Edaravone-loaded poly(amino acid) nanogel inhibits ferroptosis for neuroprotection in cerebral ischemia injury

Neurological injury caused by ischemic stroke is a major cause of permanent disability and death. The currently available neuroprotective drugs fail to achieve desired therapeutic efficacy mainly due to short circulation half-life and poor blood−brain barrier (BBB) permeability. For that, an edaravone-loaded pH/glutathione (pH/GSH) dual-responsive poly(amino acid) nanogel (NG/EDA) was developed to improve the neuroprotection of EDA. The nanogel was triggered by acidic and EDA-induced high-level GSH microenvironments, which enabled the selective and sustained release of EDA at the site of ischemic injury. NG/EDA exhibited a uniform sub-spherical morphology with a mean hydrodynamic diameter of 112.3 ± 8.2 nm. NG/EDA efficiently accumulated at the cerebral ischemic injury site of permanent middle cerebral artery occlusion (pMCAO) mice, showing an efficient BBB crossing feature. Notably, NG/EDA with 50 µM EDA significantly increased neuron survival (29.3%) following oxygen and glucose deprivation by inhibiting ferroptosis. In addition, administering NG/EDA for 7 d significantly reduced infarct volume to 22.2% ± 7.2% and decreased neurobehavioral scores from 9.0 ± 0.6 to 2.0 ± 0.8. Such a pH/GSH dual-responsive nanoplatform might provide a unique and promising modality for neuroprotection in ischemic stroke and other central nervous system diseases.

Poly(lactic acid)-aspirin microspheres prepared via the traditional and improved solvent evaporation methods and its application performances

Drug-loaded microspheres are significant for the development of modern pharmaceutical products. It is well known that the taken of aspirin for long-term increases the risk of serious gastrointestinal complications, therefore a controllable delivery of aspirin is of importance to lighten those side effects. In this work, poly(lactic acid)(PLA) was chosen as the carrier to prepare PLA-aspirin microspheres by using the traditional and the improved solvent evaporation methods. It was found that no matter which experimental condition was, the encapsulation efficiency of aspirin was higher by using the improved method than that of the traditional method. Specifically, when the concentration of polyvinyl alcohol = 1%(mass),the polymer concentration = 1:20, the oil/water rate = 1:2.5, PLA-aspirin microspheres were obtained via the improved method with a high yield of 82.83%(mass) and an encapsulation efficiency of 44.09%. PLAaspirin microspheres were then prepared continuously using the improved method, which further enhanced the encapsulation efficiency to 54.56%. Approximate 85% aspirin released from microspheres within 7 days. Obvious degradation which was represented by reduction on hardness was observed by soaking microspheres in PBS for 60 days. This work is of interest because it provides a continuous route to prepare PLA-aspirin microspheres continuously with a high drug encapsulation efficiency.

Methods for the Determination of Stable Isotopes of Carbon and Nitrogen Directly in Valine, Proline, Glutamine, and Glutamic Acid

Amino acids are very important compounds for the body and are involved in important functions that keep us healthy. Amino acids are essential components such as valine, proline, glutamine and glutamic acid. They can be synthesized either naturally or artificially. To examine the metabolism and regulate the synthesis process, compounds labeled with nitrogen or carbon isotopes need to be used. These isotopic compounds allow for more extensive research and enable studies that would otherwise be impossible. However, their use is dependent on the availability of simple, efficient methods for isotopic analysis. Currently, the determination of the atomic fraction of carbon and nitrogen isotopes is only possible through their conversion into molecular nitrogen or carbon monoxide or carbon dioxide. This leads to the loss of information about isotopic enrichment in specific centers of the molecule. This article explores a new direct approach to determining the atomic fraction of carbon and nitrogen isotopes in the isotope-modified or identical centers of these compounds. This method eliminates the transfer process and dilution due to nitrogen and carbon impurities. It is now possible to simultaneously determine the atomic fraction of nitrogen and carbon isotopes in the research substance. This method can be applied to amino acids, making it an effective tool for proposing new research methods. Several articles [1] [2] [3] have proposed similar methods for organic compounds and amino acids.

