RESUMO
Achieving high-performance luminescence for underwater bonding remains a significant challenge in materials science. This study addresses this issue by synthesizing a luminescent material based on an aggregation-induced emission (AIE) monomer and copolymerizing it with lipoic acid (LA) to create an AIE supramolecular polymer. The resulting copolymer exhibits strong fluorescence under ultraviolet (UV) irradiation at 365 nm due to the AIE of TPEE and enables underwater adhesion. The P(LA-TPEE) polymer demonstrates potential for digital encryption and decryption of quick response (QR) codes underwater. Furthermore, it can dissolve well in anhydrous ethanol, producing an environment-friendly and super waterproof adhesive. Most notably, the P(LA-TPEE) solution can be sprayed on human skin, creating an invisible tattoo that only became visible under UV light due to the hydrogen bond (H-bond) and π-π structures. This smart tattoo can be quickly wiped away with alcohol, avoiding the painful and harmful process of tattoo removal. It can also be repeatedly applied to draw the preferred tattoo pattern. This AIE supramolecular polymer shows great potential in underwater adhesion and repair, underwater message encryption, and non-toxic and painless invisible tattooing. Overall, this study provides a valuable approach for material design in the future.
Assuntos
Tatuagem , Humanos , Corantes , Pele , Adesivos , Polímeros/químicaRESUMO
BACKGROUND: Pseudomonas aeruginosa is an opportunistic pathogen, and because of its specificity, its treatments appear tricky in postrhinoplasty infections with internal implants. This study summarizes the clinical characteristics and treatment of this type of infections to provide some reference for clinical work. METHODS: We retrospectively analyzed 10 patients who were diagnosed with a nasal infection of P. aeruginosa after implant nasal augmentation. The results of the bacterial culture and drug sensitivity test of the patients' wound secretions were summarized and analyzed. We summarized the characteristics of the patients' infection and the treatments, and we also summarized the patients' prognosis. RESULTS: In these 10 cases, their implants included rib cartilage and ear cartilage alone, as well as their own cartilage combined with expanded polytetrafluoroethylene and silicone. All patients developed wound infections within 1 month after rhinoplasty, with bacterial cultures of P. aeruginosa . Prolonged use of sensitive antibiotics, as well as wound dressing changes, failed to keep the infection well under control. Patients whose implant was removed and thoroughly debrided within 1 week of infection did not experience any serious complications. In patients who were infected for >1 week before surgery to remove the implants, complications such as nasal column necrosis and nasal contracture occurred, and later the nasal repair was performed after multiple surgeries. CONCLUSIONS: For bacterial infections in postrhinoplasty wounds with implants, we recommend early bacterial culture. If the infection is clearly P. aeruginosa , the implant should be removed and thoroughly debrided as soon as possible to avoid serious complications. LEVEL OF EVIDENCE: Level IV.
Assuntos
Implantes Dentários , Infecções por Pseudomonas , Rinoplastia , Humanos , Rinoplastia/métodos , Estudos Retrospectivos , Resultado do Tratamento , Cartilagem da Orelha , Pseudomonas aeruginosaRESUMO
Cellulolytic fungi have evolved a complex regulatory network to maintain the precise balance of nutrients required for growth and hydrolytic enzyme production. When fungi are exposed to cellulose, the transcript levels of cellulase genes rapidly increase and then decline. However, the mechanisms underlying this bell-shaped expression pattern are unclear. We systematically screened a protein kinase deletion set in the filamentous fungus Neurospora crassa to search for mutants exhibiting aberrant expression patterns of cellulase genes. We observed that the loss of stk-12 (NCU07378) caused a dramatic increase in cellulase production and an extended period of high transcript abundance of major cellulase genes. These results suggested that stk-12 plays a critical role as a brake to turn down the transcription of cellulase genes to repress the overexpression of hydrolytic enzymes and prevent energy wastage. Transcriptional profiling analyses revealed that cellulase gene expression levels were maintained at high levels for 56 h in the Δstk-12 mutant, compared to only 8 h in the wild-type (WT) strain. After growth on cellulose for 3 days, the transcript levels of cellulase genes in the Δstk-12 mutant were 3.3-fold over WT, and clr-2 (encoding a transcriptional activator) was up-regulated in Δstk-12 while res-1 and rca-1 (encoding two cellulase repressors) were down-regulated. Consequently, total cellulase production in the Δstk-12 mutant was 7-fold higher than in the WT. These results strongly suggest that stk-12 deletion results in dysregulation of the cellulase expression machinery. Further analyses showed that STK-12 directly targets IGO-1 to regulate cellulase production. The TORC1 pathway promoted cellulase production, at least partly, by inhibiting STK-12 function, and STK-12 and CRE-1 functioned in parallel pathways to repress cellulase gene expression. Our results clarify how cellulase genes are repressed at the transcriptional level during cellulose induction, and highlight a new strategy to improve industrial fungal strains.
