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Background: Genetic factors and microbial imbalances play crucial roles in colorectal cancers (CRCs), yet the impact of infections on cancer initiation remains poorly understood. While bioinformatic approaches offer valuable insights, the rising incidence of CRCs creates a pressing need to precisely identify early CRC events. We constructed a network model to identify continuum states during CRC initiation spanning normal colonic tissue to pre-cancer lesions (adenomatous polyps) and examined the influence of microbes and host genetics. Methods: A Boolean network was built using a publicly available transcriptomic dataset from healthy and adenoma affected patients to identify an invariant Microbe-Associated Colorectal Cancer Signature (MACS). We focused on Fusobacterium nucleatum ( Fn ), a CRC-associated microbe, as a model bacterium. MACS-associated genes and proteins were validated by RT-qPCR, RNA seq, ELISA, IF and IHCs in tissues and colon-derived organoids from genetically predisposed mice ( CPC-APC Min+/- ) and patients (FAP, Lynch Syndrome, PJS, and JPS). Results: The MACS that is upregulated in adenomas consists of four core genes/proteins: CLDN2/Claudin-2 (leakiness), LGR5/leucine-rich repeat-containing receptor (stemness), CEMIP/cell migration-inducing and hyaluronan-binding protein (epithelial-mesenchymal transition) and IL8/Interleukin-8 (inflammation). MACS was induced upon Fn infection, but not in response to infection with other enteric bacteria or probiotics. MACS induction upon Fn infection was higher in CPC-APC Min+/- organoids compared to WT controls. The degree of MACS expression in the patient-derived organoids (PDOs) generally corresponded with the known lifetime risk of CRCs. Conclusions: Computational prediction followed by validation in the organoid-based disease model identified the early events in CRC initiation. MACS reveals that the CRC-associated microbes induce a greater risk in the genetically predisposed hosts, suggesting its potential use for risk prediction and targeted cancer prevention.
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Artificial intelligence (AI) has been an important topic within radiology. Currently, AI is used clinically to assist with the detection of lesions through detection systems. However, a number of recent studies have demonstrated the increased value of neural networks in radiology. With an increasing number of screening requirements for cancers, this review aims to study the accuracy of the numerous AI models used in the detection and diagnosis of breast, lung, and prostate cancers. This study summarizes pertinent findings from reviewed articles and provides analysis on the relevancy to clinical radiology. This study found that whereas AI is showing continual improvement in radiology, AI alone does not surpass the effectiveness of a radiologist. Additionally, it was found that there are multiple variations on how AI should be integrated with a radiologist's workflow.
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BACKGROUND: Standards for reporting surgical adverse events (AEs) vary widely within the scientific literature. Failure to adequately capture AEs hinders efforts to measure the safety of healthcare delivery and improve the quality of care. The aim of the present study is to assess the prevalence and typology of perioperative AE reporting guidelines among surgery and anesthesiology journals. MATERIALS AND METHODS: In November 2021, three independent reviewers queried journal lists from the SCImago Journal & Country Rank (SJR) portal (www.scimagojr.com), a bibliometric indicator database for surgery and anesthesiology academic journals. Journal characteristics were summarized using SCImago, a bibliometric indicator database extracted from Scopus journal data. Quartile 1 (Q1) was considered the top quartile and Q4 bottom quartile based on the journal impact factor. Journal author guidelines were collected to determine whether AE reporting recommendations were included and, if so, the preferred reporting procedures. RESULTS: Of 1409 journals queried, 655 (46.5%) recommended surgical AE reporting. Journals most likely to recommend AE reporting were: by category surgery (59.1%), urology (53.3%), and anesthesia (52.3%); in top SJR quartiles (i.e. more influential); by region, based in Western Europe (49.8%), North America (49.3%), and the Middle East (48.3%). CONCLUSIONS: Surgery and anesthesiology journals do not consistently require or provide recommendations on perioperative AE reporting. Journal guidelines regarding AE reporting should be standardized and are needed to improve the quality of surgical AE reporting with the ultimate goal of improving patient morbidity and mortality.
