RESUMEN
Hydrogels are currently in the limelight for applications in soft electronics but they suffer from the tendency to lose water or freeze when exposed to dry environments or low temperatures. Molecular crowding is a prevalent occurrence in living cells, in which molecular crowding agents modify the hydrogen bonding structure, causing a significant reduction in water activity. Here, a wide-humidity range applicable, anti-freezing, and robust hydrogel is developed through the incorporation of natural amino acid proline (Pro) and conductive MXene into polyvinyl alcohol (PVA) hydrogel networks. Theoretical calculations reveal that Pro can transform "free water" into "locked water" via the molecular-crowding effect, thereby suppressing water evaporation and ice forming. Accordingly, the prepared hydrogel exhibits high water retention capability, with 77% and 55% being preserved after exposure to 20 °C, 28% relative humidity (RH) and 35 °C, 90% RH for 12 h. Meanwhile, Pro lowers the freezing temperature of the hydrogel to 34 °C and enhances its stretchability and strength. Finally, the PVA/Pro/MXene hydrogels are assembled as multifunctional on-skin strain sensors and conductive electrodes to monitor human motions and detect tiny electrophysiological signals. Collectively, this work provides a molecular crowding strategy that will motivate researchers to develop more advanced hydrogels for versatile applications.
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Electrónica , Congelación , Humedad , Hidrogeles , Alcohol Polivinílico , Hidrogeles/química , Alcohol Polivinílico/química , Humanos , Piel , Prolina/químicaRESUMEN
Covalent organic frameworks (COFs) have emerged as a promising class of crystalline porous materials for cancer phototherapy, due to their exceptional characteristics, including light absorption, biocompatibility, and photostability. However, the aggregation-caused quenching effect and apoptosis resistance often limit their therapeutic efficacy. Herein, we demonstrated for the first time that linking luminogens with aggregation-induced emission effect (AIEgens) into COF networks via vinyl linkages was an effective strategy to construct nonmetallic pyroptosis inducers for boosting antitumor immunity. Mechanistic investigations revealed that the formation of the vinyl linkage in the AIE COF endowed it with not only high brightness but also strong light absorption ability, long lifetime, and high quantum yield to favor the generation of reactive oxygen species for eliciting pyroptosis. In addition, the synergized system of the AIE COF and αPD-1 not only effectively eradicated primary and distant tumors but also inhibited tumor recurrence and metastasis in a bilateral 4T1 tumor model.
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Estructuras Metalorgánicas , Fotoquimioterapia , Piroptosis , Apoptosis , Carbono , Cloruro de PoliviniloRESUMEN
Historically, the interlacing of strands at the molecular level has mainly been limited to coordination polymers and DNA. Despite being proposed on a number of occasions, the direct, bottom-up assembly of molecular building blocks into woven organic polymers remained an aspirational, but elusive, target for several decades. However, recent successes in two-dimensional and three-dimensional molecular-level weaving now offer new opportunities and research directions at the interface of polymer science and molecular nanotopology. This Perspective provides an overview of the features and potential of the periodic nanoscale weaving of polymer chains, distinguishing it from randomly entangled polymer networks and rigid crystalline frameworks. We review the background and experimental progress so far, and conclude by considering the potential of molecular weaving and outline some of the current and future challenges in this emerging field.
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ADN , Polímeros , Polímeros/químicaRESUMEN
Entangling strands in a well-ordered manner can produce useful effects, from shoelaces and fishing nets to brown paper packages tied up with strings. At the nanoscale, non-crystalline polymer chains of sufficient length and flexibility randomly form tangled mixtures containing open knots of different sizes, shapes and complexity. However, discrete molecular knots of precise topology can also be obtained by controlling the number, sequence and stereochemistry of strand crossings: orderly molecular entanglements. During the last decade, substantial progress in the nascent field of molecular nanotopology has been made, with general synthetic strategies and new knotting motifs introduced, along with insights into the properties and functions of ordered tangle sequences. Conformational restrictions imparted by knotting can induce allostery, strong and selective anion binding, catalytic activity, lead to effective chiral expression across length scales, binding modes in conformations efficacious for drug delivery, and facilitate mechanical function at the molecular level. As complex molecular topologies become increasingly synthetically accessible they have the potential to play a significant role in molecular and materials design strategies. We highlight particular examples of molecular knots to illustrate why these are a few of our favourite things.
