Monocytes are a major population of circulating immune cells that play a crucial role in producing pro-inflammatory cytokines in the body. The actions of monocytes are known to be influenced by the ...combinations and concentrations of certain fatty acids (FAs) in blood and dietary fats. However, systemic comparisons of the effects of FAs on cytokine secretion by monocytes have not be performed. In this study, we compared how six saturated FAs (SFAs), two monounsaturated FAs (MUFAs), and seven polyunsaturated FAs (PUFAs) modulate human THP-1 monocyte secretion of TNF, IL-1β, and IL-6 in the absence or presence of lipopolysaccharide. SFAs generally stimulated resting THP-1 cells to secrete pro-inflammatory cytokines, with stearic acid being the most potent species. In contrast, MUFAs and PUFAs inhibited lipopolysaccharide-induced secretion of pro-inflammatory cytokines. Interestingly, the inhibitory potentials of MUFAs and PUFAs followed U-shaped (TNF and IL-1β) or inverted U-shaped (IL-6) dose-response curves. Among the MUFAs and PUFAs that were analyzed, docosahexaenoic acid (C22:6 n-3) exhibited the largest number of double bonds and was found to be the most potent anti-inflammatory compound. Together, our findings reveal that the chemical compositions and concentrations of dietary FAs are key factors in the intricate regulation of monocyte-mediated inflammation.
Transition metal nitride coatings, such as CrN, AlCrN and AlTiN, have excellent mechanical properties such as high strength, hardness, wear resistance and thermal stability. In this study, AlCrN and ...AlCrBN thin films were deposited by cathodic arc evaporation (CAE) using binary AlCr and ternary AlCrB alloy targets. The adhesion strength of the films to the substrate was effectively improved using composition-gradient interlayers. To study the thermal stabilities, the AlCrN and AlCrBN coatings were annealed at high temperature up to 900 °C, and their oxidation resistance, mechanical properties and thermal stabilities were studied. AlCrN and AlCrBN coated WC-Co samples were tested using pin-on-disk wear test configuration to evaluate the tribological performance. According to experimental results, the AlCrBN is composed of a face-centered cubic B1 (FCC) nanocrystalline structure, which can effectively inhibit the growth of grains, resulting in formation of a compact structure of grain refinement, and hinder the plastic deformation, thus obtaining high hardness and excellent wear resistance. The addition of 0.6 at.% B into the AlCrN decreased the grain size to 8.7 ± 0.8 nm from 13.7 ± 1.1 nm of AlCrN. Due to the addition of B element, the grains of AlCrBN coatings were refined to form a compact structure. Oxygen (O) did not penetrate and oxidize easily along the grain boundaries during annealing at high temperature. In addition, the AlCrBN coatings maintained a certain hardness (27.9–30 GPa) after high temperature oxidation, and the AlCrBN coating after annealing at 900 °C had the lowest wear rate (1.25 × 10−7 mm3/Nm). The AlCrBN coating annealed at high temperature still possessed predominant tribological properties, excellent thermal stability and good adhesion. This study demonstrates the feasibility of improving the life and performance of WC-Co tools by the application of cathodic arc deposited AlCrBN coatings using ternary AlCrB alloy targets.
•AlCrBN coatings were deposited using ternary AlCrB alloy targets.•The addition of small fraction of B into the AlCrN decreased the grain size.•The AlCrBN coating had good thermal stability and oxidation resistance.•The AlCrBN coating showed improved wear resistance especially after annealing at 900 °C.
Single-mode VCSEL technology has advanced significantly in the past few years. The advantages of single-mode VCSELs lie primarily on the narrower linewidth, lower numerical aperture, and smaller spot ...size compared to multimode VCSELs. They are suitable for transmitting over both multimode fibers and few-mode fibers. For multimode fiber systems, the narrow linewidth can reduce the chromatic dispersion penalty and increase the system reach. A single-mode VCSEL also allows the coupling into graded-index single-mode fiber, which is few-mode around 850 nm with high bandwidth, for few-mode transmission. We review recent progress and present new experimental results and modeling analyses of single-mode VCSEL transmission over both types of fibers. The experiments and analyses shed new light on how single-mode VCSELs can be used with multimode fibers and graded-index single-mode fibers and relative merits between 850 nm single-mode VCSELs versus 980 nm and 1060 nm single-mode VCSELs to address the needs of various applications.
Diclofenac sodium has a short half-life (about 1.5 hours), requiring repeated administration, and as a result, serious complications, such as GI bleeding, peptic ulcer, and kidney and liver ...dysfunction, are generated. Hence, a sustained/controlled drug delivery system is needed to overcome the complications caused by the administration of diclofenac sodium.
