The role of the endogenous secretory receptor for advanced glycation end products (esRAGE) in depression of diabetes patients and its clinical significance are unclear. This study investigated the role of serum esRAGE in patients with type 2 diabetes mellitus with depression in the Chinese population.
Patients and Methods
One hundred nineteen hospitalized patients with type 2 diabetes were recruited at Fujian Provincial Hospital (Fuzhou, China) from February 2010 to January 2011. All selected subjects were assessed with the Hamilton Rating Scale for Depression (HAMD). Among them, 71 patients with both type 2 diabetes and depression were included. All selected subjects were examined for the following: esRAGE concentration, glycosylated hemoglobin (HbA1c), blood lipids, C-reactive protein, trace of albumin in urine, and carotid artery intima-media thickness (IMT). Association between serum esRAGE levels and risk of type 2 diabetes mellitus with depression was also analyzed.
There were statistically significant differences in gender, age, body mass index, waist circumference, and treatment methods between the group with depression and the group without depression (P<0.05). Multiple linear regression analysis showed that HAMD scores were negatively correlated with esRAGE levels (standard regression coefficient −0.270, P<0.01). HAMD-17 scores were positively correlated with IMT (standard regression coefficient 0.183, P<0.05) and with HbA1c (standard regression coefficient 0.314, P<0.01).
Female gender, younger age, obesity, poor glycemic control, complications, and insulin therapy are all risk factors of type 2 diabetes mellitus with combined depression in the Chinese population. Inflammation and atherosclerosis play an important role in the pathogenesis of depression. esRAGE is a protective factor of depression among patients who have type 2 diabetes.
Knowledge of the diversity of magnetotactic bacteria in natural environments is crucial for understanding their contribution to various biological and geological processes. Here we report a high diversity of magnetotactic bacteria in a freshwater site. Ten out of 18 operational taxonomic units (OTUs) were affiliated with the Deltaproteobacteria. Some rod-shaped bacteria simultaneously synthesized greigite and magnetite magnetosomes.
Nanomaterials have been increasingly employed as drug(s)-incorporated vectors for drug delivery due to their potential of maximizing therapeutic efficacy while minimizing systemic side effects. However, there have been two main challenges for these vectors: (i) the existing synthetic approaches are cumbersome and incapable of achieving precise control of their structural properties, which will affect their biodistribution and therapeutic efficacies, and (ii) lack of an early checkpoint to quickly predict which drug(s)-incorporated vectors exhibit optimal therapeutic outcomes. In this work, we utilized a new rational developmental approach to rapidly screen nanoparticle (NP)-based cancer therapeutic agents containing a built-in companion diagnostic utility for optimal therapeutic efficacy. The approach leverages the advantages of a self-assembly synthetic method for preparation of two different sizes of drug-incorporated supramolecular nanoparticles (SNPs), and a positron emission tomography (PET) imaging-based biodistribution study to quickly evaluate the accumulation of SNPs at a tumor site in vivo and select the favorable SNPs for in vivo therapeutic study. Finally, the enhanced in vivo anti-tumor efficacy of the selected SNPs was validated by tumor reduction/inhibition studies. We foresee our rational developmental approach providing a general strategy in the search of optimal therapeutic agents among the diversity of NP-based therapeutic agents.
Supramolecular assembly; Nanoparticles; Drug delivery; Positron emission tomography; Cancer therapeutics
The human SLC25A13 gene encodes citrin, the liver-type mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), and SLC25A13 mutations cause citrin deficiency (CD), a disease entity that encompasses different age-dependant clinical phenotypes such as Adult-onset Citrullinemia Type II (CTLN2) and Neonatal Intrahepatic Cholestasis caused by Citrin Deficiency (NICCD). The analyses of SLC25A13 gene and its protein/mRNA products remain reliable tools for the definitive diagnoses of CD patients, and so far, the SLC25A13 mutation spectrum in Chinese CD patients has not been well-characterized yet.
Methods and Results
By means of direct DNA sequencing, cDNA cloning and SNP analyses, 16 novel pathogenic mutations, including 9 missense, 4 nonsense, 1 splice-site, 1 deletion and 1 large transposal insertion IVS4ins6kb (GenBank accession number KF425758), were identified in CTLN2 or NICCD patients from China, Japan and Malaysia, respectively, making the SLC25A13 variations worldwide reach the total number of 81. A large NICCD cohort of 116 Chinese cases was also established, and the 4 high-frequency mutations contributed a much larger proportion of the mutated alleles in the patients from south China than in those from the north (χ2 = 14.93, P<0.01), with the latitude of 30°N as the geographic dividing line in mainland China.
