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OBJECTIVES: Cancer morbidity and mortality can be reduced if the cancer is detected early. Cell-free DNA (cfDNA) fragmentomics emerged as a novel epigenetic biomarker for early cancer detection, however, it is still at its infancy and requires technical improvement. We sought to apply a single-strand DNA sequencing technology, for measuring genetic and fragmentomic features of cfDNA and evaluate the performance in detecting multiple cancers. METHODS: Blood samples of 364 patients from six cancer types (colorectal, esophageal, gastric, liver, lung, and ovarian cancers) and 675 healthy individuals were included in this study. Circulating tumor DNA mutations, cfDNA fragmentomic features and a set of protein biomarkers were assayed. Sensitivity and specificity were reported by cancer types and stages. RESULTS: Circular Ligation Amplification and sequencing (CLAmp-seq), a single-strand DNA sequencing technology, yielded a population of ultra-short fragments (<100â¯bp) than double-strand DNA preparation protocols and reveals a more significant size difference between cancer and healthy cfDNA fragments (25.84â¯bp vs. 16.05â¯bp). Analysis of the subnucleosomal peaks in ultra-short cfDNA fragments indicates that these peaks are regulatory element "footprints" and correlates with gene expression and cancer stages. At 98â¯% specificity, a prediction model using ctDNA mutations alone showed an overall sensitivity of 46â¯%; sensitivity reaches 60â¯% when protein is added, sensitivity further increases to 66â¯% when fragmentomics is also integrated. More improvements observed for samples representing earlier cancer stages than later ones. CONCLUSIONS: These results suggest synergistic properties of protein, genetic and fragmentomics features in the identification of early-stage cancers.
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Ácidos Nucleicos Libres de Células , ADN Tumoral Circulante , Neoplasias , Humanos , Detección Precoz del Cáncer , Mutación , ADN Tumoral Circulante/genética , Neoplasias/diagnóstico , Neoplasias/genética , Biomarcadores de Tumor/genéticaRESUMEN
BACKGROUND: Temporomandibular joint disorders (TMD) is the most common non-dental pain complaint in the maxillofacial region, which presents a variety of symptoms and signs, including temporomandibular joints (TMJ) and masticatory muscle pain, joint noise, tinnitus, headaches, irregular or restricted mandibular function, masticatory difficulty, and restricted mouth opening. When comes to the relationship between obesity and TMD, it has remained controversial and inconsistent, therefore, we first conducted this meta-analysis to estimate the unclear relationship between obesity and TMD. METHODS: Searches were conducted in PubMed, Web of Science, Embase, and Cochrane Library. Subjects were divided into five groups according to BMI level in this study, including the normal weight group: 18.5 ≤ BMI < 25, overweight group: 25 ≤ BMI < 30, obesity group: BMI ≥ 30, control group: BMI < 25, and overweight and obesity group: BMI ≥ 25. Statistics analyses were conducted using Stata (15.0). The number of PROSPERO was CRD42022368315. RESULTS: Eight studies were included in this study, and six articles with a total of 74,056 participants were synthesized for meta-analysis. Compared to normal weight individuals, overweight and obesity together decreased the risk of TMD (OR = 0.66, 95% CI = 0.46-0.95), and it was significantly decreased by obesity alone (OR = 0.58). Moreover, it was lower in obesity compared with control subjects (OR = 0.83, 95% CI = 0.73-0.94). Furthermore, in overweight and obese individuals, it was much lower in obesity than in overweight (OR = 0.82, 95% CI = 0.71-0.94). CONCLUSIONS: Obesity is not a risk factor for TMD, and maybe a protective factor for TMD, of which patients with larger BMI are less likely to suffer from TMD pain. Therefore, the value of BMI should be taken into consideration in the assessment of TMD.
