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1.
J Nanobiotechnology ; 22(1): 368, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918787

RESUMEN

Active artificial bone substitutes are crucial in bone repair and reconstruction. Calcium phosphate bone cement (CPC) is known for its biocompatibility, degradability, and ability to fill various shaped bone defects. However, its low osteoinductive capacity limits bone regeneration applications. Effectively integrating osteoinductive magnesium ions with CPC remains a challenge. Herein, we developed magnesium malate-modified CPC (MCPC). Incorporating 5% magnesium malate significantly enhances the compressive strength of CPC to (6.18 ± 0.49) MPa, reduces setting time and improves disintegration resistance. In vitro, MCPC steadily releases magnesium ions, promoting the proliferation of MC3T3-E1 cells without causing significant apoptosis, proving its biocompatibility. Molecularly, magnesium malate prompts macrophages to release prostaglandin E2 (PGE2) and synergistically stimulates dorsal root ganglion (DRG) neurons to synthesize and release calcitonin gene-related peptide (CGRP). The CGRP released by DRG neurons enhances the expression of the key osteogenic transcription factor Runt-related transcription factor-2 (RUNX2) in MC3T3-E1 cells, promoting osteogenesis. In vivo experiments using minipig vertebral bone defect model showed MCPC significantly increases the bone volume fraction, bone density, new bone formation, and proportion of mature bone in the defect area compared to CPC. Additionally, MCPC group exhibited significantly higher levels of osteogenesis and angiogenesis markers compared to CPC group, with no inflammation or necrosis observed in the hearts, livers, or kidneys, indicating its good biocompatibility. In conclusion, MCPC participates in the repair of bone defects in the complex post-fracture microenvironment through interactions among macrophages, DRG neurons, and osteoblasts. This demonstrates its significant potential for clinical application in bone defect repair.


Asunto(s)
Cementos para Huesos , Péptido Relacionado con Gen de Calcitonina , Fosfatos de Calcio , Osteogénesis , Porcinos Enanos , Animales , Fosfatos de Calcio/química , Fosfatos de Calcio/farmacología , Cementos para Huesos/farmacología , Cementos para Huesos/química , Ratones , Porcinos , Péptido Relacionado con Gen de Calcitonina/metabolismo , Osteogénesis/efectos de los fármacos , Regeneración Ósea/efectos de los fármacos , Columna Vertebral/cirugía , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , Línea Celular , Magnesio/farmacología , Magnesio/química
2.
Proc Natl Acad Sci U S A ; 118(4)2021 01 26.
Artículo en Inglés | MEDLINE | ID: mdl-34871179

RESUMEN

The radial spoke (RS) heads of motile cilia and flagella contact projections of the central pair (CP) apparatus to coordinate motility, but the morphology is distinct for protozoa and metazoa. Here we show the murine RS head is compositionally distinct from that of Chlamydomonas Our reconstituted murine RS head core complex consists of Rsph1, Rsph3b, Rsph4a, and Rsph9, lacking Rsph6a and Rsph10b, whose orthologs exist in the protozoan RS head. We resolve its cryo-electron microscopy (cryo-EM) structure at 3.2-Å resolution. Our atomic model further reveals a twofold symmetric brake pad-shaped structure, in which Rsph4a and Rsph9 form a compact body extended laterally with two long arms of twisted Rsph1 ß-sheets and potentially connected dorsally via Rsph3b to the RS stalk. Furthermore, our modeling suggests that the core complex contacts the periodic CP projections either rigidly through its tooth-shaped Rsph4a regions or elastically through both arms for optimized RS-CP interactions and mechanosignal transduction.


Asunto(s)
Axonema/química , Axonema/metabolismo , Microscopía por Crioelectrón/métodos , Animales , Antígenos de Superficie , Chlamydomonas , Cilios , Proteínas del Citoesqueleto/química , Proteínas de Unión al ADN/química , Epítopos , Flagelos , Células HEK293 , Humanos , Ratones , Modelos Moleculares , Mutación , Conformación Proteica , Proteínas Recombinantes
3.
Int J Mol Sci ; 25(12)2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38928419

RESUMEN

Lignin is a crucial substance in the formation of the secondary cell wall in plants. It is widely distributed in various plant tissues and plays a significant role in various biological processes. However, the number of copies, characteristics, and expression patterns of genes involved in lignin biosynthesis in maize are not fully understood. In this study, bioinformatic analysis and gene expression analysis were used to discover the lignin synthetic genes, and two representative maize inbred lines were used for stem strength phenotypic analysis and gene identification. Finally, 10 gene families harboring 117 related genes involved in the lignin synthesis pathway were retrieved in the maize genome. These genes have a high number of copies and are typically clustered on chromosomes. By examining the lignin content of stems and the expression patterns of stem-specific genes in two representative maize inbred lines, we identified three potential stem lodging resistance genes and their interactions with transcription factors. This study provides a foundation for further research on the regulation of lignin biosynthesis and maize lodging resistance genes.


