Magnetic resonance imaging (MRI) is used extensively for clinical diagnoses. It is critical to design and develop highly efficient MR contrast agents with simple preparation procedure, low toxicity, and high biocompatibility. Here, we report a carbon quantum dot (CQDs)-stabilized gadolinium hybrid nanoprobe (Gd-CQDs) prepared via a one-pot hydrothermal treatment of the mixture of citrate acid, ethanediamine, and GdCl3 at 200 °C for 4 h. In vitro and in vivo tests confirmed their low toxicity and high biocompatibility. Gd-CQDs were observed to have a higher MR response than gadopentetic acid dimeglumine (Gd-DTPA) because of their high Gd content and hydrophilicity. Moreover, the fluorescence of CQDs was remained in Gd-CQDs. The in vivo MR and fluorescence dual-modality imaging of Gd-CQDs was confirmed with zebrafish embryo and mice as models. The modification of Gd-CQDs with arginine-glycine-aspartic acid (RGD) tripeptide provided a high affinity to U87 cancer cells for targeted imaging. Whereas the MR response showed a depth penetration and spatial visualization, fluorescence revealed the fine distribution of Gd-CQDs in tissues because of its high resolution and sensitivity. We found that Gd-CQDs distributed in the tissues in a heterogeneous mode: they entered into the tissue cells but were observed less in the extracellular matrix. The MR and fluorescence dual-modality imaging of Gd-CQDs makes them a potential contrast agent for clinic applications because of their simple preparation procedure, ease of functionalization, high contrast efficiency, low toxicity, and high biocompatibility.
The programmed cell death 6 (PDCD6), discovered as a proapoptotic calcium-binding protein, has recently been found dysregulated in tumors of various origin and contributed to cancer cell viability. The aim of this study was to determine whether SNPs in PDCD6 are associated with cervical squamous cell carcinoma (CSCC). Polymerase chain reaction-restriction fragment length polymorphism method was used to genotype two tag SNPs (rs3756712 and rs4957014) of PDCD6 in 328 CSCC patients and 541 controls. Significantly increased CSCC risks were found to be associated with T allele of rs3756712 and G allele of rs4957014 (P = 0.017, OR = 1.320, and P = 0.007, OR = 1.321, respectively). CSCC risks were associated with these two SNPs in different genetic model (P = 0.04, OR = 1.78 for rs3756712 in a recessive model, and P = 0.006, OR = 2.01 for rs4957014 in a codominant model, respectively). Results of stratified analyses revealed that rs4957014 is associated with parametrial invasion of CSCC (P = 0.044, OR = 1.414). Our results suggest that these two tag SNPs of PDCD6 are associated with CSCC, indicating that PDCD6 may play an important role in the pathogenesis of CSCC.
Aim. To analyze the serum nicotinamide phosphoribosyltransferase (Nampt) level and its prognostic value in bladder cancer (BC). Methods. The study included 131 patients with transitional cell BC and 109 healthy controls from the West China Hospital of Sichuan University in the period between 2007 and 2013. Nampt concentration in serum was measured by commercial ELISA kits for human Nampt. Results. The serum Nampt protein level in patients with BC (mean±standard deviation, 16.02±7.95 ng/mL) was significantly higher than in the control group (6.46±2.08 ng/mL) (P<0.001). Serum Nampt level was an independent prognostic marker of non-muscle-invasive BC, with a higher serum Nampt level (>14.74 ng/mL) indicating shorter recurrence-free survival rate (hazard ratio=2.85, 95% confidence interval, 1.01-8.06; P=0.048). Conclusion. Our results suggest that serum Nampt level may serve as a biomarker of BC and an independent prognostic marker of non-muscle-invasive BC.