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Sobrepeso , Trastornos de la Articulación Temporomandibular , Humanos , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Obesidad/complicaciones , Obesidad/epidemiología , Trastornos de la Articulación Temporomandibular/complicaciones , Trastornos de la Articulación Temporomandibular/epidemiología , Factores de Riesgo , DolorRESUMEN
Although resistance to poly(ADP-ribose) polymerase inhibitors (PARPi) has gradually become a major challenge in the maintenance therapy for high-grade serous ovarian carcinoma (HGSOC), there are no universal indicators for resistance monitoring in patients. A key resistance mechanism to PARPi is the restoration of homologous recombination repair (HRR), including BRCA reversion mutations and changes in DNA damage repair proteins. To explore mutation profiles associated with PARPi resistance, we undertook targeted 42-gene deep sequencing of circulating cell-free DNA (cfDNA) extracted from HGSOC patients pre- and post-treatment with olaparib maintenance therapy. We found that pathogenic germline mutations in the HRR pathway, including BRCA1/2, were strongly associated with improved clinical outcomes, and newly acquired MRE11A mutations significantly shortened the progression-free survival (PFS) of patients. Furthermore, dynamic fluctuations of somatic mutation sites in CHEK2:p.K373E and CHEK2:p.R406H can be used for evaluating the therapeutic efficacy of patients. MRE11A:p.K464R might be a vital driving factor of olaparib resistance, as patients with newly acquired MRE11A:p.K464R in post-treatment cfDNA had significantly shorter PFS than those without it. These findings provide potential noninvasive biomarkers for efficacy evaluation and resistance monitoring of olaparib treatment, and lay the foundation for developing combination treatment after olaparib resistance.
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Ácidos Nucleicos Libres de Células , Neoplasias Ováricas , Resistencia a Antineoplásicos/genética , Femenino , Humanos , Mutación , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Ftalazinas/farmacología , Ftalazinas/uso terapéutico , Piperazinas , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéuticoRESUMEN
BACKGROUND: Fragility fracture is one of the most serious consequences of female aging, which can increase the risk of death. Therefore, paying attention to the pathogenesis of postmenopausal osteoporosis (PMOP) is very important for elderly women. METHODS AND MATERIALS: Forty 12-week-old female rats were divided into two groups including the ovariectomy (OVX) group and the control group. Four rats in each group were selected at 1, 4, 8, 12 and 16 weeks after operation. Vertebral bones and femurs were dissected completely for micro-Computed Tomography (micro-CT) scanning, biological modulus detection and histomorphological observation. RESULTS: In OVX group, bone volume/total volume (BV/TV), bone trabecular connection density (Conn.D) and trabecular bone number (Tb.N) decreased significantly with time (P < 0.05). The elastic modulus of femur in OVX group was lower than that in control group, but there was no significant difference between them (P > 0.05). Over time, the tartrate resistant acid phosphatase (TRAP), osteocalcin (BGP), type I procollagen amino terminal propeptide (PINP) and type I collagen carboxy terminal peptide (CTX-I) in OVX group increased significantly (P < 0.05). The micrographs of the OVX group showed sparse loss of the trabecular interconnectivity and widening intertrabecular spaces with time. CONCLUSION: The bone loss patterns of vertebral body and femur were different in the early stage of estrogen deficiency. The bone turnover rate of OVX rats increased, however the changes of biomechanical properties weren't obvious.
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Osteoporosis , Anciano , Animales , Remodelación Ósea , Femenino , Humanos , Osteoporosis/etiología , Ovariectomía/efectos adversos , Ratas , Ratas Sprague-Dawley , Microtomografía por Rayos XRESUMEN
BACKGROUND: Osteoporosis is associated with a decrease of bone mineralized component as well as a increase of bone marrow fat. At present, there are few studies using radiomics nomogram based fat-water material decomposition (MD) images of dual-energy spectral CT as an evaluation method of abnormally low Bone Mineral Density (BMD). This study aims to establish and validate a radiomics nomogram based the fat-water imaging of dual-energy spectral CT in diagnosing low BMD. METHODS: Ninety-five patients who underwent dual-energy spectral CT included T11-L2 and dual x-ray absorptiometry (DXA) were collected. The patients were divided into two groups according to T-score, normal BMD(T ≥ -1) and abnormally low BMD (T < -1). Radiomic features were selected from fat-water imaging of the dual-energy spectral CT. Radscore was calculated by summing the selected features weighted by their coefficients. A nomogram combining the radiomics signature and significant clinical variables was built. The ROC curve was performed to evaluate the performance of the model. Finally, we used decision curve analysis (DCA) to evaluate the clinical usefulness of the model. RESULTS: Five radiomic features based on fat-water imaging of dual-energy spectral CT were constructed to distinguish abnormally low BMD from normal BMD, and its differential performance was high with an area under the curve (AUC) of 0.95 (95% CI, 0.89-1.00) in the training cohort and 0.97 (95% CI, 0.91-1.00) in the test cohort. The radiomics nomogram showed excellent differential ability with AUC of 0.96 (95%CI, 0.91-1.00) in the training cohort and 0.98 (95%CI, 0.93-1.00) in the test cohort, which performed better than the radiomics model and clinics model only. The DCA showed that the radiomics nomogram had a higher benefit in differentiating abnormally low BMD from normal BMD than the clinical model alone. CONCLUSION: The radiomics nomogram incorporated radiomics features and clinical factor based the fat-water imaging of dual-energy spectral CT may serve as an efficient tool to identify abnormally low BMD from normal BMD well.
