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1.
J Agric Food Chem ; 72(32): 17964-17976, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39096281

RESUMO

Spinal cord injury (SCI) is one of the most serious health problems, with no effective therapy. Recent studies indicate that Fisetin, a natural polyphenolic flavonoid, exhibits multiple functions, such as life-prolonging, antioxidant, antitumor, and neuroprotection. However, the restorative effects of Fisetin on SCI and the underlying mechanism are still unclear. In the present study, we found that Fisetin reduced LPS-induced apoptosis and oxidative damage in PC12 cells and reversed LPS-induced M1 polarization in BV2 cells. Additionally, Fisetin safely and effectively promoted the motor function recovery of SCI mice by attenuating neurological damage and promoting neurogenesis at the lesion. Moreover, Fisetin administration inhibited glial scar formation, modulated microglia/macrophage polarization, and reduced neuroinflammation. Network pharmacology, RNA-seq, and molecular biology revealed that Fisetin inhibited the activation of the JAK2/STAT3 signaling pathway. Notably, Colivelin TFA, an activator of JAK2/STAT3 signaling, attenuated Fis-mediated neuroinflammation inhibition and therapeutic effects on SCI mice. Collectively, Fisetin promotes functional recovery after SCI by inhibiting microglia/macrophage M1 polarization and the JAK2/STAT3 signaling pathway. Thus, Fisetin may be a promising therapeutic drug for the treatment of SCI.


Assuntos
Flavonóis , Janus Quinase 2 , Macrófagos , Microglia , Fator de Transcrição STAT3 , Transdução de Sinais , Traumatismos da Medula Espinal , Animais , Humanos , Masculino , Camundongos , Ratos , Polaridade Celular/efeitos dos fármacos , Flavonoides/farmacologia , Flavonoides/administração & dosagem , Flavonóis/farmacologia , Janus Quinase 2/metabolismo , Janus Quinase 2/genética , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/imunologia , Células PC12 , Recuperação de Função Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/fisiopatologia , Traumatismos da Medula Espinal/imunologia , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética
2.
Adv Biol (Weinh) ; : e2400201, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39113431

RESUMO

Cryopreservation of immune cells is considered as a key enabling technology for adoptive cellular immunotherapy. However, current immune cell cryopreservation technologies face the challenges with poor biocompatibility of cryoprotection materials, low efficiency, and impaired post-thaw function, limiting their clinical translation. This review briefly introduces the adoptive cellular immunotherapy and the approved immune cell-based products, which involve T cells, natural killer cells and etc. The cryodamage mechanisms to these immune cells during cryopreservation process are described, including ice formation related mechanical and osmotic injuries, cryoprotectant induced toxic injuries, and other biochemical injuries. Meanwhile, the recent advances in the cryopreservation medium and freeze-thaw protocol for several representative immune cell type are summarized. Furthermore, the remaining challenges regarding on the cryoprotection materials, freeze-thaw protocol, and post-thaw functionality evaluation of current cryopreservation technologies are discussed. Finally, the future perspectives are proposed toward advancing highly efficient cryopreservation of immune cells.

3.
Mater Today Bio ; 26: 101113, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38933414

RESUMO

Burns represent a prevalent global health concern and are particularly susceptible to bacterial infections. Severe infections may lead to serious complications, posing a life-threatening risk. Near-infrared (NIR)-assisted photothermal antibacterial combined with antioxidant hydrogel has shown significant potential in the healing of infected wounds. However, existing photothermal agents are typically metal-based, complicated to synthesize, or pose biosafety hazards. In this study, we utilized plant-derived blackcurrant extract (B) as a natural source for both photothermal and antioxidant properties. By incorporating B into a G-O hydrogel crosslinked through Schiff base reaction between gelatin (G) and oxidized pullulan (O), the resulting G-O-B hydrogel exhibited good injectability and biocompatibility along with robust photothermal and antioxidant activities. Upon NIR irradiation, the controlled temperature (around 45-50 °C) generated by the G-O-B hydrogel resulted in rapid (10 min) and efficient killing of Staphylococcus aureus (99 %), Escherichia coli (98 %), and Pseudomonas aeruginosa (82 %). Furthermore, the G-O-B0.5 hydrogel containing 0.5 % blackcurrant extract promoted collagen deposition, angiogenesis, and accelerated burn wound closure conclusively, demonstrating that this well-designed and extract-contained hydrogel dressing holds immense potential for enhancing the healing process of bacterial-infected burn wounds.

