Effect of water migration on changes of quality and volatile compounds in frozen Penaeus monodon.

The purpose of this study was to clarify effects of water changes on the quality and volatile compounds of Penaeus monodon during frozen storage. The content of immobilized water decreased significantly while the bound water and free water increased significantly. Total sulfhydryl content, and Ca2+-ATPase activity decreased significantly to 68.31 µmol/g and 0.127 U/mg, meantime, carbonyl content and MFI value increased significantly to 2.04 µmol/g prot and 55.10. Total of 50 volatile compounds were identified. Nonanal (M & D), 2-nonanone and octanal were only detected in fresh samples, while 3-hydroxy-2-butanone and 1-hydroxy-2-propanone were only found in the samples after 20 days of storage. Correlation analysis revealed that 6 of the volatile compounds were associated with the change of free water. Total of 28 and 17 volatile compounds showed significant correlations with the immobilized water and bound water, respectively. Four volatile compounds have the potential to be used as the flavor marker.

Three Ru(II) complexes modulate the antioxidant transcription factor Nrf2 to overcome cisplatin resistance.

Here, we designed, synthesized and characterized three new cyclometalated Ru(II) complexes, [Ru(phen)2(1-(4-Ph-Ph)-IQ)]+ (phen = 1,10-phenanthroline, IQ = isoquinoline, RuIQ9), [Ru(phen)2(1-(4-Ph-Ph)-7-OCH3-IQ)]+ (RuIQ10), and [Ru(phen)2(1-(4-Ph-Ph)-6,7-(OCH3)2-IQ)]+ (RuIQ11). The cytotoxicity experiments conducted on both 2D and 3D multicellular tumor spheroids (MCTSs) indicated that complexes RuIQ9-11 exhibited notably higher cytotoxicity against A549 and A549/DDP cells when compared to the ligands and precursor compounds as well as clinical cisplatin. Moreover, the Ru(II) complexes displayed low toxicity when tested on normal HBE cells in vitro and exposed to zebrafish embryos in vivo. In addition, complexes RuIQ9-11 could inhibit A549 and A549/DDP cell migration and proliferation by causing cell cycle arrest, mitochondrial dysfunction, and elevating ROS levels to induce apoptosis in these cells. Mechanistic studies revealed that RuIQ9-11 could suppress the expression of Nrf2 and its downstream antioxidant protein HO-1 by inhibiting Nrf2 gene transcription in drug-resistant A549/DDP cells. Simultaneously, they inhibited the expression of efflux proteins MRP1 and p-gp in drug-resistant cells, ensuring the accumulation of the complexes within the cells. This led to an increase in intracellular ROS levels in drug-resistant cells, ultimately causing damage and cell death, thus overcoming cisplatin resistance. More importantly, RuIQ11 could effectively inhibit the migration and proliferation of drug-resistant cells within zebrafish, addressing the issue of cisplatin resistance. Accordingly, the prepared Ru(II) complexes possess significant potential for development as highly effective and low-toxicity lung cancer therapeutic agents to overcome cisplatin resistance.

Fabrication and hemostasis evaluation of a carboxymethyl chitosan/sodium alginate/Resina Draconis composite sponge.

Hemostasis is the first step of emergency medical treatment. It is particularly important to develop rapid-acting and efficacious hemostatic materials. Carboxymethyl chitosan (CMCS), sodium alginate (SA) and Resina Draconis (RD) were composited uniformly by polyelectrolyte blending. Their composite sponges (CMCS/SA/RD) were prepared by freeze-induced phase separation. CMCS/SA/RD sponges were characterized by Fourier transform infrared spectroscopy and scanning electron microscopy, and their blood absorption and hemolysis ratio were analyzed. The hemostatic effect of the composite sponges was evaluated by coagulation in vitro and in vivo. The composite sponges had a porous network structure. The water absorption ratio was >8000 %, and hemolysis ratio was <5 %. CMCS/SA/RD-II and CMCS/SA/RD-III composite sponges shortened the coagulation time in vitro by 11.33 s and 9.66 s, the hepatic hemostasis time by 13.8 % and 23.3 %, and the hemostasis time after mouse-tail amputation by 28.9 % and 23.9 %, respectively. A preliminary study on its coagulation mechanism showed that CMCS/SA/RD had significant effects on erythrocyte adsorption, platelet adhesion, and shortening of the activated partial thromboplastin time.