Development of a Freeze-Dried Skin Care Product Composed of Hyaluronic Acid and Poly(γ-Glutamic Acid) Containing Bioactive Components for Application after Chemical Peels

Eight types of spongy sheet were prepared by freeze-drying aqueous solutions of hyaluronic acid (HA) and poly(γ-glutamic acid) (PGA) with or without bioactive components including vitamin C derivative (VC), glucosylceramide (GC), and epidermal growth factor (EGF). Spongy sheets were categorized into the following groups: Group I (HA/PGA), Group II (HA/PGA + VC), Group III (HA/PGA + GC), Group IV (HA/PGA + VC, GC), Group V (HA/PGA + EGF), Group VI (HA/PGA + VC, EGF), Group VII (HA/PGA + GC, EGF), and Group VIII (HA/PGA + VC, GC, EGF). In the first experiment, we examined fibroblast proliferation in conditioned medium that had been prepared by immersing each spongy sheet in a conventional culture medium. EGF-incorporating spongy sheets (Groups V-VIII) enhanced fibroblast proliferation more than EGF-free spongy sheets (Groups I-IV). In the second experiment, cytokine production by fibroblasts was evaluated using a wound surface model. This involved elevation of fibroblasts-incorporating collagen gel sheets to the air-liquid interface, on which a spongy sheet (Groups I, IV, V and VIII) was placed and cultured for 1 week. EGF-incorporating spongy sheets (Groups V and VIII) enhanced the production of vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) by fibroblasts more than EGF-free spongy sheets (Groups I and IV). The effect of these four types of spongy sheet on wounds was investigated in animal experiments. Chemical peel was performed by contacting 50% trichloroacetic acid (TCA) on the dorsal region of mice, after which a spongy sheet was placed, and the wound condition was then observed in a two-week period. Angiogenesis was facilitated to a greater degree in Group VIII compared with Groups I, IV and V. This finding indicates that Group VIII spongy sheet is a promising aid for skin recovery after chemical peel.

Preparation and Evaluation of Poly-γ-Glutamic Acid Hydrogel Mixtures with Basic Drugs or Acidic Drugs: Effect on Ease of Swallowing and Taste Masking

The purpose of this study was to prepare a poly-γ-glutamic acid hydrogel (PGA gel), to examine its ease of swallowing using texture profile analysis (TPA) and to evaluate its taste-masking effects on basic or acidic drugs using the artificial taste sensor. Using TPA, 0.5% and 1.0% PGA gels, 0.5% and 1.0% agar and 1.0% ι-carrageenan in the absence of drug was examined the hardness, adhesiveness and cohesiveness, ranked according to permission criteria published by the Japanese Consumers Affairs Agency. 0.5% PGA gel and 1.0% agar were classified into grade II. In the taste sensor measurement, the bitterness suppressions by 0.5% PGA gel were larger than that by 1.0% agar in all drugs and the bitterness suppressions of basic drugs in 0.5% PGA gel were more potent than those of acidic drugs in 0.5% PGA gel. 1H-nuclear magnetic resonance spectroscopic analysis was carried out to examine the difference in mechanism of bitterness suppression between basic drugs and acidic drugs mixed with PGA gel. The signals of the proton nearest to the nitrogen atom of basic drugs shifted clearly upfield, suggesting an interaction between the amino group of basic drugs and the carboxyl group of PGA gel. In conclusion, PGA gel is expected to be a useful excipient in formulations contained various drugs, especially basic drugs;it also has advantage for not only increasing ease of swallowing but also masking the bitterness of drugs even though a small amount of a single drug dose might be preferred.

