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1.
ACS Appl Mater Interfaces ; 16(14): 17267-17284, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38556996

RESUMO

Postoperative peritoneal adhesions are a prevalent clinical issue following abdominal and pelvic surgery, frequently resulting in heightened personal and societal health burdens. Traditional biomedical barriers offer limited benefits because of practical challenges for doctors and their incompatibility with laparoscopic surgery. Hydrogel materials, represented by hyaluronic acid gels, are receiving increasing attention. However, existing antiadhesive gels still have limited effectiveness or carry the risk of complications in clinical applications. Herein, we developed a novel hydrogel using polysaccharide hemoadhican (HD) as the base material and polyethylene glycol diglycidyl ether (PEGDE) as the cross-linking agent. The HD hydrogels exhibit appropriate mechanical properties, injectability, and excellent cytocompatibility. We demonstrate resistance to protein adsorption and L929 fibroblast cell adhesion to the HD hydrogel. The biodegradability and efficacy against peritoneal adhesion are further evaluated in C57BL/6 mice. Our results suggest a potential strategy for anti-postoperative tissue adhesion barrier biomaterials.


Assuntos
Implantes Absorvíveis , Hidrogéis , Ratos , Camundongos , Animais , Hidrogéis/farmacologia , Ratos Sprague-Dawley , Aderências Teciduais/prevenção & controle , Camundongos Endogâmicos C57BL , Complicações Pós-Operatórias/prevenção & controle
2.
Biomacromolecules ; 25(2): 1119-1132, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38252967

RESUMO

Hydrogels composed of natural polysaccharides have been widely used as filling materials, with a growing interest in medical cosmetology and skin care. However, conventional commercial dermal fillers still have limitations, particularly in terms of mechanical performance and durability in vivo. In this study, a novel injectable and implantable hydrogel with adjustable characteristics was prepared from succinoglycan riclin by introducing PEG diglycidyl ether as a cross-linker. FTIR spectra confirmed the cross-linking reaction. The riclin hydrogels exhibited shear-thinning behavior, excellent mechanical properties, and cytocompatibility through in vitro experiments. Furthermore, when compared with subcutaneous injection of a commercial hyaluronic acid hydrogel, the riclin hydrogels showed enhanced persistence and biocompatibility in Balb/c mice after 16 weeks. These results demonstrate the great potential of the riclin-based hydrogel as an alternative to conventional commercial soft tissue fillers.


Assuntos
Hidrogéis , Engenharia Tecidual , Animais , Camundongos , Injeções Subcutâneas , Ácido Hialurônico , Excipientes , Camundongos Endogâmicos BALB C , Polietilenoglicóis , Éteres
3.
Int Immunopharmacol ; 128: 111512, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38199195

RESUMO

Acute lung injury (ALI) is a severe clinical condition with high mortality, characterized by rapid onset and limited treatment options. The pathogenesis of ALI involves inflammation and oxidative stress. The polysaccharide salecan, a water-soluble ß-(1,3)-D-glucan, has been found to possess numerous pharmaceutical effects, including anti-inflammatory properties, inhibition of oxidative stress, and anti-fatigue effects. This study aims to investigate the protective effect and underlying mechanism of salecan against LPS-induced ALI in mice. Using an in vivo LPS-induced ALI mouse model and an in vitro RAW264.7 cell system, we investigated the role of salecan in ALI with various experimental approaches, including histological staining, quantitative real-time PCR, flow cytometry, western blot analysis, and other relevant assays. Pre-treatment with salecan effectively attenuated LPS-induced ALI in vivo, reducing the severity of pulmonary edema, inflammation, and oxidative stress. NMR-based metabolomic profiling analysis revealed that salecan attenuated LPS-induced metabolic imbalances associated with ALI. Furthermore, salecan downregulated Keap1 and upregulated Nrf2 and HO-1 protein levels, indicating its modulation of the Keap1-Nrf2/HO-1 signaling pathway as a potential mechanism underlying its protective effects against ALI. In vitro studies on RAW264.7 cells revealed that salecan exhibited binding affinity towards macrophages, thereby alleviating LPS-induced apoptosis and inflammation, which underpin its therapeutic potential against ALI. Our study suggests that salecan can alleviate LPS-induced ALI by modulating oxidative stress, inflammatory response, and apoptosis through the activation of the Keap1-Nrf2/HO-1 pathway. These findings provide novel insights into the potential therapeutic use of salecan for the treatment of ALI.


