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1.
Bioorg Chem ; 153: 107862, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39362080

RESUMEN

Ergosterol peroxide (EP) is a natural steroid compound that has been reported to have significant antitumor activity. However, its poor water solubility and cellular uptake mean that it has weak efficacy against tumor cells. Herein, we designed and synthesized a series of EP derivatives with mitochondrial targeting properties. Of these, compound 15a showed an IC50 value of 0.32 µM against MCF-7 cells, which was 67-fold higher than that of the parental EP (IC50 = 21.46 µM), and was better than cisplatin (IC50 = 4.23 µM), had a selectivity index of 25.28 (IC50MCF-10A/IC50MCF-7). Additionally, compound 15a promoted an increase in intracellular reactive oxygen species levels and a decrease in mitochondrial membrane potential, and blocked the cell cycle in the G0/G1 phase. In a mouse model of breast cancer, 15a showed 89.85 % tumor inhibition at a dose of 20 mg/kg, which is similar to the therapeutic effect of the cisplatin. On the basis of these results, 15a could be considered for further preclinical evaluation for cancer therapy.

2.
Molecules ; 29(18)2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39339370

RESUMEN

In this study, novel ergosterol peroxide (EP) derivatives were synthesized and evaluated to assess their antiproliferative activity against four human cancer cell lines (A549, HepG2, MCF-7, and MDA-MB-231). Compound 3g exhibited the most potent antiproliferative activity, with an IC50 value of 3.20 µM against MDA-MB-231. This value was 5.4-fold higher than that of the parental EP. Bioassay optimization further identified 3g as a novel glutaminase 1 (GLS1) inhibitor (IC50 = 3.77 µM). In MDA-MB-231 cells, 3g reduced the cellular glutamate levels by blocking the glutamine hydrolysis pathway, which triggered reactive oxygen species production and induced caspase-dependent apoptosis. Molecular docking indicated that 3g interacts with the reaction site of the variable binding pocket by forming multiple interactions with GLS1. In a mouse model of breast cancer, 3g showed remarkable therapeutic effects at a dose of 50 mg/kg, with no apparent toxicity. Based on these results, 3g could be further evaluated as a novel GLS1 inhibitor for triple-negative breast cancer (TNBC) therapy.


Asunto(s)
Antineoplásicos , Proliferación Celular , Ergosterol , Glutaminasa , Simulación del Acoplamiento Molecular , Neoplasias de la Mama Triple Negativas , Humanos , Glutaminasa/antagonistas & inhibidores , Glutaminasa/metabolismo , Animales , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Ratones , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Ergosterol/análogos & derivados , Ergosterol/química , Ergosterol/farmacología , Apoptosis/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/síntesis química , Ensayos Antitumor por Modelo de Xenoinjerto , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad
3.
Zhongguo Zhong Yao Za Zhi ; 49(15): 4139-4147, 2024 Aug.
Artículo en Zh | MEDLINE | ID: mdl-39307746

RESUMEN

This study aims to explore the effect and mechanism of a mitochondrion-targeted derivative of ergosterol peroxide(Mito-EP) on breast cancer. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the proliferation of MDA-MB-231 cells treated with different concentrations(0, 0.075, 0.15, 0.3, 0.6, 1.2, and 2.4 µmol·L~(-1)) of Mito-EP. Cells were grouped for treatment with water(blank control), low, medium, and high concentrations(0.15, 0.3, and 0.6 µmol·L~(-1)) of Mito-EP, and ergosterol peroxide(EP)(0.6 µmol·L~(-1)). After the cells were treated for 48 h, flow cytometry was employed to examine the apoptosis rate, reactive oxygen species(ROS) level, mitochondrial membrane potential, and cell cycle distribution, and the apoptosis, ROS, and mitochondrial membrane potential were observed by laser confocal microscopy. A mouse model bearing subcutaneous xenograft tumor was established by injecting 4T1 cell suspension and used to study the inhibitory effect of Mito-EP on breast cancer. Western blot was employed to determine the protein levels of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), cytochrome C(Cyt C), cleaved caspase-7, and cleaved caspase-9 in cells and the tumor tissue. The results showed that Mito-EP reduced the proliferation rate of MDA-MB-231 cells in a concentration-dependent manner. Compared with the blank control group, EP(0.6 µmol·L~(-1)) caused slight changes in the apoptosis rate, ROS level, and mitochondrial membrane potential. However, Mito-EP increased the apoptosis rate, elevated the ROS level, decreased mitochondrial membrane potential, up-regulated the protein levels of Bax, Cyt C, cleaved caspase-7, and cleaved caspase-9, and down-regulated the protein level of Bcl-2(all P<0.05). Moreover, Mito-EP reduced the tumor volume and weight. In summary, Mito-EP may promote apoptosis in breast cancer cells by activating the mitochondrial apoptosis pathway.