Asunto(s)
Regulación de la Expresión Génica de las Plantas , Genoma de Planta , Lignina , Zea mays , Zea mays/genética , Zea mays/metabolismo , Lignina/biosíntesis , Lignina/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Tallos de la Planta/genética , Tallos de la Planta/metabolismo , Genes de Plantas , Perfilación de la Expresión Génica/métodos , Pared Celular/metabolismo , Pared Celular/genética , Estudio de Asociación del Genoma Completo , Fenotipo
4.
Int J Mol Sci ; 25(13)2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-39000154

RESUMEN

Putatively, tooth agenesis was attributed to the initiation failure of tooth germs, though little is known about the histological and molecular alterations. To address if constitutively active FGF signaling is associated with tooth agenesis, we activated Fgf8 in dental mesenchyme with Osr-cre knock-in allele in mice (Osr2-creKI; Rosa26R-Fgf8) and found incisor agenesis and molar microdontia. The cell survival assay showed tremendous apoptosis in both the Osr2-creKI; Rosa26R-Fgf8 incisor epithelium and mesenchyme, which initiated incisor regression from cap stage. In situ hybridization displayed vanished Shh transcription, and immunostaining exhibited reduced Runx2 expression and enlarged mesenchymal Lef1 domain in Osr2-creKI; Rosa26R-Fgf8 incisors, both of which were suggested to enhance apoptosis. In contrast, Osr2-creKI; Rosa26R-Fgf8 molar germs displayed mildly suppressed Shh transcription, and the increased expression of Ectodin, Runx2 and Lef1. Although mildly smaller than WT controls prenatally, the Osr2-creKI; Rosa26R-Fgf8 molar germs produced a miniature tooth with impaired mineralization after a 6-week sub-renal culture. Intriguingly, the implanted Osr2-creKI; Rosa26R-Fgf8 molar germs exhibited delayed odontoblast differentiation and accelerated ameloblast maturation. Collectively, the ectopically activated Fgf8 in dental mesenchyme caused incisor agenesis by triggering incisor regression and postnatal molar microdontia. Our findings reported tooth agenesis resulting from the regression from the early bell stage and implicated a correlation between tooth agenesis and microdontia.


Asunto(s)
Factor 8 de Crecimiento de Fibroblastos , Incisivo , Mesodermo , Diente Molar , Animales , Factor 8 de Crecimiento de Fibroblastos/genética , Factor 8 de Crecimiento de Fibroblastos/metabolismo , Ratones , Incisivo/anomalías , Incisivo/metabolismo , Mesodermo/metabolismo , Mesodermo/patología , Diente Molar/anomalías , Diente Molar/metabolismo , Anodoncia/genética , Anodoncia/metabolismo , Anodoncia/patología , Apoptosis , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Factor de Unión 1 al Potenciador Linfoide/metabolismo , Factor de Unión 1 al Potenciador Linfoide/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Transducción de Señal , Regulación del Desarrollo de la Expresión Génica , Odontogénesis/genética , Ratones Transgénicos
5.
Environ Sci Technol ; 57(43): 16477-16488, 2023 10 31.
Artículo en Inglés | MEDLINE | ID: mdl-37867432

RESUMEN

The iron and steel industry (ISI) is important for socio-economic progress but emits greenhouse gases and air pollutants detrimental to climate and human health. Understanding its historical emission trends and drivers is crucial for future warming and pollution interventions. Here, we offer an exhaustive analysis of global ISI emissions over the past 60 years, forecasting up to 2050. We evaluate emissions of carbon dioxide and conventional and unconventional air pollutants, including heavy metals and polychlorinated dibenzodioxins and dibenzofurans. Based on this newly established inventory, we dissect the determinants of past emission trends and future trajectories. Results show varied trends for different pollutants. Specifically, PM2.5 emissions decreased consistently during the period 1970 to 2000, attributed to adoption of advanced production technologies. Conversely, NOx and SO2 began declining recently due to stringent controls in major contributors such as China, a trend expected to persist. Currently, end-of-pipe abatement technologies are key to PM2.5 reduction, whereas process modifications are central to CO2 mitigation. Projections suggest that by 2050, developing nations (excluding China) will contribute 52-54% of global ISI PM2.5 emissions, a rise from 29% in 2019. Long-term emission curtailment will necessitate the innovation and widespread adoption of new production and abatement technologies in emerging economies worldwide.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Humanos , Contaminación del Aire/análisis , Hierro , Material Particulado/análisis , Acero , Contaminantes Atmosféricos/análisis , China
6.
Macromol Rapid Commun ; 44(7): e2200890, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36594427