This paper further enriched the SLC25A13 variation spectrum worldwide, and formed a substantial contribution to the in-depth understanding of the genotypic feature of Chinese CD patients.
mRNA decay mediated by the AU-rich elements (AREs) is one of the most studied post-transcriptional mechanisms and is modulated by ARE-binding proteins (ARE-BPs). To understand the regulation of K homology splicing regulatory protein (KSRP), a decay-promoting ARE-BP, we purified KSRP protein complexes and identified an RNA helicase, DDX1. We showed that down-regulation of DDX1 expression elevated cytoplasmic levels of KSRP and facilitated ARE-mediated mRNA decay. Association of KSRP with 14-3-3 proteins, that are predominately located in the cytoplasm, increased upon reduction of DDX1. We also demonstrated that KSRP associated with DDX1 or 14-3-3, but not both. These observations indicate that subcellular localization of KSRP is regulated by competing interactions with DDX1 or 14-3-3.
Mesenchymal stem cells (MSCs) are promising tools for the treatment of diseases such as infarcted myocardia and strokes because of their ability to promote endogenous angiogenesis and neurogenesis via a variety of secreted factors. MSCs found in the Wharton’s jelly of the human umbilical cord are easily obtained and are capable of transplantation without rejection. We isolated MSCs from Wharton’s jelly and bone marrow (WJ-MSCs and BM-MSCs, respectively) and compared their secretomes. It was found that WJ-MSCs expressed more genes, especially secreted factors, involved in angiogenesis and neurogenesis. Functional validation showed that WJ-MSCs induced better neural differentiation and neural cell migration via a paracrine mechanism. Moreover, WJ-MSCs afforded better neuroprotection efficacy because they preferentially enhanced neuronal growth and reduced cell apoptotic death of primary cortical cells in an oxygen-glucose deprivation (OGD) culture model that mimics the acute ischemic stroke situation in humans. In terms of angiogenesis, WJ-MSCs induced better microvasculature formation and cell migration on co-cultured endothelial cells. Our results suggest that WJ-MSC, because of a unique secretome, is a better MSC source to promote in vivo neurorestoration and endothelium repair. This study provides a basis for the development of cell-based therapy and carrying out of follow-up mechanistic studies related to MSC biology.
Due to increased needs for Positron Emission Tomography (PET) scanning, high demands for a wide variety of radiolabeled compounds will have to be met by exploiting novel radiochemistry and engineering technologies to improve the production and development of PET probes. The application of microfluidic reactors to perform radiosyntheses is currently attracting a great deal of interest because of their potential to deliver many advantages over conventional labeling systems. Microfluidic-based radiochemistry can lead to the use of smaller quantities of precursors, accelerated reaction rates and easier purification processes with greater yield and higher specific activity of desired probes. Several ‘proof-of-principle’ examples, along with basics of device architecture and operation, and potential limitations of each design are discussed here. Along with the concept of radioisotope distribution from centralized cyclotron facilities to individual imaging centers and laboratories (“decentralized model”), an easy-to-use, standalone, flexible, fully-automated radiochemical microfluidic platform can open up to simpler and more cost-effective procedures for molecular imaging using PET.
Positron Emission Tomography (PET); microfluidic; PET probe; molecular imaging; single-patient dose on demand
Controlling the size distribution of polymer-based nanoparticles is a challenging task due to their flexible core and surface structures. To accomplish such as task requires a very precise control at the molecular level. Here, we demonstrate a new approach whereby uniform-sized supramolecular nanoparticles (SNPs) can be reliably generated using a digital microfluidic droplet generator (DMDG) chip. A microfluidic environment enabled precise control over the processing parameters and, therefore, high batch-to-batch reproducibility and robust production of SNPs with a very narrow size distribution could be realized. Digitally adjusting the mixing ratios of the building blocks on the DMDG chip allowed us to rapidly scan a variety of synthesis conditions without consuming significant amounts of reagents. Nearly uniform SNPs with sizes ranging from 35 to 350 nm were obtained and characterized by transmission electron microscopy and dynamic light scattering. In addition, we could fine-tune the surface chemistry of the SNPs by incorporating an additional building block functionalized with specific ligands for targeting cells. The sizes and surface properties of these SNPs correlated strongly with their cell uptake efficiencies. This study showed a feasible microfluidic-assisted SNP production and provided a great means for preparing size-controlled SNP with desired surface ligand coverage.
