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1.
Biomacromolecules ; 25(4): 2114-2135, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38011222

RESUMEN

Polymersomes, composed of amphiphilic block copolymers, are self-assembled vesicles that have gained attention as potential drug delivery systems due to their good biocompatibility, stability, and versatility. Various experimental techniques have been employed to characterize the self-assembly behaviors and properties of polymersomes. However, they have limitations in revealing molecular details and underlying mechanisms. Computational modeling techniques have emerged as powerful tools to complement experimental studies and enabled researchers to examine drug delivery mechanisms at molecular resolution. This review aims to provide a comprehensive overview of the state of the art in the field of polymersome-based drug delivery systems, with an emphasis on insights gained from both experimental and computational studies. Specifically, we focus on polymersome morphologies, self-assembly kinetics, fusion and fission, behaviors in flow, as well as drug encapsulation and release mechanisms. Furthermore, we also identify existing challenges and limitations in this rapidly evolving field and suggest possible directions for future research.


Asunto(s)
Sistemas de Liberación de Medicamentos , Polímeros , Preparaciones Farmacéuticas , Sistemas de Liberación de Medicamentos/métodos
2.
Nature ; 553(7687): 217-221, 2018 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-29258297

RESUMEN

Although genetic factors contribute to almost half of all cases of deafness, treatment options for genetic deafness are limited. We developed a genome-editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9-guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness. We designed and validated, both in vitro and in primary fibroblasts, genome editing agents that preferentially disrupt the dominant deafness-associated allele in the Tmc1 (transmembrane channel-like gene family 1) Beethoven (Bth) mouse model, even though the mutant Tmc1Bth allele differs from the wild-type allele at only a single base pair. Injection of Cas9-guide RNA-lipid complexes targeting the Tmc1Bth allele into the cochlea of neonatal Tmc1Bth/+ mice substantially reduced progressive hearing loss. We observed higher hair cell survival rates and lower auditory brainstem response thresholds in injected ears than in uninjected ears or ears injected with control complexes that targeted an unrelated gene. Enhanced acoustic startle responses were observed among injected compared to uninjected Tmc1Bth/+ mice. These findings suggest that protein-RNA complex delivery of target gene-disrupting agents in vivo is a potential strategy for the treatment of some types of autosomal-dominant hearing loss.


Asunto(s)
Proteínas Asociadas a CRISPR/administración & dosificación , Edición Génica/métodos , Genes Dominantes/genética , Terapia Genética/métodos , Pérdida Auditiva/genética , Estimulación Acústica , Alelos , Animales , Animales Recién Nacidos , Umbral Auditivo , Secuencia de Bases , Proteínas Asociadas a CRISPR/metabolismo , Proteínas Asociadas a CRISPR/uso terapéutico , Sistemas CRISPR-Cas , Supervivencia Celular , Cóclea/citología , Cóclea/metabolismo , Modelos Animales de Enfermedad , Potenciales Evocados Auditivos del Tronco Encefálico , Femenino , Fibroblastos , Células Ciliadas Auditivas/citología , Pérdida Auditiva/fisiopatología , Pérdida Auditiva/prevención & control , Humanos , Liposomas , Masculino , Proteínas de la Membrana/genética , Ratones , Reflejo de Sobresalto
3.
Chembiochem ; 24(16): e202300132, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37340829

RESUMEN

Self-assembly of block copolymers has recently drawn great attention due to its remarkable performance and wide variety of applications in biomedicine, biomaterials, microelectronics, photoelectric materials, catalysts, etc. Poly(amino acid)s (PAAs), formed by introducing synthetic amino acids into copolymer backbones, are able to fold into different secondary conformations when compared with traditional amphiphilic copolymers. Apart from changing the chemical composition and degree of polymerization of copolymers, the self-assembly behaviors of PAAs could be controlled by their secondary conformations, which are more flexible and adjustable for fine structure tailoring. In this article, we summarize the latest findings on the variables that influence secondary conformations, in particular the regulation of order-to-order conformational changes and the approaches used to manage the self-assembly behaviors of PAAs. These strategies include controlling pH, redox reactions, coordination, light, temperature, and so on. Hopefully, we can provide valuable perspectives that will be useful for the future development and use of synthetic PAAs.


