Bone marrow-derived stem cells (BMSCs) are locally adjacent to the tumor tissues and may interact with tumor cells directly. The purpose of this study was to explore the effects of BMSCs on the proliferation and invasion of osteosarcoma cells in vitro and the possible mechanism involved.
BMSCs were co-cultured with osteosarcoma cells, and CCK-8 assay was used to measure cell proliferation. The ELISA method was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. Reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the expression of CXCR4 in osteosarcoma cells and BMSCs. Matrigel invasion assay was performed to measure tumor cell invasion.
SDF-1 was detected in the supernatants of BMSCs, but not in osteosarcoma cells. Higher CXCR4 mRNA levels were detected in the osteosarcoma cell lines compared to BMSCs. In addition, conditioned medium from BMSCs can promote the proliferation and invasion of osteosarcoma cells, and AMD3100, an antagonist for CXCR4, can significantly downregulate these growth-promoting effects.
BMSCs can promote the proliferation and invasion of osteosarcoma cells, which may involve the SDF-1/CXCR4 axis.
Bone marrow mesenchymal stem cells; Osteosarcoma
Frequency-dependent electrical properties (EPs; conductivity and permittivity) of biological tissues provide important diagnostic information (e.g. tumor characterization), and also play an important role in quantifying radiofrequency (RF) coil induced Specific Absorption Rate (SAR) which is a major safety concern in high- and ultrahigh-field Magnetic Resonance Imaging (MRI) applications. Cross-sectional imaging of EPs has been pursued for decades. Recently introduced Electrical Properties Tomography (EPT) approaches utilize the measurable RF magnetic field induced by the RF coil in an MRI system to quantitatively reconstruct the EP distribution in vivo and non-invasively with a spatial resolution of a few millimeters or less. This paper reviews the Electrical Properties Tomography approach from its basic theory in electromagnetism to the state of the art research outcomes. Emphasizing on the imaging reconstruction methods rather than experimentation techniques, we review the developed imaging algorithms, validation results in physical phantoms and biological tissues, as well as their applications in in vivo tumor detection and subject-specific SAR prediction. Challenges for future research are also discussed.
Electrical Properties Tomography; EPT; Bioimepdance; Magnetic Resonance Imaging; B1-mapping; SAR
Intercellular adhesion molecule-1 (ICAM-1) K469E polymorphism has been implicated in susceptibility to coronary artery disease (CAD). Several studies investigated the association of this polymorphism with CAD in different populations but the results were contradictory. A meta-analysis was conducted to assess the association between ICAM-1 K469E polymorphism and CAD susceptibility.
Databases including PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. A random-effects model was used.
Fifteen case-control studies including 3088 cases and 3466 controls were included. Overall, a significant association between ICAM-1 K469E polymorphism and CAD was observed in the dominant model (OR=1.80; 95% CI 1.62–2.01; P<0.00001; Pheterogeneity=0.40). In subgroup analysis by ethnicity, a significant association was found among Asians (OR=1.92; 95% CI 1.51–2.43; P<0.00001; Pheterogeneity=0.98) and among Caucasians (OR=1.64; 95% CI 1.30–2.08; P<0.0001; Pheterogeneity=0.04). In the subgroup analysis by age, a significant association was found among young patients (OR=1.46; 95% CI 1.10–1.93; P=0.008; Pheterogeneity=0.21) and old patients (OR=1.92; 95% CI 1.75–2.10; P<0.00001; Pheterogeneity=0.99).
Results of this meta-analysis suggest that ICAM-1 K469E polymorphism confers a risk factor of CAD.
