To measure perceptions of organizational culture among employees of public hospitals in China and to determine whether perceptions are associated with hospital performance.
Hospital, employee, and patient surveys from 87 Chinese public hospitals conducted during 2009.
Developed and administered a tool to assess organizational culture in Chinese public hospitals. Used factor analysis to create measures of organizational culture. Analyzed the relationships between employee type and perceptions of culture and between perceptions of culture and hospital performance using multivariate models.
Employees perceived the culture of Chinese public hospitals as stronger in internal rules and regulations, and weaker in empowerment. Hospitals in which employees perceived that the culture emphasized cost control were more profitable and had higher rates of outpatient visits and bed days per physician per day but also had lower levels of patient satisfaction. Hospitals with cultures perceived as customer-focused had longer length of stay but lower patient satisfaction.
Managers in Chinese public hospitals should consider whether the culture of their organization will enable them to respond effectively to their changing environment.
Business and management; comparative health systems/international health; hospitals; organization theory
Recent genetic analyses have implicated several candidate susceptibility variants for schizophrenia. The single nucleotide polymorphism (SNP) rs7294919 is likely a schizophrenia-susceptibility variant according to its significant association with hippocampal volume, hippocampus function, and cognitive performance as well as the nominal association with schizophrenia. However, all previous analyses were conducted only in Europeans, and whether rs7294919 is associated with schizophrenia in other populations are yet to be tested. Here, we conducted a case-control analysis of rs7294919 with schizophrenia in six independent Chinese (N = 3) and Japanese (N = 3) samples, including a total of 7,352 cases and 10,824 controls. The results of our association analysis were not able to confirm the association of rs7294919 with schizophrenia (p = 0.51 in total samples, odds ratio = 1.02 for allele[C]). The absence of rs7294919’s association in Chinese and Japanese suggest a potential genetic heterogeneity in the susceptibility of schizophrenia on this locus and also demonstrate the difficulties in replicating associations of schizophrenia across different ethnic populations.
The Medipix All Resolution System (MARS) system is a commercial spectral/multi-energy micro-CT scanner designed and assembled by the MARS Bioimaging, Ltd. in New Zealand. This system utilizes the state-of-the-art Medipix photon-counting, energy-discriminating detector technology developed by a collaboration based at European Organization for Nuclear Research (CERN). In this paper, we report our preliminary experimental results using this system, including geometrical alignment, photon energy characterization, protocol optimization, and spectral image reconstruction. We produced our scan datasets with a multi-material phantom, and then applied ordered subset-simultaneous algebraic reconstruction technique (OS-SART) to reconstruct images in different energy ranges and principal component analysis (PCA) to evaluate spectral deviation between the energy ranges.
Spectral/Multi-Energy Micro-CT; OS-SART; Multi-Material Phantom; PCA
In clinical practice, Epimedii Herba and Ginkgo Folium preparations are widely used in treatment of diseases such as coronary heart disease (angina) in China. However, there are no studies on the two-drug combination.
To explore the effect of the mixture of the Epimedii Herba extract (EE) and Ginkgo Folium extract (GE) on coronary flow of isolated hearts in rats.
Materials and Methods:
EE and GE were prepared by reflux in alcohol, and processed with HPD-100 macro-reticular resins; icariin from EE and total bilobalides from GE were determined by high performance liquid chromatography (HPLC). Fifty male Sprague–Dawley (SD) mice were subdivided into five groups (10 rats each): Normal control group (NC), EE – 10 mg group, GE – 10 mg group, EE – 5 mg + GE – 5 mg group, and EE – 10 mg + GE – 10 mg group. Isolated hearts uniform pressure perfusion was proceeded with Langendorff system.
The content of icariin in EE was 20.8%. The total content including four kinds of bilobalides (ginkolide A–C and bilobalide) in GE was 8.6%. The coronary flow in the NC group remained stable before and after treatment, and the coronoray flow in the EE, GE, EE + GE groups was increased and the relative magnitude of heightening was 25.0–33.3%, and the coronary flow in EE + GE was significantly different from that in the single EE or GE group.
EE or GE itself can heighten coronary flow of isolated hearts in rats. The activity of the mixture including EE and GE is better than that of single EE or GE, and the activity becomes larger when the dosage is doubled, and is related with dosage.
Bilobalide; Coronary flow; icariin; macro-reticular resins; traditional Chinese medicine
The content of icaritin and genistein in herba is very low, preparation with relatively large quantities is an important issue for extensive pharmacological studies.
This study focuses on preparing and enzymic hydrolysis of flavonoid glycosides /β-cyclodextrin inclusion complex to increase the hydrolysis rate.