High-performance and robust high-temperature polymer electrolyte membranes with moderate microphase separation by implementation of terphenyl-based polymers

Acid loss and plasticization of phosphoric acid(PA)-doped high-temperature polymer electrolyte membranes(HT-PEMs)are critical limitations to their practical application in fuel cells.To overcome these barriers,poly(terphenyl piperidinium)s constructed from the m-and p-isomers of terphenyl were synthesized to regulate the microstructure of the membrane.Highly rigid p-terphenyl units prompt the formation of moderate PA aggregates,where the ion-pair interaction between piperidinium and biphosphate is reinforced,leading to a reduction in the plasticizing effect.As a result,there are trade-offs between the proton conductivity,mechanical strength,and PA retention of the membranes with varied m/p-isomer ratios.The designed PA-doped PTP-20m membrane exhibits superior ionic conductivity,good mechanical strength,and excellent PA retention over a wide range of temperature(80–160°C)as well as satisfactory resistance to harsh accelerated aging tests.As a result,the membrane presents a desirable combination of performance(1.462 W cm^(-2) under the H_(2)/O_(2)condition,which is 1.5 times higher than that of PBI-based membrane)and durability(300 h at 160°C and 0.2 A cm^(-2))in the fuel cell.The results of this study provide new insights that will guide molecular design from the perspective of microstructure to improve the performance and robustness of HT-PEMs.

Combretastatin A4/poly(L-glutamic acid)-graft-PEG conjugates self-assembled to nanoparticles

Combretastatin A4(CA4) possesses varying ability to cause vascular disruption in tumors,while the short half-life, low water solubility and deactivation of many CA4 analogs during storage limited its antitumor efficacy and drug stability. A novel macromolecular conjugate of CA4(CA4-PL) was synthesized by covalent bonding of CA4 onto poly(L-glutamic acid)-graft-polyethylene glycol(PLG-g-PEG) via Yamaguchi reaction. The obtained CA4-PL was characterized by ~1H NMR, GPC, and UV methods, and the properties of the nanoparticles composed of CA4-PL, including critical aggregation concentration, size and size distribution, and morphology, were investigated. CA4-PL can self-assemble to form micelle-like nanoparticles of 80～120 nm in diameter, which may have potential to improve the blood circulation period as well as the targetability of CA4, and find applications to treat various tumors when combined with traditional chemotherapy or radio therapy.

An Anionic Polymer Incorporating Low Amounts of Hydrophobic Residues Is a Multifunctional Surfactant. Part 2: Emulsification, Moisture Absorption, and Moisture Retention of Alkyl Esterified Poly-γ-Glutamic Acid

In the accompanying paper (Part 1), we showed that the fatty acid moiety and the acidity of the polysaccharide-backbone of a fatty acid-containing polysaccharide might be involved in its emul-sification, moisture absorption, and moisture retention abilities. In this study, we synthesized alkyl esterified poly-γ-glutamic acid (PGA) with various chain lengths and degrees of substitution of the alkyl moieties to examine how hydrophobic groups incorporated in the anionic polymer contribute to enhanced emulsification, moisture absorption, and moisture retention. With a low degree of alkylation of PGA, these abilities were drastically improved. To improve the moisture absorption of PGA, alkylation with a short chain length is effective in forming interspaces between PGA chains to trap water molecules. Hydrophobic-hydrophilic balance may also be important to improve the emulsification and moisture retention abilities of PGA alkylates. To the best of our knowledge, this is the first report of the relationship between the structure and the multifunctional abilities of an anionic polymer incorporated with a small amount of hydrophobic residue. PGA alkylates, as well as fatty acid-containing polysaccharides, have potential use as multifunctional surfactants throughout various industries.