Semiconductor nanocrystals (NCs) possess unique photoluminescent properties which can be used to design fluorescence probes for chemo/biosensing applications. Several have recently emerged that offer excellent turn-on or ratiometric fluorescence chemosensory protocols by sophisticated procedures, but it has been challenging to realize all of these advantages in a single construct. Herein, we develop an intrinsic dual-emitting Mn-doped ZnS nanocrystal-based probe that achieves this goal with turn-on and ratiometric fluorescence response for the determination of organophosphate (diethylphosphorothioate, DEP). The probe relies on the modification of dopamine dithiocarbamate on the surface of NCs and the modulation of dual emission through a photoinduced electron transfer process, which makes use of red fluorescence of Mn(2+) ions doped in the NCs as specific recognition for the target analyte and blue defect emission of the NCs as stable internal reference. In presence of DEP, the red emission of the probe is thus enhanced by switching off the electron transfer pathway, while the blue emission is almost unchanged. With the addition of different amounts DEP, the two emission intensity ratios gradually vary and display color changes from dark-blue to purple to red. Thus, this method generates turn-on and ratiometric fluorescence signals for quantitative and visual detection of the analyte. Significantly, the dual-emitting probe has been used to fabricate paper-based test strips for visual detection of DEP residues, which validate the method for its rapid, on-site, and visual identification.
Highly green emissive gold nanoclusters (Au NCs) are synthesized using glutathione as a stabilizing agent and mercaptopropionic acid as a ligand, and the intensity of fluorescence is specifically sensitive to lead ions. We then fabricated a ratiometric fluorescence nanohybrid by covalently linking the green Au NCs to the surface of silica nanoparticles embedded with red quantum dots (QDs) for on-site visual determination of lead ions. The green fluorescence can be selectively quenched by lead ions, whereas the red fluorescence is inert to lead ions as internal reference. The different response of the two emissions results in a continuous fluorescence color change from green to yellow that can be clearly observed by the naked eyes. The nanohybrid sensor exhibits high sensitivity to lead ions with a detection limit of 3.5 nM and has been demonstrated for determination of lead ions in real water samples including tap water, mineral water, groundwater, and seawater. For practical application, we dope the Au NCs in poly(vinyl alcohol) (PVA) film and fabricate fluorescence test strips to directly detect lead ions in water. The PVA-film method has a visual detection limit of 0.1 ?M, showing its promising application for on-site identification of lead ions without the need for elaborate equipment.
The development of convenient methods for sulfur dioxide and its derivatives analysis is critically important because SO2 causes worldwide serious environmental problems and human diseases. In this work, we show an unprecedented example of an energy-transfer-based fluorescence nanoprobe for selective and quantitative detection of SO2, through molecular engineering of the fluorescent carbon nanodots by a cyanine dye which have a unique reactivity to bisulfite, achieving a detection limit of 1.8 ?M with a linear relationship (R(2) = 0.9987). The specific detection was not interfered with other potential coexisted species. In addition, the probe is demonstrated for the determination of SO2 gas in aqueous solution as well as for visually monitoring of SO2 gas in air. This nanomaterial based probe is easily prepared, fast responding, and thus potentially attractive for extensive application for the determination of SO2 and other similar air pollutants.
Atherosclerosis has been widely considered as a chronic inflammation process, which triggers a wide range of cardiovascular diseases such as ischemic coronary artery disease (CAD). Toll-like receptor 4 (TLR4), a primary receptor of the innate immune system, plays a pivotal role in the initiation and progression of atherosclerosis. Here we summarize recent progress on understanding the activation and function of TLR4 signaling in the initiation and development of CAD, with the focus on the role of TLR4 as a link between CAD and other inflammatory diseases. Furthermore, we list a variety of drugs which exert anti-atherosclerosis effects via targeting TLR4 signaling. Finally, we discuss the promise of TLR4 signaling as a therapeutic target for CAD.
(13)C-engineered carbon quantum dots ((13)C-QDs) were used as magnetic resonance (MR) and fluorescence dual-response probe. The enhanced (13)C-MR signal was observed at 171 ppm from carboxylic and carboxyl carbons in (13)C-QDs with 160-fold improvement on signal-to-noise ratio even when no hyperpolarization was applied, whereas the intrinsic fluorescence of C-QDs was still maintained. The stable MR and fluorescence dual-response was successfully used for long-term observation of zebrafish embryonic development. Cross-validation between MR and fluorescence confirmed the distribution of (13)C-QD in zebrafish. (13)C-MR provides specific information about the presence, magnitude, and progression of (13)C-QDs by defining MR intensity, whereas fluorescence reveals the location of (13)C-QDs with its high sensitivity. (13)C-MR and fluorescence was simultaneously observed within (13)C-QDs, and this work may expand the applications of isotope-engineered nanomaterials.