Coronary Artery Disease; Intercellular Adhesion Molecule-1; Meta-Analysis; Polymorphism, Single Nucleotide
We compared transcriptomes of terminally differentiated mouse 3T3-L1 and human adipocytes to identify cell-specific differences. Gene expression and high content analysis (HCA) data identified the androgen receptor (AR) as both expressed and functional, exclusively during early human adipocyte differentiation. The AR agonist dihydrotestosterone (DHT) inhibited human adipocyte maturation by downregulation of adipocyte marker genes, but not in 3T3-L1. Interestingly, AR induction corresponded with dexamethasone activation of the glucocorticoid receptor (GR); however, when exposed to the differentiation cocktail required for adipocyte maturation, AR adopted an antagonist conformation and was transcriptionally repressed. To further explore effectors within the cocktail, we applied a novel, image-based support vector machine (SVM) classification scheme to show adipocyte differentiation components inhibit AR action. The results demonstrate human adipocyte differentiation, via GR activation, upregulates AR but also inhibits AR transcriptional activity.
Human enterovirus 68 (EV68) is a member of the EV-D species, which belongs to the EV genus of the Picornaviridae family. Over the past several years, there have been increasingly documented outbreaks of respiratory disease associated with EV68. As a globally emerging pathogen, EV68 infects both adults and children. However, the molecular basis of EV68 pathogenesis is unknown. Here we report that EV68 inhibits Toll-like receptor 3 (TLR3)-mediated innate immune responses by targeting the TIR domain-containing adaptor inducing beta interferon (TRIF). In infected HeLa cells, EV68 inhibits poly(I·C)-induced interferon regulatory factor 3 (IRF3) activation and beta interferon (IFN-β) expression. Further investigations revealed that TRIF, a critical adaptor downstream of TLR3, is targeted by EV68. When expressed alone, 3Cpro, an EV68-encoded protease, cleaves TRIF. 3Cpro mediates TRIF cleavage at Q312 and Q653, which are sites in the amino- and carboxyl-terminal domains, respectively. This cleavage relies on 3Cpro's cysteine protease activity. Cleavage of TRIF abolishes the capacity of TRIF to activate NF-κB and IFN-β signaling. These results suggest that control of TRIF by 3Cpro may be a mechanism by which EV68 subverts host innate immune responses.
IMPORTANCE EV68 is a globally emerging pathogen, but the molecular basis of EV68 pathogenesis is unclear. Here we report that EV68 inhibits TLR3-mediated innate immune responses by targeting TRIF. Further investigations revealed that TRIF is cleaved by 3Cpro. These results suggest that control of TRIF by 3Cpro may be a mechanism by which EV68 impairs type I IFN production in response to TLR3 activation.
Maternal malnutrition during pregnancy may give rise to female offspring with disrupted ovary functions in adult age. Neonatal ovary development predisposes adult ovary function, yet the effect of maternal nutrition on the neonatal ovary has not been described. Therefore, here we show the impact of maternal protein restriction on the expression of folliculogenic and steroidogenic genes, their regulatory microRNAs and promoter DNA methylation in the ovary of neonatal piglets. Sows were fed either standard-protein (SP, 15% crude protein) or low-protein (LP, 7.5% crude protein) diets throughout gestation. Female piglets born to LP sows showed significantly decreased ovary weight relative to body weight (p<0.05) at birth, which was accompanied with an increased serum estradiol level (p<0.05). The LP piglets demonstrated higher ratio of bcl-2 associated X protein/B cell lymphoma/leukemia-2 mRNA (p<0.01), which was associated with up-regulated mRNA expression of bone morphogenic protein 4 (BMP4) (p<0.05) and proliferating cell nuclear antigen (PCNA) (p<0.05). The steroidogenic gene, cytochrome P450 aromatase (CYP19A1) was significantly down-regulated (p<0.05) in LP piglets. The alterations in ovarian gene expression were associated with a significant down-regulation of follicle-stimulating hormone receptor mRNA expression (p<0.05) in LP piglets. Moreover, three microRNAs, including miR-423-5p targeting both CYP19A1 and PCNA, miR-378 targeting CYP19A1 and miR-210 targeting BMP4, were significantly down-regulated (p<0.05) in the ovary of LP piglets. These results suggest that microRNAs are involved in mediating the effect of maternal protein restriction on ovarian function through regulating the expression of folliculogenic and steroidogenic genes in newborn piglets.
