Klotho was originally characterized as an aging suppressor gene that predisposed Klotho-deficient mice to premature aging-like syndrome. Although Klotho was recently reported to exhibit tumor suppressive properties during various malignant transformations, the functional role and molecular mechanism of Klotho in hepatocarcinogenesis remains poorly understood. In our present study, immunohistochemical Klotho staining levels in a clinical follow-up of 52 hepatoma patients were significantly associated with liver cirrhosis, tumor multiplicity and venous invasion. The overall survival rate of hepatoma patients with high Klotho expression was significantly lower than those patients with low Klotho expression. Moreover, Klotho overexpression increased cellular migration, anchorage-independent growth, and anoikis resistance in hepatoma cells. Klotho overexpression elevated p21-activated kinase 1 (PAK1) expression and shRNA-mediated PAK1 knockdown and kinase activity inhibition with kinase dead mutant PAK1 K299R coexpression or allosteric inhibitor IPA3 treatment reversed anoikis resistance in Klotho-overexpressed hepatoma cells. More importantly, the pivotal significance of upregulated VEGFR2 protein levels mediated by Klotho expression was confirmed by VEGFR2 inhibitor Axitinib and blocking antibody treatment in hepatoma cells. Axitinib treatment sensitized anoikis was reversed by constitutive active mutant PAK1 T423E coexpression in Klotho-overexpressed hepatoma cells. Conversely, knockdown of Klotho reduced VEGFR2/PAK1 dependent anoikis resistance, which could be reversed by PAK1 T423E. These results revealed a novel oncogenic function of Klotho in promoting anoikis resistance via activating VEGFR2/PAK1 signaling, thus facilitating tumor migration and invasion during hepatoma progression, which could provide a putative molecular mechanism for tumor metastasis.
Conventional ways of making bio-electrodes are generally complicated, expensive and unconformable. Here we describe for the first time the method of applying Ga-based liquid metal ink as drawable electrocardiogram (ECG) electrodes. Such material owns unique merits in both liquid phase conformability and high electrical conductivity, which provides flexible ways for making electrical circuits on skin surface and a prospective substitution of conventional rigid printed circuit boards (PCBs).
Fundamental measurements of impedance and polarization voltage of the liquid metal ink were carried out to evaluate its basic electrical properties. Conceptual experiments were performed to draw the alloy as bio-electrodes to acquire ECG signals from both rabbit and human via a wireless module developed on the mobile phone. Further, a typical electrical circuit was drawn in the palm with the ink to demonstrate its potential of implementing more sophisticated skin circuits.
With an oxide concentration of 0.34%, the resistivity of the liquid metal ink was measured as 44.1 µΩ·cm with quite low reactance in the form of straight line. Its peak polarization voltage with the physiological saline was detected as −0.73 V. The quality of ECG wave detected from the liquid metal electrodes was found as good as that of conventional electrodes, from both rabbit and human experiments. In addition, the circuit drawn with the liquid metal ink in the palm also runs efficiently. When the loop was switched on, all the light emitting diodes (LEDs) were lit and emitted colorful lights.
The liquid metal ink promises unique printable electrical properties as both bio-electrodes and electrical wires. The implemented ECG measurement on biological surface and the successfully run skin circuit demonstrated the conformability and attachment of the liquid metal. The present method is expected to innovate future physiological measurement and biological circuit manufacturing technique in a large extent.