Asunto(s)
Aminoácidos , Polímeros , Polímeros/química , Conformación Molecular , Polimerizacion , Micelas
4.
Appl Microbiol Biotechnol ; 107(5-6): 1983-1995, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36763115

RESUMEN

Polyurethanes (PU) are one of the most used categories of plastics and have become a significant source of environmental pollutants. Degrading the refractory PU wastes using environmentally friendly strategies is in high demand. In this study, three microbial consortia from the landfill leachate were enriched using PU powder as the sole carbon source. The consortia efficiently degraded polyester PU film and accumulated high biomass within 1 week. Scanning electron microscopy, Fourier transform infrared spectroscopy, and contact angle analyses showed significant physical and chemical changes to the PU film after incubating with the consortia for 48 h. In addition, the degradation products adipic acid and butanediol were detected by high-performance liquid chromatography in the supernatant of the consortia. Microbial composition and extracellular enzyme analyses revealed that the consortia can secrete esterase and urease, which were potentially involved in the degradation of PU. The dominant microbes in the consortia changed when continuously passaged for 50 generations of growth on the PU films. This work demonstrates the potential use of microbial consortia in the biodegradation of PU wastes. KEY POINTS: • Microbial consortia enriched from landfill leachate degraded polyurethane film. • Consortia reached high biomass within 1 week using polyurethane film as the sole carbon source. • The consortia secreted potential polyurethane-degrading enzymes.


Asunto(s)
Poliuretanos , Contaminantes Químicos del Agua , Poliuretanos/metabolismo , Consorcios Microbianos , Microbiología del Suelo , Biodegradación Ambiental , Instalaciones de Eliminación de Residuos
5.
Arch Toxicol ; 97(6): 1783-1794, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37148319

RESUMEN

Pathogens co-evolved with ticks to facilitate blood collection and pathogen transmission. Although tick saliva was recently found to be rich in bioactive peptides, it is still elusive which saliva peptide promotes virus transmission and which pathways are invovled. Here, we used a saliva peptide HIDfsin2 and a severe fever with thrombocytopenia syndrome virus (SFTSV) both carried by the tick Haemaphysalis longicornis to elucidate the relationship between tick saliva components and tick-borne viruses. HIDfsin2 was found to promote the replication of SFTSV in a dose-dependent manner in vitro. HIDfsin2 was further revealed to MKK3/6-dependently magnify the activation of p38 MAPK. The overexpression, knockdown and phosphorylation site mutation of p38α indicated that p38 MAPK activation facilitated SFTSV infection in A549 cells. Moreover, the blockade of p38 MAPK activation significantly suppressed SFTSV replication. Differently, HIDfsin2 or pharmacological inhibition of p38 MAPK activation had no effect on a mosquito-borne Zika virus (ZIKV). All these results showed that HIDfsin2 specifically promoted SFTSV replication through the MKK3/6-dependent enhancement of p38 MAPK activation. Our study provides a new perspective on the transmission of tick-borne viruses under natural conditions, and supports that the blockade of p38 MAPK activation can be a promising strategy against the mortal tick-borne virus SFTSV.


Asunto(s)
Phlebovirus , Garrapatas , Replicación Viral , Animales , Humanos , Proteínas Quinasas p38 Activadas por Mitógenos , Saliva , Transducción de Señal , Garrapatas/virología , Phlebovirus/fisiología
6.
Ecotoxicol Environ Saf ; 263: 115232, 2023 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-37429089

RESUMEN

Polyolefin plastics, such as polyethylene (PE) and polystyrene (PS), are the most widely used synthetic plastics in our daily life. However, the chemical structure of polyolefin plastics is composed of carbon-carbon (C-C) bonds, which is extremely stable and makes polyolefin plastics recalcitrant to degradation. The growing accumulation of plastic waste has caused serious environmental pollution and has become a global environmental concern. In this study, we isolated a unique Raoultella sp. DY2415 strain from petroleum-contaminated soil that can degrade PE and PS film. After 60 d of incubation with strain DY2415, the weight of the UV-irradiated PE (UVPE) film and PS film decreased by 8% and 2%, respectively. Apparent microbial colonization and holes on the surface of the films were observed by scanning electron microscopy (SEM). Furthermore, the Fourier transform infrared spectrometer (FTIR) results showed that new oxygen-containing functional groups such as -OH and -CO were introduced into the polyolefin molecular structure. Potential enzymes that may be involved in the biodegradation of polyolefin plastics were analyzed. These results demonstrate that Raoultella sp. DY2415 has the ability to degrade polyolefin plastics and provide a basis for further investigating the biodegradation mechanism.


