Antivenom is the mainstay of treatment of snakebite envenoming. However, adverse reactions to snake antivenom that is available are common in many parts of the world where snakebite is prevalent. ...Both acute (anaphylactic or pyrogenic) and delayed (serum sickness type) reactions occur. Acute reactions are usually mild but severe systemic anaphylaxis may develop, often within an hour or so of exposure to antivenom. Serum sickness after antivenom has a delayed onset between 5 and 14 days after its administration. Ultimately, the prevention reactions will depend mainly on improving the quality of antivenom. Until these overdue improvements take place, doctors will have to depend on pharmacological prophylaxis, where the search for the best prophylactic agent is still on‐going, as well as careful observation of patients receiving antivenom in preparation for prompt management of acute as well as delayed reactions when they occur.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The choice of an optimal strategy of stem cell culture is at the moment an impossible task, and the elaboration of a culture medium adapted to the production of embryonic and adult mesenchymal stem ...cells for the clinical application of cell therapy remains a crucial matter. To make an informed choice, it is crucial to not underestimate the theoretical health risk of using xenogenic compounds, to limit the immunological reactions once stem cells are transplanted, to not overestimate the controversial results obtained with human serum, plasma, and blood derivatives, as well as to carefully examine the pros and cons of serum‐free and ad hoc formulation strategies; besides that, to also maintain multipotentiality, self‐renewal, and transplantability. The extent to which we are able to achieve effective cell therapies will depend on assimilating a rapidly developing base of scientific knowledge with the practical considerations of design, delivery, and host response. Although clinical studies have already started, many questions remain unsolved, and concomitantly even more evidence on suitable and safe off‐the‐shelf products (mainly xeno‐free) for embryonic and mesenchymal stem cells is cropping up, even though there should be no rush to enter the clinical stage while the underlying basic research is still not so solid; this solely will lead to high‐quality translational research, without making blunders stemming from the assumption that all that glitters is not gold.
Disclosure of potential conflicts of interest is found at the end of this article.
•This study establishes a simple and fast method for the preparation of albumin nanoparticles.•Different parameters were considered to determine their effects on the size of ...nanoparticles.•Preparation procedure was simplified by using an apparatus for the addition of ethanol.•By using EDC, the time of nanoparticles preparation procedure was reduced to 3h.•Nanoparticles with the size of around 100nm and polydispersity below 0.2 were obtained.
The current study tried to establish a simple and fast method for the preparation of BSA and HSA nanoparticles, based on an improved desolvation procedure under the aspect of a controllable particle size around 100nm for drug delivery applications. The Procedure used for the nanoparticles preparation was simplified by using a designed apparatus for controlling the addition of ethanol and it was used instead of conventional tubing pump which enabled the preparation of nanoparticles under defined conditions. By using EDC as cross-linker instead of glutharaldehyde, the time of nanoparticles preparation procedure was reduced to 3h. Several factors of the preparation process, such as the volume of the albumin solution, desolvating agent volume, the amount of cross-linker, the presence of salts and protein concentration were evaluated. Nanoparticles with smaller size were obtained under experimental conditions without the presence of salts or the use of buffers, 250mg of protein/4ml water, 5mg cross-linker, the addition of 4 and 8ml ethanol by using the designed apparatus to the HSA and BSA solution, respectively. By using this improved method, BSA and HSA nanoparticles of the size around 100nm and polydispersity below 0.2 were obtained.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Protein aggregation is one of the greatest challenges in biopharmaceuticals as it could decrease therapeutic efficacy, induce immunogenicity, and reduce shelf life of protein drugs. However, there ...lacks high-throughput methods than can count and size protein aggregates in the nanometer size range, especially for those smaller than 100 nm. Employing a laboratory-built nano-flow cytometer (nFCM) that enables light scattering detection of single silica nanoparticles as small as 24 nm with sizing resolution and accuracy comparable to those of electron microscopy, here, we report a new benchmark to analyze single protein aggregates as small as 40 nm. With an analysis rate of up to 10,000 particles/min, the size distribution and particle concentration of nanometer protein aggregates can be acquired in 2–3 min. Employing heat-induced aggregation of bovine serum albumin (BSA) at high concentrations as the model system, effects of different categories of excipients, including sugars, polyols, salts, and amino acids on the inhibition of protein aggregation were investigated. Strikingly enough, as high as 1010 to 1012 particles/mL of protein aggregates were observed in the size range of 40 to 200 nm for therapeutic proteins of human serum albumin injection, reconstituted recombinant human interieukin-2 solution, and human immunoglobulin injection. nFCM opens a new avenue to count and size nanometer protein aggregates, suggesting its future usability in the quality assessment and formulation promotion of therapeutic proteins.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM
Surfaces that resist nonspecific protein adsorption in a complex biological milieu are required for a variety of applications. However, few strategies can achieve a robust antifouling coating on a ...surface in an easy and reliable way, regardless of material type, morphology, and shape. Herein, the preparation of an antifouling coating by one‐step aqueous supramolecular assembly of bovine serum albumin (BSA) is reported. Based on fast amyloid‐like protein aggregation through the rapid reduction of the intramolecular disulfide bonds of BSA by tris(2‐carboxyethyl)phosphine, a dense proteinaceous nanofilm with controllable thickness (≈130 nm) can be covered on virtually arbitrary material surfaces in tens of minutes by a simple dipping or spraying. The nanofilm shows strong stability and adhesion with the underlying substrate, exhibiting excellent resistance to the nonspecific adsorption of a broad‐spectrum of contaminants including proteins, serum, cell lysate, cells, and microbes, etc. In vitro and in vivo experiments show that the nanofilm can prevent the adhesion of microorganisms and the formation of biofilm. Compared with native BSA, the proteinaceous nanofilm coating exposes a variety of functional groups on the surface, which have more‐stable adhesion with the surface and can maintain the antifouling in harsh conditions including under ultrasound, surfactants, organic solvents, and enzymatic digestion.
Few strategies can achieve a robust antifouling coating on a surface in an easy and reliable way. The preparation of an antifouling coating by one‐step aqueous amyloid‐like aggregation of bovine serum albumin (PTB) is reported, showing strong stability and adhesion with the underlying substrate, as well as excellent resistance to the nonspecific adsorption of a broad‐spectrum of biological contaminants.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
RATIONALE:The transport of interstitial fluid and solutes into lymphatic vessels is important for maintaining interstitial homeostasis and delivering antigens and soluble factors to the lymph node ...for immune surveillance. Transendothelial transport across lymphatic endothelial cells (LECs) is commonly considered to occur paracellularly, or between cell–cell junctions, and driven by local pressure and concentration gradients. However, emerging evidence suggests that LECs also play active roles in regulating interstitial solute balance and can scavenge and store antigens, raising the possibility that vesicular or transcellular pathways may be important in lymphatic solute transport.
OBJECTIVE:The aim of this study was to determine the relative importance of transcellular (vesicular) versus paracellular transport pathways by LECs and how mechanical stress (ie, fluid flow conditioning) alters either pathway.
METHODS AND RESULTS:We demonstrate that transcellular transport mechanisms substantially contribute to lymphatic solute transport and that solute uptake occurs in both caveolae- and clathrin-coated vesicles. In vivo, intracelluar uptake of fluorescently labeled albumin after intradermal injection by LECs was similar to that of dermal dendritic cells. In vitro, we developed a method to differentially quantify intracellular solute uptake versus transendothelial transport by LECs. LECs preconditioned to 1 µm/s transmural flow demonstrated increased uptake and basal-to-apical solute transport, which could be substantially reversed by blocking dynamin-dependent vesicle formation.
CONCLUSIONS:These findings reveal the importance of intracellular transport in steady-state lymph formation and suggest that LECs use transcellular mechanisms in parallel to the well-described paracellular route to modulate solute transport from the interstitium according to biomechanical cues.
Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific ...laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework.
Cross-sectional individual participant-level analyses in a global consortium.
17 CKD and 38 general population and high-risk cohorts.
Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension.
Data were obtained and analyzed between July 2015 and January 2018.
We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses.
The CKD cohorts (n=254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n=1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 95% CI, 2.68-3.97 to 8.91 95% CI, 7.22-10.99 comparing eGFRs of 15 to 29 with eGFRs of 45 to 59mL/min/1.73m2), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 95% CI, 0.60-0.99 to 1.92 95% CI, 1.65-2.24 comparing urinary albumin-creatinine ratio > 300 vs < 30mg/g).
Variations in study era, health care delivery system, typical diet, and laboratory assays.
Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD.
