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1.
Cancer Med ; 12(1): 513-524, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-35607944

RESUMEN

Colorectal cancer (CRC) is a major leading cause of cancer mortality worldwide in which dysregulated protein synthesis plays an etiologic role. The eukaryotic elongation factor 1 A1 (eEF1A1) exerts significant effects on protein synthesis by contributing to peptide chain extension. Whereas its role in CRC remains to be investigated. In this study, we found that the mRNA and protein levels of eEF1A1 were significantly upregulated in CRC cell lines and tissues. Elevated expression of eEF1A1 was correlated with shorter overall survival in 94 CRC patients. The inhibition of proliferation and cell cycle block were observed in CRC cells after eEF1A1 downregulation. Mechanistically, weighted gene correlation network analysis and further Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that mitogen-activated protein kinases (MAPKs) signaling pathways were significantly enriched in high-eEF1A1 expression group, and the levels of phosphorylated p38/JNK/ERK MAPK were dramatically decreased after eEF1A1 downregulation. Overexpression of eEF1A1 in CRC correlated with a poor prognosis. Collectively, this study determined the oncogenic role of eEF1A1 in CRC proliferation and tumorigenesis. eEF1A1 might be a promising therapeutic target and prognostic biomarker in CRC.


Asunto(s)
Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Factor 1 de Elongación Peptídica/genética , Factor 1 de Elongación Peptídica/metabolismo , Sistema de Señalización de MAP Quinasas , Línea Celular , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Pronóstico , Proliferación Celular , Línea Celular Tumoral
2.
J Transl Med ; 20(1): 454, 2022 10 04.
Artículo en Inglés | MEDLINE | ID: mdl-36195882

RESUMEN

BACKGROUND: Liver metastases are a major contributor to the poor immunotherapy response in colorectal cancer patients. However, the distinctions in the immune microenvironment between primary tumors and liver metastases are poorly characterized. The goal of this study was to compare the expression profile of multiple immune cells to further analyze the similarities and differences between the microenvironments of liver metastases and the primary tumor. METHODS: Tissues from 17 patients with colorectal cancer who underwent resection of primary and liver metastases was analyzed using multispectral immunofluorescence. The expression of multiple immune cells (CD8, Foxp3, CD68, CD163, CD20, CD11c, CD66b, CD56, PD-L1, INF-γ, Ki67 and VEGFR-2) in the tumor center (TC), tumor invasive front (< 150 µm from the tumor center, TF) and peritumoral region (≥ 150 µm from the tumor center, PT) was evaluated via comparison. The expression of CD68 and CD163 in different regions was further analyzed based on the cell colocalization method. In addition, different immune phenotypes were studied and compared according to the degree of CD8 infiltration. RESULTS: The expression trends of 12 markers in the TF and TC regions were basically the same in the primary tumor and liver metastasis lesions. However, in comparison of the TF and PT regions, the expression trends were not identical between primary and liver metastases, especially CD163, which was more highly expressed in the PT region relative to the TF region. In the contrast of different space distribution, the expression of CD163 was higher in liver metastases than in the primary foci. Further analysis of CD68 and CD163 via colocalization revealed that the distribution of macrophages in liver metastases was significantly different from that in the primary foci, with CD68-CD163+ macrophages predominating in liver metastases. In addition, among the three immunophenotypes, CD163 expression was highest in the immune rejection phenotype. CONCLUSIONS: The immune cells found in the primary tumors of colorectal cancer differed from those in liver metastases in terms of their spatial distribution. More immunosuppressive cells were present in the liver metastases, with the most pronounced differential distribution found for macrophages. CD68-CD163+ macrophages may be associated with intrahepatic immunosuppression and weak immunotherapeutic effects.