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Nomogramas , Osteoporosis , Humanos , Osteoporosis/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , AguaRESUMEN
BACKGROUND: In vertebrae, the amount of cortical bone has been estimated at 30-60%, but 45-75% of axial load on a vertebral body is borne by cortical bone. OBJECTIVE: To compare the role of L1 CT-attenuation and cortical thickness in predicting osteoporosis by opportunistic CT and explore cortical thickness value in osteoporosis. METHODS: We collected data of 94 patients who underwent DXA and thoracic and/or abdominal CT to demonstrate an entire L1 for other indications in routine practice. Patients were divided into three groups according to T-score: osteoporosis, osteopenia, or normal. CT-attenuation value and cortical thickness of L1 were measured. ANOVA analysis was utilized to analyze CT-attenuation and cortical thickness among the three groups. Sensitivity, specificity, and area under the curve (AUC) predicting low BMD were determined using ROC. Pearson correlations were employed to describe relationship between L1 BMD and CT-attenuation value, BMD, as well as cortical thickness. RESULTS: The mean cortical thickness was 0.83±0.11, 0.72±0.10, and 0.64±0.09âmm for normal, osteopenia, and osteoporotic subgroups, respectively. A statistically significant difference was observed in cortical thickness and CT-attenuation value among these three subgroups. A mean CT-attenuation value threshold of >â148.7 yielded 73.0% sensitivity and 86.0% specificity for distinguishing low BMD from normal with an AUCâ=â0.83. Pearson correlation analysis indicated that BMD was positively correlated with CT-attenuation (râ=â0.666, Pâ<â0.001) and cortical thickness (râ=â0.604, Pâ<â0.001). CONCLUSIONS: L1 CT-attenuation and cortical thickness measured on opportunistic CT can help predict osteoporosis. Compared with cortical thickness, CT-attenuation is a more sensitive and accurate index for distinguishing low BMD from normal.
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Enfermedades Óseas Metabólicas , Osteoporosis , Absorciometría de Fotón , Densidad Ósea , Humanos , Vértebras Lumbares , Osteoporosis/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
Clinical studies have shown that persistent hyperglycemia following oxidative stress is associated with the apoptosis of osteocytes in diabetics. Adiponectin (APN) can ameliorate oxidative stress, and its receptors have been identified in bone-forming cells. However, the relationship between APN and osteocyte apoptosis has not been fully elucidated. This study aimed to investigate whether APN could prevent osteocyte apoptosis and regulate reactive oxygen species (ROS) generation in a high-glucose environment. Hoechst staining and fluorescence microscopy were used to observe the apoptosis of osteocytic MLO-Y4 cells. Real-time quantitative polymerase chain reaction and Western blot analysis were used to detect the expression of Caspase 3, Caspase 8, and Bcl-2. ROS generation was investigated with an active oxygen kit and fluorescence microscopy. Furthermore, the expression of proteins in the AMPK/FoxO3A signaling pathway was also studied by Western blot analysis. In a high-glucose environment, APN promoted the proliferation of MLO-Y4 osteocytes and the expression of Bcl-2 but inhibited the expression of Caspase 3, Caspase 8, and ROS in a dose-dependent manner. APN promoted the activation of p-AMPK and p-AMPK/AMPK, which reached their highest levels at 10 min and returned to baseline at 30 min. The expression of p-FoxO3A/FoxO3A in both the cytoplasm and nucleus peaked at 15 min, and this expression was returned to baseline at 60 min. In summary, APN has an antiapoptotic effect and regulates ROS generation in MLO-Y4 osteocytes in a high-glucose environment. The AMPK/FoxO3A signaling pathway might be a key signaling pathway that participates in the effect of APN on regulating osteocyte apoptosis in diabetics.