Asunto(s)
Apoptosis , Neoplasias de la Mama , Ergosterol , Mitocondrias , Especies Reactivas de Oxígeno , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Femenino , Animales , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Apoptosis/efectos de los fármacos , Ratones , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Ergosterol/análogos & derivados , Ergosterol/farmacología , Proliferación Celular/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Endogámicos BALB C , Antineoplásicos/farmacología , Antineoplásicos/química , Ratones Desnudos , Ciclo Celular/efectos de los fármacos
4.
Eur J Nucl Med Mol Imaging ; 49(7): 2189-2198, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34988625

RESUMEN

PURPOSE: Recently, a "U" hazard ratio curve between resting left ventricular ejection fraction (LVEF) and prognosis has been observed in patients referred for routine clinical echocardiograms. The present study sought to explore whether a similar "U" curve existed between resting LVEF and coronary flow reserve (CFR) in patients without severe cardiovascular disease (CVD) and whether impaired CFR played a role in the adverse outcome of patients with supra-normal LVEF (snLVEF, LVEF ≥ 65%). METHODS: Two hundred ten consecutive patients (mean age 52.3 ± 9.3 years, 104 women) without severe CVD underwent clinically indicated rest/dipyridamole stress electrocardiography (ECG)-gated 13 N-ammonia positron emission tomography/computed tomography (PET/CT). Major adverse cardiac events (MACE) were followed up for 27.3 ± 9.5 months, including heart failure, late revascularization, re-hospitalization, and re-coronary angiography for any cardiac reason. Clinical characteristics, corrected CFR (cCFR), and MACE were compared among the three groups categorized by resting LVEF detected by PET/CT. Dose-response analyses using restricted cubic spline (RCS) functions, multivariate logistic regression, and Kaplan-Meier survival analysis were conducted to evaluate the relationship between resting LVEF and CFR/outcome. RESULTS: An inverted "U" curve existed between resting LVEF and cCFR (p = 0.06). Both patients with snLVEF (n = 38) and with reduced LVEF (rLVEF, LVEF < 55%) (n = 66) displayed a higher incidence of reduced cCFR than those with normal LVEF (nLVEF, 55% ≤ LVEF < 65%) (n = 106) (57.9% vs 54.5% vs 34.3%, p < 0.01, respectively). Both snLVEF (p < 0.01) and rLVEF (p < 0.05) remained independent predictors for reduced cCFR after multivariable adjustment. Patients with snLVEF encountered more MACE than those with nLVEF (10.5% vs 0.9%, log-rank p = 0.01). CONCLUSIONS: Patients with snLVEF are prone to impaired cCFR, which may be related to the adverse prognosis. Further investigations are warranted to explore its underlying pathological mechanism and clinical significance.


Asunto(s)
Enfermedades Cardiovasculares , Función Ventricular Izquierda , Adulto , Angiografía Coronaria , Femenino , Humanos , Persona de Mediana Edad , Tomografía Computarizada por Tomografía de Emisión de Positrones , Pronóstico , Volumen Sistólico
5.
BMC Musculoskelet Disord ; 20(1): 65, 2019 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-30736770

RESUMEN

BACKGROUND: The aim of this study was to evaluate the efficacy of the use of three-dimensional (3D) printing models for preoperative planning in cases of complex fracture. METHODS: In total, 48 patients with AO type C fractures of the distal radius were enrolled in the study between January 2014 and January 2015. They were divided randomly into 3D model (n = 23) and routine treatment (n = 25) groups. A 3D digital model of each distal radius fracture in the former group was constructed. The model was exported to a 3D printer for construction of a full solid model. During each operation, the operative time, amount of blood loss, and frequency of intraoperative fluoroscopy were recorded, which were regarded as primary outcome measures. Patients were followed to evaluate surgical outcomes by Gartland-Werley scores, radiological evaluation, and range of motion of wrist, and these were regarded as the secondary outcome measures. In addition, we invited surgeons and patients to complete questionnaires. RESULTS: The treatment of complex fractures using the 3D printing approach reduced the frequency of intraoperative fluoroscopy, blood loss volume, and operative time, but did not improve postoperative function compared with routine treatment. The patients wanted the doctor to use the 3D model to describe the condition and introduce the operative plan because it facilitated their understanding. The orthopaedic surgeons thought that the 3D model was useful for communication with patients, but were much less satisfied with its use in preoperative planning. CONCLUSION: Our study revealed that 3D printing models effectively help the doctors plan and perform the operation and provide more effective communication between doctors and patients, but can not improve postoperative function compared with routine treatment. TRIAL REGISTRATION: This trial was registered at the Chinese Clinical Trial Registry on May 9, 2017 (ChiCTR-IRP-17011343, http://www.chictr.org.cn/showproj.aspx?proj=19264 ).