Asunto(s)
Neoplasias Colorrectales , Neoplasias Hepáticas , Antígeno B7-H1 , Neoplasias Colorrectales/patología , Factores de Transcripción Forkhead , Humanos , Antígeno Ki-67 , Neoplasias Hepáticas/secundario , Pronóstico , Microambiente Tumoral , Receptor 2 de Factores de Crecimiento Endotelial Vascular
5.
Eur Rev Med Pharmacol Sci ; 26(24): 9447-9456, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36591853

RESUMEN

OBJECTIVE: To investigate the incidence of hepatocellular carcinoma (HCC) in Chengdu, identify the risk factors for the development of HCC in Chengdu and provide a reference for the prevention of HCC. PATIENTS AND METHODS: The study population was recruited from Chengdu, Sichuan Province, China. The study group recruited volunteers in Chengdu from 2007 to 2012, conducted a baseline survey, and subsequently conducted long-term follow-up until December 31, 2019. A total of 22,525 study subjects were enrolled, excluding those who reported a previous history of liver disease, malignancy, and HCC within three months of enrollment. Cox proportional risk regression models were used to screen and determine the various risk factors and their hazard ratios (HR) for HCC in Chengdu, as well as to determine whether the association between other risk factors and HCC was modified by gender. RESULTS: The study population had a median follow-up of 5.35 years, and a total of 142 people developed HCC, with an incidence rate of 0.71%. Analysis of the multifactorial Cox proportional risk regression model showed that age (age 10 years for 1 group, HR= 1.98, 95% CI: 1.86-2.11, p<0.001), current smoking (HR= 1.25, 95% CI: 1.07-1.31, p=0.031), weekly consumption of pickled vegetables (HR= 1.70, 95% CI: 1.49-1.81, p=0.003) and consumption of pickled vegetables daily (HR= 1.36, 95% CI: 1.21-1.42, p=0.021) were risk factors for HCC, and women (HR= 0.39, 95% CI: 0.28-0.55, p=0.002) and the use of air conditioning (10 years for 1 group, HR= 0.79, 95% CI: 0.68-0.83, p=0.002) were protective factors against HCC. Further analysis revealed that the association between length of time using air conditioning and HCC was heterogeneous among men and women (p=0.007) and that there was an interaction between sex and use of air conditioning in the association with HCC development (p<0.001). CONCLUSIONS: The Chengdu population has a high incidence of HCC and numerous risk factors for HCC. There is a synergistic interaction between sex and length of time using air conditioning in their role in the development of HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Niño , Femenino , Humanos , Masculino , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , Incidencia , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , China/epidemiología
6.
Zhonghua Shao Shang Za Zhi ; 37(4): 356-362, 2021 Apr 20.
Artículo en Chino | MEDLINE | ID: mdl-33874708

