RESUMO
Microplastics are readily accumulated in coastal sediments, where active sulfur (S) cycling takes place. However, the effects of microplastics on S cycling in coastal sediments and their underlying mechanisms remain poorly understood. In this study, the transformation patterns of different S species in mangrove sediments amended with different microplastics and their associated microbial communities were investigated using stable isotopic analysis and metagenomic sequencing. Biodegradable poly(lactic acid) (PLA) microplastics treatment increased sulfate (SO42-) reduction to yield more acid-volatile S and elementary S, which were subsequently transformed to chromium-reducible S (CRS). The S isotope fractionation between SO42- and CRS in PLA treatment increased by 9.1 from days 0 to 20, which was greater than 6.8 in the control. In contrast, recalcitrant petroleum-based poly(ethylene terephthalate) (PET) and polyvinyl chloride (PVC) microplastics had less impact on the sulfate reduction, resulting in 7.6 and 7.7 of S isotope fractionation between SO42- and CRS from days 0 to 20, respectively. The pronounced S isotope fractionation in PLA treatment was associated with increased relative abundance of Desulfovibrio-related sulfate-reducing bacteria, which contributed a large proportion of the microbial genes responsible for dissimilatory sulfate reduction. Overall, these findings provide insights into the potential impacts of microplastics exposure on the biogeochemical S cycle in coastal sediments.
Assuntos
Microplásticos , Plásticos , Isótopos de Enxofre/análise , Enxofre , Isótopos/análise , Poliésteres , Sulfatos/análise , Sedimentos Geológicos/análiseRESUMO
Current nanoparticle (NP) drug carriers mostly depend on the enhanced permeability and retention (EPR) effect for selective drug delivery to solid tumors. However, in the absence of a persistent EPR effect, the peritumoral endothelium can function as an access barrier to tumors and negatively affect the effectiveness of NPs. In recognition of the peritumoral endothelium as a potential barrier in drug delivery to tumors, poly(lactic-co-glycolic acid) (PLGA) NPs are modified with a quinic acid (QA) derivative, synthetic mimic of selectin ligands. QA-decorated NPs (QA-NP) interact with human umbilical vein endothelial cells expressing E-/P-selectins and induce transient increase in endothelial permeability to translocate across the layer. QA-NP reach selectin-upregulated tumors, achieving greater tumor accumulation and paclitaxel (PTX) delivery than polyethylene glycol-decorated NPs (PEG-NP). PTX-loaded QA-NP show greater anticancer efficacy than Taxol or PTX-loaded PEG-NP at the equivalent PTX dose in different animal models and dosing regimens. Repeated dosing of PTX-loaded QA-NP for two weeks results in complete tumor remission in 40-60% of MDA-MB-231 tumor-bearing mice, while those receiving control treatments succumb to death. QA-NP can exploit the interaction with selectin-expressing peritumoral endothelium and deliver anticancer drugs to tumors to a greater extent than the level currently possible with the EPR effect.
Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Células Endoteliais/metabolismo , Nanopartículas/química , Ácido Quínico/química , Animais , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Feminino , Citometria de Fluxo , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Mamárias Animais/tratamento farmacológico , Neoplasias Mamárias Animais/metabolismo , Camundongos , Camundongos Nus , Microscopia Confocal , Polímeros/química , Selectinas/química , Microambiente Tumoral/fisiologiaRESUMO
Arsenic decontamination from groundwater is an urgent but still challenging task. Polystyrene-based hydrated ferric oxide (denoted as D201-HFO) nanocomposite is a new emerging current adsorbent for efficient arsenate removal in natural waters; the resulting materials can interact with arsenate, mainly driven by inner complexation and static interaction and the existing HA effects on adsorption was well investigated. Results reveals that low concentrations of HA (below 25 mg/L) coexistence led to negligible effects on As(V) removal, but high levels of HA (100 mg/L) exerted outstanding sorption competition to As(V) removal; kinetics results revealed the HA additions brought about the diffusion prolonging and capacity decline, due to the large molecule structure of HA. Column experiments further showed the slight decrease application capacity of 810 BV by HA additions, with satisfactory saturation capacity; significantly, the presence of HA also exerted negligible influences on regeneration performances. All the sorbents with or without HA could be well regenerated by binary alkaline and salt mixture.
