RESUMO
The migration and risk of organophosphate esters (OPEs) in agricultural air-soil-plant multimedia systems due to plastic film application remain unclear. This study investigates the multimedia distribution of traditional OPEs (TOPEs), novel OPEs (NOPEs), and their transformation products (POPEs) in plastic and solar greenhouses. The total concentration of OPE-associated contaminants in air and airborne particles ranged from 594 to 1560 pg/m3 and 443 to 15600 ng/g, respectively. Significant correlations between air OPE concentrations and those in polyolefin film (P < 0.01) indicate plastic film as the primary source. Contaminants were also found in soils (96.8-9630 ng/g) and vegetables (197-7540 ng/g). The primary migration pathway for NOPEs was particle dry deposition onto the soil and leaf, followed by plant accumulation. Leaf absorption was the main uptake pathway for TOPEs and POPEs, influenced by vegetable specific leaf surface area. Moreover, total exposure to OPE-associated contaminants via vegetable intake was assessed at 2250 ng/kg bw/day for adults and 2900 ng/kg bw/day for children, with an acceptable hazard index. However, a high ecological risk was identified for NOPE compounds (median risk quotient, 975). This study provides the first evidence of the multimedia distribution and potential threat posed by OPE-associated contaminants in agricultural greenhouses.
Assuntos
Ésteres , Plásticos , Verduras , Verduras/química , Organofosfatos , Humanos , Solo/químicaRESUMO
Specific recognition and strong affinities of bacteria receptors with the host cell glycoconjugates pave the way to control the bacteria aggregation and kill bacteria. Herein, using aggregation-induced emission (AIE) molecules decorated upper critical solution temperature (UCST) polyvalent scaffold (PATC-GlcN), an approach toward visualizing bacteria aggregation and controlling bacteria-polyvalent scaffolds affinities under temperature stimulus is described. Polyvalent scaffolds with diblocks, one UCST block PATC of polyacrylamides showing a sharp UCST transition and typical AIE behavior, the second bacteria recognition block GlcN of hydrophilic glucosamine modified polyacrylamide, are prepared through a reversible addition and fragmentation chain transfer polymerization. Aggregated chain conformation of polyvalent scaffolds at temperature below UCST induces the aggregation of E. coli ATCC8739, because of the high density of glucosamine moieties, whereas beyond UCST, the hydrophilic state of the scaffolds dissociates the bacteria aggregation. The sweet-talking of bacteria toward the polyvalent scaffolds can be visualized by the fluorescent imaging technique, simultaneously. Due to the specific recognition of polyvalent scaffolds with bacteria, the photothermal agent IR780 loaded PATC-GlcN shows the targeted killing ability toward E. coli ATCC8739 in vitro and in vivo under NIR radiation.
Assuntos
Escherichia coli , Polímeros , Polimerização , TemperaturaRESUMO
Polystyrene microplastics (PS-MPs, particle size<5 mm) cause great harm to aquatic organisms. However, their precise effects are not completely understood. In China, placing plastic film at the pond bottom has become an important loach aquaculture mode. In this mode, MPs will affect loach health. This study investigated the enrichment of PS-MPs and its effects on the growth, liver histomorphology, antioxidant enzymes, and Keap1-Nrf2 signaling pathway-related gene expression in loach juveniles (Paramisgurnus dabryanus). The loach juveniles were raised at the concentration of 1000 µg/L fluorescent polystyrene microplastics (PS-MPs) with particle size of 0.5 µm or 5 µm for seven days, the results showed that fluorescent PS-MPs were found to be enriched in liver, intestine, and gill, and the enrichment amount was higher in liver than in gill and intestine (P < 0.05). Furthermore, the enrichment amount of different-sized PS-MPs was different in liver, gill, and intestine. The loach juveniles were cultured for 21 days in the water of the concentration of 100 or 1000 µg/L PS-MPs with particle size of 0.5 µm or 5 µm, the results showed that the survival rate, weight gain rate, and specific growth rate of loach juveniles were significantly reduced. The histological analysis revealed that PS-MPs caused liver damage. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX), and acetylcholinesterase (AChE) were decreased with the extended exposure to PS-MPs. Generally, the expressions of Nrf2 and Keap1 showed the similar change trend. From 7-14 day, the expression trend of oxidative stressed-related genes was not completely consistent with that of Nrf2 gene, but on day 21, the gene expression trend of oxidative stress-related SOD, CAT, and GSH-PX in the downstream of Keap1-Nrf2 signaling pathway was roughly consistent with that of Nrf2 gene. Basically, the change trends of these three gene expression were similar to those of their corresponding enzyme activities. This study provides theoretical basis for the toxicological effects of PS-MPs on freshwater fish.
