-
Psychoneuroendocrinology Sep 2017Changes in levels of the stress-sensitive hormone cortisol from morning to evening are referred to as diurnal cortisol slopes. Flatter diurnal cortisol slopes have been... (Meta-Analysis)
Meta-Analysis Review
Changes in levels of the stress-sensitive hormone cortisol from morning to evening are referred to as diurnal cortisol slopes. Flatter diurnal cortisol slopes have been proposed as a mediator between chronic psychosocial stress and poor mental and physical health outcomes in past theory and research. Surprisingly, neither a systematic nor a meta-analytic review of associations between diurnal cortisol slopes and health has been conducted to date, despite extensive literature on the topic. The current systematic review and meta-analysis examined associations between diurnal cortisol slopes and physical and mental health outcomes. Analyses were based on 179 associations from 80 studies for the time period up to January 31, 2015. Results indicated a significant association between flatter diurnal cortisol slopes and poorer health across all studies (average effect size, r=0.147). Further, flatter diurnal cortisol slopes were associated with poorer health in 10 out of 12 subtypes of emotional and physical health outcomes examined. Among these subtypes, the effect size was largest for immune/inflammation outcomes (r=0.288). Potential moderators of the associations between diurnal cortisol slopes and health outcomes were examined, including type of slope measure and study quality indices. The possible roles of flatter slopes as either a marker or a mechanism for disease etiology are discussed. We argue that flatter diurnal cortisol slopes may both reflect and contribute to stress-related dysregulation of central and peripheral circadian mechanisms, with corresponding downstream effects on multiple aspects of biology, behavior, and health.
Topics: Circadian Rhythm; Emotions; Female; Humans; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Mental Health; Pituitary-Adrenal System; Saliva; Stress, Psychological
PubMed: 28578301
DOI: 10.1016/j.psyneuen.2017.05.018 -
International Journal of Molecular... May 2020While antibodies remain established therapeutic and diagnostic tools, other protein scaffolds are emerging as effective and safer alternatives. Affibodies in particular...
While antibodies remain established therapeutic and diagnostic tools, other protein scaffolds are emerging as effective and safer alternatives. Affibodies in particular are a new class of small proteins marketed as bio-analytic reagents. They feature tailorable binding affinity, low immunogenicity, high tissue permeation, and high expression titer in bacterial hosts. This work presents the development of affibody-binding peptides to be utilized as ligands for their purification from bacterial lysates. Affibody-binding candidates were identified by screening a peptide library simultaneously against two model affibodies (anti-immunoglobulin G (IgG) and anti-albumin) with the aim of selecting peptides targeting the conserved domain of affibodies. An ensemble of homologous sequences identified from screening was synthesized on Toyopearl resin and evaluated via binding studies to select sequences that afford high product binding and recovery. The affibody-peptide interaction was also evaluated by in silico docking, which corroborated the targeting of the conserved domain. Ligand IGKQRI was validated through purification of an anti-ErbB2 affibody from an lysate. The values of binding capacity (~5 mg affibody per mL of resin), affinity (K ~1 μM), recovery and purity (64-71% and 86-91%), and resin lifetime (100 cycles) demonstrate that IGKQRI can be employed as ligand in affibody purification processes.
Topics: Amino Acid Sequence; Humans; Immunoglobulin G; Ligands; Molecular Docking Simulation; Peptide Library; Peptides; Recombinant Fusion Proteins; Serum Albumin, Human; Temperature
PubMed: 32471034
DOI: 10.3390/ijms21113769 -
Journal of Lipid Research Apr 2020Analyzing global steroid metabolism in humans can shed light on the etiologies of steroid-related diseases. However, existing methods require large amounts of serum and...
Analyzing global steroid metabolism in humans can shed light on the etiologies of steroid-related diseases. However, existing methods require large amounts of serum and lack the evaluation of accuracy. Here, we developed an LC/MS/MS method for the simultaneous quantification of 12 steroid hormones: testosterone, pregnenolone, progesterone, androstenedione, corticosterone, 11-deoxycortisol, cortisol, 17-hydroxypregnenolone, 17-hydroxyprogesterone, dehydroepiandrosterone, estriol, and estradiol. Steroids and spiked internal standards in 100 μl serum were extracted by protein precipitation and liquid-liquid extraction. The organic phase was dried by evaporation, and isonicotinoyl chloride was added for steroid derivatization, followed by evaporation under nitrogen and redissolution in 50% methanol. Chromatographic separation was performed on a reverse-phase PFP column, and analytes were detected on a triple quadrupole mass spectrometer with ESI. The lower limits of quantification ranged from 0.005 ng/ml for estradiol to 1 ng/ml for cortisol. Apparent recoveries of steroids at high, medium, and low concentrations in quality control samples were between 86.4% and 115.0%. There were limited biases (-10.7% to 10.5%) between the measured values and the authentic values, indicating that the method has excellent reliability. An analysis of the steroid metabolome in pregnant women highlighted the applicability of the method in clinical serum samples. We conclude that the LC/MS/MS method reported here enables steroid metabolome analysis with high accuracy and reduced serum consumption, indicating that it may be a useful tool in both clinical and scientific laboratory research.
