CHO-produced RBD-Fc subunit vaccines with alternative adjuvants generate immune responses against SARS-CoV-2.

Subunit vaccines feature critical advantages over other vaccine platforms such as stability, price, and minimal adverse effects. To maximize immunological protection of subunit vaccines, adjuvants are considered as main components that are formulated within the subunit vaccine. They can modulate adverse effects and enhance immune outcomes.

Quantification of CYP3A and Drug Transporters Activity in Healthy Young, Healthy Elderly and Chronic Kidney Disease Elderly Patients by a Microdose Cocktail Approach.

Ageing and chronic kidney disease (CKD) affect pharmacokinetic (PK) parameters. Since mechanisms are related and remain unclear, cytochrome P450 (CYP) 3A and drug transporter activities were investigated in the elderly with or without CKD and compared to healthy adults using a microdose cocktail. Healthy young participants ( = 20), healthy elderly participants ( = 16) and elderly patients with CKD ( = 17) received, in study period 1, a single dose of microdose cocktail probe containing 30 µg midazolam, 750 µg dabigatran etexilate, 100 µg atorvastatin, 10 µg pitavastatin, and 50 µg rosuvastatin.

Genome analysis and optimization of γ-aminobutyric acid (GABA) production by lactic acid bacteria from plant materials.

Gamma-aminobutyric acid (GABA) plays a key role as an inhibitory neurotransmitter in the mammalian sympathetic nervous system and has other health benefits. Molecular characterization, genome analysis, and optimization were investigated to improve GABA production of a selected strain of lactic acid bacteria. Eleven isolates from plant materials were screened for GABA productivity and were identified based on phenotypic and genotypic characteristics.

Development and Qualification of a Physiologically Based Pharmacokinetic Model of Finasteride and Minoxidil Following Scalp Application.

In this study, we aimed to develop and qualify a PBPK model for scalp application using two drugs with marked differences in physicochemical properties and PK profiles. The parameters related to scalp physiology, drug PK, and formulations were incorporated into a Multi-Phase and Multi-Layer (MPML) Mechanistic Dermal Absorption (MechDermA) model within the Simcyp® Simulator V17. The finasteride PBPK model was linked to its effect on dihydrotestosterone (DHT) levels in plasma and scalp using an indirect response model.

Asiaticoside but not its aglycone exhibits neuritogenicity through TrkA receptor signaling: a bridge between ERK1/2-CREB and Akt-GSK3β/RhoA.

The neuritogenicity and the neuroregenerative potential of asiaticoside (AS) and its aglycone, asiatic acid (AA), has been generally reported. We recently identified the participation of extracellular signal-regulated protein kinases 1/2 (ERK1/2) and protein kinase B (Akt) in the neuritogenic mechanism of AS and AA. In this study, we further investigated the possible upstream target molecule and the associated downstream signaling of both triterpenoids in mouse neuroblastoma Neuro-2a cells.

Interspecies differences in stability kinetics and plasma esterases involved in hydrolytic activation of curcumin diethyl disuccinate, a prodrug of curcumin.

The investigation of plasma metabolism of ester prodrugs is an important part of ADME assays during preclinical drug development. Here, we show that the metabolism including plasma stability and metabolizing enzymes of curcumin diethyl disuccinate (CDD), an ester prodrug of curcumin, in dog and human plasma are similar but markedly different from those in rat plasma. HPLC and nonlinear regression analyses indicated that the hydrolysis of CDD in plasma followed a consecutive pseudo-first order reaction.

Differences in Neuritogenic Activity and Signaling Activation of Madecassoside, Asiaticoside, and Their Aglycones in Neuro-2a cells.

Madecassoside (MS) and asiaticoside (AS) along with their aglycones, madecassic acid (MA) and asiatic acid (AA), are considered the major neuroactive triterpenoid constituents of . In this study, we aimed to compare MS, AS, MA, and AA for their neurite outgrowth activities and mechanisms in Neuro-2a cells. Immunofluorescent cell staining showed MS and AS significantly increased the percentage of neurite-bearing cells (%NBC) and the neurite length with higher potency than MA and AA.

Simultaneous determination of curcumin diethyl disuccinate and its active metabolite curcumin in rat plasma by LC-MS/MS: Application of esterase inhibitors in the stabilization of an ester-containing prodrug.

