HDL. However, CETP deficiency would decrease cholesterol esterification rate, thereby inhibiting maturation of preb-HDL to α-migrating spherical HDL. Therefore, in CETP deficiency, large-to-small HDL remodeling is decreased and preb-HDL catabolism is also decreased. © 2010 Elsevier Inc. All rights reserved.[Book Chapter
Ameliorating effect of Erxian decoction combined with Fructus Schisandrae chinensis (Wu Wei Zi) on menopausal sweating and serum hormone profiles in a rat model
The effect of high hydrostatic pressure on the physiological and biochemical properties of pepper ( Capsicum annuum
Suppression of serum lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism by intensive insulin therapy in the first year of type 1 diabetes mellitus: Prospective InLipoDiab1 study
Tutorial for the 2022 ACM SIGMOD Conference: Spatial Data Quality in the IoT Era: Management and Exploitation
Within the rapidly expanding Internet of Things (IoT), growing amounts of spatially referenced data are being generated. Due to the dynamic, decentralized, and heterogeneous nature of the IoT, spatial IoT data (SID) quality has attracted considerable attention in academia and industry. How to invent and use technologies for managing spatial data quality and exploiting low-quality spatial data are key challenges in the IoT. In this tutorial, we highlight the SID consumption requirements in applications and offer an overview of spatial data quality in the IoT setting. In addition, we review pertinent technologies for quality management and low-quality data exploitation, and we identify trends and future directions for quality-aware SID management and utilization. The tutorial aims to not only help researchers and practitioners to better comprehend SID quality challenges and solutions, but also offer insights that may enable innovative research and applications