Assuntos
Arseniatos/química , Nanopartículas/química , Poliestirenos/química , Poluentes Químicos da Água/química , Adsorção , Arseniatos/análise , Arsênio , Recuperação e Remediação Ambiental/métodos , Compostos Férricos/química , Água Subterrânea , Concentração de Íons de Hidrogênio , Poliestirenos/análise , Poluentes Químicos da Água/análise , Purificação da Água/métodosRESUMO
Disulfiram (DSF) exerts potent anticancer activity via the formation of chelates with copper or zinc ions in tumor tissues, but the low abundance of these ions in the tumor cannot sustain its antitumor activity. Herein, we show that a zwitterionic water-soluble N-oxide polymer, poly[2-(N-oxide-N,N-dimethylamino)ethyl methacrylate] (OPDMA), can complex cupric ions and form nanogels (OPDMA/Cu), which efficiently deliver copper ions to tumor tissue to potentiate DSF significantly for effective antitumor therapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Cobre/administração & dosagem , Dissulfiram/administração & dosagem , Administração Intravenosa , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Dissulfiram/farmacologia , Sinergismo Farmacológico , Feminino , Humanos , Camundongos , Nanogéis , Óxidos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
We report the first neutral and water-soluble polymer capable of strong mitochondrial targeting in vitro and in vivo, zwitterionic poly[2-(N-oxide-N,N-diethylamino)ethyl methacrylate] (OPDEA). OPDEA is quickly internalized via macropinocytosis by various cancer cells and transferred into the mitochondria, which slightly lowers the mitochondrial membrane potential as determined by the JC-1 assay.
Assuntos
Mitocôndrias/metabolismo , Ácidos Polimetacrílicos/química , Animais , Linhagem Celular Tumoral , Corantes Fluorescentes/química , Humanos , Concentração de Íons de Hidrogênio , Potencial da Membrana Mitocondrial , Camundongos , Imagem Óptica/métodos , Permeabilidade , Ácidos Polimetacrílicos/metabolismo , Solubilidade , ÁguaRESUMO
Salecan is a biological macromolecular and biocompatible polysaccharide that has been investigated for recent years. Herein, we report a novel cationic hydrogel fabricated by graft-polymerizing 3-(methacryloylamino)propyl-trimethylammonium chloride (MAPTAC) onto salecan chains. The obtained hydrogels were transparent, solid-elastic, macro-porous, ion-sensitive, and non-cytotoxic. The swelling ratios increased with salecan content, while mechanical strength does the opposite. Moreover, drug delivery test was studied as a potential application. Diclofenac sodium (DS) and insulin were selected as model drugs. Interestingly, in drug loading process, DS molecules exhibited highly affinity to these cationic hydrogels. Almost all the DS molecules in loading solution were absorbed and spread into the hydrogel. For drug release profiles, insulin-loaded hydrogel showed an initial rapid release and a sustained release. As a comparison, DS-loaded hydrogel exhibited a more sustained release profile. Results suggested salecan-g-PMAPTAC hydrogel could be a good candidate for anionic drug loading and delivery.
Assuntos
Portadores de Fármacos/química , Portadores de Fármacos/síntese química , Hidrogel de Polietilenoglicol-Dimetacrilato/química , beta-Glucanas/química , beta-Glucanas/síntese química , Técnicas de Química Sintética , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Células HEK293 , Humanos , Polimerização , Reologia , beta-Glucanas/toxicidadeRESUMO
Salecan is a novel water soluble polysaccharide produced by a salt-tolerant strain Agrobacterium sp. ZX09. Poly(dimethylaminoethyl methacrylate) (PDMAEMA) is a pH, thermo, and ionic strength multi-sensitive polymer with anti-bacterial property. Here, we report a semi-interpenetrating polymer network (semi-IPN) hydrogel based on salecan and PDMAEMA. The obtained hydrogel is simultaneous sensitive to pH, ionic strength and temperature: the swelling ratio maximizes at pH 1.2 and shrinks at pH value greater than 3; besides, water content of the hydrogel decreases as the ionic strength increases; in terms of temperature, the hydrogel swells/deswells at temperatures below/above 40°C. Cytotoxicity test shows the hydrogel is non-cytotoxic to COS-7 cells. Protein drug insulin was selected as model drug to test the in vitro release behavior of the hydrogel. Results show the release rate increases with the swelling ratio of the hydrogel. In addition, when the temperature is higher than the lower critical solution temperature (LCST) of PDMAEMA, the hydrogel shrinks to extrude more drug molecules. Moreover, the release rate and release amount were higher in acid condition (pH 1.2) than at pH 7.4. In summary, this polysaccharide hydrogel is a promising material for drug delivery.