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Proteínas Quinasas Activadas por AMP/metabolismo , Adiponectina/farmacología , Apoptosis/efectos de los fármacos , Proteína Forkhead Box O3/metabolismo , Glucosa/toxicidad , Osteocitos/efectos de los fármacos , Animales , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular , Proliferación Celular/efectos de los fármacos , Ratones , Osteocitos/enzimología , Osteocitos/patología , Fosforilación , Especies Reactivas de Oxígeno/metabolismo , Transducción de SeñalRESUMEN
Oxygen detection by organic-inorganic halide perovskites (OIHPs) has demonstrated advantages in operating temperature, response time, and reversibility over traditional materials. However, OIHPs can only sense O2 in light and the unavoidable O2 exposure during detection easily induces the degradation of OIHPs. The trade-off between sensitivity and stability makes the OIHP-based oxygen sensors impractical. By replacing organic groups with Cs, the compact films of all-inorganic halide perovskites (AIHPs) that can adsorb O2 at grain boundaries in dark are developed. AIHPs show conductance increase of 1875.5% from 1 × 10-5 to 700 Torr of O2 pressure, associated with full reversibility and long-term stability. Combining experiments and modeling, this work reveals the donor-acceptor competition via halide vacancy filling leading to the modulation of carrier concentration and mobility. This work offers understandings on oxygen sensing by perovskite materials and paves the way for further optimization of AIHPs as promising oxygen sensors with high sensitivity and stability.
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Transition metal oxides with high theoretical capacities are widely investigated as potential anodes for alkali-metal ion batteries. However, the intrinsic conductivity deficiency and large volume changes during cycles result in poor cycling stability and low rate capabilities. Graphene has been widely used to support metal oxide for enhanced performance, but the cycling life is limited by the aggregation/collapse of active materials on graphene surface. Herein, we significantly improve the battery performance of graphene-metal oxide composite via pore engineering and surface protection. In this architecture, the mesoporous NiFe2O4 is designed for fast ion diffusion and volume accommodation, and the outer graphene protection can further enhance the electrical conductivity and prevent the aggregation during cycle. Thus, as-prepared G@p-NiFe2O4@G composite for lithium storage delivers high capacity (1244 mA h g-1 after 300 cycles at 0.2 A g-1), excellent rate performance (563 mA h g-1 at 4 A g-1), and outstanding cycling life up to 1200 cycles at 1.5 A g-1. For sodium storage, it also displays good cycling stability and superior rate performance. Moreover, the effects of various microstructures on the battery performance, the reaction kinetics of various electrodes, and the reaction mechanism of NiFe2O4 have been systematically investigated in this work.
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BACKGROUND: There is a noticeable lack of systematic researches on evaluating the correlation between serum estrogen levels and changes in brain functional areas of perimenopausal women.The aim of this study is to investigate the regional spontaneous brain activity changes in perimenopausal women. METHODS: Based on the resting-state functional magnetic resonance imaging datasets acquired from 25 perimenopausal women and 20 healthy women of reproductive age, a two-sample t-test was performed on individual normalized regional homogeneity (ReHo) maps. Relationships between abnormal ReHo values and the self-rating anxiety scale (SAS), the self-rating depression scale (SDS) were investigated with Pearson correlation analysis. We also investigated the correlation between abnormal ReHo values and serum estrogen level. RESULTS: In the perimenopausal group, we found increased ReHo in the right posterior cerebellum (region 2), left middle frontal gyrus and left middle cingulate gyrus ([Formula: see text]). Additionally, the ReHo values in left middle frontal gyrus and leftt middle cingulate gyrus showed positively significant correlation with the SAS, SDS scores. On the contrary, there was no significant correlation between the ReHo value in right posterior cerebellum and SDS, SAS scores. In the perimenopausal group, the ReHo values in the left middle frontal gyrus and left middle cingulate gyrus were negatively correlated with the serum estrogen level ([Formula: see text]). CONCLUSION: The results of this preliminary study have suggested that abnormal spontaneous activities of multiple brain regions during resting state was already altered in perimenopausal women. Alterative activities might be related to emotional regulation deficits and cognitive impairment, and might potentially represent the neural mechanism underlying perimenopausal period.
