The ankle injuries create great pain to a great number of patients worldwide. Past studies have focused on the development of practical treatments to relieve pain and improve recovery, but the molecular mechanisms underlying the ankle injuries, especially the local inflammation in the damaged ankle joint, have been rarely studied. Moreover, although reduction of production and secretion of pro-inflammatory cytokines may reduce the pain and promote the recovery, a practical approach is currently lacking. Here, we detected significantly higher levels of placental growth factor (PLGF) and pro-inflammatory cytokines in the joint fluid from the patients of acute ankle joint injury (AAJI). Interestingly, the levels of PLGF and pro-inflammatory cytokines in the joint fluid strongly correlated. In order to examine whether PLGF may regulate the production and secretion of pro-inflammatory cytokines in the injured joint, we used a rat carrageenan-induced ankle injury model for AAJI in humans. We injected soluble Flt-1 (sFlt-1) into the articular cavity of the injured ankle joint to block PLGF signaling and found that injection of sFlt-1 significantly improved the rat behavior in activity wheels test, which appeared to result from reduced secretion of the pro-inflammatory cytokines in the ankle joint. Thus, our study suggests that blocking PLGF signaling may be a novel therapeutic approach for treating AAJI in humans.
Soluble Flt-1 (sFlt-1); acute ankle joint injury (AAJI); inflammation; placental growth factor (PLGF)
In the present study, we developed a novel type of reduction-sensitive nanoparticles (NPs) for docetaxel (DTX) delivery based on cross-linked lipoic acid NPs (LANPs). The physicochemical properties, cellular uptake and in vitro cytotoxicity of DTX loaded LANPs (DTX-LANPs) on A549 cells were investigated. Furthermore, the in vivo distribution and in vivo efficacy of DTX-LANPs was evaluated. The results showed that DTX-LANPs had a particle size of 110 nm and a negative zeta potential of −35 mv with excellent colloidal stability. LANPs efficiently encapsulated DTX with a high drug loading of 4.51% ± 0.49% and showed remarkable reduction-sensitive drug release in vitro. Cellular uptake experiments demonstrated that LANPs significantly increased intracellular DTX uptake by about 10 fold as compared with free DTX. The cytotoxicity of DTX-LANPs showed significantly higher potency in inhibiting A549 cell growth than free DTX, while blank LANPs had a good biocompatibility. In addition, in vivo experiments demonstrated that DTX-LANPs could enhance tumour targeting and anti-tumour efficacy with low systemic toxicity. In conclusion, LANPs may prove to be a potential tumour microenvironment-responsive delivery system for cancer treatment, with the potential for commercialization due to the simple component, controllable synthesis, stability and economy.
Recent studies suggested that the androgen receptor (AR) might play important roles to influence the bladder cancer (BCa) progression, yet its clinical application remains unclear. Here we developed a new combined therapy with Bacillus Calmette-Guérin (BCG) and the AR degradation enhancer ASC-J9® or anti-androgen hydroxyflutamide (HF) to better suppress the BCa progression. Mechanism dissection revealed that ASC-J9® treatment enhanced BCG efficacy to suppress BCa cell proliferation via increasing the recruitment of monocytes/macrophages that involved the promotion of BCG attachment/internalization to the BCa cells through increased integrin-α5β1 expression and IL-6 release. Such consequences might then enhance BCG-induced BCa cell death via increased TNF-α release. Interestingly, we also found ASC-J9® treatment could directly promote BCG-induced HMGB1 release to enhance the BCG cytotoxic effects for the suppression of BCa cell growth. In vivo approaches also concluded that ASC-J9® could enhance the BCG efficacy to better suppress the BCa progression in BBN-induced BCa mouse models. Together, these results suggest that the newly developed therapy combining BCG plusASC-J9® may become a novel therapy to better suppress BCa progress.