RESUMEN

Objective: To investigate the clinical effects of retrograde anterolateral thigh perforator flaps assisted with computed tomography angiography (CTA) in repairing skin and soft tissue defects around the knee or in proximal lower leg. Methods: A retrospective cohort study was conducted. From May 2015 to October 2019, 17 patients with skin and soft tissue defects around the knee or in proximal lower leg were admitted to the Department of Orthopedics of Jizhong Energy Xingtai Mig General Hospital, including 12 males and 5 females, aged 16-65 years, with an average age of 35 years. The areas of skin and soft tissue defects after debridement ranged from 6.0 cm×3.0 cm to 15.0 cm×9.0 cm. The retrograde anterolateral thigh perforator flaps were designed according to the origin and distribution of the perforating branches in flaps and the length of the vascular pedicle examined with CTA and the condition of the wound to repair the wounds. The areas of resected flaps ranged from 6.5 cm×3.5 cm to 15.5 cm×9.5 cm. The wounds in donor sites of flaps were sutured directly or covered with medium-thickness skin grafts from healthy upper leg. The sources of the perforating branches in flaps were recorded. The lateral circumflex femoral artery, its branches, and the relative length of the vascular pedicle were compared between preoperative CTA detection and intraoperative observation. The survivals of the flaps were observed. At the last follow-up, the effects of flaps in repairing wounds were evaluated according to evaluation standard of efficacy satisfaction; the motion ranges of flexion and extension of the knee joint were measured, and the knee joint function was evaluated according to the Hohl knee joint function evaluation standard; the sensory function in the flap area was evaluated according to the sensory function evaluation standard formulated by the British Medical Research Council; the wound healing and the occurrence of complication affecting motor function of limb of flap donor sites was observed. Data were statistically analyzed with paired sample t test. Results: The perforating branches in flaps originated from descending branches, oblique branches, and rectus femoris branches of lateral circumflex femoral artery in 7, 6, and 4 patients, respectively. The flaps with blood supply from descending branches, oblique branches, and rectus femoris branches of lateral circumflex femoral artery were type 1, 2, and 3 retrograde anterolateral thigh perforator flaps, respectively. The preoperative CTA examination of lateral circumflex femoral artery and its branches were consistent with those observed during operation. The relative lengths of vascular pedicles of type 1, 2, and 3 retrograde anterolateral thigh perforator flaps calculated after CTA examination were 0.32±0.13, 0.56±0.07, and 0.56±0.15, which were close to 0.35±0.12, 0.52±0.10, and 0.53±0.12 measured and calculated during operation, respectively (t=0.45, 0.80, 0.31, P>0.05). All flaps survived in 17 cases without vascular crisis. At the last follow-up, 16 patients were satisfied with effects of flaps in wound repair, with 1 patient feeling average about the effect; the flexion range of knee joint was 100-120°, and the extension range of knee joint was -2-0°; knee joint function was evaluated as excellent in 9 cases, good in 7 cases, and poor in 1 case; the sensory function of the flap area reached S4 level in 2 cases, S3 level in 8 cases, and S2 level in 7 cases; the wounds in flap donor sites healed well; there was no adverse effect in motor function of limbs. Conclusions: Retrograde anterolateral thigh perforator flap is an effective method for repairing skin and soft tissue defects around the knee or in proximal lower leg. Preoperative CTA examination can fully show the anatomical characteristics of the branches of the lateral circumflex femoral artery and the perforating vessels of each branch, which can guide preoperative flap design and operation, thus shortening operation time and improving flap survival rate, with good clinical effects.


Asunto(s)
Colgajo Perforante , Procedimientos de Cirugía Plástica , Traumatismos de los Tejidos Blandos , Adulto , Angiografía por Tomografía Computarizada , Femenino , Humanos , Articulación de la Rodilla , Pierna , Masculino , Estudios Retrospectivos , Trasplante de Piel , Traumatismos de los Tejidos Blandos/cirugía , Muslo , Resultado del Tratamiento
7.
Rev Sci Instrum ; 92(12): 124701, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34972396

RESUMEN

Carbon fiber reinforced polymers (CFRPs) are composite materials in which carbon provides strength and stiffness, whereas polymers provide cohesiveness and toughness. The electrical impedance of CFRP laminates is changed due to different kinds of damages. Electrical impedance tomography (EIT) has significant advantages such as non-intrusion, portability, low cost, and quick response and has widely been used as a nondestructive testing method. Therefore, EIT has great potential in structural health monitoring of CFRPs. Regularization can solve the ill-posed inverse problem of EIT. However, conventional regularization algorithms have their own limitations, such as over-smoothness of reconstructed edges and unstable solution caused by measurement noise. In addition, the anisotropic property of CFRPs also affects the image quality based on traditional methods. In this paper, the sorted L1-norm regularization is proposed. It promotes grouping highly correlated variables while encouraging sparsity by using more effective penalty terms. The sharp edges between different materials can be obtained, and the obtained solution is more stable. The image quality of different objects, especially the image quality of multi-targets, can be significantly improved with this new method. In addition, the sorted L1 norm can generate adaptive regularization parameters without empirical selection. The new regularization problem is solved by the alternating direction method of multipliers. Both experimental and simulation results demonstrate that the sorted L1 norm improves the quality of reconstructed images under various noise levels. The proposed method is comprehensively evaluated with three image quality criteria by numerical simulation quantitatively.