Asunto(s)
Fijación de Fractura/métodos , Modelos Anatómicos , Modelación Específica para el Paciente , Impresión Tridimensional , Fracturas del Radio/cirugía , Adulto , Actitud del Personal de Salud , Pérdida de Sangre Quirúrgica , China , Comunicación , Comprensión , Femenino , Fijación de Fractura/efectos adversos , Curación de Fractura , Conocimientos, Actitudes y Práctica en Salud , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Cirujanos Ortopédicos/psicología , Educación del Paciente como Asunto/métodos , Relaciones Médico-Paciente , Estudios Prospectivos , Fracturas del Radio/diagnóstico por imagen , Fracturas del Radio/fisiopatología , Recuperación de la Función , Método Simple Ciego , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
6.
Int Orthop ; 41(9): 1803-1811, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28616706

RESUMEN

PURPOSE: To explore the diagnosis, treatment, and clinical prognosis of patients with both unstable pelvic fractures and concomitant acetabular fractures. MATERIAL AND METHODS: We retrospectively analyzed 21 cases of unstable pelvic fractures with concomitant acetabular fractures treated between January 2013 and December 2014. All 21 patients (18 males, 3 females), aged 43.5-55 years (range: 21-55 years), underwent surgery within four to 15 days (average = 6.5 days) after injury. We evaluated the pre-operative diagnoses, surgical approaches, types of fixation used, and prognoses. RESULTS: All 21 patients were followed-up for six to 18 months. The quality of post-operative pelvic fracture reduction (determined using the Matta scoring criteria) was excellent in five cases, good in 12, and fair in four. The clinical outcomes at the final follow-up (scored using the Majeed criteria) were excellent in ten cases, good in eight, and fair in three. The quality of post-operative acetabular fracture reduction (determined using the Matta scoring criteria) was excellent in five cases, good in 11, and poor in five. Hip joint function was evaluated at the final follow-up (using the D'Aubigné scoring system) and was excellent in eight cases, good in nine, and fair in four. The healing time was 12-18 weeks for pelvic fractures and 12-22 weeks for acetabular fractures. Post-operative wound infections in two patients were controlled after second operations featuring debridement and irrigation. We found no instance of heterotopic ossification, ischemic necrosis of the femoral head, or iatrogenic vascular or nerve injury. CONCLUSIONS: Good therapeutic outcomes in patients with unstable pelvic fractures and concomitant acetabular fractures can be achieved via accurate diagnosis, careful pre-operative planning, a well-performed operation, effective reduction and surgical fixation, and appropriate exercise to allow functional rehabilitation.


Asunto(s)
Acetábulo/lesiones , Fijación Interna de Fracturas/métodos , Fijación de Fractura/métodos , Fracturas de Cadera/cirugía , Huesos Pélvicos/lesiones , Acetábulo/cirugía , Adulto , Femenino , Estudios de Seguimiento , Fijación de Fractura/efectos adversos , Fijación Interna de Fracturas/efectos adversos , Fracturas de Cadera/complicaciones , Articulación de la Cadera/cirugía , Humanos , Fijadores Internos/efectos adversos , Masculino , Persona de Mediana Edad , Huesos Pélvicos/cirugía , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento
7.
Int Orthop ; 41(9): 1875-1880, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28396929

RESUMEN

PURPOSE: This study was conducted to compare traditional surgery and surgery assisted by 3D printing technology in the treatment of tibial plateau fractures. In addition, we also investigated the effect of 3D printing technology on the communication between doctors and patients. METHODS: Seventy two patients with tibial plateau fractures were enrolled in the study from April 2014 to October 2015. They were divided into two groups: 34 cases of 3D model group, 38 cases of traditional surgery group. The individual models were used to simulate the surgical procedures and carry out the surgery according to plan. Operation time, blood loss, and number of intra-operative fluoroscopy were recorded. Through the follow-up, the recovery of patients were observed. Besides, we designed questionnaires to verify the satisfaction for both surgeons and patients. RESULTS: The average operation time, average amount of blood loss, and number of intra-operative fluoroscopy for 3D model group was 85.2±0.9 minutes, 186.3± 5.5ml, 5.3± 0.2 times, and for traditional surgery group was 99.2±1.0 minutes, 216.2 ±6.9 ml,7.1 ± 0.2 times respectively. There was statistically significant difference between the traditional surgery group and 3D model group (P < 0.05). Via follow-up, we can see that the 3D printing group has a better clinical efficacy. The average score of the questionnaires to Patient and doctors were 7.3 ± 0.1 points and 8.5± 0.1 points respectively. CONCLUSION: This study suggested the clinical feasibility of 3D printing technology in treatment of tibial plateau fractures.