bladder cancer; BCG; HF; androgen receptor
Formation of the three embryonic germ layers is a fundamental developmental process that initiates differentiation. How the zebrafish pluripotency factor Pou5f3 (homologous to mammalian Oct4) drives lineage commitment is unclear. Here, we introduce fluorescence lifetime imaging microscopy and fluorescence correlation spectroscopy to assess the formation of Pou5f3 complexes with other transcription factors in real-time in gastrulating zebrafish embryos. We show, at single-cell resolution in vivo, that Pou5f3 complexes with Nanog to pattern mesendoderm differentiation at the blastula stage. Later, during gastrulation, Sox32 restricts Pou5f3–Nanog complexes to the ventrolateral mesendoderm by binding Pou5f3 or Nanog in prospective dorsal endoderm. In the ventrolateral endoderm, the Elabela / Aplnr pathway limits Sox32 levels, allowing the formation of Pou5f3–Nanog complexes and the activation of downstream BMP signaling. This quantitative model shows that a balance in the spatiotemporal distribution of Pou5f3–Nanog complexes, modulated by Sox32, regulates mesendoderm specification along the dorsoventral axis.
As an animal embryo develops, cells divide and establish three distinct layers called the ectoderm, mesoderm and endoderm. Proteins called transcription factors control this process by regulating the activity of particular genes. Two or more transcription factors may interact to modulate each other’s activity. Zebrafish embryos provide an ideal model system for monitoring how these embryonic layers form and the interactions between transcription factors in real-time because they are transparent and develop outside their parents. Pou5f3 and Nanog are two key transcription factors involved in this process in zebrafish. However, it is not clear how Pou5f3 and Nanog instruct cells to become ectoderm, mesoderm or endoderm.
Perez Camps et al. used imaging techniques to study Pou5f3 and Nanog. The experiments show that Pou5f3 and Nanog bind together to form complexes that instruct cells to form the temporary layer that later gives rise to both the mesoderm and endoderm. The cells in which there are less Pou5f3 and Nanog complexes form the ectoderm layer.
To develop the body shape of adult zebrafish, the embryos need to give individual cells information about their location in the body. For example, a signal protein called bone morphogenetic protein (BMP) accumulates on the side of the embryo that will become the underside of the fish. Perez Camps et al. show that once the endoderm, mesoderm and ectoderm have formed, Pou5f3–Nanog complexes regulate BMP signalling to specify the underside of the fish. Meanwhile, in the endoderm on the opposite side, another transcription factor called Sox32 binds to individual Pou5f3 and Nanog proteins. This prevents Pou5f3 and Nanog from forming complexes and determines which side of the embryo will make the topside of the fish. A future challenge is to explore other transcription factors that may prevent Pou5f1 and Nanog from binding in the mesoderm and ectoderm of the topside of the fish.
transcription factor dynamics; pluripotency; gastrulation; FLIM; FCS; elabela; aplnr; nanog; oct4; sox32; Zebrafish
Refractive error (RE) is a complex multifactorial disease. Genome-wide association studies (GWAS) have provided significant insight into the genetic architecture and identified plenty of robust genetic variations or single nucleotide polymorphisms (SNPs) associated with complex disease. A major current challenge is to convert those resources into causal variants and target genes. We used RegulomeDB and HaploReg to annotate regulatory information onto associated SNPs derived from the two largest RE GWAS, and additional SNPs in linkage disequilibrium (LD) with GWAS significant SNPs. Overall 868 SNPs were investigated, out of which 662 returned RegulomeDB scores of 1 to 6. It was observed that 36 out of those SNPs show strong evidence of regulatory effects with a RegulomeDB score of 1, while only four of them were GWAS significant SNPs (CD55/rs1652333, CNDP2/rs12971120, RDH5/rs3138142 and rs3138144). The results encourage us to explore those putative pathogenic variants, both GWAS significant SNPs as well as the SNPs in LD, for future discernment of functional consequence. This study offers the attractive approach for prioritizing potential functional variants by combining ENCODE data and GWAS information, and provide further insights into the pathogenesis and mechanism and ultimately therapeutics.