4.
Acta Biomater ; 184: 156-170, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38897336

RESUMO

Bacterial infections are a serious threat to wound healing and skin regeneration. In recent years, photothermal therapy (PTT) has become one of the most promising tools in the treatment of infectious diseases. However, wound dressings with photo-responsive properties are currently still limited by the difficulties of biosafety and thermal stability brought by the introduction of photosensitizers or photothermal agents. Therefore, how to improve the therapeutic efficiency and biosafety from material design is still a major challenge at present. In this study, the carboxymethyl chitosan (CMCS) and protocatechuic aldehyde (PA) hydrogels based on horseradish peroxidase (HRP) and hydrogen peroxide (H2O2) enzymatic catalysis was developed. Therein, HRP and H2O2 catalyzed cross-linking while polymerizing PA, which not only endowed the hydrogels with photothermal responsiveness but also with good biosafety through this enzyme-catalyzed green approach. Meanwhile, the hydrogels possessed highly efficient bacteriostatic ability with the assistance of near infrared (NIR). Moreover, the ultra-rapid gelation, strong tissue adhesion, high swelling ability, good antioxidant property and hemostatic property of the CMCS-PA hydrogels based on HRP/H2O2 enzymatic catalysis were suitable for the treatment of skin wounds. Meanwhile, NIR-assistant CMCS-PA hydrogels based on HRP/H2O2 enzymatic catalysis reduced inflammation, decreased bacterial infection, and promoted collagen deposition and angiogenesis, which showed remarkable therapeutic effects in a skin wound infection model. All results indicate that this green approach to introduce photothermal property by HRP-catalyzed PA polymerization endows the hydrogels with efficient photothermal conversion efficiency, suggesting that they are promising to provide new options for replacing photothermal agents and photosensitizers. STATEMENT OF SIGNIFICANCE: In recent years, wound dressings with photo-responsive properties are currently still limited by the difficulties of biosafety and thermal stability brought by the introduction of agent photosensitizers or photothermal agents. In this study, the carboxymethyl chitosan and protocatechuic aldehyde hydrogels based on horseradish peroxidase and hydrogen peroxide enzymatic catalysis was developed. The photothermal properties of hydrogels were transformed from absent to present just by horseradish peroxidase-catalyzed protocatechuic aldehyde polymerization in a green approach. Meanwhile, the hydrogels possessed highly efficient bacteriostatic ability with the assistance of near infrared. The green approach of introducing photothermal properties from material design solves the biosafety challenge. Therefore, this study is expected to provide new options for alternative photothermal agents and photosensitizers.


Assuntos
Antibacterianos , Antioxidantes , Quitosana , Hidrogéis , Cicatrização , Hidrogéis/química , Hidrogéis/farmacologia , Hidrogéis/síntese química , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Antioxidantes/farmacologia , Antioxidantes/química , Quitosana/química , Quitosana/farmacologia , Quitosana/análogos & derivados , Peróxido de Hidrogênio , Química Verde , Pele/patologia , Pele/efeitos dos fármacos , Hemostasia/efeitos dos fármacos , Camundongos , Peroxidase do Rábano Silvestre/química , Infecção dos Ferimentos/tratamento farmacológico , Infecção dos Ferimentos/patologia , Infecção dos Ferimentos/microbiologia
5.
Int J Biol Macromol ; 268(Pt 1): 131739, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38657920