Assuntos
Lesão Pulmonar Aguda , beta-Glucanas , Animais , Camundongos , Lesão Pulmonar Aguda/tratamento farmacológico , beta-Glucanas/uso terapêutico , Inflamação/tratamento farmacológico , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão/patologia , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo
4.
Int J Biol Macromol ; 257(Pt 2): 128695, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38072343

RESUMO

Effective management of excessive bleeding requires liquid hemostatic agents, especially in scenarios involving uncompressible and postoperative hemorrhage. This study introduces the microbial exopolysaccharide floccuronic acid (FA) as a liquid hemostatic agent, characterized by a high weight average molecular weight of 2.38 × 108 Da. The investigation focuses on the flocculation effect, hemostatic efficiency in both in vitro and in vivo settings, elucidating its hemostatic mechanism, and assessing its safety profile. Results reveal that FA solution significantly accelerates the coagulation process, leading to the formation of compact clots while specifically interfering with fibrin. Notably, FA demonstrates excellent hemostatic effects in animal liver models and a rat arterial rebleeding model. The biocompatible and biodegradable characteristics further underscore FA's potential as a valuable liquid hemostatic material, particularly suited for non-compressible and re-bleeding scenarios.


Assuntos
Hemostáticos , Ratos , Animais , Hemostáticos/farmacologia , Hemorragia/tratamento farmacológico , Hemostasia , Coagulação Sanguínea , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico
5.
Adv Healthc Mater ; 12(24): e2300705, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37029455

RESUMO

Uncontrolled hemorrhage is a leading cause of death, emphasizing the need for novel hemostatic agents. Here, a novel hemostatic polysaccharide hemoadhican (HD) is screened out by analyzing the rheological properties of screened material mixed blood sludges, which is prepared by mixing polysaccharide granules and whole blood to mimic the coagulation in vitro. HD is produced by a bacterial isolate Paenibacillus sp.1229, and the repeating units of HD are →)-α-L-Rhap-(1→3)-ß-D-Glcp-(1→4)[4,6-ethylidene-α-D-Galp-(1→4)-α-D-Glcp-(1→3)]-α-D-Manp-(1→. Compared to chitosan and celox, HD achieves more effective hemostasis in animal models with mouse and rat femoral arteries, rat carotid arteries, and rabbit femoral arteries. Especially, HD maintains an excellent hemostatic capability in animals with heparin-induced hemorrhage diathesis. In vitro experiments show HD granules can quickly absorb a small amount of blood component to create a hemophobic blood sludge resistant to high pressure. The blood sludge firmly adheres to damaged tissue and efficiently repels blood. In vitro experiments show that HD does not actively trigger blood coagulation cascade and is independent of blood conditions including heparin treatment. In addition, HD moisturizes wounds and accelerates wound healing, exhibiting excellent biodegradability, and hemocompatibility. The results indicate that HD is a promising hemostatic material for treating traumatic hemorrhages and uncontrollable surgical bleeding.


Assuntos
Quitosana , Hemostáticos , Ratos , Camundongos , Animais , Coelhos , Hemostáticos/farmacologia , Esgotos , Aderências Teciduais , Coagulação Sanguínea , Hemostasia , Hemorragia/tratamento farmacológico , Polissacarídeos , Heparina/farmacologia
6.
Carbohydr Polym ; 291: 119561, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35698387

RESUMO

Bioflocculants like polysaccharides are excellent alternatives to harmful synthetic flocculants and usability under stricter levels of ecosystem protection. In this study, an exopolysaccharide producing strain Paenibacillus sp. M21629 was isolated. The exopolysaccharide was abundant in carboxylic groups and named floccuronic acid with a high weight average molecular weight of 2.38 × 108 Da. The hexasaccharide repeating units of floccuronic acid were →3)-α-D-Manp-(1 â†’ 3)-4-Suc-ß-D-Manp-(1 â†’ 3)-ß-D-Glcp-(1 â†’ 4)-ß-D-GlcpA-(1 â†’ 4)[4,6-Pyr-ß-D-Galp-(1 â†’ 3)]-ß-D-Galp-(1→. The floccuronic acid at 0.5-1 ppm showed high turbidity removal efficiency in kaolin suspension (99.8%), coal wastewater (98.8%), and high-turbidity drinking water (89.2%). The flocculation ability of floccuronic acid depended on the instability of solid particles. Owing to these encouraging results, floccuronic acid is expected to be a useful bioflocculant applied in wastewater treatment and the utilization of water resources.


Assuntos
Paenibacillus , Purificação da Água , Ácidos , Ecossistema , Floculação , Águas Residuárias/química , Purificação da Água/métodos
7.
Int J Nanomedicine ; 17: 2629-2641, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35721271

RESUMO

Purpose: In order to overcome the inflammatory response to bacterial infection during wound healing, we have fabricated an antibacterial and anti-inflammatory wound dressing based on polysaccharide riclin and silver nanoparticles (AgNPs). Methods: The riclin-AgNPs nanocomposite was developed by borohydride method and was characterized by UV-Vis, TEM, XRD, Zeta potential, DLS. In vitro, we assessed the cumulative release, antibacterial activities and cytotoxicity. In vivo, we examined the wound healing in mice wound infection experiment and inflammatory mediators using histological observations and gene expression analysis. Results: The riclin/AgNPs nanocomposite hydrogel exhibited nanosized orbicular particles with high purity and stability. In vitro, the riclin/AgNPs showed sustained release of AgNPs, effective suppression in pathogen growth and negligible toxicity toward mammalian fibroblasts and macrophage cells. In vivo, the riclin/AgNPs treatment leads to faster and smoother growth of fresh skin with suppressed expression of inflammatory mediators. Conclusion: The reported Riclin-AgNPs nanocomposite hydrogel showed both antibacterial and anti-inflammatory functions, which induce significantly accelerated wound healing, indicating great potential as a novel attractive wound dressing material.


