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1.
Osteoporos Int ; 35(4): 727-731, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38062162

RESUMEN

Gorham-Stout syndrome is an aggressive, non-hereditary, and rare disease affecting bone metabolism. Its etiology and pathogenesis remain elusive. The syndrome manifests with diverse clinical symptoms, often leading to frequent misdiagnoses and presenting challenges in treatment. In this study, we report a case of cranial and maxillary osteolysis in a 47-year-old female patient with somatic mutations in the VEGF-A, VEGF-B, and VEGF-C genes and the EPHB4 gene. After treatment with bisphosphonates, this patient still had persistent resorption of the mandible, but switching to a teriparatide and denosumab combination yielded substantial improvement. This study is the first report to show that teriparatide combined with denosumab can be used to treat Gorham-Stout syndrome.


Asunto(s)
Osteólisis Esencial , Femenino , Humanos , Persona de Mediana Edad , Osteólisis Esencial/diagnóstico por imagen , Osteólisis Esencial/tratamiento farmacológico , Teriparatido/uso terapéutico , Denosumab/uso terapéutico , Difosfonatos/uso terapéutico , Síndrome
2.
Clin Oral Investig ; 28(2): 147, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38351377

RESUMEN

BACKGROUND: Phosphorous necrosis of the jaw (PNJ) exhibits similar clinical and pathological features as medical-related osteonecrosis of the jaw (MRONJ). This study aims at comparing the similarities and differences between PNJ and MRONJ regarding pathological features and to provide a theoretical basis for the clinical diagnosis and management of PNJ. MATERIAL AND METHODS: A retrospective analysis was conducted to assess clinical differences among 38 PNJ patients and 31 MRONJ patients, who were diagnosed and treated between January 2009 and October 2022. Pathological alterations in bone tissue were evaluated using EDS, H&E, Masson, and TRAP staining on five specimens from both MRONJ and PNJ cases; furthermore, immunohistochemistry was used to determine the expression levels of OPG, RANKL, and Runx2. The mandibular coronoid process was removed from individuals with temporomandibular joint ankylosis to serve as a control. RESULTS: CBCT imaging demonstrated necrotic bone formation in block, strip, or plaque shapes. EDS analysis showed that the calcium/phosphorus ratio in the bone tissue of PNJ and MRONJ was significantly lower than that of the control group (P < 0.05). Additionally, staining indicated reduced osteoblast counts, disrupted bone trabecular structure, and decreased collagen fiber content in the bone tissues of PNJ and MRONJ. Immunohistochemistry demonstrated that RANKL expression was significantly lower in MRONJ compared to PNJ and control groups (P < 0.05). Conversely, Runx2 expression was significantly higher in PNJ than in MRONJ and control groups (P < 0.05), and there was no significant difference in OPG expression. CONCLUSION: PNJ and MRONJ demonstrate comparable clinical manifestations and pathological traits, although disparities may exist in their underlying exhibit comparable clinical manifestations, pathological traits, and molecular mechanisms.


Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos , Conservadores de la Densidad Ósea , Trastornos de la Articulación Temporomandibular , Humanos , Osteonecrosis de los Maxilares Asociada a Difosfonatos/patología , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Estudios Retrospectivos , Maxilares , Difosfonatos/uso terapéutico
3.
Electrophoresis ; 43(16-17): 1746-1754, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35656648

RESUMEN

The laser print, cut, and laminate (PCL) method for microfluidic device fabrication can be leveraged for rapid and inexpensive prototyping of electrophoretic microchips useful for optimizing separation conditions. The rapid prototyping capability allows the evaluation of fluidic architecture, applied fields, reagent concentrations, and sieving matrix, all within the context of using fluorescence-compatible substrates. Cyclic olefin copolymer and toner-coated polyethylene terephthalate (tPeT) were utilized with the PCL technique and bonding methods optimized to improve device durability during electrophoresis. A series of separation channel designs and centrifugation conditions that provided successful loading of sieving polymer in less than 3 min was described. Separation of a 400-base DNA sizing ladder provided calculated base resolution between 3 and 4 bases, a greater than 18-fold improvement over separations on similar substrates. Finally, the accuracy and precision capabilities of these devices were demonstrated by separating and sizing DNA fragments of 147 and 167 bases as 148.62 ± 2 and 166.48 ± 3 bases, respectively.