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Polímeros , AnionesRESUMEN
2D conducting polymer thin film recently has garnered numerous interests as a means of combining the molecular aggregate ordering and promoting in-plane charge transport for large-scale/flexible organic electronics. However, it remains far from satisfactory for conducting polymer chains to achieve desirable surface topography and crystallinity due to lack of control over the precursor-involved interfacial assembly. Herein, wafer-size polyaniline (PANI) and tetra-aniline thin films are developed via a controlled interfacial synthesis with customized surface morphology and crystallinity through two typical aniline precursors selective polymerization. Two crucial competing assembly mechanisms, a) direct interfacial polymerization, b) solution polymerization and subsequent interfacial assembly, are investigated to play a vital role in determining elemental chain length and aggregate architecture. The optimal PANI thin film manifests ultraflat surface topography and unambiguous crystalline domains, which also enabling fascinating ammonia sensing capability with 31.4% ppm-1 sensitivity, fast response time (88 s) with astonishing selectivity, repeatability, and recovery capability. The thus-demonstrated strategy with wafer-scale processing potential and flexible microdevice offers a promising route for large-scale manufacturing thin-film organic electronics.
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Compuestos de Anilina , Polímeros , Polimerizacion , Compuestos de Anilina/químicaRESUMEN
BACKGROUND: To compare high- versus low-viscosity bone cement on the clinical outcomes and complications in patients with Osteoporotic vertebral compression fractures (OVCFs) who underwent percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP). METHODS: PubMed, Embase, and the Cochrane Library were searched for papers published from inception up to February 2021 for potentially eligible studies comparing high- versus low-viscosity cement for PVP/PKP. The outcomes were the leakage rate, visual analog scale (VAS), and Oswestry Disability Index (ODI). RESULTS: Eight studies (558 patients; 279 in each group) were included. The meta-analysis showed that the leakage rate was lower with high-viscosity cement than with low-viscosity cement (OR = 0.23, 95%CI 0.14-0.39, P < 0.001; I2 = 43.5%, Pheterogeneity = 0.088); similar results were observed specifically for the disk space, paravertebral space, and peripheral vein, but there were no differences regarding the epidural space and intraspinal space. The VAS was decreased more significantly with high-viscosity cement than with low-viscosity cement (WMD = - 0.21, 95%CI - 0.38, - 0.04, P = 0.015; I2 = 0.0%, Pheterogeneity = 0.565). Regarding the ODI, there was no difference between high- and low-viscosity cement (WMD = - 0.88, 95%CI - 3.06, 1.29, P = 0.426; I2 = 78.3%, Pheterogeneity < 0.001). CONCLUSIONS: There were lower cement leakage rates in PVP/PKP with high-viscosity bone cement than low-viscosity bone cement. The two groups have similar results in ODI, but the VAS scores favor high-viscosity bone cement. Therefore, the administration of high-viscosity bone cement in PVP/ PKP could be a potential option for improving the complications of leakage in OVCFs, while the clinical efficacy of relieving pain is not certain.