SYNTHESIS AND CATALYTIC PROPERTY OF POLYSTYRENE SUPPORTED GLUTAMIC ACID SCHIFF BASE COMPLEX OF Mn(Ⅱ) IN AEROBIC OXIDATION OF CYCLOHEXENE

The polystyrene supported glutamic acid Schiff base complex of Mn (Ⅱ) (PS-Sal-Glue-Mn) was prepared with chloromethylated styrene polymer beads, 2,4-dihydroxybenzaldehyde, L-glutamic acid and manganese (Ⅱ) acetate tetrahyrate. The polymeric ligand and the complex were characterized by FT-IR, small area X-ray photoelectron spectroscopy (XPS) and ICP-AES. In the presence of the manganese complex, cyclohexene (1) was effectively oxidized by molecular oxygen without reductant. The major products of the reaction were 2-cyclohexen-1-ol (2), 2-cyclohexen-1-one (3) and 2-cyclohexen-1- hydroperoxide (4), which was different with typical oxidation of cyclohexene. The influence of reaction temperature and additive for oxidation had been studied. The selectivity of 2-cyclohexen-1-hydroperoxide varied with reaction time and different additives. The mechanism of cyclohexene oxidation had also been discussed.

Synthesis of the Biomimetic Polymer: Aliphatic Diamine and RGDS Modified Poly(d,l-lactic acid)

A novel poly（d, /-lactic acid） （PDLLA） based biomimetic polymer was synthesized by grafting maleic anhydride, butanediamine and arg-gly-asp-ser （RGDS） peptides onto the backbone of PDLLA, aiming to overcome the acidity and auto-accelerating degradation of PDLLA during degradation and to improve its biospecificity and biocompatibility. The synthetic copolymer was characterized by FTIR, ^13C NMR and amino acid analyzer （AAA）.

CLAY CATALYZED SYNTHESIS OF BIO-DEGRADABLE POLY(GLYCOLIC ACID)

Glycolic acid was polymerized under vacuum in the presence and absence of nano sized clay.The added clay catalyzed the condensation polymerization which can be confirmed by recording FTIR spectroscopy and intrinsic viscosity (Ⅳ)values.The relative intensity of C=O/CH is increased while increasing the amount of clay.DSC showed the appearance of multiple endotherms of poly(glycolic acid).TGA showed the percentage weight residue remain above 750℃for polymer-nano composite system was 21% and hence proved the fl...

Dietary saturated fatty acid and polyunsaturated fatty acid oppositely affect hepatic NOD-like receptor protein 3 inflammasome through regulating nuclear factor-kappa B activation

AIM: To investigate the effect of different dietary fatty acids on hepatic inflammasome activation.METHODS: Wild-type C57BL/6 mice were fed either a high-fat diet or polyunsaturated fatty acid(PUFA)-enriched diet. Primary hepatocytes were treated with either saturated fatty acids(SFAs) or PUFAs as well as combined with lipopolysaccharide(LPS). The expression of NOD-like receptor protein 3(NLRP3) inflammasome, peroxisome proliferator-activated receptor-γ and nuclear factor-kappa B(NF-κB) was determined by real-time PCR and Western blot. The activity of Caspase-1 and interleukine-1β production were measured.RESULTS: high-fat diet-induced hepatic steatosis was sufficient to induce and activate hepatic NLRP3 inflammasome. SFA palmitic acid(PA) directly activated NLRP3 inflammasome and increased sensitization to LPS-induced inflammasome activation in hepatocytes. In contrast, PUFA docosahexaenoic acid(Dh A) had thepotential to inhibit NLRP3 inflammasome expression in hepatocytes and partly abolished LPS-induced NLRP3 inflammasome activation. Furthermore, a highfat diet increased but PUFA-enriched diet decreased sensitization to LPS-induced hepatic NLRP3 inflammasome activation in vivo. Moreover, PA increased but Dh A decreased phosphorylated NF-κB p65 protein expression in hepatocytes.CONCLUSION:Hepatic NLRP 3 inflammasome activation played an important role in the development of non-alcoholic fatty liver disease. Dietary SFAs and PUFAs oppositely regulated the activity of NLRP3 inflammasome through direct activation or inhibition of NF-κB.

