RESUMO
Colorectal cancer (CRC) therapy is a big challenge, and seeking an effective and safe drug is a pressing clinical need. Gambogic acid is a potent antineoplastic agent without the drawback of bone marrow suppression. To improve its druggability (e.g., poor water solubility and tumor delivery), a lactoferrin-modified gambogic acid liposomal delivery system (LF-lipo) was developed to enhance the treatment efficacy of CRC. The LF-lipo can specifically bind LRP-1 expressed on colorectal cancer cells to enhance drug delivery to the tumor cells and yield enhanced therapeutic efficacy. The LF-lipo promoted tumor cell apoptosis and autophagy, reduced reactive oxygen species (ROS) levels in tumor cells, and inhibited angiogenesis; moreover, it could also repolarize tumor-associated macrophages from the M2 to M1 phenotype and induce ICD to activate T cells, exhibiting the capability of remodeling the tumor immune microenvironment. The liposomal formulation yielded an efficient and safe treatment outcome and has potential for clinical translation.
Assuntos
Neoplasias Colorretais , Lipossomos , Humanos , Lipossomos/uso terapêutico , Lactoferrina , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Microambiente TumoralRESUMO
OBJECTIVE: This study examined the dental care utilization and self-preserved dental health of Asian immigrants relative to non-immigrants in Canada. Factors associated with oral health-related disparities between Asian immigrants and other Canadians were further examined. METHODS: We analyzed 37,935 Canadian residents aged 12 years and older in the Canadian Community Health Survey 2012-2014 microdata file. Factors (e.g., demographics, socioeconomic status, lifestyles, dental insurance coverage, and year of immigration) associated with disparities in dental health (e.g., self-perceived teeth health, dental symptoms during past one month, and teeth removed due to decay in past one year) and service utilization (e.g., visiting dentist within the last three years, visiting dentist more than once per year) between Asian immigrants and other Canadians were examined using multi-variable logistic regression models. RESULTS: The frequency of dental care utilization was significantly lower in Asian immigrants than their non-immigrant counterparts. Asian immigrants had lower self-perceived dental health, were less likely to be aware of recent dental symptoms, and more likely to report tooth extractions due to tooth decay. Low education (OR = 0.42), male gender(OR = 1.51), low household income(OR = 1.60), non-diabetes(OR = 1.87), no dental insurance(OR = 0.24), short immigration length (OR = 1.75) may discourage Asian immigrants from dental care utilization. Additionally, a perceived lack of necessity to dentist-visiting was a crucial factor accounting for the disparities in dental care uptake between Asian immigrants and non-immigrants. CONCLUSION: Asian immigrants showed lower dental care utilization and oral health than native-born Canadians.
Assuntos
Emigrantes e Imigrantes , Humanos , Masculino , Canadá , Nível de Saúde , Cobertura do Seguro , Odontólogos , Seguro OdontológicoRESUMO
Chronic intestinal inflammation is a key risk factor of colorectal cancer (CRC). It is known that microbial dysbiosis induces increased inflammatory factors which promote tumorigenesis and cellulose can be beneficial to CRC. In the present study, we investigated the regulatory effects of cellulose on intestinal flora composition and colorectal carcinogenesis in an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC mouse model. Supplementation of cellulose significantly attenuated inflammation and tumor formation in AOM/DSS-treated CRC mice. The survival rate and the tumor inhibition rate were higher in the medium-dose cellulose group (MCEG) and high-dose cellulose group (HCEG) than in the model group (MG; P < 0.05). Cellulose supplementation stimulated shifts in the intestinal flora in AOM/DSS-treated CRC mice. Additionally, levels of inflammatory mediators involved in colorectal carcinogenesis, such as IL-6, IL-1ß, and TNF-α, were lower in the serum of the low-dose cellulose group, MCEG, and HCEG when compared with the MG (P < 0.05). Whereas the abundance of differential bacteria was correlated with the concentration of IL-6, IL-1ß, and TNF-α. These results showed cellulose changed the composition of intestinal flora and inhibited colon inflammation and neoplasm formation caused by the AOM/DSS treatment.