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Fracturas por Compresión , Cifoplastia , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Vertebroplastia , Cementos para Huesos/uso terapéutico , Fracturas por Compresión/complicaciones , Fracturas por Compresión/cirugía , Humanos , Cifoplastia/métodos , Fracturas Osteoporóticas/cirugía , Estudios Retrospectivos , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/cirugía , Resultado del Tratamiento , Vertebroplastia/métodos , ViscosidadRESUMEN
Objective: To analyze the epidemiological characteristics of hand, foot, and mouth disease (HFMD) in Chengdu from 2012 to 2020, to make comparison in order to examine the changes in incidence before and after vaccination was introduced, and to provide basis for the prevention of HFMD in the future. Methods: Descriptive epidemiological methods were adopted to analyze the incidence, mortality and rate of severe cases of HFMD cases reported in Chengdu from 2012 to 2020. Results: From 2012 to 2020, the cumulative cases of HFMD reported in Chengdu were as many as 279216, of which, there were 2201 severe cases and 16 deaths. The incidence increased every other year, reaching 326.43 per 100000 person-years, the highest ever, in 2018. The rate of severe cases and mortality had shown a decreasing trend since 2016. A total of 11892 cases of EV71, CoxA16 and other enteroviruses were detected in the laboratory, accounting for 14.8%, 18.8% and 66.3%, respectively. Since 2016, HFMD cases caused by EV71 virus infection had shown an overall decreasing trend, cases caused by Cox A16 virus infection had increased every other year, and cases caused by other enteroviral infections had shown an overall increasing trend. The reported cases were mainly concentrated in children aged 0-5 years (92.1%), with those in the age group of 1-2 years reporting the highest number of cases. For children of different ages, male patients always outnumber female patients. The geographic distribution showed that the areas with high HFMD incidence were always located in the central part of Chengdu City, and the three districts with the highest incidence growth rate were Qingbaijiang District, Shuangliu District, and Longquanyi District. Temporal distribution of HFMD cases showed an obvious bimodal distribution, with most of the cases concentrated in May through August and October through December of each year. The number of new cases reached the highest (12309 cases) in July 2018. Conclusion: While continuing to promote EV71 vaccination in the future, Chengdu also needs to pay more attention to viral infection serotypes other than EV71 and Cox A16 and conduct research on multivalent vaccines against a variety of enteroviruses. The focus of prevention and control can be placed on areas with high population density, large floating populations, large numbers of agriculture-related communities, and insufficient individual awareness of hygiene. For the second circle of Chengdu city, the disinfection of agriculture-related communities should be strengthened, and information sessions or other health education activities could be organized for individuals and daycare facilities with low awareness of the importance of hygiene. In addition, more attention should be given to the prevention and control of HFMD in the high incidence seasons.
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Infecciones por Enterovirus , Enfermedad de Boca, Mano y Pie , Niño , Humanos , Femenino , Masculino , Lactante , Preescolar , Enfermedad de Boca, Mano y Pie/epidemiología , Enfermedad de Boca, Mano y Pie/prevención & control , Vacunación , Antígenos ViralesRESUMEN
The enzymes exopolyphosphatase/guanosine pentaphosphate phosphohydrolase (PPX/GppA) play important roles in the bacterial stringent response. PPX degrades inorganic polyphosphate (polyP), a polymer composed of a few to hundreds of phosphate residues supporting cell survival in the stationary phase. The crystal structure of PPX from Porphyromonas gingivalis (PgPPX) in complex with catalytic magnesium ions and several sulfate ions was solved. PgPPX contained two domains and represented a "closed" configuration. Four sulfate ions forming a linear dispersed chain were observed in the aqueduct of the PPX dimer, which the long polyP chain most likely occupied. The side chain of R255 stretched into the cavity where polyP could be located, obstructing the entrance of larger substrates such as NTP and NDP. This study provided the first view into the structure of the PPX/GppA homolog in complex with magnesium ions and substrate analogs and explained how PgPPX implemented its functionality.
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Polifosfatos , Porphyromonas gingivalis , Ácido Anhídrido Hidrolasas/química , Magnesio , Polifosfatos/metabolismo , Porphyromonas gingivalis/metabolismoRESUMEN
Hepatocellular carcinoma (HCC) is one of the most aggressive tumours with marked fibrosis. Mycophenolate mofetil (MMF) was well-established to have antitumour and anti-fibrotic properties. To overcome the poor bioavailability of MMF, this study constructed two MMF nanosystems, MMF-LA@DSPE-PEG and MMF-LA@PEG-PLA, by covalently conjugating linoleic acid (LA) to MMF and then loading the conjugate into polymer materials, PEG5k -PLA8k and DSPE- PEG2k , respectively. Hepatocellular carcinoma cell lines and C57BL/6 xenograft model were used to examine the anti-HCC efficacy of nanoparticles (NPs), whereas NIH-3T3 fibroblasts and highly-fibrotic HCC models were used to explore the anti-fibrotic efficacy. Administration of NPs dramatically inhibited the proliferation of HCC cells and fibroblasts in vitro. Animal experiments revealed that MMF-LA@DSPE-PEG achieved significantly higher anti-HCC efficacy than free MMF and MMF-LA@PEG-PLA both in C57BL/6 HCC model and highly-fibrotic HCC models. Immunohistochemistry further confirmed that MMF-LA@DSPE-PEG dramatically reduced cancer-associated fibroblast (CAF) density in tumours, as the expression levels of alpha-smooth muscle actin (α-SMA), fibroblast activation protein (FAP) and collagen IV were significantly downregulated. In addition, we found the presence of CAF strongly correlated with increased HCC recurrence risk after liver transplantation. MMF-LA@DSPE-PEG might act as a rational therapeutic strategy in treating HCC and preventing post-transplant HCC recurrence.