Asunto(s)
Petróleo , Poliestirenos , Poliestirenos/metabolismo , Polietileno/química , Suelo , Enterobacteriaceae , Biodegradación Ambiental , Carbono , Plásticos/metabolismo
7.
Int J Mol Sci ; 24(10)2023 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-37240036

RESUMEN

Medication-related osteonecrosis of the jaw (MRONJ) is a severe disease with unclear pathogenesis. Adipose tissue-derived mesenchymal stromal cells (MSC(AT)s) serve as a special source for cell therapy. Herein, we explored whether exosomes (Exo) derived from MSC(AT)s promote primary gingival wound healing and prevent MRONJ. An MRONJ mice model was constructed using zoledronate (Zol) administration and tooth extraction. Exosomes were collected from the conditioned medium (CM) of MSC(AT)s (MSC(AT)s-Exo) and locally administered into the tooth sockets. Interleukin-1 receptor antagonist (IL-1RA)-siRNA was used to knock down the expression of IL-1RA in MSC(AT)s-Exo. Clinical observations, micro-computed tomography (microCT), and histological analysis were used to evaluate the therapeutic effects in vivo. In addition, the effect of exosomes on the biological behavior of human gingival fibroblasts (HGFs) was evaluated in vitro. MSC(AT)s-Exo accelerated primary gingival wound healing and bone regeneration in tooth sockets and prevented MRONJ. Moreover, MSC(AT)s-Exo increased IL-1RA expression and decreased interleukin-1 beta (IL-1ß) and tumor necrosis factor-α (TNF-α) expression in the gingival tissue. The sequent rescue assay showed that the effects of preventing MRONJ in vivo and improving the migration and collagen synthesis abilities of zoledronate-affected HGFs in vitro were partially impaired in the IL-1RA-deficient exosome group. Our results indicated that MSC(AT)s-Exo might prevent the onset of MRONJ via an IL-1RA-mediated anti-inflammatory effect in the gingiva wound and improve the migration and collagen synthesis abilities of HGFs.


Asunto(s)
Exosomas , Células Madre Mesenquimatosas , Osteonecrosis , Ratones , Animales , Humanos , Ácido Zoledrónico , Proteína Antagonista del Receptor de Interleucina 1/genética , Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Exosomas/metabolismo , Microtomografía por Rayos X , Osteonecrosis/metabolismo , Células Madre Mesenquimatosas/metabolismo , Colágeno/metabolismo
8.
J Occup Environ Hyg ; 20(7): 289-303, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37084391

RESUMEN

The objective of this study is to evaluate a prototype local ventilation system (LVS) intended to reduce retail store workers' exposure to aerosols. The evaluation was carried out in a large aerosol test chamber where relatively uniform concentrations of polydisperse sodium chloride and glass-sphere particles were generated to test the system with nano- and micro-size particles. In addition, a cough simulator was constructed to mimic aerosols released by mouth breathing and coughing. Particle reduction efficiencies of the LVS were determined in four different experimental conditions using direct reading instruments and inhalable samplers. The particle reduction efficiency (%) depended on the position beneath the LVS, but the percentage was consistently high at the LVS center as follows: (1) > 98% particle reduction relative to background aerosols; (2) > 97% in the manikin's breathing zone relative to background aerosols; (3) > 97% during mouth breathing and coughing simulation; and (4) > 97% with a plexiglass barrier installation. Lower particle reduction (<70%) was observed when the LVS airflow was disturbed by background ventilation airflow. The lowest particle reduction (<20%) was observed when the manikin was closest to the simulator during coughing.