Assuntos
Colite , Neoplasias Colorretais , Microbioma Gastrointestinal , Animais , Azoximetano , Celulose , Colite/induzido quimicamente , Colite/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Sulfato de Dextrana/toxicidade , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Increasing attention has been paid on the application of biodegradable materials such as magnesium and its alloys in neuron repair. AZ91D magnesium alloy coated with carbon nanotubes (CNTs) and/or calcium phosphate (CaP)/chitosan (CS) was fabricated in this study. To evaluate the bioactivity of these AZ91D-based composites, the extracts were prepared by immersing samples in modified simulated body fluid (m-SBF) for 0, 2, 8, 16, 24, 34, 44, 60, or 90 days. Immunofluorescence staining for neuronal class III ß-tubulin (TUJ1) revealed that both CNTs-CaP/CS-AZ91D and CaP/CS-AZ91D extracts promoted axon outgrowth of dorsal root ganglia (DRG) neurons, accompanied with increased expression of phosphorylated focal adhesion kinase (p-FAK) and growth associated protein-43 (GAP-43). Besides, the extracts increased the expression and the release of neurotrophic factors including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). ERK signalling was activated in DRG neurons after treating with either CNTs-CaP/CS-AZ91D or CaP/CS-AZ91D extracts, and its inhibition with U0126 counteracted the beneficial effects of these extracts on DRG neuron. Overall, the extracts from these AZ91D-based composites might promote DRG neuron growth via activating ERK signalling pathway. Notably, CNTs-CaP/CS-AZ91D extracts showed a better promoting effect on neuron growth than CaP/CS-AZ91D. Assessment of ion elements showed that the addition of CNTs coating enhanced magnesium corrosion resistance and reduced the deposition of calcium and phosphorus on the surface of CaP/CS-AZ91D alloy. These findings demonstrate that CNTs-CaP/CS-AZ91D likely provide a more suitable environment for neuron growth, which suggests a potential implantable biomaterial for the treatment of nerve injury. SIGNIFICANCE: AZ91D magnesium alloy coated with carbon nanotubes (CNTs) and/or calcium phosphate (CaP)/chitosan (CS) was fabricated and their immersion extracts were prepared using modified simulated body fluid in this study. Both extracts from CNTs-CaP/CS and CaP/CS-coated AZ91D magnesium alloy promotes rat dorsal root ganglia (DRG) neuron growth via activating ERK signalling pathway. Notably, the addition of CNTs improves the performance of CaP/CS-AZ91D. For the first time, our research demonstrates that CNTs-CaP/CS-AZ91D likely provide a suitable environment for neuron growth, suggesting these AZ91D-based composites as potential implantable biomaterials for the treatment of nerve injury.
Assuntos
Ligas/farmacologia , Fosfatos de Cálcio/farmacologia , Quitosana/farmacologia , Magnésio/farmacologia , Nanotubos de Carbono/química , Ligas/química , Ligas/isolamento & purificação , Animais , Fosfatos de Cálcio/química , Fosfatos de Cálcio/isolamento & purificação , Quitosana/química , Quitosana/isolamento & purificação , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/crescimento & desenvolvimento , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Magnésio/química , Magnésio/isolamento & purificação , Neurônios/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
The demand for natural lactone gamma-decalactone (GDL) has increased in the fields of food and cosmetic products. However, low productivity during bioprocessing limits its industrial production. In this study, a novel composite porous cell carrier, bacterial cellulose-alginate (BC-ALG), was used for long-term biotransformation and production of GDL. The effects of this carrier on biotransformation and related mechanisms were investigated. BC-ALG carriers showed improved mechanical strength over ALG carriers, with their internal embedded cell pattern changed to an interconnected porous structure. In five repeated-batch biotransformation experiments, the maximum concentration of GDL obtained in culture with BC-ALG carriers was 8.37 g/L, approximately 3.7 times higher than that from the medium with an ALG carrier alone. The result indicated that multiple hydrogen bonding interactions at the interface between BC and ALG contributed to the compatibility and stability of BC-ALG carriers. On the basis of the above results, the BC-ALG composite carrier can be considered ideal for immobilisation of cells for the production of GDL on an industrial scale, and has the potential to be utilised in other biological processes.