Topics: Analytic Sample Preparation Methods; Blood Chemical Analysis; Chromatography, Liquid; Female; Humans; Limit of Detection; Metabolomics; Pregnancy; Solvents; Steroids; Tandem Mass Spectrometry
PubMed: 31964762
DOI: 10.1194/jlr.D119000591 -
Chemical Reviews Sep 2022Adeno-associated virus (AAV) has a single-stranded DNA genome encapsidated in a small icosahedrally symmetric protein shell with 60 subunits. AAV is the leading delivery... (Review)
Review
Adeno-associated virus (AAV) has a single-stranded DNA genome encapsidated in a small icosahedrally symmetric protein shell with 60 subunits. AAV is the leading delivery vector in emerging gene therapy treatments for inherited disorders, so its structure and molecular interactions with human hosts are of intense interest. A wide array of electron microscopic approaches have been used to visualize the virus and its complexes, depending on the scientific question, technology available, and amenability of the sample. Approaches range from subvolume tomographic analyses of complexes with large and flexible host proteins to detailed analysis of atomic interactions within the virus and with small ligands at resolutions as high as 1.6 Å. Analyses have led to the reclassification of glycan receptors as attachment factors, to structures with a new-found receptor protein, to identification of the epitopes of antibodies, and a new understanding of possible neutralization mechanisms. AAV is now well-enough characterized that it has also become a model system for EM methods development. Heralding a new era, cryo-EM is now also being deployed as an analytic tool in the process development and production quality control of high value pharmaceutical biologics, namely AAV vectors.
Topics: Cryoelectron Microscopy; Dependovirus; Epitopes; Genetic Therapy; Humans
PubMed: 35575684
DOI: 10.1021/acs.chemrev.1c00936 -
Scientific Reports Jan 2023In this article, we demonstrate the viability of highly monochromatic full-field X-ray absorption near edge structure based tomography using a laboratory-scale...
In this article, we demonstrate the viability of highly monochromatic full-field X-ray absorption near edge structure based tomography using a laboratory-scale Johann-type X-ray absorption spectrometer utilising a conventional X-ray tube source. In this proof-of-concept, by using a phantom embedded with elemental Se, Na[Formula: see text]SeO[Formula: see text], and Na[Formula: see text]SeO[Formula: see text], we show that the three-dimensional distributions of Se in different oxidation states can be mapped and distinguished from the phantom matrix and each other with absorption edge contrast tomography. The presented method allows for volumetric analyses of chemical speciation in mm-scale samples using low-brilliance X-ray sources, and represents a new analytic tool for materials engineering and research in many fields including biology and chemistry.
Topics: Tomography, X-Ray Computed; Radiography; Phantoms, Imaging; X-Rays
PubMed: 36611113
DOI: 10.1038/s41598-023-27409-6 -
Current Opinion in Pediatrics Apr 2017The purpose of this review is to identify emerging developmental toxicants that are understudied in children's health. Exposures may arise from new products designed to... (Review)
Review
PURPOSE OF REVIEW
The purpose of this review is to identify emerging developmental toxicants that are understudied in children's health. Exposures may arise from new products designed to improve utility, to reduce toxicity, or to replace undesirable chemicals. Exposures to less-toxic chemicals may also be significant if they are very commonly used, thereby generating widespread exposure. Sources of exposure include the workplace, personal, home, and office products; food, water, and air.
RECENT FINDINGS
We describe eight exposure categories that contain numerous potential developmental toxicants. References are discussed if reported in PubMed during the past decade at least 10 times more frequently than in 1990-2000. Examples included phthalates, phenols, sunscreens, pesticides, halogenated flame retardants, perfluoroalkyl coatings, nanoparticles, e-cigarettes, and dietary polyphenols. Replacements are often close structural homologs of their precursors. We suggest biomonitoring as preferred means of exposure assessment to emerging chemicals. Some existing analytic methods would require minimal modification to measure these exposures, but others require toxicokinetic and analytic investigation.
SUMMARY
A deliberate strategy for biomonitoring of emerging replacement chemicals is warranted, especially in view of concerns regarding developmental toxicity. To prevent adverse health effects, it is important to characterize such exposures before they become widely disseminated.