Folliculogenesis; Steroidogenesis; Maternal Dietary Protein; MicroRNA; Ovary; Neonatal Piglet
With the advance of next generation sequencing (NGS) technologies, a large number of insertion and deletion (indel) variants have been identified in human populations. Despite much research into variant calling, it has been found that a non-negligible proportion of the identified indel variants might be false positives due to sequencing errors, artifacts caused by ambiguous alignments, and annotation errors.
In this paper, we examine indel redundancy in dbSNP, one of the central databases for indel variants, and develop a standalone computational pipeline, dubbed Vindel, to detect redundant indels. The pipeline first applies indel position information to form candidate redundant groups, then performs indel mutations to the reference genome to generate corresponding indel variant substrings. Finally the indel variant substrings in the same candidate redundant groups are compared in a pairwise fashion to identify redundant indels. We applied our pipeline to check for redundancy in the human indels in dbSNP. Our pipeline identified approximately 8% redundancy in insertion type indels, 12% in deletion type indels, and overall 10% for insertions and deletions combined. These numbers are largely consistent across all human autosomes. We also investigated indel size distribution and adjacent indel distance distribution for a better understanding of the mechanisms generating indel variants.
Vindel, a simple yet effective computational pipeline, can be used to check whether a set of indels are redundant with respect to those already in the database of interest such as NCBI’s dbSNP. Of the approximately 5.9 million indels we examined, nearly 0.6 million are redundant, revealing a serious limitation in the current indel annotation. Statistics results prove the consistency of the pipeline on indel redundancy detection for all 22 chromosomes. Apart from the standalone Vindel pipeline, the indel redundancy check algorithm is also implemented in the web server http://bioinformatics.cs.vt.edu/zhanglab/indelRedundant.php.
Electronic supplementary material
The online version of this article (doi:10.1186/s12859-014-0359-1) contains supplementary material, which is available to authorized users.
Indel redundancy; Gap opening; Gap extension
Although the etiology of intervertebral disc degeneration is poorly understood, one approach to prevent this process may be to inhibit apoptosis. In the current study, the anti-apoptotic effects of carboxymethylated chitosan (CMCS) in nucleus pulposus (NP) cells were investigated with the aim to enhance disc cell survival. Rat NP cells were isolated and cultured in vitro, and hydrogen peroxide (H2O2) was used to build the NP cell apoptosis model. Cell viability was assessed with a cell counting kit-8 assay. The ratio of apoptotic cells was surveyed by annexin V-fluorescein isothiocyanate (FITC) and propidium iodide (PI) double staining analysis, and the morphology was observed by Hoechst 33342 staining. The mitochondrial membrane potential of NP cells was evaluated by rhodamine 123 fluorescence staining. Reverse transcription (RT)-quantitative polymerase chain reaction (qPCR) was performed to measure mRNA levels of inducible nitric oxide synthase (iNOS), caspase-3, B-cell lymphoma (Bcl)-2, type II collagen and aggrecan. Western blot analysis was performed to detect protein levels of iNOS and Bcl-2. The annexin V-FITC/PI and Hoechst 33342 staining results indicated that CMCS was able to prevent NP cells from apoptosis in a dose-dependent manner. Rhodamine 123 staining clarified that CMCS reduced the impairment of the mitochondrial membrane potential in H2O2-treated NP cells. Reduced caspase-3 and increased Bcl-2 activity were detected in CMCS-treated NP cells by RT-qPCR and western blot analysis. CMCS also promoted the proliferation and secretion of type II collagen and aggrecan in H2O2-treated NP cells. CMCS was indicated to be effective in preventing apoptotic cell death in vitro, demonstrating the potential advantages of this therapeutic approach in regulating disc degeneration.