Assuntos
Alginatos/química , Células Imobilizadas/metabolismo , Celulose/química , Lactonas/metabolismo , Yarrowia/metabolismoRESUMO
Forward osmosis (FO) treatment of desulfurization wastewater shows great potential in laboratory scale tests. To explore the adaptability of the forward osmosis system in the practical treatment of desulfurization wastewater, we carried out a pilot test on desulfurization wastewater treated by the traditional method under the conditions of adding soda ash (SA) and adding FO scale inhibitor (FOSI). The results showed that the FO system could concentrate desulfurization wastewater with an average TDS of 15,816-32,820 mg/L in the influent water to an average TDS of more than 120,000 mg/L, which was concentrated 3.8-7.8 times. The removal rates of Ca2+, Mg2+ and Cl- were more than 99% and the system could operate stably for a long time. Under the condition of adding SA and FOSI, the system recovery rate was 85.38% and 73.02%, respectively. The operating cost was 25 RMB/ton and 21.77 RMB/ton, respectively. The results showed that the application of forward osmosis in desulfurization wastewater treatment was technically feasible and economically effective.
Assuntos
Águas Residuárias , Purificação da Água , Membranas Artificiais , Osmose , ÁguaRESUMO
INTRODUCTION: In this study, we evaluated the reproducibility of natural head position for pitch and roll acquired using 3 methods. METHODS: The participants were 30 Chinese adults (ages, 23-28 years) who had normal occlusion with no history of orthodontic therapy, maxillofacial trauma, or surgery. The natural head position was acquired using the self-balanced, mirror, and estimated positions, which were performed in duplicate and repeated after 1 week. Three-dimensional photographs were recorded with a horizontal laser line projected onto the face. The laser lines were observed by registering the repeated 3-dimensional photographs. The roll and pitch of the head orientation were measured with a digital ruler. Reproducibility was calculated using Dahlberg's formula and the Bland-Altman method. RESULTS: The reproducibility values calculated with Dahlberg's formula were 1.51°, 1.2°, and 0.99° for pitch, and 0.78°, 0.76°, and 0.41° for roll in the self-balanced, mirror, and estimated positions, respectively. CONCLUSIONS: The 3 methods are reproducible for both pitch and roll, and the estimated position showed the best reproducibility among these methods. This indicates that the estimated position could be used for acquiring the reference plane in preoperative planning for orthognathic surgery.
Assuntos
Cabeça/anatomia & histologia , Adulto , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Lasers , Masculino , Fotografação/métodos , Postura , Reprodutibilidade dos Testes , Adulto JovemRESUMO
We have developed a new method to fabricate multilayer films, which uses prepared thin films as modular blocks and transfer as operation mode to build up multilayer structures. In order to distinguish it from the in situ fabrication manner, this method is called modular assembly in this study. On the basis of such concept, we have fabricated a multilayer film using the silver mirror film as the modular block and poly(lactic acid) as the transfer tool. Due to the special double-layer structure of the silver mirror film, the resulting multilayer film had a well-defined stratified architecture with alternate porous/compact layers. As a consequence of the distinct structure, the interaction between the adjacent layers was so weak that the multilayer film could be layer-by-layer stripped. In addition, the top layer in the film could provide an effective protection on the morphology and surface property of the underlying layers. This suggests that if the surface of the film was deteriorated, the top layer could be peeled off and the freshly exposed surface would still maintain the original function. The successful preparation of the layer-by-layer strippable silver multilayer demonstrates that modular assembly is a feasible and effective method to build up multilayer films capable of creating novel and attractive micro/nanostructures, having great potential in the fabrication of nanodevices and coatings.