Assuntos
Sistemas de Liberação de Medicamentos , Hidrogéis/química , Metacrilatos/química , Nylons/química , Polissacarídeos Bacterianos/química , beta-Glucanas/química , Agrobacterium/química , Concentração de Íons de Hidrogênio , Polímeros , TemperaturaRESUMO
Selective gene expression in tumors via responsive dissociation of polyplexes triggered by intracellular signals is demonstrated. An esterase-responsive charge-reversal polymer mediates selective gene expression in the cancer cells high in esterases over fibroblasts low in esterase activity. Its gene therapy with the TRAIL suicide gene effectively induces apoptosis of HeLa cells but does not activate fibroblasts to secrete WNT16B, enabling potent cancer gene therapy with few side effects.
Assuntos
Esterases/metabolismo , Fibroblastos , Regulação Neoplásica da Expressão Gênica , Terapia Genética , Neoplasias/genética , Neoplasias/terapia , Polímeros/química , Apoptose/genética , Fibroblastos/enzimologia , Fibroblastos/metabolismo , Genes Transgênicos Suicidas/genética , Células HeLa , Humanos , Neoplasias/enzimologia , Proteínas Wnt/metabolismoRESUMO
OBJECTIVE: To investigate the effect of coenzyme Q10 on the levels of tumor necrosis factor-α(TNF-α) and interleukin-10 (IL-10) in gingival tissue of experimental periodontitis in rats. METHODS: A total of 48 healthy Wistar rats were divided into 3 groups of 16 randomly, normal group, coenzyme Q10 treatment group (Q10 group) and periodontitis group.Normal group was fed with normal diet and water. Periodontitis models were established in other two groups.Q10 group received coenzyme Q10 for 12 weeks and periodontitis group was fed with the same dose of normal saline.Four rats in each group were sacrified before administration and 4, 8 and 12 weeks after administration. Gingival tissue samples from mandiblar first permanent molar were taken. The levels of TNF-α and IL-10 were detected by immunohistochemistry. RESULTS: The expression of TNF-α in periodontitis group [54.9% (52.9%, 57.3%)] was significantly higher than that in Q10 group [15.1% (12.7%, 17.5%)] at 12 weeks (P < 0.0167) . The expression of IL-10 in periodontitis group [8.9% (7.9%, 10.0%)]was significantly lower than that in the Q10 group [38.9% (38.0%, 40.4%)] (P < 0.0167) . The expression of TNF-α in periodontitis group was significantly higher than that in Q10 group at 12th weeks (P < 0.0167) . The expression of IL-10 in periodontitis group was significantly lower than that in the Q10 group (P < 0.0167). CONCLUSIONS: Coenzyme Q10 inhibits the expression of TNF-α and promotes the expression of IL-10 in periodontal tissues of experimental periodontitis rats. Coenzyme Q10 may play a role in treating periodontitis.
Assuntos
Gengiva/metabolismo , Interleucina-10/metabolismo , Periodontite/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Ubiquinona/análogos & derivados , Animais , Antioxidantes/farmacologia , Distribuição Aleatória , Ratos , Ratos Wistar , Ubiquinona/farmacologiaRESUMO
OBJECTIVE: To study the effects of jaw advancement in treating micromandibular deformity associated with obstructive sleep apnea syndrome (OSAS) by ramus osteotomy and genioplasty. METHODS: From April 1998 to February 2002, 12 patients with micromandibular deformity associated with OSAS (aged 14-36 years, 7 females and 5 males) were treated. Invert "L" shape ramus osteotomy and inverted replantation of posterior segment of ramus were performed to reconstruct the TMJ with the jaw advancement and genioplasty at the same time in 7 cases; mandibular angle osteotomy, bone grafts and genioplasty in 3 cases; and the jaw advancement by ramus sagittal osteotomy and genioplasty in 2 cases of the first branchial arch syndrome. RESULTS: The follow-up period was 6 months to 4 years. All the patients gained good appearance and had the distance of opening movement over 3.0 cm. Micromandible and facial asymmetries were corrected satisfactorily. The ratio of SaO2 was ascended from 82%-92% (preoperation) to 97%-99% (postoperation). OSAS was relieved. CONCLUSION: The jaw advancement by ramus osteotomy and genioplasty for treating micromandibular deformity associated with OSAS can correct the maxillofacial deformities and enlarge the upper airway space to relieve OSAS. This method has achieved satisfactory result.