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Carcinoma Hepatocelular/tratamiento farmacológico , Composición de Medicamentos/métodos , Sistemas de Liberación de Medicamentos/métodos , Ácido Micofenólico/farmacología , Nanopartículas/uso terapéutico , Actinas/metabolismo , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Colágeno/metabolismo , Modelos Animales de Enfermedad , Endopeptidasas/metabolismo , Fibroblastos/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Ácido Linoleico/química , Neoplasias Hepáticas/tratamiento farmacológico , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos C57BL , Células 3T3 NIH , Nanopartículas/química , Polímeros/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Mono-therapeutic modality has limitations in combating metastatic lesions with complications. Although emerging immunotherapy exhibits preliminary success, solid tumors are usually immunosuppressive, leading to ineffective antitumor immune responses and immunotherapeutic resistance. The rational combination of several therapeutic modalities may potentially become a new therapeutic strategy to effectively combat cancer. RESULTS: Poly lactic-co-glycolic acid (PLGA, 50 mg) nanospheres were constructed with photothermal transduction agents (PTAs)-Prussian blue (PB, 2.98 mg) encapsulated in the core and chemotherapeutic docetaxel (DTX, 4.18 mg)/ immune adjuvant-imiquimod (R837, 1.57 mg) loaded in the shell. Tumor cell membranes were further coated outside PLGA nanospheres (designated "M@P-PDR"), which acted as "Nano-targeted cells" to actively accumulate in tumor sites, and were guided/monitored by photoacoustic (PA)/ magnetic resonance (MR) imaging. Upon laser irradiation, photothermal effects were triggered. Combined with DTX, PTT induced in situ tumor eradication. Assisted by the immune adjuvant R837, the maturation rate of DCs increased by 4.34-fold compared with that of the control. In addition, DTX polarized M2-phenotype tumor-associated macrophages (TAMs) to M1-phenotype, relieving the immunosuppressive TME. The proportion of M2-TAMs decreased from 68.57% to 32.80%, and the proportion of M1-TAMs increased from 37.02% to 70.81%. Integrating the above processes, the infiltration of cytotoxic T lymphocytes (CTLs) increased from 17.33% (control) to 35.5%. Primary tumors and metastasis were significantly inhibited when treated with "Nano-targeted cells"-based cocktail therapy. CONCLUSION: "Nano-targeted cells"-based therapeutic cocktail therapy is a promising approach to promote tumor regression and counter metastasis/recurrence.