RESUMO

Alzheimer's disease (AD) is a chronic neurodegenerative disease with high prevalence, long duration and poor prognosis. The blood-brain barrier (BBB) is a physiologic barrier in the central nervous system, which hinders the entry of most drugs into the brain from the blood, thus affecting the efficacy of drugs for AD. Natural products are recognized as one of the promising and unique therapeutic approaches to treat AD. To improve the efficiency and therapeutic effect of the drug across the BBB, a natural polyphenolic compound, procyanidin C-1 (C1) was encapsulated in glucose-functionalized bovine serum albumin (BSA) nanoparticles to construct Glu-BSA/C1 NPs in our study. Glu-BSA/C1 NPs exhibited good stability, slow release, biocompatibility and antioxidant properties. In addition, Glu-BSA/C1 NPs penetrated the BBB, accumulated in the brain by targeting Glut1, and maintained the BBB integrity both in vitro and in vivo. Moreover, Glu-BSA/C1 NPs alleviated memory impairment of 5 × FAD mice by reducing Aß deposition and Tau phosphorylation and promoting neurogenesis. Mechanistically, Glu-BSA/C1 NPs significantly activated the PI3K/AKT pathway and inhibited the NLRP3/Caspase-1/IL-1ß pathway thereby suppressing neuroinflammation. Taken together, Glu-BSA/C1 NPs could penetrate the BBB and mitigate neuroinflammation in AD, which provides a new therapeutic approach targeting AD.


Assuntos
Doença de Alzheimer , Barreira Hematoencefálica , Modelos Animais de Doenças , Glucose , Nanopartículas , Soroalbumina Bovina , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/efeitos dos fármacos , Animais , Soroalbumina Bovina/química , Camundongos , Glucose/metabolismo , Nanopartículas/química , Proantocianidinas/farmacologia , Proantocianidinas/química , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Biflavonoides/farmacologia , Biflavonoides/química , Catequina/farmacologia , Catequina/química , Catequina/análogos & derivados , Humanos , Masculino
6.
Mil Med Res ; 11(1): 27, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38685116

RESUMO

BACKGROUND: The channel-forming protein Pannexin1 (Panx1) has been implicated in both human studies and animal models of chronic pain, but the underlying mechanisms remain incompletely understood. METHODS: Wild-type (WT, n = 24), global Panx1 KO (n = 24), neuron-specific Panx1 KO (n = 20), and glia-specific Panx1 KO (n = 20) mice were used in this study at Albert Einstein College of Medicine. The von Frey test was used to quantify pain sensitivity in these mice following complete Freund's adjuvant (CFA) injection (7, 14, and 21 d). The qRT-PCR was employed to measure mRNA levels of Panx1, Panx2, Panx3, Cx43, Calhm1, and ß-catenin. Laser scanning confocal microscopy imaging, Sholl analysis, and electrophysiology were utilized to evaluate the impact of Panx1 on neuronal excitability and morphology in Neuro2a and dorsal root ganglion neurons (DRGNs) in which Panx1 expression or function was manipulated. Ethidium bromide (EtBr) dye uptake assay and calcium imaging were employed to investigate the role of Panx1 in adenosine triphosphate (ATP) sensitivity. ß-galactosidase (ß-gal) staining was applied to determine the relative cellular expression levels of Panx1 in trigeminal ganglia (TG) and DRG of transgenic mice. RESULTS: Global or neuron-specific Panx1 deletion markedly decreased pain thresholds after CFA stimuli (7, 14, and 21 d; P < 0.01 vs. WT group), indicating that Panx1 was positively correlated with pain sensitivity. In Neuro2a, global Panx1 deletion dramatically reduced neurite extension and inward currents compared to the WT group (P < 0.05), revealing that Panx1 enhanced neurogenesis and excitability. Similarly, global Panx1 deletion significantly suppressed Wnt/ß-catenin dependent DRG neurogenesis following 5 d of nerve growth factor (NGF) treatment (P < 0.01 vs. WT group). Moreover, Panx1 channels enhanced DRG neuron response to ATP after CFA injection (P < 0.01 vs. Panx1 KO group). Furthermore, ATP release increased Ca2+ responses in DRGNs and satellite glial cells surrounding them following 7 d of CFA treatment (P < 0.01 vs. Panx1 KO group), suggesting that Panx1 in glia also impacts exaggerated neuronal excitability. Interestingly, neuron-specific Panx1 deletion was found to markedly reduce differentiation in cultured DRGNs, as evidenced by stunted neurite outgrowth (P < 0.05 vs. Panx1 KO group; P < 0.01 vs. WT group or GFAP-Cre group), blunted activation of Wnt/ß-catenin signaling (P < 0.01 vs. WT, Panx1 KO and GFAP-Cre groups), and diminished cell excitability (P < 0.01 vs. GFAP-Cre group) and response to ATP stimulation (P < 0.01 vs. WT group). Analysis of ß-gal staining showed that cellular expression levels of Panx1 in neurons are significantly higher (2.5-fold increase) in the DRG than in the TG. CONCLUSIONS: The present study revealed that neuronal Panx1 is a prominent driver of peripheral sensitivity in the setting of inflammatory pain through cell-autonomous effects on neuronal excitability. This hyperexcitability dependence on neuronal Panx1 contrasts with inflammatory orofacial pain, where similar studies revealed a prominent role for glial Panx1. The apparent differences in Panx1 expression in neuronal and non-neuronal TG and DRG cells are likely responsible for the distinct impact of these cell types in the two pain models.