9.
Int J Cosmet Sci ; 41(4): 371-377, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31190339

RESUMEN

OBJECTIVE: The microbial community plays an important role in the generation of human axillary odour by transforming odourless natural secretions into volatile odorous molecules. A limited number of traditional culturing methods and molecular based research have been performed to characterize the human axillary microbiome in small collection sample sizes. Moreover, only a few have considered the interpersonal variations across age, gender or race/ethnicity, and none have included all three variables within one single study. The aim of this study was to characterize the axillary microbiome of healthy subjects across different age groups, genders and races/ethnicities in a large sample size. METHODS: The underarm skin swab samples were collected from 169 healthy subjects. The axillary microbiome was analysed by IS-pro, a clinically validated high-throughput DNA fingerprinting technique. RESULTS: The results indicate that the senior subjects (55+) tend to have a higher number of total bacterial than younger adults (of a defined age). The diversity of odour causing bacteria, e.g. corynebacteria, increases with age. Among the three races/ethnicities studied, East Asians have a unique microbial composition compared to Caucasians and Hispanics, which may contribute to the different odour profiles observed among the races/ethnicities studied. CONCLUSION: Human axillary microbiome varies by age, gender and race/ethnicity. This study has provided an unprecedented fundamental knowledge about the axillary microbiota as a function of age, gender and race/ethnicity.


OBJECTIF: La population microbienne joue un rôle important dans la génération de l'odeur axillaire par la transformation de sécrétions naturelles inodores en molécules odorantes et volatiles. Un nombre limité d'études par culture traditionnelle et de recherches moléculaires ont été réalisées pour caractériser le microbiome axillaire humain dans des échantillons de prélèvements de petite taille. En outre, seules quelques-unes de ces études ont tenu compte des variations interpersonnelles à travers l'âge, le sexe ou la race/l'origine ethnique, et aucune n'a inclus les trois variables dans une seule et même recherche. Le but de cette étude est de caractériser le microbiome de sujets sains est de réunir différents groupes d'âge, sexes et races/origines ethniques dans un échantillon important. MÉTHODES: Les échantillons de frottis cutanés de l'aisselle ont été recueillis sur 169 sujets sains. Le microbiome axillaire a été analysé par ISpro, une technique cliniquement validée d'empreinte ADN à haut débit. RÉSULTATS: Les résultats indiquent que les sujets séniors (55 ans et plus) ont tendance à présenter un plus grand nombre de bactéries que les adultes plus jeunes (d'un âge défini). La diversité des bactéries odorantes, par exemple, de type corynebacterium, augmente avec l'âge. Parmi les trois races/origines ethniques étudiées, les populations asiatiques présentent une composition microbienne unique par rapport aux populations caucasiennes et hispaniques, ce qui pourrait contribuer aux différents profils d'odeur observés dans les races/origines ethniques prises en compte. CONCLUSION: Le microbiome axillaire varie selon l'âge, le sexe et la race/l'origine ethnique. Cette étude fournit une connaissance fondamentale sans précédent sur la flore axillaire en fonction de l'âge, du sexe et de la race/l'origine ethnique.


Asunto(s)
Factores de Edad , Axila/microbiología , Etnicidad , Microbiota , Grupos de Población , Factores Sexuales , Adolescente , Adulto , Biodiversidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
10.
Phys Rev Lett ; 122(13): 131301, 2019 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-31012624

RESUMEN

The scattering of dark matter (DM) particles with sub-GeV masses off nuclei is difficult to detect using liquid xenon-based DM search instruments because the energy transfer during nuclear recoils is smaller than the typical detector threshold. However, the tree-level DM-nucleus scattering diagram can be accompanied by simultaneous emission of a bremsstrahlung photon or a so-called "Migdal" electron. These provide an electron recoil component to the experimental signature at higher energies than the corresponding nuclear recoil. The presence of this signature allows liquid xenon detectors to use both the scintillation and the ionization signals in the analysis where the nuclear recoil signal would not be otherwise visible. We report constraints on spin-independent DM-nucleon scattering for DM particles with masses of 0.4-5 GeV/c^{2} using 1.4×10^{4} kg day of search exposure from the 2013 data from the Large Underground Xenon (LUX) experiment for four different classes of mediators. This analysis extends the reach of liquid xenon-based DM search instruments to lower DM masses than has been achieved previously.