RESUMEN

Fully bio-based ion-conductive organo-hydrogels with multi-functionalities such as high mechanical properties, self-healing, anti-freezing, and non-drying capabilities are still extremely rare so far, and achieving it remains a great challenge. In this work, a starch/natural rubber composite hydrogel is first obtained by a simple one-pot method, and then an ion-conductive organo-hydrogel composed of starch, natural rubber, lithium chloride, and glycerol with adjustable mechanical properties (ultimate tensile stress of 0.15-2.33 MPa with a failure strain of 675-1367%, elastic modulus of 0.087-15.2 MPa) is fabricated by a solvent replacement strategy. The organo-hydrogels exhibit excellent fatigue resistance, elasticity, and good self-healing, anti-freezing, non-drying properties (with no obvious change after 10 days at ambient environment). The obtained hydrogels are successfully applied to monitor human movement with high durability (over 1000 cycles) and low hysteresis. In addition, the sensors exhibit high stability in a wide temperature range from -20 °C to 100 °C that endows it with a wide range of potential applications in flexible sensing and wearable devices.


Asunto(s)
Hidrogeles , Goma , Humanos , Módulo de Elasticidad , Elasticidad , Conductividad Eléctrica , Almidón
7.
Macromol Rapid Commun ; 44(1): e2200501, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35877188

RESUMEN

To realize advanced electrical applications for ferroelectric liquid crystalline polymers, high spontaneous polarization (Ps ) is highly desired. However, current ferroelectric liquid crystalline polymers usually exhibit a low Ps . In this work, mesogen-free, chiral polyethers containing sulfonylated methyl-branched alkyl side chains with a (CH2 )3 O spacer between the sulfonyl and the branched alkyl groups are designed and synthesized. In contrast to the linear n-alkyl side chains, the methyl-branched alkyl side chains induce chain tilting in the smectic layers. When double chirality exists in both the main chain and the side chains, a crystalline structure is observed after mechanical stretching. Intriguingly, when single chirality exists in either the backbone or the side chains, a liquid crystalline smectic C phase is obtained. The electric displacement-electric field study, however, does not show typical ferroelectric switching, although the dielectric constants are relatively high for these liquid crystalline polymers. This is likely because the dipole-dipole interactions among neighboring sulfonyl groups along the main chain are so strong that the ferroelectric switching is hindered in the samples. For the future work, it is desired to weaken the dipole-dipole interaction to achieve ferroelectricity in these mesogen-free liquid crystalline polymers.


Asunto(s)
Polímeros , Polímeros/química
8.
Ann Vasc Surg ; 92: 240-248, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36503024

RESUMEN

BACKGROUND: This retrospective multicenter study aimed to compare the midterm results of the Rotarex rotational thrombectomy device combined with drug-coated balloon (DCB) and DCB-alone for the treatment of subacute femoropopliteal artery thrombotic occlusion. METHODS: All patients (74, aged 70.1 ± 9.3 years) were nonrandomized and divided into 2 groups based on treatment strategy between 2018 and 2020. Intraoperative technical success (defined as <30% residual stenosis), dissection types and bailout-stenting rates were assessed. Ankle-brachial index (ABI), primary patency (PP, restenosis <50%) and freedom from clinically driven target lesion reintervention (CD-TLR) were documented at follow-up. RESULTS: Among them, 35 patients were treated with the Rotarex catheter combined with DCB while 39 patients underwent DCB-alone. The-overall technical success rate was 100%. Patients in the Rotarex + DCB group showed lower rate of bailout stenting than those in the DCB alone group (22.9% vs. 59.0%; P = 0.01). ABI at discharge was significantly higher in both groups. Mean follow-up time was 18.5 ± 3.4 months; 62 patients completed Doppler ultrasound investigation while 12 patients were censored. According to Kaplan-Meier analysis, the estimated PP was 82.0 ± 6.7% in the Rotarex + DCB group, whereas a significantly lower rate in the DCB alone group (60.9 ± 8.3%, P = 0.04). In addition, the freedom from CD-TLR rate was 82.9 ± 6.4% in the Rotarex + DCB group and 61.5 ± 7.8% in the DCB-alone group (P = 0.04). CONCLUSIONS: These initial data indicate that the Rotarex thrombectomy device combined with DCB is an effective choice for the treatment of subacute femoropopliteal artery thrombotic occlusion compared to DCB-alone. The combined procedure had superior midterm results.