A rate feed forward control-based sensor fusion is proposed to improve the closed-loop performance for a charge couple device (CCD) tracking loop. The target trajectory is recovered by combining line of sight (LOS) errors from the CCD and the angular rate from a fiber-optic gyroscope (FOG). A Kalman filter based on the Singer acceleration model utilizes the reconstructive target trajectory to estimate the target velocity. Different from classical feed forward control, additive feedback loops are inevitably added to the original control loops due to the fact some closed-loop information is used. The transfer function of the Kalman filter in the frequency domain is built for analyzing the closed loop stability. The bandwidth of the Kalman filter is the major factor affecting the control stability and close-loop performance. Both simulations and experiments are provided to demonstrate the benefits of the proposed algorithm.
sensor fusion; charge couple device; feedforward control; time delay; light of sight error, FOG
In the inversion of land surface temperature (LST) from satellite data, obtaining the information on land surface emissivity is most challenging. How to solve both the emissivity and the LST from the underdetermined equations for thermal infrared radiation is a hot research topic related to quantitative thermal infrared remote sensing. The academic research and practical applications based on the temperature-emissivity retrieval algorithms show that directly measuring the emissivity of objects at a fixed thermal infrared waveband is an important way to close the underdetermined equations for thermal infrared radiation. Based on the prior research results of both the authors and others, this paper proposes a new approach of obtaining the spectral emissivity of the object at 8–14 µm with a single-band CO2 laser at 10.6 µm and a 102F FTIR spectrometer. Through experiments, the spectral emissivity of several key samples, including aluminum plate, iron plate, copper plate, marble plate, rubber sheet, and paper board, at 8–14 µm is obtained, and the measured data are basically consistent with the hemispherical emissivity measurement by a Nicolet iS10 FTIR spectrometer for the same objects. For the rough surface of materials, such as marble and rusty iron, the RMSE of emissivity is below 0.05. The differences in the field of view angle and in the measuring direction between the Nicolet FTIR method and the method proposed in the paper, and the heterogeneity in the degree of oxidation, polishing and composition of the samples, are the main reasons for the differences of the emissivities between the two methods.
10.6 µm single-band CO2 laser; temperature-emissivity retrieval; active/passive synergistic measurement and inversion
The aim of the study was to investigate the significance of the level of serum 25-hydroxyvitamin D3 [25-(OH)D3] and interleukin (IL)-6 in serum prior to and after immunoglobulin treatment in children suffering from Kawasaki disease in order to provide a reference for the successful treatment of Kawasaki disease in children. From February, 2013 to February, 2015, 45 patients with Kawasaki disease were enrolled in the observation group. The normal control group comprised 43 healthy volunteers and the feverish control group 46 patients with respiratory infection and fever. Venous blood was collected from each case before and after immunoglobulin treatment and the level of 25-(OH)D3 and IL-6 in the serum were measured using fluorescent quantitative PCR, enzyme-linked immunosorbent assay and western blotting. Before treatment, the level of 25-(OH)D3 in the feverish control group was significantly lower than that of the normal control group, while the level of 25-(OH)D3 in the observation group was significantly higher than that of the normal control group. The level of 25-(OH)D3 in the feverish control group was lower than the IL-6 level in the normal children, but the difference was not statistically significant (P>0.05). The level 25-(OH)D3 in the observation group was significantly higher than the IL-6 level in the normal control group. The serum content of 25-(OH)D3 was significantly higher after the treatment compared to before treatment levels and after treatment IL-6 level was only slightly lower. It was observed that the 25-(OH)D3 level in the observation group was significantly increased after immunoglobulin treatment and this was positively correlated with the effects of the treatment. The IL-6 level had no significant changes after treatment and had little correlation with the treatment effect. The results suggested that 25-(OH)D3 may be involved in the occurrence of Kawasaki disease in children and in the aggravation of the disease to some extent.