11.
JDR Clin Trans Res ; 4(3): 271-275, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31009581

RESUMEN

OBJECTIVES: To determine the frequency and severity of 17 requests for inappropriate analysis and reporting of data that biostatisticians received from researchers in statistical consultations, as indirectly experienced (i.e., either heard about or observed being asked of other biostatisticians). METHODS: A randomly drawn sample of 522 members of the American Statistical Association who self-identified as consulting biostatisticians were selected to participate in an online survey with the Bioethical Issues in Biostatistical Consulting Questionnaire, specifically developed for this study. RESULTS: Of the 522 consulting biostatisticians contacted, 390 (74.7%) completed the survey. The top 4 most frequently reported indirectly experienced inappropriate requests rated as "high severity" by at least 50% of the respondents were as follows: 1) proposing a study with a flawed design, including insufficient power; 2) setting aside values when the outcome turns on a few outliers; 3) reporting results of data analysis from only subsets of the data; and 4) overstating the statistical findings well beyond what the data support so that readers are misled. CONCLUSIONS: This article is a follow-up report to our recently published article on 18 directly experienced inappropriate and/or unethical requests by biomedical researchers of their consulting biostatisticians. These additional survey findings from the Bioethical Issues in Biostatistical Consulting Questionnaire on 17 indirectly experienced inappropriate requests show the following: 1) the widespread nature of inappropriate, if not, frankly unethical requests made by biomedical researchers of their consulting biostatisticians and 2) the urgent need to develop and offer educational programs for biomedical researchers in training to correct these behaviors-be they intentional or accidental. This report speaks to the urgency for developing training programs for new and existing researchers to reduce the frequency of these inappropriate bioethical requests during biostatistical consultations. KNOWLEDGE TRANSFER STATEMENT: The findings from this U.S. national survey of biostatisticians on inappropriate requests for data analyses by biomedical researchers strongly suggest a need for remedial actions, including 1) new educational modules for in-development and currently employed biomedical researchers, 2) improved institutional environments by research universities and companies regarding job and publication pressures, and 3) inclusion of a collaborating biostatistician as a working research team member from the early planning stages of all biomedical studies.


Asunto(s)
Discusiones Bioéticas , Investigadores , Biometría , Humanos , Derivación y Consulta , Encuestas y Cuestionarios , Estados Unidos
12.
Neuroimage ; 187: 116-127, 2019 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-29544818

RESUMEN

The BOLD contrast mechanism has a complex relationship with functional brain activity, oxygen metabolism, and neurovascular factors. Accurate interpretation of the BOLD signal for neuroscience and clinical applications necessitates a clear understanding of the sources of BOLD contrast and its relationship to underlying physiology. This review describes the physiological components that contribute to the BOLD signal and the steady-state calibrated BOLD models that enable quantification of functional changes with a separate challenge paradigm. The principles derived from these biophysical models are then used to interpret BOLD measurements in different neurological disorders in the presence of confounding vascular factors related to disease.


Asunto(s)
Mapeo Encefálico/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Imagen por Resonancia Magnética/métodos , Neuronas/metabolismo , Acoplamiento Neurovascular , Volumen Sanguíneo , Encéfalo/irrigación sanguínea , Calibración , Humanos , Modelos Neurológicos , Oxígeno/metabolismo
13.
Carbohydr Res ; 472: 103-114, 2019 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-30544044

RESUMEN

A critical step in the synthesis of the hydroxypyrrolidines, 1,4-dideoxy-1,4-imino-l-lyxitol and 1,4-dideoxy-1,4-imino-d-lyxitol, from the corresponding d-sugars is the synthesis of O-methyl 2,3-O-isopropylidenepentofuranoses. Instead of applying homogeneous catalysis process with conventional inorganic acid catalysts like HCl and HClO4, it was found that heterogeneous catalysis using zeolites could be used for the one-pot synthesis of O-methyl 2,3-O-isopropylidenepentofuranoses directly from d-sugars, MeOH and acetone at mild condition. The best catalyst was H-beta zeolite containing a Si/Al molar ratio of 150, where a yield of >83% was obtained. The overall yields of the five-step procedure to 1,4-dideoxy-1,4-imino-l-lyxitol and 1,4-dideoxy-1,4-imino-d-lyxitol were 57% and 50%, respectively. This synthetic procedure has several advantages such as competitive overall yield, reduced number of steps, and mild reaction conditions. Furthermore, the zeolite catalyst can be easily recovered from the reaction mixture and reused with no loss of activity.