Assuntos
Ácido Láctico/química , Polímeros/química , Prata/química , Tamanho da Partícula , Poliésteres , Propriedades de SuperfícieRESUMO
Co-combustion of industrial and municipal solid wastes has emerged as the most promising disposal technology, yet its effect on unknown contaminants generation remains rarely revealed due to waste complexity. Hence, six batches of large-scale engineering experiments were designed in an incinerator of 650 t/d, which overcame the inauthenticity and deviation of laboratory tests. 953-1772 non-targeted compounds were screened in fly ash. Targeting the impact of co-combustion, a pseudo-component matrix model was innovatively integrated to quantitatively extract nine components from complex wastes grouped into biomass and plastic. Thus, the influence was evaluated across eight dimensions, covering molecular characteristics and toxicity. The effect of co-combustion with biomass pseudo-components was insignificant. However, co-combustion with high ratios of plastic pseudo-components induced higher potential risks, significantly promoting the formation of unsaturated hydrocarbons, highly unsaturated compounds (DBE≥15), and cyclic compounds by 19 %- 49 %, 17 %- 31 %, and 7 %- 27 %, respectively. Especially, blending with high ratios of PET plastic pseudo-components produced more species of contaminants. Unique 2 Level I toxicants, bromomethyl benzene and benzofuran-2-carbaldehyde, as well as 4 Level II toxicants, were locked, receiving no concern in previous combustion. The results highlighted risks during high proportion plastics co-combustion, which can help pollution reduction by tuning source wastes to enable healthy co-combustion.
Assuntos
Incineração , Cinza de Carvão , Plásticos/química , Biomassa , Resíduos Sólidos/análise , Poluentes Atmosféricos/análiseRESUMO
The sophisticated hierarchical structure that precisely combines contradictory mechanical and biological characteristics is ideal for biomaterials, but it is challenging to achieve. Herein, we engineer a spatiotemporally hierarchical guided bone regeneration (GBR) membrane by rational bilayer integration of densely porous N-halamine functionalized bacterial cellulose nanonetwork facing the gingiva and loosely porous chitosan-hydroxyapatite composite micronetwork facing the alveolar bone. Our GBR membrane asymmetrically combine stiffness and flexibility, ingrowth barrier and ingrowth guiding, as well as anti-bacteria and cell-activation. The dense layer has a mechanically matched space maintenance capacity toward gingiva, continuously blocks fibroblasts, and prevents bacterial invasion with multiple mechanisms including release-killing, contact-killing, anti-adhesion, and nanopore-blocking; the loose layer is ultra-soft to conformally cover bone surfaces and defect cavity edges, enables ingrowth of osteogenesis-associated cells, and creates a favorable osteogenic microenvironment. As a result, our all-in-one porous membrane possesses full protective abilities in GBR.
Assuntos
Regeneração Óssea , Membranas Artificiais , Porosidade , Regeneração Óssea/fisiologia , Osteogênese , Materiais Biocompatíveis/químicaRESUMO
Two new alkoxy-substituted quinoxaline (Qx)-based copolymers, PBDTQx and PBDTPz, are designed and synthesized. The only difference between these two polymers is that two methyl groups of the Qx are replaced by one additional fused benzene ring. The UV-Vis absorptions, thermal stability, energy levels, field-effect carrier mobility, and photovoltaic characteristics of the two copolymers are systematically evaluated to understand the relationships between the polymer structure at the molecular level and the photovoltaic performances. Photovoltaic cells based on the PBDTPz with a structure of ITO/PEDOT:PSS/Polymer:PC(71) BM/PEO/Ca/Al exhibit a promising efficiency of 4.40%, while that of PBDTQx is relatively much poorer.