Asunto(s)
ADN , Dispositivos Laboratorio en un Chip , Centrifugación , ADN/análisis , Electroforesis , Polímeros
4.
J Environ Manage ; 312: 114934, 2022 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-35339793

RESUMEN

This study evaluated the inhibitory effect and mitigation strategy of dodecyl dimethyl benzyl ammonium chloride (DDBAC) suppression on anaerobic digestion. With the 12 h-suppression, only 16.64% of anaerobes were alive, and acetotrophic methanogens were significantly inhibited. As for batch test, DDBAC suppression significantly prolonged the start-up of systems and decreased the biogas production. In cellulose semi-continuous digestion process, the DDBAC suppression induced volatile fatty acids accumulation and pH decrease. However, the biochar amended reactor effectively mitigated the DDBAC suppression and achieved 370.5 mL/d·g-chemical-oxygen-demand biogas production. Moreover, 17.8% more protein in extracellular polymeric substances was secreted as the bio-barrier to defense the DDBAC suppression. Furthermore, microbial analysis showed that biochar addition selectively enriched directed interspecies electron transfer (DIET) participant bacteria (Anaerolineaceae and Syntrophomonas) and methanogens (Methanosaeta and Methanobacterium). Meanwhile, the potential metabolic pathway analysis showed that the abundance of amino acids and energy metabolism were increased 28% and 8%, respectively. The abundance of encoding enzyme related to hydrogenotrophic and acetotrophic methanogenesis enriched 1.88 times and 1.48 times, respectively. These results showed the performance and mechanisms involved in DIET establishment with ethanol stimulation biochar addition.


Asunto(s)
Compuestos de Amonio , Celulosa , Cloruro de Amonio , Anaerobiosis , Biocombustibles , Reactores Biológicos , Carbón Orgánico , Humanos , Metano , Aguas del Alcantarillado
5.
Soft Matter ; 16(30): 7033-7039, 2020 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-32667008

RESUMEN

We herein report the construction of peroxidase (POD)-mimicking catalysts based on the strategy of peptide assembly and molecular imprinting. Upon co-assembly of Fmoc-FFH and Hemin, we firstly fabricated CA-H/Hemin which displayed POD-like catalytic activity and showed a 21-fold rate acceleration in the oxidation of 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) compared to the uncatalyzed reaction. Then, upon combining CA-H/Hemin with the ABTS-imprinted polymer, the obtained imprinted catalyst (MIP-H/Hemin) showed 52-fold acceleration due to the enhanced re-binding toward ABTS. Moreover, by introducing cationic monomers, a 137-fold rate enhancement was further achieved for the positively charged imprinted catalyst (MIP+-H/Hemin), from the synergistic effect of molecular imprinting and electrostatic attraction. Remarkably, by comparing the catalytic activity of these POD mimics towards ABTS and 3,3',5,5'-tetramethylbenzidine (TMB), we also highlighted the substrate specificity of MIP-H/Hemin and MIP+-H/Hemin toward ABTS. This study provides a promising approach to improve the catalytic activity and specificity of peptide-based enzyme mimics.


Asunto(s)
Impresión Molecular , Catálisis , Hemina , Péptidos , Polímeros
6.
Cell Physiol Biochem ; 50(3): 1100-1112, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30355954

RESUMEN

BACKGROUND/AIMS: Aseptic loosening is a common reason for failed artificial hip replacement after total hip arthroplasty. Aseptic loosening is mostly the result of wear debris that causes osteolysis and weakens the structures that support the prosthesis. Wear debris plays a crucial role in osteolysis during the loosening process, and polyethylene (PE) particles are found as wear debris more frequently than any other type of particle. In the absence of effective therapeutic agents, osteolysis has been hard to treat. Previous studies have demonstrated that curcumin influences signalosome-associated kinases and the proteasome-ubiquitin system during osteoclastogenesis. The aims of this study were to explore the anti-osteolysis effect of curcumin and if possible to identify the signaling pathway involved in a model of PE-induced osteolysis. METHODS: Differentiation of osteoclasts was induced in vitro by PE particles in RAW264.7 (monocyte/macrophage) cells and in vivo by calvarial and air pouch models of osteolysis established by PE stimulation in mice. We performed a set of TRAP staining, realtime polymerase chain reaction (PCR), and Western blot experiments to evaluate the anti-osteolytic effect of curcumin by comparing specimens that were exposed and not exposed to curcumin. RESULTS: Curcumin had a promising inhibitory effect on osteolysis induced by wear debris and suppressed the RANK/c-Fos/NFATc1 signaling pathway. CONCLUSION: Curcumin can prevent PE-induced osteolysis and bone loss. An inhibitory effect on the RANK/c-Fos/NFATc1 signaling pathway may explain the anti-osteolysis activity of curcumin.