Asunto(s)
Pirrolidinas/síntesis química , Zeolitas/química , Catálisis , Tecnología Química Verde , Estructura Molecular , Pirrolidinas/química
14.
Eur J Med Chem ; 163: 896-910, 2019 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-30580241

RESUMEN

In current work, a class of novel 4,5-dihydro-1H-pyrazole-1-carboxylate derivatives (E01-E28) were designed, synthesized and evaluated. Among them, the most potent compound E24 exhibited comparable activity against a panel of cancer cells (GI50 ranging 0.05-0.98 µM) and tubulin polymerization inhibition (IC50 = 1.49 µM) with reference drug CA-4(P) (GI50 ranging 0.019-0.32 µM, IC50 = 2.18 µM). The following assays indicated that compound E24 disturbed the dynamics of tubulin catastrophe and rescue, which triggered G2/M arrest, leading to ROS accumulation, cleavage of PARP and apoptosis. Molecular dynamics simulation validated that compound E24 could tightly bind into tubulin heterodimers with ß Lys 254 and ß Cys 241 of tubulin in the docking pose. Metabolic stability and pharmacokinetics parameters were also determined. The half time (t1/2) displayed species differences in three microsomes. The plasma elimination half-life (t1/2), peak plasma concentration (Cmax), mean retention time (MRT), the area under the curve (AUC0-∞) and distribution volume (Vz) of E24 after intravenous administration were 0.90 ± 0.22 h, 594.50 ± 97.23 ng/mL, 1.09 ± 0.22 h, 413.67 ± 105.64 ng/mL*h and 5.03 ± 1.82 L/kg, respectively. In HeLa-xenografts, compound E24 exhibited obvious antitumor efficacy via the suppression of tumor growth without weight loss of body or organ. In brief, compound E24 might be a hopeful candidate with excellent properties for oncotherapy as tubulin polymerization inhibitor.


Asunto(s)
Antineoplásicos/síntesis química , Polimerizacion/efectos de los fármacos , Moduladores de Tubulina/farmacología , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Células HeLa , Xenoinjertos , Humanos , Ratones , Poli(ADP-Ribosa) Polimerasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Relación Estructura-Actividad , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntesis química
16.
Osteoarthritis Cartilage ; 26(6): 790-796, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29656143

RESUMEN

OBJECTIVE: To investigate changes in bone metabolism by positron emission tomography (PET), as well as spatial relationships between bone metabolism and magnetic resonance imaging (MRI) quantitative markers of early cartilage degradation, in anterior cruciate ligament (ACL)-reconstructed knees. DESIGN: Both knees of 15 participants with unilateral reconstructed ACL tears and unaffected contralateral knees were scanned using a simultaneous 3.0T PET-MRI system following injection of 18F-sodium fluoride (18F-NaF). The maximum pixel standardized uptake value (SUVmax) in the subchondral bone and the average T2 relaxation time in cartilage were measured in each knee in eight knee compartments. We tested differences in SUVmax and cartilage T2 relaxation times between the ACL-injured knee and the contralateral control knee as well as spatial relationships between these bone and cartilage changes. RESULTS: Significantly increased subchondral bone 18F-NaF SUVmax and cartilage T2 times were observed in the ACL-reconstructed knees (median [inter-quartile-range (IQR)]: 5.0 [5.8], 36.8 [3.6] ms) compared to the contralateral knees (median [IQR]: 1.9 [1.4], 34.4 [3.8] ms). A spatial relationship between the two markers was also seen. Using the contralateral knee as a control, we observed a significant correlation of r = 0.59 between the difference in subchondral bone SUVmax (between injured and contralateral knees) and the adjacent cartilage T2 (between the two knees) [P < 0.001], with a slope of 0.49 ms/a.u. This correlation and slope were higher in deep layers (r = 0.73, slope = 0.60 ms/a.u.) of cartilage compared to superficial layers (r = 0.40, slope = 0.43 ms/a.u.). CONCLUSIONS: 18F-NaF PET-MR imaging enables detection of increased subchondral bone metabolism in ACL-reconstructed knees and may serve as an important marker of early osteoarthritis (OA) progression. Spatial relationships observed between early OA changes across bone and cartilage support the need to study whole-joint disease mechanisms in OA.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Cartílago Articular/diagnóstico por imagen , Articulación de la Rodilla/diagnóstico por imagen , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Adulto , Lesiones del Ligamento Cruzado Anterior/cirugía , Reconstrucción del Ligamento Cruzado Anterior , Remodelación Ósea/fisiología , Cartílago Articular/fisiología , Estudios Transversales , Femenino , Humanos , Articulación de la Rodilla/fisiología , Masculino
17.
Artículo en Inglés | MEDLINE | ID: mdl-31501807