Assuntos
Conexinas , Proteínas do Tecido Nervoso , Animais , Conexinas/genética , Camundongos , Proteínas do Tecido Nervoso/genética , Modelos Animais de Doenças , Dor/fisiopatologia , Dor/etiologia , Neurônios/metabolismo , Inflamação/fisiopatologia , Camundongos Knockout , Masculino
7.
Int J Biol Macromol ; 267(Pt 2): 131520, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38615859

RESUMO

The adverse microenvironment, including neuroinflammation, hinders the recovery of spinal cord injury (SCI). Regulating microglial polarization to alleviate neuroinflammation at the injury site is an effective strategy for SCI recovery. MG53 protein exerts obvious repair ability on multiple tissues damage, but with short half-life. In this study, we composited an innovative MG53/GMs/HA-Dex neural scaffold using gelatin microspheres (GMs), hyaluronic acid (HA), and dextran (Dex) loaded with MG53 protein. This novel neural scaffold could respond to MMP-2/9 protein and stably release MG53 protein with good physicochemical properties and biocompatibility. In addition, it significantly improved the motor function of SCI mice, suppressed M1 polarization of microglia and neuroinflammation, and promoted neurogenesis and axon regeneration. Further mechanistic experiments demonstrated that MG53/GMs/HA-Dex hydrogel inhibited the JAK2/STAT3 signaling pathway. Thus, this MG53/GMs/HA-Dex neural scaffold promotes the functional recovery of SCI mice by alleviating neuroinflammation, which provides a new intervention strategy for the neural regeneration and functional repair of SCI.


Assuntos
Gelatina , Ácido Hialurônico , Janus Quinase 2 , Doenças Neuroinflamatórias , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismo , Animais , Camundongos , Recuperação de Função Fisiológica/efeitos dos fármacos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Doenças Neuroinflamatórias/tratamento farmacológico , Gelatina/química , Gelatina/farmacologia , Janus Quinase 2/metabolismo , Dextranos/química , Alicerces Teciduais/química , Microesferas , Fator de Transcrição STAT3/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Regeneração Nervosa/efeitos dos fármacos , Metaloproteinase 9 da Matriz/metabolismo , Modelos Animais de Doenças , Neurogênese/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Metaloproteinase 2 da Matriz/metabolismo , Hidrogéis/química , Hidrogéis/farmacologia
8.
J Cell Mol Med ; 28(6): e18129, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38426936