Assuntos
Cipriniformes , Microplásticos , Acetilcolinesterase , Animais , Cipriniformes/genética , Expressão Gênica , Glutationa Peroxidase/genética , Proteína 1 Associada a ECH Semelhante a Kelch , Microplásticos/toxicidade , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo , Plásticos , Poliestirenos/toxicidade , Transdução de Sinais , Superóxido Dismutase/genéticaRESUMO
Accumulating evidence has shown that poor oral hygiene is associated with increased risk of cardiometabolic diseases in Western populations. However, its relevance about the relationships in Chinese adults remains unclear. The China Kadoorie Biobank enrolled 512 715 adults aged 30-79 years in China during 2004-2008. Cox regression was used to estimate adjusted hazard ratios (HRs) for each disease associated with measures of oral hygiene. Overall 9.3% of the participants reported rarely or never brushing teeth at baseline. Participants who rarely or never brushed teeth had adjusted HR of 1.12 (95% CI: 1.09, 1.15) for MVE, with similar HRs for stroke (1.08, 1.05-1.12), intracerebral haemorrhage (1.18, 1.11-1.26) and pulmonary heart disease (1.22, 1.13-1.32) compared with those who brushed teeth regularly. Those who did not brush teeth also had increased risk of cancer (1.09, 1.04-1.14), chronic obstructive pulmonary disease (COPD) (1.12, 1.05-1.20), liver cirrhosis (1.25, 1.09-1.44) and all-cause death (1.25, 1.21-1.28) but not type 2 diabetes (0.94, 0.86-1.03) and chronic kidney disease (0.98, 0.81-1.18). Among Chinese adults, we found that poor oral hygiene is associated with higher risks of major vascular disease, cancer, COPD, liver cirrhosis and all-cause deaths, but not type 2 diabetes and chronic kidney disease.
Assuntos
Doenças Cardiovasculares/epidemiologia , Cirrose Hepática/epidemiologia , Mortalidade , Neoplasias/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Escovação Dentária/estatística & dados numéricos , Adulto , Idoso , Hemorragia Cerebral/epidemiologia , China/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Higiene Bucal , Modelos de Riscos Proporcionais , Doença Cardiopulmonar/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Fatores de Risco , Acidente Vascular Cerebral/epidemiologiaRESUMO
Dentin matrix protein 1 (DMP1) is an extracellular matrix phosphoprotein that is known to facilitate mineralization of collagen in bone and promote osteoblast/odontoblast differentiation. Blood-brain barrier (BBB) disruption is the major pathogenesis in secondary brain injury after intracerebral hemorrhage (ICH). This study aimed to investigate the expression pattern of DMP1 in the mouse brain and explore the role of DMP1 in BBB disruption and brain injury in a mouse model of ICH. Mice were subjected to autologous blood injection-induced ICH. Immunofluorescence staining, western blot analysis, neurobehavioral tests, brain water content measurements, Evans blue permeability assay, and transmission electron microscopy were performed. Small interfering RNA targeting DMP1 (DMP1 siRNA) was administered at 72 h prior to ICH. Results showed that DMP1 is expressed extensively in the mouse brain, and is upregulated in the ICH model. Administration of DMP1 siRNA effectively ameliorated BBB disruption, attenuated brain edema, and improved neurological function after ICH. Moreover, the expression of zonula occludens-1 (ZO-1) and occludin were upregulated, and matrix metalloproteinase-9 (MMP-9) was downregulated in the ICH model. DMP1 siRNA administration reversed the expression of ZO-1, occludin, and MMP-9. These results demonstrated that DMP1 upregulation plays an essential role in inducing BBB disruption and brain injury after ICH. The inhibition of DMP1 could be a potential therapeutic strategy for ICH treatment.
