Genome-Wide Association Studies to Drug: Identifying Retinoic Acid Metabolism Blocking Agents to Suppress Mechanoflammation in Osteoarthritis.

Osteoarthritis (OA) is a highly prevalent debilitating joint disease for which there are currently no licensed disease-modifying treatments. The pathogenesis of OA is complex, involving genetic, mechanical, biochemical, and environmental factors. Cartilage injury, arguably the most important driving factor in OA development, is able to activate both protective and inflammatory pathways within the tissue.

A vital parameter? Systematic review of spirometry in evaluation for intensive care unit admission and intubation and ventilation for Guillain-Barré syndrome.

Background: Patients with Guillain-Barré syndrome (GBS) may require intensive care unit (ICU) admission for intubation and ventilation (I + V). The means to predict which patients will require I + V include spirometry measures. The aims of this study were to determine, for adult patients with GBS, how effectively different spirometry parameter thresholds predict the need for ICU admission and the requirement for I + V; and what effects these different parameter thresholds have on GBS patient outcomes.

Treatment of Liver Fibrosis after Hepatitis B with TCM Combined with NAs Evaluated by Noninvasive Diagnostic Methods: A Retrospective Study.

. Chronic hepatitis B liver fibrosis is an important intermediate link in the development of liver cirrhosis. A retrospective cohort study was conducted in Longhua Hospital affiliated to the Shanghai University of Traditional Chinese Medicine in order to prove whether integrated traditional Chinese and Western medicine could improve the incidence of CHB complications and clinical prognosis.

Targeted Drug Delivery for the Treatment of Blood Cancers.

Blood cancers are a type of liquid tumor which means cancer is present in the body fluid. Multiple myeloma, leukemia, and lymphoma are the three common types of blood cancers. Chemotherapy is the major therapy of blood cancers by systemic administration of anticancer agents into the blood.

Identifying typologies of quality of life in patients with moderate to severe hand trauma based on patient-reported outcomes.

Background: This study sought to classify the level of quality of life in patients with moderate to severe hand trauma, and explore differences in their potential profile characteristics based on the Patient-Reported Outcomes Measurement Information System (PROMIS).

Methods: This was a survey research. A convenience sampling method was used to investigate 296 patients with moderate to severe hand trauma.

Role of Ciliary Protein Intraflagellar Transport Protein 88 in the Regulation of Cartilage Thickness and Osteoarthritis Development in Mice.

Objective: Mechanical and biologic cues drive cellular signaling in cartilage development, health, and disease. Primary cilia proteins, which are implicated in the transduction of biologic and physiochemical signals, control cartilage formation during skeletal development. This study was undertaken to assess the influence of the ciliary protein intraflagellar transport protein 88 (IFT88) on postnatal cartilage from mice with conditional knockout of the Ift88 gene (Ift88-KO).

TSG-6 Is Weakly Chondroprotective in Murine OA but Does not Account for FGF2-Mediated Joint Protection.

Objective: Tumor necrosis factor α-stimulated gene 6 (TSG-6) is an anti-inflammatory protein highly expressed in osteoarthritis (OA), but its influence on the course of OA is unknown.

Methods: Cartilage injury was assessed by murine hip avulsion or by recutting rested explants. Forty-two previously validated injury genes were quantified by real-time polymerase chain reaction in whole joints following destabilization of the medial meniscus (DMM) (6 hours and 7 days).

Partition and Solubilization of Phospholipid Vesicles by Noncovalently Constructed Oligomeric-like Surfactants.

This work has investigated the interaction of 1,2-dioleoyl--glycero-3-phosphocholine (DOPC) vesicles with oligomeric surfactants noncovalently formed by sodium dodecyl sulfate (SDS) and a series of polyamines, 1,3-diaminopropane (PDA), triamine, spermidine, and spermine. The partition coefficients () of these surfactants between lipid bilayers and the aqueous phase are measured by isothermal titration microcalorimetry (ITC), showing that the value increases and the Gibbs free energy of the partition becomes more negative with increasing oligomerization degree of the surfactants. This changing trend is similar to that of synthetic oligomeric surfactants regardless of the charge properties, suggesting that the polyamine and SDS molecules interact with the DOPC bilayer simultaneously.

Optimizing the Calibration Error of Refraction Angles in Ultrasonic Angle Beam Testing.