Breast cancer cell lines and mouse models are valuable tools for investigating the biology of and developing potential therapeutics for human breast carcinoma. The PTEN-/-/NIC mouse is a genetically engineered mouse model for ErbB2/Neu-overexpressing/?PTEN deficient breast carcinoma with histopathological and molecular features relevant to the luminal subtype of primary human breast cancer. However, the PTEN-/-/NIC model develops multifocal and aggressive mammary tumors with a short life-span, which greatly impedes its preclinical usage. To complement the genetic engineering approach and to facilitate the future application of this model, in the present study, two newly established cell lines, NICP20 and NICP21, from PTEN-/-/NIC mammary tumors are described. These NICP20 and NICP21 cells retained the crucial molecular phenotype similar to the origin, as confirmed by genotyping and western blot analysis. These cells induced tumors in immunocompetent syngeneic mice by mammary fat pad injection and produced lung metastasis when injected intravenously. Tumors induced by these cells displayed luminal?like histologic morphology and hyperactivation of Akt which are similar to PTEN-/-/NIC tumors. Immunohistochemical staining also revealed that tumors induced by the NICP20 and NICP21 cells showed a high proliferative level, comparable angiogenesis and T-cell infiltration properties similar to PTEN-/-/NIC tumors. Therefore, these NICP20 and NICP21 cells represent an alternative and useful model system to enhance our understanding of the nature of ErbB2-positive breast cancers, particularly accompanying PTEN loss and to facilitate further experimental therapeutic studies.
The majority of killer cell immunoglobin-like receptor (KIR) genes are detected as either present or absent using locus-specific genotyping technology. Ambiguity arises from the presence of a specific KIR gene since the exact copy number (one or two) of that gene is unknown. Therefore, haplotype inference for these genes is becoming more challenging due to such large portion of missing information. Meantime, many haplotypes and partial haplotype patterns have been previously identified due to tight linkage disequilibrium (LD) among these clustered genes thus can be incorporated to facilitate haplotype inference. In this paper, we developed a hidden Markov model (HMM) based method that can incorporate identified haplotypes or partial haplotype patterns for haplotype inference from present-absent data of clustered genes (e.g., KIR genes). We compared its performance with an expectation maximization (EM) based method previously developed in terms of haplotype assignments and haplotype frequency estimation through extensive simulations for KIR genes. The simulation results showed that the new HMM based method outperformed the previous method when some incorrect haplotypes were included as identified haplotypes and/or the standard deviation of haplotype frequencies were small. We also compared the performance of our method with two methods that do not use previously identified haplotypes and haplotype patterns, including an EM based method, HPALORE, and a HMM based method, MaCH. Our simulation results showed that the incorporation of identified haplotypes and partial haplotype patterns can improve accuracy for haplotype inference. The new software package HaploHMM is available and can be downloaded at http://www.soph.uab.edu/ssg/files/People/KZhang/HaploHMM/haplohmm-index.html.
The objective of this study was to identify the association between gender norms and family planning practices among men in Western Jamaica. A cross-sectional survey of 549 men aged 19 to 54 years attending or visiting four government-operated hospitals was conducted in 2011. Logistic regression models were used to identify factors associated with taking steps to prevent unwanted pregnancy, intention to have a large family size (three or more children), and fathering children with multiple women. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated from the models. Reduced odds for taking steps to prevent unwanted pregnancy among men with moderate (AOR = 0.5; 95% CI = 0.3-0.8) and high (AOR = 0.3; 95% CI = 0.1-0.6) support for inequitable gender norms was observed. Desiring large family size was associated with moderate (AOR = 2.0; 95% CI = 1.3-2.5) and high (AOR = 2.6; 95% CI = 1.5-4.3) support for macho scores. For men with two or more children (41%), there were increased odds of fathering children with multiple women among those who had moderate (AOR = 2.1; 95% CI = 1.0-4.4) and high (AOR = 2.4; 95% CI = 1.1-5.6) support for masculinity norms. Support for inequitable gender norms was associated with reduced odds of taking steps to prevent unwanted pregnancy, while support for masculinity norms was associated with desiring a large family size and fathering children with multiple women. These findings highlight the importance of including men and gender norms in family planning programs in Jamaica.