Topics: Electronic Nicotine Delivery Systems; Environmental Exposure; Environmental Health; Environmental Monitoring; Environmental Pollutants; Female; Flame Retardants; Humans; Male; Particle Size; Pesticides; Phthalic Acids; Risk Assessment; United States
PubMed: 28059904
DOI: 10.1097/MOP.0000000000000455 -
Molecules (Basel, Switzerland) Jul 2020Covalent organic frameworks (COFs) can be classified as emerging porous crystalline polymers with extremely high porosity and surface area size, and good thermal... (Review)
Review
Covalent organic frameworks (COFs) can be classified as emerging porous crystalline polymers with extremely high porosity and surface area size, and good thermal stability. These properties have awakened the interests of many areas, opening new horizons of research and applications. In the Analytical Chemistry field, COFs have found an important application in sample preparation approaches since their inherent properties clearly match, in a good number of cases, with the ideal characteristics of any extraction or clean-up sorbent. The review article is meant to provide a detailed overview of the different COFs that have been used up to now for sample preparation (i.e., solid-phase extraction in its most relevant operational modes-conventional, dispersive, magnetic/solid-phase microextraction and stir-bar sorptive extraction); the extraction devices/formats in which they have been applied; and their performances and suitability for this task.
Topics: Adsorption; Analytic Sample Preparation Methods; Metal-Organic Frameworks; Nanotubes, Carbon; Solid Phase Extraction
PubMed: 32698393
DOI: 10.3390/molecules25143288 -
Rheumatology (Oxford, England) Jan 2024Calprotectin (CLP) is a calcium-binding protein produced by neutrophils and monocytes in the course of inflammation. Today, the role of faecal CLP in chronic IBD is well... (Review)
Review
Calprotectin (CLP) is a calcium-binding protein produced by neutrophils and monocytes in the course of inflammation. Today, the role of faecal CLP in chronic IBD is well known, but in recent years attention has shifted towards circulating CLP. In fact, this molecule can be measured in different biological fluids: blood, saliva and urine, using different analytic methods that are described in this review. Furthermore, different data confirm the relevant role of serum CLP in autoimmune diseases. In this review we will highlight the correlation between high levels of circulating CLP and specific autoantibodies of major autoimmune pathologies paving the way to the employment of CLP measurement as useful biomarker for monitoring outcome in different pathologies.
Topics: Humans; Leukocyte L1 Antigen Complex; Inflammation; Biomarkers; Feces; Neutrophils; Inflammatory Bowel Diseases
PubMed: 37603715
DOI: 10.1093/rheumatology/kead405 -
Sensors (Basel, Switzerland) Dec 2022Sucrose is a primary metabolite in plants, a source of energy, a source of carbon atoms for growth and development, and a regulator of biochemical processes. Most of the... (Review)
Review
Sucrose is a primary metabolite in plants, a source of energy, a source of carbon atoms for growth and development, and a regulator of biochemical processes. Most of the traditional analytical chemistry methods for sucrose quantification in plants require sample treatment (with consequent tissue destruction) and complex facilities, that do not allow real-time sucrose quantification at ultra-low concentrations (nM to pM range) under in vivo conditions, limiting our understanding of sucrose roles in plant physiology across different plant tissues and cellular compartments. Some of the above-mentioned problems may be circumvented with the use of bio-compatible ligands for molecular recognition of sucrose. Nevertheless, problems such as the signal-noise ratio, stability, and selectivity are some of the main challenges limiting the use of molecular recognition methods for the in vivo quantification of sucrose. In this review, we provide a critical analysis of the existing analytical chemistry tools, biosensors, and synthetic ligands, for sucrose quantification and discuss the most promising paths to improve upon its limits of detection. Our goal is to highlight the criteria design need for real-time, in vivo, highly sensitive and selective sucrose sensing capabilities to enable further our understanding of living organisms, the development of new plant breeding strategies for increased crop productivity and sustainability, and ultimately to contribute to the overarching need for food security.
Topics: Sucrose; Carbon; Chemistry, Analytic; Crop Production; Recognition, Psychology
PubMed: 36502213
DOI: 10.3390/s22239511 -
Biosensors Mar 2022Rapid, on-site diagnostics allow for timely intervention and response for warfighter support, environmental monitoring, and global health needs. Portable optical...
Rapid, on-site diagnostics allow for timely intervention and response for warfighter support, environmental monitoring, and global health needs. Portable optical biosensors are being widely pursued as a means of achieving fieldable biosensing due to the potential speed and accuracy of optical detection. We recently developed the portable engineered analytic sensor with automated sampling (PEGASUS) with the goal of developing a fieldable, generalizable biosensing platform. Here, we detail the development of PEGASUS's sensing hardware and use a test-bed system of identical sensing hardware and software to demonstrate detection of a fluorescent conjugate at 1 nM through biotin-streptavidin chemistry.
Topics: Biosensing Techniques; Environmental Monitoring; Streptavidin
PubMed: 35448255
DOI: 10.3390/bios12040195