2-Methoxyestradiol (2-ME), an endogenous derivative of 17β-estradiol, has been reported to elicit antiproliferative responses in various tumors. In this study, we investigated the effects of 2-ME on cell viability, proliferation, cell cycle, and apoptosis in human urothelial carcinoma (UC) cell lines. We used two high-grade human bladder UC cell lines (NTUB1 and T24). After treatment with 2-ME, the cell viability and apoptosis were measured by MTT assay and flow cytometry (fluorescence-activated cell sorting), with annexin V-FITC staining and propidium iodide (PI) labeling. DNA fragmentation was analyzed by agarose gel electrophoresis. Flow cytometry with PI labeling was used for the cell cycle analyses. The protein levels of caspase activations, poly (ADP-ribose) polymerase (PARP) cleavage, phospho-histone H2A.X, phospho-Bad, and cell cycle regulatory molecules were measured by Western blot. The effects of the drug combinations were analyzed using the computer software, CalcuSyn. We demonstrated that 2-ME effectively induces dose-dependent cytotoxicity and apoptosis in human UC cells after 24 h exposure. DNA fragmentation, PARP cleavage, and caspase-3, 7, 8, 9 activations can be observed with 2-ME-induced apoptosis. The decreased phospho-Bad (Ser136 and Ser155) and mitotic arrest of the cell cycle in the process of apoptosis after 2-ME treatment was remarkable. In response to mitotic arrest, the mitotic forms of cdc25C, phospho-cdc2, cyclin B1, and phospho-histone H3 (Ser10) were activated. In combination with arsenic trioxide (As2O3), 2-ME elicited synergistic cytotoxicity (combination index <1) in UC cells. We concluded that 2-ME significantly induces apoptosis through decreased phospho-Bad and arrests bladder UC cells at the mitotic phase. The synergistic antitumor effect with As2O3 provides a novel implication in clinical treatment of UC.
Spica Prunellae has long been used as a significant component in numerous traditional Chinese medicine (TCM) formulas to clinically treat cancers. Previously, Spica Prunellae was shown to promote cancer cell apoptosis and inhibit angiogenesis in vivo and in vitro. To further elucidate the precise mechanism of its tumoricidal activity, the effect of the ethanol extract of Spica Prunellae (EESP) on the proliferation of human colon carcinoma HT-29 cells was elucidated and the underlying molecular mechanisms were investigated. The proliferation of HT-29 cells was evaluated using 3-(4, 5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and colony formation analyses. The cell cycle was determined using fluorescence-activated cell sorting (FACS) with propidium iodide (PI) staining. The mRNA and protein expression of cyclin-dependent kinase 4 (CDK4) and cyclin D1 was examined using RT-PCR and western blotting, respectively. EESP was observed to inhibit HT-29 viability and survival in a dose- and time-dependent manner. Furthermore, EESP treatment blocked G1/S cell cycle progression and reduced the expression of pro-proliferative cyclin D1 and CDK4 at the transcriptional and translational levels. Altogether, these data suggest that the inhibition of cell proliferation via G1/S cell cycle arrest may be one of the mechanisms through which Spica Prunellae treats cancer.