Preparation, Characterization, and Antioxidant Properties of Self-Assembled Nanomicelles of Curcumin-Loaded Amphiphilic Modified Chitosan.

Curcumin (Cur) is a phytochemical with various beneficial properties, including antioxidant, anti-inflammatory, and anticancer activities. However, its hydrophobicity, poor bioavailability, and stability limit its application in many biological approaches. In this study, a novel amphiphilic chitosan wall material was synthesized. The process was carried out via grafting chitosan with succinic anhydride (SA) as a hydrophilic group and deoxycholic acid (DA) as a hydrophobic group; 1H-NMR, FTIR, and XRD were employed to characterize the amphiphilic chitosan (CS-SA-DA). Using a low-cost, inorganic solvent-based procedure, CS-SA-DA was self-assembled to load Cur nanomicelles. This amphiphilic polymer formed self-assembled micelles with a core-shell structure and a critical micelle concentration (CMC) of 0.093 mg·mL-1. Cur-loaded nanomicelles were prepared by self-assembly and characterized by the Nano Particle Size Potential Analyzer and transmission electron microscopy (TEM). The mean particle size of the spherical Cur-loaded micelles was 770 nm. The drug entrapment efficiency and loading capacities were up to 80.80 ± 0.99% and 19.02 ± 0.46%, respectively. The in vitro release profiles of curcumin from micelles showed a constant release of the active drug molecule. Cytotoxicity studies and toxicity tests for zebrafish exhibited the comparable efficacy and safety of this delivery system. Moreover, the results showed that the entrapment of curcumin in micelles improves its stability, antioxidant, and anti-inflammatory activity.

Self-assembled gel microneedle formed by MS deep eutectic solvent as a transdermal delivery system for hyperpigmentation treatment.

Hyperpigmentation (HP) is an unfavorable skin disease that typically caused by injury, inflammation, or photoaging and leads to numerous physical and psychological issues in patients. Recently, development and application of natural whitening substances, particularly compound curcumin (CUR), is one of the most prevalent treatments for HP. However, it is still a formidable challenge to improve the percutaneous delivery of CUR due to its inadequate solubility in water and excellent barrier function of skin. To overcome the limitations of conventional delivery and increase the percutaneous absorption of CUR, the efficient delivery of CUR is urgently required. Herein, we developed a new malic acid-sorbitol deep eutectic solvent (MS/DES) gel microneedle loaded with CUR as a transdermal delivery system for HP treatment. The MS/DES gel produces three-dimensional (3D) network structure by self-assembly of hydrogen bond interactions, which conferred the CUR-MS/DES-GMN with sufficient mechanical properties to successfully penetrate skin tissue while also helping to enhance the drug's release rate. The CUR-MS/DES-GMN exhibit high biocompatibility and mechanical property in vivo of mice. The zebrafish experiments also show that CUR-MS/DES gel has significant effect of anti-pigmentation. Therefore, the designed CUR-MS/DES-GMN system provides a novel strategy for HP treatment based on self-assembly of naturally molecules.

Cyclometalated ruthenium complexes overcome cisplatin resistance through PI3K/mTOR/Nrf2 signaling pathway.

Currently, cisplatin resistance remains a primary clinical obstacle in the successful treatment of non-small cell lung cancer. Here, we designed, synthesized, and characterized two novel cyclometalated Ru(II) complexes, [Ru(bpy)2(1-Ph-7-OCH3-IQ)] (PF6) (bpy = 2,2'-bipyridine, IQ = isoquinoline, RuIQ7)and [Ru(bpy)2(1-Ph-6,7-(OCH3)2-IQ)] (PF6) (RuIQ8). As experimental controls, we prepared complex [Ru(bpy)2(1-Ph-IQ)](PF6) (RuIQ6) lacking a methoxy group in the main ligand. Significantly, complexes RuIQ6-8 displayed higher in vitro cytotoxicity when compared to ligands, precursor cis-[Ru(bpy)2Cl2], and clinical cisplatin. Mechanistic investigations revealed that RuIQ6-8 could inhibit cell proliferation by downregulating the phosphorylation levels of Akt and mTOR proteins, consequently affecting the rapid growth of human lung adenocarcinoma cisplatin-resistant cells A549/DDP. Moreover, the results from qRT-PCR demonstrated that these complexes could directly suppress the transcription of the NF-E2-related factor 2 gene, leading to the inhibition of downstream multidrug resistance-associated protein 1 expression and effectively overcoming cisplatin resistance. Furthermore, the relationship between the chemical structures of these three complexes and their anticancer activity, ability to induce cell apoptosis, and their efficacy in overcoming cisplatin resistance has been thoroughly examined and discussed. Notably, the toxicity test conducted on zebrafish embryos indicated that the three Ru-IQ complexes displayed favorable safety profiles. Consequently, the potential of these developed compounds as innovative therapeutic agents for the efficient and low-toxic treatment of NSCLC appears highly promising.