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Imagen por Resonancia Magnética , Perimenopausia , Encéfalo/diagnóstico por imagen , Femenino , HumanosRESUMEN
BACKGROUND: To explore the impact of thoracic endovascular aortic repair (TEVAR) on aortic remodeling (AR) and the relationship between AR and complications after TEVAR. METHODS: A total of 56 patients (2 type IIIA aortic dissection [AD] and 54 type IIIB AD) with complicated acute type B aortic dissection suitable for TEVAR were prospectively enrolled. There were 44 men (78%) and 12 women (22%) with an average age of 54 ± 13.8 years. Aortic enhanced computed tomography (CT) was performed pre-TEVAR and 3, 6, and 12 months postoperatively. The morphological changes in AR, namely aortic volume and false lumen thrombosis, were obtained by analyzing the CT data. The effect of TEVAR on AR was determined by the morphological changes in the aorta. The relationship between AR index, false lumen thrombosis, and complications was analyzed. RESULTS: The volume of the thoracic aortic true lumen gradually increased post-TEVAR, whereas the volume of the thoracic aortic false lumen gradually decreased. The volume of abdominal aortic total lumen and false lumen increased 6 months postoperatively. The AR index increased significantly 3 months postoperatively, which was negatively correlated with complications and mortality. The thoracic and abdominal aortic false lumen thrombosis developed gradually after TEVAR, and the degree of thoracic aortic false lumen thrombosis was negatively correlated with complications and mortality. CONCLUSIONS: TEVAR promotes AR. AR index and the degree of thoracic aortic false lumen thrombosis can serve as predictors of complications and mortality.
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Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/cirugía , Disección Aórtica/cirugía , Aortografía , Implantación de Prótesis Vascular , Angiografía por Tomografía Computarizada , Procedimientos Endovasculares , Tomografía Computarizada Multidetector , Remodelación Vascular , Adulto , Anciano , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/mortalidad , Disección Aórtica/fisiopatología , Aorta Abdominal/diagnóstico por imagen , Aorta Abdominal/fisiopatología , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/fisiopatología , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/mortalidad , Aneurisma de la Aorta Torácica/fisiopatología , Implantación de Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/mortalidad , Endofuga/diagnóstico por imagen , Endofuga/etiología , Endofuga/fisiopatología , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/mortalidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
STATEMENT OF PROBLEM: Additive manufacturing or 3D printing is gaining popularity in dentistry, including for interim fixed dental prostheses (IFDPs). However, evidence regarding the color stability of 3D-printed IFDPs is lacking. PURPOSE: The purpose of this in vitro study was to investigate whether different surface treatments could affect the color stability of milled and 3D-printed IFDPs after simulated physiological aging. MATERIAL AND METHODS: Forty milled IFDPs were fabricated with a 5-axis dental mill (DWX-51D; Roland DGA Corp) from polymethyl methacrylate disks (Temp Esthetic 98, A3.5, 98.5×16 mm; Harvest Dental Products, LLC). Forty 3D-printed IFDPs were fabricated with an in-office digital light processing 3D printer (MAX; Asiga) and light-polymerizing resin (NextDent Crown & Bridge A3.5; NextDent B.V). All milled and 3D-printed IFDPs were allocated into 4 different groups (n=10), according to different surface treatments: Control, Polish, Optiglaze, and Skinglaze. In the Control group, no surface treatment was applied to the IFDPs. For the Polish group, IFDPs were finished and polished with aluminum oxide finishers/polishers (Enhance PoGo Complete Kit; Dentsply Sirona). For the Optiglaze and Skinglaze groups, specimens were first finished and polished and prepared with additional light-polymerizing protective coatings (Optiglaze; GC America Inc, or New Outline Skin Glaze; anaxdent North America). Shade measurements were recorded with a digital spectrophotometer (Vita Easyshade V; VITA North America) before and after the thermocycling for the color stability comparisons. The effects of interim prosthesis type and surface treatments on ΔE∗, ΔL∗, Δa∗, and Δb∗ were examined using 2-way analysis of variance (ANOVA), and ΔE∗ was considered as the primary outcome variable. Post hoc pairwise comparisons were performed by using the Tukey honestly significant difference (HSD) method (α=.05 for all tests). RESULTS: Milled IFDPs had significantly smaller ΔE∗ than 3D-printed prostheses for the Control group only (P<.001). Within the milled IFDPs, Optiglaze group (mean ±standard deviation, 1.01 ±0.38) had significantly lower ΔE∗ than all the other surface treatments groups (Control group: 2.38 ±0.44, P<.001; Polish group: 1.83 ±0.51, P=.025; and Skinglaze group: 1.85 ±0.78, P=.021). Within the 3D-printed IFDPs, the Control group (3.83 ±0.71) had significantly larger ΔE∗ than all other surface treatments (Polish group: 2.66 ±0.89, P=.018; Skinglaze group: 1.40 ±0.73, P<.001; and Optiglaze group: 1.37 ±0.67, P<.001). The Polish group had significantly higher ΔE∗ than Skinglaze group (P=.009) and Optiglaze group (P=.007), while Skinglaze and Optiglaze groups were not significantly different from each other (P=1.000). CONCLUSIONS: For the milled IFDPs, only the nano-filled, light-polymerizing protective coating significantly lowered color changes after thermocycling simulating 6 months of intraoral physiological aging. For the 3D-printed IFDPs, surface polishing and both light-polymerizing protective coating agents all significantly reduced color changes of the prostheses after thermocycling. The protective effect of light-polymerizing coating agents was more substantial.