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Anestesiología , Humanos , Bibliometría , Factor de Impacto de la Revista , Europa (Continente) , Medio OrienteRESUMEN
PURPOSE: This study aimed to characterise recovery from pain and mental health symptoms, and identify whether treatment use facilitates recovery. METHODS: Victorian State Trauma Registry and Victorian Orthopaedic Trauma Outcomes Registry participants without neurotrauma who had transport injury claims with the Transport Accident Commission from 2007 to 2014 were included (n = 5908). Latent transition analysis of pain Numeric Rating Scale, SF-12, and EQ-5D-3L pain and mental health items from 6 to 12 months, and 12 to 24 months post-injury were used to identify symptom transitions. RESULTS: Four transition groups were identified: transition to low problems by 12-months; transition to low problems at 24-months; stable low problems; and no transition from problems. Group-based trajectory modelling of pain and mental health treatments found three treatment trajectories: low/no treatment, a moderate treatment that declined to low treatment 3-12 months post-injury, and increasing treatment over time. Predictors of pain and mental health recovery transitions, identified using multinomial logistic regression, were primarily found to be non-modifiable socioeconomic and health-related characteristics (e.g., higher education, working pre-injury, and not having comorbidities), and low treatment trajectories. CONCLUSIONS: Targeted and collaborative rehabilitation should be considered for people at risk of persistent pain or mental health symptoms to optimise their recovery, particularly patients with socioeconomic disadvantage.IMPLICATIONS FOR REHABILITATIONTwo-thirds of people experience pain and/or mental health within the first 24-months after hospitalization for road trauma, of whom only 6-7% recover by 12-months, and a further 6% recover by 24-months post-injury.There were three main trajectories of administrative records of treatments received in the first two years after injury: 76 and 83% had low treatment, 18 and 12% had moderate then declining treatment levels, and 6 and 5% had stable high treatment for pain or mental health, respectively.People who recovered from pain or mental health symptoms generally had lower treatment and higher socioeconomic position, highlighting that coordinated rehabilitation care should be prioritized for people living with socioeconomic disadvantage.
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Trastornos Mentales , Salud Mental , Humanos , Estudios de Cohortes , Dolor/epidemiología , Dolor/etiología , Dolor/psicología , Trastornos Mentales/epidemiología , Trastornos Mentales/terapia , Sistema de RegistrosRESUMEN
Magnetic resonance imaging (MRI) guided robotic procedures require safe robotic instrument navigation and precise target localization. This depends on reliable tracking of the instrument from MR images, which requires accurate registration of the robot to the scanner. A novel differential image based robot-to-MRI scanner registration approach is proposed that utilizes a set of active fiducial coils, where background subtraction method is employed for coil detection. In order to use the presented preoperative registration approach jointly with the real-time high speed MRI image acquisition and reconstruction methods in real-time interventional procedures, the effects of the geometric MRI distortion in robot to scanner registration is analyzed using a custom distortion mapping algorithm. The proposed approach is validated by a set of target coils placed within the workspace, employing multi-planar capabilities of the scanner. Registration and validation errors are respectively 2.05 mm and 2.63 mm after the distortion correction showing an improvement of respectively 1.08 mm and 0.14 mm compared to the results without distortion correction.
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Magnetic resonance fingerprinting (MRF) is a method to extract quantitative tissue properties such as [Formula: see text] and [Formula: see text] relaxation rates from arbitrary pulse sequences using conventional MRI hardware. MRF pulse sequences have thousands of tunable parameters, which can be chosen to maximize precision and minimize scan time. Here, we perform de novo automated design of MRF pulse sequences by applying physics-inspired optimization heuristics. Our experimental data suggest that systematic errors dominate over random errors in MRF scans under clinically relevant conditions of high undersampling. Thus, in contrast to prior optimization efforts, which focused on statistical error models, we use a cost function based on explicit first-principles simulation of systematic errors arising from Fourier undersampling and phase variation. The resulting pulse sequences display features qualitatively different from previously used MRF pulse sequences and achieve fourfold shorter scan time than prior human-designed sequences of equivalent precision in [Formula: see text] and [Formula: see text] Furthermore, the optimization algorithm has discovered the existence of MRF pulse sequences with intrinsic robustness against shading artifacts due to phase variation.