Self-Assembled Amphiphilic Chitosan Nanomicelles: Synthesis, Characterization and Antibacterial Activity.

Although amphiphilic chitosan has been widely studied as a drug carrier for drug delivery, fewer studies have been conducted on the antimicrobial activity of amphiphilic chitosan. In this study, we successfully synthesized deoxycholic acid-modified chitosan (CS-DA) by grafting deoxycholic acid (DA) onto chitosan C2-NH2, followed by grafting succinic anhydride, to prepare a novel amphiphilic chitosan (CS-DA-SA). The substitution degree was 23.93% for deoxycholic acid and 29.25% for succinic anhydride. Both CS-DA and CS-DA-SA showed good blood compatibility. Notably, the synthesized CS-DA-SA can self-assemble to form nanomicelles at low concentrations in an aqueous environment. The results of CS, CS-DA, and CS-DA-SA against Escherichia coli and Staphylococcus aureus showed that CS-DA and CS-DA-SA exhibited stronger antimicrobial effects than CS. CS-DA-SA may exert its antimicrobial effect by disrupting cell membranes or forming a membrane on the cell surface. Overall, the novel CS-DA-SA biomaterials have a promising future in antibacterial therapy.

The polymorphisms of miR-146a SNPs are associated with asthma in Southern Chinese Han population.

Asthma, a prevalent disease characterized by innate and adaptive immune responses, has been associated with several risk factors including miR-146a. To better understand the potential impact of miR-146a SNPs on asthma susceptibility and clinical features in Southern Chinese Han population, we conducted a case-control to analyze two functional SNPs (rs2910164 and rs57095329) of the miR-146a (394 patients with asthma and 395 healthy controls). Our findings suggest that the rs2910164 C/G genotype may increase the risk for asthma in females, while the rs57095329 G/G genotype may be involved in the regulation of clinical characteristics of males with asthma. In addition, we demonstrated that the SNPs rs2910164 C/G and rs57095329 A/G variations functionally affected the miR-146a levels in patients with asthma, and may alter structure of miR-146a. Our data are the first to suggest that miR-146a SNPs may be significantly associated with onset asthma in Southern Chinese Han population. Our studies may provide new insight into the potential significance of miR-146a SNPs in asthma.

Anti-Photoaging Effects of Nanocomposites of Amphiphilic Chitosan/18ß-Glycyrrhetinic Acid.

Improving the transdermal absorption of weakly soluble drugs for topical use can help to prevent and treat skin photoaging. Nanocrystals of 18ß-glycyrrhetinic acid (i.e., NGAs) prepared by high-pressure homogenization and amphiphilic chitosan (ACS) were used to form ANGA composites by electrostatic adsorption, and the optimal ratio of NGA to ACS was 10:1. Dynamic light scattering analysis and zeta potential analysis were used to evaluate the nanocomposites' suspension, and the results showed that mean particle size was 318.8 ± 5.4 nm and the zeta potential was 30.88 ± 1.4 mV after autoclaving (121 °C, 30 min). The results of CCK-8 showed that the half-maximal inhibitory concentration (IC50) of ANGAs (71.9 µg/mL) was higher than that of NGAs (51.6 µg/mL), indicating that the cytotoxicity of ANGAs was weaker than that of NGAs at 24 h. After the composite had been prepared as a hydrogel, the vertical diffusion (Franz) cells were used to investigate skin permeability in vitro, and it was shown that the cumulative permeability of the ANGA hydrogel increased from 56.5 ± 1.4% to 75.3 ± 1.8%. The efficacy of the ANGA hydrogel against skin photoaging was studied by constructing a photoaging animal model under ultraviolet (UV) irradiation and staining. The ANGA hydrogel improved the photoaging characteristics of UV-induced mouse skin significantly, improved structural changes (e.g., breakage and clumping of collagen and elastic fibers in the dermis) significantly, and improved skin elasticity, while it inhibited the abnormal expression of matrix metalloproteinase (MMP)-1 and MMP-3 significantly, thereby reducing the damage caused by UV irradiation to the collagen-fiber structure. These results indicated that the NGAs could enhance the local penetration of GA into the skin and significantly improve the photoaging of mouse skin. The ANGA hydrogel could be used to counteract skin photoaging.