Four esterase inhibitors, ethylenediamine tetraacetic acid disodium (Na2EDTA), sodium fluoride (NaF), bis(4-nitrophenyl) phosphate (BNPP) and phenylmethanesulfonyl fluoride (PMSF), were evaluated for their inhibitory effects on enzymatic hydrolysis of labile phenolate esters in curcumin diethyl disuccinate (CDD), a prodrug of curcumin (CUR), in rat plasma. BNPP and PMSF at 10mM exhibited stabilization by preventing degradation of CDD. BNPP at a final concentration of 10mM was subsequently selected to prevent ex vivo metabolism of CDD throughout LC-MS/MS analysis of CDD and CUR in rat plasma.

Pharmacokinetics of Compound D, the Major Bioactive Component of Zingiber cassumunar, in Rats.

Rhizomes of Zingiber cassumunar have been used for many years in traditional Thai medicine as an anti-inflammatory agent. The major bioactive component of this plant is Compound D [E-4-(3', 4'-dimethoxyphenyl)but-3-en-1-ol], which is a strong smooth muscle relaxant, and has antihistamine and anti-inflammatory actions. There is, however, incomplete information available for the pharmacokinetics of Compound D in mammals.

Canarosine: a new guanidine alkaloid from Canavalia rosea with inhibitory activity on dopamine D1 receptors.

A new acyclic guanidine alkaloid, canarosine (1), together with five known compounds, beta-sitosterol (2), stigmasterol (3), daucosterol (4), epi-inositol 6-O-methyl ether (5), and rutin (6), were isolated from the aerial parts of Canavalia rosea. Their structures were established on the basis of their spectroscopic data. In the radioligand receptor binding assay, canarosine (1), at a concentration of 100 microg/ml, caused 91% inhibition of the dopamine D1 receptor binding with an IC50 value of 39.

Influence of incorporation methods on partitioning behavior of lipophilic drugs into various phases of a parenteral lipid emulsion.

The purpose of this study was to investigate the effect of drug incorporation methods on the partitioning behavior of lipophilic drugs in parenteral lipid emulsions. Four lipophilic benzodiazepines, alprazolam, clonazepam, diazepam, and lorazepam, were used as model drugs. Two methods were used to incorporate drugs into an emulsion: dissolving the compound in the oil phase prior to emulsification (de novo emulsification), and directly adding a concentrated solution of drug in a solubilizer to the emulsion base (extemporaneous addition).

Preparation and characterization of propylthiouracil niosomes.

Propylthiouracil, a lyophobic drug with an antiproliferative activity, was formulated into niosomes using various classes of nonionic surfactants. Feasibility of vesicle formation by the sonication method was evaluated. Size and size distribution was measured by laser diffraction.

The influence of physicochemical properties of preservative compounds on their distribution into various phases of oil in water submicron emulsion.

Phospholipids--stabilized submicron emulsions require the addition of preservatives to destroy or inhibit the growth of microorganisms when these preparations are non-sterile products or when packed in multi-dose containers. This study examined the distribution of four paraben esters--methylparaben, ethylparaben, propylparaben, and butylparaben--that were added into submicron emulsions by de novo emulsification. The distribution of preservative compounds among different phases was determined after separation of submicron emulsions by ultracentrifugation.

Periodontal repair in dogs: effect of transforming growth factor-beta 1 on alveolar bone and cementum regeneration.

Background: Transforming growth factor-beta (TGF-beta) represents a family of growth-modulating proteins with fundamental roles in connective tissue and bone development. The objective of this study was to evaluate the potential for regeneration of alveolar bone and cementum following surgical implantation of recombinant human TGF-beta 1 (rhTGF-beta 1).

Method: Bilateral, critical size, supra-alveolar periodontal defects in 5 beagle dogs were surgically implanted with rhTGF-beta 1 in a calcium carbonate carrier (CaCO3) or with carrier alone.

Combination of bone marrow and TGF-beta1 augment the healing of critical-sized bone defects.

A 1.5 cm segmental defect in the radius of rabbits was used to compare healing at sites administered TGF-beta, with or without autologous bone marrow, to autogenous cortical bone graft. The carrier for TGF-beta consisted of tricalcium phosphate (TCP) granules and hetastarch.

Periodontal repair in dogs: effect of recombinant human transforming growth factor-beta1 on guided tissue regeneration.

This study evaluated alveolar bone and cementum regeneration following surgical implantation of recombinant human transforming growth factor-beta1 (rhTGF-beta1) in conjunction with guided tissue regeneration (GTR). Supraalveolar, critical size, periodontal defects were surgically created around the 3rd and 4th mandibular premolar teeth in right and left jaw quadrants in 5 beagle dogs. Alternate jaw quadrants in consecutive animals received rhTGF-beta1, in a CaCO3/hydroxyethyl starch carrier with GTR, or carrier with GTR alone (control).