Assuntos
Celulase/genética , Proteínas Fúngicas/genética , Fatores de Transcrição/genética , Celulose/genética , Regulação Fúngica da Expressão Gênica/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Neurospora crassa/enzimologia , Neurospora crassa/genéticaRESUMO
BACKGROUND: A variety of bone graft substitutes have been introduced into the treatment of bone non-unions. However, clinical outcomes from current evidences are various and conflicting. This study aimed to present the preliminary outcomes of a treatment protocol in which the combination of demineralized bone matrix (DBM) and platelet rich plasma (PRP) was used as a bone graft substitute for long bone non-unions. METHODS: Data of this retrospective study were reviewed and collected from a consecutive case series involving 43 patients who presented with a long bone non-union and were treated in our department from October 2018 to May 2019. The combination of DMB and PRP was applied as a bone defect filler in 16 patients, whilst the other 27 patients were treated with iliac bone autografting. Patients' demographics, postoperative complications and the result of bone union were compared and evaluated. RESULTS: The demographic data between the two groups were comparable. No significant difference was found with regard to the incidence of postoperative complications. No graft rejection, heterotopic ossification or other complications were noted. The distribution of bony healing time was rather scattered but did not differ significantly between the groups (7.533 ± 3.357 months vs. 6.625 ± 2.516 months; P=0.341). Union was identified radiographically in 15 of 16 patients in the DBM+PRP group and in 24 of 27 patients in autograft group. CONCLUSIONS: The present study identified that low incidence of postoperative complications and satisfactory bony healing rate could be achieved in the treatment of long bone non-unions augmented with the combination of DBM and PRP. Although these findings might indicate the promising future of this treatment protocol, larger and higher quality studies should also be executed to assess its routine use.
Assuntos
Substitutos Ósseos , Plasma Rico em Plaquetas , Matriz Óssea , Transplante Ósseo , Humanos , Estudos Retrospectivos , Transplante AutólogoRESUMO
Radiation-induced oral mucositis has a dismal outcome with limited treatment options. We conducted a phase I study to evaluate the safety and preliminary efficacy of epigallocatechin-3-gallate (EGCG) mouthwash when given along with radiation in head and neck cancer. Patients with pathologically confirmed head and neck cancer were eligible for this study. EGCG mouthwash was administered at the assigned dosage level (starting at 440 µmol/L, three times a day) in a standard 3 + 3 dose escalation design. Mucosal toxicity, patient satisfaction, and mucositis-related pain (MTP) were assessed weekly. The primary endpoint was safety of EGCG, and the secondary endpoint was to determine the relief of the mucositis symptom. The pre- and post-treatment parameters were compared using the paired t-test. 20 patients were enrolled. The maximum tolerated dose of the EGCG mouthwash was 2200 µmol/L. Burning (n = 1/20) and nausea (n = 3/20) were the most common toxicities. No patients experienced WHO Grade 3 or higher mucositis. MTP scores significantly decreased after EGCG administration over time (p < 0.05). Adding EGCG mouthwash to radiotherapy is feasible without increasing toxicities. The recommended dose for phase II study is determined to be 1760 µmol/L, and EGCG administration reduces radiation-induced oral mucosal injury in patients.