A synthetic peptide from Sipunculus nudus promotes bone formation via Estrogen/MAPK signal pathway based on network pharmacology.

The tripeptide Leu-Pro-Lys (LPK), derived from the Sipunculus nudus protein, was synthesized and studied to investigate its potential protective effect on bone formation. The effect and mechanism of LPK were analyzed through network pharmacology, bioinformatics, and experimental pharmacology. The study found that LPK at concentrations of 25 µg/mL and 50 µg/mL significantly increased ALP activity and mineralization in C3H10 cells. LPK also increased the expression of COL1A1 and promoted bone formation in zebrafish larvae. Network pharmacology predicted 148 interaction targets between LPK and bone development, and analysis of the protein-protein interaction network identified 13 hub genes, including ESR1, MAPK8, and EGFR, involved in bone development. Through KEGG enrichment pathways analysis, it was determined that LPK promotes bone development by regulating endocrine resistance, the relaxin signaling pathway, and the estrogen signaling pathway. Molecular docking results showed direct interactions between LPK and ESR1, MAPK8, and MAPK14. Additional verification experiments using western blot assay revealed that LPK significantly upregulated the expression of genes related to bone formation, including COL1A1, OPG, RUNX2, ESR1, phosphorylated MAPK14, and phosphorylated MAPK8 in C3H10 cells. These results suggest that LPK promotes bone formation by activating the estrogen/MAPK signaling pathway.

A Chitosan-Based Flocculation Method for Efficient Recovery of High-Purity B-Phycoerythrin from a Low Concentration of Phycobilin in Wastewater.

Increasing the yield and purity of B-phycoerythrin (B-PE) can improve the economic state of microalgae industrial processing. One method of cost reduction involves the recovery of remaining B-PE from wastewater. In this study, we developed a chitosan (CS)-based flocculation technique for the efficient recovery of B-PE from a low concentration of phycobilin in wastewater. We investigated the effects of the molecular weight of chitosan, B-PE/CS mass ratio, and solution pH on the flocculation efficiency of CS and the effects of phosphate buffer concentration and pH on the recovery rate of B-PE. The maximum flocculation efficiency of CS, recovery rate, and purity index of B-PE were 97.19% ± 0.59%, 72.07% ± 1.37%, and 3.20 ± 0.025 (drug grade), respectively. The structural stability and activity of B-PE were maintained during the recovery process. Economic evaluation revealed that our CS-based flocculation method is more economical than the ammonium sulfate precipitation method is. Furthermore, the bridging effect and electrostatic interaction play important roles in B-PE/CS complex flocculation process. Hence, our study provides an efficient and economical method to recover high-purity B-PE from a low concentration of phycobilin in wastewater, which promoted the application of B-PE as a natural pigment protein in food and chemical applications.

Pathogenicity Analysis of a Novel Variant in GTPBP3 Causing Mitochondrial Disease and Systematic Literature Review.