Materials and Methods:
The physical property of newly prepared inclusion complex was tested by differential scanning calorimetry (DSC). The conditions of enzymatic hydrolysis were optimized for the bioconversion of flavonoid glycosides /β-cyclodextrin inclusion complex by mono-factor experimental design. The experiments are using the icariin and genistein as the model drugs.
The solubility of icariin and genistein were increased almost 17 times from 29.2 μg/ml to 513.5 μg/ml at 60°C and 28 times from 7.78 μg/ml to 221.46 μg/ml at 50°C, respectively, demonstrating that the inclusion complex could significantly increase the solubility of flavonoid glycosides. Under the optimal conditions, the reaction time of icariin and genistin decreased by 68% and 145%, when compared with that without β-CD inclusion. By using this enzymatic condition, 473 mg icaritin (with the purity of 99.34%) and 567 mg genistein(with the purity of 99.46%), which was finally determined by melt point, ESI-MS, UV, IR, 1H NMR and 13C NMR, was obtained eventually by transforming the inclusion complex(contains 1.0 g substrates).
This study can clearly indicate a new attempt to improve the speed of enzyme-hydrolysis of poorly water-soluble flavonoid glycosides and find a more superior condition which is used to prepare icaritin and genistein.
Cellulase; enzymatic hydrolysis; flavonoid glycosides; snailase; β-CD inclusion complex
The long-standing interior problem has important mathematical and practical implications. The recently developed interior tomography methods have produced encouraging results. A particular scenario for theoretically exact interior reconstruction from truncated projections is that there is a known subregion in the region of interest (ROI). In this paper, we improve a novel continuous singular value decomposition (SVD) method for interior reconstruction assuming a known subregion. First, two sets of orthogonal eigen-functions are calculated for the Hilbert and image spaces respectively. Then, after the interior Hilbert data are calculated from projection data through the ROI, they are projected onto the eigen-functions in the Hilbert space, and an interior image is recovered by a linear combination of the eigen-functions with the resulting coefficients. Finally, the interior image is compensated for the ambiguity due to the null space utilizing the prior subregion knowledge. Experiments with simulated and real data demonstrate the advantages of our approach relative to the projection onto convex set type interior reconstructions.
Hilbert transform; interior tomography; singular value decomposition (SVD); X-ray computed tomography (CT)
The present study examined the expression of podocalyxin (PODX) in surgically-resected astrocytomas, associated the levels of PODX expression with the clinicopathological characteristics and survival outcomes of astrocytoma and assessed how PODX affected the viability of astrocytoma cells following the administration of chemotherapeutic agents. The immunohistochemical analysis of 102 patient samples revealed that a high expression of PODX was significantly associated with high-grade astrocytomas (P<0.001) and a high Ki-67 labeling index (LI; P<0.001). A Kaplan-Meier survival analysis demonstrated that the high PODX expression group had significantly shorter disease-free survival (DFS) and overall survival (OS) rates compared with the low expression group (P<0.001). The multivariate analysis using the Cox’s proportional hazards model revealed that a high expression of PODX, a high World Health Organization grade and a high Ki-67 LI were independent factors for shorter DFS and OS times. A subsequent in vitro study using SW1783 and U-87 human astrocytoma cell lines revealed that knocking down PODX decreased astrocytoma cell viability against temozolomide-induced apoptotic stress through the inhibition of the Akt survival signaling pathway. In conclusion, the in vivo findings indicated that a high expression of PODX is predictive of a poor survival outcome and, thus, may be used as a prognostic factor to predict the survival outcomes of astrocytoma patients. The in vitro findings indicated that PODX may promote astrocytoma cell viability against chemotherapeutic agent-induced apoptotic stress through the Akt pathway, indicating that PODX may be a novel target for overcoming chemoresistance in astrocytomas.
