RESUMO
Self-healing hydrogel is a promising soft material for applications in wound dressings, drug delivery, tissue engineering, biomimetic electronic skin, and wearable electronic devices. However, it is a challenge to fabricate the self-healing hydrogels without external stimuli. Inspired by mussel, the metal-catechol complexes were introduced into the hydrogel systems to prepare the mussel-inspired hydrogels by regulating the gelation kinetics of Fe3+ crosslinkers with gallic acid (GA) in this research. The amine-functionalized carboxymethyl cellulose (CMC) was grafted with GA and then chelated with Fe3+ to form a multi-response system. The crosslinking of carboxymethyl cellulose-ethylenediamine-gallic acid (CEG) hydrogel was controlled by adjusting the pH to affect the iron coordination chemistry, which could enhance the self-healing properties and mechanical strength of hydrogels. In addition, the CEG hydrogel exhibited great antibacterial and antioxidant properties. And the CEG hydrogel could strongly adhere to the skin tissue. The adhesion strength of CEG hydrogel on pigskin was 11.44 kPa, which is higher than that of commercial wound dressings (â¼5 kPa). Moreover, the thixotropy of the CEG hydrogel was confirmed with rheological test. In summary, it has great potential in the application field of wound dressing.
Assuntos
Carboximetilcelulose Sódica , Ácido Gálico , Hidrogéis , Ácido Gálico/química , Hidrogéis/química , Hidrogéis/farmacologia , Carboximetilcelulose Sódica/química , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Antibacterianos/química , Antibacterianos/farmacologia , Ferro/química , Suínos , Reagentes de Ligações Cruzadas/química , Reologia , Cicatrização/efeitos dos fármacosRESUMO
Corneal neovascularization (CNV) is a common multifactorial sequela of anterior corneal segment inflammation, which could lead to visual impairment and even blindness. The main treatments available are surgical sutures and invasive drug injections, which could cause serious ocular complications. To solve this problem, a thermo-sensitive drug-loaded hydrogel with high transparency was prepared in this study, which could achieve the sustained-release of drugs without affecting normal vision. In briefly, the thermo-sensitive hydrogel (PFNOCMC) was prepared from oxidized carboxymethyl cellulose (OCMC) and aminated poloxamer 407 (PF127-NH2). The results proved the PFNOCMC hydrogels possess high transparency, suitable gel temperature and time. In the CNV model, the PFNOCMC hydrogel loading bone morphogenetic protein 4 (BMP4) showed significant inhibition of CNV, this is due to the hydrogel allowed the drug to stay longer in the target area. The animal experiments on the ocular surface were carried out, which proved the hydrogel had excellent biocompatibility, and could realize the sustained-release of loaded drugs, and had a significant inhibitory effect on the neovascularization after ocular surface surgery. In conclusion, PFNOCMC hydrogels have great potential as sustained-release drug carriers in the biomedical field and provide a new minimally invasive option for the treatment of neovascular ocular diseases.
Assuntos
Neovascularização da Córnea , Hidrogéis , Animais , Hidrogéis/farmacologia , Neovascularização da Córnea/tratamento farmacológico , Neovascularização da Córnea/metabolismo , Carboximetilcelulose Sódica/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Poloxâmero/uso terapêuticoRESUMO
Corneal neovascularization (CNV) can lead to impaired corneal transparency, resulting in vision loss or blindness. The primary pathological mechanism underlying CNV is an imbalance between pro-angiogenic and anti-angiogenic factors, with inflammation playing a crucial role. Notably, a vascular endothelial growth factorï¼VEGFï¼-A gradient triggers the selection of single endothelial cellsï¼ECsï¼ into primary tip cells that guide sprouting, while a dynamic balance between tip and stalk cells maintains a specific ratio to promote CNV. Despite the central importance of tip-stalk cell selection and shuffling, the underlying mechanisms remain poorly understood. In this study, we examined the effects of bone morphogenetic protein 4 (BMP4) on VEGF-A-induced lumen formation in human umbilical vein endothelial cells (HUVECs) and CD34-stained tip cell formation. In vivo, BMP4 inhibited CNV caused by corneal sutures. This process was achieved by BMP4 decreasing the protein expression of VEGF-A and VEGFR2 in corneal tissue after corneal suture injury. By observing the ultrastructure of the cornea, BMP4 inhibited the sprouting of tip cells and brought forward the appearance of intussusception. Meanwhile, BMP4 attenuated the inflammatory response by inhibiting neutrophil extracellular traps ï¼NETsï¼formation through the NADPH oxidase-2ï¼NOX-2ï¼pathway. Our results indicate that BMP4 inhibits the formation of tip cells by reducing the generation of NETs, disrupting the dynamic balance of tip and stalk cells and thereby inhibiting CNV, suggesting that BMP4 may be a potential therapeutic target for CNV.