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Imagen por Resonancia Magnética/métodos , Algoritmos , Automatización , Encéfalo/diagnóstico por imagen , Simulación por Computador , Epilepsia/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Neoplasias/diagnóstico por imagen , Fantasmas de ImagenRESUMEN
BACKGROUND: Quantitative T1 and T2 mapping in the abdomen provides valuable information in tissue characterization but is technically challenging due to respiratory motions. The proposed technique integrates magnetic resonance fingerprinting (MRF) and pilot tone (PT) navigator with retrospective gating to provide simultaneous quantification of multiple tissue properties in a single acquisition without breath-holding or patient set-up. PURPOSE: To develop a free-breathing abdominal MRF technique for quantitative mapping in the abdomen. STUDY TYPE: Prospective. POPULATION: Twelve healthy volunteers. FIELD STRENGTH/SEQUENCE: A 3 T, two-dimensional (2D) and three-dimensional (3D) spiral MRF sequence with fast imaging with steady-state free precession (FISP) readout. ASSESSMENT: The PT navigator was compared to standard respiratory belt performance. The T1 and T2 values acquired using 2D and 3D MRF with and without PT were obtained in a phantom and compared to reference values. Digital phantom simulation was performed to evaluate PT MRF reconstruction with varying breathing patterns. In the in vivo studies, T1 and T2 values derived from PT 2D MRF were compared to 2D breath-hold MRF. T1 and T2 values derived from PT 3D MRF were compared to published values. STATISTICAL TESTS: Principal component analysis (PCA), linear regression, relative error, Pearson correlation, paired Student's t-test, Bland-Altman Analysis. RESULTS: The phantom study showed PT MRF T1 values had a mean difference of 0.2% ± 0.1%, and T2 values had a mean difference of 0.1% ± 0.4% when compared to no-PT MRF values. The digital phantom experiment suggested the T1 and T2 maps at both end-exhalation and end-inhalation states resemble the corresponding ground-truth maps. DATA CONCLUSION: The phantom study showed good agreement between MRF T1 and T2 values and with reference values. In vivo studies demonstrated that 2D and 3D quantitative imaging in the abdomen could be achieved with integration of PT navigation with MRF reconstruction using retrospective gating of respiratory motion. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.
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Contencion de la Respiración , Imagen por Resonancia Magnética , Abdomen/diagnóstico por imagen , Humanos , Procesamiento de Imagen Asistido por Computador , Espectroscopía de Resonancia Magnética , Fantasmas de Imagen , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
OBJECTIVES: There are limited data on the natural history of chronic hepatitis B virus (HBV) infection in Asian American children. The aim of the present study was to describe a single-center experience of chronic HBV infection in Chinese American patients in New York City. METHODS: A retrospective chart review was conducted for patients with chronic HBV infection who had pediatric visits from 2006 to 2017. Clinical and laboratory data were collected to characterize the status of HBV infection and its disease course both cross-sectionally and longitudinally. Available maternal charts were reviewed. RESULTS: Of the total 353 patients, 72 patients (20%) were US-born. Positive hepatitis B envelope antigen (HBeAg) was documented in 208 patients (58%). Three phases of chronic HBV infection were categorized for 329 patients: immune-tolerant 112 (34%), HBeAg-positive immune-active 47 (14%), and inactive carrier 82 (25%). The remaining 88 patients (27%) did not fit into a particular category with 26 of 88 patients meeting the criteria for inactive carrier except for mildly elevated alanine aminotransferase. Age and liver enzyme levels were significantly different between HBeAg-positive and HBeAg-negative groups (Pâ<â0.05). Among 179 patients followed for ≥5âyears, the spontaneous seroconversion rate was 38%. In eight patients with linked maternal data, all children completed the HBV vaccine series and seven of eight received hepatitis B immunoglobulin. All mothers were HBeAg-positive with high HBV DNA and had no anti-viral therapy during pregnancy. CONCLUSIONS: Both immune-tolerant and inactive carrier phases were common for chronic HBV infection with a spontaneous seroconversion rate of 38%. All US-born patients were born in the era of implemented universal immune-prophylaxis.