Asunto(s)
Fijación Interna de Fracturas/métodos , Fracturas Intraarticulares/cirugía , Impresión Tridimensional , Fracturas de la Tibia/cirugía , Adulto , Simulación por Computador , Femenino , Fluoroscopía/estadística & datos numéricos , Fijación Interna de Fracturas/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento
8.
Am J Ther ; 23(3): e730-6, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-24413367

RESUMEN

The purpose of this study was to evaluate and compare the outcome of single- and double-elastic stable intramedullary nailing (ESIN) for the treatment of pediatric both-bone forearm fractures. We retrospectively analyzed 49 children with both-bone forearm fractures treated with ESIN. Twenty-four patients were treated with single-ESIN (S-ESIN) to fixate the radius only, and the other 25 patients were treated with double-ESIN (D-ESIN) to fixate the radius and ulna. The duration of surgery, times of fluoroscopy, cost of hospitalization, period of castoff, union time, radiographic outcomes, clinical results, and postoperative complications were compared. The duration of surgery, times of fluoroscopy, and cost of hospitalization were significantly lower in the S-ESIN group; however, the average period of castoff was longer in the S-ESIN group. The incidence of delayed union of the ulna was significantly higher in the D-ESIN than in the S-ESIN group. Although the mean angulation deformity of the ulna in the S-ESIN group was significantly larger than in the D-ESIN group, both of them were acceptable (<10 degrees). Despite this, there was no difference in the loss of forearm motion and complication rates between the 2 groups. In conclusion, our data suggest that S-ESIN to fixate the radius alone remains an equally effective fixation method in the pediatric population compared with both-bone fixation and is our treatment of choice.


Asunto(s)
Fijación Intramedular de Fracturas/métodos , Fracturas del Radio/cirugía , Fracturas del Cúbito/cirugía , Niño , Femenino , Fluoroscopía , Estudios de Seguimiento , Fijación Intramedular de Fracturas/economía , Hospitalización/economía , Humanos , Masculino , Tempo Operativo , Complicaciones Posoperatorias , Fracturas del Radio/diagnóstico por imagen , Estudios Retrospectivos , Resultado del Tratamiento , Fracturas del Cúbito/diagnóstico por imagen
9.
J Orthop Sci ; 20(5): 844-8, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26201394

RESUMEN

PURPOSE: The objective of this study was to discuss the risk factors of postoperative limb overgrowth after the application of titanium elastic nailing (TEN) in the treatment of pediatric femoral fractures as well as analyze the causes and provide guidance for clinical treatment. METHODS: The study included children with femoral fractures who were treated with TEN at our hospital from February 2005 to December 2009. Their age, gender, weight, cause of injury, having head trauma or not, fracture site, fracture type and nail-canal diameter (NCD) ratio were recorded. Student's t-test, chi-square test or Fisher's exact test was used for univariate analysis of the above factors, and then multivariate logistic regression analysis was used to analyze the possible risk factors in order to determine which ones are associated with limb overgrowth after the application of TEN to treat children with femoral fractures. RESULTS: Univariate analysis showed that the age, gender, weight, cause of injury, having head trauma or not, and the fracture site did not have a statistically significant association with limb overgrowth (P = 0.741, 0.900, 0.253, 0.739, 0.967 and 0.105, respectively). The fracture type and NCD ratio were significantly associated with limb overgrowth (P = 0.003 and 0.000, respectively). Multivariate logistic regression analysis demonstrated that the fracture type (P = 0.021, OR = 2.757) and NCD ratio (P = 0.002, OR = 2.422) were independent risk factors for limb overgrowth. CONCLUSIONS: The main factors affecting postoperative limb overgrowth are the fracture type and NCD ratio. In order to avoid limb overgrowth, unstable fractures should be fixed as firmly as possible, and the NCD ratio should be ≥0.8.


Asunto(s)
Clavos Ortopédicos/efectos adversos , Fracturas del Fémur/cirugía , Fijación Intramedular de Fracturas/efectos adversos , Diferencia de Longitud de las Piernas/etiología , Medición de Riesgo , Niño , Elasticidad , Femenino , Fracturas del Fémur/diagnóstico por imagen , Estudios de Seguimiento , Curación de Fractura , Humanos , Incidencia , Diferencia de Longitud de las Piernas/epidemiología , Masculino , Radiografía , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
10.
Arch Orthop Trauma Surg ; 135(8): 1093-9, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-26130438

RESUMEN

PURPOSES: Our objective was to measure the sagittal plane rotational (flexion and extension) displacement of hemipelvis radiologically and analyze the ratio of flexion and extension displacement of unstable pelvic fractures. METHODS: We used 8 cadaveric models to study the radiographic evidence of pelvic fractures in the sagittal plane. We performed pelvic osteotomy on 8 cadavers to simulate anterior and posterior pelvic ring injury. Radiological data were measured in the flexion and extension group under different angles (5°, 10°, 15°, 20°, and 25°). We retrospectively reviewed 164 patients who were diagnosed with a unilateral fracture of the pelvis. Pelvic ring displacement was identified and recorded radiographically in cadaveric models. RESULTS: The flexion and extension displacement of pelvic fractures was measured in terms of the vertical distance of fracture from the top of iliac crest to the pubic tubercle (CD) or from the top of iliac crest to the lowest point of ischial tuberosity (AB). Fifty-seven pelves showed flexion displacement and 15 showed extension displacement. Closed reduction including internal fixation and external fixation was successfully used in 141 cases (86.0 %). The success rates of closed reduction in flexion and extension displacement groups were 77 and 73 %, respectively, which were lower than in unstable pelvic ring fractures. CONCLUSIONS: The sagittal plane rotation (flexion and extension) displacement of pelvic fractures could be measured by special points and lines on the radiographs. Minimally invasive reduction should be based on clearly identified differences between the sagittal plane rotation and the vertical displacement of pelvic fractures.