Assuntos
Catequina/análogos & derivados , Quimiorradioterapia , Neoplasias de Cabeça e Pescoço/terapia , Antissépticos Bucais/administração & dosagem , Mucosite/tratamento farmacológico , Lesões por Radiação/tratamento farmacológico , Adulto , Idoso , Catequina/administração & dosagem , Catequina/efeitos adversos , Humanos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Mucosa Bucal/efeitos dos fármacos , Antissépticos Bucais/efeitos adversos , Mucosite/etiologia , Estudos Prospectivos , Adulto JovemRESUMO
Further to conventional linear, branched, crosslinked, and dendritic polymers, single chain cyclized/knotted polymers (SCKPs) have emerged as a new class of polymer structure with unique properties. Herein, the development of bacteria-resistant SCKPs is reported and the effect of this structure on the resistance of polymer materials to bacteria is investigated. Four SCKPs were synthesized by reversible addition fragmentation chain transfer (RAFT) homopolymerization of multivinyl monomers (MVMs) and then crosslinked by UV light to form SCKP films. Regardless of MVM type used, the resulting SCKP films showed much higher resistance to bacteria, and up to 75 % less bacterial attachment and biofilm formation, in comparison with the corresponding non-SCKP films. This is due to the altered surface morphology and hydrophobicity of the SCKP films. These results highlight the critical role of the SCKP structure in enhancing the resistance of polymeric materials to bacteria.
Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Polímeros/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Interações Hidrofóbicas e Hidrofílicas , Testes de Sensibilidade Microbiana , Estrutura Molecular , Polimerização , Polímeros/síntese química , Polímeros/químicaRESUMO
Porphyromonas endodontalis (P. endodontalis) lipopolysaccharide (LPS) is associated with the progression of bone resorption in periodontal and periapical diseases. Matrix metalloproteinase-2 (MMP-2) expression and activity are elevated in apical periodontitis and have been suggested to participate in bone resorption. Therefore, inhibiting MMP-2 activation may be considered a therapeutic strategy for treating apical periodontitis. Resveratrol is a natural non-flavonoid polyphenol that has been reported to have antioxidant, anti-cancer, and anti-inflammatory properties. However, the capacity of resveratrol to protect osteoblast cells from P. endodontalis LPS insults and the mechanism of its inhibitory effects on MMP-2 activation is poorly understood. Here, we demonstrate that cell viability is unchanged when 10 mg L-1P. endodontalis LPS is used, and MMP-2 expression is drastically induced by P. endodontalis LPS in a concentration- and time-dependent manner. Twenty micromolar resveratrol did not reduce MC3T3-E1 cell viability. Resveratrol increased AMP-activated protein kinase (AMPK) phosphorylation, and Compound C, a specific AMPK inhibitor, partially abolished the resveratrol-mediated phosphorylation of AMPK. In addition, AMPK inhibition blocked the effects of resveratrol on MMP-2 expression and activity in LPS-induced MC3T3-E1 cells. Treatment with resveratrol also induced suppressor of cytokine signaling 1 (SOCS1) expression in MC3T3-E1 cells. SOCS1 siRNA negated the inhibitory effects of resveratrol on LPS-induced MMP-2 production. Additionally, resveratrol-induced SOCS1 upregulation was reduced by treatment with compound C. These results demonstrate that AMPK and SOCS1 activation are important signaling events during resveratrol-mediated inhibition of MMP-2 production in response to LPS in MC3T3-E1 cells, and there is crosstalk between AMPK and SOCS1 signaling.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Lipopolissacarídeos/efeitos adversos , Metaloproteinase 2 da Matriz/metabolismo , Osteoblastos/citologia , Porphyromonas endodontalis/metabolismo , Resveratrol/farmacologia , Proteínas Quinases Ativadas por AMP/genética , Animais , Proteínas de Bactérias/efeitos adversos , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Metaloproteinase 2 da Matriz/genética , Camundongos , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Fatores de TempoRESUMO
By setting up a coarse-grained model of polymer nanocomposites, we monitored the change in the elastic modulus as a function of the strain, derived from the stress-strain behavior by determining uniaxial tension and simple shear of two typical spatial distribution states (aggregation and dispersion) of nanoparticles (NPs). In both these cases, we observed that the elastic modulus decreases non-linearly with the increase of strain and reaches a low plateau at larger strains. This phenomenon is similar to the so-called "Payne effect" for elastomer nanocomposites. Particularly, the modulus of the aggregation case is more sensitive to the imposed strain. By examining the structural parameters, such as the number of neighboring NPs, coordination number of NPs, root-mean-squared average force exerted on the NPs, local strain, chain conformations (bridge, dangle, loop, interface bead and connection bead), and the total interaction energy of NP-polymer and NP-NP, we inferred that the underlying mechanism of the aggregation case is the disintegration of the NP network or clusters formed through direct contact; however, for the dispersion case, the non-linear behavior is attributed to the destruction of the NP network or clusters formed through the bridging of adsorbed polymer segments among the NPs. The former physical network is influenced by NP-NP interaction and NP volume fraction, while the latter is influenced by NP-polymer interaction and NP volume fraction. Lastly, we found that for the dispersion case, further increasing the inter-particle distance or grafting NPs with polymer chains can effectively reduce the non-linear behavior due to the decrease of the physical network density. In general, this simulation work, for the first time, establishes the correlation between the micro-structural evolution and the strain-induced non-linear behavior of polymer nanocomposites, and sheds some light on how to reduce the "Payne effect".