Spica Prunellae; colorectal cancer; herbal medicine; proliferation; cell cycle
The rabbit is a classical experimental animal species. A major limitation in using rabbits for biomedical research is the lack of germ-line-competent rabbit embryonic stem cells (rbESCs). We hypothesized that the use of homologous feeder cells and recombinant rabbit leukemia inhibitory factor (rbLIF) might improve the chance in deriving germ-line-competent rbES cells. In the present study, we established rabbit embryonic fibroblast (REF) feeder layers and synthesized recombinant rbLIF. We derived a total of seven putative rbESC lines, of which two lines (M5 and M23) were from culture Condition I using mouse embryonic fibroblasts (MEFs) as feeders supplemented with human LIF (hLIF) (MEF+hLIF). Another five lines (R4, R9, R15, R21, and R31) were derived from Condition II using REFs as feeder cells supplemented with rbLIF (REF+rbLIF). Similar derivation efficiency was observed between these two conditions (8.7% vs. 10.2%). In a separate experiment with 2×3 factorial design, we examined the effects of feeder cells (MEF vs. REF) and LIFs (mLIF, hLIF vs. rbLIF) on rbESC culture. Both Conditions I and II supported satisfactory rbESC culture, with similar or better population doubling time and colony-forming efficiency than other combinations of feeder cells with LIFs. Rabbit ESCs derived and maintained on both conditions displayed typical ESC characteristics, including ESC pluripotency marker expression (AP, Oct4, Sox2, Nanog, and SSEA4) and gene expression (Oct4, Sox2, Nanog, c-Myc, Klf4, and Dppa5), and the capacity to differentiate into three primary germ layers in vitro. The present work is the first attempt to establish rbESC lines using homologous feeder cells and recombinant rbLIF, by which the rbESCs were derived and maintained normally. These cell lines are unique resources and may facilitate the derivation of germ-line-competent rbESCs.
To study the angiogenesis modulation mechanism of Xuefu Zhuyu Decoction(
) on endothelial cell ECV304.
ECV304 cells were treated by 2.5% Xuefu Zhuyu Decoction-containing serum (XFZYD-CS) for 24h, 48h and 72h respectively. MTT, FACS, migration, adhesion and in vitro tube formation assay confirmed an angiogenesis effect of XFZYD at 3 time points. Then an analysis of angiogenesis regulator profiles at 3 times with Real-time PCR Supperarray was performed.
At 48h, XFZYD-CS induced ECV304 significantly improved cell vigor, number in S phase, migration, adhesion and tube formation. At 24h and 72h, only cell migration was elevated. Microarray results showed that 18,14 and 16 genes changed expressions at 24h, 48h and 72h respectively. 6 genes changed consistently and 7 genes varied between 48h and the other two times.
The changes of ECV304 induced by XFZYD-CS at 48h. The regulation mode at 48h had less genetic change but had greater cellular effect.
Xuefu Zhuyu Decoction; angiogenesis; Microarray; Chinese herbs
DNA damage and replication checkpoints mediated by the ATR-CHEK1 pathway are key to the maintenance of genome stability, and both ATR and CHEK1 have been proposed as potential breast cancer susceptibility genes. Many novel variants recently identified by the large resequencing projects have not yet been thoroughly tested in genome-wide association studies for breast cancer susceptibility. We therefore used a tagging SNP (tagSNP) approach based on recent SNP data available from the 1000 genomes projects, to investigate the roles of ATR and CHEK1 in breast cancer risk and survival. ATR and CHEK1 tagSNPs were genotyped in the Sheffield Breast Cancer Study (SBCS; 1011 cases and 1024 controls) using Illumina GoldenGate assays. Untyped SNPs were imputed using IMPUTE2, and associations between genotype and breast cancer risk and survival were evaluated using logistic and Cox proportional hazard regression models respectively on a per allele basis. Significant associations were further examined in a meta-analysis of published data or confirmed in the Utah Breast Cancer Study (UBCS). The most significant associations for breast cancer risk in SBCS came from rs6805118 in ATR (p=7.6x10-5) and rs2155388 in CHEK1 (p=3.1x10-6), but neither remained significant after meta-analysis with other studies. However, meta-analysis of published data revealed a weak association between the ATR SNP rs1802904 (minor allele frequency is 12%) and breast cancer risk, with a summary odds ratio (confidence interval) of 0.90 (0.83-0.98) [p=0.0185] for the minor allele. Further replication of this SNP in larger studies is warranted since it is located in the target region of 2 microRNAs. No evidence of any survival effects of ATR or CHEK1 SNPs were identified. We conclude that common alleles of ATR and CHEK1 are not implicated in breast cancer risk or survival, but we cannot exclude effects of rare alleles and of common alleles with very small effect sizes.