RESUMO

ATP citrate lyase (ACLY), as a key enzyme in lipid metabolism, plays an important role in energy metabolism and lipid biosynthesis of a variety of tumours. Many studies have shown that ACLY is highly expressed in various tumours, and its pharmacological or gene inhibition significantly inhibits tumour growth and progression. However, the roles of ACLY in oesophageal squamous cell carcinoma (ESCC) remain unclear. Here, our data showed that ACLY inhibitor significantly attenuated cell proliferation, migration, invasion and lipid synthesis in different ESCC cell lines, whereas the proliferation, migration, invasion and lipid synthesis of ESCC cells were enhanced after ACLY overexpression. Furthermore, ACLY inhibitor dramatically suppressed tumour growth and lipid metabolism in ESCC cells xenografted tumour model, whereas ACLY overexpression displayed the opposite effect. Mechanistically, ACLY protein harboured acetylated modification and interacted with SIRT2 protein in ESCC cells. The SIRT2 inhibitor AGK2 significantly increased the acetylation level of ACLY protein and inhibited the proliferation and migration of ESCC cells, while overexpression of ACLY partially reversed the inhibitory effect of AGK2 on ESCC cells. Overall, these results suggest that targeting the SIRT2/ACLY signalling axis may be a potential therapeutic strategy for ESCC patients.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Humanos , Carcinoma de Células Escamosas do Esôfago/genética , ATP Citrato (pro-S)-Liase , Sirtuína 2/genética , Sirtuína 2/metabolismo , Proliferação de Células , Neoplasias Esofágicas/metabolismo , Lipídeos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica
9.
Am J Pathol ; 194(6): 975-988, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38423356

RESUMO

Radiation-induced enteritis, a significant concern in abdominal radiation therapy, is associated closely with gut microbiota dysbiosis. The mucus layer plays a pivotal role in preventing the translocation of commensal and pathogenic microbes. Although significant expression of REGγ in intestinal epithelial cells is well established, its role in modulating the mucus layer and gut microbiota remains unknown. The current study revealed notable changes in gut microorganisms and metabolites in irradiated mice lacking REGγ, as compared to wild-type mice. Concomitant with gut microbiota dysbiosis, REGγ deficiency facilitated the infiltration of neutrophils and macrophages, thereby exacerbating intestinal inflammation after irradiation. Furthermore, fluorescence in situ hybridization assays unveiled an augmented proximity of bacteria to intestinal epithelial cells in REGγ knockout mice after irradiation. Mechanistically, deficiency of REGγ led to diminished goblet cell populations and reduced expression of key goblet cell markers, Muc2 and Tff3, observed in both murine models, minigut organoid systems and human intestinal goblet cells, indicating the intrinsic role of REGγ within goblet cells. Interestingly, although administration of broad-spectrum antibiotics did not alter the goblet cell numbers or mucin 2 (MUC2) secretion, it effectively attenuated inflammation levels in the ileum of irradiated REGγ absent mice, bringing them down to the wild-type levels. Collectively, these findings highlight the contribution of REGγ in counteracting radiation-triggered microbial imbalances and cell-autonomous regulation of mucin secretion.


Assuntos
Enterite , Microbioma Gastrointestinal , Células Caliciformes , Homeostase , Camundongos Knockout , Mucina-2 , Complexo de Endopeptidases do Proteassoma , Animais , Humanos , Camundongos , Disbiose/microbiologia , Disbiose/metabolismo , Enterite/microbiologia , Enterite/metabolismo , Enterite/patologia , Células Caliciformes/patologia , Células Caliciformes/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Camundongos Endogâmicos C57BL , Mucina-2/metabolismo , Proteínas Associadas a Pancreatite/metabolismo , Lesões por Radiação/metabolismo , Lesões por Radiação/microbiologia , Lesões por Radiação/patologia , Lesões Experimentais por Radiação/metabolismo , Lesões Experimentais por Radiação/patologia , Lesões Experimentais por Radiação/microbiologia , Fator Trefoil-3/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Complexo de Endopeptidases do Proteassoma/efeitos da radiação , Autoantígenos/genética , Autoantígenos/metabolismo , Autoantígenos/efeitos da radiação
10.
Mol Carcinog ; 63(5): 897-911, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38353358