Assuntos
Simulação de Dinâmica Molecular , Nanocompostos/química , Nanopartículas/química , Polímeros/química , Módulo de Elasticidade , Estresse MecânicoRESUMO
Spinal cord injury (SCI), a prevalent and disabling neurological condition, prompts a growing interest in stem cell therapy as a promising avenue for treatment. Dental-derived stem cells, including dental pulp stem cells (DPSCs), stem cells from human exfoliated deciduous teeth (SHED), stem cells from the apical papilla (SCAP), dental follicle stem cells (DFSCs), are of interest due to their accessibility, minimally invasive extraction, and robust differentiating capabilities. Research indicates their potential to differentiate into neural cells and promote SCI repair in animal models at both tissue and functional levels. This review explores the potential applications of dental-derived stem cells in SCI neural repair, covering stem cell transplantation, conditioned culture medium injection, bioengineered delivery systems, exosomes, extracellular vesicle treatments, and combined therapies. Assessing the clinical effectiveness of dental-derived stem cells in the treatment of SCI, further research is necessary. This includes investigating potential biological mechanisms and conducting Large-animal studies and clinical trials. It is also important to undertake more comprehensive comparisons, optimize the selection of dental-derived stem cell types, and implement a functionalized delivery system. These efforts will enhance the therapeutic potential of dental-derived stem cells for repairing SCI.
RESUMO
Resveratrol (RES) has recently been reported as a potential antioxidant in treatment of ischemia/reperfusion injury through attenuating oxidative stress and apoptosis. However, application of RES is limited for its insolubility and short half-time. Latest evidence raises the possibility of developing nanoparticle-based delivery systems with improved solubility, stability and cytotoxicity of lipophilic drug. Here, we reported first a simple way to produce RES-loaded nanoparticles (RES-NPs) based on poly(N-vinylpyrrolidone)-b-poly(ε-caprolactone) polymer and further evaluated the protective effect of RES-NPs on hydrogen peroxide-induced oxidative stress and apoptosis in rat cortical cell culture. The controlled release pattern of RES-loaded nanoparticles was characterized by in vitro release experiments. Cytotoxicity tests proved cytocompatibility of these nanoparticles with neurons. Shown by coumarin-6 loaded nanoparticles, the uptake of nanoparticles by neurons was considered through endocytosis, which could lead to higher uptake efficiency at lower concentration. Thereby, the hypothesis is raised that RES-NPs could demonstrate enhanced neuroprotection compared to an equivalent dose of free RES at lower concentration, especially. It was further supported by enhanced reduction of LDH release, elimination of ROS and MDA, and attenuation of apoptosis signal (ratio of Bax/Bcl-2, activation of caspase-3). RES-NPs could be a potential treatment needing intensive research for ischemia/reperfusion related disorder including stroke.
Assuntos
Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Estilbenos/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Sistemas de Liberação de Medicamentos , Peróxido de Hidrogênio/farmacologia , Nanopartículas/administração & dosagem , Nanopartículas/química , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/farmacocinética , Estresse Oxidativo/efeitos dos fármacos , Poliésteres/química , Povidona/análogos & derivados , Povidona/química , Ratos , Espécies Reativas de Oxigênio/metabolismo , Resveratrol , Estilbenos/farmacocinéticaRESUMO
AIM: The aim of this study was to investigate histological and biomechanical properties of oviduct anastomosis with 2-octyl cyanoacrylate (OCA) in the rabbit. MATERIAL AND METHODS: Sixty female rabbits were randomly divided equally into three groups: A (control), B (traditional catgut suture), and C (non-suture technique using OCA). After suture or OCA anastomosis, gross examination (adhesion formation) and histopathology (hematoxylin-eosin), ultrastructure (transmission electron microscopy), and biomechanics (bursting pressure) on para-anastomotic site were investigated on oviduct taken at 1 (A1, B1, C1) and 4 (A2, B2, C2) weeks, respectively. RESULTS: Adhesion score in group B was more severe than that in groups A and C at 1 and 4 weeks. Histopathology showed that acute endosalpingitis in group B was the most intense at 1 week, followed by significantly more tissue stimulation induced by catgut and foreign-body giant cells in group B than in group C at 4 weeks. Ultrastructural damage of ciliated cells was reversed partly (B2) and completely (C2) at 4 weeks. Bursting pressure in C1 was weaker than that in B1, followed by no significant difference at 4 weeks. CONCLUSION: Non-suture using OCA for oviduct anastomosis can be accepted as a new-perspective technique.