Asunto(s)
Exposición por Inhalación , Respiración por la Boca , Humanos , Tamaño de la Partícula , Aerosoles y Gotitas Respiratorias
9.
BMC Oral Health ; 23(1): 14, 2023 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-36627695

RESUMEN

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a serious debilitating disease caused by anti-resorption and anti-angiogenesis drugs, significantly affecting patients' quality of life. Recent studies suggested that primary gingival wound healing may effectively prevent the development of MRONJ. This study aimed to evaluate the effects of low-level light therapy (LLLT) on promoting gingival wound healing in extraction sockets of MRONJ-like mice and preventing the occurrence of MRONJ. Furthermore, we explored underlying mechanisms. METHODS: Mice were randomly divided into the Ctrl, Zol, and Zol + LLLT groups. Administration of zoledronate and tooth extraction of bilateral maxillary second molars were used to build the MRONJ model, and LLLT was locally administered into the tooth sockets to examine the effect of LLLT. Next, to explore the function of IL-1RA, we performed LLLT with interleukin-1 receptor antagonist (IL-1RA) neutralizing antibody (named Zol + LLLT + IL-1RA NAb group) or negative control antibodies for tooth extraction in subsequent rescue animal experiments. Stereoscope observations, micro-computed tomography, and histological examination were conducted to evaluate gingival wound healing and bone regeneration in tooth sockets. The effects of LLLT on the migration capacities of zoledronate-treated epithelial cells were assessed in vitro. RESULTS: LLLT promoted primary gingival wound healing without exposed necrotic bone. Micro-computed tomography results showed higher bone volume and mineral density of the tooth sockets after LLLT. Histology analysis showed complete gingival coverage, obvious bone regeneration, and reduced soft tissue inflammation, with down-regulated pro-inflammation cytokines, like interleukin-1 beta (IL-1ß) and tumor necrosis factor-α (TNF-α), and up-regulated IL-1RA expression in the gingival tissue in the LLLT group. The rescue assay further showed that the effects of LLLT promoting gingival wound healing and preventing MRONJ might be partially abolished by IL-1RA neutralizing antibodies. In vitro studies demonstrated that LLLT accelerated zoledronate-treated epithelial cell migration. CONCLUSIONS: LLLT might promote primary gingival wound healing and contribute to subsequent bone regeneration of the tooth extractions in MRONJ-like lesions via IL-1RA-mediated pro-inflammation signaling suppression.


Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos , Conservadores de la Densidad Ósea , Enfermedades de las Encías , Terapia por Luz de Baja Intensidad , Animales , Ratones , Osteonecrosis de los Maxilares Asociada a Difosfonatos/prevención & control , Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Enfermedades de las Encías/radioterapia , Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Calidad de Vida , Extracción Dental , Cicatrización de Heridas , Microtomografía por Rayos X , Ácido Zoledrónico/efectos adversos
10.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 52(6): 738-743, 2023 Dec 07.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-38105692

RESUMEN

An 11-day-old female neonate was admitted for cough with mouth foaming and feeding difficulties. The laboratory results indicated hyperlactatemia, elevated markers of myocardial injury and inflammation, and high levels of acylcarnitine octanoylcarnitine and decanoylcarnitine in tandem mass spectrometry. Ultrasonography and MRI suggested cardiac insufficiency and hypertrophic cardiomyopathy. Whole exome sequencing showed that both the proband and her elderly sister had a compound heterozygous variant of c.1492dup (p.T498Nfs*13) and c.1376T>C (p.F459S) in the ATAD3A gene, inherited from their father and mother, respectively. The diagnosis of Harel-Yoon syndrome was confirmed. The proband and her sister were born with clinical manifestations of metabolic acidosis, hyperlactatemia, feeding difficulties, elevated markers of myocardial injury as well as cardiac insufficiency, and both died in early infancy.