Ultrasonic testing is a useful approach for quantifying the flaws in mechanical components. The height of the flaws in ultrasonic angle beam testing is closely related to the calibration value of the probe refraction angle. In order to reduce the calibration error, some ignored data during the traditional calibration process are reanalyzed and fused to determine the refraction angle.

Functional Characterization of the Osteoarthritis Genetic Risk Residing at ALDH1A2 Identifies rs12915901 as a Key Target Variant.

Objective: To identify the functional single-nucleotide polymorphisms (SNPs) and mechanisms conferring increased risk of hand osteoarthritis (OA) at the ALDH1A2 locus, which is a retinoic acid regulatory gene.

Methods: Tissue samples from 247 patients with knee, hip, or hand OA who had undergone joint surgery were included. RNA-sequencing analysis was used to investigate differential expression of ALDH1A2 and other retinoic acid signaling pathway genes in cartilage.

Ultra-low friction between boundary layers of hyaluronan-phosphatidylcholine complexes.

Unlabelled: The boundary layers coating articular cartilage in synovial joints constitute unique biomaterials, providing lubricity at levels unmatched by any human-made materials. The underlying molecular mechanism of this lubricity, essential to joint function, is not well understood. Here we study the interactions between surfaces bearing attached hyaluronan (hyaluronic acid, or HA) to which different phosphatidylcholine (PC) lipids had been added, in the form of small unilamellar vesicles (SUVs or liposomes), using a surface force balance, to shed light on possible cartilage boundary lubrication by such complexes.

Aggregation of Oligomeric Surfactant Constructed by Four-Armed Carboxylic Acid Sodium and Cationic Surfactant.

A star-shaped oligomeric-like surfactant with variable oligomeric degrees has been formed with a four-arm carboxylate salt (4EOCOONa) and cationic single chain surfactant dodecyl trimethylammonium bromide (DTAB). The aggregation of the 4EOCOONa/(DTAB) complexes has been investigated by surface tension, electrical conductivity, isothermal titration microcalorimetry, ζ potential, dynamic light scattering, H NMR spectroscopy, and steady-state fluorescence measurements. The calorimetric result shows that 4EOCOONa interacts strongly with DTAB and each 4EOCOONa molecule binds with six DTAB molecules, wherein four DTAB molecules electrostatically bind to one 4EOCOONa molecule and additional two DTAB molecules further bind to the 4EOCOONa/(DTAB) complex by hydrophobic interaction.

Hydration lubrication and shear-induced self-healing of lipid bilayer boundary lubricants in phosphatidylcholine dispersions.

Measurements of normal and shear (frictional) forces between mica surfaces across small unilamellar vesicle (SUV) dispersions of the phosphatidylcholine (PC) lipids DMPC (14:0), DPPC (16:0) and DSPC (18:0) and POPC (16:0, 18:1), at physiologically high pressures, are reported. We have previously studied the normal and shear forces between two opposing surfaces bearing PC vesicles across pure water and showed that liposome lubrication ability improved with increasing acyl chain length, and correlated strongly with the SUV structural integrity on the substrate surface (DSPC > DPPC > DMPC). In the current study, surprisingly, we discovered that this trend is reversed when the measurements are conducted in SUV dispersions, instead of pure water.

Supramolecular synergy in the boundary lubrication of synovial joints.

Hyaluronan, lubricin and phospholipids, molecules ubiquitous in synovial joints, such as hips and knees, have separately been invoked as the lubricants responsible for the remarkable lubrication of articular cartilage; but alone, these molecules cannot explain the extremely low friction at the high pressures of such joints. We find that surface-anchored hyaluronan molecules complex synergistically with phosphatidylcholine lipids present in joints to form a boundary lubricating layer, which, with coefficient of friction μ≈0.001 at pressures to over 100 atm, has a frictional behaviour resembling that of articular cartilage in the major joints.

Aggregation behavior of sodium lauryl ether sulfate with a positively bicharged organic salt and effects of the mixture on fluorescent properties of conjugated polyelectrolytes.

The aggregation behavior of anionic single-chain surfactant sodium lauryl ether sulfate containing three ether groups (SLE3S) with positively bicharged organic salt 1,2-bis(2-benzylammoniumethoxy)ethane dichloride (BEO) has been investigated in aqueous solution, and the effects of the BEO/SLE3S aggregate transitions on the fluorescent properties of anionic conjugated polyelectrolyte MPS-PPV with a larger molecular weight and cationic conjugated oligoelectrolyte DAB have been evaluated. Without BEO, SLE3S does not affect the fluorescent properties of MPS-PPV and only affects the fluorescent properties of DAB at a higher SLE3S concentration. With the addition of BEO, SLE3S and BEO form gemini-like surfactant (SLE3S)2-BEO.