Assuntos
Barreira Hematoencefálica/metabolismo , Edema Encefálico/prevenção & controle , Hemorragia Cerebral/terapia , Proteínas da Matriz Extracelular/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Animais , Barreira Hematoencefálica/ultraestrutura , Edema Encefálico/genética , Edema Encefálico/metabolismo , Edema Encefálico/patologia , Hemorragia Cerebral/genética , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patologia , Modelos Animais de Doenças , Proteínas da Matriz Extracelular/genética , Masculino , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Ocludina/genética , Ocludina/metabolismo , RNA Interferente Pequeno/genética , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismoRESUMO
In this study, mixed micelles of Soluplus® and TPGS were developed for co-administering docetaxel (DTX) and piperine (PIP) for exerting the synergistic effect, which increased the cytotoxicity and improved the anti-cancer activity in HepG2 cell lines compared to free DTX. These in vitro (MTT assay, intracellular uptake of micelles) and in vivo (pharmacokinetic study, immunostaining, TUNEL analysis) studies exhibited the advantages of co-delivery of anticancer drugs with Soluplus®/TPGS by mixed micelles and furthermore established that co-delivery of DTX and PIP via the mixed micelles of Soluplus®/TPGS could be a promising strategy for the treatment of liver cancer.
Assuntos
Alcaloides/química , Alcaloides/farmacologia , Benzodioxóis/química , Benzodioxóis/farmacologia , Docetaxel/química , Docetaxel/farmacologia , Neoplasias/tratamento farmacológico , Piperidinas/química , Piperidinas/farmacologia , Polietilenoglicóis/química , Alcamidas Poli-Insaturadas/química , Alcamidas Poli-Insaturadas/farmacologia , Polivinil/química , Vitamina E/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Células Hep G2 , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Micelas , Ratos , Ratos Sprague-DawleyRESUMO
Fenretinide (4-HPR), as a semi-synthetic retinoid, has apoptosis-promoting effects as a single agent and chemotherapy synergist in vitro. When a human ovarian cancer cells line (A2780s) was treated with both PTX and 4-HPR, there was a synergistic anti-cancer effect demonstrated with a average combination index of 0.44. In this research, a new TPGS-Soluplus® mixed micelles were developed which encapsulation efficiencies of paclitaxel (PTX) and fenretinide (4-HPR) were as high as 98%, and the average diameter of the micelles was 66.26 nm. Cytotoxicity of the mixed micelles co-delivered with PTX and 4-HPR reduced significantly 7.3 and 25.1 times compared with free drug respectively in A2780s cells. More importantly, in vivo pharmacokinetic study, the loaded drugs in mixed micelles exhibited higher AUC and t1/2 values than free drugs. Furthermore, in vivo antitumor efficacy experiments demonstrated that PF-TS exhibited superior in vivo antitumor activity on the inhibition rate of tumor growth than other treatment groups (77.8% corresponding tumor growth inhibition in PF-TS treated group vs 19.9, 12.5, and 26.0% of tumor growth inhibition rate in Taxol®, 4-HPR, and Taxol®+4-HPR, respectively). Therefore, the mixed micelles of co-deliver PTX and 4-HPR successfully constructed may hopefully be applied to the cancer combination treatment with less toxic effect and more antitumor activity.