Asunto(s)
Fracturas Óseas/diagnóstico por imagen , Huesos Pélvicos/diagnóstico por imagen , Adulto , Cadáver , Fijadores Externos , Femenino , Fijación Interna de Fracturas , Fracturas Óseas/cirugía , Humanos , Imagenología Tridimensional , Masculino , Huesos Pélvicos/lesiones , Huesos Pélvicos/cirugía , Radiografía , Estudios Retrospectivos , Rotación
11.
Acta Orthop Belg ; 81(1): 123-30, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26280865

RESUMEN

The objective of this study was to compare prospectively the complications and the radiographic and clinical outcomes of reverse less invasive stabilization system (LISS) and titanium elastic nailing (TEN) for the treatment of subtrochanteric femur fractures in older children. From April 2004 to February 2012, 52 children aged from 10 to 15 years old with subtrochanteric fractures were included in this study. 26 patients were treated with reverse LISS (LISS group) and 26 children treated with titanium elastic nails (TEN group) respectively. Perioperative care was standardized. Surgical time, blood loss, length of hospitalization, hospital costs, fracture union time, full weight-bearing time and complications were analyzed. The radiologic results as well as hip functional outcomes were evaluated. The average follow-up time of LISS group was 36.5±9.3 months and TEN group was 40.2±10.6 months. No significant difference between these two groups was found in union time, full weight-bearing time and average length of hospitalization. However, the patients of LISS group had longer operation time (60.0±10.6 min vs. 40.5±7.4 min, p<0.01), more blood loss (130.0±45.0 ml vs. 15.5±10.2 ml, p<0.01), and more hospital costs (25000±700 RMB vs. 10800±500 RMB, p<0.01). The overall complication rate was significantly higher in the LISS group than in the TEN group (12/26 vs. 5/26, p=0.039). There was no significant difference between the two groups in terms of early and late radiological results. Using the Sanders score system, there were 13 excellent, 6 good and 7 fair results in the LISS group compared with 22 excellent and 4 good results in the TEN group. The excellent and good rate was significantly different between the two groups (p=0.010). Our results indicated that TEN fixation of subtrochanteric femur fractures in older children was associated with better function scores and a lower overall complication rate when compared with reverse LISS.


Asunto(s)
Fijación Interna de Fracturas/métodos , Fracturas de Cadera/cirugía , Adolescente , Clavos Ortopédicos , Niño , Femenino , Fijación Interna de Fracturas/economía , Fracturas de Cadera/diagnóstico por imagen , Costos de Hospital , Humanos , Tiempo de Internación , Masculino , Tempo Operativo , Radiografía
12.
Cell Biol Int ; 38(3): 309-17, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24155130

RESUMEN

Phosphoserine has potential effectiveness as a simple substrate in preparing bone replacement materials, which could enhance bone forming ability. However, there is a need to investigate the independent effect of phosphoserine on osteogenic differentiation of human adipose stem cells (hADSCs). hADSCs were cultured in an osteogenic medium with phosphoserine. Cell proliferation was analysed by CCK8 and osteogenic differentiation was measured by alkaline phosphatase (ALP) activity, von Kossa staining and real time-polymerase chain reaction (RT-PCR). No stimulatory effect of phosphoserine on cell proliferation was noted at Days 1, 4 and 7. Deposition of calcium increased after the addition of phosphoserine. mRNA expression of type I collagen (COL-I), alkaline phosphatase (ALP), osteocalcin (OCN), Osterix, bone morphogenetic protein-2 (BMP-2) and RUNX2 increased markedly with phosphoserine treatment. The BMP-2 antagonist, noggin, and its receptor kinase inhibitors, dorsomorphin and LDN-193189, attenuated phosphoserine-promoted ALP activity. BMP-responsive and Runx2-responsive reporters were activated by phosphoserine treatment. Thus phosphoserine can promote osteogenic differentiation of hADSCs, probably by activating BMP and Runx2 pathways, which could be a promising approach for enhancing osteogenic capacity of cell-based construction in bone tissue engineering.