apoptosis; intervertebral disc degeneration; nucleus pulposus cells; carboxymethylated chitosan
Widespread premature termination codon mutations (PTCs) were recently observed in human and fly populations. We took advantage of the population resequencing data in the Drosophila Genetic Reference Panel to investigate how the expression profile and the evolutionary age of genes shaped the allele frequency distribution of PTCs. After generating a high-quality data set of PTCs, we clustered genes harboring PTCs into three categories: genes encoding low-frequency PTCs (≤1.5%), moderate-frequency PTCs (1.5–10%), and high-frequency PTCs (>10%). All three groups show narrow transcription compared with PTC-free genes, with the moderate- and high-PTC frequency groups showing a pronounced pattern. Moreover, nearly half (42%) of the PTC-encoding genes are not expressed in any tissue. Interestingly, the moderate-frequency PTC group is strongly enriched for genes expressed in midgut, whereas genes harboring high-frequency PTCs tend to have sex-specific expression. We further find that although young genes born in the last 60 My compose a mere 9% of the genome, they represent 16%, 30%, and 50% of the genes containing low-, moderate-, and high-frequency PTCs, respectively. Among DNA-based and RNA-based duplicated genes, the child copy is approximately twice as likely to contain PTCs as the parent copy, whereas young de novo genes are as likely to encode PTCs as DNA-based duplicated new genes. Based on these results, we conclude that expression profile and gene age jointly shaped the landscape of PTC-mediated gene loss. Therefore, we propose that new genes may need a long time to become stably maintained after the origination.
gene loss; premature termination codon; midgut; young gene; gene duplication
Ionogel electrolytes can be fabricated for electrochemical actuators with many desirable advantages, including direct low-voltage control in air, high electrochemical and thermal stability, and complete silence during actuation. However, the demands for active actuators with above features and load-driving ability remain a challenge; much work is necessary to enhance the mechanical strength of electrolyte materials. Herein, we describe a cross-linked supramolecular approach to prepare tough nanocomposite gel electrolytes from HEMA, BMIMBF4, and TiO2 via self-initiated UV polymerization. The tough and stable ionogels are emerging to fabricate electric double-layer capacitor-like soft actuators, which can be driven by electrically induced ion migration. The ionogel-based actuator shows a displacement response of 5.6 mm to the driving voltage of 3.5 V. After adding the additional mass weight of the same as the actuator, it still shows a large displacement response of 3.9 mm. Furthermore, the actuator can not only work in harsh temperature environments (100°C and −10°C) but also realize the goal of grabbing an object by adjusting the applied voltage.
Many studies have demonstrated that SIRT1, an NAD+-dependent deacetylase, reduces apoptosis in several different cells. However, the role of SIRT1 in apoptosis of disc nucleus pulposus (NP) cells remains unclear. The present study was performed to determine whether degenerative human NP would express SIRT1, and to investigate the role of SIRT1 in NP cells apoptosis. The expression of SIRT1 in disc NP of patients (>55 years) with lumbar disc degenerative disease (DDD) and the disc NP of patients (<25 years) with lumbar vertebra fracture (LVF) was assessed by immunohistochemistry, reverse transcription polymerase chain reaction, and Western blot analysis. The results showed that SIRT1 mRNA and protein levels were greater in LVF disc NP than those in DDD disc NP. Degenerative human NP cells were treated in culture with activator or inhibitor of SIRT1, resveratrol or nicotinamide, or SIRT1 small interfering RNA (siRNA), and cell apoptosis was quantified via flow cytometry. The rate of apoptosis was far fewer in resveratrol-treated NP cells than in SIRT1 siRNA-transfected or nicotinamide-treated NP cells. After SIRT1 siRNA was transfected, NP cells decreased phosphorylation of Akt, while resveratrol phosphorylated Akt. Treatment with LY294002 or Akt siRNA increased the rate of apoptosis. Our results suggested that SIRT1 plays a critical role in survival of degenerative human NP cells through the Akt anti-apoptotic signaling pathway.
SIRT1; Apoptosis; Nucleus pulposus cells; Akt pathway; Degenerative disc disease
Imaging myocardial activation from noninvasive body surface potentials promises to aid in both cardiovascular research and clinical medicine.