Asunto(s)
Curcumina/farmacología , Polietileno/toxicidad , Transducción de Señal/efectos de los fármacos , Animales , Diferenciación Celular/efectos de los fármacos , Curcumina/uso terapéutico , Quinasa I-kappa B/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , FN-kappa B/metabolismo , Factores de Transcripción NFATC/genética , Factores de Transcripción NFATC/metabolismo , Osteoclastos/citología , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteólisis/patología , Osteólisis/prevención & control , Proteínas Proto-Oncogénicas c-fos/genética , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ligando RANK/metabolismo , Células RAW 264.7 , Cráneo/diagnóstico por imagen , Cráneo/patología , Microtomografía por Rayos X
7.
Analyst ; 141(3): 947-55, 2016 Feb 07.
Artículo en Inglés | MEDLINE | ID: mdl-26658961

RESUMEN

Rapid, inexpensive and simplistic nucleic acid testing (NAT) is pivotal in delivering biotechnology solutions at the point-of-care (POC). We present a poly(methylmethacrylate) (PMMA) microdevice where on-board infrared-mediated PCR amplification is seamlessly integrated with a particle-based, visual DNA detection for specific detection of bacterial targets in less than 35 minutes. Fluidic control is achieved using a capillary burst valve laser-ablated in a novel manner to confine the PCR reagents to a chamber during thermal cycling, and a manual torque-actuated pressure system to mobilize the fluid from the PCR chamber to the detection reservoir containing oligonucleotide-adducted magnetic particles. Interaction of amplified products specific to the target organism with the beads in a rotating magnetic field allows for near instantaneous (<30 s) detection based on hybridization-induced aggregation (HIA) of the particles and simple optical analysis. The integration of PCR with this rapid, sequence-specific DNA detection method on a single microdevice presents the possibility of creating POC NAT systems that are low cost, easy-to-use, and involve minimal external hardware.


Asunto(s)
Dispositivos Laboratorio en un Chip , Reacción en Cadena de la Polimerasa/instrumentación , Salmonella enterica/aislamiento & purificación , ADN Bacteriano/análisis , ADN Bacteriano/genética , Hibridación de Ácido Nucleico , Polimetil Metacrilato/química , Presión , Salmonella enterica/genética , Integración de Sistemas , Torque
8.
Analyst ; 141(15): 4667-75, 2016 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-27250903

RESUMEN

To date, the forensic community regards solid phase extraction (SPE) as the most effective methodology for the purification of DNA for use in short tandem repeat (STR) polymerase chain reaction (PCR) amplification. While a dominant methodology, SPE protocols generally necessitate the use of PCR inhibitors (guanidine, IPA) and, in addition, can demand timescales of up to 30 min due to the necessary load, wash and elution steps. The recent discovery and characterization of the EA1 protease has allowed the user to enzymatically extract (not purify) DNA, dramatically simplifying the task of producing a PCR-ready template. Despite this, this procedure has yet to make a significant impact on microfluidic technologies. Here, we describe a microfluidic device that implements the EA1 enzyme for DNA extraction by incorporating it into a hybrid microdevice comprising laminated polyester (Pe) and PMMA layers. The PMMA layer provides a macro-to-micro interface for introducing the biological sample into the microfluidic architecture, whilst also possessing the necessary dimensions to function as the swab acceptor. Pre-loaded reagents are then introduced to the swab chamber centrifugally, initiating DNA extraction at 75 °C. The extraction of DNA occurs in timescales of less than 3 min and any external hardware associated with the transportation of reagents by pneumatic pumping is eliminated. Finally, multiplexing is demonstrated with a circular device containing eight separate chambers for the simultaneous processing of eight buccal swab samples. The studies here provide DNA concentrations up to 10 ng µL(-1) with a 100% success rate in less than 3 minutes. The STR profiles generated using these extracted samples demonstrate that the DNA is of PCR forensic-quality and adequate for human identification.