children Kawasaki disease; immunoglobulin; serum 25-(OH)D3; interleukin-6; treatment
This study was conducted to evaluate the toxicity and efficacy of pemetrexed plus dendritic cells (DCs) when administered as third-line treatment for metastatic esophageal squamous cell carcinoma (ESCC). All patients in the study group had previously failed first-line treatment with 5-fluorouracil and cisplatin-based regimens, as well as second-line treatment with taxane-based regimens. A total of 31 patients were treated with pemetrexed (500 mg/m2) plus DCs on day 1, every 3 weeks. DCs were given for one cycle of 21 days. Thirty patients were evaluated for their response. No patient had a complete response, three patients (10.0%) had a partial response, ten patients (33.3%) had stable disease, and 17 patients (56.7%) had progressive disease. The overall response rate was 10.0%. The median progression-free survival (PFS) time was 2.9 months (95% CI, 2.7–3.2), and the median overall survival (OS) time was 7.1 months (95% CI, 6.4–7.9). The median PFS and OS times among patients with high and low levels of miR-143 expression in their blood serum were significantly different: median PFS times =3.2 months (95% CI, 2.9–3.4) and 2.7 months (95% CI, 2.4–3.0), respectively (P=0.017), and median OS times =7.8 months (95% CI, 6.8–8.9) and 6.3 months (95% CI, 5.3–7.3), respectively (P=0.036). No patient experienced Grade 4 toxicity. Combined third-line treatment with pemetrexed and DCs was marginally effective and well tolerated in patients with advanced ESCC. Serum miR-143 levels are a potential biomarker for predicting the efficacy of pemetrexed plus DCs in the treatment of ESCC.
metastatic esophageal cancer; pemetrexed; dendritic cells; serum miR-143
We examined community diversity, structure and carbon footprint of nematode food web along a chronosequence of T. Sinensis reforestation on degraded Karst. In general, after the reforestation: a serious of diversity parameters and community indices (Shannon-Weinier index (H′), structure index (SI), etc.) were elevated; biomass ratio of fungivores to bacterivores (FFC/BFC), and fungi to bacteria (F/B) were increased, and nematode channel ratio (NCR) were decreased; carbon footprints of all nematode trophic groups, and biomass of bacteria and fungi were increased. Our results indicate that the Karst aboveground vegetation restoration was accompanied with belowground nematode food web development: increasing community complexity, function and fungal dominance in decomposition pathway, and the driving forces included the bottom-up effect (resource control), connectedness of functional groups, as well as soil environments.
Recent studies showed the potential linkage of estrogen/estrogen receptor signaling with bladder tumorigenesis, yet detailed mechanisms remain elusive. Here we found a new potential therapy with the combination of Bacillus Calmette Guerin (BCG) and the anti-estrogen ICI 182,780 led to better suppression of bladder cancer (BCa) than BCG alone. Mechanism dissection found ICI 182,780 could promote BCG attachment/internalization to the BCa cells through increased integrin-α5β1 expression and IL-6 release, which may enhance BCG-induced suppression of BCa cell growth via recruiting more monocytes/macrophages to BCa cells and increased TNF-α release. Consistently, in vivo studies found ICI 182,780 could potentiate the anti-BCa effects of BCG in the carcinogen-induced mouse BCa models. Together, these in vitro and in vivo results suggest that combining BCG with anti-estrogen may become a new therapeutic approach with better efficacy to suppress BCa progression and recurrence.
Bacillus Calmette-Guérin; bladder cancer; estrogen; estrogen receptor alpha
Early growth response gene-1 (EGR1) widely exists in the cell nucleus of such as, zebrafish, mice, chimpanzees and humans, an it also can be observed in the cytoplasm of some tumors. EGR1 was named just after its brief and rapid expression of different stimuli. Accumulating studies have extensively demonstrated that the widespread dysregulation of EGR1 is involved in hematological malignancies such as human acute myeloid leukemia (AML), chronic myelogenous leukemia, chronic lymphocytic leukemia, multiple myeloma, and B cell lymphoma. With the deep research on EGR1, its expression, function and regulatory mechanism has been gradually elucidated, and provides more possibilities for treatment strategies of patients with leukemia. Herein, we summarize the roles of EGR1 in its biological function and relationship with leukemia.
Early growth response gene-1 (EGR1); acute myeloid leukemia; tumor
Pelvic fracture combined with massive bleeding (PFCMB) is a complex issue in clinical practice. Currently, the use of angiography and embolization for the treatment of PFCMB obtains good results. The aim of this study is to observe the effects of early internal iliac artery embolization on the SIRS in dogs with simulated-pelvic-fracture combined with massive bleeding.