Assuntos
Anastomose Cirúrgica/métodos , Cianoacrilatos/uso terapêutico , Oviductos/cirurgia , Adesivos Teciduais/uso terapêutico , Anastomose Cirúrgica/efeitos adversos , Animais , Fenômenos Biomecânicos , Feminino , Oviductos/ultraestrutura , Coelhos , Estresse Mecânico , Aderências Teciduais/etiologiaRESUMO
The present study investigated the shock of NaCl and C/N ratio on properties of soluble microbial products (SMPs), focusing on their sized fractions. The results indicated that the NaCl stress increased the content of biopolymers, humic substances, building blocks, and LMW substances in SMPs, while the addition of 40 g NaCl L-1 significantly changed their relative abundance in SMPs. The acute impact of both N-rich and N-deficient conditions accelerated the secretion of SMPs, but the characteristics of LMW substances differed. Meanwhile, the bio-utilization of SMPs has been enhanced with the increase of NaCl dosage but decreased with the increase of the C/N ratio. The mass balance of sized fractions in SMPs + EPS could be set up when NaCl dosage <10 g/L and C/N ratio >5, which indicates the hydrolysis of sized fractions in EPS mainly compensated for their increase/reduction in SMPs. Besides, the results of the toxic assessment indicated that the oxidative damage caused by the NaCl shock was an important factor affecting the property of SMPs, and the abnormal expression of DNA transcription cannot be neglected for bacteria metabolisms with the change of C/N ratio.
Assuntos
Salinidade , Esgotos , Esgotos/microbiologia , Cloreto de Sódio , Biopolímeros , DNA , Reatores BiológicosRESUMO
Microplastics (MPs) are ubiquitous emerging pollutants that have been found in the marine, freshwater, air, and soil environments. Wastewater treatment plants (WWTPs) play an important role in releasing MPs to the environment. Therefore, understanding the occurrence, fate, and removal mechanism of MPs in WWTPs is of great importance towards microplastic control. In this review, the occurrence characteristics and removal rates of MPs in 78 WWTPs from 57 studies were discussed based on Meta-analysis. Specifically, the key aspects regarding MPs removal in WWTPs, such as wastewater treatment processes and MPs shapes, sizes, and polymer compositions were analyzed and compared. The results showed that:â the abundances of MPs in the influent and effluent were 1.56×10-2-3.14×104 n·L-1 and 1.70×10-3-3.09×102 n·L-1, respectively. The abundance of MPs in the sludge ranged from 1.80×10-1 to 9.38×103 n·g-1. â¡ The total removal rate (>90%) of MPs by WWTPs using oxidation ditch, biofilm, and conventional activated sludge treatment processes was higher than that using sequencing batch activated sludge, anaerobic-anoxic-aerobic, and anoxic-aerobic processes. ⢠The removal rate of MPs in primary, secondary, and tertiary treatment process were 62.87%, 55.78%, and 58.45%, respectively. The combination process of "grid+ sedimentation tank+primary sedimentation tank" had the highest removal rate towards MPs in primary treatment processes, and the membrane bioreactor had the highest one beyond other secondary treatment processes. Filtration was the best process in tertiary treatment. ⣠The film, foam, and fragment MPs were easier to remove (>90%) than fiber and spherical (<90%) MPs by WWTPs. The MPs with particle size larger than 0.5 mm were easier to remove than those with particle size smaller than 0.5 mm. The removal efficiencies of polyethylene (PE), polyethylene terephthalate (PET), and polypropylene (PP) MPs were higher than 80%.