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Diseño Asistido por Computadora , Estética Dental , Color , Dentadura Parcial Provisoria , Humanos , Ensayo de Materiales , Impresión Tridimensional , Propiedades de SuperficieRESUMEN
BACKGROUND: Currently, few studies have described the relationship between functional MRI findings and histology of normal sacroiliac joint (SIJ). Besides, due to the difficulties in access to SIJ, authentic animal models are important in providing opportunities for quantitative parameter extraction on imaging. AIMS: This study aimed at exploring the parameters of Intravoxel Incoherent Motion Diffusion-Weighted Imaging (IVIM-DWI) and Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) and comparing them with the histology of the SIJ in normal rats with different ages. METHODS: A total of thirty 7-week-old male Wistar rats were included in the study. The parameters of IVIM-DWI and DCE-MRI in the bone marrow and the joint space of SIJ were measured at 8, 13, 18, 23, 28, and 33 weeks. The histological analysis of the SIJ was examined using light microscopy. One-way ANOVA was used for statistical analysis. RESULTS: The D values in the sacral and iliac bone marrow of normal rats decreased with an increase in age. One-way ANOVA analysis indicated a significant difference in D values in different age groups (P<0.005). The normal values of D*, f, Fenh (%), Senh (%/s) in the sacral bone marrow, the iliac bone marrow, and the joint space in SIJ of normal rats were obtained. The results showed that in the six groups of rats of different ages, the histology of the SIJ surface was smooth and clear, the cartilage cells were intact, and no thickening or pannus formation was observed. CONCLUSIONS: This study obtained the IVIM-DWI and DCE-MRI parameters of the sacral and iliac bone marrow and the synovial area of the joint space in normal rats. The parameters in normal rats can be used in future research to compare to similar parameters in animal models or patients with SIJ diseases. This study serves as a guide for future research in SIJ diseases.
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Medios de Contraste , Articulación Sacroiliaca , Animales , Imagen de Difusión por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética , Masculino , Movimiento (Física) , Ratas , Ratas Wistar , Articulación Sacroiliaca/diagnóstico por imagenRESUMEN
BACKGROUND: In the management of early inflammatory joint of ankylosing spondylitis (AS), there is a need for reliable noninvasive quantitative monitoring biomarker to closely assess status of synovitis progression. Cognizant to this,studies geared on improving techniques for quantitative evaluation of micro-environment permeability of the joint space are necessary. Such improved techniques may provide tissue perfusion as important biological parameters and can further help in understanding the origin of early changes associated with AS. The purpose of this study was to prospectively evaluate the diagnostic performance and determine longitudinal relationships of early micro-environment active in the joint space of the sacroiliac joint (SIJ) with a rat model by using quantitative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). METHODS: Thirty wistar male rats were randomly assigned to the model (n = 15) or control (n = 15) group. All rats underwent DCE-MRI of SIJ region at fixed time points (12, 17 and 22 weeks),between September 2018 and October 2019. Differences in permeability parameters between the two groups at the same time point were compared by using an independent samples t test. Spearman correlations of DCE-MRI parameters with different time points in model group were analyzed. All statistical analyses were performed with software. RESULTS: At 12 weeks,the Ktrans,Kep and Ve values in the model group were slightly lower than those in control group,but all the differences were not statistically significant (p > 0.05). Compared with control group,the transfer constant (Ktrans) values increased significantly at 17 weeks and 22 weeks in model group,while the rate constant (Kep) and volume of extravascular extracellular space (Ve) significantly increased only at 22 weeks(p < 0.05). The Ktrans,Kep and Ve were positively correlated with increasing time points (r = 0.946, P<0.01 for Ktrans; r = 0.945, P<0.01 for Kep; and r = 0.832, P<0.01 for Ve). CONCLUSION: Quantitative DCE-MRI parameters are valuable for evaluating the early longitudinal relationship of micro-environment permeability changes in the joint space of SIJ.