RESUMEN

PARP1/2 inhibitors are effective against BRCA2-deficient tumors. The PARP inhibitor (PARPi) olaparib received FDA breakthrough designation for treatment of metastatic castration-resistant prostate cancers (CRPC) carrying mutations in BRCA1/2 or ATM genes. Emergent resistance to PARPi has been associated with tumor-specific BRCA2 mutations that revert the normal open reading frame rescuing homologous recombination. We describe a case of metastatic CRPC with germline BRCA2 mutation with acquired resistance to olaparib related to biallelic BRCA2 reversion mutations of both the germline and somatic loss of function alleles detected by circulating tumor DNA testing. We also summarize a retrospective analysis of 1,534 prostate cancer cases with ctDNA analysis showing a 1.6% incidence of germline BRCA2 mutations. Within the germline BRCA2-positive cases exposed to platinum chemotherapy or PARP inhibition, the prevalence of reversion mutations was 40%. This report documents the frequency of reversion mutations in a large cohort of prostate cancer patients carrying of BRCA mutations. It also shows the potential utility of ctDNA analyses for early detection of reversion mutation driving tumor resistance.

18.
Beijing Da Xue Xue Bao Yi Xue Ban ; 49(3): 388-393, 2017 Jun 18.
Artículo en Chino | MEDLINE | ID: mdl-28628137

RESUMEN

OBJECTIVE: To explore the antagonistic effect of quercetin on fine particulate matter (PM2.5)-induced embryonic developmental toxicity in vitro. METHODS: PM2.5 was collected on glass fiber filters by PM2.5 samplers during the heating period of Dec. 2015 to Mar. 2016 in an area of Haidian District, Beijing City. The sampled filters were cut into 1 cm×3 cm pieces followed by sonication. The PM2.5 suspension was filtered into a 10 cm glass dish through 8 layers of sterile carbasus and stored at -80 °C until freeze drying. Frozen PM2.5 suspension was dried by vacuum freeze-drying. In vitro post-implantation whole embryo culture was used in this study. Pregnant rats with 9.5 gestation days (GD) were killed by cervical dislocation and the uteri were removed into sterile Hank's solution. The embryos with intact yolk sacs and ecto placental cones were induced by PM2.5, and then subjected to intervention of quercetin at the doses of 0.1 µmol/L, 0.5 µmol/L, 1.0 µmol/L and 5.0 µmol/L, respectively. At the end of the 48 h culture period, the cultures were terminated, and all embryos were removed from the culture bottles and placed in prewarmed Hank's solution for evaluation. Morphological evaluation of the embryos was conducted under a stereomicroscope using the morphologic scoring system by Brown and Fabro. The mitochondrial reactive oxygen species (ROS) level was detected by FACSCalibur flow cyto-metry using MitoSOXTM Red staining. RESULTS: An obvious antagonistic effect was achieved through quercetin at the dose of 1.0 µmol/L, which could result in an increase of visceral yolk sac (VYS) diameter, crown-rump length and head length, somite number, and the differentiation of visceral yolk sac vascular vessels. The scores of allantois, flexion, heart, hind brain, midbrain, forebrain, auditory system, visual system, olfactory system, branchialarch, maxillary process, forelimb bud and hindlimb bud also revealed a significant increase and the relative mitochondrial ROS level of embryonic cells was significantly decreased when compared with PM2.5 group. Although quercetin at the doses of 0.1 µmol/L, 0.5 µmol/L, 5.0 µmol/L also exhibited protective effects against PM2.5-induced embryonic developmental toxicity, the protective effect was weaker when compared with the dose of 1.0 µmol/L. CONCLUSION: Quercetin at proper dose may be of great benefit for the development of embryos exposed to PM2.5 in the uterus of the rats. Quercetin provides an effective strategy for the prevention of PM2.5-induced embryonic developmental toxicity. Clearance of mitochondrial ROS may be one of its mechanisms.