Preparation and properties of short natural fiber reinforced poly(lactic acid) composites

The natural fiber/poly(lactic acid) (PLA) composites were prepared with ramie and jute short fiber as reinforcement and PLA as matrix. The mechanical and thermal properties of the composites were investigated. The results show that the properties of the composites are better than those of plain PLA. When the content of the fiber is 30%, the composites can get the best mechanical properties. The dynamic mechanical analysis results show that the storage moduli of the PLA/ramie and PLA/jute composites increase with respect to the plain PLA. The Vicat softening temperature of the composites is greatly higher than that of PLA. The results of thermogravimetric analysis show that adding fiber to the PLA matrix can improve the degradation temperature of PLA.

Preparation and phase change performance of Na_2HPO_4·12H_2O@poly(lactic acid) capsules for thermal energy storage

Micro-encapsulated phase-change materials(micro PCMs) with Na_2 HPO_4·12 H_2 O encapsulated in poly(lactic acid)(PLA) shell were prepared by a solvent evaporation–precipitation method that involves the use of a coaxial needle. The effects of PLA concentration, stirring speed, injection rate of core and shell solutions, and polyvinyl alcohol(PVA) concentration on phase change properties were investigated. The thermal properties of microP CMs were characterized by differential scanning calorimetry(DSC). The capsules prepared under the optimal conditions are about 2 mm in diameter and show a latent heat of up to 122.2 J·g^(-1).

Poly (Acrylamide-co-Acrylic Acid) Hydrogel Induced by Glow-Discharge Electrolysis Plasma and Its Adsorption Properties for Cationic Dyes

In this paper, poly （acrylamide-co-acrylic acid） （P（AM-co-AA）） hydrogel was pre- pared in an aqueous solution by using glow-discharge electrolysis plasma （GDEP） induced copoly- merization of acrylamide （AM） and acrylic acid （AA）, in which N,N＇-methylenebisacrylamide （MBA） was used as a crosslinker. A mechanism for the synthesis of P（AM-co-AA） hydrogel was proposed. To optimize the synthesis condition, the following parameters were examined in detail： the discharge voltage, discharge time, the content of the crosslinker, and the mass ratio of AM to AA. The results showed that the optimum pH range for cationic dyes removal was found to be 5.0-10.0. The P（AM-co-AA） hydrogel exhibits a very high adsorption potential and the ex- perimental adsorption capacities for Crystal violet （CV） and Methylene blue （MB） were 2974.3 mg/g and 2303.6 mg/g, respectively. The adsorption process follows a pseudo-second-order kinetic model. In addition, the adsorption mechanism of P（AM-co-AA） hydrogel for cationic dyes was also discussed.

Transplantation of Nogo-66 receptor gene-silenced cells in a poly(D,L-lactic-co-glycolic acid) scaffold for the treatment of spinal cord injury

Inhibition of neurite growth, which is in large part mediated by the Nogo-66 receptor, affects neural regeneration following bone marrow mesenchymal stem cell transplantation. The tissue engineering scaffold poly（D,L-lactide-co-glycolic acid） has good histocompatibility and can promote the growth of regenerating nerve fibers. The present study used small interfering RNA to silence Nogo-66 receptor gene expression in bone marrow mesenchymal stem cells and Schwann cells, which were subsequently transplanted with poly（D,L-lactide-co-glycolic acid） into the spinal cord lesion regions in rats. Simultaneously, rats treated with scaffold only were taken as the control group. Hematoxylin-eosin staining and immunohistochemistry revealed that at 4 weeks after transplantation, rats had good motor function of the hind limb after treatment with Nogo-66 receptor gene-silenced ceils prus the poly（O,L-lactide-co-glycolic acid） scaffold compared with rats treated with scaffold only, and the number of bone marrow mesenchymal stem cells and neuron-like cells was also increased. At 8 weeks after transplantation, horseradish peroxidase tracing and transmission electron microscopy showed a large number of unmyelinated and myelinated nerve fibers, as well as intact regenerating axonal myelin sheath following spinal cord hemisection injury. These experimental findings indicate that transplantation of Nogo-66 receptor gene-silenced bone marrow mesenchymal stem cells and Schwann cells plus a poly（D,L-lactide-co-glycolic acid） scaffold can significantly enhance axonal regeneration of spinal cord neurons and improve motor function of the extremities in rats following spinal cord injury.