Assuntos
Microplásticos , Plásticos , Esgotos , Biofilmes , Reatores BiológicosRESUMO
PURPOSE: To investigate whether resveratrol promotes odontogenic differentiation of human dental pulp stem cells(DPSCs) by up-regulating the expression of silent information regulator 1 (SIRT1) and activating ß-catenin signaling pathway. METHODS: Different concentrations of resveratrol(0, 10, 15, 20 and 50 µmol/L) were used to treat DPSCs for 7 days and 14 days, and cell proliferative activity was detected by CCK-8. After odontogenic differentiation induced by 15 µmol/L resveratrol for 7 days, alkaline phosphatase(ALP) staining was performed and real-time quantitative reverse transcription PCR(qRT-PCR) was used to detect the mRNA expression of Runt-related transcription factor 2 (Runx2), dentin sialophosphoprotein(DSPP) and dentin matrix protein-1(DMP-1) in DPSCs. Western blot was used to detect the expression of SIRT1 in DPSCs on a specific day (0, 3rd, 5th, 7th and 14th) after differentiation induction. Western blot was also used to detect the expression of SIRT1 and activated ß-catenin during odontogenic differentiation of DPSCs treated by 15 µmol/L resveratrol for 7 days. The experimental data was analyzed with GraphPad Prism 9 software package. RESULTS: 15 µmol/L resveratrol had no significant effect on proliferation of DPSCs on the 7th and 14th day; 15 µmol/L resveratrol promoted odontogenic differentiation of DPSCs and up-regulated mRNA expression of RUNX2, DSPP, and DMP-1 in DPSCs; the expression of SIRT1 was the highest on the 7th day during odontogenic differentiation induction. Resveratrol resulted in the increasing protein expressions of SIRT1 and activated ß-catenin when DPSCs was induced to odontogenic differentiation for 7 days. CONCLUSIONS: Resveratrol promotes odontogenic differentiation of human DPSCs by up-regulating the expression of SIRT1 protein and activating ß-catenin signaling pathway.
Assuntos
Subunidade alfa 1 de Fator de Ligação ao Core , beta Catenina , Humanos , Resveratrol/farmacologia , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , beta Catenina/metabolismo , beta Catenina/farmacologia , Polpa Dentária/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Sirtuína 1/farmacologia , Proliferação de Células , Diferenciação Celular , Odontogênese/genética , Células-Tronco/metabolismo , RNA Mensageiro/metabolismo , Células CultivadasRESUMO
Paclitaxel (Ptx) has demonstrated encouraging activity in the treatment of gastric cancer. Development of drug-containing biodegradable polymeric nanoparticles (np) becomes one of the solutions to relieve side effects of Ptx. However, Ptx-loaded nanoparticles prepared by the nanoprecipitation method are unstable in the aqueous phase. Here we report that tetrandrine (Tet) effectively increases the stability of Ptx-loaded nanoparticles when Tet is coencapsulated with Ptx into mPEG-PCL nanoparticles. The current study demonstrates the synergistic antitumor effect of Tet and Ptx against gastric cancer cells, which provides the basis of coadministration of Tet and Ptx by nanoparticles. It is reported that the cellular chemoresistance to Ptx correlates with intracellular antioxidant capacity and the depletion of cellular antioxidant capacity could enhance the cytotoxicity of Ptx. Tet effectively induces intracellular ROS production. Therefore, the present study provides a promising novel therapeutic strategy basing on "oxidation therapy" that it could amplify the antitumor effect of paclitaxel by employing Tet as a pro-oxidant. More intracellular Tet accumulation by endocytosis of Ptx/Tet-np than equivalent doses of free drug leads to more intracellular ROS induction, which could efficiently enhance the cytotoxicity of Ptx by sequential inhibition of ROS-dependent Akt pathway and activation of apoptotic pathways, all of which would mediate the superior cytotoxicity of Ptx/Tet-np over free drug. The present results suggest that the codelivery of Ptx and Tet by nanoparticles provides a novel therapeutic strategy basing on "oxidation therapy" against gastric cancer.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Apoptose/efeitos dos fármacos , Benzilisoquinolinas/administração & dosagem , Portadores de Fármacos/química , Paclitaxel/administração & dosagem , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Caspase 3/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Sinergismo Farmacológico , Genes bcl-2 , Humanos , Nanopartículas/química , Tamanho da Partícula , Poliésteres/química , Polietilenoglicóis/química , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Vitamina E/farmacologia , Proteína X Associada a bcl-2/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: There is no consensus concerning small bowel preparation before capsule endoscopy (CE). This study evaluated the effects of 4 regimens on small bowel cleansing and diagnostic yield. METHODS: Patients were randomly divided into 4 groups. Group A consumed a clear liquid diet after lunch on the day before CE, followed by overnight fasting. Group B took 250 mL 20% mannitol and 1 L 0.9% saline orally at 05:00 hours on the day of the procedure. In group C, the same regimen was taken at 20:00 hours on the day before and at 05:00 hours on the day of CE. In group D, in addition to the group C regimen, 20 mL oral simethicone was taken 30 minutes before CE. RESULTS: Two hundred patients were prospectively enrolled, and 7 were excluded from the final analysis because of incomplete small bowel transit. No significant difference was noted among the 4 groups for small bowel transit time. Bowel preparation in group D was significantly better than for the other regimens for overall cleansing of the proximal small bowel, and showed improved overall cleansing of the distal small bowel when compared with 10-hours overnight fasting. Pathological lesions of the proximal and distal small bowel were, respectively, achieved in 82 and 74 patients, mostly distributed in group D. CONCLUSIONS: Small bowel preparation that involves split-dose oral mannitol plus single-dose simethicone for CE can improve mucosal visualization and subsequent diagnostic yield when compared with 10-hours overnight fasting.