Asunto(s)
ADN/aislamiento & purificación , Enzimas , Técnicas Analíticas Microfluídicas , Polimetil Metacrilato , Humanos , Poliésteres , Reacción en Cadena de la Polimerasa
9.
Langmuir ; 31(48): 13094-100, 2015 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-26548328

RESUMEN

Here we present the generation of uniform microparticles with tunable diameters from azobenzene-based homopolymer by combining the microfluidics technique and emulsion-solvent evaporation route. In addition, the photoinduced deformation behavior of these microspheres, irradiated by a linearly polarized beam with different irradiation time and direction, are systemically studied. The deformation process through real time optical microscope observation can be investigated, benefiting from the uniform and microscaled size of the polymer particles. These results indicate that the deformation degree characterized by relative variation of the long axial for the particles can be controlled by the irradiation time. Moreover, elongated particles with tunable aspect ratio or tilted shape can be generated by manipulating the irradiation direction and/or time. Interestingly, the shape transformation kinetics displays a significant dependence on initial size of the polymer particle. In addition, the shape transformation of the polymer particle can lead to the variation of the orientation and distribution of the encapsulated anisotropic gold nanorods.


Asunto(s)
Compuestos Azo/química , Microesferas , Polímeros/química
10.
Langmuir ; 30(40): 11883-9, 2014 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-25233156

RESUMEN

We demonstrate a rapid and robust method to fabricate uniform core-shell photonic crystal (PC) microbeads by the microfluidic and centrifugation-redispersion technique. Colored crystalline colloidal arrays (CCAs) were first prepared through centrifugation-redispersion approach by self-assembly of polystyrene-poly(N-isopropylacrylamide) (PS-PNIPAm) core/shell nanoparticles (NPs). Different from the conventional NPs (e.g., charged PS or PNIPAm NPs), PS-PNIPAm NPs could easily self-assemble into well-ordered CCAs by only one purification step without laborious pretreatment (e.g., dialysis or ion exchange) or slow solvent-evaporation process. The CCAs is then encapsulated into a transparent polymer shell with functional groups (e.g., copolymer of ETPTA and butyl acrylate (BA)), triggering the formation of core-shell PC microbeads which can be used as optical encoding microcarriers. Importantly, this technique allows us to produce core-shell PC microbeads in a rapid and robust way, and the optical reflections of the PC microbeads appear highly stable to various external stimuli (e.g., temperature, pH value, and ionic strength) relying on the features of the CCAs core and protection of the polymer shell. Moreover, various probe biomolecules (e.g., proteins, antibodies, and so on) can be easily linked on the surface of the core-shell PC microbeads owing to the hydrophilic modification induced by the hydrolysis of BA on the microbead surface, enabling the multiplex biomolecular detection.


Asunto(s)
Inmunoglobulina G/análisis , Nanopartículas/química , Dispositivos Ópticos , Acrilatos/química , Resinas Acrílicas/química , Animales , Centrifugación , Pollos , Coloides , Color , Cristalización , Humanos , Microfluídica/métodos , Microesferas , Poliestirenos/química , Soluciones , Porcinos
11.
Mater Today Bio ; 27: 101130, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39027678

RESUMEN

Preserving vital pulp in cases of dental pulpitis is desired but remains challenging. Previous research has shown that bioactive glass (BG) possesses notable capabilities for odontogenic differentiation. However, the immunoregulatory potential of BG for inflamed pulp is still controversial, which is essential for preserving vital pulp in the context of pulpitis. This study introduces a novel approach utilizing polydopamine-coated BG (BG-PDA) which demonstrates the ability to alleviate inflammation and promote odontogenesis for vital pulp therapy. In vitro, BG-PDA has the potential to induce M2 polarization of macrophages, resulting in decreased intracellular reactive oxygen species levels, inhibition of pro-inflammatory factor, and enhancement of anti-inflammatory factor expression. Furthermore, BG-PDA can strengthen the mitochondrial function in macrophages and facilitate odontogenic differentiation of human dental pulp cells. In a rat model of pulpitis, BG-PDA exhibits the capacity to promote M2 polarization of macrophages, alleviate inflammation, and facilitate dentin bridge formation. This study highlights the notable immunomodulatory and odontogenesis-inducing properties of BG-PDA for treating dental pulpitis, as evidenced by both in vitro and in vivo experiments. These results imply that BG-PDA could serve as a promising biomaterial for vital pulp therapy.