A novel artificial nerve graft for repairing longdistance sciatic nerve defects:a self-assembling peptide nanofiber scaffold-containing poly (lactic-co-glycolic acid) conduit

In this study, we developed a novel artificial nerve graft termed self-assembling peptide nanofiber scaffold （SAPNS）-containing poly（lactic-co-glycolic acid） （PLGA） conduit （SPC） and used it to bridge a 10-mm-long sciatic nerve defect in the rat. Retrograde tracing, behavioral testing and histomorphometric analyses showed that compared with the empty PLGA conduit implantation group, the SPC implantation group had a larger number of growing and extending axons, a markedly increased diameter of regenerated axons and a greater thickness of the myelin sheath in the conduit. Furthermore, there was an increase in the size of the neuromuscular junction and myofiber diameter in the target muscle. These findings suggest that the novel artificial SPC nerve graft can promote axonal regeneration and remyelination in the transected peripheral nerve and can be used for repairing peripheral nerve injury.

Synergistic effect of MXene on the flame retardancy and thermal degradation of intumescent flame retardant biodegradable poly(lactic acid)composites

The effect of Ti3C2 MXene nanosheets on the intumescent flame retardant(IFR)poly(lactic acid)(PLA)composites was investigated among a series of PLA/IFR/MXene,which were prepared by melt blending 0-2.0 wt%MXene,10.0 wt%-12.0 wt%IFR and PLA together.The results of limiting oxygen index(LOI)and vertical burning(UL-94)discover that the combination of 0.5 wt%MXene and 11.5 wt%IFR synergistically improves the fire safety of PLA to reach UL-94 V-0 rating with LOI value of 33.0%.The PLA/IFR/MXene composites perform an obvious reduction in peak of heat release rate(HRR)in cone calorimeter tests(CCTs).Furthermore,the carbon residues after CCTs were characterized by scanning electron microscope(SEM),laser Raman spectroscopy(LRS),X-ray diffraction(XRD)and X-ray photoelectron spectroscopy(XPS).It is demonstrated that both the titanium composition of the MXene structure and the characteristics of the two-dimensional material enhance the PLA/IFR/MXene composite materials’ability to produce a dense barrier layer to resist burnout during thermal degradation.

Synthesis and Characterization of Chitosan-g-poly- (D, L-lactic acid) Copolymer

Biodegradable chitosan-g-poly (D, L-lactic acid) copolymers were prepared via two methods. (1) The lactide was grafted onto hydroxyl groups of chitosan by using macromolecular initiator sodium of trimethylsilyl-chitosan, (2) poly (D,L-lactic acid)(PLA) with low molecular weight can be linked to the amino group by coupling activated PLA to trimethylsilyl-chitosan. Two graft copolymers had hydrophilic-hydrophobic character and can be applied as carriers for drug delivery.

Tanshinone IIa antagonizes spinal ischemia/reperfusion injury by interfering with upstream glutamic acid factors

Based on the hypothesis that upstream factor inhibition results in better treatment effects than downstream factor inhibition,the present study interfered with glutamic acid（Glu）-released upstream factors,such as Glu transporter function and Na＋-K＋-adenosine triphosphatases（ATPase）activity relativly.Rats with spinal cord ischemia/reperfusion injury received intraperitoneal injections of tanshinone Ila and Glu uptake and Na＋-K＋-ATPase activity were increased.Results showed that tanshinone Ila influenced Glu-released upstream factors following spinal ischemia/reperfusion injury and protected against spinal ischemia/reperfusion injury.