The goal of this study is to evaluate the ability of a bimodal technique integrating time-resolved fluorescence spectroscopy (TRFS) and ultrasound backscatter microscopy (UBM) for nondestructive detection of changes in the biochemical, structural, and mechanical properties of self-assembled engineered articular cartilage constructs. The cartilage constructs were treated with three chemical agents (collagenase, chondroitinase-ABC, and ribose) to induce changes in biochemical content (collagen and glycosaminoglycan [GAG]) of matured constructs (4 weeks); and to subsequently alter the mechanical properties of the construct. The biochemical changes were evaluated using TRFS. The microstructure and the thickness of the engineered cartilage samples were characterized by UBM. The optical and ultrasound results were validated against those acquired via conventional techniques including collagen and GAG quantification and measurement of construct stiffness. Current results demonstrated that a set of optical parameters (e.g., average fluorescence lifetime and decay constants) showed significant correlation (p<0.05) with biochemical and mechanical data. The high-resolution ultrasound images provided complementary cross-section information of the cartilage samples morphology. Therefore, the technique was capable of nondestructively evaluating the composition of extracellular matrix and the microstructure of engineered tissue, demonstrating great potential as an alternative to traditional destructive assays.
In silico screening of metazoan genome data identified multiple endogenous hepadnaviral elements in the budgerigar (Melopsittacus undulatus) genome, most notably two elements comprising about 1.3× and 1.0× the full-length genome. Phylogenetic and molecular dating analyses show that endogenous budgerigar hepatitis B viruses (eBHBV) share an ancestor with extant avihepadnaviruses and infiltrated the budgerigar genome millions of years ago. Identification of full-length genomes with preserved key features like ε signals could enable resurrection of ancient BHBV.
The risk factors for No. 12p and No. 12b lymph node (LN) metastases in advanced gastric cancer (GC) remain controversial. The aim of this study was to investigate the risk factors for No. 12p and No. 12b LN metastases in advanced GC.
From January 1999 to December 2005, a retrospective analysis of 163 patients with advanced GC who underwent D2 lymphadenectomy in addition to No. 12p and No. 12b LN dissections was conducted. Potential clinicopathological factors that could influence No. 12p and No. 12b LN metastases were statistically analyzed.
There were 15 cases (9.2%) with No. 12p LN metastases and 5 cases (3.1%) with synchronous No. 12b LN metastases. A logistic regression analysis revealed that the Borrmann type (III/IV versus I/II, P = 0.029), localization (lesser/circular versus greater, P = 0.025), and depth of invasion (pT4 versus pT2/pT3, P = 0.009) were associated with 11.1-, 3.8-, and 5.6-fold increases, respectively, for risk of No. 12p and No. 12b LN metastases. A logistic regression analysis also showed that No. 5 (P = 0.006) and No. 12a (P = 0.004) LN metastases were associated with 6.9- and 11.3-fold increases, respectively, for risk of No. 12p and No. 12b LN metastases. In addition, significant differences in 5-year survival of patients with and without No. 12p and No. 12b LN metastases were observed (13.3% versus 35.1%, P = 0.022).
We conclude that Borrmann type, localization, and depth of invasion are significant variables for identifying patients with No. 12p and No. 12b LN metastases. Individuals with No. 5 or No. 12a LN metastases should be on high alert for the possibility of additional metastases to the No. 12p and No. 12b LNs.
Gastrectomy; gastric cancer; lymphadenectomy; metastasis; risk factor
Specific chromatin marks keep master regulators of differentiation silent, yet poised for activation by extracellular signals. We report that nodal TGF-β signals use the poised histone mark H3K9me3 to trigger differentiation of mammalian embryonic stem cells. Nodal receptors induce the formation of companion Smad4-Smad2/3 and TRIM33-Smad2/3 complexes. TRIM33-Smad2/3 binds the histone marks H3K9me3 and K18ac on the promoters of mesendoderm regulators Gsc and Mixl1. Binding is through the PHD-Bromo cassette of TRIM33. In the crystal structure of this cassette bound to histone H3 peptides, PHD recognizes K9me3 and Bromo an adjacent K18ac. Binding of TRIM33-Smad2/3 to H3K9me3 displaces the chromatin compacting factor HP1γ and makes nodal response elements accessible to Smad4-Smad2/3 for Pol II recruitment. In turn, Smad4 increases K18 acetylation to augment TRIM33-Smad2/3 binding. Thus, nodal cues use the H3K9me3 mark as a platform to switch master regulators of stem cell differentiation from the poised to the active state.