Asunto(s)
Angioplastia de Balón , Arteriopatías Oclusivas , Enfermedad Arterial Periférica , Humanos , Arteria Poplítea/diagnóstico por imagen , Angioplastia de Balón/efectos adversos , Resultado del Tratamiento , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/terapia , Enfermedad Arterial Periférica/etiología , Grado de Desobstrucción Vascular , Arteria Femoral/diagnóstico por imagen , Trombectomía/efectos adversos , Arteriopatías Oclusivas/diagnóstico por imagen , Arteriopatías Oclusivas/terapia , Arteriopatías Oclusivas/etiología , Materiales Biocompatibles Revestidos
9.
Int J Mol Sci ; 24(11)2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-37298583

RESUMEN

Cleft palate is one of the most common birth defects. Previous studies revealed that multiple factors, including impaired intracellular or intercellular signals, and incoordination of oral organs led to cleft palate, but were little concerned about the contribution of the extracellular matrix (ECM) during palatogenesis. Proteoglycans (PGs) are one of the important macromolecules in the ECM. They exert biological functions through one or more glycosaminoglycan (GAG) chains attached to core proteins. The family with sequence similarity 20 member b (Fam20b) are newly identified kinase-phosphorylating xylose residues that promote the correct assembly of the tetrasaccharide linkage region by creating a premise for GAG chain elongation. In this study, we explored the function of GAG chains in palate development through Wnt1-Cre; Fam20bf/f mice, which exhibited complete cleft palate, malformed tongue, and micrognathia. In contrast, Osr2-Cre; Fam20bf/f mice, in which Fam20b was deleted only in palatal mesenchyme, showed no abnormality, suggesting that failed palatal elevation in Wnt1-Cre; Fam20bf/f mice was secondary to micrognathia. In addition, the reduced GAG chains promoted the apoptosis of palatal cells, primarily resulting in reduced cell density and decreased palatal volume. The suppressed BMP signaling and reduced mineralization indicated an impaired osteogenesis of palatine, which could be rescued partially by constitutively active Bmpr1a. Together, our study highlighted the key role of GAG chains in palate morphogenesis.


Asunto(s)
Fisura del Paladar , Micrognatismo , Animales , Ratones , Catálisis , Fisura del Paladar/genética , Fisura del Paladar/metabolismo , Regulación del Desarrollo de la Expresión Génica , Glicosaminoglicanos/metabolismo , Mesodermo/metabolismo , Micrognatismo/metabolismo , Cresta Neural/metabolismo , Hueso Paladar/metabolismo , Proteoglicanos/genética , Proteoglicanos/metabolismo
10.
J Environ Manage ; 340: 117996, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37087889

RESUMEN

Potassium ferrate (PF) pretreatment in anaerobic sludge and its potential influence mechanisms have received widely attention. This study investigated the coupling effect of PF loading on steel slag (SS) on excess sludge anaerobic fermentation. Results showed that SS loading increase the treatment performance of PF on short chain volatile fatty acids (SCFAs) production from anaerobic fermented sludge. It was showed that the modified PF loaded SS (MPF-SS) promoted the dissolution and release of organic substrates from intracellular to extracellular. Further exploration showed the promotion of PF and MPF-SS exposure to acid production microorganisms was much more than that to acid consumption microorganisms. MPF-SS addition can also effectively reinforce the carbohydrate transport, amino acid metabolism and the key enhanced genes associated with fatty acid biosynthesis pathways. This study fills the knowledge gap about modified PF on sludge treatment and also expands a new perspective for its application for sludge resource recovery.


Asunto(s)
Aguas del Alcantarillado , Acero , Fermentación , Aguas del Alcantarillado/química , Anaerobiosis , Ácidos Grasos Volátiles , Concentración de Iones de Hidrógeno
11.
J Med Virol ; 94(2): 587-593, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-30942492

RESUMEN

Brain dysfunction is a prerequisite for critical complications in children with hand, foot, and mouth disease (HFMD). Aquaporin 4 (AQP-4) may be involved in the pathological process of cerebral oedema and injury in children with severe and critical HFMD. This study aimed to assess the association of AQP-4 with the severity of enterovirus 71 (EV71)-associated HFMD. Children with EV71-infected HFMD were divided into a common group (clinical stage 1), a severe group (clinical stage 2), and a critical group (clinical stage 3) according to Chinese guidelines. The levels of AQP-4, interleukin-6 (IL-6), norepinephrine (NE), and neuron-specific enolase (NSE) before and after treatment were tested. Serum AQP-4, IL-6, NE, and NSE levels showed significant differences among the critical, severe, and common groups before and after treatment (P < 0.01). No significant differences in AQP-4 levels in cerebrospinal fluid (CSF) were observed between the critical and severe groups before and after treatment, but the CSF AQP-4 levels in these two groups were higher than those in the common group before treatment (P < 0.01). Serum AQP-4 levels, but not CSF AQP-4 levels, closely correlated with serum IL-6, NE, and NSE levels. These results suggest that the level of AQP-4 in serum, but not in CSF, is a candidate biomarker for evaluating the severity and prognosis of EV71-associated HFMD.