Asunto(s)
Adipocitos/efectos de los fármacos , Proteína Morfogenética Ósea 2/metabolismo , Osteogénesis/efectos de los fármacos , Fosfoserina/farmacología , Transducción de Señal/efectos de los fármacos , Células del Estroma/efectos de los fármacos , Adipocitos/citología , Adulto , Fosfatasa Alcalina/metabolismo , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Femenino , Humanos , Masculino , Osteocalcina/metabolismo , Células del Estroma/citología
13.
Int Orthop ; 38(11): 2349-55, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25086821

RESUMEN

PURPOSE: The objective of this study was to compare combined internal and external fixation (CIEF) with minimally invasive percutaneous plate osteosynthesis (MIPPO) in the treatment of distal third tibial fractures, and explore the benefits and defects of these two techniques. METHODS: From April 2004 to February 2012, a total of 44 patients were randomised to operative stabilisation either by two closed titanium elastic nails combined with an external fixator (CIEF, 22) or by minimally invasive percutaneous osteosynthesis with a locking plate (MIPPO, 22). Pre-operative variables included the patients' age, sex, fracture side, cause of injury, Tscherne classification of soft tissue injury, fracture pattern, presence of open fracture and interval from injury to surgery. Peri-operative variables were the operating time and the radiation time. Postoperative variables were wound problems, bone union time, time of recovery to work, the functional American Orthopaedic Foot and Ankle surgery (AOFAS) score and removal of hardware. RESULTS: There was no significant difference in the time to union, the time of recovery to work, function, alignment and total AOFAS scores between the two groups (P = 0.704, 0.835, 0.551, 0.716 and 0.212, respectively). The mean operating time and radiation time were longer in the MIPPO group than in the CIEF group (85.3 ± 12.5 vs. 73.2 ± 12.0 minutes, P = 0.002, and 3.1 ± 1.5 vs. 2.1 ± 1.2 minutes, P = 0.019, respectively). Wound complications were more common in the MIPPO group (18.2% vs. 0% with CIEF, P = 0.105). There was a trend for patients with MIPPO to have a higher incidence of ankle pain (31.8% vs. 9.1% with CIEF, P = 0.135). Painful implants were removed in 31.8% of patients with MIPPO versus 9.1% with CIEF (P = 0.135). Of the 165 self-tapping locking screws of the locking plates seven (four patients) were removed with some difficulty because of stripping of the hexagonal recess. CONCLUSIONS: Our results indicated that both CIEF and MIPPO were all efficient methods for treating distal third tibial fractures. However, CIEF had the advantages of a shorter operating and radiation time, less wound complication and ankle pain, less secondary operations for implant removal and easier removal of the implants.


Asunto(s)
Fijación Interna de Fracturas/métodos , Fijación de Fractura/métodos , Fracturas de la Tibia/cirugía , Adulto , Anciano , Clavos Ortopédicos , Placas Óseas , Remoción de Dispositivos , Fijadores Externos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Tempo Operativo , Radiografía , Fracturas de la Tibia/diagnóstico por imagen
14.
Rev Sci Instrum ; 95(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38456759

RESUMEN

A hollow core fiber (HCF) is spliced with a single-mode fiber, and then, the end face of the HCF is etched to form a microsphere interferometer for measuring gas pressure and environmental temperature. The total length of each microsphere is less than 200 µm. We fabricated two such structures and used femtosecond laser pulses to drill micro-holes on the HCF walls of both structures. One of the structures is directly used to measure air pressure, achieving a sensitivity of up to 2.857 nm/MPa while being almost insensitive to temperature. This structure is capable of assessing pressure down to 3.4 kPa within the range of 0-0.5 MPa. Another structure is filled with thermally sensitive material dimethyl silicone oil through a micro-hole, and then, it is sealed with AB adhesive to form a harmonic Vernier effect temperature sensor, with a sensitivity of up to -5.16 nm/°C. This structure is capable of assessing temperature down to 0.38 °C within the range of 30-60 °C. Additionally, the sensors have good repeatability and stability and compact structure and simple manufacturing and can be used as a sensing probe for monitoring gas pressure and temperature under extreme environments.

15.
J Am Heart Assoc ; 13(17): e032169, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39189479

RESUMEN

BACKGROUND: Adverse left ventricular remodeling is a significant cardiovascular predictor for patients with coronary artery disease and preserved left ventricular ejection fraction (LVEF). However, the remodeling indexes reflecting left ventricular spherization by myocardial perfusion imaging are underexplored. METHODS AND RESULTS: 727 patients (mean age 59.8±13.5 years, 329 women) diagnosed or suspected coronary artery disease with preserved LVEF who underwent resting myocardial perfusion imaging were retrospectively enrolled. The myocardial perfusion imaging findings including the total perfusion deficit and sphericity indexes (shape index (SI) and eccentricity index (EI) obtained from gated (QGS) and non-gated (QPS) images) were collected. Major adverse cardiovascular events (MACE) were followed up for 45.1±22.0 months. All patients were divided into 4 subgroups based on total perfusion deficit at 10% and LVEF at 65%. Univariable comparative analyses were performed in 5 cohorts (all patients and 4 subgroups). Patients who experienced MACE displayed higher SI and/or lower EI (all P<0.05). Kaplan-Meier survival analyses suggested significant differences for SIQPS in all 5 cohorts, for EIQPS and EIQGS in 4 cohorts, and for end-systolic and end-diastolic SIQGS in 3 cohorts (all P<0.05). Multivariate Cox analysis showed that abnormal SI and EI remained statistically significant predictors for MACE after adjusting for total perfusion deficit, LVEF, and other confounding factors. CONCLUSIONS: For patients diagnosed or suspected of coronary artery disease with preserved or supra-normal LVEF, resting sphericity indexes by myocardial perfusion imaging displayed incremental long-term prognostic value. Among these indicators, SIQPS is particularly promising across different perfusion or preserved functional conditions.