Assuntos
Antiespumantes/uso terapêutico , Endoscopia por Cápsula/métodos , Diuréticos Osmóticos/uso terapêutico , Intestino Delgado/efeitos dos fármacos , Manitol/uso terapêutico , Pré-Medicação , Simeticone/uso terapêutico , Administração Oral , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antiespumantes/administração & dosagem , Diuréticos Osmóticos/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Trânsito Gastrointestinal/efeitos dos fármacos , Humanos , Masculino , Manitol/administração & dosagem , Pessoa de Meia-Idade , Estudos Prospectivos , Simeticone/administração & dosagem , Irrigação Terapêutica/métodos , Resultado do Tratamento , Adulto JovemRESUMO
As a potential anticancer agent, curcumin (Cum) has been reported for its chemopreventive and chemotherapeutic activity in a series of cancers through influencing cell cycle arrest, differentiation, apoptosis, etc. Therefore, the potential activity against various cancers of Cum raises the possibility of its application as a novel model drug in nanoparticle-based delivery systems. The current study reported a spherical core-shell structure curcumin-loaded nanoparticle (Cum-np) formed by amphilic methoxy polyethylene glycol-poly(caprolactone) (mPEG-PCL) block copolymers. Characterization tests indicated that Cum was incorporated into mPEG-PCL-based nanoparticles with high encapsulation efficiency due to its lipophilicity. The incorporated Cum could be released from Cum-np in a sustained manner. Cum was effectively transported into the cells by nanoparticles through endocytosis and localized around the nuclei in the cytoplasms. In vitro studies proved that the cytotoxicity of Cum-np would be pro-apoptosis effect against rat C6 glioma cell line in a dose-dependent manner. The present results suggest that Cum-np could be a potential useful chemotherapeutic formulation for malignant glioma therapy. Moreover, the development of traditional Chinese medicine with nanoscale drug formation warrants more intensive research for its clinical applications.
Assuntos
Curcumina/administração & dosagem , Nanopartículas/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Curcumina/metabolismo , Citoplasma/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Citometria de Fluxo , Glioma/metabolismo , Glioma/patologia , Glioma/prevenção & controle , Concentração Inibidora 50 , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Nanopartículas/ultraestrutura , Poliésteres/química , Polietilenoglicóis/química , Ratos , Fatores de TempoRESUMO
BACKGROUND: Patients with osteoporosis have a high risk of implant loosening due to poor osteointegration, possibly leading to implant failure, implant revision, and refracture. RNA interference therapy is an emerging epigenetic treatment, and we found that miR-20a could enhance osteogenesis. Moreover, small extracellular vesicles (sEVs) derived from bone marrow mesenchymal stem cells (hBM-MSCs) were utilized as nanoscale carriers for the protection and transportation of miR-20a (sEV-20a). In this study, we intended to determine whether sEVs overexpressing miR-20a could exert a superior effect on osteoporotic bone defects and the underlying mechanism. METHODS: For evaluating the effect of sEV-20a on osteogenesis, in vitro and in vivo studies were performed. In vitro, we first showed that miR-20a was upregulated in the osteogenic process and overexpressed sEVs with miR-20a by the transfection method. Then, the proliferation, migration, and osteogenic differentiation abilities of hBM-MSCs treated with sEV-20a were detected by CCK-8 assays, alkaline phosphatase staining and alizarin red staining, qRT-PCR, and western blot. In vivo, we established an osteoporotic bone defect model and evaluated the effect of sEV-20a on bone formation by micro-CT, sequential fluorescent labeling, and histological analysis. To further explore the mechanism, we applied a bioinformatics method to identify the potential target of miR-20a. RESULTS: In vitro, sEV-20a was successfully established and proved to promote the migration and osteogenesis of hBM-MSCs. In vivo, sEV-20a promoted osteointegration in an osteoporotic rat model. To further elucidate the related mechanism, we proved that miR-20a could enhance osteogenesis by targeting BAMBI. CONCLUSIONS: Collectively, the in vitro and in vivo results confirmed that MSC-derived sEV-20a therapy effectively promoted osteoporotic porous titanium alloy osteointegration via pro-osteogenic effects by targeting BAMBI.