Asunto(s)
Acuaporina 4/sangre , Acuaporina 4/líquido cefalorraquídeo , Enterovirus Humano A/aislamiento & purificación , Enfermedad de Boca, Mano y Pie/virología , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Preescolar , Infecciones por Enterovirus , Femenino , Enfermedad de Boca, Mano y Pie/sangre , Enfermedad de Boca, Mano y Pie/líquido cefalorraquídeo , Humanos , Lactante , Interleucina-6/sangre , Masculino , Norepinefrina/sangre , Fosfopiruvato Hidratasa/sangre , Pronóstico , Curva ROC , Índice de Severidad de la Enfermedad
12.
Environ Sci Technol ; 56(10): 6243-6252, 2022 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-35482889

RESUMEN

We developed a regional atmospheric transport model for microplastics (MPs, 10 µm to 5 mm in size) over Asia and the adjacent Pacific and Indian oceans, accounting for MPs' size- and shape-dependent aerodynamics. The model was driven by tuned atmospheric emissions of MPs from the land and the ocean, and the simulations were evaluated against coastal (n = 19) and marine (n = 56) observations. Our tuned atmospheric emissions of MPs from Asia and the adjacent oceans were 310 Gg y-1 (1 Gg = 1 kton) and 60 Gg y-1, respectively. MP lines and fragments may be transported in the atmosphere >1000 km; MP pellets in our model mostly deposited near-source. We estimated that 1.4% of the MP mass emitted into the Asian atmosphere deposited into the oceans via atmospheric transport; the rest deposited over land. The resulting net atmospheric transported MP flux from Asia into the oceans was 3.9 Gg y-1, twice as large as a previous estimate for the riverine-transported MP flux from Asia into the oceans. The uncertainty of our simulated atmospheric MP budget was between factors of 3 and 7. Our work highlighted the impacts of the size and morphology on the aerodynamics of MPs and the importance of atmospheric transport in the source-to-sink relationship of global MP pollution.


Asunto(s)
Microplásticos , Contaminantes Químicos del Agua , Asia , Monitoreo del Ambiente , Océano Índico , Plásticos , Contaminantes Químicos del Agua/análisis
13.
Int J Med Sci ; 19(8): 1307-1319, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35928717

RESUMEN

Tissue regeneration is the preferred treatment for dentin and bone tissue defects. Dental pulp stem cells (DPSCs) have been extensively studied for their use in tissue regeneration, including the regeneration of dentin and bone tissue. LIM mineralization protein-1 (LMP-1) is an intracellular non-secretory protein that plays a positive regulatory role in the mineralization process. In this study, an LMP-1-induced DPSCs model was used to explore the effect of LMP-1 on the proliferation and odonto/osteogenic differentiation of DPSCs, as well as the underlying mechanisms. As indicated by the cell counting kit-8 assay, the results showed that LMP-1 did not affect the proliferation of DPSCs. Overexpression of LMP-1 significantly promoted the committed differentiation of DPSCs and vice versa, as shown by alkaline phosphatase activity assay, alizarin red staining, western blot assay, quantitative real-time polymerase chain reaction assay, and in vivo mineralized tissue formation assay. Furthermore, inhibiting the activation of the extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) pathways using specific pathway inhibitors showed that the ERK1/2 and p38 MAPK pathways attenuated the differentiation of DPSCs. Besides, the expression of BMP signaling pathway components were also determined, which suggested that LMP-1 could activate BMP-2/Smad1/5 signaling pathway. Our results not only indicated the underlying mechanism of LMP-1 treated DPSCs but also provided valuable insight into therapeutic strategies in regenerative medicine.