RESUMO

Increasing evidence has demonstrated that glutaminase (GLS) as a key mitochondrial enzyme plays a pivotal role in glutaminolysis, which widely participates in glutamine metabolism serving as main energy sources and building blocks for tumor growth. However, the roles and molecular mechanisms of GLS in esophageal squamous cell carcinoma (ESCC) remains unknown. Here, we found that GLS was highly expressed in ESCC tissues and cells. GLS inhibitor CB-839 significantly suppressed cell proliferation, colony formation, migration and invasion of ESCC cells, whereas GLS overexpression displayed the opposite effects. In addition, CB-839 markedly suppressed glucose consumption and lactate production, coupled with the downregulation of glycolysis-related proteins HK2, PFKM, PKM2 and LDHA, whereas GLS overexpression exhibited the adverse results. In vivo animal experiment revealed that CB-839 dramatically suppressed tumor growth, whereas GLS overexpression promoted tumor growth in ESCC cells xenografted nude mice. Mechanistically, GLS was localized in mitochondria of ESCC cells, which interacted with PDK1 protein. CB-839 attenuated the interaction of GLS and PDK1 in ESCC cells by suppressing PDK1 expression, which further evoked the downregulation of p-PDHA1 (s293), however, GLS overexpression markedly enhanced the level of p-PDHA1 (s293). These findings suggest that interaction of GLS with PDK1 accelerates the glycolysis of ESCC cells by inactivating PDH enzyme, and thus targeting GLS may be a novel therapeutic approach for ESCC patients.


Assuntos
Benzenoacetamidas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Glutaminase , Glicólise , Piruvato Desidrogenase Quinase de Transferência de Acetil , Tiadiazóis , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Glutaminase/genética , Glutaminase/metabolismo , Glicólise/genética , Camundongos Nus , Piruvato Desidrogenase Quinase de Transferência de Acetil/genética , Piruvato Desidrogenase Quinase de Transferência de Acetil/metabolismo
11.
Int J Biol Macromol ; 262(Pt 1): 129988, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38325692

RESUMO

Bacterial infection and oxidative stress impede clinical wound healing. Herein, the plant-derived cowberry extract (CE) was first explored as a natural photothermal agent and antioxidant to deal with bacterial infection and oxidative stress. After loading in the carboxymethyl chitosan (CMCs)/oxidized dextran (Odex) hydrogel, the photothermal effect of CE was highly enhanced by CMCs. The controlled temperature induced by CE-containing hydrogel under NIR laser irradiation could rapidly (10 min) and effectively kill Staphylococcus aureus (S. aureus, 99.3 %) and Escherichia coli (E. coli, 94.6 %). Besides, this hydrogel exhibited a fast gelation and hemostasis abilities, high stability, adhesion and ROS scavenging capabilities, as well as good injectability and biocompatibility. Above superior properties make this hydrogel to accelerate the wound healing in S. aureus-infected mice, and it is expected to be a potential clinical wound dressing.


Assuntos
Quitosana , Infecções Estafilocócicas , Infecção dos Ferimentos , Animais , Camundongos , Antioxidantes/farmacologia , Hidrogéis/farmacologia , Escherichia coli , Staphylococcus aureus , Extratos Vegetais/farmacologia , Cicatrização , Antibacterianos/farmacologia
13.
Int J Biol Macromol ; 254(Pt 3): 128027, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37952801

RESUMO

Infected wounds pose a serious threat to public health and pose a significant challenge and financial burden worldwide. The treatment of infected wounds is now an urgent problem to be solved. Herein, mild hyperthermia-assisted hydrogels composed of carboxymethyl chitosan (CMCs), oxidized dextran (Odex), epigallocatechin gallate (EGCG) and PtNPs@PVP (CAT-like nanoenzymes) were proposed for the repair of infected wounds. The incorporation of PtNPs@PVP nanoenzymes give the hydrogels excellent photothermal property and CAT-like activity. When the temperature is maintained at 42-45 °C under 808 nm near infrared (NIR) exposure, the CMCs/Odex/EGCG/Nanoenzymes (COEN2) hydrogel demonstrated highly enhanced antibacterial ability (95.9 % in vivo), hydrogen peroxide (H2O2) scavenging ratio (85.1 % in vitro) and oxygen supply (20.7 mg/L in vitro). Furthermore, this mild-heat stimulation also promoted angiogenesis in the damaged skin area. Overall, this multifunctional hydrogel with antibacterial, antioxidant, oxygen supply, hemostasis, and angiogenesis capabilities has shown great promise in the repair of infected wounds. This study establishes the paradigm of enhanced infected wound healing by mild hyperthermia-assisted H2O2 scavenging, oxygen supplemental, and photothermal antibacterial hydrogels.