Disaggregation ability of different chelating molecules on copper ion-triggered amyloid fibers.

Dysfunctional interaction of amyloid-β (Aβ) with excess metal ions is proved to be related to the etiology of Alzheimer's disease (AD). Using metal-binding compounds to reverse metal-triggered Aβ aggregation has become one of the potential therapies for AD. In this study, the ability of a carboxylic acid gemini surfactant (SDUC), a widely used metal chelator (EDTA), and an antifungal drug clioquinol (CQ) in reversing the Cu(2+)-triggered Aβ(1-40) fibers have been systematically studied by using turbidity essay, BCA essay, atomic force microscopy, transmission electron microscopy, and isothermal titration microcalorimetry.

Complex formation and aggregate transitions of sodium dodecyl sulfate with an oligomeric connecting molecule in aqueous solution.

Anionic single-tail surfactant sodium dodecyl sulfate (SDS) and a molecule with multiple amido and amine groups (Lys-12-Lys) were used as building blocks to fabricate oligomeric surfactants through intermolecular interactions. Their interactions and the resultant complex and aggregate structures were investigated by turbidity titration, isothermal titration microcalorimetry, dynamic light scattering, cryogenic transmission electron microscopy, freeze-fracture transmission electron microscopy, (1)H NMR, and 1D NOE techniques. At pH 11.

Modulation of Aβ(1-40) peptide fibrillar architectures by Aβ-based peptide amphiphiles.

Modulation of the fibrillogenesis of amyloid peptide Aβ(1-40) with two Aβ-based peptide amphiphiles has been studied. Both peptide amphiphiles contain two alkyl chains but in different positions. The two alkyl chains of 2C12-Aβ(11-17) are attached to the same terminus of Aβ(11-17), while those of C12-Aβ(11-17)-C12 are separately attached to opposite termini of Aβ(11-17).

Development of oleanane-type triterpenes as a new class of HCV entry inhibitors.

Development of hepatitis C virus (HCV) entry inhibitors represents an emerging approach that satisfies a tandem mechanism for use with other inhibitors in a multifaceted cocktail. By screening Chinese herbal extracts, oleanolic acid (OA) was found to display weak potency to inhibit HCV entry with an IC50 of 10 μM. Chemical exploration of this triterpene compound revealed its pharmacophore requirement for blocking HCV entry, rings A, B, and E, are conserved while ring D is tolerant of some modifications.

Aggregate transitions in mixtures of anionic sulfonate gemini surfactant with cationic ammonium single-chain surfactant.

Aggregation behaviors in mixtures of an anionic gemini surfactant 1,3-bis(N-dodecyl-N-propanesulfonate sodium)-propane (C(12)C(3)C(12)(SO(3))(2)) and a cationic single-chain surfactant cetyltrimethylammonium bromide (CTAB) have been investigated in aqueous solutions at pH 9.5 by turbidity, rheology, isothermal titration microcalorimetry (ITC), cryogenic transmission electron microscopy, and dynamic light scattering. Reversible aggregate transitions from spherical micelles to wormlike micelles, vesicles, and back to wormlike micelles and spherical micelles are successfully realized through fine regulation over the mixing ratio of surfactants, i.

Association behaviors of dodecyltrimethylammonium bromide with double hydrophilic block co-polymer poly(ethylene glycol)-block-poly(glutamate sodium).

The association behaviors of single-chain surfactant dodecyltrimethylammonium bromide (DTAB) with double hydrophilic block co-polymers poly(ethylene glycol)-b-poly(sodium glutamate) (PEG(113)-PGlu(50) or PEG(113)-PGlu(100)) were investigated using isothermal titration microcalorimetry, cryogenic transmission electron microscopy, circular dichroism, ζ potential, and particle size measurements. The electrostatic interaction between DTAB and the oppositely charged carboxylate groups of PEG-PGlu induces the formation of super-amphiphiles, which further self-assemble into ordered aggregates. Dependent upon the charge ratios between DTAB and the glutamic acid residue of the co-polymer, the mixture solutions can change from transparent to opalescent without precipitation.