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1.
Molecules ; 29(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38893567

RESUMO

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.


Assuntos
Antioxidantes , Quitosana , Curcumina , Micelas , Curcumina/farmacologia , Curcumina/química , Quitosana/química , Antioxidantes/farmacologia , Antioxidantes/química , Nanopartículas/química , Animais , Peixe-Zebra , Portadores de Fármacos/química , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Tensoativos/química
2.
Molecules ; 28(8)2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37110834

RESUMO

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.

3.
Molecules ; 28(11)2023 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-37298838

RESUMO

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.


Assuntos
Quitosana , Envelhecimento da Pele , Dermatopatias , Camundongos , Animais , Quitosana/farmacologia , Quitosana/metabolismo , Dermatopatias/metabolismo , Pele/metabolismo , Colágeno/metabolismo , Raios Ultravioleta
4.
Mar Drugs ; 20(8)2022 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-36005539

RESUMO

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.


Assuntos
Quitosana , Antibacterianos/química , Antibacterianos/farmacologia , Quitina/química , Quitosana/química , Solubilidade
5.
Molecules ; 26(2)2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33467083

RESUMO

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.


Assuntos
Quitosana , Ácido Glicirretínico/análogos & derivados , Teste de Materiais , Ácido N-Acetilneuramínico , Linhagem Celular , Quitosana/análogos & derivados , Quitosana/síntese química , Quitosana/química , Quitosana/farmacologia , Ácido Glicirretínico/química , Ácido Glicirretínico/farmacologia , Humanos , Ácido N-Acetilneuramínico/química , Ácido N-Acetilneuramínico/farmacologia , Solubilidade
6.
Mar Drugs ; 18(5)2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32365733

RESUMO

Our earlier research indicated that chitosan-gentamicin conjugate (CS-GT) possesses superior antimicrobial activity and good water solubility. To develop CS-GT-based scald dressings, the antibacterial properties of CS-GT were further studied, and the biosafety of CS-GT and the healing mechanism of CS-GT hydrogel was systematically explored in this article. It was found that cell viability shows a declined inclination with the prolonged culture time and the increased concentration of CS-GT. After three day's culture, the cell viability could still remain at 79.72% when CS-GT concentration was as high as 1000 µg/mL. On the other hand, the hemolysis rate of CS-GT was lower than 5% when its concentration is 800 µg/mL. Therefore CS-GT has good cytocompatibility and hemocompatibility. A wound-healing experiment has shown that the skin healing rate of CS-GT hydrogel was the highest at 99.61%, followed by the positive control (wet burn ointment) 94.98%, GT hydrogel 87.50%, and matrix 77.39%. The blank control group, however, possessed the lowest healing rate of 75.45%. Further analysis indicated that CS-GT hydrogel could promote the synthesis of total protein (TP) in skin granulation tissue, resulting in the enhanced hydroxyproline (HYP) content, which facilitated collagen fibrogenesis, reduced cytokine expression in an inflammatory response, and, ultimately, accelerated wound healing. To sum up, CS-GT hydrogel is a promising scald dressing.


Assuntos
Antibacterianos/administração & dosagem , Queimaduras/tratamento farmacológico , Quitosana/administração & dosagem , Gentamicinas/administração & dosagem , Administração Cutânea , Animais , Antibacterianos/farmacologia , Curativos Hidrocoloides , Sobrevivência Celular/efeitos dos fármacos , Quitosana/farmacologia , Quimioterapia Combinada , Feminino , Gentamicinas/farmacologia , Hidrogéis , Masculino , Testes de Sensibilidade Microbiana , Modelos Animais , Coelhos , Cicatrização/efeitos dos fármacos
7.
Molecules ; 24(14)2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31315269

RESUMO

Mussel adhesive proteins (MAPs) have a unique ability to firmly adhere to different surfaces in aqueous environments via the special amino acid, 3,4-dihydroxyphenylalanine (DOPA). The catechol groups in DOPA are a key group for adhesive proteins, which is highly informative for the biomedical domain. By simulating MAPs, medical products can be developed for tissue adhesion, drug delivery, and wound healing. Hydrogel is a common formulation that is highly adaptable to numerous medical applications. Based on a discussion of the adhesion mechanism of MAPs, this paper reviews the formation and adhesion mechanism of catechol-functionalized hydrogels, types of hydrogels and main factors affecting adhesion, and medical applications of hydrogels, and future the development of catechol-functionalized hydrogels.