Twenty adult dogs were randomly divided into an embolization group (EG) and a control group (CG). For the two groups, heart rate, respiratory rate and body temperature and other physiological variables were measured, and IL-6, TNF-α and arterial blood gas levels were monitored. These variables were assayed every 30 min until death in the CG, while dogs in the EG underwent arterial angiography after 60 min of modeling. The internal iliac artery was embolized on the injured side.
The average time to SIRS in the CG was 3.56 h, occurring at a rate of 90 % (9/10) within 24 h, with a mortality rate of 50 % (5/10); the average time to SIRS for the EG was 5.33 h, occurring at a rate of 30 % (3/10) within 24 h, with a mortality rate of 10 % (1/10). When SIRS occurred in the EG, the mean plasma IL-6 level was 52.66 ± 7.38 pg/ml and the TNF-α level was 11.45 ± 2.72 ng/ml, showing a significant difference with those of the CG (P < 0.05). In the two groups, the respiratory rate and leukocyte levels were higher at each monitored time after modeling than those before modeling; the mean arterial pressure, levels of hemoglobin and oxygen partial pressure were significantly lower at each time point after modeling than those before modeling except for the mean arterial pressure at 0 h in EG; the platelet levels at 4 and 8 h were higher than those before modeling; and the differences were statistically significant (P < 0.05). In the EG, the mean arterial pressure, heart rate, respiratory rate and hemoglobin levels at 2 , 4 and 8 h were lower than those at 0 h; the levels of leukocytes, platelets and carbon dioxide partial pressure at 4 and 8 h after modeling were higher than those at 0 h, and the differences were statistically significant (P < 0.05, P < 0.01); in the CG after modeling, the mean arterial pressure, levels of hemoglobin and carbon dioxide partial pressure at 2, 4 and 8 h were lower than those at 0 h; the levels of heart rate and leukocytes were higher than those before modeling; the respiratory rate and platelet levels at 4 and 8 h were higher than those at 0 h; and the differences were statistically significant (P < 0.05). The levels of the mean arterial pressure and hemoglobin at 4 and 8 h and the pH values at 8 h after modeling in the EG were significantly higher than those in the CG, while the heart rate and respiratory rate at 4 and 8 h were significantly lower than those in the CG. The pH values at 8 h after modeling were significantly lower than those of the other monitored times in the CG (P < 0.05, P < 0.01). The two groups had elevated levels of alkaline phosphatase after injury induction.
Through the use of an on-spot interventional treatment cabin, early internal iliac artery embolization can control bleeding associated with pelvic fractures, delay the occurrence of SIRS, and improve the success rate of the treatment of pelvic fracture combined with bleeding.
Internal iliac artery embolization; Systemic inflammatory response syndrome; Interventional treatment cabin
In this study, we mainly investigated the effects of Shengmai San (SMS) on diabetic cardiomyopathy (DCM) in db/db mice. The db/db mice were randomly divided into model group and SMS group, while C57BLKS/J inbred mice were used as controls. After 24-week treatment, blood glucose, body weight, and heart weight were determined. Hemodynamic changes in the left ventricle were measured using catheterization. The myocardial structure and subcellular structural changes were observed by HE staining and electron microscopy; the myocardium collagen content was quantified by Masson staining. To further explore the protective mechanism of SMS, we analyzed the expression profiles of fibrotic related proteins. Compared to nondiabetic mice, db/db mice exhibited enhanced diastolic myocardial dysfunction and adverse structural remodeling. Higher expression of profibrotic proteins and lower levels of extracellular matrix degradation were also observed. After SMS oral administration for 24 weeks, cardiac dysfunction, hypertrophy, and fibrosis in diabetic mice were greatly improved. Moreover, increased profibrotic protein expression was strongly reversed by SMS treatment in db/db mice. The results demonstrate that SMS exerts a cardioprotective effect against DCM by attenuating myocardial hypertrophy and fibrosis via a TGF-β dependent pathway.