12.
Environ Pollut ; 345: 123473, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38301820

RESUMEN

Emerging evidence has demonstrated the association between microplastics (MPs) with a diameter of <5 mm and the risk of intestinal diseases. However, the molecular mechanisms contributing to MP-induced intestinal barrier dysfunction have not been fully appreciated. In this study, C57BL/6 J mice were exposed to polystyrene microplastics (PS-MPs, 0.2, 1 or 5 µm) at 1 mg/kg body weight daily by oral gavage for 28 days. We found that PS-MPs exposure induced oxidative stress and inflammatory cell infiltration in mice colon, leading to an increased expression of pro-inflammatory cytokine. Moreover, there were an increase in intestinal permeability and decrease in mucus secretion, accompanied by downregulation of tight junction (TJ)-related zonula occluden-1 (ZO-1), occluding (OCLN) and claudin-1 (CLDN-1) in mice colon. Especially, 5 µm PS-MPs (PS5)-induced intestinal epithelial TJ barrier damage was more severe than 0.2 µm PS-MPs (PS0.2) and 1 µm PS-MPs (PS1). In vitro experiments indicated that PS5-induced oxidative stress upregulated the expression of nuclear factor kappa B (NF-κB), nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome, and myosin light chain kinase (MLCK). Meanwhile, pre-treatment with the antioxidant NAC, NLRP3 inhibitor MCC950 and MLCK inhibitor ML-7 considerably reduced PS5-triggered reactive oxygen species (ROS) production and inflammatory response, inhibited the activation of the NF-κB/NLRP3/MLCK pathway, and upregulated ZO-1, OCLN and CLDN-1 expression in Caco-2 cells. Taken together, our study demonstrated that PS-MPs cause intestinal barrier dysfunction through the ROS-dependent NF-κB/NLRP3/IL-1ß/MLCK pathway.


Asunto(s)
Enfermedades Intestinales , FN-kappa B , Humanos , Animales , Ratones , FN-kappa B/metabolismo , Plásticos/metabolismo , Células CACO-2 , Microplásticos/metabolismo , Poliestirenos/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Especies Reactivas de Oxígeno , Ratones Endogámicos C57BL , Estrés Oxidativo
13.
ACS Appl Mater Interfaces ; 16(24): 30715-30727, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38833722

RESUMEN

Pulp and periapical diseases can lead to the cessation of tooth development, resulting in compromised tooth structure and functions. Despite numerous efforts to induce pulp regeneration, effective strategies are still lacking. Growth factors (GFs) hold considerable promise in pulp regeneration due to their diverse cellular regulatory properties. However, the limited half-lives and susceptibility to degradation of exogenous GFs necessitate the administration of supra-physiological doses, leading to undesirable side effects. In this research, a heparin-functionalized bioactive glass (CaO-P2O5-SiO2-Heparin, abbreviated as PSC-Heparin) with strong bioactivity and a stable neutral pH is developed as a promising candidate to addressing challenges in pulp regeneration. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and thermogravimetric analysis reveal the successful synthesis of PSC-Heparin. Scanning electron microscopy and X-ray diffraction show the hydroxyapatite formation can be observed on the surface of PSC-Heparin after soaking in simulated body fluid for 12 h. PSC-Heparin is capable of harvesting various endogenous GFs and sustainably releasing them over an extended duration by the enzyme-linked immunosorbent assay. Cytological experiments show that developed PSC-Heparin can facilitate the adhesion, migration, proliferation, and odontogenic differentiation of stem cells from apical papillae. Notably, the histological analysis of subcutaneous implantation in nude mice demonstrates PSC-Heparin is capable of promoting the odontoblast-like layers and pulp-dentin complex formation without the addition of exogenous GFs, which is vital for clinical applications. This work highlights an effective strategy of harvesting endogenous GFs and avoiding the involvement of exogenous GFs to achieve pulp-dentin complex regeneration, which may open a new horizon for regenerative endodontic therapy.