Asunto(s)
Hiperlactatemia , Humanos , Recién Nacido , Femenino , Anciano , Mutación , ATPasas Asociadas con Actividades Celulares Diversas/genética , ATPasas Asociadas con Actividades Celulares Diversas/química , Proteínas de la Membrana/genética , Proteínas Mitocondriales/genética
11.
Angew Chem Int Ed Engl ; 62(6): e202213000, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-36353928

RESUMEN

Metal ions play critical roles in facilitating peptide folding and inducing conformational transitions, thereby impacting on the biological activity of many proteins. However, the effect of metal sites on the hierarchical structures of biopolymers is still poorly understood. Herein, inspired by metalloproteins, we report an order-to-order conformational regulation in synthetic polymers mediated by a variety of metal ions. The copolymers are decorated with clinically available desferrioxamine (DFO) as an exogenous ligand template, which presents a geometric constraint toward peptide backbone via short-range hydrogen bonding interactions, thus dramatically altering the secondary conformations and self-assembly behaviors of polypeptides and allowing for a controllable ß-sheet to α-helix transition modulated by metal-ligand interactions. These metallopolymers could form ferritin-inspired hierarchical structures with high stability and membrane activity for efficient brain delivery across the blood-brain barrier (BBB) and long-lasting magnetic resonance imaging (MRI) in vivo.


Asunto(s)
Polímeros , Proteínas , Polímeros/química , Ligandos , Péptidos/química , Metales/química , Iones
12.
Br J Anaesth ; 129(6): 970-976, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36243580

RESUMEN

BACKGROUND: HYR-PB21 is a new sustained-release formulation of bupivacaine indicated for controlling postoperative pain. The objectives of this study were to investigate the analgesic efficacy and safety profile of HYR-PB21 in patients after haemorrhoidectomy. METHODS: This was a multicentre, randomised, double-blind, positive-controlled trial. Patients were assigned randomly to receive a single dose of HYR-PB21 (150 mg or 300 mg) or bupivacaine HCl (75 mg) after surgery for prolapsing haemorrhoids. Postoperative pain was evaluated using a numeric rating scale at rest to calculate a cumulative pain score. Total rescue opioid usage and the proportion of subjects receiving rescue opioid were also assessed. RESULTS: We enrolled 72 patients with haemorrhoidectomy, and 71 patients completed the study. The average cumulative pain score through 72 h after surgery in the 300 mg HYR-PB21 group (87 scores) was lower than in the bupivacaine HCl group (166 scores) in an intention-to-treat analysis (P<0.001). There was a dose-response effect in reducing total opioid usage and the proportion of rescue opioid use between the 150 mg and 300 mg HYR-PB21 groups, with bupivacaine HCl as a reference group. The HYR-PB21 groups did not show more adverse effects than the bupivacaine HCl group. CONCLUSIONS: Local infiltration of a single dose of HYR-PB21 sustained-release bupivacaine had better efficacy in controlling postoperative pain, with similar adverse effects, compared with a single dose of bupivacaine HCl in patients after haemorrhoidectomy. CLINICAL TRIAL REGISTRATION: ChiCTR2000041318 (Chinese Clinical Trial Registry).


Asunto(s)
Analgesia , Hemorreoidectomía , Humanos , Bupivacaína/efectos adversos , Analgésicos Opioides/uso terapéutico , Preparaciones de Acción Retardada , Anestésicos Locales/efectos adversos , Dimensión del Dolor , Liposomas/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/prevención & control , Dolor Postoperatorio/inducido químicamente , Método Doble Ciego
13.
Int J Mol Sci ; 23(19)2022 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-36232310

RESUMEN

Plastic waste is rapidly accumulating in the environment and becoming a huge global challenge. Many studies have highlighted the role of microbial metabolic engineering for the valorization of polyethylene terephthalate (PET) waste. In this study, we proposed a new conceptual scheme for upcycling of PET. We constructed a multifunctional Pseudomonas putida KT2440 to simultaneously secrete PET hydrolase LCC, a leaf-branch compost cutinase, and synthesize muconic acid (MA) using the PET hydrolysate. The final product MA and extracellular LCC can be separated from the supernatant of the culture by ultrafiltration, and the latter was used for the next round of PET hydrolysis. A total of 0.50 g MA was produced from 1 g PET in each cycle of the whole biological processes, reaching 68% of the theoretical conversion. This new conceptual scheme for the valorization of PET waste should have advantages over existing PET upcycling schemes and provides new ideas for the utilization of other macromolecular resources that are difficult to decompose, such as lignin.