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Medios de Contraste , Espondilitis Anquilosante , Animales , Imagen por Resonancia Magnética , Masculino , Permeabilidad , Ratas , Espondilitis Anquilosante/diagnóstico por imagenRESUMEN
The objective of this study was to evaluate the protection conferred by lactoferrin, α-lactalbumin, and ß-lactoglobulin in cerebral ischemia reperfusion (I/R) injury. Rat pheochromocytoma (PC12) cells were used to construct an oxygen and glucose deprivation model in vitro, and ICR mice underwent carotid artery "ligation-relaxation" to construct a cerebral I/R injury model in vivo. The levels of toll-like receptor 4 (TLR4) and downstream factors including nuclear factor-κB, tumor necrosis factor-α, and IL-1ß were measured. Metabonomics detection and data mining were conducted to identify the specific metabolic sponsor of the 3 proteins. The results showed that lactoferrin, α-lactalbumin, and ß-lactoglobulin protected neurons from cerebral I/R injury by increasing the level of bopindolol and subsequently inhibiting the TLR4-related pathway to different degrees; ß-lactoglobulin had the strongest activity of the 3 proteins. In summary, this study is the first to investigate and compare the protective effects of lactoferrin, α-lactalbumin, and ß-lactoglobulin in a cerebral stroke model. The results implicate TLR4 as a novel target of the 3 bioactive proteins to prevent cerebral I/R injury.
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Lactalbúmina/uso terapéutico , Lactoferrina/uso terapéutico , Lactoglobulinas/uso terapéutico , Daño por Reperfusión/prevención & control , Animales , Glucosa/metabolismo , Interleucina-1beta/metabolismo , Lactalbúmina/metabolismo , Lactoferrina/metabolismo , Lactoglobulinas/metabolismo , Masculino , Ratones , Ratones Endogámicos ICR , FN-kappa B/metabolismo , Oxígeno/metabolismo , Células PC12 , Ratas , Receptor Toll-Like 4/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
The ß2-adrenergic receptor (ß2-AR) signaling on bone cells is the major contributor in the effect of the sympathetic nervous system on bone turnover. However, it remains unclear whether receptor activator of nuclear factor κ-Β ligand (RANKL) modulation and neuropeptides expression in osteocytes are responsible for the mechanism. This study used ß2-AR stimulation to investigate cell cycle and proliferation, the gene and protein expression of RANKL, and osteoprotegerin (OPG), as well as neuropeptides regulation in osteocytic MLO-Y4 cells. Clenbuterol (CLE; a ß2-AR agonist) slightly promoted the growth of MLO-Y4 cells in a concentration-dependent effect but had no effect on the proliferation index. And the concentration of 10-8 M showed a significant increase in the S-phase fraction on day 3 in comparison with the control. Additionally, CLE-promoted osteoclast formation and bone resorption in osteocytic MLO-Y4 cell-RAW264.7 cell cocultures. RANKL expression level and the ratio of RANKL to OPG in MLO-Y4 cells were enhanced in CLE treatment but were rescued by blocking ß2-AR signaling. However, neuropeptide Y and α-calcitonin gene-related peptide, two neurogenic markers, were inhibited in CLE treatment of MLO-Y4 cells, which was reversed by a ß2-AR blocker. The results indicate that osteocytic ß2-AR plays an important role in the regulation of RANKL/OPG and neuropeptides expression, and ß2-AR signaling in osteocytes can be used as a new valuable target for osteoclast-related pathologic disease.
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In this work, we report a high-performance anode material created by rationally encapsulating multi-walled carbon nanotubes (MWNTs) within hollow Fe3O4 nanotubes followed by applying a carbon coating. When tested for lithium storage, as-prepared MWNT@hollow Fe3O4@C coaxial nanotubes present high specific capacity, superior rate performance, and outstanding cycling stability. It is capable of delivering high capacities of 758 mA h g-1 at 500th cycle at 0.2 A g-1, and 409 mA h g-1 after 1000 cycles at a high rate of 1.5 A g-1. This excellent performance can be attributed to its unique architecture, which provides high electrical conductivity, offers enough void space for volume accommodation, and mitigates the pulverization of Fe3O4 during cycles.