The pathophysiology of amyotrophic lateral sclerosis (ALS) is very complex and still rather elusive but in recent years evidence of early involvement of the neuromuscular junctions (NMJs) has accumulated. We have recently reported that the human extraocular muscles (EOMs) are far less affected than limb muscles at the end-stage of ALS from the same donor. The present study aimed to compare the differences in synaptic protein composition at NMJ and in nerve fibers between EOM and limb muscles from ALS donors and controls. Neurofilament light subunit and synaptophysin decreased significantly at NMJs and in nerve fibers in limb muscles with ALS whereas they were maintained in ALS EOMs. S100B was significantly decreased at NMJs and in nerve fibers in both EOMs and limb muscles of ALS donors, but other markers confirmed the presence of terminal Schwann cells in these NMJs. p75 neurotrophin receptor was present in nerve fibers but absent at NMJs in ALS limb muscles. The EOMs were able to maintain the integrity of their NMJs to a very large extent until the end-stage of ALS, in contrast to the limb muscles. Changes in Ca2+ homeostasis, reflected by altered S100B distribution, might be involved in the breakdown of nerve-muscle contact at NMJs in ALS.
We report a novel method for estimating fluorescence impulse response function (fIRF) from noise-corrupted time-domain fluorescence measurements of biological tissue. This method is based on the use of higher-order Laguerre basis functions (LBFs) and a constrained least-square (CLS) approach that addresses the problem of overfitting due to increased model complexity. The method was extensively evaluated on fluorescence data from simulation, fluorescent standard dyes, ex vivo tissue samples of atherosclerotic plaques, and in vivo oral carcinoma. Current results demonstrate that this new method allows for rapid and accurate deconvolution of multiple channel fluorescence decays without adaptively adjusting the Laguerre scale parameter. The appropriate choice of the scale parameter is essential for accurate estimation of the fIRF. The method described here is anticipated to play an important role in the development of computational techniques for real-time analysis of time-resolved fluorescence data from biological tissues and to support the advancement of fluorescence lifetime instrumentation for biomedical diagnostics by providing a means for on-line robust analysis of fluorescence decay.
The magnetic susceptibility of tissue can be determined in gradient echo MRI by deconvolving the local magnetic field with the magnetic field generated by a unit dipole. This Quantitative Susceptibility Mapping (QSM) problem is unfortunately ill-posed. By transforming the problem to the Fourier domain, the susceptibility appears to be undersampled only at points where the dipole kernel is zero, suggesting that a modest amount of additional information may be sufficient for uniquely resolving susceptibility. A Morphology Enabled Dipole Inversion (MEDI) approach is developed that exploits the structural consistency between the susceptibility map and the magnitude image reconstructed from the same gradient echo MRI. Specifically, voxels that are part of edges in the susceptibility map but not in the edges of the magnitude image are considered to be sparse. In this approach an L1 norm minimization is used to express this sparsity property. Numerical simulations and phantom experiments are performed to demonstrate the superiority of this L1 minimization approach over the previous L2 minimization method. Preliminary brain imaging results in healthy subjects and in patients with intracerebral hemorrhages illustrate that QSM is feasible in practice.
quantitative susceptibility mapping; gradient echo; inverse problem; morphology enabled dipole inversion; tissue susceptibility; L1 norm; L2 norm; constraint minimization; sparsity
The identification of stem-cell-like cancer cells through conventional methods that depend on stem-cell markers is often unreliable. We developed a mechanical method of selecting tumourigenic cells by culturing single cancer cells in fibrin matrices of ~100 Pa in stiffness. When cultured within these gels, primary human cancer cells or single cancer cells from mouse or human cancer cell lines grew within a few days into individual round colonies that resembled embryonic stem-cell colonies. Subcutaneous or intravenous injection of 10 or 100 fibrin-cultured cells in syngeneic or severe-combined-immunodeficiency mice led to the formation of solid tumours at the site of injection or at the distant lung organ much more efficiently than control cancer cells selected using conventional surface marker methods or cultured on conventional rigid dishes or on soft gels. Remarkably, as few as 10 such cells were able to survive and form tumours in the lungs of wild-type non-syngeneic mice.