Assuntos
Antineoplásicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Fenretinida/administração & dosagem , Micelas , Paclitaxel/administração & dosagem , Polietilenoglicóis/administração & dosagem , Polivinil/administração & dosagem , Vitamina E/administração & dosagem , Animais , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/farmacocinética , Feminino , Fenretinida/farmacocinética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Paclitaxel/farmacocinética , Polietilenoglicóis/farmacocinética , Polivinil/farmacocinética , Ratos , Ratos Wistar , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/fisiologia , Vitamina E/farmacocinética , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
Fenretinide (4-HPR), a synthetic retinoid, has shown its antitumor activity in many tumor types with low cytotoxicity to normal cells and high clinical safety. However, the low water solubility limits its further biological applications. To increase solubility, 4-HPR was conjugated with methoxy polyethylene glycol carboxylic acid (mPEG2K-COOH) by an ester linkage between the phenol hydroxyl of 4-HPR and the carboxyl of mPEG2K-COOH. The 4-HPR-PEG2K conjugate micelles had mean size of 76.70 ± 1.248 nm with a narrow distribution and a low critical micelle concentration. In vitro cytotoxicity studies showed the micelles have higher cytotoxicity to A2780s and MCF-7 cells. Its IC50 was 4.7 and 4.1-fold lower than the free 4-HPR, respectively. Importantly, in vivo pharmacokinetic studies, the AUC of 4-HPR was found to be 2.3-fold higher in 4-HPR-PEG2K micelles compared to free 4-HPR. And the 4-HPR-PEG2K micelles had higher antitumor activity. Meanwhile, the histopathology analysis exhibited that the micellar treatment decreased the viability of A2780s cells and increased the level of induced apoptosis. Therefore, the enhanced activity of 4-HPR by the method of conjugation with mPEG2K-COOH could hopefully provide new insights into the matter of ovarian cancer and breast cancer treatment.
Assuntos
Antineoplásicos/farmacologia , Fenretinida/farmacologia , Polietilenoglicóis/química , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , Células MCF-7 , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Micelas , Ratos Sprague-Dawley , Solubilidade/efeitos dos fármacosRESUMO
Clinically, co-delivery of chemotherapeutics has been limited by poor water-solubility and severe systemic toxicity. This study was aimed at integrating the merits of combination chemotherapy and mixed micellar technology and demonstrating the anticancer potential of doxorubicin (DOX) and dihydroartemisinin (DHA) co-loaded Soluplus®-TPGS mixed micellar system. In this study, physiochemically stable multidrug loaded mixed micelles were successfully prepared, encapsulation efficiencies of DOX and DHA were as high as 90%, and the average diameter of the micelles was 64.27 nm. The cellular uptake of DOX from the mixed micelles increased by 1.3 and 1.2 times for MCF-7 and MCF-7/ADR cell lines, respectively. The micelles were more cytotoxic than free DHA-DOX. Surprisingly, the co-loaded mixed micelles exhibited higher antitumor activity, while the systemic toxicity was reduced during the treatment. Therefore, the DOX and DHA mixed micelle might be a potential, effective, and less toxic drug-delivery system for cancer therapy.
Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Antimaláricos/administração & dosagem , Artemisininas/administração & dosagem , Doxorrubicina/administração & dosagem , Polietilenoglicóis/química , Polivinil/química , Vitamina E/química , Antibióticos Antineoplásicos/farmacologia , Antimaláricos/farmacologia , Artemisininas/farmacologia , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Combinação de Medicamentos , Feminino , Humanos , Células MCF-7 , MicelasRESUMO
BACKGROUND: Although piperine can inhibit cells of tumors, the poor water solubility restricted its clinical application. This paper aimed to develop mixed micelles based on Soluplus® and D-α-tocopherol polyethylene glycol succinate (TPGS) to improve the aqueous solubility and anti-cancer effect. METHODS: Piperine-loaded mixed micelles were prepared using a thin-film hydration method, and their physicochemical properties were characterized. The cellular uptake of the micelles was confirmed by confocal laser scanning microscopy in A549 lung cancer cells and HepG2 liver cancer cells. In addition, cytotoxicity of the piperine mixed micelles was studied in A549 lung cancer cells and HepG2 liver cancer cells. Free piperine or piperine-loaded Soluplus®/TPGS mixed micelles were administered at an equivalent dose of piperine at 3.2 mg/kg via a single intravenous injection in the tail vain for the pharmacokinetic study in vivo. RESULTS: The diameter of piperine-loaded Soluplus®/TPGS (4:1) mixed micelles was about 61.9 nm and the zeta potential -1.16 ± 1.06 mV with 90.9% of drug encapsulation efficiency and 4.67% of drug-loading efficiency. Differential scanning calorimetry (DSC) studies confirmed that piperine is encapsulated by the Soluplus®/TPGS. The release results in vitro showed that the piperine-loaded Soluplus®/TPGS mixed micelles presented sustained release behavior compared to the free piperine. The mixed micelles exhibited better antitumor efficacy compared to free piperine and physical mixture against in A549 and HepG2 cells by MTT assay. The pharmacokinetic study revealed that the AUC of piperine-loaded mixed micelles was 2.56 times higher than that of piperine and the MRT for piperine-loaded mixed micelles was 1.2-fold higher than piperine (p < .05). CONCLUSION: The results of the study suggested that the piperine-loaded mixed micelles developed might be a potential nano-drug delivery system for cancer chemotherapy. These results demonstrated that piperine-loaded Soluplus®/TPGS mixed micelles are an effective strategy to deliver piperine for cancer therapy.