Assuntos
Bivalves/química , Catecóis/química , Animais , Bivalves/metabolismo , Di-Hidroxifenilalanina/química , Sistemas de Liberação de Medicamentos , Hidrogéis , Proteínas/metabolismo , Aderências Teciduais , Cicatrização
8.
Mar Drugs ; 15(11)2017 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-29112116

RESUMO

Classic hypotheses of Alzheimer's disease (AD) include cholinergic neuron death, acetylcholine (ACh) deficiency, metal ion dynamic equilibrium disorder, and deposition of amyloid and tau. Increased evidence suggests neuroinflammation and oxidative stress may cause AD. However, none of these factors induces AD independently, but they are all associated with the formation of Aß and tau proteins. Current clinical treatments based on ACh deficiency can only temporarily relieve symptoms, accompanied with many side-effects. Hence, searching for natural neuroprotective agents, which can significantly improve the major symptoms and reverse disease progress, have received great attention. Currently, several bioactive marine products have shown neuroprotective activities, immunomodulatory and anti-inflammatory effects with low toxicity and mild side effects in laboratory studies. Recently, chitosan (CTS), chitooligosaccharide (COS) and their derivatives from exoskeletons of crustaceans and cell walls of fungi have shown neuroprotective and antioxidative effects, matrix metalloproteinase inhibition, anti-HIV and anti-inflammatory properties. With regards to the hypotheses of AD, the neuroprotective effect of CTS, COS, and their derivatives on AD-like changes in several models have been reported. CTS and COS exert beneficial effects on cognitive impairments via inhibiting oxidative stress and neuroinflammation. They are also a new type of non-toxic ß-secretase and AChE inhibitor. As neuroprotective agents, they could reduce the cell membrane damage caused by copper ions and decrease the content of reactive oxygen species. This review will focus on their anti-neuroinflammation, antioxidants and their inhibition of ß-amyloid, acetylcholinesterase and copper ions adsorption. Finally, the limitations and future work will be discussed.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Quitina/análogos & derivados , Quitosana/análogos & derivados , Quitosana/uso terapêutico , Quitina/química , Quitina/uso terapêutico , Inibidores da Colinesterase/química , Inibidores da Colinesterase/uso terapêutico , Cobre , Humanos , Oligossacarídeos
9.
Int J Biol Macromol ; 274(Pt 1): 133265, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38909732

RESUMO

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.

10.
Metallomics ; 16(1)2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-38183290

RESUMO

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.


Assuntos
2,2'-Dipiridil/análogos & derivados , Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Complexos de Coordenação , Neoplasias Pulmonares , Compostos Organometálicos , Rutênio , Animais , Humanos , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/patologia , Rutênio/química , Fator 2 Relacionado a NF-E2/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias Pulmonares/patologia , Peixe-Zebra/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Antineoplásicos/química , Linhagem Celular Tumoral , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico
11.
Mater Today Bio ; 26: 101090, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38800564

RESUMO

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.

12.
Stem Cell Res ; 66: 102992, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36502619

RESUMO

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.


Assuntos
Células-Tronco Pluripotentes Induzidas , Doenças Neurodegenerativas , Humanos , Feminino , Criança , Células-Tronco Pluripotentes Induzidas/metabolismo , Leucócitos Mononucleares/metabolismo , Proteínas de Transporte/genética , Doenças Neurodegenerativas/genética , Encéfalo/metabolismo , Diferenciação Celular
13.
Genes (Basel) ; 14(3)2023 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-36980825

RESUMO

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.