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Hepatitis B Crónica , Hepatitis B , Niño , China/epidemiología , Femenino , Antígenos e de la Hepatitis B , Hepatitis B Crónica/epidemiología , Humanos , Embarazo , Estudios Retrospectivos , Adulto JovenRESUMEN
The goal of this study was to evaluate the accuracy, reproducibility, and efficiency of a 31 P magnetic resonance spectroscopic fingerprinting (31 P-MRSF) method for fast quantification of the forward rate constant of creatine kinase (CK) in mouse hindlimb. The 31 P-MRSF method acquired spectroscopic fingerprints using interleaved acquisition of phosphocreatine (PCr) and γATP with ramped flip angles and a saturation scheme sensitive to chemical exchange between PCr and γATP. Parameter estimation was performed by matching the acquired fingerprints to a dictionary of simulated fingerprints generated from the Bloch-McConnell model. The accuracy of 31 P-MRSF measurements was compared with the magnetization transfer (MT-MRS) method in mouse hindlimb at 9.4 T (n = 8). The reproducibility of 31 P-MRSF was also assessed by repeated measurements. Estimation of the CK rate constant using 31 P-MRSF (0.39 ± 0.03 s-1 ) showed a strong agreement with that using MT-MRS measurements (0.40 ± 0.05 s-1 ). Variations less than 10% were achieved with 2 min acquisition of 31 P-MRSF data. Application of the 31 P-MRSF method to mice subjected to an electrical stimulation protocol detected an increase in CK rate constant in response to stimulation-induced muscle contraction. These results demonstrated the potential of the 31 P-MRSF framework for rapid, accurate, and reproducible quantification of the chemical exchange rate of CK in vivo.
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Forma MM de la Creatina-Quinasa/metabolismo , Miembro Posterior/diagnóstico por imagen , Proteínas Musculares/metabolismo , Resonancia Magnética Nuclear Biomolecular/métodos , Adenosina Trifosfato/metabolismo , Animales , Miembro Posterior/enzimología , Concentración de Iones de Hidrógeno , Cinética , Masculino , Ratones Endogámicos C57BL , Fósforo , Reproducibilidad de los ResultadosRESUMEN
OBJECTIVE: To enable non-invasive dynamic metabolic mapping in rodent model studies of mitochondrial function using 31P-MR spectroscopic imaging (MRSI). METHODS: We developed a novel method for high-resolution dynamic 31P-MRSI. The method synergistically integrates physics-based models of spectral structures, biochemical modeling of molecular dynamics, and subspace learning to capture spatiospectral variations. Fast data acquisition was achieved using rapid spiral trajectories and sparse sampling of (k, t, T)-space; image reconstruction was accomplished using a low-rank tensor-based framework. RESULTS: The proposed method provided high-resolution dynamic metabolic mapping in rat hindlimb at spatial and temporal resolutions of 4[Formula: see text]2 mm3 and 1.28 s, respectively. This allowed for in vivo mapping of the time-constant of phosphocreatine resynthesis, a well established index of mitochondrial oxidative capacity. Multiple rounds of in vivo experiments were performed to demonstrate reproducibility, and in vitro experiments were used to validate the accuracy of the estimated metabolite maps. CONCLUSIONS: A new model-based method is proposed to achieve high-resolution dynamic 31P-MRSI. The proposed method's ability to delineate metabolic heterogeneity was demonstrated in rat hindlimb. SIGNIFICANCE: Abnormal mitochondrial metabolism is a key cellular dysfunction in many prevalent diseases such as diabetes and heart disease; however, current understanding of mitochondrial function is mostly gained from studies on isolated mitochondria under nonphysiological conditions. The proposed method has the potential to open new avenues of research by allowing in vivo and longitudinal studies of mitochondrial dysfunction in disease development and progression.