Assuntos
Benzeno/química , Polímeros/química , Quinoxalinas/química , Estrutura Molecular , Polímeros/síntese químicaRESUMO
The construction of an efficient photothermal antibacterial platform is a promising strategy for the treatment of drug-resistant bacterial infections. Herein, through the introduction of excited-state intramolecular proton transfer to promote the photothermal effect, N-(2,4-dihydroxybenzylidene)-4-aminophenol (DOA)-polyvinyl alcohol (PVA) systems (DPVA) can reach 55 °C within 10 s under irradiation. They show superior antibacterial behavior against drug-resistant bacteria and a therapeutic effect on infected skin wounds with only 100 s of irradiation, much faster than those of reported photothermal materials (5-10 min). This work provides a convenient approach to fabricate broad-spectrum antibacterial wound dressings for treating bacteria-infected wounds, greatly contributing to the design and applications of photothermal antibacterial platforms.
Assuntos
Infecções Bacterianas , Prótons , Humanos , Antibacterianos/farmacologia , Pele , Álcool de PolivinilRESUMO
PURPOSE: To explore the value of virtual surgery and 3D printing model combined with guide plate in treatment of mandibular condylar neck fracture. METHODS: Seven patients with mandibular condylar neck fracture were scanned by CT for original data. The data were exported in DICOM format. A three-dimensional model was reconstructed using software, the fracture was reduced by virtual surgery, and the 3D model was printed by a 3D printer. A prebent titanium plate was used to fabricate the guide plate, which was used for reduction and fixation of the fracture block during surgery. RESULTS: All the postoperative incisions revealed no signs of infection, the wounds were hidden and beautiful. The implanted titanium plates were highly compatible with the reduced fracture segments. The patients were followed up for 6 months after surgery, the condylar fracture healed well and there was no obvious displacement. The patient developed no mandibular deviation with a stable occlusion, and no occlusal pain was reported. No obvious temporomandibular joint disorder was present. CONCLUSIONS: Virtual surgery and 3D printing model combined with guide plate can ensure an accurate reduction of condylar neck fracture and simplify the operation process, which can be used as an accurate, efficient and predictable auxiliary method.
Assuntos
Fraturas Mandibulares , Procedimentos de Cirurgia Plástica , Humanos , Fraturas Mandibulares/diagnóstico por imagem , Fraturas Mandibulares/cirurgia , Fixação Interna de Fraturas/métodos , Titânio , Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/cirurgia , Placas ÓsseasRESUMO
Introduction: The oral cavity and the gut tract are interconnected, and both contain abundant natural microbiota. Gut microbiota may interact with oral flora and participate in the development of periodontitis. However, the specific role of certain gut microbiota taxa for periodontitis has not been investigated. Mendelian Randomization is an ideal method to explore causal relationships avoiding reverse causality and potential confounding factors. Thus, we conducted a two-sample Mendelian Randomization study to comprehensively reveal the potential genetic causal effect of gut microbiota on periodontitis. Methods: SNPs strongly associated with 196 gut microbiota taxa (18,340 individuals) were selected as instrument variables, and periodontitis (17,353 periodontitis cases and 28,210 controls) was used as the outcome. The causal effect was analyzed via random effect inverse variance-weighted, weighted median, and MR-Egger. The sensitivity analyses were conducted using Cochran's Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests. Results: Nine gut microbiota taxa (Prevotella 7, Lachnospiraceae UCG-008, Enterobacteriales, Pasteurellales, Enterobacteriaceae, Pasteurellaceae, Bacteroidales S24.7 group, Alistipes, and Eisenbergiella) are predicted to play a causal role in enhancing the risk of periodontitis (p< 0.05). Besides, two gut microbiota taxa (Butyricicoccus and Ruminiclostridium 6) have potentially inhibitive causal effects on the risk of periodontitis (p< 0.05). No significant estimation of heterogeneity or pleiotropy is detected. Conclusion: Our study demonstrates the genetic causal effect of 196 gut microbiota taxa on periodontitis and provides guidance for the clinical intervention of periodontitis.