Human serum albumin (HSA) is widely used in clinical and cell culture applications. Conventional production of HSA from human blood is limited by the availability of blood donation and the high risk ...of viral transmission from donors. Here, we report the production of Oryza sativa recombinant HSA (OsrHSA) from transgenic rice seeds. The level of OsrHSA reached 10.58% of the total soluble protein of the rice grain. Large-scale production of OsrHSA generated protein with a purity >99% and a productivity rate of 2.75 g/kg brown rice. Physical and biochemical characterization of OsrHSA revealed it to be equivalent to plasma-derived HSA (pHSA). The efficiency of OsrHSA in promoting cell growth and treating liver cirrhosis in rats was similar to that of pHSA. Furthermore, OsrHSA displays similar in vitro and in vivo immunogenicity as pHSA. Our results suggest that a rice seed bioreactor produces cost-effective recombinant HSA that is safe and can help to satisfy an increasing worldwide demand for human serum albumin.
Full text
Available for:
BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
In this work, binding interactions of artemisinin (ART) and dihydroartemisinin (DHA) with human serum albumin (HSA) and bovine serum albumin (BSA) were investigated thoroughly to illustrate the ...conformational variation of serum albumin. Experimental results indicated that ART and DHA bound strongly with the site I of serum albumins via hydrogen bond (H‐bond) and van der Waals force and subsequently statically quenched the intrinsic fluorescence of serum albumins through concentration‐dependent manner. The quenching abilities of two drugs on the intrinsic fluorescence of HSA were much higher than the quenching abilities of two drugs on the intrinsic fluorescence of BSA. Both ART and DHA, especially DHA, caused the conformational variation of serum albumins and reduced the α‐helix structure content of serum albumins. DHA with hydrophilic hydroxyl group bound with HSA more strongly, suggesting the important roles of the chemical polarity and the hydrophilicity during the binding interactions of two drugs with serum albumins. These results reveal the molecular understanding of binding interactions between ART derivatives and serum albumins, providing vital information for the future application of ART derivatives in biological and clinical areas.
Interaction mechanisms of artemisinin and dihydroartemisinin with HSA and BSA were systematically investigated via multispectral and molecular docking techniques. Artemisinin and dihydroartemisinin statically quenched the intrinsic fluorescence of HSA and BSA under van der Waals forces and hydrogen bond forces. Artemisinin and dihydroartemisinin changed the secondary conformation of HSA and BSA to varying degrees and decreased their activities to some extent.
Full text
Available for:
FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Display omitted
•Interaction mechanism of NMB with SAs examined through experimental and Insilico approach.•Emission studies established the static quenching mechanism between SAs and NMB.•Molecular ...docking analysis revealed the stabilization of NMB inside the binding pocket Subdomain IIA (Site I) of SAs.•Insilico findings were correlates well with the emission results.
Herein, the interaction mechanism of new methylene blue (NMB) with human serum albumin (HSA) and bovine serum albumin (BSA) was carefully investigated both experimentally and conceptually, employing experimental and insilico analysis. The steady-state emission spectral studies showed that the emission intensity of HSA and BSA was quenched significantly by NMB. The findings of the Stern–Volmer and double logarithmic plot revealed that the observed emission quenching process was through a static quenching mechanism and the measured binding constant values (Kb) for HSA–NMB and BSA–NMB are 2.766 and 1.187 × 105 dm3 mol−1 respectively. The time-resolved fluorescence lifetime measurement and UV–vis absorption investigation further verify the complex formation between NMB and HSA/BSA. The assessment of thermodynamic parameters disclosed the binding process was spontaneous driven by hydrogen bonds (H-bond) and van der Waals interactions, which contributed a significant role in the complexation. Moreover, the secondary structural conformation and microenvironment of HSA/BSA were modified in the presence of NMB, as evidenced by circular dichroism and synchronous fluorescence data. Molecular docking study predicted a plausible binding mode of NMB inside the binding pocket of HSA and BSA. These results demonstrated that the stabilized NMB is found at the Subdomain IIA (site I) of both the proteins and the results were correlated well with the competitive binding assay. Additionally, the principal components analysis revealed less variation of docked poses for HSA, while, more dispersed docked poses were observed for the BSA model. This also highlights the effects of docking towards a modeled protein (BSA). Molecular dynamic (MD) simulation based binding free energy (ΔGmmgbsa) estimation obtained at 298, 303, 308 and 313 K, were in good agreement with our experimental (ΔGbind) values.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