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Antineoplásicos/uso terapéutico , Membrana Celular/química , Docetaxel/química , Nanopartículas/química , Neoplasias/terapia , Adyuvantes Inmunológicos/química , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Docetaxel/farmacología , Docetaxel/uso terapéutico , Ferrocianuros/química , Ferrocianuros/farmacología , Ferrocianuros/uso terapéutico , Humanos , Imiquimod/química , Imiquimod/inmunología , Inmunoterapia/métodos , Rayos Infrarrojos , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Ratones , Ratones Desnudos , Neoplasias/diagnóstico por imagen , Imagen Óptica , Terapia Fototérmica/métodos , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/químicaRESUMEN
BACKGROUND: Photodynamic therapy (PDT) is a promising therapeutic modality that can convert oxygen into cytotoxic reactive oxygen species (ROS) via photosensitizers to halt tumor growth. However, hypoxia and the unsatisfactory accumulation of photosensitizers in tumors severely diminish the therapeutic effect of PDT. In this study, a multistage nanoplatform is demonstrated to overcome these limitations by encapsulating photosensitizer IR780 and oxygen regulator 3-bromopyruvate (3BP) in poly (lactic-co-glycolic acid) (PLGA) nanocarriers. RESULTS: The as-synthesized nanoplatforms penetrated deeply into the interior region of tumors and preferentially remained in mitochondria due to the intrinsic characteristics of IR780. Meanwhile, 3BP could efficiently suppress oxygen consumption of tumor cells by inhibiting mitochondrial respiratory chain to further improve the generation of ROS. Furthermore, 3BP could abolish the excessive glycolytic capacity of tumor cells and lead to the collapse of ATP production, rendering tumor cells more susceptible to PDT. Successful tumor inhibition in animal models confirmed the therapeutic precision and efficiency. In addition, these nanoplatforms could act as fluorescence (FL) and photoacoustic (PA) imaging contrast agents, effectuating imaging-guided cancer treatment. CONCLUSIONS: This study provides an ideal strategy for cancer therapy by concurrent oxygen consumption reduction, oxygen-augmented PDT, energy supply reduction, mitochondria-targeted/deep-penetrated nanoplatforms and PA/FL dual-modal imaging guidance/monitoring. It is expected that such strategy will provide a promising alternative to maximize the performance of PDT in preclinical/clinical cancer treatment.
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Mitocondrias/efectos de los fármacos , Nanopartículas/química , Fármacos Fotosensibilizantes/farmacología , Hipoxia Tumoral/efectos de los fármacos , Animales , Línea Celular Tumoral , Sinergismo Farmacológico , Femenino , Humanos , Indoles/química , Indoles/farmacocinética , Indoles/farmacología , Indoles/uso terapéutico , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Ratones Desnudos , Mitocondrias/metabolismo , Neoplasias/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacocinética , Fármacos Fotosensibilizantes/uso terapéutico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Piruvatos/química , Piruvatos/farmacocinética , Piruvatos/farmacología , Piruvatos/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Distribución Tisular , Trasplante HeterólogoRESUMEN
In this study, oridonin-loaded long-circulating liposomes (LC-lipo@ORI) were prepared with the ethanol injection method. Its physicochemical properties and the morphology were characterized, and its stability and release profiles were evaluated. Furthermore, its antitumor effects were studied using two in vitro cell models of colon cancer and two tumor-bearing models in nude mice. The prepared LC-lipo@ORI was quasi-spherical, with a mean particle size of 109.55 ± 2.30 nm. The zeta potential was -1.38 ± 0.21 mV, the encapsulation efficiency was 85.79%±3.25%, and the drug loading was 5.87%±0.21%. In vitro release results showed that the cumulative release rate of LC-lipo@ORI at 12 h was 63.83%. However, ORI dispersion was almost completely released after 12 h. In vitro cytotoxicity results showed that, the inhibiting effects of LC-lipo@ORI on the proliferation of two types of colon cancer cells were apparently higher than those of ORI dispersion, whereas those of the blank carrier were not noticeable. In vivo studies confirmed that, the encapsulation of LC-lipo enhanced the inhibitory effects of ORI on tumor growth. These results indicated that LC-lipo@ORI a promising formulations for colon cancer treatment.