Senecio changii (Asteraceae: Senecioneae), a new species from Muli, Sichuan, southwestern China, is described. It is distinguished in Chinese Senecio s.s. by having lyrate-pinnatisect to pinnatisect leaves and a single terminal large discoid capitulum which is somewhat nodding. Evidence from floral micromorphology, karyology and molecular phylogenetic analyses based on the nuclear ITS/ETS sequence data all support its membership within Senecio s.s.
The internet enables the rapid and easy creation, storage, and transfer of knowledge; however, services that transfer geographic knowledge and facilitate the public understanding of geographic knowledge are still underdeveloped to date. Existing online maps (or atlases) can support limited types of geographic knowledge. In this study, we propose a framework for map-based services to represent and transfer different types of geographic knowledge to the public. A map-based service provides tools to ensure the effective transfer of geographic knowledge. We discuss the types of geographic knowledge that should be represented and transferred to the public, and we propose guidelines and a method to represent various types of knowledge through a map-based service. To facilitate the effective transfer of geographic knowledge, tools such as auxiliary background knowledge and auxiliary map-reading tools are provided through interactions with maps. An experiment conducted to illustrate our idea and to evaluate the usefulness of the map-based service is described; the results demonstrate that the map-based service is useful for transferring different types of geographic knowledge.
Oxidative stress is a key event in the onset and progression of neurodegenerative diseases, including Alzheimer’s disease (AD). To investigate the role of oxidative stress in AD and to search for potential biomarkers in peripheral blood, serums were collected in this study from the 3-, 6-, and 12-month-old triple transgenic AD mice (3×Tg-AD mice) and the age- and sex-matched non-transgenic (non-Tg) littermates. The serum oxidized proteins were quantified by slot-blot analysis and enzyme-linked immunosorbent assay (ELISA) to investigate the total levels of serum protein carbonyl groups. Western blotting, in conjunction with two-dimensional gel electrophoresis (2D-Oxyblot), was employed to identify and quantify the specifically-carbonylated proteins in the serum of 3×Tg-AD mice. The results showed that the levels of serum protein carbonyls were increased in the three month old 3×Tg-AD mice compared with the non-Tg control mice, whereas no significant differences were observed in the six and 12 months old AD mice, suggesting that oxidative stress is an early event in AD progression. With the application of 2D-Oxyblot analysis, (immunoglobin) Ig gamma-2B chain C region (IGH-3), Ig lambda-2 chain C region (IGLC2), Ig kappa chain C region (IGKC), and Ig kappa chain V-V region HP R16.7 were identified as significantly oxidized proteins compared with the control. Among them IGH-3 and IGKC were validated via immunoprecipitation and Western blot analysis. Identification of oxidized proteins in the serums of 3×Tg-AD mice can not only reveal potential roles of those proteins in the pathogenesis of AD but also provide potential biomarkers of AD at the early stage.
Alzheimer’s disease; biomarker; oxidative stress; protein carbonylation; redox proteomics; serum; triple transgenic mice
In a charge-coupled device (CCD)-based fast steering mirror (FSM) tracking control system, high control bandwidth is the most effective way to enhance the closed-loop performance. However, the control system usually suffers a great deal from mechanical resonances and time delays induced by the low sampling rate of CCDs. To meet the requirements of high precision and load restriction, fiber-optic gyroscopes (FOGs) are usually used in traditional FSM tracking control systems. In recent years, the MEMS accelerometer and gyroscope are becoming smaller and lighter and their performance have improved gradually, so that they can be used in a fast steering mirror (FSM) to realize the stabilization of the line-of-sight (LOS) of the control system. Therefore, a tentative approach to implement a CCD-based FSM tracking control system, which uses MEMS accelerometers and gyroscopes as feedback components and contains an acceleration loop, a velocity loop and a position loop, is proposed. The disturbance suppression of the proposed method is the product of the error attenuation of the acceleration loop, the velocity loop and the position loop. Extensive experimental results show that the MEMS accelerometers and gyroscopes can act the similar role as the FOG with lower cost for stabilizing the LOS of the FSM tracking control system.