astrocytoma; podocalyxin; overall survival; disease-free survival; Ki-67; temozolomide; cell survival; Akt
In this study, a five-generation Chinese family (family F013) with progressive autosomal dominant hearing loss was mapped to a critical region spanning 28.54 Mb on chromosome 9q31.3-q34.3 by linkage analysis, which was a novel DFNA locus, assigned as DFNA56. In this interval, there were 398 annotated genes. Then, whole exome sequencing was applied in three patients and one normal individual from this family. Six single nucleotide variants and two indels were found co-segregated with the phenotypes. Then using mass spectrum (Sequenom, Inc.) to rank the eight sites, we found only the TNC gene be co-segregated with hearing loss in 53 subjects of F013. And this missense mutation (c.5317G>A, p.V1773M ) of TNC located exactly in the critical linked interval. Further screening to the coding region of this gene in 587 subjects with nonsyndromic hearing loss (NSHL) found a second missense mutation, c.5368A>T (p. T1796S), co-segregating with phenotype in the other family. These two mutations located in the conserved region of TNC and were absent in the 387 normal hearing individuals of matched geographical ancestry. Functional effects of the two mutations were predicted using SIFT and both mutations were deleterious. All these results supported that TNC may be the causal gene for the hearing loss inherited in these families. TNC encodes tenascin-C, a member of the extracellular matrix (ECM), is present in the basilar membrane (BM), and the osseous spiral lamina of the cochlea. It plays an important role in cochlear development. The up-regulated expression of TNC gene in tissue repair and neural regeneration was seen in human and zebrafish, and in sensory receptor recovery in the vestibular organ after ototoxic injury in birds. Then the absence of normal tenascin-C was supposed to cause irreversible injuries in cochlea and caused hearing loss.
Delphinidin-3-glucoside (Dp) is a member of a family of bioactive compounds known as anthocyanins that occur naturally in pigmented plants and are known to ameliorate oxidative stress. Previous studies have showed that Dp decreased oxidative stress in vascular endothelial cells, however, the underlying mechanisms remain largely unknown. In the present study, we showed that pretreatment with Dp significantly suppressed oxidized low-density lipoprotein (oxLDL)-induced cell proliferation inhibition and apoptosis in primary human umbilical vein endothelial cells (HUVECs). Also, Dp pretreatment attenuated oxLDL-induced mitochondrial dysfunction via decreased reactive oxygen species (ROS) and superoxide anion generation, thereby repressing mitochondrial membrane potential and closing mitochondrial permeability transition pore. Furthermore, in vitro and in vivo data showed that Dp was transported into endothelial cells in a temperature, concentration, and time-dependent manner via the sodium-dependent glucose transporter (SGLT1). Suppression of SGLT1 by its substrate glucose, its inhibitor phlorizin or SGLT1 siRNA blocked Dp transportation. Repression of SGLT1 significantly inhibited Dp function of ameliorating mitochondrial dysfunction induced by pro-apoptotic factors (Apoptosis-inducing factor, Cytochrome c, Caspase-3 and Bax/Bcl-2 ratio). Taken together, our data indicate that Dp protects VECs via the SGLT1-ROS-mitochodria pathway. This new insight may help to elucidate the molecular mechanisms underlying the vascular protection afforded by Dp, and anthocyanins in general, in the context of prevention of endothelial dysfunction and atherosclerosis.
Residents of the Tibetan Plateau show heritable adaptations to extreme altitude. We sequenced 50 exomes of ethnic Tibetans, encompassing coding sequences of 92% of human genes, with an average coverage of 18X per individual. Genes showing population-specific allele frequency changes, which represent strong candidates for altitude adaptation, were identified. The strongest signal of natural selection came from EPAS1, a transcription factor involved in response to hypoxia. One SNP at EPAS1 shows a 78% frequency difference between Tibetan and Han samples, representing the fastest allele frequency change observed at any human gene to date. This SNP’s association with erythrocyte abundance supports the role of EPAS1 in adaptation to hypoxia. Thus, a population genomic survey has revealed a functionally important locus in genetic adaptation to high altitude.
Growing evidences indicate microRNAs play important roles in cancer development, progression, metastasis and may constitute robust biomarkers for cancer prognosis. The aim of this study was to identify the clinical and functional association of microRNA-20a (miR-20a) in hepatocellular carcinoma (HCC).
MiR-20a was detected using Taqman real-time polymerase chain reaction. Kaplan-Meier and Cox proportional regression analyses were utilized to determine the association of miR-20a with survival of patients. The potential functions of miR-20a on proliferation were evaluated by proliferation and flow cytometry analysis. The direct target gene of miR-20a was also identified by luciferase reporter assays.
MiR-20a was lower in primary HCC than normal liver, and were further decreased in those with post-liver transplantation (LT) HCC recurrence compared with those with non-recurrence (p = 0.001). Patients with lower miR-20a expression had significantly poorer recurrence-free survival (RFS, Log rank p < 0.001) and overall survival (OS, Log rank p < 0.001). Multivariate analysis revealed that lower miR-20a was an independent predictor of poor prognosis. MiR-20a restoration could suppress HepG2 and SMMC-7721 cells proliferation and induce cell cycle G1 arrest and apoptosis. Subsequent investigations revealed that miR-20a directly targeted myeloid cell leukemia sequence 1 (Mcl-1) and reduced the endogenous protein level of Mcl-1 in HCC cells.