Assuntos
Microbioma Gastrointestinal , Microbiota , Periodontite , Humanos , Microbioma Gastrointestinal/genética , Análise da Randomização Mendeliana , Periodontite/genética , Microbiota/genética , Bacteroidetes , ClostridialesRESUMO
OBJECTIVES: This study examined the dental insurance coverage, dentist visits, self-perceived oral health status, and dental problems among Asian immigrant women of childbearing age in contrast to Canadian women of childbearing age and non-Asian immigrant women of childbearing age. Potential barriers to dental care services among Asian immigrant women were explored. METHODS: This analysis utilized data from the combined Canadian Community Health Survey from 2011 to 2014. The analytical sample consisted of 5737 females whose age was between 20 and 39 years. Multivariable logistic regression models assessed immigrant status and other factors in relation to the indicators of dental health (i.e., dental visit, self-perceived oral health, acute teeth issue, and teeth removed due to decay). RESULTS: Amongst Asian women immigrants of childbearing age, there was a significantly lower frequency of dentist visits compared to non-immigrant counterparts (OR = 0.53; 95% CI: 0.37-0.76). The most commonly reported reason for not seeking dental care in the last three years was that the "respondent did not think it was necessary". Relative to Canadian born women of same age bracket, Asian women of childbearing age reported fewer acute teeth issues (OR = 0.67; 95% CI: 0.49-0.91) and had a greater risk of tooth extracted due to tooth decay (OR = 3.31; 95% CI: 1.64-6.68). Furthermore, for Asian women immigrants, their major barriers to dental care included low household income (≤$39,999 vs. $40,000-$79,999 OR = 0.26) and a lack of dental insurance (no vs. yes OR = 0.33). CONCLUSIONS: Asian immigrant women showed lower utilization of dental services than non-immigrant women. A perceived lack of necessity, lower household income, and dental insurance coverage were major barriers to professional dental usage for most Asian immigrants of childbearing age.
RESUMO
Self-assembly has emerged as an extensively used method for constructing biomaterials with sizes ranging from nanometers to micrometers. Peptides have been extensively investigated for self-assembly. They are widely applied owing to their desirable biocompatibility, biodegradability, and tunable architecture. The development of peptide-based nanoparticles often requires complex synthetic processes involving chemical modification and supramolecular self-assembly. Stimuli-responsive peptide nanoparticles, also termed "smart" nanoparticles, capable of conformational and chemical changes in response to stimuli, have emerged as a class of promising materials. These smart nanoparticles find a diverse range of biomedical applications, including drug delivery, diagnostics, and biosensors. Stimuli-responsive systems include external stimuli (such as light, temperature, ultrasound, and magnetic fields) and internal stimuli (such as pH, redox environment, salt concentration, and biomarkers), facilitating the generation of a library of self-assembled biomaterials for biomedical imaging and therapy. Thus, in this review, we mainly focus on peptide-based nanoparticles built by self-assembly strategy and systematically discuss their mechanisms in response to various stimuli. Furthermore, we summarize the diverse range of biomedical applications of peptide-based nanomaterials, including diagnosis and therapy, to demonstrate their potential for medical translation.
Assuntos
Nanopartículas , Nanoestruturas , Nanopartículas/química , Sistemas de Liberação de Medicamentos/métodos , Materiais Biocompatíveis/química , Peptídeos/químicaRESUMO
Microplastics (MPs) as emerging contaminants have become a major global concern, however, the distribution and origin of MPs in Qinghai-Tibet Plateau (QTP) and their impacts on ecosystem are poorly known. Hence, we systematically evaluated the profile of MPs on the representative metropolitan locations of Lhasa and Huangshui Rivers and the scenic sites of Namco and Qinghai Lake. The average abundance of MPs in the water samples was 7020 items/m3, which was 34 and 52 times higher than those for the sediment (206.7 items/m3) and soil samples (134.7 items/m3), respectively. Huangshui River had the highest levels, followed by Qinghai Lake, Lhasa River and Namco. Human activities rather than altitude and salinity impacted the distribution of MPs in those areas. Besides the consumption of plastic products by locals and tourists, laundry wastewater and exogenous tributary inputs, the unique prayer flag culture also contributed to the MPs emission in QTP. Notably, the stability and fragment of MPs were crucial for their fate. Multiple assessment models were employed to evaluate the risk of MPs. PERI model took MP concentration, background value and toxicity into account, comprehensively describing the risk differences of each site. The large PVC proportion in Qinghai Lake posed the highest risk. Furthermore, concerns should be raised about PVC, PE and PET in Lhasa and Huangshui Rivers, and PC in Namco Lake. Risk quotient suggested that aged MPs in sediments slowly released biotoxic DEHP and should be cleaned up promptly. The findings offer baseline data of MPs in QTP and ecological risks, providing important support for the prioritization of future control measures.