Asunto(s)
Enfermedad de la Arteria Coronaria , Imagen de Perfusión Miocárdica , Volumen Sistólico , Función Ventricular Izquierda , Humanos , Femenino , Masculino , Persona de Mediana Edad , Enfermedad de la Arteria Coronaria/fisiopatología , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Volumen Sistólico/fisiología , Imagen de Perfusión Miocárdica/métodos , Estudios Retrospectivos , Pronóstico , Anciano , Función Ventricular Izquierda/fisiología , Remodelación Ventricular/fisiología , Valor Predictivo de las Pruebas , Ventrículos Cardíacos/fisiopatología , Ventrículos Cardíacos/diagnóstico por imagen
16.
Food Chem ; 404(Pt B): 134660, 2023 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-36283309

RESUMEN

Low temperature can affect DNA methylation. Since exogenous use of NO can reduce cold damage in peach fruit during cold storage, this study investigated the roles of NO on DNA methylation of peaches suffering cold stress. The results showed that exogenous NO effectively alleviated the decrease in total DNA methyltransferase (DNMT) activity and transcript levels induced by cold stress, whereas c-PTIO exacerbated the decrease in total DNMT activity and transcript levels. Further BSP analysis of the promoter regions of four cold resistance genes (PpCBF5-IS2, PpICE1-IS, PpMYC2-IS, PpCOR-IS1) in peaches showed that in peaches treated with exogenous NO, PpCBF5-IS2 and PpICE1-IS were modified by hypermethylation, PpMYC2-IS was modified by methylation, PpCOR-IS1 was modified by demethylation and insensitive to NO. It was suggested that NO could enhance the cold resistance of postharvest peaches by mediating DNA methylation.


Asunto(s)
Prunus persica , Prunus persica/genética , Frutas/genética , Óxido Nítrico/farmacología , Metilación de ADN , Frío
17.
EJNMMI Res ; 13(1): 33, 2023 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-37093329

RESUMEN

BACKGROUND: The IQ-SPECT system is equipped with multifocal collimators and uses ordered-subset conjugate gradient minimization (OSCGM) as its reconstruction algorithm, achieving a shorter acquisition time than conventional SPECT. Left ventricular ejection fraction (LVEF) is overestimated by conventional SPECT in patients with small heart size. In this study, we compared IQ-SPECT with conventional SPECT and cardiovascular magnetic resonance (CMR) for the estimation of LVEF in patients with small hearts (males: EDV ≤ 60 ml, ESV ≤ 25 ml; females: EDV ≤ 45 ml, ESV ≤ 20 ml). METHODS: The study consisted of 49 consecutive patients (20 normal and 29 with small heart size) undergoing gated myocardial perfusion imaging (GMPI) with a 99mTc-labelled agent during stress or rest to assess the risk of coronary artery disease (CAD). The data were reconstructed using filtered back-projection (FBP) for conventional SPECT and OSCGM for IQ-SPECT. ESV, EDV, and LVEF were calculated using quantitative gated SPECT (QGS). To determine the optimal ordered-subset reconstruction parameters, we compared the LVEF from SPECT to the corresponding measurement from CMR. RESULTS: EDV, ESV, and LVEF values obtained from IQ-SPECT and conventional SPECT showed that the results of these two forms of SPECT were significantly correlated, although the EDV and ESV obtained by IQ-SPECT were higher than those obtained by conventional SPECT. IQ-SPECT yielded lower LVEF measurements than conventional SPECT (normal heart size: 50.6 ± 4.3% vs. 73.4 ± 8.4%, P = 0.002; small heart size: 62.1 ± 7.8% vs. 75.0 ± 11.4%, P < 0.001). There were no significant differences in LVEF measurements made by IQ-SPECT and CMR (normal heart size: 50.6 ± 4.3% vs. 53.2 ± 5.8%, P > 0.05; small heart size: 62.1 ± 7.8% vs. 64.6 ± 8.8%, P > 0.05). Five subsets (S) and 12 iterations (I) did not differ significantly in LVEF between CMR and IQ-SPECT for patients with small hearts (64.6 ± 8.8% vs. 62.1 ± 7.8%, P = 0.120), while 3 S and 10 I were the best parameters for patients with normal heart size (50.6 ± 4.3% vs. 53.1 ± 5.8%, P = 0.117). CONCLUSION: With CMR as the standard, IQ-SPECT yields more reliable LVEF values than conventional SPECT for populations with small heart size. The best reconstruction parameters from IQ-SPECT were 5 S and 12 I for patients with small hearts.