MiR-20a is decreased in HCCs and correlates with HCC recurrence and prognosis. Down-regulation of miR-20a increases the proliferation abilities of HCC cells. Our findings suggest miR-20a may represent a novel potential therapeutic target and biomarker for survival of HCC patients.
MicroRNA-20a; Hepatocellular Carcinoma; Recurrence; Prognosis; Liver transplantation
Generalization is an important process that allows animals to extract rules from regularities of past experience and apply them to analogous situations. In particular, the generalization of previously learned actions to novel instruments allows animals to use past experience to act faster and more efficiently in an ever-changing environment. However, generalization of actions to a dissimilar instrument or situation may also be detrimental. In this study, we investigate the neural bases of action generalization and discrimination in mice trained on a lever-pressing task. Using specific schedules of reinforcement known to bias animals towards habitual or goal-directed behaviors, we confirmed that action generalization is more prominent in animals using habitual rather than goal-directed strategies. We uncovered that selective excitotoxic lesions of the dorsolateral and dorsomedial striatum have opposite effects on the generalization of a previously learned action to a novel lever. While lesions of the dorsolateral striatum impair action generalization, dorsomedial striatum lesions affect action discrimination and bias subjects towards action generalization. Importantly, these lesions do not affect the ability of animals to explore or match their lever-pressing rate to the reinforcement rate, or the ability to distinguish between different levers. The data presented here reveal that dorsolateral and dorsomedial striatal circuits have opposing roles in the generalization of previously learned actions to novel instruments, and suggest that these circuits compete for the expression of generalization in novel situations.
habit; goal-directed; basal ganglia; motor; learning; memory
AIM: To compare the prognostic assessment of lymph node ratio and absolute number based staging system for gastric cancer after D2 resection.
METHODS: The clinical, pathologic, and long-term follow-up data of 427 patients with gastric cancer that underwent D2 curative gastrectomy were retrospectively analyzed. The relationships between the metastatic lymph node ratio (MLR), log odds of positive lymph nodes (LODDS), and positive lymph nodes (pN) staging methods and the long-term prognoses of the patients were compared. In addition, the survival curves, accuracy, and homogeneity were compared with stratification to evaluate the prognostic assessment of the 3 methods when the number of tested lymph nodes was insufficient (< 10 and 10-15).
RESULTS: MLR [hazard ratio (HR) = 1.401, P = 0.012], LODDS (HR = 1.012, P = 0.034), and pN (HR = 1.376, P = 0.005) were independent risk factors for gastric cancer patients. The receiver operating characteristic (ROC) curves showed that the prognostic accuracy of the 3 methods was comparable (P > 0.05). Spearman correlation analysis confirmed that MLR, LODDS, and pN were all positively correlated with the total number of tested lymph nodes. When the number of tested lymph node was < 10, the value of survival curves staged by MLR and LODDS was superior to those of pN staging. However, the difference in survival curves between adjacent stages was not significant. In addition, the survival rate of stage 4 patients using the MLR and LODDS staging methods was 26.7% and 27.3% with < 10 lymph node, respectively which were significantly higher than the survival rate of patients with > 15 tested lymph nodes (< 4%). The ROC curve showed that the accuracy of the prognostic assessment of MLR, LODDS, and pN staging methods was comparable (P > 0.05), and the area under the ROC curve of all 3 methods were increased progressively with the enhanced levels of examined lymph nodes. In addition, the homogeneity of the 3 methods in patients with ≤ 15 tested lymph nodes also showed no significant difference.
CONCLUSION: Neither MLR or LODDS could reduce the staging bias. A sufficient number of tested lymph nodes is key to ensure an accurate prognosis for patients underwent D2 radical gastrectomy.
Gastric cancer; Metastatic lymph node ratio; Lymph node metastasis; Prognosis
Endothelial hyperpermeability induced by hyperglycemia is the initial step in the development of atherosclerosis, one of the most serious cardiovascular complications in diabetes. In the present study, we investigated the effects of resveratrol (RSV), a bioactive ingredient extracted from Chinese herb rhizoma polygonum cuspidatum, on permeability in vitro and the molecular mechanisms involved. Permeability was assessed by the efflux of fluorescein isothiocyanate (FITC)-dextran permeated through the monolayer endothelial cells (ECs). The mRNA levels, protein expressions, and secretions were measured by quantitative real-time PCR, western blot, and ELISA, respectively. Increased permeability and caveolin-1 (cav-1) expression were observed in monolayer ECs exposed to high glucose. Resveratrol treatment alleviated the hyperpermeability and the overexpression of cav-1 induced by high glucose in a dose-dependent manner. β-Cyclodextrin, a structural inhibitor of caveolae, reduced the hyperpermeability caused by high glucose. Resveratrol also down-regulated the increased expressions of vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR, or VEGF receptor-2) induced by high glucose. Inhibition of VEGF/KDR pathway by using SU5416, a selective inhibitor of KDR, alleviated the hyperpermeability and the cav-1 overexpression induced by high glucose. The above results demonstrate that RSV ameliorates caveolae-mediated hyperpermeability induced by high glucose via VEGF/KDR pathway.