Asunto(s)
Pulpa Dental , Heparina , Regeneración , Heparina/química , Heparina/farmacología , Pulpa Dental/efectos de los fármacos , Pulpa Dental/citología , Pulpa Dental/metabolismo , Animales , Regeneración/efectos de los fármacos , Ratones , Vidrio/química , Humanos , Ratones Desnudos , Péptidos y Proteínas de Señalización Intercelular/farmacología , Péptidos y Proteínas de Señalización Intercelular/química , Células Madre/efectos de los fármacos , Células Madre/citología , Células Madre/metabolismo , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos
14.
Nat Commun ; 15(1): 5689, 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-38971796

RESUMEN

Leukemia is a kind of hematological malignancy originating from bone marrow, which provides essential signals for initiation, progression, and recurrence of leukemia. However, how to specifically deliver drugs to the bone marrow remains elusive. Here, we develop biomimetic vesicles by infusing hematopoietic stem and progenitor cell (HSPC) membrane with liposomes (HSPC liposomes), which migrate to the bone marrow of leukemic mice via hyaluronic acid-CD44 axis. Moreover, the biomimetic vesicles exhibit superior binding affinity to leukemia cells through intercellular cell adhesion molecule-1 (ICAM-1)/integrin ß2 (ITGB2) interaction. Further experiments validate that the vesicles carrying chemotherapy drug cytarabine (Ara-C@HSPC-Lipo) markedly inhibit proliferation, induce apoptosis and differentiation of leukemia cells, and decrease number of leukemia stem cells. Mechanically, RNA-seq reveals that Ara-C@HSPC-Lipo treatment induces apoptosis and differentiation and inhibits the oncogenic pathways. Finally, we verify that HSPC liposomes are safe in mice. This study provides a method for targeting bone marrow and treating leukemia.


Asunto(s)
Apoptosis , Médula Ósea , Citarabina , Sistemas de Liberación de Medicamentos , Células Madre Hematopoyéticas , Leucemia , Liposomas , Animales , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/metabolismo , Ratones , Citarabina/farmacología , Médula Ósea/efectos de los fármacos , Médula Ósea/patología , Médula Ósea/metabolismo , Apoptosis/efectos de los fármacos , Leucemia/tratamiento farmacológico , Leucemia/patología , Humanos , Diferenciación Celular/efectos de los fármacos , Membrana Celular/metabolismo , Membrana Celular/efectos de los fármacos , Línea Celular Tumoral , Antígenos CD18/metabolismo , Proliferación Celular/efectos de los fármacos , Receptores de Hialuranos/metabolismo , Ácido Hialurónico/química , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/metabolismo
15.
Protein Cell ; 15(8): 612-632, 2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-38577810

RESUMEN

Aging has a profound impact on the gingiva and significantly increases its susceptibility to periodontitis, a worldwide prevalent inflammatory disease. However, a systematic characterization and comprehensive understanding of the regulatory mechanism underlying gingival aging is still lacking. Here, we systematically dissected the phenotypic characteristics of gingiva during aging in primates and constructed the first single-nucleus transcriptomic landscape of gingival aging, by which a panel of cell type-specific signatures were elucidated. Epithelial cells were identified as the most affected cell types by aging in the gingiva. Further analyses pinpointed the crucial role of YAP in epithelial self-renew and homeostasis, which declined during aging in epithelial cells, especially in basal cells. The decline of YAP activity during aging was confirmed in the human gingival tissues, and downregulation of YAP in human primary gingival keratinocytes recapitulated the major phenotypic defects observed in the aged primate gingiva while overexpression of YAP showed rejuvenation effects. Our work provides an in-depth understanding of gingival aging and serves as a rich resource for developing novel strategies to combat aging-associated gingival diseases, with the ultimate goal of advancing periodontal health and promoting healthy aging.