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Algoritmos , Encéfalo , Animales , Encéfalo/metabolismo , Imagen por Resonancia Magnética , Mitocondrias , Ratas , Reproducibilidad de los ResultadosRESUMEN
In magnetic resonance imaging (MRI) guided robotic catheter ablation procedures, reliable tracking of the catheter within the MRI scanner is needed to safely navigate the catheter. This requires accurate registration of the catheter to the scanner. This paper presents a differential, multi-slice image-based registration approach utilizing active fiducial coils. The proposed method would be used to preoperatively register the MRI image space with the physical catheter space. In the proposed scheme, the registration is performed with the help of a registration frame, which has a set of embedded electromagnetic coils designed to actively create MRI image artifacts. These coils are detected in the MRI scanner's coordinate system by background subtraction. The detected coil locations in each slice are weighted by the artifact size and then registered to known ground truth coil locations in the catheter's coordinate system via least-squares fitting. The proposed approach is validated by using a set of target coils placed withing the workspace, employing multi-planar capabilities of the MRI scanner. The average registration and validation errors are respectively computed as 1.97 mm and 2.49 mm. The multi-slice approach is also compared to the single-slice method and shown to improve registration and validation by respectively 0.45 mm and 0.66 mm.
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Constitutional (Biallelic) Mismatch Repair Deficiency is a rare autosomal recessive disorder characterized by numerous cancers presenting as early as the first decade of life. Biallelic germline variants in one of four mismatch repair genes (MLH1, MSH2, MSH6, or PMS2) cause this devastating disease. Given the rarity of the syndrome, often-asymptomatic tumors, and overlap with neurofibromatosis-1, diagnosis is frequently unrecognized or delayed. We present a unique case of a 14-year-old female with minimal gastrointestinal symptoms diagnosed with invasive adenocarcinoma secondary to biallelic PMS2 variants.
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Colorectal cancer is a rare disease in the pediatric age group and, when present, suggests an underlying genetic predisposition. The most common hereditary colon cancer susceptibility condition, Lynch syndrome (LS), previously known as hereditary nonpolyposis colorectal cancer, is an autosomal dominant condition caused by a germline mutation in 1 of 4 DNA mismatch repair (MMR) genes: MLH1, MSH2, MSH6, or PMS2. The mutation-prone phenotype of this disorder is associated with gastrointestinal, endometrial, and other cancers and is now being identified in both symptomatic adolescents with malignancy as well in asymptomatic mutation carriers who are at risk for a spectrum of gastrointestinal and other cancers later in life. We review the DNA MMR system, our present understanding of LS in the pediatric population, and discuss the newly identified biallelic form of the disease known as constitutional mismatch repair deficiency syndrome. Both family history and tumor characteristics can help to identify patients who should undergo genetic testing for these cancer predisposition syndromes. Patients who carry either single allele (LS) or double allele (constitutional mismatch repair deficiency syndrome) mutations in the MMR genes benefit from cancer surveillance programs that target both the digestive and extraintestinal cancer risk of these diseases. Because spontaneous mutation in any one of the MMR genes is extremely rare, genetic counseling and testing are suggested for all at-risk family members.