18.
Arch Orthop Trauma Surg ; 132(2): 265-70, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22139387

RESUMEN

PURPOSE: Plate fixation, the conventional treatment for traumatic symphysis pubis diastasis, carries the risk of extensive exposure, blood loss and postoperative infections. Percutaneous screw fixation is a minimally invasive treatment. The goal of the present study was to compare the outcome of plate fixation and percutaneous screw technique in the treatment of traumatic pubic symphysis diastasis. METHODS: Ninety patients with traumatic symphysis pubis diastasis were treated from January 2003 to December 2009 at two level 1 regional trauma centers. The mean time of follow-up was 21 months (18 to 26). Forty-five patients were treated by percutaneous screw fixation. Forty-five patients were treated by plate and screws fixation. The demographic, distribution of fracture patterns, blood loss, incision length, fixation failure, malunion, revision surgery and functional scores were compared. RESULTS: Seven cases were lost during follow-up. Demographics (age and gender), fracture classification and Injury Severity Score were comparable in the two groups (P > 0.05). Blood loss and extensive exposure were much less in screw group (P < 0.01). Patients in screw group achieved better functional performance (P = 0.01). There were no significant differences favoring plate fixation in reduction quality (P = 0.32), implant failure (P = 0.39), malunion (P = 0.15), revision surgery rates (P = 0.27), percentage of impotence in the male patients (P = 0.2) and implant removal time (P = 0.12) between the two groups. CONCLUSIONS: Our results indicate that besides lower rate of iatrogenic injuries and better functional outcome, percutaneous screw fixation of the pubic symphysis is as strong as plate fixation.


Asunto(s)
Placas Óseas , Tornillos Óseos , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Diástasis de la Sínfisis Pubiana/cirugía , Adulto , Femenino , Humanos , Masculino , Estudios Prospectivos
19.
Rev Sci Instrum ; 93(8): 085002, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-36050096

RESUMEN

In this paper, a highly sensitive optical fiber gas pressure sensor is proposed and experimentally verified. The sensor is composed of two Fabry-Pérot (F-P) cavities, and two F-P cavities are fabricated by a single-mode fiber and two quartz capillaries with different inner diameters splicing. Among them, the small inner diameter capillary is used as a gas channel connecting the large inner diameter capillary and the external environment. The manufacturing process of the sensor only involves capillary cleaver and splicing and does not involve other complex manufacturing technologies. By correctly adjusting the length of the two quartz capillaries, when the free spectral range of the two F-P cavities is very close, the optical Vernier effect will be observed and used as a sensitive probe for detecting gas pressure. The experimental results show that, in the pressure range of 0-0.8 MPa, the gas pressure sensitivity of the sensor reaches -81.73 nm/MPa with a linearity of 99.7%, and the temperature cross-sensitivity is only 1.82 kPa/°C. Due to its easy manufacture, high sensitivity, compact structure, and small volume, the sensor has become one of the preferred structures for large-scale use in the field of gas sensing.

20.
EJNMMI Phys ; 9(1): 79, 2022 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-36394663

RESUMEN

PURPOSE: We aimed to investigate the effect and significance of the rotation method with variable-angle anterior probe corrected for the depth of two kidneys on the determination of glomerular filtration rate (GFR) in total and single kidneys by the renal dynamic imaging Gates method. METHODS: Seventy-two patients who underwent dynamic renal imaging by the rotation method and abdominal CT in our hospital were collected in the present study. CT scanning, rotation method, Tonnesen's formula, and Li-Qian's formula were compared in terms of the depth of two kidneys, the depth difference between the two kidneys, and the total renal and single GFR obtained by substituting the renal depth values into Gates' formula. RESULTS: ①The depth of kidneys and GFR: Compared to CT, Tonnesen's formula significantly underestimated the depth of both kidneys and the total and single renal GFR (P < 0.05). No significant differences were found in the depth of both kidneys and the total and single renal GFR between Li-Qian's formula and the rotation method (P > 0.05), with a strong agreement and with the least bias in the values measured by the rotation method. ②Renal depth difference: Compared to CT, Tonnesen's formula and Li-Qian's formula underestimated the difference in depth between the two kidneys (P < 0.05). None of the differences were statistically significant based on the rotation method (P > 0.05). The depth difference was positively correlated with the resulting changes in single renal function (|R(CT)-R(Li-Qian)|) and (|R(Rotation)-R(Li-Qian)|) (r = 0.881, 0.641, P < 0.001). As the depth difference increased, Li-Qian's formula could not visualize changes in single renal function accurately. In contrast, the accuracy of the rotation method in assessing single renal function remains unaffected. CONCLUSION: The rotation method obtains an accurate depth and depth difference between the two kidneys without additional CT radiation, enhancing the accuracy of the Gates method for determining total and single renal GFR. Trial registration Medical Ethics Committee of First Hospital of Shanxi Medical University, 2021BAL0146. Registered 12 January 2021.

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