Defect of GTPBP3, the human mitochondrial tRNA-modifying enzyme, can lead to Combined Oxidative Phosphorylation Deficiency 23 (COXPD23). Up to now, about 20 different variants of the GTPBP3 gene have been reported; however, genotype-phenotype analysis has rarely been described. Here, we reported a 9-year-old boy with COXPD23 who presented with hyperlactatemia, hypertrophic cardiomyopathy, seizures, feeding difficulties, intellectual disability and motor developmental delay, and abnormal visual development. Biallelic pathogenic variants of the GTPBP3 gene were identified in this boy, one novel variant c.1102dupC (p. Arg368Profs*22) inherited from the mother and the other known variant c.689A>C (p. Gln230Pro) inherited from father. We curated 18 COXPD23 patients with GTPBP3 variants to investigate the genotype-phenotype correlation. We found that hyperlactatemia and cardiomyopathy were critical clinical features in COXPD23 and the average onset age was 1.7 years (3 months of age for the homozygote). Clinical classification of COXPD23 for the two types, severe and mild, was well described in this study. We observed arrhythmia and congestive heart failure frequently in the severe type with early childhood mortality, while developmental delay was mainly observed in the mild type. The proportion of homozygous variants (71.4%) significantly differed from that of compound heterozygous variants (18.1%) in the severe type. Compared with the variants in gnomAD, the proportion of LOFVs in GTPBP3 was higher in COXPD23 patients (48.6% versus 8.9%, p < 0.0001 ****), and 31% of them were frameshift variants, showing the LOF mechanism of GTPBP3. Additionally, the variants in patients were significantly enriched in the TrmE-type G domain, indicating that the G domain was crucial for GTPBP3 protein function. The TrmE-type G domain contained several significant motifs involved in the binding of guanine nucleotides and Mg2+, the hydrolysis of GTP, and the regulation of the functional status of GTPases. In conclusion, we reported a mild COXPD23 case with typical GTPBP3-related symptoms, including seizures and abnormal visual development seldom observed previously. Our study provides novel insight into understanding the clinical diagnosis and genetic counseling of patients with COXPD23 by exploring the genetic pathogenesis and genotype-phenotype correlation of COXPD23.

Generation of an induced pluripotent stem cell line FDHPIi001-A derived from a female patient with WDR45-related neurodegeneration disease carrying non-canonical splice site c.344 + 5G > T.

The WDR45 encodes a beta-propeller scaffold protein which leads to ß-propeller protein-associated neurodegeneration (BPAN) with iron accumulation in the brain. Using episomal reprogramming approach, we generated an iPSC line from peripheral blood mononuclear cells (PBMCs) from a 9-year-old girl with a non-canonical splice site c.344 + 5G > T in the WDR45 gene. The iPSC line had been fully examined about pluripotency marker, karyotype, and three germ layer differentiation.

Bio-Multifunctional Sponges Containing Alginate/Chitosan/Sargassum Polysaccharides Promote the Healing of Full-Thickness Wounds.

Creation of bio-multifunctional wound dressings with potent hemostatic, antibacterial, anti-inflammatory, and angiogenesis features for bolstering the healing of full-thickness wounds is sought after for clinical applications. We created bio-multifunctional composite sponges by coupling alginate and chitosan with Sargassum pallidum polysaccharides through electrostatic interactions, calcium ion (Ca2+) crosslinking, and lyophilization. Alginate/chitosan (AC) sponges with different concentrations of Sargassum pallidum polysaccharides were obtained and termed AC, ACS-1%, ACS-2.5%, and ACS-5%. ACS-1% and ACS-2.5% sponges exhibited uniform porosity, high water vapor transmission rate, high water absorption, as well as good hemostatic and antibacterial abilities. ACS-2.5% sponges facilitated wound closure and promoted angiogenesis and re-epithelialization in the dermis. These data suggest that ACS sponges containing a certain amount of Sargassum pallidum polysaccharides could be employed for treatment of full-thickness skin wounds.

Solid phase synthesis of oxidized sodium alginate-tobramycin conjugate and its application for infected wound healing.