Clinical information regarding murine typhus in Taiwan is limited. In this study, 81 cases of serologically documented murine typhus during 1992–2009 at four referral hospitals in southern Taiwan were analyzed. There was a significant correlation between average environmental temperature and case numbers of murine typhus (r = 0.747, P = 0.005). Acute hepatitis was found in 67% of cases, and hyperbilirubinemia (serum total bilirubin ≥ 23.9 μmol/L) was found in 38%. The intervals between the initiation of appropriate therapy to defervescence were longer in patients with hyperbilirubinemia than those without hyperbilirubinemia (6.1 versus 4.1 days; P = 0.015). Nine (11.1%) showed development of severe illnesses such as acute respiratory distress syndrome (2 patients), aseptic meningitis (3), and acute renal failure (4). Only one died of acute respiratory distress syndrome. Cases of murine typhus were often found during the summer and had acute febrile hepatitis. Those patients with hyperbilirubinemia tended to have a delayed recovery even with appropriate therapy.
Syndecan-1 is the predominant heparan sulfate proteoglycan found on the surface of epithelial cells, and like glutamine, is essential in maintaining the intestinal epithelial barrier. We therefore hypothesized that loss of epithelial syndecan-1 would abrogate the gut protective effects of enteral glutamine. Both an in vitro and in vivo model of gut ischemia/reperfusion (I/R) was utilized. In vitro, intestinal epithelial cells underwent hypoxia/reoxygenation (H/R) to mimic gut I/R with 2mM (physiologic) or 10 mM glutamine supplementation. Permeability, caspase activity, cell growth, and cell surface and shed syndecan-1 were assessed. In vivo, wild type (WT) and syndecan-1 knockout (KO) mice received ± enteral glutamine followed by gut I/R. Intestinal injury was assessed by fluorescent dye clearance and histopathology, permeability as mucosal to serosal clearance ex vivo in everted sacs, and inflammation by myeloperoxidase (MPO) activity. In an in vitro model of gut I/R, glutamine supplementation reduced epithelial cell permeability and apoptosis and enhanced cell growth. Shed syndecan-1 was reduced by glutamine without an increase in syndecan-1 mRNA. In vivo, intestinal permeability, inflammation, and injury were increased after gut I/R in WT mice and further increased in syndecan-1 KO mice. Glutamine’s attenuation of I/R-induced intestinal hyperpermeability, inflammation, and injury were abolished in syndecan-1 KO mice. These results suggest that syndecan-1 plays a novel role in the protective effects of enteral glutamine in the post ischemic gut.
heparan sulfate; epithelial cells; gut ischemia/reperfusion; hypoxia/reoxygenation; permeability
To compare the value of ultrasonography for diagnosing carpal tunnel syndrome (CTS) in patients with and without diabetes mellitus (DM).
Eighty non-DM and 40 DM patients with electromyography-confirmed CTS were assessed and underwent high-resolution ultrasonography of the wrists. Cross-sectional area (CSA) and flattening ratio (FR) of the median nerve were measured at the carpal tunnel outlet (D) and wrist crease (W).
The 80 non-DM and 40 DM patients had 81 and 59 CTS-hands, respectively. The CSA_D and CSA_W were significantly larger in the CTS-hands and DM-CTS-hands compared to the normal control (p < 0.001). However, there is no difference of CSA_D and CSA_W between DM and non-DM CTS patients. Receiver operating characteristics [ROC] curve analysis revealed that CSA_W ≥13 mm2 was the most powerful predictor of CTS in DM (area under curve [AUC] = 0.72; sensitivity 72.9%, specificity 61.9%) and non-DM (AUC = 0.72; sensitivity 78.5%, specificity 53.2%) patients. The CSA positively correlated with the distal motor latency of the median compound motor action potential (CMAP), distal sensory latency of the median sensory nerve action potential (SNAP), and latency of the median F wave, but negatively correlated with the amplitude of the median CMAP, amplitude of the median SNAP, and sensory NCV of the median nerve. Stepwise logistic regression revealed that CSA_W (OR 1.21, 95% CI 1.07-1.38; p = 0.003) was independently associated with CTS in DM patients and any 1 mm2 increase in CSA_W increased the rate of CTS by 28%.
The CSA of the median nerve at the outlet and wrist crease are significantly larger in CTS hands in both DM and non-DM patients compared to normal hands. The CSA of the median nerve by ultrasonography may be a diagnostic tool for evaluating CTS in DM and non-DM patients.