Assuntos
Lesões da Córnea , Neovascularização da Córnea , Humanos , Neovascularização da Córnea/metabolismo , Proteína Morfogenética Óssea 4/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Córnea/metabolismo , Células Endoteliais da Veia Umbilical Humana/patologia , Lesões da Córnea/metabolismo , Neovascularização FisiológicaRESUMO
Esophageal cancer is the eighth most prevalent cancer and has high mortality in our society. Isoalantolactone, extracted from Inula helenium L, has shown potent anticancer effects on a variety of cancers. However, its effect on human esophageal cancer, and the underlying molecular mechanism, remain to be investigated. In the present study, we demonstrated that isoalantolactone induced apoptosis in esophageal cancer cells. Treatment with isoalantolactone activated caspases-3, -7, and -10, and upregulated death receptor (DR)5. Furthermore, DR5 knockdown partially reversed the effect of isoalantolactone. These results indicated the extrinsic apoptosis was induced by isoalantolactone. In addition, intracellular reactive oxygen species (ROS) were significantly elevated after treatment with isoalantolactone. N-Acetylcysteine, an ROS scavenger, blocked both the apoptosis and decreased cell viability caused by isoalantolactone. In vivo, significant suppression of tumor growth by isoalantolactone was observed in an ECA109 cell xenograft mouse model. Isoalantolactone showed no obvious adverse effects on mouse weight and histology of heart, liver, spleen, lung, and kidney. In conclusion, our results revealed that isoalantolactone induced apoptosis through the extrinsic pathway via upregulation of DR5 and elevation of ROS in human esophageal cancer cells. Isoalantolactone, therefore, could be a potential candidate in developing anticancer agents for esophageal cancer patients.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias Esofágicas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Sesquiterpenos/farmacologia , Animais , Linhagem Celular Tumoral , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Receptores do Ligante Indutor de Apoptose Relacionado a TNF/genética , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To investigate the immunological parameters of chromic acid exposure among electroplating workers. METHODS: Forty-six subjects were selected from five electroplating plants in central Taiwan. Each subject was interviewed by questionnaire, and urine chromium (urine-Cr) concentration was assessed. Immunological parameters were evaluated by interleukin (IL-2, IL-4, IL-6, IL-8, IL-10, TNF-alpha, IFN-gamma) and levels of lymphocyte subsets (T-cell, B-cell, T4, T8 and T4/T8). RESULTS: Levels of IL-6 and IL-8 significantly increased in subjects with high urine Cr concentration, but TNF-alpha levels decreased. IL-2, IL-4, IL-10 and IFN-gamma were undetected. Flow cytometry was used to determine levels of lymphocyte subsets: only B-cells percentage had a negative correlation with urine-Cr. Smoking was an important factor that influenced levels of lymphocyte subsets. CONCLUSION: Exposure to Cr has a detrimental effect on the immune system, so it is evident that worker exposure to chromic acid in the electroplating workplace must be reduced to a minimum.