Assuntos
Alcaloides/química , Alcaloides/farmacologia , Benzodioxóis/química , Benzodioxóis/farmacologia , Neoplasias/tratamento farmacológico , Piperidinas/química , Piperidinas/farmacologia , Polietilenoglicóis/química , Alcamidas Poli-Insaturadas/química , Alcamidas Poli-Insaturadas/farmacologia , Polivinil/química , Vitamina E/química , Células A549 , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Células Hep G2 , Humanos , Masculino , Micelas , Ratos Sprague-Dawley , Solubilidade/efeitos dos fármacosRESUMO
PURPOSE: Emodin (EMO) has multi-targets and multi-way antitumor effect, which was limited by the instability and poor solubility of EMO. The aim of this study was to formulate EMO-loaded poly (lactide-co-glycolide)-d-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (EPTN) to increase the liver targeting of EMO for cancer therapy. METHODS: EMO/coumarin-6-loaded PLGA-TPGS nanoparticles (ECPTN) and EMO-loaded PLGA nanoparticles (EPN) were also prepared as comparison. The cellular uptake of ECPTN by HepG2 and HCa-F cells was investigated using Confocal laser scanning microscopy. The apoptosis of HepG2 cells handled with EPTN was assayed by flow cytometry. The liver targeting property of ECPTN in mice was evaluated using the drug concentration determined by RP-HPLC and the freezing slices were investigated via fluorescence inversion microscopy. The blood samples were obtained from vein intubation to illustrate the pharmacokinetics process of EPTN. The tumor-bearing mice model was established to elucidate the in vivo therapeutic effect of EPTN. RESULTS: The results demonstrated that ECPTN could be internalized by HepG2 and HCa-F cells respectively. The ratio of apoptosis cells was increased after dealing with EPTN. The detection indexes of drug concentration and fluorescence inversion microscopy images indicated ECPTN had an excellent effect on liver targeting property than EMO solutions (EMS). The pharmacokinetics process of EPTN showed obvious sustained-release effect than EMS. Compared with EPN, the in vivo antitumor activity of EPTN against tumor cells were better. CONCLUSIONS: In conclusion, EPTN could be used in the treatment of liver cancer acted as a kind of promising intravenous dosage forms.
Assuntos
Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Emodina/administração & dosagem , Emodina/uso terapêutico , Ácido Láctico/química , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas/química , Polietilenoglicóis/química , Ácido Poliglicólico/química , alfa-Tocoferol/química , Animais , Antineoplásicos/farmacocinética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos , Emodina/farmacocinética , Humanos , Camundongos , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Ratos Sprague-DawleyRESUMO
OBJECTIVES: Hepatocellular carcinoma is the third most common cause of cancer death. Oleanolic acid (OA) is a natural triterpenoid, has many important biological actions, including antitumor effect, but its poor solubility often leads to poor pharmacodynamics. The aim of our work is to make OA-loaded poly (lactide-co-glycolide)-d-α-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) nanoparticles (OPTN) to improve its efficacy to liver cancer and characterize it. METHODS: OPTN were prepared by ultrasonic emulsification-solvent evaporation technique using PLGA with or without the addition of TPGS (OPN). The coumarin-6-loaded nanoparticles were used as a fluorescence marker. The nanoparticles were characterized for surface morphology, surface charge, particle size, drug loading, encapsulation efficiency, in vitro drug-release, cellular uptake, cytotoxicity by human liver cancer cell line HepG2 cells, and therapeutic effect in vivo. KEY FINDINGS: The prepared nanoparticles were found to be spherical in shape. The in vitro drug-release profile of both nanoparticle formulations showed a biphasic release pattern. There was an increased level of uptake and cytotoxicity of OPTN in the HepG2 cells compared with that of OPN. The treatment of OPTN group was better than OPN and FS groups in vivo. CONCLUSION: The results showed advantages of OPTN in terms of sustainable release and efficacy in liver cancer chemotherapy compared with OPN. OPTN could be acted as a novel and new dosage form to be used in cancer treatment study.
Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Nanopartículas , Ácido Oleanólico/administração & dosagem , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/patologia , Cumarínicos/administração & dosagem , Cumarínicos/química , Preparações de Ação Retardada , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Células Hep G2 , Humanos , Ácido Láctico/química , Neoplasias Hepáticas/patologia , Ácido Oleanólico/química , Ácido Oleanólico/farmacologia , Polietilenoglicóis/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Solubilidade , Tiazóis/administração & dosagem , Tiazóis/química , Vitamina E/análogos & derivados , Vitamina E/químicaRESUMO
OBJECTIVES: This paper describes the development and optimization of curcumin thermosensitive hydrogels (CTH), a kind of gel injection for intratumoral injection treatment. METHODS: Aimed at increasing the content and stability of effective components, an optimal formulation of CTH was chosen based on the results from orthogonal tests and the optimal pH was determined by stability test. To investigate the hydrogels drug release in vitro, residence time by RP-HPLC and therapeutic effects on ascitic hepatocarcinoma cell strain with high metastasis potential in lymphatic system (HCA-F) solid tumors in mice. KEY FINDINGS: The selected optimal formulation of CTH was: 0.2% curcumin, 20% poloxamer 407, 4% poloxamer 188, 8% polyethylene glycol 400, 12% 1,2-propanediol and pH was 6.0. The drug release determined by RP-HPLC fit to the Higuchi model. The residence time of CTH was longer than the curcumin suspensions. Intratumoral injection of the CTH can effectively inhibit the growth of HCA-F solid tumors in mice. CONCLUSIONS: The CTH prepared in this test demonstrates proper gel temperature and viscosity. It improves the solubility of curcumin with a relatively long period of drug release in vitro and residence time. Intratumoral injection of the CTH can effectively inhibit the growth of HCA-F solid tumors in mice.
Assuntos
Curcumina/administração & dosagem , Curcumina/farmacologia , Hidrogéis/química , Poloxâmero/química , Polietilenoglicóis/química , Animais , Química Farmacêutica , Cromatografia de Fase Reversa , Portadores de Fármacos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Camundongos , Temperatura , ViscosidadeRESUMO
A free-standing electrode based on carbon cloth-supported Fe-doped polydopamine-derived carbon (Fe/PDA-C/CC) was developed for the simultaneous detection of dopamine (DA) and uric acid (UA). First, dopamine was self-polymerized on the surface of the carbon cloth to obtain polydopamine coatings. Subsequently, Fe3+ was introduced through the formation of a coordinate bond with the hydroxyl functional group in the polydopamine layer. After calcination, a flexible and free-standing electrode was obtained. The sensing performance and mechanism of the Fe/PDA-C/CC sensor was investigated and is discussed in detail herein. Experimental results demonstrated that Fe/PDA-C/CC could simultaneously detect DA and UA with a wide detection range of 0.5-300 µM and 0.5-400 µM with low detection limits of 0.041 µM and 0.012 µM, respectively. Meanwhile, Fe/PDA-C/CC possessed excellent anti-interference performance, repeatability, stability, and accuracy in real samples. Overall, this study provides a facile and effective approach for simultaneous detection of UA and DA.