cancer; matrix stiffness; metastasis; mechanical force; tumour-repopulating cells
Poor impulse inhibition is associated with behavioral problems including aggression and violence as well as clinical diagnoses such as attention deficit hyperactivity disorder (ADHD) and substance abuse, all of which are more prevalent in men than women. Studies have found that fronto-parietal and fronto-striatal-thalamic networks are critical for successful impulse inhibition. However, few studies have investigated neural differences in these networks between men and women. In this study, we use a well established behavioral task, the parametric Go/noGo task, to explore the relationships between brain regional activity during impulse control and impulsivity trait measures, as well as sex differences in these relationships. We found that males showed heightened activation of the rostral anterior cingulate, which correlated with ratings related to impulsivity. We also found that the activation/deactivation in males and females correlates with personality ratings in a sex-specific manner.
impulsivity; fMRI; impulsivity trait measure; Go/noGo task
Mesenchymal stem cells (MSCs) can suppress dendritic cells (DCs) maturation and function, mediated by soluble factors, such as indoleamine 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2), and nitric oxide (NO). Interleukin-10 (IL-10) is a common immunosuppressive cytokine, and the downstream signaling of the JAK-STAT pathway has been shown to be involved with DCs differentiation and maturation in the context of cancer. Whether IL-10 and/or the JAK-STAT pathway play a role in the inhibitory effect of MSCs on DCs maturation remains controversial. In our study, we cultured MSCs and DCs derived from rat bone marrow under different culturing conditions. Using Transwell plates, we detected by ELISA that the level of IL-10 significantly increased in the supernatants of MSC-DC co-cultures at 48 hours. The cell immunofluorescence assay suggested that the MSCs secreted more IL-10 than the DCs in the co-cultures. Adding exogenous IL-10 to the DCs monoculture or MSC-DC co-cultures stimulated IL-10 and led to a decrease in IL-12, and lower expression of the DCs surface markers CD80, CD86, OX62, MHC-II and CD11b/c. Supplementing the culture with an IL-10 neutralizing antibody (IL-10NA) showed precisely the opposite effect of adding IL-10. Moreover, we demonstrated that the JAK-STAT signaling pathway is involved in inhibiting DCs maturation. Both JAK1 and STAT3 expression and IL-10 secretion decreased markedly after adding a JAK inhibitor (AG490) to the co-culture plate. We propose that there is an IL-10 positive feedback loop, which may explain our observations of elevated IL-10 and enhanced JAK1 and STAT3 expression. Overall, we demonstrated that MSCs inhibit the maturation of DCs through the stimulation of IL-10 secretion, and by activating the JAK1 and STAT3 signaling pathway.
Melatonin is involved in the regulation of circadian and seasonal rhythms and immune function. Prior research reported low melatonin levels in autism spectrum disorders (ASD). ASMT located in pseudo-autosomal region 1 encodes the last enzyme of the melatonin biosynthesis pathway. A previous study reported an association between ASD and single nucleotide polymorphisms (SNPs) rs4446909 and rs5989681 located in the promoter of ASMT. Furthermore, rare deleterious mutations were identified in a subset of patients. To investigate the association between ASMT and autism, we sequenced all ASMT exons and its neighboring region in 398 Chinese Han individuals with autism and 437 healthy controls. Although our study did not detect significant differences of genotypic distribution and allele frequencies of the common SNPs in ASMT between patients with autism and healthy controls, we identified new rare coding mutations of ASMT. Among these rare variants, 4 were exclusively detected in patients with autism including a stop mutation (p.R115W, p.V166I, p.V179G, and p.W257X). These four coding variants were observed in 6 of 398 (1.51%) patients with autism and none in 437 controls (Chi-Square test, Continuity Correction p = 0.032, two-sided). Functional prediction of impact of amino acid showed that p.R115W might affect protein function. These results indicate that ASMT might be a susceptibility gene for autism. Further studies in larger samples are needed to better understand the degree of variation in this gene as well as to understand the biochemical and clinical impacts of ASMT/melatonin deficiency.