Asunto(s)
Antioxidantes/farmacología , Desarrollo Embrionario/efectos de los fármacos , Material Particulado/toxicidad , Quercetina/farmacología , Animales , Beijing , Embrión de Mamíferos , Femenino , Mitocondrias , Embarazo , Ratas , Especies Reactivas de Oxígeno
19.
Eur. j. psychiatry ; 31(2): 73-79, abr.-jun. 2017. tab, graf
Artículo en Inglés | IBECS | ID: ibc-179727

RESUMEN

Background and objectives: Previous studies have identified education as an important indicator of future psychological outcomes through the lens of parental education level. Here, we seek to understand how education affects suicide through the perspective of the child's education. Methods: The current study follows a cohort from the Providence National Collaborative Perinatal Project from birth to adulthood with a follow-up at age 7. Through measures of reading, writing, and IQ administered at follow up, we examine the effects of early childhood education on adult mental health status and suicide attempt. Results: We found that among males, those scoring below 88 on the Wide Range Achievement Test (WRAT) had a suicide attempt rate of 14.4% while those whose scores were above 106 had a suicide attempt rate of 8.8%. In females, the suicide attempt rates for those with WRAT scores below 88 and above 106 were 18.6% and 9.5%, respectively. We also found that females scoring below 89 on measures of Full-Scale IQ had much higher suicide attempt rates (16.6%) than those with higher scores. Conclusions: Our findings suggest that reading and writing, and thus educational attainment at age 7, were predictive risk for suicide attempt in adulthood. Educators, parents, and mental health professionals should be aware of this association and monitor students who perform poorly academically for signs of depression and suicidal ideation, offering the appropriate support when necessary


No disponible


Asunto(s)
Humanos , Masculino , Femenino , Niño , Intento de Suicidio/psicología , Factores de Riesgo , Escalas de Valoración Psiquiátrica , Psicología Educacional/métodos , Pruebas Psicológicas , Estudios de Cohortes , Salud Mental , Disonancia Cognitiva
20.
Zhonghua Yu Fang Yi Xue Za Zhi ; 51(5): 453-456, 2017 May 06.
Artículo en Chino | MEDLINE | ID: mdl-28464600

RESUMEN

Gut microbiota provide enzymes and additional biochemical metabolic pathways for the host, which together with the host genome and the external environment, influence the body function. The composition of gut microbiota in infant is closely related to health in later life. However, it is influenced by many factors, including delivery mode, feeding pattern, prenatal diet, pregnancy psychology and antepartum antibiotic treatment. Vaginal delivery and breastfeeding is beneficial for shaping gut microbiota, while cesarean section and formula feeding would reduce the amount of gut dominant bacteria. In addition, inappropriate diet during pregnancy, prenatal stress and antepartum antibiotic treatment alters bacterial colonization of the gut in infant.


Asunto(s)
Lactancia Materna , Cesárea , Microbioma Gastrointestinal , Bacterias , Parto Obstétrico , Dieta , Femenino , Humanos , Lactante , Embarazo
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