Asunto(s)
Envejecimiento , Encía , Transcriptoma , Proteínas Señalizadoras YAP , Encía/metabolismo , Encía/patología , Animales , Humanos , Envejecimiento/genética , Envejecimiento/metabolismo , Proteínas Señalizadoras YAP/metabolismo , Queratinocitos/metabolismo , Células Epiteliales/metabolismo , Masculino
16.
World J Gastroenterol ; 29(34): 5082-5090, 2023 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-37753367

RESUMEN

BACKGROUND: Neuroendocrine tumors (NET) are rare heterogeneous tumors that arise from neuroendocrine cells throughout the body. Acromegaly, a rare and slowly progressive disorder, usually results from a growth hormone (GH)-secreting pituitary adenoma. CASE SUMMARY: We herein describe a 38-year-old patient who was initially diagnosed with diabetes. During colonoscopy, two bulges were identified and subsequently removed through endoscopic submucosal dissection. Following the surgical intervention, the excised tissue samples were examined and confirmed to be grade 2 NET. 18F-ALF-NOTATATE positron emission tomography-computed tomography (PET/CT) and 68Ga-DOTANOC PET/CT revealed metastases in the peri-intestinal lymph nodes, prompting laparoscopic low anterior resection with total mesorectal excision. The patient later returned to the hospital because of hyperglycemia and was found to have facial changes, namely a larger nose, thicker lips, and mandibular prognathism. Laboratory tests and magnetic resonance imaging (MRI) suggested a GH-secreting pituitary adenoma. The pituitary adenoma shrunk after treatment with octreotide and was neuroendoscopically resected via a trans-sphenoidal approach. Whole-exome sequencing analysis revealed no genetic abnormalities. The patient recovered well with no evidence of recurrence during follow-up. CONCLUSION: 18F-ALF-NOTATE PET/CT and MRI with pathological analysis can effectively diagnose rare cases of pituitary adenomas complicated with rectal NET.


Asunto(s)
Adenoma , Tumores Neuroendocrinos , Neoplasias Hipofisarias , Neoplasias del Recto , Humanos , Adulto , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/cirugía , Tumores Neuroendocrinos/diagnóstico por imagen , Tumores Neuroendocrinos/cirugía , Tomografía Computarizada por Tomografía de Emisión de Positrones , Adenoma/diagnóstico por imagen , Adenoma/cirugía , Neoplasias del Recto/cirugía
17.
Adv Mater ; 35(24): e2210458, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-37046183

RESUMEN

Germline stem cells (GSCs) are the only cell population capable of passing genetic information to offspring, making them attractive targets in reproductive biology and fertility research. However, it is generally more difficult to introduce exogenous biomolecules into GSCs than other cell types, impeding the exploration and manipulation of these cells for biomedical purposes. Herein, semiconductor polymer dots (Pdots)-based nanocomplex Pdot-siRNA is developed and achieves effective knockdown of target genes in female germline stem cells (FGSCs). Advantage of high fluorescence brightness of Pdots is taken for comprehensive investigation of their cellular uptake, intracellular trafficking, and exocytosis in FGSCs. Importantly, Pdots show excellent biocompatibility and minimally disturb the differentiation of FGSCs. Intracellular Pdots escape from the lysosomes and undergo active exocytosis, which makes them ideal nanocarriers for bioactive cargos. Moreover, Pdot-siRNA can penetrate into 3D ovarian organoids derived from FGSCs and down-regulate the expression levels of target genes. This study investigates the interface between a type of theranostic nanoparticles and FGSCs for the first time and sheds light on the manipulation and medical application of FGSCs.


Asunto(s)
Nanopartículas , Células Madre Oogoniales , Puntos Cuánticos , Polímeros , Semiconductores , Exocitosis
18.
Biomed Mater ; 17(4)2022 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-35477157