This study investigates the ability of a noninvasive 3-dimensional cardiac electrical imaging (3DCEI) technique for characterizing the activation patterns of dynamically changing ventricular arrhythmias during drug-induced QT prolongation in rabbit.
Simultaneous body surface potential mapping and 3-dimensional intra-cardiac mapping were performed in a closed-chest condition in eight rabbits. Data analysis was performed on premature ventricular complexes, couplets, and torsades de pointes (TdP) induced during i.v. administration of clofilium and phenylephrine with combinations of various infusion rates.
The drug infusion led to significant increase of QT interval (175±7ms to 274±31ms) and rate-corrected QT interval (183±5ms to 262±21ms) during the first dose cycle. All the ectopic beats initiated by a focal activation pattern. The initial beat of TdPs arose at focal site, whereas the subsequent beats were due to focal activity from different sites or two competing focal sites. The imaged results captured the dynamic shift of activation patterns and were in good correlation with the simultaneous measurements with a correlation coefficient of 0.65±0.02 averaged over 111 ectopic beats. Sites of initial activation were localized to be ~5mm.
The 3DCEI technique could localize the origin of activation and image activation sequence of TdP during QT prolongation induced by clofilium and phenylephrine in rabbit. It offers the potential to non-invasively investigate the proarrhythmic effects of drug infusion and assess the mechanisms of arrhythmias on a beat-to-beat basis.
cardiac imaging; electrocardiography; cardiac mapping; torsades de pointes; QT prolongation; rabbit model
Polyaniline nanomaterial (nPANI) is getting popular in many industrial fields due to its conductivity and stability. The fate and effect of nPANI in the environment is of paramount importance towards its technological applications. In this work, the cytotoxicity of nPANI, which was prepared by rapid surface polymerization, was studied on rat celiac macrophages. Cell viability of macrophages treated with various concentrations of nPANI and different periods ranging from 24 to 72 hours was tested by a MTT assay. Damages of nPANI to structures of macrophages were evaluated according to the exposure level of cellular reactive oxygen species (ROS) and change of mitochondrial membrane potential (MMP). We observed no significant effects of nPANI on the survival, ROS level and MMP loss of macrophages at concentrations up to 1 µg/ml. However, higher dose of nPANI (10 µg/ml or above) induced cell death, changes of ROS level and MMP. In addition, an increase in the expression level of caspase-3 protein and its activated form was detected in a Western blot assay under the high dose exposure of nPANI. All together, our experimental results suggest that the hazardous potential of nPANI on macrophages is time- and dose-dependent and high dose of nPANI can induce cell apoptosis through caspase-3 mediated pathway.
A fluorogenic high-throughput assay suitable for screening Sirt6 modulators is developed based on the recently discovered efficient activity of Sirt6 to hydrolyze myristoyl lysine. Sirt6 modulators will be useful for investigating the function of Sirt6 and protein lysine fatty acylation.
The current study reports a case of an extremely rare tumor that presented in an uncommon location, which was successfully treated via radical resection and reconstruction. A 37-year-old female, with no notable medical history, with the exception of a cesarean delivery, was admitted to The First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China) due to pain and a lump of the anterior chest wall. The mass was identified on the manubrium sterni and was not tender on palpation. A chest computed tomography (CT) scan reconstruction identified the abnormal mass on the manubrium sterni (size, 5×4 cm in diameter) and positron emission tomography-CT interpretation strongly indicated a type of well-differentiated malignant tumor, such as a giant cell tumor. An aspiration needle biopsy was not conducted, however, the patient underwent tumor radical resection and sternal reconstruction using steel wire and titanium mesh. Histopathological examination of the surgical specimen determined the diagnosis of chondrosarcoma. A postoperative chest X-ray revealed that the sternal defect had repaired well, therefore, this procedure may be highly beneficial in future for repairing defects in the sternum.
positron emission tomography-computed tomography; chondrosarcoma; sternum; titanium mesh
At the balanced intersection of human and machine adaptation is found the optimally functioning brain-computer interface (BCI). In this study, we report a novel experiment of BCI controlling a robotic quadcopter in three-dimensional physical space using noninvasive scalp EEG in human subjects. We then quantify the performance of this system using metrics suitable for asynchronous BCI. Lastly, we examine the impact that operation of a real world device has on subjects’ control with comparison to a two-dimensional virtual cursor task.