Asunto(s)
Pseudomonas putida , Hidrolasas/genética , Hidrolasas/metabolismo , Lignina/metabolismo , Plásticos/metabolismo , Tereftalatos Polietilenos , Pseudomonas putida/genética , Pseudomonas putida/metabolismo , Ácido Sórbico/análogos & derivados
14.
Am J Orthod Dentofacial Orthop ; 160(3): 423-429, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34052103

RESUMEN

INTRODUCTION: The objective of this research was to study the factors associated with the alveolar bone depth mesial to the mandibular third molars (M8) after the mandibular second (M7) and third molars were protracted into the space of the mandibular first molars (M6), which were newly extracted for orthodontic treatment or extracted more than 1 year before treatment. METHODS: This retrospective study included 57 adult patients (mean age 23.40 ± 4.40 years) in whom M6 were newly extracted for orthodontic treatment or extracted more than 1 year before treatment. The alveolar bone depth mesial to M8 was measured on posttreatment panoramic radiographs. The vertical, horizontal, and angular changes of M8 were measured on both pre- and posttreatment panoramic radiographs. Linear correlation and regression analyses were conducted to explore the factors associated with the alveolar bone depth mesial to M8. RESULTS: The alveolar bone conditions of M6 (R= -0.391, P <0.001) and the vertical movement directions of M8 (R= -0.433, P <0.001) were significant factors associated with the alveolar bone depth mesial to M8 after orthodontic protraction. CONCLUSIONS: Without considering the pretreatment periodontal status of M8, patients with M6 extracted exceeding 1 year before treatment and with M8 extruded after orthodontic protraction may exhibit deeper alveolar bone depth mesial to M8.


Asunto(s)
Tercer Molar , Diente Molar , Adulto , Humanos , Mandíbula/diagnóstico por imagen , Tercer Molar/diagnóstico por imagen , Radiografía Panorámica , Estudios Retrospectivos , Adulto Joven
15.
Med Sci Monit ; 26: e921626, 2020 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-32034900

RESUMEN

BACKGROUND The stability of orthodontic treatment is thought to be significantly affected by the compression and retraction of gingival tissues, but the underlying molecular mechanism is not fully elucidated. The objectives of our study were to explore the effects of mechanical force on the ECM-integrin-cytoskeleton linkage response in human gingival fibroblasts (HGFs) cultured on 3-dimension (3D) lactide-co-glycolide (PLGA) biological scaffold and to further study the mechanotransduction pathways that could be involved. MATERIAL AND METHODS A compressive force of 25 g/m² was applied to the HGFs-PLGA 3D co-cultured model. Rhodamine-phalloidin staining was used to evaluate the filamentous actin (F-actin) cytoskeleton. The expression level of type I collagen (COL-1) and the activation of the integrin alpha5ß1/focal adhesion kinase (FAK) signaling pathway were determined by using real-time PCR and Western blotting analysis. The impacts of the applied force on the expression levels of FAK, phosphorylated focal adhesion kinase (p-FAK), and COL-1 were also measured in cells treated with integrin alpha5ß1 inhibitor (Ac-PHSCN-NH 2, ATN-161). RESULTS Mechanical force increased the expression of integrin alpha5ß1, FAK (p-FAK), and COL-1 in HGFs, and induced the formation of stress fibers. Blocking integrin alpha5ß1 reduced the expression of FAK (p-FAK), while the expression of COL-1 was not fully inhibited. CONCLUSIONS The integrin alpha5ß1/FAK signaling pathway and actin cytoskeleton appear to be involved in the mechanotransduction of HGFs. There could be other mechanisms involved in the promotion effect of mechanical force on collagen synthesis in addition to the integrin alpha5ß1 pathway.