Development of tricalcium phosphate/amylopectin paste combined with recombinant human transforming growth factor beta 1 as a bone defect filler.

Tricalcium phosphate (TCP) was combined with amylopectin to form a deliverable carrier paste for recombinant human transforming growth factor beta 1 (rhTGF-beta 1) intended for bone repair applications. Approximately 80% of rhTGF-beta 1 was released from the carrier within 24 h following in vitro incubation in serum. Full biological activity was maintained, suggesting the growth factor was stable in this formulation before and after in vitro release.

Transforming growth factor-beta stimulates bone ongrowth. Hydroxyapatite-coated implants studied in dogs.

Unloaded cylindrical grit-blasted titanium (Ti-6A-4V) implants (6 x 10 mm) coated with hydroxyapatite ceramic were inserted into the proximal part of the humerus of 20 skeletally mature Labrador dogs. The implants were initially surrounded by a 2 mm gap. In 10 dogs, HA-coated implants without growth factor were inserted in one humerus and implants with 0.

Transforming growth factor-beta 1 enhances bone healing to unloaded tricalcium phosphate coated implants: an experimental study in dogs.

Growth of bone into cementless prosthetic components is compromised after revision of failed joint prostheses and by osteoporosis, gaps, and micromotion. We studied the effects of recombinant human transforming growth factor-beta 1 adsorbed on ceramic coated implants on the improvement of mechanical fixation and bone growth on the implant. Unloaded cylindrical grit-blasted titanium alloy implants were inserted bilaterally into both the medial and lateral femoral condyles of 10 skeletally mature mongrel dogs.

Transforming growth factor-beta 1 stimulates bone ongrowth to weight-loaded tricalcium phosphate coated implants: an experimental study in dogs.

Bone growth into cementless prosthetic components is compromised by osteoporosis, by any gap between the implant and the bone, by micromotion, and after the revision of failed prostheses. Recombinant human transforming growth factor-beta 1 (rhTGF-beta 1) has recently been shown to be a potent stimulator of bone healing and bone formation in various models in vivo. We have investigated the potential of rhTGF-beta 1, adsorbed on to weight-loaded tricalcium phosphate (TCP) coated implants, to enhance bone ongrowth and mechanical fixation.

Aggregation of rhDNase occurred during the compression of KBr pellets used for FTIR spectroscopy.

Purpose: To determine if a protein changes when it is compressed into a KBr pellet for FTIR spectroscopy measurement in the solid state, using recombinant human deoxyribonuclease I (rhDNase) as an example.

Methods: Lyophilized rhDNase with KBr compressed at different pressures were analyzed by FTIR spectroscopy, size exclusion HPLC and enzymatic activity assay. Different protein/KBr weight ratios and residual water contents were studied for their possible effects on aggregation.

Polymorphism in stratum corneum lipids.

Fourier transform infrared spectroscopy (FTIR) was employed to investigate the thermotropic phase behavior of stratum corneum lipid multilamellae. Stratum corneum (SC), the uppermost layer of mammalian skin, is unusual in many respects. It has been demonstrated that the lipids of the stratum corneum provide the primary electrical and transport resistance in the skin.

Plasma C3c in immune-mediated neurological diseases: a preliminary report.

Plasma C3c levels were examined in 56 patients with immune (27) and non-immune (29) mediated neurological diseases by crossed immunoelectrophoresis. Plasma samples were collected during the active phase of illness in both groups, usually within 7 days of admission. 11 patients (4 Guillain-Barré Syndrome-GBS, 3 chronic inflammatory demyelinating polyneuropathy-CIDP, 4 myasthenia gravis-MG) had their plasma saved sequentially during the active and the recovery phase.

Evidence that oleic acid exists in a separate phase within stratum corneum lipids.

Oleic acid is known to be a penetration enhancer for polar to moderately polar molecules. A mechanism related to lipid phase separation has been previously proposed by this laboratory to explain the increases in skin transport. In the studies presented here, Fourier transform infrared spectroscopy (FT-IR) was utilized to investigate whether or not oleic acid exists in a separate phase within stratum corneum (SC) lipids.

Plasma C3c changes in myasthenia gravis patients receiving high-dose intravenous immunoglobulin during crisis.

Fast-migrating C3c, a sensitive index of complement activation, was assayed in the plasma of 2 myasthenia gravis (MG) patients in crisis who received high-dose IV immunoglobulin therapy. Dramatic responses were observed in both patients. Clinical improvement paralleled a decrement in C3c levels, suggesting that regulation of complement activation may be one possible mechanism of IV immunoglobulin treatment in MG.