Five human subjects were trained to modulate their sensorimotor rhythms to control an AR Drone navigating a three-dimensional physical space. Visual feedback was provided via a forward facing camera on the hull of the drone. Individual subjects were able to accurately acquire up to 90.5% of all valid targets presented while travelling at an average straight-line speed of 0.69 m/s.
Freely exploring and interacting with the world around us is a crucial element of autonomy that is lost in the context of neurodegenerative disease. Brain-computer interfaces are systems that aim to restore or enhance a user’s ability to interact with the environment via a computer and through the use of only thought. We demonstrate for the first time the ability to control a flying robot in the three-dimensional physical space using noninvasive scalp recorded EEG in humans. Our work indicates the potential of noninvasive EEG based BCI systems to accomplish complex control in three-dimensional physical space. The present study may serve as a framework for the investigation of multidimensional non-invasive brain-computer interface control in a physical environment using telepresence robotics.
Brain-Computer Interface; BCI; EEG; 3D control; motor imagery; telepresence robotics
Elevated Specific Absorption Rate (SAR) associated with increased main magnetic field strength remains as a major safety concern in ultra-high-field (UHF) Magnetic Resonance Imaging (MRI) applications. The calculation of local SAR requires the knowledge of the electric field induced by radiofrequency (RF) excitation, and the local electrical properties of tissues. Since electric field distribution cannot be directly mapped in conventional MR measurements, SAR estimation is usually performed using numerical model-based electromagnetic simulations which, however, are highly time consuming and cannot account for the specific anatomy and tissue properties of the subject undergoing a scan. In the present study, starting from the measurable RF magnetic fields (B1) in MRI, we conducted a series of mathematical deduction to estimate the local, voxel-wise and subject-specific SAR for each single coil element using a multi-channel transceiver array coil. We first evaluated the feasibility of this approach in numerical simulations including two different human head models. We further conducted experimental study in a physical phantom and in two human subjects at 7T using a multi-channel transceiver head coil. Accuracy of the results is discussed in the context of predicting local SAR in the human brain at UHF MRI using multi-channel RF transmission.
SAR; B1-mapping; Electrical Properties Tomography (EPT); Magnetic Resonance Imaging (MRI); ultrahigh-field (UHF); parallel transmission
Ectopic thyroid tissue (ETT) is a rare developmental anomaly of the thyroid tissue which is defined as the presence of thyroid tissue in locations other than the pretracheal area. However, ectopic thyroid tissue in the lateral neck surrounding the recurrent laryngeal nerve is unusually found. Here we describe a case of a 64-year-old woman who was found bilateral thyroid goiter by the ultrasound examination. The total thyroidectomy plus a modified radical neck dissection was performed. Surprisingly we also found a nodule surrounding the right recurrent laryngeal nerve at the same time. Nevertheless the diagnosis of the nodule was confirmed by pathology and Histologic examination demonstrating that it was ectopic thyroid tissue. Ectopic thyroid tissue surrounding recurrent laryngeal nerve is a rare finding, with hardly any cases reported. For it is generally thought that any thyroid tissue found in the lateral aspect of the neck may indicate metastatic deposits from well-differentiated thyroid carcinoma. Although pathogenesis of ectopic thyroid tissue surrounding recurrent laryngeal nerve without any symptoms remains unknown, our case could suggest ectopic thyroid tissue should not be excluded in the differential diagnosis of lateral neck masses especially when the recurrent laryngeal nerves were surrounded by the nodules.