RESUMEN

Bioactive glasses (BG) have been widely utilized as a biomaterial for bone repair. However, the early angiogenesis of BG may be inadequate, which weakens its osteogenic effects in large-sized bone defects and often leads to the failure of bone regeneration. In this study, we explored the effects of photobiomodulation (PBM) combined with BG on early angiogenesis to solve this bottleneck problem of insufficient early angiogenesis.In vitro, human umbilical vein endothelial cells (HUVECs) were cultured with BG extracts and treated with PBM using 1 J cm-2. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) and tubule formation assay were utilized to detect HUVECs' proliferation, vascular growth factor genes expression and tubules formation.In vivo, bone defects at the femoral metaphysis in Sprague-Dawley rats were treated with BG particulates and PBM at 120 J cm-2. Hematoxylin-eosin staining was used to observe the inflammatory response, tissue formation and biomaterial absorption of bone defects. Immunohistochemical staining was applied to observe the vascular-like structure formation. Thein vitroresults showed that PBM combined with BG significantly promoted HUVECs' proliferation, genes expression and mature tubules formation. On days 2, 4 and 7, the mRNA expression of VEGF in BG + PBM group was 2.70-, 2.59- and 3.05-fold higher than control (P< 0.05), and significantly higher than PBM and BG groups (P< 0.05). On days 4 and 7, the bFGF gene expression in BG + PBM group was 2.42- and 1.82-fold higher than control (P< 0.05), and also higher than PBM and BG groups (P< 0.05). Tube formation assay showed that mature tubules were formed in BG + PBM and PBM groups after 4 h, and the number in BG + PBM group was significantly higher than other groups (P< 0.05).In vivoresults further confirmed PBM induced early angiogenesis, with more vascular-like structures observed in BG + PBM and PBM groups 2 week post-surgery. With the optimum PBM fluence and BG concentration, PBM combined with BG exerted additive effects on enhancing early angiogenesis.


Asunto(s)
Regeneración Ósea , Osteogénesis , Animales , Materiales Biocompatibles/farmacología , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ratas , Ratas Sprague-Dawley
19.
PeerJ ; 9: e12421, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34900414

RESUMEN

Healthy pulp tissue plays an important role in normal function and long-term retention of teeth. Mesoporous bioactive glass (MBG) as a kind of regenerative biomaterials shows the potential in preserving the vital pulp. In this study, MBG prepared by organic template method combined with sol-gel method were used in human dental pulp cell culture and ectopic mineralization experiment. Real-Time PCR was used to explore its ability to induce odontogenic differentiation of dental pulp cells. MBG and rat crowns were implanted under the skin of nude mice for 4 weeks to observe the formation of pulp dentin complex. We found that MBG can release Si and Ca ions and has a strong mineralization activity in vitro. The co-culture of MBG with human dental pulp cells promoted the expression of DMP-1 (dentin matrix protein-1) and ALP (alkalinephosphatase) without affecting cell proliferation. After 4 weeks of subcutaneous implantation in nude mice, the formation of hard tissue with regular structure under the material could be seen, and the structure was similar to dentin tubules. These results indicate that MBG can induce the differentiation of dental pulp cells and the formation of dental pulp-dentin complex and has the potential to promote the repair and regeneration of dental pulp injuries.

20.
J Dent Sci ; 16(3): 915-921, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34141105

RESUMEN

BACKGROUND/PURPOSE: Effective regulation of the inflammatory process is essential for pulp repair and regeneration. Meloxicam has anti-inflammatory activity in systemic administration. The purpose of this study is to observe effects of topically applied meloxicam on inflamed pulp and to explore its potential value in the treatment of pulpitis. MATERIALS AND METHODS: The coronal pulp tissues of rat molars were stimulated with 10 mg/mL lipopolysaccharide (LPS group) and then treated with 500 µmol/L meloxicam (meloxicam group). The untreated pulp tissues were used as the control group. After 3 h of incubation in vitro, the gene expression of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in each group was detected by real-time RT-PCR. The pulp tissues of each group were randomly subcutaneously implanted into nude mice, and 500 µmol/L meloxicam was injected into the subcutaneous pocket of the meloxicam group. Haematoxylin eosin staining, Masson staining and immunohistochemical staining were performed on samples after 3 days and 4 weeks retrieval, respectively. RESULTS: Compared with the LPS group, the mRNA expression levels of TNF-α and IL-6 of the meloxicam group were significantly reduced in vitro. The inflammatory response and cyclooxygenase-2 expression of the meloxicam group were decreased, and osteodentin-like tissue was generated in the pulp cross section of the meloxicam group in vivo. CONCLUSION: The topical application of meloxicam inhibits the inflammatory response of inflamed pulp and further promotes the formation of osteodentin-like tissues but fails to induce the formation of the pulp-dentin complex. Topically applied meloxicam has the potential to regulate pulp inflammation.

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