MEMS accelerometer; MEMS gyroscope; acceleration feedback control; multi-loop control; light of sight stabilization
Metabolomics has shown significant potential in identifying small molecules specific to tumor phenotypes. In this study we analyzed resected tissue metabolites using capillary electrophoresis-mass spectrometry and found that tissue hypotaurine levels strongly and positively correlated with glioma grade. In vitro studies were conducted to show that hypotaurine activates hypoxia signaling through the competitive inhibition of prolyl hydroxylase domain-2. This leads to the activation of hypoxia signaling as well as to the enhancement of glioma cell proliferation and invasion. In contrast, taurine, the oxidation metabolite of hypotaurine, decreased intracellular hypotaurine and resulted in glioma cell growth arrest. Lastly, a glioblastoma xenograft mice model was supplemented with taurine feed and exhibited impaired tumor growth. Taken together, these findings suggest that hypotaurine is an aberrantly produced oncometabolite, mediating tumor molecular pathophysiology and progression. The hypotaurine metabolic pathway may provide a potentially new target for glioblastoma diagnosis and therapy.
hypoxia; hypoxia-inducible factors; hypotaurine; metabolomics; glioma
Traditional Chinese medicine Jinfukang (JFK) has been clinically used for treating lung cancer. To examine whether epigenetic modifications are involved in its anticancer activity, we performed a global profiling analysis of H3K4Me3, an epigenomic marker associated with active gene expression, in JFK-treated lung cancer cells. We identified 11,670 genes with significantly altered status of H3K4Me3 modification following JFK treatment (P < 0.05). Gene Ontology analysis indicates that these genes are involved in tumor-related pathways, including pathway in cancer, basal cell carcinoma, apoptosis, induction of programmed cell death, regulation of transcription (DNA-templated), intracellular signal transduction, and regulation of peptidase activity. In particular, we found that the levels of H3K4Me3 at the promoters of SUSD2, CCND2, BCL2A1, and TMEM158 are significantly altered in A549, NCI-H1975, NCI-H1650, and NCI-H2228 cells, when treated with JFK. Collectively, these findings provide the first evidence that the anticancer activity of JFK involves modulation of histone modification at many cancer-related gene loci.
Rice bean (Vigna umbellata (Thunb.) Ohwi & Ohashi) is a warm season annual legume mainly grown in East Asia. Only scarce genomic resources are currently available for this legume crop species and no simple sequence repeat (SSR) markers have been specifically developed for rice bean yet. In this study, approximately 26 million high quality cDNA sequence reads were obtained from rice bean using Illumina paired-end sequencing technology and assembled into 71,929 unigenes with an average length of 986 bp. Of these unigenes, 38,840 (33.2%) showed significant similarity to proteins in the NCBI non-redundant protein and nucleotide sequence databases. Furthermore, 30,170 (76.3%) could be classified into gene ontology categories, 25,451 (64.4%) into Swiss-Prot categories and 21,982 (55.6%) into KOG database categories (E-value < 1.0E-5). A total of 9,301 (23.5%) were mapped onto 118 pathways using the Kyoto Encyclopedia of Genes and Genome (KEGG) pathway database. A total of 3,011 genic SSRs were identified as potential molecular markers. AG/CT (30.3%), AAG/CTT (8.1%) and AGAA/TTCT (20.0%) are the three main repeat motifs. A total of 300 SSR loci were randomly selected for validation by using PCR amplification. Of these loci, 23 primer pairs were polymorphic among 32 rice bean accessions. A UPGMA dendrogram revealed three major clusters among 32 rice bean accessions. The large number of SSR-containing sequences and genic SSRs in this study will be valuable for the construction of high-resolution genetic linkage maps, association or comparative mapping and genetic analyses of various Vigna species.