The conductivity and permittivity of tumors are known to differ significantly from those of normal tissues. Electrical impedance tomography (EIT) is a relatively new imaging method for exploiting these differences. However, the accuracy of data capture is one of the difficult problems urgently to be solved in the clinical application of EIT technology. A new concept of EIT sensitizers is put forward in this paper with the goal of expanding the contrast ratio of tumor and healthy tissue to enhance EIT imaging quality. The use of nanoparticles for changing tumor characteristics and determining the infiltration vector for easier detection has been widely accepted in the biomedical field. Ultra-pure water, normal saline, and gold nanoparticles, three kinds of material with large differences in electrical characteristics, are considered as sensitizers and undergo mathematical model analysis and animal experimentation. Our preliminary results suggest that nanoparticles are promising for sensitization work. Furthermore, in experimental and simulation results, we found that we should select different sensitizers for the detection of different types and stages of tumor.
EIT; nanoparticle sensitizer; tumor detection; EMF analysis
The epidemiology of spinal cord injury without radiographic abnormality (SCIWORA) is less frequently reported in adults as compared with children. The annual incidence of SCIWORA was approximately 5.74% per million in Tianjin from 2004 to 2008. Importantly, the epidemiological characteristics of adult SCIWORA may be different from that in children. The aim of this study was to evaluate the radiological-clinical data of patients with adult SCIWORA, and to relatively analyze the epidemiological features.
Materials and Methods
Inpatients with cervical SCIWORA who were 16 and above in Tianjin were admitted in municipal hospitals in Tianjin from 2004 to 2008; all the patients received MRI scanning in sagittal and axial views. Epidemiological characteristics, such as injury origin, injury level or severity, neurological scale and MRI feature were acquired.
In total, 203 patients were enrolled. The average age among the adult groups was 55.9 years (men 55.8 years, women 53.6 years). SCIWORA occurred more commonly in adults in the 46–60 age group, and falls were the leading cause of injury (52.2%), followed by vehicular injury (28.6%). The most predominantly affected level was C4/5 (48.7%), followed by C5/6 (30.5%) and C3/4 (12.8%), respectively. The occurrence of central cord syndrome (50.2%) with posterior longitudinal ligament tear (43.8%) was relatively higher than other injury patterns.
It is clear that adult cervical SCIWORA is different from that in the pediatric group. Our study highlights the epidemiological properties of adult SCIWORA in Tianjin, China. Differing from other reports, particularly epidemiology study, we represent the first report regarding adult SCIWORA from China. As the geriatric population increases, it is very important to set up an individualized evaluation system based on a nationally scaled epidemiological database. The results from our study will be useful in assisting in the creation of such a database.
Epidemiology; Spinal cord injury; Radiographic; Abnormalities; China
Our previous studies have demonstrated that stable microRNAs (miRNAs) in mammalian serum and plasma are actively secreted from tissues and cells and can serve as a novel class of biomarkers for diseases, and act as signaling molecules in intercellular communication. Here, we report the surprising finding that exogenous plant miRNAs are present in the sera and tissues of various animals and that these exogenous plant miRNAs are primarily acquired orally, through food intake. MIR168a is abundant in rice and is one of the most highly enriched exogenous plant miRNAs in the sera of Chinese subjects. Functional studies in vitro and in vivo demonstrated that MIR168a could bind to the human/mouse low-density lipoprotein receptor adapter protein 1 (LDLRAP1) mRNA, inhibit LDLRAP1 expression in liver, and consequently decrease LDL removal from mouse plasma. These findings demonstrate that exogenous plant miRNAs in food can regulate the expression of target genes in mammals.