Assuntos
Nanopartículas Metálicas , Prata , Animais , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Bandagens , Mediadores da Inflamação , Mamíferos , Camundongos , Testes de Sensibilidade Microbiana , Nanogéis , Prata/farmacologia
8.
FASEB J ; 33(6): 6969-6979, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30841753

RESUMO

Most organisms on Earth possess circadian rhythms in their physiology and behaviors that allow them to resonate with the cycling environment over a 24-h period. However, in human society, a substantial quantity of jobs requires non-24-h working and rest or shift schedules, which causes more or less misalignment in circadian rhythms and disorders as a consequence. In this work, we conducted a sleep deprivation (SD) and non-24-h working and rest schedule (8 h on and 4 h off) experiment over 10 d in total and measured the changes in a series of physiologic and cognitive parameters. The results show that although the subjects could sleep during the schedule, their sleepiness increased significantly. Actigraphy data suggest that a 12-h schedule might result in chronic SD. Along with the increased sleepiness revealed by the Karolinska Sleepiness Scale questionnaire, the neurobehavioral psychomotor vigilance test data reveal that, compared with the control period, the reaction time of the subjects was significantly delayed. The saliva insulin levels were significantly changed in the morning in SD and non-24-h cycles. Salivary biochemical parameters were also altered, including aspartate aminotransferase and K+. 16S rRNA-based analysis of the salivary microbiota showed differentially changed patterns in bacteria composition and concentration. Together, these data demonstrate that an abnormal working and rest schedule might produce comprehensive interference with circadian rhythms, metabolism, and cognition.-Ma, H., Li, Y., Liang, H., Chen, S., Pan, S., Chang, L., Li, S., Zhang, Y., Liu, X., Xu, Y., Shao, Y., Yang, Y., Guo, J. Sleep deprivation and a non-24-h working schedule lead to extensive alterations in physiology and behavior.


Assuntos
Ritmo Circadiano/fisiologia , Monitorização Fisiológica , Privação do Sono/fisiopatologia , Tolerância ao Trabalho Programado , Fosfatase Alcalina/metabolismo , Aspartato Aminotransferases/metabolismo , Bactérias/classificação , Cloretos/química , Cloretos/metabolismo , Humanos , Hidrocortisona/química , Hidrocortisona/metabolismo , Comportamento Impulsivo , Insulina/química , Insulina/metabolismo , Masculino , Saliva/química , Saliva/microbiologia , Sono/fisiologia , Sódio/química , Sódio/metabolismo , Ácido Úrico/química , Ácido Úrico/metabolismo , Adulto Jovem
9.
Genetics ; 206(4): 1881-1893, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28600326

RESUMO

Nonsense-mediated RNA decay (NMD) is a crucial post-transcriptional regulatory mechanism that recognizes and eliminates aberrantly processed transcripts, and mediates the expression of normal gene transcripts. In this study, we report that in the filamentous fungus Neurospora crassa, the NMD factors play a conserved role in regulating the surveillance of NMD targets including premature termination codon (PTC)-containing transcripts and normal transcripts. The circadian rhythms in all of the knockout strains of upf1-3 genes, which encode the Up-frameshift proteins, were aberrant. The upf1 knockout strain displays a shortened circadian period, which can be restored by constantly expressing exogenous Up-frameshift protein 1 (UPF1). UPF1 regulates the circadian clock by modulating the splicing of the core clock gene frequency (frq) through spliceosome and spliceosome-related arginine/serine-rich splicing factors, which partly account for the short periods in the upf1 knockout strain. We also demonstrated that the clock genes including White Collar (WC)-1, WC-2, and FRQ are involved in controlling the diurnal growth rhythm, and UPF1 may affect the growth rhythms by mediating the FRQ protein levels in the daytime. These findings suggest that the NMD factors play important roles in regulating the circadian clock and diurnal growth rhythms in Neurospora.


Assuntos
Ritmo Circadiano/genética , Proteínas Fúngicas/genética , RNA Helicases/genética , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/genética , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/metabolismo , Proteínas Fúngicas/metabolismo , Neurospora crassa/genética , Neurospora crassa/fisiologia , Degradação do RNAm Mediada por Códon sem Sentido , RNA Helicases/metabolismo , Fatores de Processamento de RNA/genética , Fatores de Processamento de RNA/metabolismo , Spliceossomos/genética , Spliceossomos/metabolismo
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