Ectopic thyroid tissue; bilateral thyroid goiter; the recurrent laryngeal nerve; thyroiditis; ultrasound
Electrical Property Tomography (EPT) is a recently developed noninvasive technology to image the electrical conductivity and permittivity of biological tissues at Larmor frequency in Magnetic Resonance (MR) scanners. The absolute phase of the complex radio-frequency (RF) magnetic field (B1) is necessary for electrical property calculation. However, due to the lack of practical methods to directly measure the absolute B1 phases, current EPT techniques have been achieved with B1 phase estimation based on certain assumptions on object anatomy, coil structure and/or electromagnetic wave behavior associated with the main magnetic field, limiting EPT from a larger variety of applications. In this study, using a multi-channel transmit/receive coil, the framework of a new general approach for EPT has been introduced, which is independent on the assumptions utilized in previous studies. Using a human head model with realistic geometry, a series of computer simulations at 7T were conducted to evaluate the proposed method under different noise levels. Results showed that the proposed method can be used to reconstruct the conductivity and permittivity images with noticeable accuracy and stability. The feasibility of this approach was further evaluated in a phantom experiment at 7T.
Tamoxifen has been a frontline treatment for estrogen receptor alpha (ERα)-positive breast tumors in premenopausal women. However, resistance to tamoxifen occurs in many patients. ER still plays a critical role in the growth of breast cancer cells with acquired tamoxifen resistance, suggesting that ERα remains a valid target for treatment of tamoxifen-resistant (Tam-R) breast cancer. In an effort to identify novel regulators of ERα signaling, through a small-scale siRNA screen against histone methyl modifiers, we found WHSC1, a histone H3K36 methyltransferase, as a positive regulator of ERα signaling in breast cancer cells. We demonstrated that WHSC1 is recruited to the ERα gene by the BET protein BRD3/4, and facilitates ERα gene expression. The small-molecule BET protein inhibitor JQ1 potently suppressed the classic ERα signaling pathway and the growth of Tam-R breast cancer cells in culture. Using a Tam-R breast cancer xenograft mouse model, we demonstrated in vivo anti-breast cancer activity by JQ1 and a strong long-lasting effect of combination therapy with JQ1 and the ER degrader fulvestrant. Taken together, we provide evidence that the epigenomic proteins BRD3/4 and WHSC1 are essential regulators of estrogen receptor signaling and are novel therapeutic targets for treatment of Tam-R breast cancer.
epigenomic; tamoxifen; breast cancer
In order to improve the diagnosis and therapy of undifferentiated embryonal liver sarcoma (UELS), the present study presents the case of a 9-year-old female with UELS and discusses UELS in childhood. The patient presented with abdominal pain and fever. The laboratory tests, radiographic examination and pathological features presented by the female were similar to those of typical cases of UELS reported in childhood. The patient initially received surgical treatment and the immunohistochemical findings suggested that the patient had UELS. The patient’s parents refused adjuvant chemotherapy and demonstrated a right prerenal mass 6 months post-surgery. Microscopic examination revealed that the tumor was evidence of undifferentiated embryonal sarcoma recurrence. However, the patient was comfortable and physical examination revealed no abnormal conditions. In addition, the laboratory results were normal. Abdominal computed tomography scan and ultrasound were performed every 3 months to monitor the tumor recurrence. At the time of writing, it has been 6 months after the second surgical procedure and there has been no appearence of abnormalities. Previous studies have shown that patients who receive combined therapy with complete tumor resection and adjuvant chemotherapy have a longer survival time than those who undergo surgical therapy alone. Complete tumor resection combined with adjuvant chemotherapy may reduce the risk of recurrence and enhance the survival time in patients with UELS.