microRNA; MIR168a; LDLRAP1; low-density lipoprotein; microvesicle; cross-kingdom
Near infrared quantum dots have been receiving great attention as fluorescent optical probes for in vivo imaging applications. In this contribution, we report the synthesis and surface functionalization of cadmium free ternary AgInS2 nanocrystals emitting in the near infrared range for successful in vitro and in vivo bioimaging applications. The FDA approved triblock copolymer Pluronic F127 was used to encapsulate the nanocrystals and made them dispersible in aqueous solution. By employing a whole body small animal optical imaging setup, we were able to use the AgInS2 nanocrystals formulation for passive targeted delivery to the tumor site. The ultra-small crystal size, near-infrared emitting luminescence, and high quantum yield make the AgInS2 nanocrystals an attractive candidate as a biological contrast agent for cancer sensing and imaging.
Near infrared quantum dots; Bioimaging; Surface functionalization; Targeted delivery; Nanotoxicity.
Background Chronic inflammation plays a crucial role in the progression of cardiac fibrosis. This study investigated whether inflammation exacerbated the progression of cardiac fibrosis in high-fat-fed apolipoprotein E knockout (ApoE KO) mice via endothelial-mesenchymal transition (EndMT).
Methods Twenty-four male ApoE KO mice were divided into normal chow diet (Control), high-fat diet (HFD), or high-fat diet plus 10% casein injection (inflamed) groups for 8 weeks. The body weight of ApoE KO mice was measured at each week. The lipid profile and serum amyloid A (SAA) levels were examined using clinical biochemistry and enzyme-linked immunosorbent assays, respectively. Cardiac lipid and collagen accumulation was visualised with haematoxylin-eosin (HE) and Masson's trichrome staining. EndMT-related molecule expression was examined by immunohistochemistry and Western blotting.
Results SAA levels were increased in the inflamed group compared with the HFD and control groups, suggesting that inflammation was successfully induced. There were no differences in body weight among three groups at each week. Interestingly, inflammation significantly reduced serum total cholesterol, triglyceride, and low-density lipoprotein (LDL) levels compared with the HFD mice. However, both foam cell formation in cardiac blood vessels and cardiac collagen deposition were increased in the inflamed group, as demonstrated by HE and Masson trichrome staining. Furthermore, inflammation reduced protein expression of CD31 and increased protein expression of alpha-smooth muscle actin (α-SMA) and collagen I, which contribute to cardiac EndMT.
Conclusions Inflammatory stress exacerbates the progression of cardiac fibrosis in high-fat-fed ApoE KO mice via EndMT, suggesting that hyperlipidaemia and inflammation act synergistically to redistribute plasma lipids to cardiac tissues and accelerate the progression of cardiac fibrosis.
Dyslipidaemia; inflammation; EndMT; cardiac fibrosis
In order to endow environmental protection features to dentifrice, hydroxyapatite (HA) was added to ordinary dentifrice. The effects on dentinal tubule occlusion and surface mineralization were compared after brushing dentine discs with dentifrice with or without HA. The two types of dentifrice were then added to 100 µg/ml of hexavalent chromium cation (Cr6+) solution in order to evaluate their capacities of adsorbing Cr6+ from water. Our results showed that the dentifrice containing HA was significantly better than the ordinary dentifrice in occluding the dentinal tubules with a plugging rate greater than 90%. Moreover, the effect of the HA dentifrice was persistent and energy-dispersive spectrometer (EDS) revealed that the atomic percentages of calcium and phosphorus on the surface of dentine discs increased significantly. Adding HA to ordinary dentifrice significantly enhanced the ability of dentifrice to adsorb Cr6+ from water with the removal rate up to 52.36%. In addition, the sorption was stable. Our study suggests that HA can be added to ordinary dentifrice to obtain dentifrice that has both relieving dentin hypersensitivity benefits and also helps to control environmental pollution.