Although sodium alginate possesses excellent biocompatibility, moisture retention and easy availability, it cannot be directly applied for infected wound treatment. Herein, a solid phase synthesis strategy was proposed to fabricate oxidized sodium alginate-tobramycin conjugate (OSA-TOB) for anti-infection dressing development. 13C nuclear magnetic resonance spectra indicated that the oxidization process does not change the ratio of ß-D-mannuronic acid (M) / α-L-guluronic acid (G) in OSA and the oxidization reaction shows no stereoselectivity. Elemental analysis disclosed that the graft ratio of tobramycin in OSA-TOB is 13.8 %. Antibacterial test indicated that OSA-TOB can effectively inhibit four prevalent pathogenic bacterial S.epidermidis, P. aeruginosa, S. aureus and E. coli via a different antibacterial mechanism compared to the original TOB. Hemolysis and cytotoxicity assays shown that OSA-TOB have superior hemocompatibility and cytocompatibility. Infected wound healing assay shown that the healing rate of OSA-TOB is the highest. Further analysis indicated that OSA-TOB can reduce the local inflammatory response, accelerate the form of epithelium and collagen deposition. In conclusions, OSA-TOB synthesized in solid phase can be potentially applied as a promising anti-infection wound dressing.

Progress in Research of Chitosan Chemical Modification Technologies and Their Applications.

Chitosan, which is derived from chitin, is the only known natural alkaline cationic polymer. Chitosan is a biological material that can significantly improve the living standard of the country. It has excellent properties such as good biodegradability, biocompatibility, and cell affinity, and has excellent biological activities such as antibacterial, antioxidant, and hemostasis. In recent years, the demand has increased significantly in many fields and has huge application potential. Due to the poor water solubility of chitosan, its wide application is limited. However, chemical modification of the chitosan matrix structure can improve its solubility and biological activity, thereby expanding its application range. The review covers the period from 1996 to 2022 and was elaborated by searching Google Scholar, PubMed, Elsevier, ACS publications, MDPI, Web of Science, Springer, and other databases. The various chemical modification methods of chitosan and its main activities and application research progress were reviewed. In general, the modification of chitosan and the application of its derivatives have had great progress, such as various reactions, optimization of conditions, new synthetic routes, and synthesis of various novel multifunctional chitosan derivatives. The chemical properties of modified chitosan are usually better than those of unmodified chitosan, so chitosan derivatives have been widely used and have more promising prospects. This paper aims to explore the latest progress in chitosan chemical modification technologies and analyze the application of chitosan and its derivatives in various fields, including pharmaceuticals and textiles, thus providing a basis for further development and utilization of chitosan.

Anti-photoaging effects of flexible nanoliposomes encapsulated Moringa oleifera Lam. isothiocyanate in UVB-induced cell damage in HaCaT cells.

Skin photoaging is premature skin aging damage that occurs after repeated exposure to ultraviolet (UV) radiation. Although isothiocyanates extracted from the moringa tree (Moringa oleifera Lam.) (MITC) exhibit excellent effects against skin photoaging, its application is restricted because of its characteristics, such as extremely low water solubility, bioavailability, and easy degradation. Currently, flexible nanoliposomes have gained increasing interest as a biocompatible polymer for applications such as transdermal drug delivery. We prepare amphiphilic hyaluronic acid (HA) conjugated with ceramide (CE) to modify nanoliposomes for MITC (HACE/MITC NPs) delivery. The HACE/MITC nanoparticles (NPs) are prepared and characterized for entrapment efficiency, particle size, polydispersity index, zeta potential, in vitro release, in vivo skin permeation, and in vitro protective effect of photoaging. The zeta potential of MITC NPs and HACE/MITC NPs is -24.46 mV and -24.93 mV, respectively. After modification of HACE, the entrapment efficient of MITC liposome increased from 62.54% to 70.67%, and the particle size decreased from 266.1 nm to 192.8 nm. In vivo skin permeation, permeated drug increased from 49.42 to 71.40%. Moreover, the results showed that the entrapment of MITC in nanoliposomes improves its stability, efficacy, and skin permeation. Further, HACE/MITC NPs are favorable for uptake by HaCaT cells without requiring changes in cell morphology, which significantly improves the activities of antioxidant enzymes, scavenges UVB-induced reactive oxygen species, protects skin from damage, and reduces MMP-1, MMP-3, and MMP-9 expression caused by radiation-induced photoaging. Our results strongly suggest that flexible nanoliposomes successfully improved the cell membrane permeation of MITC, and that anti-photoaging and HACE/MITC NPs can potentially be used as candidates for photoaging therapy.

Protective effects of GLHP from Gracilaria lemaneiformis against UVB-induced photodamage in human immortalized keratinocytes cells and BALB/c mice.