Asunto(s)
Osteogénesis , Proteínas Quinasas p38 Activadas por Mitógenos , Diferenciación Celular , Proliferación Celular/genética , Células Cultivadas , Pulpa Dental/metabolismo , Sistema de Señalización de MAP Quinasas , Proteína Quinasa 3 Activada por Mitógenos , Osteogénesis/genética , Transducción de Señal , Células Madre/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
14.
Int J Mol Sci ; 24(1)2022 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-36614010

RESUMEN

Calcium phosphate cement (CPC) has been widely studied, but its lack of osteoinductivity and inadequate mechanical properties limit its application, while strontium is able to promote bone formation and inhibit bone resorption. In this study, different proportions of tristrontium silicate were introduced to create a novel strontium-modified calcium phosphate cement (SMPC). The physicochemical properties of SMPC and CPC were compared, and the microstructures of the bone cements were characterized with scanning electron microscopy assays. Then, the effect of SMPC on cell proliferation and differentiation was examined. Furthermore, local inflammatory response and osteogenesis after SMPC implantation were also confirmed in the study. Finally, a rat model of isolated vertebral defects was used to test the biomechanical properties of the cements. The results showed that SMPC has better injectability and a shorter setting time than CPC. Meanwhile, the addition of tristrontium silicate promoted the mechanical strength of calcium phosphate cement, and the compressive strength of 5% SMPC increased to 6.00 ± 0.74 MPa. However, this promotion effect gradually diminished with an increase in tristrontium silicate, which was also found in the rat model of isolated vertebral defects. Furthermore, SMPC showed a more preferential role in promoting cell proliferation and differentiation compared to CPC. Neither SMPC nor CPC showed significant inflammatory responses in vivo. Histological staining suggested that SMPCs were significantly better than CPC in promoting new bone regeneration. Importantly, this osteogenesis effect of SMPC was positively correlated with the ratio of tristrontium silicate. In conclusion, 5% SMPC is a promising substitute material for bone repair with excellent physicochemical properties and biological activity.


Asunto(s)
Cementos para Huesos , Calcio , Animales , Ratas , Cementos para Huesos/farmacología , Cementos para Huesos/química , Fosfatos de Calcio/química , Osteogénesis , Calcio de la Dieta , Silicatos , Estroncio/farmacología , Estroncio/química
15.
Am J Med Genet A ; 182(6): 1321-1328, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32220041

RESUMEN

Piebaldism is a rare, autosomal dominant and congenital pigmentary disorder characterized by stable depigmentation of the skin and white forelock. Mutations in KIT or SNAI2 genes result in piebaldism. Most individuals with piebaldism have a family history of the disorder. Herein, we report a 5-month-old Chinese girl with severe piebaldism but no family history thereof. She has white forelock and large patches of depigmentation in the jaw, central anterior trunk, perineum and extremities. We performed whole-exome and Sanger sequencing and identified a de novo KIT mutation (NM_000222.2: c.2657G>A, p.Gly886Val) in exon 18 of KIT in the proband. Currently, this mutation is located in the most extreme C-terminal of the tyrosine kinase domain 2 of the KIT gene amongst all reported mutations and causes a severe clinical phenotype. We further reviewed literature on piebaldism and summarized 79 KIT gene mutations that lead to this disease. Our study may expand knowledge on the genotype-phenotype correlation in piebaldism and serve as a reference for genetic counseling and prenatal diagnosis of affected families.


Asunto(s)
Predisposición Genética a la Enfermedad , Piebaldismo/genética , Trastornos de la Pigmentación/genética , Proteínas Proto-Oncogénicas c-kit/genética , Preescolar , Femenino , Humanos , Mutación/genética , Linaje , Piebaldismo/patología , Trastornos de la Pigmentación/patología , Secuenciación del Exoma
16.
J Mol Cell Cardiol ; 128: 134-144, 2019 03.
Artículo en Inglés | MEDLINE | ID: mdl-30716327

RESUMEN

OBJECTIVE: The high rate of vein graft failure due to neointimal hyperplasia is a major challenge for cardiovascular surgery. Finding novel approaches to prevent neointimal hyperplasia is important. Thus, the purpose of this study was to investigate whether dedicator of cytokinesis 2 (DOCK2) plays a role in the development of neointima formation in the vein grafts. METHODS AND RESULTS: We found that DOCK2 levels were significantly elevated in the vein grafts following grafting surgery. In addition, overexpression of DOCK2 promoted venous smooth muscle cell (SMC) proliferation and migration. Conversely, knocking-down endogenous DOCK2 expression in venous SMCs inhibited SMC proliferation and migration. Consistent with this, knocking-down DOCK2 expression in the grafted veins significantly reduced neointimal formation compared with the controls 28 days after vein transplantation. Moreover, DOCK2 silencing treatment improved hemodynamics in the vein grafts. Mechanistically, knockdown of DOCK2 significantly alleviated the vein graft-induced down regulation of SMC contractile protein expression and impeded the vein graft-induction of both Cyclin D1 and PCNA expression. In particular, to ensure high efficiency when transferring the DOCK2 short hairpin RNA (shDOCK2) into the grafted veins, a 30% poloxamer F-127 gel incorporated with 0.25% trypsin was smeared around the vein grafts to increase the adenovirus contact time and penetration. CONCLUSIONS: DOCK2 silencing gene therapy effectively attenuates neointimal hyperplasia in vein grafts. Knock-down of DOCK2 would be a potential therapeutic approach for the treatment of vein graft failure.