This study aimed to fabricate and evaluate carbopol/polyvinyl alcohol-based pH-sensitive hydrogels for controlled drug delivery.
pH-sensitive carbopol/polyvinyl alcohol graft-poly(acrylic acid) hydrogels (Cp/PVA-g-PAa hydrogels) were developed for the controlled delivery of diclofenac sodium.
The combination of carbopol/polyvinyl alcohol, acrylic acid, and ethylene glycol dimethacrylate was used as polymer, monomer, and cross-linker, respectively. The effects of the formulation's composition on porosity, swelling index, and release pattern of diclofenac sodium from the developed hydrogels were investigated.
An increase in porosity and swelling was observed with the increasing amounts of carbopol and acrylic acid, whereas polyvinyl alcohol showed the opposite effect. Due to the formation of a highly viscous system, the drug release decreased with the increasing concentrations of carbopol and polyvinyl alcohol while increased with increasing acrylic acid concentration. The pH-responsive properties of the fabricated hydrogels were demonstrated by dynamic swelling and drug release studies at three different pH values. Higher dynamic swelling and diclofenac sodium (model drug) release were found at high pH values compared to low pH values,
pH 7.4 > 4.6 > 1.2, respectively. Cytotoxicity studies reported no toxic effect of the prepared hydrogels, thus indicating that the prepared hydrogels are safe to be used on clinical basis.
The prepared carbopol/polyvinyl alcohol crosslinked hydrogel can be used as a promising carrier for the controlled release of drugs.
Excessive production of radical oxygen species in skin is a contributor to a variety of skin pathologies. Naringenin is a potent antioxidant. The purpose of the present study was to develop elastic ...liposomes for naringenin topical application. Naringenin-loaded elastic liposomes containing different amounts of Tween 80 and cholesterol were prepared. The physicochemical properties including vesicle size, surface charge, encapsulation efficiency, and permeability capacity were determined to evaluate the effect of components. The stability of formulation and skin irritation caused by drug-loaded elastic liposomes were also evaluated for assessment of the clinical utility of elastic liposomes. Saturated aqueous solution of naringenin and naringenin dissolved in 10% Tween 80 solution (5 mg/mL) were used as the control group. The result showed that in using elastic liposomes as carrier, the deposition amounts in the skin of naringenin were significantly increased about 7.3~11.8-fold and 1.2~1.9-fold respectively, when compared with the saturated aqueous solution and Tween 80 solution-treated groups. The level of drug was more than 98.89±3.90% after 3 months of storage at 4℃. In a skin irritation test, the result showed experimental formulation exhibit considerably less irritating than the positive control (paraformaldehyde-treated) group, suggesting its potential therapeutic application.
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•The transdermal and deposition amount significantly increased after topical application.•The plasma concentration of resveratrol was maintained at high levels for a long ...time.•Formulation showed non-significant edema and erythema in skin irritation test.
The aim of this study was to develop and assess the potential of nanostructured emulsion carriers for resveratrol topical application. Different compositions of resveratrol-loaded nanostructured emulsions were prepared using different types and amounts of surfactants and oily phases (isopropyl myristate and caproyl 90). The produced nanostructured emulsions were within the nanosized range 23.4–422.2nm with low viscosity range 2.15–17.53cps. The transdermal amount and deposition amount in the skin after 24 applications of resveratrol-loaded nanostructured emulsion were significantly increased about 896.2-fold and 10.2-fold respectively, when compared to the drug-saturated solution-treated group. Nanostructured emulsion containing IPM and low amounts of mixed surfactant of Tween80/Span 20 showed highest permeation capacity. In vivo study showed that the plasma concentration of resveratrol could be maintained at high levels for a long time after topical application of drug-loaded nanostructured emulsion. The histological examination demonstrated that the free drug- and drug-loaded nanostructured emulsion demonstrated considerably less irritation than the standard irritation group (0.8% paraformaldehyde-treated). The residual contents of resveratrol in the tested formulations after 3 months of storage at 25°C and 40°C were more than 99.97±3.90%. The results of present work confirm the high potential of nanostructured emulsion as carriers for drug topical application.