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Neoplasias del Colon , Diterpenos de Tipo Kaurano , Animales , Neoplasias del Colon/tratamiento farmacológico , Diterpenos de Tipo Kaurano/farmacología , Liposomas , Ratones , Ratones Desnudos , Tamaño de la PartículaRESUMEN
OBJECTIVES: The objective of this randomized controlled trial was to compare alveolar ridge preservation using a bone substitute material and covered with a synthetic or porcine collagen membrane. MATERIALS AND METHODS: Thirty-two sockets in the aesthetic maxillary region of 30 patients were randomized into two groups. Randomization was stratified according to bone wall defect. Flapless technique was used, and sockets were grafted with bi-phasic calcium phosphate particulate bone substitute and covered by synthetic polyethylene glycol (PEG; test group) or porcine-derived collagen membrane (CM; control group). No primary closure was attempted. A cone beam computed tomography (CBCT) scan was performed immediately after the surgical procedure and repeated 22 weeks later. OnDemand3D was used to superimpose scan images and assess changes. The mean vertical and horizontal percentage bone loss were calculated and implants placed after 6 months with or without additional augmentation. RESULTS: There were no baseline differences between groups or dropouts. The mean percentage loss at the labial plate and at the coronal part of the sockets was statistically significantly lower in the test group compared with controls (-2.86% [SD = 13.48] versus 7.42% [SD = 11.95]; 13.45% [SD = 11.97] versus 28.59% [SD = 16.97]). Implants were placed after 6 months, and there was no difference in need for further augmentation between PEG (n = 5) or CM (n = 4). CONCLUSION: Sites treated with PEG membrane showed less percentage loss in horizontal and vertical measurements in this trial.
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Pérdida de Hueso Alveolar , Aumento de la Cresta Alveolar , Pérdida de Hueso Alveolar/diagnóstico por imagen , Pérdida de Hueso Alveolar/prevención & control , Pérdida de Hueso Alveolar/cirugía , Animales , Colágeno , Tomografía Computarizada de Haz Cónico , Estética Dental , Humanos , Maxilar/diagnóstico por imagen , Maxilar/cirugía , Porcinos , Extracción Dental , Alveolo Dental/diagnóstico por imagen , Alveolo Dental/cirugíaRESUMEN
The development of pancreatic extracellular matrices enriched with insulin-secreting ß-cells is a promising tissue engineering approach to treat type 1 diabetes. However, its long-term therapeutic efficacy is restricted by the defensive mechanism of host immune response and the lack of developed vascularization as appropriate after transplantation. Platelet-rich plasma (PRP), as an autologous platelet concentrate, contains a large number of active factors that are essential for the cell viability, vascularization, and immune regulation. In this study, we have incorporated pancreatic extracellular matrix (PEM) with PRP to develop a three-dimensional (3D) injectable PEM-PRP hydrogel to coculture and transplant rat insulinoma cells (INS-1) and human umbilical vein endothelial cells (HUVECs). Results from this study demonstrated that PEM-PRP hydrogel mimicked the biochemical compositions of native extracellular matrices, and possessed the enhanced elastic modulus and resistance to enzymatic degradation that enabled biomaterials to maintain its volume and slowly degrade. Additionally, PEM-PRP hydrogel could release growth factors in a sustained manner. In vitro, PEM-PRP hydrogel significantly promoted the viability, insulin-secreting function, and insulin gene expression of gel encapsulated INS-1 cells. Moreover, HUVECs encapsulated in PEM-PRP hydrogel were found to constitute many lumen-like structures and exhibited high expression of proangiogenic genes. In vivo transplantation of PEM-PRP hydrogel encapsulated with INS-1 cells and HUVECs improved the viability of INS-1 cells, promoted vascularization, inhibited the host inflammatory response, and reversed hyperglycemia of diabetic rats. Our study suggests that the PEM-PRP hydrogel offers excellent biocompatibility and proangiogenic property, and may serve as an effective biomaterial platform to maintain the long-term survival and function of insulin-secreting ß cells.