Resveratrol; Diabetes; Atherosclerosis; Hyperpermeability; Caveolae; VEGF
Water is essential for all living organisms. Aquaporin proteins are the major facilitator of water transport activity through cell membranes of plants including soybean. These proteins are diverse in plants and belong to a large major intrinsic (MIP) protein family. In higher plants, MIPs are classified into five subfamilies including plasma membrane intrinsic proteins (PIP), tonoplast intrinsic proteins (TIP), NOD26-like intrinsic proteins (NIP), small basic intrinsic proteins (SIP), and the recently discovered X intrinsic proteins (XIP). This paper reports genome wide assembly of soybean MIPs, their functional prediction and expression analysis. Using a bioinformatic homology search, 66 GmMIPs were identified in the soybean genome. Phylogenetic analysis of amino acid sequences of GmMIPs divided the large and highly similar multi-gene family into 5 subfamilies: GmPIPs, GmTIPs, GmNIPs, GmSIPs and GmXIPs. GmPIPs consisted of 22 genes and GmTIPs 23, which showed high sequence similarity within subfamilies. GmNIPs contained 13 and GmSIPs 6 members which were diverse. In addition, we also identified a two member GmXIP, a distinct 5th subfamily. GmMIPs were further classified into twelve subgroups based on substrate selectivity filter analysis. Expression analyses were performed for a selected set of GmMIPs using semi-quantitative reverse transcription (semi-RT-qPCR) and qPCR. Our results suggested that many GmMIPs have high sequence similarity but diverse roles as evidenced by analysis of sequences and their expression. It can be speculated that GmMIPs contains true aquaporins, glyceroporins, aquaglyceroporins and mixed transport facilitators.
To date, the only established model for assessing risk for nasopharyngeal carcinoma (NPC) relies on the sero-status of the Epstein-Barr virus (EBV). By contrast, the risk assessment models proposed here include environmental risk factors, family history of NPC, and information on genetic variants. The models were developed using epidemiological and genetic data from a large case-control study, which included 1,387 subjects with NPC and 1,459 controls of Cantonese origin. The predictive accuracy of the models were then assessed by calculating the area under the receiver-operating characteristic curves (AUC). To compare the discriminatory improvement of models with and without genetic information, we estimated the net reclassification improvement (NRI) and integrated discrimination index (IDI). Well-established environmental risk factors for NPC include consumption of salted fish and preserved vegetables and cigarette smoking (in pack years). The environmental model alone shows modest discriminatory ability (AUC = 0.68; 95% CI: 0.66, 0.70), which is only slightly increased by the addition of data on family history of NPC (AUC = 0.70; 95% CI: 0.68, 0.72). With the addition of data on genetic variants, however, our model’s discriminatory ability rises to 0.74 (95% CI: 0.72, 0.76). The improvements in NRI and IDI also suggest the potential usefulness of considering genetic variants when screening for NPC in endemic areas. If these findings are confirmed in larger cohort and population-based case-control studies, use of the new models to analyse data from NPC-endemic areas could well lead to earlier detection of NPC.
20(S)-protopanaxadiol (PPD), similar to several other anticancer agents, has low oral absorption and is extensively metabolized. These factors limit the use of PPD for treatment of human diseases.
In this study, we used cubic nanoparticles containing piperine to improve the oral bioavailability of PPD and to enhance its absorption and inhibit its metabolism. Cubic nanoparticles loaded with PPD and piperine were prepared by fragmentation of glyceryl monoolein (GMO)/poloxamer 407 bulk cubic gel and verified using transmission electron microscopy and differential scanning calorimetry. We evaluated the in vitro release of PPD from these nanoparticles and its absorption across the Caco-2 cell monolayer model, and subsequently, we examined the bioavailability and metabolism of PPD and its nanoparticles in vivo.