Assuntos
Microplásticos , Poluentes Químicos da Água , Humanos , Idoso , Tibet , Plásticos , Ecossistema , Sedimentos Geológicos , Monitoramento Ambiental , Poluentes Químicos da Água/análiseRESUMO
The health risks of exposure to 'eco-friendly' biodegradable plastics of anthropogenic origin and their effects on the gastrointestinal tract are largely unknown. Here we demonstrate that the enzymatic hydrolysis of polylactic acid microplastics generated nanoplastic particles by competing for triglyceride-degrading lipase during gastrointestinal processes. Nanoparticle oligomers were formed by hydrophobically driven self-aggregation. In a mouse model, polylactic acid oligomers and their nanoparticles bioaccumulated in the liver, intestine and brain. Hydrolysed oligomers caused intestinal damage and acute inflammation. A large-scale pharmacophore model revealed that oligomers interacted with matrix metallopeptidase 12. Mechanistically, high binding affinity (Kd = 13.3 µmol l-1) of oligomers to the catalytic zinc-ion finger domain led to matrix metallopeptidase 12 inactivation, which might mediate the adverse bowel inflammatory effects after exposure to polylactic acid oligomers. Biodegradable plastics are considered to be a solution to address environmental plastic pollution. Thus, understanding the gastrointestinal fates and toxicities of bioplastics will provide insights into potential health risks.
Assuntos
Plásticos Biodegradáveis , Animais , Camundongos , Poliésteres , Metaloproteases , Inflamação/induzido quimicamenteRESUMO
Amphiphilic copolymers have long been utilized to turn hydrophobic anticancer drugs into nanoparticles administered to patients with cancer. A lack of stability in these monotherapies may be blamed for their poor clinical results in patients with cancer. We propose novel nanotherapies based on polymeric small prodrugs that preserve pharmacologic effectiveness while significantly reducing the toxicity of the fabricated drugs in animals to overcome this problem. Doxorubicin is attached to the end of the PLA fragments through a hydrolyzable ester bond utilizing methoxypolyethylene glycol-block-poly(d, l-lactic acid) (mPEG-PCL(2K)) with conjugates to mimic the self-assembly of colloidal nanotherapies. In a gastric cancer xenograft model, this nanotherapy displays a long-lasting suppression of tumor growth once a reasonable dosage is administered. Our findings imply that a toxic chemical and hydrophobic can be converted into therapeutic effective self-delivery nanotreatment.
Assuntos
Nanopartículas , Neoplasias Gástricas , Animais , Humanos , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Gástricas/tratamento farmacológico , Doxorrubicina/química , Polímeros/química , Nanopartículas/químicaRESUMO
Liposomal technology has been widely used in the pharmaceutical field for the preparation of nano-sized drug delivery systems based on natural or synthetic lipids. Liposomes possess many attractive properties, such as easy processing, high biocompatibility, adaptable drug loading, and improved PK profiles. In recent decades, great efforts have been made in this field, and dozens of liposomal medicines have been marketed worldwide and many more are under preclinical or clinical investigations. Liposomes can enhance the aqueous dissolution and stability of the encapsulated drugs and modulate the in vivo fate of the drugs (e.g., prolonged half-life and increased drug accumulation in the pathological sites). Therefore, liposomal technology can improve the druggability of the candidates, enhance treatment efficacy and reduce side effects. This review discusses the prospects of liposomal delivery, including the specific considerations of innovation and challenges.