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Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 1/terapia , Matriz Extracelular/trasplante , Hidrogeles/administración & dosificación , Plasma Rico en Plaquetas , Ingeniería de Tejidos/métodos , Animales , Materiales Biocompatibles , Técnicas de Cultivo de Célula/métodos , Línea Celular Tumoral , Supervivencia Celular , Técnicas de Cocultivo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 1/inducido químicamente , Diabetes Mellitus Tipo 1/patología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Insulina/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Ensayo de Materiales , Páncreas/citología , Páncreas/metabolismo , Páncreas/patología , Ratas , Estreptozocina/administración & dosificación , Estreptozocina/toxicidadRESUMEN
Arachniodes (Dryopteridaceae) is one of the most confusing and controversial fern genera in terms of its circumscription, nomenclature, and taxonomy. Estimates of species number range from 40 to 200. Previous molecular works included only 2-17 accessions representing 2-12 species of Arachniodes and allied genera, leaving most of the Asian species remain unsampled and the infragneric relationships unclear. In this study DNA sequences of seven plastid markers of 343 accessions representing ca. 68 species of Arachniodes (275 accessions), and 64 outgroup accessions from subfam. Dryopteridoideae and subfam. Polybotryoideae were used to infer a phylogeny with maximum likelihood, Bayesian inference, and maximum parsimony approaches. Our major results include: (1) Two species currently assigned in Arachniodes (A. macrostegia and A. ochropteroides are resolved outside of the core Arachniodes making the currently defined Arachniodes polyphyletic, confirming earlier findings; (2) Lithostegia, Leptorumohra, and Phanerophlebiopsis are indeed synonyms of Arachniodes; (3) Leptorumohra is confirmed to be monophyletic, but Phanerophlebiopsis is polyphyletic; (4) The New World species of Arachniodes are confirmed to be not monophyletic with A. denticulata being nested within the Old World species, suggesting that this species is dispersed from the Old World; (5) Arachniodes s.s is resolved into 12 major clades, some of which are further divisable into recognizable subclades and groups, with A. mutica from Japan being resolved as the sister to the rest of the genus; (6) A number of systematic implications of the phylogeny have been suggested; and (7) the genus is estimated to contain ca. 83 species.
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Dryopteridaceae/clasificación , Filogenia , Plastidios/genética , Teorema de Bayes , Dryopteridaceae/anatomía & histología , Dryopteridaceae/genética , Funciones de Verosimilitud , Rizoma/anatomía & histología , Análisis de Secuencia de ADN , Especificidad de la EspecieRESUMEN
TX100 (Triton X-100) is a typical nonionic surfactant that is widely used in biology. However, the detailed aggregated conformation of TX100, such as the boundary between the polar region and the nonpolar region, and the arrangement of hydrophobic chains in micelles, are still controversial. In the manuscript, the aggregation pattern of TX100 has been studied using sPREs (solvent Paramagnetic Relaxation Enhancements)-based NMR (Nuclear Magnetic Resonance spectroscopy). It was found that the average positions of the protons in the TX100 micelle are consistent with those in the multilayer staggered spherical micelle model with the p-tertoctylphenyl groups dispersing in the different layers.
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Micelas , Octoxinol/química , Espectroscopía de Resonancia Magnética , Modelos Teóricos , Estructura Molecular , SolventesRESUMEN
A series of novel coumarin/2-cyanoacryloyl hybrids were prepared and evaluated for their in vitro anticancer activity. Among them, two analogs 5p and 5q showed promising antiproliferative activity against a panel of cancer cell lines, including A549, H157, HepG2, MCF7, MG63, and U2OS. Particularly, 5q showed the most potent activity towards MG63 cells with an IC50 value of 5.06 ± 0.25 µM. Morphological observation and 4,6-diamidino-2-phenylindole (DAPI) staining assay showed that 5q-treated MG63 cells displayed significant apoptosis characteristics. Moreover, flow cytometric detection of phosphatidylserine externalization revealed that 5q induced MG63 apoptosis in a dose-dependent manner. Real-time PCR and western blot assay further confirmed that 5q had strong effects to induce MG63 cell apoptosis, suggesting that the action was associated with down-regulation of the anti-apoptotic protein Bcl-2, upregulation of pro-apoptotic protein Bax, and induced activation of caspase-3, 8, and 9. The present results provide a new chemotype for anticancer drug development and continuing investigation into candidates with coumarin/2-cyanoacryloyl scaffold is warranted.