The in vitro release of PPD from these nanoparticles was less than 5% at 12 hours. PPD-cubosome and PPD-cubosome loaded with piperine (molar ratio PPD/piperine, 1:3) increased the apical to basolateral permeability values of PPD across the Caco-2 cell monolayer from 53% to 64%, respectively. In addition, the results of a pharmacokinetic study in rats showed that the relative bioavailabilities of PPD-cubosome [area under concentration–time curve (AUC)0–∞] and PPD-cubosome containing piperine (AUC0–∞) compared to that of raw PPD (AUC0–∞) were 166% and 248%, respectively.
The increased bioavailability of PPD-cubosome loaded with piperine is due to an increase in absorption and inhibition of metabolism of PPD by cubic nanoparticles containing piperine rather than because of improved release of PPD. The cubic nanoparticles containing piperine may be a promising oral carrier for anticancer drugs with poor oral absorption and that undergo extensive metabolism by cytochrome P450.
20(S)-protopanaxadiol; cubosome; piperine; Caco-2 cell monolayer; bioavailability; metabolites
Mixed micelles are widely used to increase solubility and bioavailability of poorly soluble drugs. One promising antitumor drug candidate is 20(S)-protopanaxadiol (PPD), although its clinical application is limited by low water solubility and poor bioavailability after oral administration. In this study, we developed mixed micelles consisting of PPD–phospholipid complexes and Labrasol® and evaluated their potential for oral PPD absorption. Micelles were prepared using a solvent-evaporation method, and their physicochemical properties, including particle size, zeta potential, morphology, crystal type, drug loading, drug entrapment efficiency, and solubility, were characterized. Furthermore, in vitro release was investigated using the dialysis method, and transport and bioavailability of the mixed micelles were investigated through a Caco-2 cell monolayer and in vivo absorption studies performed in rats. Compared with the solubility of free PPD (3 μg/mL), the solubility of PPD in the prepared mixed micelles was 192.41 ± 1.13 μg/mL in water at room temperature. The in vitro release profiles showed a significant difference between the more rapid release of free PPD and the slower and more sustained release of the mixed micelles. At the end of a 4-hour transport study using Caco-2 cells, the apical-to-basolateral apparent permeability coefficients (Papp) increased from (1.12 ± 0.21) × 106 cm/s to (1.78 ± 0.16) × 106 cm/s, while the basolateral-to-apical Papp decreased from (2.42 ± 0.16) × 106 cm/s to (2.12 ± 0.32) × 106. In this pharmacokinetic study, compared with the bioavailability of free PPD (area under the curve [AUC]0–∞), the bioavailability of PPD from the micelles (AUC0–∞) increased by approximately 216.36%. These results suggest that novel mixed micelles can significantly increase solubility, enhance absorption, and improve bioavailability. Thus, these prepared micelles might be potential carriers for oral PPD delivery in antitumor therapies.
20(S)-protopanaxadiol; phospholipid complex; Labrasol; mixed micelles; Caco-2 cell monolayer; bioavailability
Genetic factors account for the majority of differences in skin color and hair morphology across human populations. Although many studies have been conducted to examine differences in skin color across populations, few studies have examined differences in hair morphology.
To investigate changing of integral hair lipids after ultraviolet (UV) irradiation in three human ethnic groups.
We studied the UV irradiation induced hair damage in hairs of three human populations. UV irradiation had been performed with self-manufactured phototherapy system. Damaged hair samples were prepared at 12 and 48 hours after UVA (20 J/sec) and UVB (8 J/sec) irradiation. We evaluated the changes of hair lipid using scanning electron microscopy (SEM), transmission electron microscopy (TEM), lipid TEM and HP-TLC. After UV irradiation, hair surface damage was shown.
African hair showed more severe damage on hair surface than others. The lipid compositions across human populations were similar, but Asian hair had more integral hair lipids than other groups as a whole. Especially, free fatty acid contents were higher than other lipids. After UV irradiation, lipid contents were decreased. These patterns were shown in all human populations. Asian hair has more integral hair lipid than European or African hair. After UV irradiation, European and African hair samples exhibited more damage because they have less integral hair lipids. However, Asian hair samples have less damage.
We conclude that integral hair lipid may protect the hair against the UV light.