Assuntos
Quitosana , Hipertermia Induzida , Infecção dos Ferimentos , Humanos , Hidrogéis/farmacologia , Peróxido de Hidrogênio , Infecção dos Ferimentos/tratamento farmacológico , Oxigênio , Antibacterianos/farmacologia , Cicatrização
14.
Int J Biol Macromol ; 258(Pt 2): 128962, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38145691

RESUMO

Platelet-rich plasma (PRP) contains a variety of growth factors (GFs) and has been used in the treatment of a variety of diseases, including skin lesions. In particular, PRP with low immunogenicity will be more widely used. However, the explosive release of GFs limits its further application. In order to achieve controlled release of GFs, a multifunctional and reactive oxygen species (ROS)/pH dual responsive hydrogel was developed to load PRP derived from human cord blood for the treatment of skin wound healing. Based on the hydrogen bond and Schiff base interaction, carboxymethyl chitosan (CMCS), oxidized dextran (Odex) and oligomeric procyanidins (OPC) were crosslinked to form CMCS/Odex/OPC/PRP hydrogel with good injectability, self-healing, adhesion, ROS scavenging, antibacterial activity, controlled and sustained release of GFs. In vitro cell experiments suggested that this hydrogel possessed excellent biocompatibility and could promote the proliferation and migration of L929. In vivo healing of full-layer skin wounds further indicated that the prepared hydrogel could regulate inflammation and promote epithelialization, collagen deposition, and angiogenesis. In summary, this present study demonstrates that CMCS/Odex/OPC/PRP hydrogel may serve as a promising multifunctional dressing for skin wound healing.


Assuntos
Quitosana , Plasma Rico em Plaquetas , Humanos , Hidrogéis/química , Quitosana/química , Preparações de Ação Retardada , Espécies Reativas de Oxigênio , Cicatrização , Antibacterianos/análise , Peptídeos e Proteínas de Sinalização Intercelular , Plasma Rico em Plaquetas/química , Concentração de Íons de Hidrogênio
15.
J Mater Chem B ; 11(46): 11135-11149, 2023 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-37964663

RESUMO

Most hydrogel dressings are designed for skin wounds in flat areas, and few are focused on the joint skin regions which undergo frequent movement. The mismatch of mechanical properties and poor fit between a hydrogel dressing and a wound in joint skin results in hydrogel shedding, bacterial infection and delayed healing. Therefore, it is of great significance to design and prepare a multifunctional hydrogel with high tensile and tissue-adhesive strength as well as other therapeutic effects for the treatment of joint skin wounds. In this work, a multifunctional hydrogel was reasonably prepared by simply mixing polyvinyl alcohol (PVA), borax, tannic acid (TA) and iron(III) chloride in certain proportions, which was further used to treat the skin wounds at the joint of the hind limb. Acting as the physical crosslinkers, borax and TA dynamically bond with PVA and provide the resulting hydrogel with strong tensile, fast shape-adaptive and self-healing properties. The photothermal bacteriostatic activity of the hydrogel is attributed to the formation of a metallic polyphenol network (MPN) between ferric ions and TA. In addition, the hydrogel exhibits high levels of adhesion, hemostatic performance, antioxidant abilities, and biocompatibility, and shows great potential to promote joint skin wound healing.