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Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Reparación de la Incompatibilidad de ADN/genética , Pediatría , Alelos , Neoplasias Colorrectales/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/patología , Mutación de Línea Germinal , HumanosRESUMEN
Typical photoluminescent semiconductor nanoparticles, called quantum dots (QDs), have potential applications in biological labeling. When used to label stem cells, QDs may impair the differentiation capacity of the stem cells. In this study, we synthesized zinc oxide (ZnO) QDs in methanol with an average size of â¼2 nm. We then employed two different types of polyethylene glycol (PEG) molecules (SH-PEG-NH2 and NH2-PEG-NH2) to conjugate ZnO QDs and made them water-dispersible. Fourier transform infrared spectroscopy spectra indicated the attachment of PEG molecules on ZnO QDs. No obvious size alteration was observed for ZnO QDs after PEG conjugation. The water-dispersible ZnO QDs still retained the antibacterial activity and fluorescence intensity. The cytotoxicity evaluation revealed that ZnO QDs at higher concentrations decreased cell viability but were generally safe at 30 ppm or below. Cell lines of hepatocytes (HepG2), osteoblasts (MC3T3-E1) and mesenchymal stem cells (MSCs) were successfully labeled by the water-dispersible ZnO QDs at 30 ppm. The ZnO QD-labeled MSCs maintained their stemness and differentiation capacity. Therefore, we conclude that the water-dispersible ZnO QDs developed in this study have antibacterial activity, low cytotoxicity, and proper labeling efficiency, and can be used to label a variety of cells including stem cells.
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Antibacterianos/síntesis química , Antibacterianos/farmacología , Puntos Cuánticos/toxicidad , Coloración y Etiquetado , Agua/química , Óxido de Zinc/síntesis química , Tejido Adiposo/citología , Células Madre Adultas/citología , Células Madre Adultas/efectos de los fármacos , Animales , Antibacterianos/química , Muerte Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Metabolismo Energético/efectos de los fármacos , Resinas Epoxi/síntesis química , Resinas Epoxi/química , Escherichia coli/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Humanos , Hidrodinámica , Ratones , Pruebas de Sensibilidad Microbiana , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Anhídridos Ftálicos/síntesis química , Anhídridos Ftálicos/química , Puntos Cuánticos/química , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Electricidad Estática , Óxido de Zinc/químicaRESUMEN
Ultrasmall water-soluble silver nanoclusters are synthesized, and their properties are investigated. The silver nanoclusters have high colloidal stability and show fluorescence in the red. This demonstrates that like gold nanoclusters also silver nanoclusters can be fluorescent.
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Fluorescencia , Nanopartículas del Metal/química , Plata/química , Coloides/síntesis química , Coloides/química , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
PURPOSE: The present study was designed to address whether osteoblasts play a synergistic role in promoting mesenchymal stem cell (MSC) osteogenesis in a direct cell-cell contact co-culture model. METHODS: Murine C3H10T1/2 and MC3T3-E1 cell lines were mixed and plated onto 12-well culture plates and co-cultured at various ratios of initial cell densities. To compare the possible improvement on osteogenic differentiation, co-culture cells were served with or without osteogenic supplements in culture medium. RESULTS: Weak osteogenesis was induced in MSCs co-cultured in an untreated medium with different ratios of osteoblasts. An osteoblast-dependent increase in osteogenic gene expression of Runx2, type I collagen, and osteocalcin was observed over time. Moreover, both alkaline phosphatase (ALP) activity and calcium deposition were distinctly enhanced at levels that were proportional to the quantity of osteoblasts in the culture. The increases in mRNA expression and ALP activity were greater in co-cultures treated with osteogenic supplements than in untreated cultures. However, the production of ALP activity followed by a distinct matrix mineralization was lower in osteogenic-treated cultures containing greater numbers of osteoblasts. This suggests that a higher density of osteoblasts may lead to weak osteogenesis of MSCs by direct cell-cell contact co-culture in an untreated environment. Furthermore, additional osteogenic supplements may act synergistically with osteoblasts to accelerate matrix mineralization by reducing the process of osteogenic differentiation in osteogenic treated co-cultures. CONCLUSIONS: The present work may improve the understanding of MSC osteogenesis and may provide benefits for regenerative medicine.