S-phase kinase protein 2 (Skp2), an oncogenic protein, is a key regulator in different cellular and molecular processes, through ubiquitin-proteasome degradation pathway. Increased levels of Skp2 are observed in various types of cancer and associated with poor prognosis. However, in human breast carcinomas, the underlying mechanism and prognostic significance of cytoplasmic Skp2 is still undefined.
To investigate the role of cytoplasmic Skp2 expression in human breast carcinomas, we immnohistochemically assessed cytoplasmic Skp2, p-Akt1, and p27 expression in 251 patients with invasive ductal carcinomas of the breast. Association of cytoplasmic Skp2 expression with p-Akt1 and p27 was analyzed as well as correspondence with other clinicopathological parameters. Disease-free survival and overall survival were determined based on the Kaplan-Meier method and Cox regression models.
Cytoplasmic of Skp2 was detected in 165 out of 251 (65.7%) patients. Cytoplasmic Skp2 expression was associated with larger tumor size, more advanced histological grade, and positive HER2 expression. Increased cytoplasmic Skp2 expression correlated with p-Akt1 expression, with 54.2% (51/94) of low p-Akt1-expressing breast carcinomas, but 72.6% (114/157) of high p-Akt1-expressing breast carcinomas exhibiting cytoplasmic Skp2 expression. Elevated cytoplasmic Skp2 expression with low p-Akt1 expression was associated with poor disease-free and overall survival (DFS and OS), and Cox regression models demonstrated that cytoplasmic Skp2 expression was an independent prognostic marker for invasive breast carcinomas.
Cytoplasmic Skp2 expression is associated with aggressive prognostic factors, such as larger tumor size, and advanced histological grade of the breast cancers. Results demonstrate that combined cytoplasmic Skp2 and p-Akt1 expression may be prognostic for patients with invasive breast carcinomas, and cytoplasmic Skp2 may serve as a potential therapeutic target.
Pokemon (POK erythroid myeloid ontogenic factor), which belongs to the POK protein family, is also called LRF, OCZF and FBI-1. As a transcriptional repressor, Pokemon assumes a critical function in cellular differentiation and oncogenesis. Our study identified an oncogenic role for Pokemon in human hepatocellular carcinoma (HCC). We successfully established human HepG2 and Huh-7 cell lines in which Pokemon was stably knocked down. We demonstrated that Pokemon silencing inhibited cell proliferation and migration. Pokemon knockdown inhibited the PI3K/Akt and c-Raf/MEK/ERK pathways and modulated the expression of various cell cycle regulators in HepG2 and Huh-7 cells. Therefore, Pokemon may also be involved in cell cycle progression in these cells. We confirmed that Pokemon silencing suppresses hepatocellular carcinoma growth in tumor xenograft mice. These results suggest that Pokemon promotes cell proliferation and migration in hepatocellular carcinoma and accelerates tumor development in an Akt- and ERK-signaling-dependent manner.
Background. Tai Chi is a traditional Chinese medicine exercise used for improving neuromuscular function. This study aimed to investigate the effects of Tai Chi versus proprioception exercise program on neuromuscular function of the ankle in elderly people. Methods. Sixty elderly subjects were randomly allocated into three groups of 20 subjects per group. For 16 consecutive weeks, subjects participated in Tai Chi, proprioception exercise, or no structured exercise. Primary outcome measures included joint position sense and muscle strength of ankle. Subjects completed a satisfaction questionnaire upon study completion in Tai Chi and proprioception groups. Results. (1) Both Tai Chi group and proprioception exercise group were significantly better than control group in joint position sense of ankle, and there were no significant differences in joint position sense of ankle between TC group and PE group. (2) There were no significant differences in muscle strength of ankle among groups. (3) Subjects expressed more satisfaction with Tai Chi than with proprioception exercise program. Conclusions. None of the outcome measures on neuromuscular function at the ankle showed significant change posttraining in the two structured exercise groups. However, the subjects expressed more interest in and satisfaction with Tai Chi than proprioception exercise.