Asunto(s)
Citoesqueleto de Actina/metabolismo , Fibroblastos/citología , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Encía/citología , Integrina alfa5beta1/metabolismo , Mecanotransducción Celular , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/farmacología , Citoesqueleto de Actina/efectos de los fármacos , Actinas/metabolismo , Adolescente , Células Cultivadas , Niño , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Proteína-Tirosina Quinasas de Adhesión Focal/genética , Humanos , Mecanotransducción Celular/efectos de los fármacos , Fosforilación/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Fibras de Estrés/efectos de los fármacos , Fibras de Estrés/metabolismo , Estrés Mecánico
16.
J Am Chem Soc ; 139(9): 3312-3315, 2017 03 08.
Artículo en Inglés | MEDLINE | ID: mdl-28121424

RESUMEN

Covalent conjugation of water-soluble polymers to proteins is critical for evading immune surveillance in the field of biopharmaceuticals. The most common and long-standing polymer modification is the attachment of methoxypoly(ethylene glycol) (mPEG), termed PEGylation, which has led to several clinically approved pharmaceuticals. Recent data indicate that brush-type polymers significantly enhance in vitro and in vivo properties. Herein, the polymer conformation of poly(ethylene glycol) is detailed and compared with those of water-soluble polyacrylate and polynorbornene (PNB) when attached to icosahedral virus-like particles. Small-angle neutron scattering reveals vastly different polymer conformations of the multivalent conjugates. Immune recognition of conjugated particles was evaluated versus PEGylated particles, and PNB conjugation demonstrated the most effective shielding from antibody recognition.


Asunto(s)
Acrilatos/química , Plásticos/química , Polietilenglicoles/química , Vacunas de Partículas Similares a Virus/química , Animales , Ratones , Modelos Moleculares , Estructura Molecular , Difracción de Neutrones , Dispersión del Ángulo Pequeño
17.
EMBO J ; 31(3): 534-51, 2012 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-22157745

RESUMEN

The small GTPase Rac1 plays important roles in many processes, including cytoskeletal reorganization, cell migration, cell-cycle progression and gene expression. The initiation of Rac1 signalling requires at least two mechanisms: GTP loading via the guanosine triphosphate (GTP)/guanosine diphosphate (GDP) cycle, and targeting to cholesterol-rich liquid-ordered plasma membrane microdomains. Little is known about the molecular mechanisms governing this specific compartmentalization. We show that Rac1 can incorporate palmitate at cysteine 178 and that this post-translational modification targets Rac1 for stabilization at actin cytoskeleton-linked ordered membrane regions. Palmitoylation of Rac1 requires its prior prenylation and the intact C-terminal polybasic region and is regulated by the triproline-rich motif. Non-palmitoylated Rac1 shows decreased GTP loading and lower association with detergent-resistant (liquid-ordered) membranes (DRMs). Cells expressing no Rac1 or a palmitoylation-deficient mutant have an increased content of disordered membrane domains, and markers of ordered membranes isolated from Rac1-deficient cells do not correctly partition in DRMs. Importantly, cells lacking Rac1 palmitoylation show spreading and migration defects. These data identify palmitoylation as a mechanism for Rac1 function in actin cytoskeleton remodelling by controlling its membrane partitioning, which in turn regulates membrane organization.


Asunto(s)
Membrana Celular/metabolismo , Ácido Palmítico/metabolismo , Proteína de Unión al GTP rac1/fisiología , Secuencia de Aminoácidos , Biopolímeros/metabolismo , Guanosina Trifosfato/metabolismo , Datos de Secuencia Molecular , Prenilación de Proteína , Homología de Secuencia de Aminoácido
18.
Phys Chem Chem Phys ; 17(16): 10726-36, 2015 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-25811660

RESUMEN

The role of polymers in artificial photosystems has been studied in detail. The photosystems were composed of tris(2,2'-bipyridyl) ruthenium(II) chloride as a photosensitizer (PS), colloidal Pt stabilized by polymer as a hydrogen-evolving catalyst and sodium ascorbate as an electron donor, without the addition of a traditional molecular electron mediator. Comprehensive insights into the production of hydrogen on irradiation with visible light were achieved. Several polymers, including neutral polyvinyl pyrrolidone, anionic poly(sodium 4-styrene sulfonate) and poly(acrylic acid) not only stabilized the nanoparticles, but were also effective in the production of hydrogen. Under the optimum conditions, an outstanding apparent quantum efficiency of 12.8% for the evolution of hydrogen was achieved. The formation of self-assembled and spatially separated donor-acceptor complexes via the non-covalent intermolecular interaction between PS and the polymer-Pt was pivotal in the efficient conversion of solar energy to hydrogen fuel. Important details of the photo-induced electron and energy transfer processes in the self-assembled artificial photosystems were determined by nanosecond transient absorption spectrometry and time-resolved fluorescence spectrometry. The initial step in the photo-catalytic production of hydrogen was a reductive quenching of the triplet excited state of the PS by sodium ascorbate, leading to a reduced form of PS, which could then be quickly quenched by the polymer. The rate-determining step was the electron transfer from PS to the catalyst via the polymer bridge.