Assuntos
Proteínas de Ligação ao GTP , Doenças Mitocondriais , Criança , Pré-Escolar , Humanos , Lactente , Masculino , Proteínas de Ligação ao GTP/genética , Hiperlactatemia , Doenças Mitocondriais/complicações , Doenças Mitocondriais/genética , Doenças Mitocondriais/patologia , Convulsões
14.
Front Pharmacol ; 14: 1173110, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37168991

RESUMO

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.

15.
Biomolecules ; 13(11)2023 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-38002276

RESUMO

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.


Assuntos
Quitosana , Quitosana/farmacologia , Anidridos Succínicos , Micelas , Antibacterianos/farmacologia , Ácido Desoxicólico/farmacologia
16.
Gene ; 879: 147587, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37364699

RESUMO

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.


Assuntos
MicroRNAs , Polimorfismo de Nucleotídeo Único , Feminino , Humanos , Masculino , Estudos de Casos e Controles , População do Leste Asiático , Predisposição Genética para Doença , Genótipo , MicroRNAs/genética
17.
Carbohydr Polym ; 295: 119843, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35988976

RESUMO

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.


Assuntos
Anti-Infecciosos , Infecção dos Ferimentos , Humanos , Alginatos/farmacologia , Antibacterianos/farmacologia , Escherichia coli , Pseudomonas aeruginosa , Técnicas de Síntese em Fase Sólida , Staphylococcus aureus , Tobramicina/farmacologia , Cicatrização , Infecção dos Ferimentos/microbiologia
18.
Drug Deliv ; 29(1): 871-881, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35277099

RESUMO

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.


Assuntos
Moringa oleifera , Nanopartículas , Células HaCaT , Humanos , Isotiocianatos/farmacologia , Tamanho da Partícula
19.
Biomolecules ; 12(11)2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36358951

RESUMO

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.


Assuntos
Quitosana , Hemostáticos , Sargassum , Quitosana/farmacologia , Alginatos/farmacologia , Polissacarídeos/farmacologia , Antibacterianos/farmacologia
20.
Int J Biol Macromol ; 173: 591-606, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33508359

RESUMO

Chitosan-based thermosensitive hydrogels have been widely used in drug delivery and tissue engineering, but their poor bioactivity has limited their further applications. Integral active oyster peptide microspheres (OPM) with an average particle diameter of 3.9 µm were prepared with high encapsulation efficiency (72.8%) and loading capacity (11.9%), exhibiting desirable sustained release effects. Using catechol functionalized chitosan (CS-C) as the polymeric matrix, OPM as the filler, and ß-sodium glycerophosphate (ß-GP) as a thermal sensitizer, the thermosensitive hydrogel CS-C/OPM/ß-GP was prepared. Besides, the application of the hydrogel on wound healing was studied, and its biosafety was evaluated. The results of cell migration in vitro showed that the cell migration rate of CS-C/OPM/ß-GP reached 97.47 ± 5.41% within 48 h, indicating that the hydrogel accelerated the migration of L929 cells. As demonstrated in the mouse skin wound experiment, CS-C/OPM/ß-GP hydrogel not only inhibited the aggregation of diversified inflammatory cells and accelerated the generation of collagen fibers and new blood vessels of the wound, but also enhanced the synthesis of total protein (TP) in granulation tissue, and up-regulated the expression of Ki-67 and VEGF in the injury, thereby achieving fast wound healing. Safety evaluation results showed that CS-C/OPM/ß-GP hydrogel was not cytotoxic to L929 cells, and the hemolysis ratio was less than 5% within 1 mg/mL. In conclusion, CS-C/OPM/ß-GP hydrogel is expected as a promising medical dressing for wound healing.


Assuntos
Antibacterianos/administração & dosagem , Catecóis/administração & dosagem , Quitosana/administração & dosagem , Ostreidae/metabolismo , Peptídeos/química , Pele/lesões , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Catecóis/química , Catecóis/farmacologia , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Quitosana/química , Quitosana/farmacologia , Glicerofosfatos/química , Hemólise , Hidrogéis , Camundongos , Microesferas , Pele/efeitos dos fármacos
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