Carpal tunnel syndrome; Cross-sectional area; Median nerve; Ultrasonography
Constitutive activation of STAT3 is one of the major oncogenic pathways involved in the development of various types of malignancies including colorectal cancer (CRC); and thus becomes a promising therapeutic target. Spica Prunellae has long been used as an important component in many traditional Chinese medicine formulas to clinically treat CRC. Previously, we found that Spica Prunellae inhibits CRC cell growth through mitochondrion-mediated apoptosis. Furthermore, we demonstrated its anti-angiogenic activities in vivo and in vitro. To further elucidate the precise mechanism of the potential tumoricidal activity of Spica Prunellae, using a CRC mouse xenograft model, in this study we evaluated its therapeutic efficacy against CRC and investigated the underlying molecular mechanisms.
CRC mouse xenograft model was generated by subcutaneous injection of human colon carcinoma HT-29 cells into nude mice. Animals were given intra-gastric administration with 6 g/kg of the ethanol extract of Spica Prunellae (EESP) daily, 5 days a week for 16 days. Body weight and tumor growth were measured every two days. Tumor growth in vivo was determined by measuring the tumor volume and weight. HT-29 cell viability was examined by MTT assay. Cell apoptosis and proliferation in tumors from CRC xenograft mice was evaluated via immunohistochemical staining (IHS) for TUNEL and PCNA, and the intratumoral microvessel density (MVD) was examined by using IHS for the endothelial cell-specific marker CD31. The activation of STAT3 was evaluated by determining its phosphorylation level using IHS. The mRNA and protein expression of Bcl-2, Bax, Cyclin D1, VEGF-A and VEGFR2 was measured by RT-PCR and IHS, respectively.
EESP treatment reduced tumor volume and tumor weight but had no effect on body weight change in CRC mice; decreased HT-29 cell viability in a dose-dependent manner, suggesting that EESP displays therapeutic efficacy against colon cancer growth in vivo and in vitro, without apparent toxicity. In addition, EESP significantly inhibited the phosphorylation of STAT3 in tumor tissues, indicating its suppressive action on the activation of STAT3 signaling. Consequently, the inhibitory effect of EESP on STAT3 activation resulted in an increase in the pro-apoptotic Bax/Bcl-2 ratio, decrease in the expression of the pro-proliferative Cyclin D1 and CDK4, as well as down-regulation of pro-angiogenic VEGF-A and VEGFR-2 expression. Finally, these molecular effects led to the induction of apoptosis, the inhibition of cell proliferation and tumor angiogenesis.
Spica Prunellae possesses a broad range of anti-cancer activities due to its ability to affect STAT3 pathway, suggesting that Spica Prunellae could be a novel potent therapeutic agent for the treatment of CRC.
Spica prunellae; Colorectal cancer; Herbal medicine; STAT3 pathway; Apoptosis; Proliferation; Angiogenesis
Given the complexity of tumor microenvironment, no single marker from cancer cells could adequately predict the clinical outcomes of gastric cancer (GC). The objective of this study was to evaluate the prognostic role of combined features including conventional pathology, proteinase and immune data in GC.
In addition to pathological studies, immunohistochemistry was used to assess membrane-type 1 matrix metalloproteinase (MT1-MMP) expression and CD11b + immunocytes density in three independent GC tissue microarrays containing 184 GC tissues. Separate and combined features were evaluated for their impact on overall survival (OS).
We found that traditional factors including tumor size, histological grade, lymph node status, serosa invasion and TNM stage were associated with OS (P < 0.05 for all). Moreover, statistically significant differences in OS were found among lymph node ratio (LNR) subgroups (P < 0.001), MT1-MMP subgroups (P = 0.015), and CD11b + immunocytes density subgroups (P = 0.031). Most importantly, combined feature (MT1-MMP positive, low CD11b + immunocytes density and high LNR) was found by multivariate analysis to be an independent prognostic factors for OS after excluding other confounding factors (HR = 3.818 [95%CI: 2.223-6.557], P < 0.001). In addition, this combined feature had better performance in predicting clinical outcomes after surgery long before recurrence had occurred (Area under the curve: 0.689 [95%CI: 0.609-0.768], P < 0.001).
These findings indicate that better information on GC prognosis could be obtained from combined clinico-pathological factors, tumor cells and the tumor microenvironment.