Ethnic groups; Integral hair lipid; UV irradiation
The aim of this study was to investigate whether abnormal expression of matrix metalloproteinase (MMP)-9/tissue inhibitors of MMPs (TIMP)-1 and B cell lymphoma 2 (BCL-2)/BCL-2-associated X protein (BAX) are correlated with the characteristic accelerated fibrosis and apoptosis during ageing and in atrial fibrillation (AF). Four groups of dogs were studied: adult dogs in sinus rhythm (SR), aged dogs in SR, adult dogs with AF induced by rapid atrial pacing and aged dogs with AF induced by rapid atrial pacing. The mRNA and protein expression levels of the target gene in the left atrium were measured by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis. Pathohistological and ultrastructural changes were assessed by light and electron microscopy. The apoptotic indices of myocytes were detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL). The mRNA and protein expression levels of MMP-9 and BAX and those of TIMP-1 and BCL-2 were significantly upregulated and down-regulated, respectively, in the aged groups compared with the adult groups. Compared with the control groups, the adult and aged groups with AF exhibited significantly increased mRNA and protein expression levels of MMP-9 and BAX and decreased expression levels of TIMP-1 and BCL-2. Samples of atrial tissue demonstrated abnormal pathohistological and ultrastructural changes, accelerated fibrosis and apoptosis. MMP-9/TIMP-1 and BCL-2/BAX hold potential for use as substrates conducive to AF and their abnormal expression plays a major role in structural remodeling of the atrium.
atrial fibrillation; ageing; structural remodeling; atrial fibrosis; apoptosis
Hypoadiponectinemia contributes to the development of obesity and related disorders such as diabetes, hyperlipidemia, and cardiovascular diseases. In this study we investigated the effects of green tea polyphenols (GTPs) on adiponectin levels and fat deposits in high fat (HF) fed rats, the mechanism of signaling pathway was explored as well.
Methods and Results
Male Wistar rats were fed with high-fat diet. GTPs (0.8, 1.6, 3.2 g/L) were administered via drinking water. Serum adiponectin and insulin were measured by ELISA, mRNA levels of adiponectin and PPARγ in visceral adipose tissue (VAT) were determined by Real-time PCR, protein levels of PPARγ, phospho (p) - PPARγ, extracellular signal regulated kinase (erk) 1/2 and p-erk1/2 in VAT were determined by western blot. GTPs treatment attenuated the VAT accumulation, hypoadiponectinemia and the decreased mRNA level of adiponectin in VAT induced by HF. Decreased expression and increased phosphorylation of PPARγ (the master regulator of adiponectin), and increased activation of erk1/2 were observed in HF group, and these effects could be alleviated by GTPs treatment. To explore the underlying mechanism, VAT was cultured in DMEM with high glucose to mimic the hyperglycemia condition in vitro. Similar to the results of in vivo study, decreased adiponectin levels, decreased expression and increased phosphorylation of PPARγ, and elevated erk1/2 phosphorylation in cultured VAT were observed. These effects could be ameliorated by co-treatment with GTPs or PD98059 (a selective inhibitor of erk1/2).
GTPs reduced fat deposit, ameliorated hypoadiponectinemia in HF-fed rats, and relieved high glucose-induced adiponectin decrease in VAT in vitro. The signaling pathway analysis indicated that PPARγ regulation mediated via erk1/2 pathway was involved.
Sensitivity to pain varies considerably between individuals and is known to be heritable. Increased sensitivity to experimental pain is a risk factor for developing chronic pain, a common and debilitating but poorly understood symptom. To understand mechanisms underlying pain sensitivity and to search for rare gene variants (MAF<5%) influencing pain sensitivity, we explored the genetic variation in individuals' responses to experimental pain. Quantitative sensory testing to heat pain was performed in 2,500 volunteers from TwinsUK (TUK): exome sequencing to a depth of 70× was carried out on DNA from singletons at the high and low ends of the heat pain sensitivity distribution in two separate subsamples. Thus in TUK1, 101 pain-sensitive and 102 pain-insensitive were examined, while in TUK2 there were 114 and 96 individuals respectively. A combination of methods was used to test the association between rare variants and pain sensitivity, and the function of the genes identified was explored using network analysis. Using causal reasoning analysis on the genes with different patterns of SNVs by pain sensitivity status, we observed a significant enrichment of variants in genes of the angiotensin pathway (Bonferroni corrected p = 3.8×10−4). This pathway is already implicated in animal models and human studies of pain, supporting the notion that it may provide fruitful new targets in pain management. The approach of sequencing extreme exome variation in normal individuals has provided important insights into gene networks mediating pain sensitivity in humans and will be applicable to other common complex traits.
Chronic widespread pain is a complex clinical problem. Identification of underlying genetic factors would shed light on the biology of pain and offer targets for novel therapies. We aimed to identify rare genetic variants in the normal population associated with pain sensation by performing exome sequencing on individuals who were more or less sensitive to heat pain. While we did not identify any single variants having large effect, we did observe major group differences between the sensitive and insensitive individuals. Network analysis suggested a role for the angiotensin pathway, which previous work in animal models has suggested is important in pain mediation. Our results cast light on the genetic factors underlying normal pain sensation in humans and the utility of exome analyses. It suggests that further exploration of the angiotensin pathway may reveal novel targets for the treatment of pain.