Our previous study showed that the water-soluble heteropolysaccharide extracted from Gracilaria lemaneiformis (GLHP) has excellent anti-inflammation and anti-oxidant properties. This study explored the efficacy of GLHP against skin anti-photoaging in human immortalized keratinocytes (HaCaT) cells and BALB/c mice under UVB irradiation. Cell viability, antiapoptotic, reactive oxygen species (ROS) scavenging activity, mitochondrial membrane potential, and cell wound scratch assays were conducted, as well as assessment of inflammation markers and sun protection factors. The in vitro results showed that GLHP pretreatment significantly inhibited UVB-induced apoptosis, reversed the decrease of cell viability via downregulating the expression of apoptosis-related protein caspase-3, accelerated the migration of HaCaT cells, and promoted wound healing. Notably, the protective effect of GLHP may be associated with the scavenging of ROS and the decrease of mitochondrial membrane potential. Moreover, GLHP pretreatment significantly restrained the upregulation of iNOS (UVB-induced inflammation marker), suppressed the expression of P-ERK and NF-κB, and decreased the activity of MMPs, suggesting that it exerts the therapeutic effects by inhibiting the MAPK/NF-κB signal pathway. Results obtained after conducting the in vivo assay confirmed that GLHP could reverse the UVB-induced increase of epidermal thickness in BALB/c mice. In conclusion, this study shows that GLHP can be utilized as a safer resource in the manufacture of anti-aging cosmetics because it exerts excellent anti-photoaging effects.

Use of 18ß-glycyrrhetinic acid nanocrystals to enhance anti-inflammatory activity by improving topical delivery.

18ß-Glycyrrhetinic acid (GA) is often topically applied in clinical treatment of inflammatory skin diseases. However, GA has poor solubility in water, which results in poor skin permeability and low bioavailability. Nanocrystallization of drugs can enhance their permeability and improve bioavailability. We prepared GA nanocrystals (Nano GA) by high-pressure homogenization. These nanocrystals were characterized by photon correlation spectroscopy, scanning electron microscopy, thermogravimetric analysis, and X-ray diffractometry. The ability of Nano GA to improve dermal permeability was investigated ex vivo using Franz diffusion vertical cells and mouse skin. The topical anti-inflammatory activity of Nano GA was assessed in vivo by a 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced model in mouse ears. The average particle size of a GA nanocrystalline suspension was 288.6 ± 7.3 nm, with a narrow particle-size distribution (polydispersity index ∼0.13 ± 0.10), and the particle size of the lyophilized powder increased (552.0 ± 9.8 nm). After nanocrystallization, the thermal stability and crystallinity decreased but solubility increased significantly. Nano GA showed higher dermal permeability than Coarse GA. Macroscopic and staining-based observations of mouse ears and the levels of proinflammatory factors and myeloperoxidase revealed that the Nano GA hydrogel exhibited better anti-edema ability and more strongly inhibited inflammation development than the Coarse GA hydrogel and indomethacin hydrogel (positive drug). These results suggest that Nano GA could be an efficacious topical therapeutic agent for skin inflammation.

Grafting of 18ß-Glycyrrhetinic Acid and Sialic Acid onto Chitosan to Produce a New Amphipathic Chitosan Derivative: Synthesis, Characterization, and Cytotoxicity.

Chitosan is the only cationic polysaccharide found in nature. It has broad application prospects in biomaterials, but its application is limited due to its poor solubility in water. A novel chitosan derivative was synthesized by amidation of chitosan with 18ß-glycyrrhetinic acid and sialic acid. The chitosan derivatives were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, and measurement of the zeta potential. We also investigated the solubility, cytotoxicity, and blood compatibility of chitosan derivatives. 18ß-glycyrrhetinic acid and sialic acid could be grafted onto chitosan molecular chains. The thermal stability of the synthesized chitosan derivatives was decreased and the surface was positively charged in water and phosphate-buffered saline. After chitosan had been modified by 18 ß-glycyrrhetinic acid and sialic acid, the solubility of chitosan was improved greatly in water and phosphate-buffered saline, and percent hemolysis was <5%. Novel amphiphilic chitosan derivatives could be suitable polymers for biomedical purposes.