Assuntos
Carbono , Dopamina , Técnicas Eletroquímicas , Indóis , Ferro , Polímeros , Ácido Úrico , Ácido Úrico/análise , Ácido Úrico/química , Indóis/química , Polímeros/química , Dopamina/análise , Dopamina/química , Carbono/química , Técnicas Eletroquímicas/métodos , Ferro/química , Ferro/análise , Limite de Detecção , Humanos , EletrodosRESUMO
PURPOSE: The aim of this study was to evaluate the long-term effects of serial intravitreal injections (IVI) on measures of dry eye. METHODS: The PubMed, EMBASE, and Cochrane databases were searched according to the PROSPERO protocol (CRD42023455727). Studies evaluating the influence of serial IVI on the ocular surface compared with untreated fellow eyes were included. The measures of dry eye after IVI were used as outcome variables. The results are presented as mean difference (MD) with a corresponding 95% confidence interval (CI). RESULTS: A total of 4 studies with 259 participants were included in this meta-analysis. Significant increases in ocular surface disease index (OSDI) scores (MD 10.26, 95 % CI 5.05 to 15.46, p ï¼ 0.01) and tear film osmolarity (TOsm; MD 4.40, 95 % CI 0.87 to 7.92, p = 0.01) were observed in the IVI treated eyes compared to the untreated fellow eyes. There was no significant difference between the groups with respect to fluorescein tear film break-up time (TBUT; p = 0.05), average non-invasive tear film break-up time (NITBUT; p = 0.94), first NITBUT (p = 0.78) and Schirmer test (p = 0.94). CONCLUSION: Repeated IVI of anti-VEGF agents with preoperative povidone-iodine application was associated with increased OSDI scores and TOsm, while no significant difference was found in fluorescein TBUT, average NITBUT, first NITBUT and Schirmer test. The ocular surface may partially recover after the procedures, but IVI still has deleterious effects on the ocular surface.
Assuntos
Síndromes do Olho Seco , Humanos , Injeções Intravítreas , Síndromes do Olho Seco/tratamento farmacológico , Povidona-Iodo , Lágrimas , FluoresceínaRESUMO
Oral cancer is introduced as the uncontrolled cells' growth that causes destruction and damage to nearby tissues. This occurs when a sore or lump grows in the mouth that does not disappear. Cancers of the cheeks, lips, floor of the mouth, tongue, sinuses, hard and soft palate, and lungs (throat) are types of this cancer that will be deadly if not detected and cured in the beginning stages. The present study proposes a new pipeline procedure for providing an efficient diagnosis system for oral cancer images. In this procedure, after preprocessing and segmenting the area of interest of the inputted images, the useful characteristics are achieved. Then, some number of useful features are selected, and the others are removed to simplify the method complexity. Finally, the selected features move into a support vector machine (SVM) to classify the images by selected characteristics. The feature selection and classification steps are optimized by an amended version of the competitive search optimizer. The technique is finally implemented on the Oral Cancer (Lips and Tongue) images (OCI) dataset, and its achievements are confirmed by the comparison of it with some other latest techniques, which are weight balancing, a support vector machine, a gray-level co-occurrence matrix (GLCM), the deep method, transfer learning, mobile microscopy, and quadratic discriminant analysis. The simulation results were authenticated by four indicators and indicated the suggested method's efficiency in relation to the others in diagnosing the oral cancer cases.
RESUMO
The 1,3-dipolar cycloaddition of azides and active internal alkynes has been well studied, but is rarely utilized as a tool for polymer preparation. In this work, an efficient polymerization route is developed. Polycycloaddition of diazide (4) and bis(benzoylethynyl)-benzenes and -butane (3) at elevated temperature has produced the first examples of soluble 1,4,5-trisubstituted polytriazoles PI with satisfactory molecular weights (M(w) up to 16 400) in excellent yields (up to 98.6%). All the obtained polymers are thermally stable, losing merely 5% of their weights at temperatures higher than 367 °C. They exhibit higher refractive indices than some commercial plastics and can be crosslinked upon UV irradiation to generate a 3D photopattern with high resolution. The metal-free feature of such a methodology offers a facile tool to prepare functional materials free from the contamination of metal species.