AIM: To investigate whether the expression of kallikrein 12 (KLK12) is related to the development of gastric cancer (GC) and to determine the role of KLK12 in gastric cancer cells growth, invasion and migration.
METHODS: Between September 2007 and March 2008, 133 patients with histologically confirmed GC were recruited for the study. Expression of KLK12 was detected in samples from GC patients by quantitative real-time reverse transcription polymerase chain reaction and immunohistochemistry. The relationship between KLK12 protein expression and clinicopathological features of GC was analyzed. The difference in 5-year survival rates between the high KLK12 protein expression group and the low KLK12 expression group was compared. Additionally, the expression of KLK12 was examined in various human GC cell lines, including MKN-28, SGC-7901 and MKN-45. Small interfering RNA (siRNA) was used to inhibit KLK12 expression in MKN-45 cells. Cell clones stably transfected with KLK12 siRNA were tested for KLK12 expression by quantitative real-time reverse transcription-polymerase chain reaction and Western blotting. Furthermore, a series of functional assays were performed in this study to assess the biological features of transfected cells. Cell proliferation was assessed using the methylthiazolyltetrazoliumassay. Finally, cell migration and invasion were assessed using transwell chamber assays.
RESULTS: Of the 133 GC patients included in the study, 126 (94.7%) showed a higher expression level of KLK12 mRNA when compared to noncancerous tissue specimens. Expression of KLK12 mRNA was significantly higher in GC tissues than in normal tissue (P < 0.001). KLK12 protein expression was detected in 96 of 133 (72.2%) GC samples with moderate or strong staining primarily in the cytoplasm. In contrast, negative immunostaining for KLK12 protein was observed in the corresponding normal gastric mucosal tissue. Overexpression of KLK12 protein was significantly associated with lymph node metastasis (P = 0.001), histological type (P < 0.001) and tumor-node-metastasis stage (P = 0.005), while no significant correlation was observed between expression of KLK12 protein and sex, age, depth of invasion, tumor size or lymphatic invasion. Furthermore, patients with high KLK12 expression had a significantly poorer 5-year survival rate than those with low KLK12 expression (P = 0.002). Expression of KLK12 mRNA was significantly higher in MKN-45 GC cells compared to normal mucosal cells or two other GC cell lines (P < 0.01). Expression of KLK12 in MKN-45 cells was downregulated after transfection with siRNA. Knockdown of KLK12 markedly decreased the proliferation of MKN-45 cells when compared with parent or mock-transfected cells (P = 0.001), especially from the 3rd to the 5th day of the assay. In migration assays, fewer KLK12 siRNA cells migrated through the chambers (22.00 ± 1.81) when compared to the parent (46.47 ± 2.42) or mock-transfected cells (45.40 ± 1.99); these differences were statistically significant (P < 0.001). However, in the invasion assay, the number of KLK12 siRNA cells that invaded the chambers was 18.40 ± 1.12, closely similar to both the parent (18.67 ± 0.98) and mock-transfected cells (18.53 ± 0.92). There was no significantly difference between the three groups in the invasion assay (P = 0.054).
CONCLUSION: The KLK12 gene is markedly overexpressed in GC tissue, and its expression status may be a powerful prognostic indicator for patients with GC. KLK12 might serve as a novel diagnosis and prognosis biomarker in GC.
Gastric cancer; Human kallikrein 12; Immunohistochemistry; Prognosis; Small interfering RNA; Migration; Invasion
Soil salinity has very adverse effects on growth and yield of crop plants. Several salt tolerant wild accessions and cultivars are reported in soybean. Functional genomes of salt tolerant Glycine soja and a salt sensitive genotype of Glycine max were investigated to understand the mechanism of salt tolerance in soybean. For this purpose, four libraries were constructed for Tag sequencing on Illumina platform. We identify around 490 salt responsive genes which included a number of transcription factors, signaling proteins, translation factors and structural genes like transporters, multidrug resistance proteins, antiporters, chaperons, aquaporins etc. The gene expression levels and ratio of up/down-regulated genes was greater in tolerant plants. Translation related genes remained stable or showed slightly higher expression in tolerant plants under salinity stress. Further analyses of sequenced data and the annotations for gene ontology and pathways indicated that soybean adapts to salt stress through ABA biosynthesis and regulation of translation and signal transduction of structural genes. Manipulation of these pathways may mitigate the effect of salt stress thus enhancing salt tolerance.