Assuntos
Adesivos , Hidrogéis , Adesivos/farmacologia , Hidrogéis/farmacologia , Compostos Férricos , Bandagens , Ferro
16.
Gels ; 9(11)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37998998

RESUMO

Spinal cord injury (SCI) is a severe neurological injury caused by traffic accidents, trauma, or falls, which leads to significant loss of sensory, motor, and autonomous functions and seriously affects the patient's life quality. Although considerable progress has been made in mitigating secondary injury and promoting the regeneration/repair of SCI, the therapeutic effects need to be improved due to drug availability. Given their good biocompatibility, biodegradability, and low immunogenicity, injectable hydrogels can be used as delivery systems to achieve controlled release of drugs and other substances (cells and proteins, etc.), offering new hope for SCI repair. In this article, we summarized the types of injectable hydrogels, analyzed their application as delivery systems in SCI, and further discussed the mechanisms of hydrogels in the treatment of SCI, such as anti-inflammatory, antioxidant, anti-apoptosis, and pro-neurogenesis. Moreover, we highlighted the potential benefits of hydrogels in the treatment of SCI in combination with therapies, including the recent advances and achievements of these promising tools. Our review may offer new strategies for the development of SCI treatments based on injectable hydrogels as delivery systems.

17.
Int J Biol Macromol ; 253(Pt 4): 126854, 2023 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-37729986

RESUMO

Melanoma excision surgery is usually accompanied by neoplasm residual, tissue defect, and bacterial infection, resulting in high tumor recurrence and chronic wound. Nanocomposite hydrogels can satisfy the twin requirements of avoiding tumor recurrence and skin wound healing following skin melanoma surgery due to their photothermal anti-tumor and anti-bacterial activities. In this study, carboxymethyl chitosan, oxidized fucoidan and polyphenol-metal nanoparticle (PMN) of tannic acid capped gold nanoparticles were used to fabricate multifunctional nanocomposite hydrogels through Schiff base reaction. The prepared hydrogel demonstrated outstanding photothermal effect, and the controlled high temperature will rapidly kill melanoma cells as well as bacteria within 10 min. Good injectability, self-healing and adhesion combined with high reactive oxygen species (ROS) scavenging capacity, hemostasis and biocompatibility made this hydrogel platform perfect for the postoperative treatment of melanoma and promoting wound healing. With the assistance of NIR irradiance, hydrogel can inhibit tumor tissue proliferation and promote tumor cell apoptosis, thereby helping to prevent melanoma recurrence after surgical removal of tumors. Simultaneously, the irradiance heat and polyphenol component kill bacteria on the wound surface, eliminate ROS, inhibit inflammatory responses, and promote angiogenesis, collagen deposition, and skin regeneration, all of which help to speed up wound healing.


Assuntos
Quitosana , Melanoma , Nanopartículas Metálicas , Humanos , Polifenóis/farmacologia , Hidrogéis/farmacologia , Quitosana/farmacologia , Ouro , Nanogéis , Recidiva Local de Neoplasia , Espécies Reativas de Oxigênio , Melanoma/terapia , Antibacterianos
20.
J Mater Chem B ; 11(30): 7055-7068, 2023 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-37395053

RESUMO

Glioma is one of the most common malignant tumors with characteristics of strong invasion and high postoperative recurrence rate, which seriously threatens human health. Nanoparticles as an emerging drug delivery system have promoted the development of glioma therapy. However, blocking of nanoparticles by the blood-brain barrier is still serious problem for the use of nanoparticles in glioma therapy. In this context, traditional nanoparticles are dressed with natural cell membranes to prepare biomimetic nanoparticles. Biomimetic nanoparticles show longer blood circulation time, excellent homologous targeting and outstanding immune escape capacity, which significantly improve the accumulation of nanoparticles at the tumor site. The therapeutic effect for glioma has been raised to an advanced level. This review focuses on the preparations and applications of cell membrane-functionalized biomimetic nanoparticles, as while as the advantages and problems of biomimetic nanoparticles in the treatment of glioma. In particular, the approach of using biomimetic nanoparticles to cross the blood-brain barrier is analyzed, in the hope of providing new ideas for further developments in crossing the blood-brain barrier and in glioma therapy.


Assuntos
Glioma , Nanopartículas , Humanos , Biomimética , Glioma/tratamento farmacológico , Glioma/metabolismo , Nanopartículas/uso terapêutico , Barreira Hematoencefálica/metabolismo , Membrana Celular/metabolismo
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