This study investigates pH-sensitive hydrogels based on biocompatible, biodegradable polysaccharides and natural polymers such as chondroitin sulfate and alginate in combination with synthetic ...monomer such as acrylic acid, as controlled drug carriers. Investigations were conducted for chondroitin sulfate/alginate-graft-poly(acrylic acid) hydrogel in various mixing ratios of chondroitin sulfate, alginate and acrylic acid in the presence of ammonium persulfate and N′,N′-Methylene bisacrylamide. Crosslinking and loading of drug were confirmed by Fourier transform infrared spectroscopy. Thermal stability of both polymers was enhanced after crosslinking as indicated by thermogravimetric analysis and differential scanning calorimeter thermogram of developed hydrogel. Similarly, surface morphology was evaluated by scanning electron microscopy, whereas crystallinity of the polymers and developed hydrogel was investigated by powder X-ray diffraction. Furthermore, swelling and drug-release studies were investigated in acidic and basic medium of pH 1.2 and 7.4 at 37 °C, respectively. Maximum swelling and drug release were detected at pH 7.4 as compared to pH 1.2. Increased incorporation of hydrogel contents led to an increase in porosity, drug loading, and gel fraction while a reduction in sol fraction was seen. The polymer volume fraction was found to be low at pH 7.4 compared to pH 1.2, indicating a prominent and greater swelling of the prepared hydrogels at pH 7.4. Likewise, a biodegradation study revealed a slow degradation rate of the developed hydrogel. Hence, we can conclude from the results that a fabricated system of hydrogel could be used as a suitable carrier for the controlled delivery of ketorolac tromethamine.
Psoriasis is a chronic autoimmune skin disorder that involves keratinocyte hyperproliferation and inflammatory cell recruitment. A strategy to mitigate psoriatic lesions is to induce keratinocyte ...apoptosis for proliferation suppression. Herein we designed a nanoformulation capable of treating psoriasis via hyperthermia-induced apoptosis in response to near-infrared (NIR) irradiation. To this end, gold nanorods (GNRs) and isatin, which is an anti-inflammatory agent for synergizing antipsoriatic activity, were loaded into a poly (lactic-co-glycolic acid) (PLGA) matrix to form the nanocomplexes. The physicochemical and photothermal properties of the nanocomplexes were determined in terms of size, surface charge, NIR-absorbing feature, isatin release, keratinocyte uptake, and cytotoxicity. The nanocomplexes showed a spherical shape with an average size of about 180 nm. The GNR-loaded nanoparticles can efficiently convert NIR light at 0.42 W/cm2 into heat with an increased temperature of 10 °C. When combined with NIR exposure, the nanocomplexes were internalized into keratinocyte cytoplasm with an inhibition of keratinocyte viability to about 60%. Live/dead cell assay and flow cytometry confirmed that the nanocomplexes could serve as NIR-absorbers to specifically elicit keratinocyte apoptosis through caspase and poly ADP-ribose polymerase (PARP) pathways. The in vivo psoriasiform murine model indicated that the combined nanocomplexes and NIR inhibited epidermal hyperplasia and neutrophil infiltration. The overexpressed cytokines in the lesion could be recovered to normal baseline level after the photothermal management. The subcutaneous nanocomplexes remained in the skin for at least 5 days. The nanocomposites produced a negligible toxicity in the skin or liver of healthy mice. The photothermal nanosystems, as designed in this study, shed new light on the therapeutic approach against psoriasis.
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The objective of the present work was to investigate the specific brain targeting of baicalein by intravenous injection after incorporation into nanostructured lipid carriers (NLCs). The NLC system, ...composed of tripalmitin, Gelucires, vitamin E, phospholipids, and poloxamer 188 (referred to as tocol NLCs), was characterized in terms of its physicochemical properties, differential scanning calorimetry (DSC), stability, in vivo pharmacokinetics, and brain distribution. The lipid nanoparticles were spherical with an average size of ∼100nm. The zeta potential of the nanoparticles was about −50mV. DSC studies suggested that the majority of the inner cores of tocol NLCs had a slightly disordered crystal arrangement. The nanoparticulate dispersions demonstrated good physical stability during storage for 6 days. The incorporation of vitamin E in the formulations greatly reinforced baicalein's stability. The aqueous control and tocol NLCs were intravenously administered to rats. The plasma level of baicalein in NLCs was much higher and the half-life much longer than those in the free control. In the experiment on the brain distribution, NLCs respectively revealed 7.5- and 4.7-fold higher baicalein accumulations compared to the aqueous solution in the cerebral cortex and brain stem. Greater baicalein accumulations with NLCs were also detected in the hippocampus, striatum, thalamus, and olfactory tract. A 2–3-fold increase in baicalein amounts were achieved in these regions. Tocol NLCs improved baicalein's stability and the ability of baicalein to penetrate the brain; thus, this is a promising drug-targeting system for the treatment of central nervous system disorders.
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