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Allogeneic haematopoietic stem cell transplantation (HSCT) is the only available curative therapy for patients with thalassaemia major. With the progress in human leucocyte antigen (HLA) antigen typing technology and supportive care, the outcomes of thalassaemia major have greatly improved in recent years, even in high-risk patients. However, the problem of finding a suitable donor is still a major obstacle to curing these patients. In recent decades, the lack of available HSCT donors has led to the increased use of haploidentical donors (HDs) for HSCT in haematological malignancies. Recently, we explored the effect of HD HSCT to eight children with thalassaemia major based on the FBCA conditioning regimen (fludarabine, busulphan, cyclophosphamide, antithymocyte globulin), which is usually used in leukaemia patients receiving haploidentical HSCT in our centre. So far, all of the transplanted patients have a stable engraftment and are transfusion independent in daily life. This encouraging result has revised our previous conception about haploidentical HCST for thalassaemia major and strongly suggests that HD HSCT is a feasible and safe method for thalassaemia major patients.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Supervivencia de Injerto , Trasplante de Células Madre Hematopoyéticas , Acondicionamiento Pretrasplante , Talasemia beta/terapia , Adulto , Aloinjertos , Suero Antilinfocítico/administración & dosificación , Busulfano/administración & dosificación , Niño , Preescolar , Ciclofosfamida/administración & dosificación , Femenino , Humanos , Masculino , Vidarabina/administración & dosificación , Vidarabina/análogos & derivadosRESUMEN
wnt/ß-catenin signaling has been shown to influence bone homeostasis and is important for parathyroid hormone (PTH)-induced bone gain. To further understand the role of ß-catenin in the early stages of osteoblastic lineage cells for postnatal bone homeostasis and the anabolic actions of PTH on bone, we examined mice with postnatal disruption of ß-catenin in osterix-expressing cells (ß-catenin KO mice) by mating floxed ß-catenin mice with transgenic mice expressing cre under the control of the osterix promoter suppressible by doxycycline. After withdrawal of doxycycline, ß-catenin KO mice developed progressive bone loss, ectopic cartilage formation, accumulation of mesenchymal stromal cells, and bone marrow adiposity. The ß-catenin-defective osteoblasts sorted by flow cytometry from ß-catenin KO mice exhibited decreased EdU incorporation, increased annexin V activity, and profound alterations in gene expression including wnt target genes, osteoclast regulators, and osteoblast markers. A dramatic increase in osteoclasts was observed in both neonatal and postnatal ß-catenin KO mice. Intermittent administration of PTH for 4 weeks significantly increased bone mass in control mice; however, this anabolic effect of PTH was substantially blunted in ß-catenin KO mice. Our data indicate that ß-catenin in osterix-expressing cells is required for postnatal osteoblast differentiation, osteoblast proliferation, and bone resorption, and is essential for the anabolic actions of PTH in bone.
Asunto(s)
Desarrollo Óseo/efectos de los fármacos , Huesos/metabolismo , Eliminación de Gen , Hormona Paratiroidea/farmacología , Factor de Transcripción Sp7/metabolismo , beta Catenina/genética , Adiposidad/efectos de los fármacos , Anabolizantes/farmacología , Animales , Animales Recién Nacidos , Apoptosis/efectos de los fármacos , Médula Ósea/efectos de los fármacos , Médula Ósea/metabolismo , Resorción Ósea/metabolismo , Resorción Ósea/patología , Cartílago/efectos de los fármacos , Cartílago/metabolismo , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Doxiciclina/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Integrasas/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Tamaño de los Órganos/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoclastos/patología , Osteogénesis/efectos de los fármacos , Osteoprotegerina/metabolismo , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , beta Catenina/metabolismoRESUMEN
The sympathetic nervous system play a pivotal role in bone remodeling through ß-adrenoceptor (ß-AR). However, it is not well documented whether the ß-adrenoceptor pathway has the potential to influence osteocytes. In this study, cell viability, the expression of ß-AR subtypes, enzymes of catecholamine synthesis or degradation, bone-related gene and protein in osteocytic MLO-Y4 cells were investigated by ß-adrenergic stimulation. Isoproterenol (ISO) promoted RANKL to OPG expression in osteocytes, as well as osteoclasts formation in osteocytes-RAW264.7 cell co-cultures but not RAW264.7 cell monoculture. The ISO-stimulated effect was enhanced in ß1-AR antagonist pretreatment, but was rescued by blocking ß2-AR. The results indicate that ß1-and ß2-AR play reciprocal roles on MLO-Y4 cells in the regulation of osteoclastogenesis, and osteocyte ß-adrenergic signaling might be a new valuable therapy for bone disease.