Asunto(s)
Procedimientos Quirúrgicos Cardiovasculares/efectos adversos , Rechazo de Injerto/genética , Factores de Intercambio de Guanina Nucleótido/genética , Trasplantes/crecimiento & desarrollo , Venas/crecimiento & desarrollo , Animales , Ciclina D1/genética , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Rechazo de Injerto/patología , Rechazo de Injerto/terapia , Factores de Intercambio de Guanina Nucleótido/antagonistas & inhibidores , Humanos , Hiperplasia/metabolismo , Hiperplasia/patología , Hiperplasia/terapia , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Neointima/genética , Neointima/patología , Poloxámero/farmacología , Antígeno Nuclear de Célula en Proliferación/genética , Ratas , Trasplantes/patología , Venas/efectos de los fármacos , Venas/cirugía
17.
Mol Pharm ; 16(2): 825-833, 2019 02 04.
Artículo en Inglés | MEDLINE | ID: mdl-30575400

RESUMEN

Process-induced phase transformations (PIPTs) of active pharmaceutical ingredients (APIs) can alter APIs' physicochemical properties and impact performance of pharmaceutical drug products. In this study, we investigated compression-induced amorphization of crystalline posaconazole (POSA), where the impact of mechanical stresses and excipients on amorphization were explored. 19F solid-state NMR (ssNMR) was utilized to detect and quantify amorphous content in the compressed tablets, and finite element analysis (FEA) was conducted to understand stress distributions in the compression process. Both applied macroscopic axial stress and shear stress were found to be important to amorphization of crystalline POSA. Punch velocity, an important compression process parameter, had negligible effect on amorphization up to 100 mm/s. Two diluents, microcrystalline cellulose (MCC) and dibasic calcium phosphate anhydrous (DCPA), and one lubricant, magnesium stearate (MgSt), were evaluated for their impact on amorphization in this study. It was found that both MCC and DCPA significantly enhanced amorphization of POSA at a low drug loading (5% w/w). The 1% (w/w) blended lubricant effectively reduced the amorphous content in MCC-POSA tablets; however, it had minimal effect on either neat POSA or DCPA-POSA tablets. Drug loading, or excipient concentration, was demonstrated to have a significant impact on the extent of amorphization. These observed excipient effects support the important role of interparticulate stresses in amorphization of crystalline POSA.


Asunto(s)
Triazoles/química , Fosfatos de Calcio/química , Rastreo Diferencial de Calorimetría , Celulosa/química , Análisis de Elementos Finitos , Espectroscopía de Resonancia Magnética , Estructura Molecular , Tamaño de la Partícula , Ácidos Ftálicos/química
18.
Eur J Clin Microbiol Infect Dis ; 38(7): 1343-1349, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31028503

RESUMEN

To evaluate the clinical value of aquaporin-4 (AQP-4) in hand, foot, and mouth disease (HFMD) and to evaluate therapeutic efficacy of magnesium sulfate (MgSO4) and its effect on AQP-4 expression. Children with HFMD were divided into a common group, a severe group and a critical group according to Chinese guidelines; children in the critical group were further divided into two subgroups: routine treatment group and MgSO4 group. Outcome measures included systolic blood pressure (SBP), Heart rate (HR), the levels of AQP-4, interleukin-6 (IL-6), norepinephrine (NE), and neuron-specific enolase (NSE). Serum AQP-4, IL-6, NE, and NSE levels varied significantly among the critical, severe, and common groups before and after treatment. There were no significant differences in AQP-4 levels in cerebrospinal fluid (CSF) between the critical and severe groups before and after treatment; however, CSF AQP-4 levels in these two groups were higher than those in the common group before treatment. Serum and CSF AQP-4 levels in convalescence decreased significantly in the critical and severe groups. SBP, HR and serum AQP-4, IL-6, NE, NSE levels, but not CSF AQP-4 levels, were significantly lower in MgSO4 group than in the routine treatment group. AQP-4 in serum, but not in CSF, is a candidate biomarker for evaluating the severity and prognosis of HFMD; MgSO4 can provide protection on children with critical HFMD.