undifferentiated embryonal sarcoma; liver; children; treatment
As radio frequency (RF) catheter ablation becomes increasingly prevalent in the management of ventricular arrhythmia in patients, an accurate and rapid determination of the arrhythmogenic site is of important clinical interest. The aim of this study was to test the hypothesis that the inversely reconstructed ventricular endocardial current density distribution from body surface potential maps (BSPMs) can localize the regions critical for maintenance of a ventricular ectopic activity. Patients with isolated and monomorphic premature ventricular contractions (PVCs) were investigated by noninvasive BSPMs and subsequent invasive catheter mapping and ablation. Equivalent current density (CD) reconstruction (CDR) during symptomatic PVCs was obtained on the endocardial ventricular surface in 6 patients (4 men, 2 women, years 23–77), and the origin of the spontaneous ectopic activity was localized at the location of the maximum CD value. Compared with the last (successful) ablation site (LAS), the mean and standard deviation of localization error of the CDR approach were 13.8 mm and 1.3 mm, respectively. In comparison, the distance between the LASs and the estimated locations of an equivalent single moving dipole (SMD) in the heart was 25.5 ± 5.5 mm. The obtained CD distribution of activated sources extending from the catheter ablation site also showed a high consistency with the invasively recorded electroanatomical maps. The noninvasively reconstructed endocardial CD distribution is suitable to predict a region of interest containing or close to arrhythmia source, which may have the potential to guide RF catheter ablation.
electrocardiographic inverse problem; current density reconstruction; radio frequency catheter ablation; premature ventricular contraction; body surface potential mapping
Androgens regulate body composition by interacting with the androgen receptor (AR) to control gene expression in a tissue-specific manner. To identify novel regulatory roles for AR in preadipocytes, we created a 3T3-L1 cell line stably expressing human AR. We found AR expression is required for androgen-mediated inhibition of 3T3-L1 adipogenesis. This inhibition is characterized by decreased lipid accumulation, reduced expression of adipogenic genes, and induction of genes associated with osteoblast differentiation. Collectively, our results suggest androgens promote an osteogenic gene program at the expense of adipocyte differentiation.
Adipocyte; Osteoblast; Androgen receptor; Gene regulation
The electric properties (EPs) of biological tissue provide important diagnostic information within radio and microwave frequencies, and also play an important role in specific absorption rate (SAR) calculation which is a major safety concern at ultrahigh field (UHF). The recently proposed electrical properties tomography (EPT) technique aims to reconstruct EPs in biological tissues based on B1 measurement. However, for individual coil element in multi-channel transceiver coil which is increasingly utilized at UHF, current B1-mapping techniques could not provide adequate information (magnitude and absolute phase) of complex transmit and receive B1 which are essential for EPT, electric field, and quantitative SAR assessment. In this study, using a 16-channel transceiver coil at 7T, based on hybrid B1-mapping techniques within the human brain, a complex B1-mapping method has been developed, and in-vivo EPs imaging of the human brain has been demonstrated by applying a logarithm-based inverse algorithm. Computer simulation studies as well as phantom and human experiments have been conducted at 7T. The average bias and standard deviation for reconstructed conductivity in vivo were 28% and 67%, and 10% and 43% for relative permittivity, respectively. The present results suggest the feasibility and reliability of proposed complex B1-mapping technique and EPs reconstruction method.
electric properties; B1-mapping; B1 phase; ultrahigh field MRI; multi-channel transceiver array
Quercus infectoria galls (QIG) is being widely used in Traditional Uyghur Medicine. To gather preclinical safety information for the aqueous extract of QIG, a toxicity study was performed.
Subject animals were randomized, and devided into exposure and control groups. In the acute toxicity phase, three different doses—5, 7.5, and 10 g/kg, respectively—were administered via enema to imprinting control region (ICR) mice. An experiment using the maximum tolerance dose (MTD) i.e.10 g/kg was also performed. Data were gathered for 14 days, and study parameters were clinical signs, body weight, general behavior, adverse effects and mortality. At the day 14, major organs of the subjects were examined histologically. Chronic toxicity was also evaluated in Wistar rats for over 180 consecutive days. The rats were divided into three groups with different doses of 0.2 g/kg, 0.8 g/kg, and 2 g/kg, QIG. Furthermore, observations were carried out in rabbits to investigate if there were signs of irritation.
In comparison to control group, acute, chronic toxicity and mortality were not significantly increased in exposure group.
Study result suggests that the aqueous extract of QIG is unlikely to have significant toxicity and that clinical trials may proceed safely.