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Comunicación Celular/fisiología , Diferenciación Celular/fisiología , Células Madre Mesenquimatosas/citología , Osteoblastos/citología , Osteogénesis/fisiología , Células 3T3 , Fosfatasa Alcalina/metabolismo , Animales , Calcio/metabolismo , Técnicas de Cocultivo , Expresión Génica , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos C3H , Osteoblastos/metabolismoRESUMEN
BACKGROUND: San-Huang-Xie-Xin-Tang (SHXXT) decoction, a traditional Chinese medicine containing Rhei rhizome, Coptidis rhizome, and Scutellariae radix, is widely used in hepatoprotective therapy. However, preparation of the decoction requires addition of boiling water that causes loss of numerous effective components. METHODS: To improve the bioavailability of the decoction, nanoscale SHXXT was developed. Chloroform-induced liver injury and hepatic stellate cell activity in mice were used to demonstrate the hepatoprotective characteristics of nanoscale SHXXT decoction. RESULTS: Liver/body weight ratio and serum aspartate and alanine aminotranferase levels were recovered by the nanoscale SHXXT. TIMP-1 gene expression was inhibited and MMP-2 gene expression was accelerated in activated hepatic stellate cells. CONCLUSION: Nanoscale SHXXT decoction prepared in room temperature water could have preserved hepatoprotective ability. The results of this study indicate that nanoscale SHXXT could be extracted easily. The simple preparation of this herbal decoction is more convenient and energy-efficient.
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Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Células Estrelladas Hepáticas/efectos de los fármacos , Nanopartículas/química , Sustancias Protectoras/farmacología , Animales , Peso Corporal/efectos de los fármacos , Cloroformo/efectos adversos , Sistemas de Liberación de Medicamentos , Medicamentos Herbarios Chinos/química , Femenino , Histocitoquímica , Hígado/efectos de los fármacos , Hígado/patología , Cirrosis Hepática/tratamiento farmacológico , Metaloproteinasa 2 de la Matriz/metabolismo , Ratones , Ratones Endogámicos ICR , Nanopartículas/ultraestructura , Nanotecnología , Tamaño de los Órganos/efectos de los fármacos , Tamaño de la Partícula , Sustancias Protectoras/química , Inhibidor Tisular de Metaloproteinasa-1/metabolismoRESUMEN
BACKGROUND: Patients with hamartomatous polyposis syndromes have increased risk for colorectal cancer (CRC). Although progression of polyps to carcinoma is observed, pathogenic mechanisms remain unknown. The authors examined whether familial hamartomatous polyps harbor defects in DNA mismatch repair (MMR), and assayed for somatic mutation of PTEN, a gene inactivated in the germline of some hamartomatous polyposis syndrome patients. METHODS: Ten hamartomatous polyposis syndrome patients were genotyped for germline mutations. Epithelial and nonepithelial polyp DNA were assayed for microsatellite instability (MSI) and PTEN frameshift mutation. DNA MMR and PTEN protein expression were assessed in all polyps by immunohistochemistry. In addition, 99 MSI-high sporadic CRCs and 50 each of hMLH1(-/-) and hMSH3(-/-) cell clones were examined for PTEN frameshifts. RESULTS: Twenty-five (58%) of 43 hamartomatous polyposis syndrome polyps demonstrated dinucleotide or greater MSI in polyp epithelium, consistent with hMSH3 deficiency. MSI domains lost hMSH3 expression, and PTEN expression was lost in polyps from germline PTEN patients; sporadic hamartomatous polyps did not show any of these findings. PTEN analysis revealed wild type exon 7 and 8 sequences suggestive of nonexistent or rare events for PTEN frameshifts; however, MSI-high sporadic CRC showed 11 (11%) of 99 frameshifts within PTEN, with 4 tumors having complete loss of PTEN expression. Subcloning hMLH1(-/-) and hMSH3(-/-) cells revealed somatic PTEN frameshifts in 4% and 12% of clones, respectively. CONCLUSIONS: Nondysplastic epithelium from hamartomatous polyposis syndrome polyps harbors hMSH3 defects, which may prime neoplastic transformation. Polyps from PTEN(+/-) patients lose PTEN expression, but loss is not a universal early feature of all hamartomatous polyposis syndrome. However, PTEN frameshifts can occur in hMSH3-deficient cells, suggesting that hMSH3 deficiency could drive hamartomatous polyposis syndrome tumorigenesis.