Assuntos
Vesículas Extracelulares , MicroRNAs , Ligas/farmacologia , Animais , Diferenciação Celular , Células Cultivadas , Humanos , Proteínas de Membrana , MicroRNAs/genética , Osteogênese/genética , Porosidade , Ratos , Titânio/farmacologiaRESUMO
Microspheres based on cellulose nanocrystal (CNC)/metal oxide hybrid materials have great application prospects in wastewater treatment due to simultaneously adsorption, degradation ability, easily separation and recycling properties. However, the relatively small porosity and specific surface area of the CNC-based microspheres limit their adsorption ability. Herein, we reported a facile strategy to prepare porous microsphere based on CNC/MnO2 by freeze-drying the air-bubble templated emulsion, in which the sodium alginate (SA) was used as the crosslinked matrix. Thus-obtained CNC/MnO2/SA microspheres showed low density of 0.027 g/cm3 and high porosity of 98.23%. Benefiting from the high porosity, synergetic effect of CNC electrostatic adsorption and oxidative degradation ability of MnO2, the decolorization ratio of methylene blue (800 mg/mL) could be up to 95.4% in 10 min, and the equilibrium decolorization could reach 114.5 mg/g. This study provides a green and facile strategy to design porous CNC-based material for dye wastewater treatment.
Assuntos
Celulose/química , Compostos de Manganês/química , Nanopartículas Metálicas/química , Microesferas , Óxidos/química , Purificação da Água/métodos , Adsorção , Alginatos/química , Emulsões , Química Verde/métodos , Azul de Metileno/química , PorosidadeRESUMO
PURPOSE: To explore whether resveratrol dependents on the production of suppressor of cytokine signaling suppressor 3 (SOCS-3) in inhibiting mRNA production of macrophage inflammatory protein-2 (MIP-2) in osteoblasts induced by lipopolysaccharides(LPS) extracted from Porphyromonas endodontalis(P.e). METHODS: MC3T3-E1 cells were treated with different concentrations of resveratrol (0, 5, 10 and 20 µmol/L) and 20 µmol/L resveratrol for different time( 0, 10, 30, 60, 120 and 180 min). The expression of SOCS-3 protein was detected by Western blot. MC3T3-E1 cells were transfected with mouse SOCS3 siRNA (si-SOCS-3) and control siRNA(si-control). Reverse transcription real-time PCR(real-time RT-PCR) and Western blot was used to detect the silencing efficiency of SOCS-3. Cells were stimulated by 20 µg/mL P.e-LPS for 24 h after transfection, in the absence or presence of 20 µmol/L resveratrol for 1 h , and the changes of MIP-2 mRNA were determined by real-time RT-PCR. Statistical analysis was performed using one-way ANOVA and Dunnett t test with SPSS 13.0 software package. RESULTS: Treatment of MC3T3-El cells with different concentrations of resveratrol caused a significant increase in SOCS-3 protein expression in a dose-dependent manner. During the observation time of 180 min, SOCS-3 protein expression was the highest at 20 µmol/L resveratrol-treated osteoblasts for 60 min. The silencing efficiency of SOCS-3 mRNA was 63.7%. Transfection with SOCS-3 siRNA increased MIP-2 mRNA expression in LPS-stimulated MC3T3-E1 cells and negated the inhibitory effects of resveratrol on LPS-induced MIP-2 mRNA expression(P<0.05). CONCLUSIONS: Resveratrol inhibits the expression of MIP-2 mRNA in osteoblasts induced by P.e-LPS by up-regulating the expression of SOCS-3 protein.