Gastric cancer; Prognosis; Tumor microenvironment; Lymph node ratio
Eukaryotic cells make many types of primary and processed RNAs that are found either in specific sub-cellular compartments or throughout the cells. A complete catalogue of these RNAs is not yet available and their characteristic sub-cellular localizations are also poorly understood. Since RNA represents the direct output of the genetic information encoded by genomes and a significant proportion of a cell’s regulatory capabilities are focused on its synthesis, processing, transport, modifications and translation, the generation of such a catalogue is crucial for understanding genome function. Here we report evidence that three quarters of the human genome is capable of being transcribed, as well as observations about the range and levels of expression, localization, processing fates, regulatory regions and modifications of almost all currently annotated and thousands of previously unannotated RNAs. These observations taken together prompt to a redefinition of the concept of a gene.
Plasma-assisted thermal chemical vapor deposition (CVD) was carried out to synthesize high-quality graphene film at a low temperature of 600°C. Monolayer graphene films were thus synthesized on Cu foil using various ratios of hydrogen and methane in a gaseous mixture. The in situ plasma emission spectrum was measured to elucidate the mechanism of graphene growth in a plasma-assisted thermal CVD system. According to this process, a distance must be maintained between the plasma initial stage and the deposition stage to allow the plasma to diffuse to the substrate. Raman spectra revealed that a higher hydrogen concentration promoted the synthesis of a high-quality graphene film. The results demonstrate that plasma-assisted thermal CVD is a low-cost and effective way to synthesis high-quality graphene films at low temperature for graphene-based applications.
Graphene; Chemical vapor deposition; Plasma; Low temperature
Targeted delivery of drugs to tumors represents a significant advance in cancer diagnosis and therapy. Therefore, development of novel tumor-specific ligands or pharmaceutical nanocarriers is highly desirable. In this study, we utilized phage display to identify a new targeting peptide, SP90, which specifically binds to breast cancer cells, and recognizes tumor tissues from breast cancer patients. We used confocal and electron microscopy to reveal that conjugation of SP90 with liposomes enables efficient delivery of drugs into cancer cells through endocytosis. Furthermore, in vivo fluorescent imaging demonstrated that SP90-conjugated quantum dots possess tumor-targeting properties. In tumor xenograft and orthotopic models, SP90-conjugated liposomal doxorubicin was found to improve the therapeutic index of the chemotherapeutic drug by selectively increasing its accumulation in tumors. We conclude that the targeting peptide SP90 has significant potential in improving the clinical benefits of chemotherapy in the treatment and the diagnosis of breast cancer.
We developed a computational framework to robustly identify RNA editing sites using transcriptome and genome deep-sequencing data from the same individual. As compared with previous methods, our approach identified a large number of RNA editing sites with high specificity in both Alu and non-Alu regions. We also found that the editing of non-Alu sites appears to be dependent on nearby edited Alu sites, possibly through the locally formed double-stranded RNA structure.
Most cases of adult-onset tuberculosis (TB) result from reactivation of a pre-existing Mycobacterium tuberculosis infection. Mycobacterium tuberculosis usually invades the respiratory tract and most patients develop intrapulmonary TB; however, some patients develop concurrent pulmonary and extra-pulmonary TB. The purpose of the present study was to identify the demographic and clinical factors associated with an increased risk of concurrent extra-pulmonary diseases in patients with pulmonary TB. We compared patients who had isolated pulmonary TB with patients who had concurrent pulmonary and extra-pulmonary TB. We initially analyzed one-million randomly selected subjects from the population-based Taiwan National Health Insurance database. Based on analysis of 5414 pulmonary TB patients in this database, women were more likely than men to have concurrent extra-pulmonary TB (OR: 1.30, p = 0.013). A separate analysis of the Kaohsiung Medical University Hospital database, which relied on sputum culture-proven pulmonary TB, indicated that women were more likely than men to have concurrent extra-pulmonary TB (OR: 1.62, p = 0.039). There was no significant gender difference in extra-pulmonary TB for patients younger than 45 years in either database. However, for patients 45 years and older, women were more likely than men to have concurrent extra-pulmonary TB (insurance database: 9.0% vs. 6.8%, p = 0.016, OR: 1.36; hospital database: 27.3% vs. 16.0%, p = 0.008, OR = 1.98). Our results indicate that among patients who have pulmonary TB, older females have an increased risk for concurrent extra-pulmonary TB.