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Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Cumarinas/síntesis química , Cumarinas/farmacología , Cianoacrilatos/síntesis química , Cianoacrilatos/farmacología , Diseño de Fármacos , Transducción de Señal , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Cumarinas/química , Cianoacrilatos/química , Activación Enzimática/efectos de los fármacos , Humanos , Transducción de Señal/efectos de los fármacosRESUMEN
Sludge aggregation and biofilm formation are the most effective approaches to solve the washout of anammox microorganisms. In this study, the structure and composition of EPS (extracellular polymeric substances) were investigated to elucidate the factors for the anammox aggregation property. Anammox sludge taken from 18 lab-scale and pilot-scale reactors treating different types of wastewater was analyzed using EEM-PARAFAC (excitation-emission matrix and parallel factor analysis), FTIR (Fourier transform infrared spectroscopy) and real-time PCR combined with multivariate statistical analysis. The results showed that slime and TB-EPS (tightly bound EPS) were closely related with water quality and sludge morphology, and could be used as the indicators for anammox microbial survival ability and microbial aggregate morphology. Furthermore, slime secreted from anammox bacterial cells may be exhibited higher viscosity to the sludge surface and easily formed the gel network to aggregate. Large amounts of hydrophobic groups of protein in TB-EPS promoted the microbial aggregation. The mechanisms of anammox aggregation explored in this study enhanced the understanding of anammox stability in wastewater treatment processes.
Asunto(s)
Aguas del Alcantarillado/química , Aguas Residuales/química , Interacciones Hidrofóbicas e Hidrofílicas , Polímeros/química , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
Objective To investigate the effects of low-intensity pulsed ultrasound (LIPUS) on the mandibular remodeling following inferior alveolar nerve transection (IANX) and to optimize the parameters of LIPUS in the treatment of nerve injury. Methods IANX was performed in male Sprague-Dawley rats. Four weeks after IANX,the effect of daily LIPUS (from day 1) on the transected inferior alveolar nerve was examined in terms of sensitivity to mechanical stimulation. Moreover,histopathologic changes of mandibles were analyzed by micro-CT,HE staining,Masson trichrome staining,and immunohistochemical staining. Results LIPUS promoted the recovery of inferior alveolar nerve injury after transection. HE staining displayed the improvement of trabecular thickness and continuity. LIPUS with higher duty ratios had more obvious effect on bone remodeling. Conclusion LIPUS promotes the mandibular remodeling following IANX.
Asunto(s)
Remodelación Ósea/efectos de la radiación , Mandíbula/efectos de la radiación , Nervio Mandibular/cirugía , Traumatismos del Nervio Trigémino/radioterapia , Ondas Ultrasónicas , Animales , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
This study investigated the therapeutic efficiency of monomethoxy polyethylene glycol-poly(lactic-co-glycolic acid) (mPEG-PLGA) co-loaded with syringopicroside and hydroxytyrosol as a drug with effective targeting and loading capacity as well as persistent circulation in vivo. The nanoparticles were prepared using a nanoprecipitation method with mPEG-PLGA as nano-carrier co-loaded with syringopicroside and hydroxytyrosol (SH-NPs). The parameters like in vivo pharmacokinetics, biodistribution in vivo, fluorescence in vivo endomicroscopy, and cellular uptake of SH-NPs were investigated. Results showed that the total encapsulation efficiency was 32.38 ± 2.76 %. Total drug loading was 12.01 ± 0.42 %, particle size was 91.70 ± 2.11 nm, polydispersity index was 0.22 ± 0.01, and zeta potential was -24.5 ± 1.16 mV for the optimized SH-NPs. The nanoparticle morphology was characterized using transmission electron microscopy, which indicated that the particles of SH-NPs were in uniformity within the nanosize range and of spherical core shell morphology. Drug release followed Higuchi kinetics. Compared with syringopicroside and hydroxytyrosol mixture (SH), SH-NPs produced drug concentrations that persisted for a significantly longer time in plasma following second-order kinetics. The nanoparticles moved gradually into the cell, thereby increasing the quantity. ALT, AST, and MDA levels were significantly lower on exposure to SH-NPs than in controls. SH-NPs could inhibit the proliferation of HepG2.2.15 cells and could be taken up by HepG2.2.15 cells. The results confirmed that syringopicroside and hydroxytyrosol can be loaded simultaneously into mPEG-PLGA nanoparticles. Using mPEG-PLGA as nano-carrier, sustained release, high distribution in the liver, and protective effects against hepatic injury were observed in comparison to SH.