Assuntos
Alcinos/química , Azidas/química , Polímeros/síntese química , Estrutura Molecular , Polimerização , Polímeros/químicaRESUMO
Magnesium (Mg) alloys as implant materials with excellent biodegradation ability have promising clinical applications for tissue repair and restoration. Although the corrosion processes of Mg alloys in biophysiological media are closely related with their biodegradation ability, only limited methods have been developed for characterization of their corrosion processes, including electrochemical analysis, weight loss measurement, and hydrogen evolution analysis. Moreover, these methods suffer from drawbacks of poor spatiotemporal resolution, static observation, and tedious operation. To tackle these challenges, we herein developed a fluorescent probe PSPA for in situ 3D monitoring of the dynamic corrosion processes of Mg alloys on the basis of its selective turn-on detection ability toward magnesium hydroxide [Mg(OH)2], which is the main corrosion product of Mg alloys in biophysiological media. As far as we know, this is the first example of a fluorescent probe for the monitoring of corrosion processes of Mg alloys in biophysiological media. We believe this fluorescence analysis method with easy operation and high spatiotemporal resolution advantages will contribute greatly to the clinical applications of Mg alloy implants.
Assuntos
Ligas , Magnésio , Ligas/química , Corrosão , Corantes Fluorescentes , Imageamento Tridimensional , Magnésio/químicaRESUMO
Coxsackievirus A16 (CVA16) is one of the major pathogens responsible for human hand, foot, and mouth disease (HFMD), which has threatened the health of young children, particularly in Asia-Pacific nations. Vaccination is an effective strategy for protecting children from CVA16 infection. However, there is currently no licensed CVA16 vaccine for use in humans. In this study, we isolated a high-growth CVA16 virus strain in MRC-5 cells and developed an MRC-5-adapted vaccine candidate strain termed CVA16-393 via two rounds of plaque purification. The CVA16-393 strain was grouped into the B1b subgenotype and grew to a titre of over 107 TCID50/ml in MRC-5 cells. The VP1 gene region of this strain, which contains the major neutralizing epitopes, displayed high stability during serial passages. The inactivated whole-virus vaccine produced by the CVA16-393 strain induced an effective neutralizing antibody response in Meriones unguiculatus (gerbils) after two doses of intraperitoneal inoculation. One week after the booster immunization, the geometric mean titres of the neutralizing antibodies for the 10246, 40812TXT, 11203SD, TJ-224 and CA16-194 strains from different regions of China were 137.8, 97.8, 113.4, 64.1 and 122.3, respectively. A CVA16 vaccine dose above 25 U was also able to provide 100% cross-protection against lethal challenges with these five clinical strains in gerbils. Immunization at a one-week interval could maintain a high level of neutralizing antibody titres for at least 8 weeks. Thus, the vaccine produced by this CVA16-393 strain might be promising.
Assuntos
Enterovirus Humano A , Enterovirus , Doença de Mão, Pé e Boca , Vacinas Virais , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Criança , Pré-Escolar , Enterovirus/genética , Enterovirus Humano A/genética , Gerbillinae , Doença de Mão, Pé e Boca/prevenção & controle , Humanos , Vacinas de Produtos InativadosRESUMO
With the vigorous development of electronics and the increasingly prominent problem of environmental pollution, it is particularly important to exploit environmentally friendly electronic devices. Transient electronics represent a kind of device that once the specified functions have completed can completely or partially disappear through physical or chemical actions. In this work, we introduce a novel guar gum-cellulose aerogel (GCA) membrane based on natural biomaterials and successfully use it as an electrolyte film to fabricate a degradable zinc-ion battery (DZIB). All components of the prepared DZIBs can be successfully degraded or disintegrate in phosphate-buffered saline (PBS) containing a solution of proteinase K after approximately 40 days. This electrolyte film has a high ionic conductivity of approximately 4.73 × 10-2 S cm-1 and a good mechanical stress property. When applied to DZIB, the production of zinc dendrites can be restrained, leading to the battery showing excellent electrochemical performance. The battery exhibits a specific capacity of 309.1 mA h g-1 at a current density of 308 mA g-1 after 100 cycles and a steady cycling ability (100% capacity retention after 200 cycles). More importantly, the electrochemical performance of DZIB is better than that of transient batteries reported in the past, taking a solid step in the field of transient electronics in the initial stage.