Asunto(s)
Acuaporina 4/sangre , Acuaporina 4/líquido cefalorraquídeo , Enfermedad de Boca, Mano y Pie/tratamiento farmacológico , Sulfato de Magnesio/uso terapéutico , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Preescolar , Femenino , Humanos , Lactante , Interleucina-6/sangre , Masculino , Norepinefrina/sangre , Fosfopiruvato Hidratasa/sangre , Pronóstico , Estudios Prospectivos
19.
Am J Otolaryngol ; 40(2): 197-204, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30553601

RESUMEN

PURPOSE: To explore the impact of H-uvulopalatopharyngoplasty (H-UPPP) in obstructive sleep apnea syndrome (OSAS) and gain insights into the potential mechanism underlying improvement by H-UPPP. METHODS: In a cohort of 11 OSAS patients, computational fluid dynamics (CFD) models of the upper airway were obtained using commercial software from computed tomography (CT) datasets before and after H-UPPP. Morphological and numerical parameters were respectively computed and compared during the peak tidal inspiratory flow. The correlations among polysomnography endpoints, airway dimensions, and pre- and post-operative airflow properties were analyzed with Spearman's rank correlation. RESULTS: The preoperative minimum cross-sectional area was significantly increased by 89.56% (p < .05), with a positive correlation to the apnea hypoapnea index (AHI) (r = 0.974). However, the capacity of all pharyngeal regions was not significantly altered (p > .05). Following H-UPPP, we observed a significant increase in pressure and reduction of velocity (p < .05) in the previously constricted areas. The change in pressure and velocity were significantly correlated with AHI (r = 0.922 and r = 0.946, respectively). In addition, the pressure drop in the constricted area, oropharynx, and hypopharynx were also significantly decreased (p < .05). CONCLUSIONS: H-UPPP is capable of expanding the constricted region of the velopharynx and can decrease the airway resistance which will in turn decrease the workload necessary for breathing and facilitate inspiration.


Asunto(s)
Hidrodinámica , Procedimientos Quirúrgicos Otorrinolaringológicos/métodos , Hueso Paladar/cirugía , Faringe/cirugía , Procedimientos de Cirugía Plástica/métodos , Apnea Obstructiva del Sueño/fisiopatología , Apnea Obstructiva del Sueño/cirugía , Úvula/cirugía , Adulto , Resistencia de las Vías Respiratorias , Estudios de Cohortes , Femenino , Humanos , Masculino , Resultado del Tratamiento
20.
BMC Oral Health ; 19(1): 216, 2019 10 07.
Artículo en Inglés | MEDLINE | ID: mdl-31590650

RESUMEN

BACKGROUND: The resin bond strength of sclerotic dentine is significantly lower than that of the normal dentine, which paused a challenge for bonding procedures clinically. The aim of this study was to compare the effects of different surface pretreatments on the micro-tensile bond strength and microstructure between sclerotic dentine and normal dentine. METHODS: Eighty teeth that were collected, forty premolars with typical wedge-shaped defects visually graded as class III were assigned as the sclerotic dentine group (SD), the other forty normal premolars with artificial wedge-shaped defects were assigned as the normal dentine group (ND). Each group was randomly subdivided into eight subgroups according to the solution used: 35% phosphoric acid, 15% EDTA, 5% or 10% NaClO. Then the dentine surface was examined using a scanning electron microscope (SEM). The lesions were restored using self-etching adhesive and the subsequent resin composite. The teeth were sectioned into sticks for the micro-tensile bond strength analysis, and the data were analysed using the SPSS17.0 software package (α = 0.05). RESULTS: First, for the ND groups, after pretreatment using 35% phosphoric acid, and 35% phosphoric acid + 5% or 10% sodium hypochlorite, the bonding strengths of the normal dentine were higher than that of the other groups (P < 0.05). Second, for the SD groups, after pretreatment using 35% phosphoric acid, 15% EDTA, and 35% phosphoric acid + 5% or 10% sodium hypochlorite, the bonding strengths of the sclerotic dentine were higher than that of the other groups (P < 0.05). Third, the bond strengths of the sclerotic dentine were lower than that of the normal dentine without any pretreatment (P < 0.05). After pretreatment using 35% phosphoric acid + 5% or 10% sodium hypochlorite, the bonding strengths of the sclerotic dentine were higher than that of the normal dentine (P < 0.05). SEM observation showed that the appearances of dentine surface were changed after pretreatment using the above solutions, with the reduced smear layer, opened small groove and increased dentinal tubules. CONCLUSION: Pretreatment of dentine using 35% phosphoric acid+ 5% or + 10% sodium hypochlorite changed the microstructure of the sclerotic dentine surface and subsequently increased the micro-tensile bond strength.


Asunto(s)
Recubrimiento Dental Adhesivo , Recubrimientos Dentinarios , Dentina , Grabado Ácido Dental , Resinas Compuestas , Ensayo de Materiales , Microscopía Electrónica de Rastreo , Cementos de Resina , Propiedades de Superficie , Resistencia a la Tracción
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