Fabricating ideal scaffolds for bone tissue engineering is a great challenge to researchers. To better mimic the mineral component and the microstructure of natural bone, several kinds of materials were adopted in our study, namely gelatin, polycaprolactone (PCL), nanohydroxyapatite (nHA), and bone powder. Three types of scaffolds were fabricated using electrospinning; gelatin/PCL, gelatin/PCL/nHA, and gelatin/PCL/bone powder. Scaffolds were examined using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) observations. Then, Adipose-derived Stem Cells (ADSCs) were seeded on these scaffolds to study cell morphology, cell viability, and proliferation. Through this study, we found that nHA and bone powder can be successfully united in gelatin/PCL fibers. When compared with gelatin/PCL and gelatin/PCL/nHA, the gelatin/PCL/bone powder scaffolds could provide a better environment to increase ADSCs’ growth, adhesion, and proliferation. Thus, we think that gelatin/PCL/bone powder has good biocompatibility, and, when compared with nHA, bone powder may be more effective in bone tissue engineering due to the bioactive factors contained in it.
gelatin; polycaprolactone; electrospinning; bone tissue engineering; scaffold
Rheumatoid arthritis (RA) is a systemic, inflammatory, and autoimmune disorder. Gut microbiota play an important role in the etiology of RA. With the considerable progress made in next-generation sequencing techniques, the identified gut microbiota difference between RA patients and healthy individuals provides an updated overview of the association between gut microbiota and RA. We reviewed the reported correlation and underlying molecular mechanisms among gut microbiota, the immune system, and RA. It has become known that gut microbiota contribute to the pathogenesis of RA via multiple molecular mechanisms. The progressive understanding of the dynamic interaction between gut microbiota and their host will help in establishing a highly individualized management for each RA patient, and achieve a better efficacy in clinical practice, or even discovering new drugs for RA.
rheumatoid arthritis; gut microbiota; molecular mechanism
Although mental fatigue was well-recognized as one of the long-term consequences following mild traumatic brain injury (MTBI) that required ongoing support, evidences for the optimal management remained inadequate.
To investigate the temporal profile of mental fatigue during the first year after MTBI and examine the impact of perceived social support on the recovery from post-MTBI fatigue.
Observational case-control study.
This study was conducted among post-MTBI patients admitted to the emergency department in a tertiary-care hospital in Sichuan, China. During four waves of assessments at 1 week, 3, 6 and 12 months, mental fatigue was assessed through Mental Fatigue Scale (MFS) whereas social support was assessed by the Multidimensional Scale of Perceived Social Support (MSPSS).
There were 65.1%, 37.1%, 34.8% and 32.5% individuals being identified as those with mental fatigue at 1 week, 3, 6 and 12 months, respectively. The scores of MFS didn’t change substantially since 3 months post-injury. Compared to non-fatigued MTBI patients, those with long-lasting post- MTBI fatigue reported extremely lower level of perceived social support. Moreover, improved social support at 1 week was negatively associated with the occurrence of long-lasting fatigue.
Sufficient social support could significantly decrease the occurrence of long-lasting mental fatigue among MTBI cases. It seemed of great importance to modify the emphasis of rehabilitation to include assessment and improvement of perceived social support at earlier stages after injury.
Mental fatigue; social support; traumatic brain injury
This study examined the risk factors for decreased bone mineral density (BMD) in postmenopausal women with schizophrenia.
Cluster sampling method was adopted in this large-sample, cross-sectional study. A total of 219 postmenopausal female inpatients with schizophrenia were selected and interviewed in Beijing. The average age of the patients was 60.4±7.0 years. Clinical assessment instruments included the Positive and Negative Syndrome Scale (PANSS) and a questionnaire with detailed general information and disease-related investigations. Laboratory measurements included prolactin (PRL), estradiol, progesterone, thyroid stimulating hormone, FT3, and FT4. BMD testing was performed by dual-energy X-ray absorptiometry.
The prevalence of osteoporosis or osteopenia was 66.2% (n=145). Decreased BMD was associated with age, illness duration, therapeutic dose (equivalent chlorpromazine dose), treatment duration, PANSS-negative scores, body mass index (BMI), daily exercises (min/d), drinking (unit/wk), PRL, and estradiol. Multiple logistic regression analysis revealed that age, treatment duration, PANSS-negative score, BMI, and PRL were significantly associated with decreased BMD.
Prevalence of BMD loss was higher in Chinese postmenopausal women with schizophrenia compared to the normal BMD group. A combination of demographic and clinical factors play important roles in determining decreased BMD, including older age, longer treatment duration, more PANSS-negative scores, higher BMI, and higher PRL level.
schizophrenia; bone density; risk factors