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Proteínas de Unión al ADN/genética , Fosfohidrolasa PTEN/genética , Síndrome de Peutz-Jeghers/genética , Adolescente , Adulto , Línea Celular Tumoral , Niño , Preescolar , Neoplasias Colorrectales/genética , Eliminación de Gen , Inestabilidad Genómica , Humanos , Proteína 3 Homóloga de MutSRESUMEN
Familial adenomatous polyposis [FAP (OMIM 175100)] is an autosomal dominant colorectal cancer predisposition syndrome characterized by hundreds to thousands of colonic polyps and, if untreated by a combination of screening and/or surgical intervention, an approximately 99% lifetime risk of colorectal cancer. A subset of FAP patients develop an attenuated form of the condition characterized by lower numbers of colonic polyps (highly variable, but generally less than 100) and a lower lifetime risk of colorectal cancer, on the order of 70%. We report the diagnosis of three attenuated FAP families due to a 1.4-kb deletion within intron 14 of APC, originally reported clinically as a variant of unknown significance (VUS). Sequence analysis suggests that this arose through an Alu-mediated recombination event with a locus on chromosome 6q22.1. This mutation is inherited by family members who presented with an attenuated FAP phenotype, with variable age of onset and severity. Sequence analysis of mRNA revealed an increase in the level of aberrant splicing of exon 14, resulting in the generation of an exon 13-exon 15 splice-form that is predicted to lead to a frameshift and protein truncation at codon 673. The relatively mild phenotypic presentation and the intra-familial variation are consistent with the leaky nature of exon 14 splicing in normal APC. The inferred founder of these three families may account for as yet undetected affected branches of this kindred. This and similar types of intronic mutations may account for a significant proportion of FAP cases where APC clinical analysis fails because of the current limitations of testing options.
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Poliposis Adenomatosa del Colon/diagnóstico , Poliposis Adenomatosa del Colon/genética , Empalme Alternativo/genética , Genes APC , Intrones/genética , Polimorfismo Genético , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Femenino , Eliminación de Gen , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Linaje , Polimorfismo Genético/fisiología , Sitios de Empalme de ARN/genética , Adulto JovenRESUMEN
Taking calcium supplements can reduce the risk of developing osteoporosis, but they are not readily absorbed in the gastrointestinal tract. Nanotechnology is expected to resolve this problem. In the present study, we examined whether the bioavailability of calcium carbonate and calcium citrate can be improved by reducing the particle size. The morphology of nano calcium carbonate and nano calcium citrate was characterized by dynamic laser-light scattering (DLS), field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The measurements obtained from DLS, FE-SEM and TEM were comparable. Acute and sub-chronic toxicity tests were performed to establish the safety of these products after oral administration. The no-observed-adverse-effect levels of nano calcium carbonate and nano calcium citrate were 1.3 and 2.3 g kg(-1) body weight, respectively. The results of our in vivo studies indicate that administering nano calcium carbonate and nano calcium citrate can enhance the serum calcium concentration and maintain the whole-body bone mineral density in ovariectomized mice. These data suggest that nano calcium carbonate and nano calcium citrate are more bioavailable than micro calcium carbonate and micro calcium citrate, respectively.