Asunto(s)
2,2'-Dipiridil/análogos & derivados , Hidrógeno/química , Procesos Fotoquímicos , Platino (Metal)/química , Polímeros/química , 2,2'-Dipiridil/química , Ácido Ascórbico/química , Catálisis , Complejos de Coordinación , Transporte de Electrón , Nanopartículas/química , Tamaño de la Partícula
19.
ScientificWorldJournal ; 2014: 845721, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24574925

RESUMEN

The study aims to investigate fungal community structures and dynamic changes in forest soil lignocellulose-degrading process. rRNA gene clone libraries for the samples collected in different stages of lignocellulose degradation process were constructed and analyzed. A total of 26 representative RFLP types were obtained from original soil clone library, including Mucoromycotina (29.5%), unclassified Zygomycetes (33.5%), Ascomycota (32.4%), and Basidiomycota (4.6%). When soil accumulated with natural lignocellulose, 16 RFLP types were identified from 8-day clone library, including Basidiomycota (62.5%), Ascomycota (36.1%), and Fungi incertae sedis (1.4%). After enrichment for 15 days, identified 11 RFLP types were placed in 3 fungal groups: Basidiomycota (86.9%), Ascomycota (11.5%), and Fungi incertae sedis (1.6%). The results showed richer, more diversity and abundance fungal groups in original forest soil. With the degradation of lignocellulose, fungal groups Mucoromycotina and Ascomycota decreased gradually, and wood-rotting fungi Basidiomycota increased and replaced the opportunist fungi to become predominant group. Most of the fungal clones identified in sample were related to the reported lignocellulose-decomposing strains. Understanding of the microbial community structure and dynamic change during natural lignocellulose-degrading process will provide us with an idea and a basis to construct available commercial lignocellulosic enzymes or microbial complex.


Asunto(s)
Biomasa , Ecosistema , Hongos/metabolismo , Lignina/metabolismo , Características de la Residencia , Microbiología del Suelo , Hongos/química , Hongos/genética , Lignina/análisis , Lignina/genética , Filogenia
20.
Heliyon ; 10(1): e23285, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38163099

RESUMEN

Objectives: This study intends to explore the effects of the surgery-first approach (SFA) on quality of life and mental health of patients who undergo orthognathic surgery compared to the conventional three-stage approach (CTA). Data: The analysis included eight studies with a total of 307 patients, of which one was randomized controlled trial (RCT), one was clinical controlled trial (CCT), and six were non-randomized studies of interventions (NRSIs). Sources: Electronic databases such as Medline, Embase, Scopus, and Web of Science were searched for eligible trials up to April 2023. Study selection: RCTs, CCTs, and NRSIs, which compared the quality of life or mental health of orthognathic patients treated with SFA and CTA, were included in this study. The meta-analysis showed that the standardized mean differences (SMD) of Oral Health Impact Profiles-14 (OHIP-14) scores and the Orthognathic Quality of Life Questionnaire (OQLQ) between SFA and CTA were -1.58 (P = 0.05) and -2.99 (P < 0.00001) at the termination of the first-stage treatment, which altered to -0.94 (P = 0.54) and 0.09 (P = 0.65) after total treatment. Two studies applied the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) and the Beck Depression Inventory (BDI-II) to examine mental health, resulting in a trend similar to the former scales. Conclusion: In contrast to the conventional procedure, orthognathic treatment with SFA can instantly enhance the quality of life at the end of the first-stage treatment but has similar effects after the overall treatment. Moreover, SFA has a positive impact on psychological conditions. Clinical significance: This study first systematically reviewed the effect of SFA on patients' mental well-being. According to our findings, it is better to select SFA if possible. Otherwise, the patient's psychological condition should be monitored appropriately throughout decompensation for better well-being both physically and mentally.

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