Mesoporous silica nanoparticles (MSNs) were co-doped with Gd(3+) and Al(3+) and then loaded with Ru(bpy)3(2+) by ion-exchange to prepare Ru/Gd-Al@MSNs. The as-prepared Ru/Gd-Al@MSNs were applied as contrast agents for in vivo fluorescence and magnetic resonance (MR) dual-modality imaging with a mouse as a model. The effects of Al(3+) and MSNs on longitudinal relaxivity (r1) and fluorescence were investigated using a series of Gd-containing silica nanoparticles, including Gd@MSNs, Gd-Al@MSNs, and Ru/Gd-Al@nonporous silica nanoparticles. Co-doping with Al(3+) improved the loading of Gd(3+); the mesoporous structure improved the water exchange rate. The improvement enhanced the MR imaging efficiency of the Ru/Gd-Al@MSN probe. A higher relaxivity (19.2 mM(-1) s(-1)) was observed compared to that from a commercial contrast agent, Gd-diethylene triamine pentaacetic acid (Gd-DTPA). Importantly, the mesoporous structure provided a large specific surface area for the loading of Ru(bpy)3(2+) by a simple ion-exchange procedure. Intense red fluorescence was observed from Ru/Gd-Al@MSN probes. The versatility of Ru/Gd-Al@MSNs for dual-modality imaging was demonstrated using in vivo fluorescence imaging and T1-weighted MR imaging with a mouse model. The nanoparticles are biocompatible and may be attractive for clinical applications.
Functional quantum dots (QDs) grafted with ferric dithiocarbamate complex layers (QDs-Fe(III)(DTC)3) were fabricated and demonstrated to be selectively reactive to nitric oxide. The dithiocarbamate (DTC) was covalently conjugated to the amine-coated QDs by a condensation reaction of the carboxyl in DTC and the amino polymer in surface of QDs. The weak fluorescence of QDs-Fe(III)(DTC)3 was attributed to the energy transfer between CdSe/ZnS and Fe(III)(DTC)3 complex at the surface of the functionalized quantum dots. Nitric oxide could greatly switch on the fluorescence of QDs-Fe(III)(DTC)3 by displacing the DTC in the Fe(III)(DTC)3 accompanied by reducing Fe(III) to Fe(II), thus shutting off the energy transfer way. The limit of detection for nitric oxide was estimated to be 3.3 ?M and the specific detection was not interfered with other reactive oxygen species. Moreover, the probe was demonstrated for the sensing of gaseous nitric oxide, and the visual detection limit was as low as 10 ppm, showing the potential for sensing nitric oxide by the naked eye.
Emerging evidence has demonstrated that polymorphisms of interleukin-1 (IL-1) may be involved in human tumorigenesis by regulating the production of this cytokine. Previous studies have investigated the association between two genetic variants (rs3783553 and rs17561) of IL1A and many diseases. The present study was conducted to evaluate whether these two variants are associated with cervical carcinoma (CC). These two polymorphisms were genotyped in 319 CC patients and 424 healthy controls by polymerase chain reaction polyacrylamide gel electrophoresis (PCR-PAGE) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Significantly reduced CC risk was observed to be associated with the insertion allele of rs3783553 (P=0.014, OR=0.71, 95% CI=0.57-0.88). Stratification analysis based on different certain clinical features showed that patients with the heterozygous genotype were associated with a reduced predisposition advancing to clinical stage II-III or developing non-squamous cell carcinoma. Furthermore, patients with the insertion homozygous genotype were also associated with a reduced risk to have a poor tumor differentiation. No significant association was observed between rs17561 and CC. The present study provided evidence that the rs3783553 in IL1A 3'-UTR is inversely associated with CC risk, suggesting an important role IL-1? may play in cervical carcinogenesis.
To investigate whether the Fc? receptor IIIa-66L/R/H (Fc?RIIIa-66L/R/H) polymorphism influences net effective receptor function and to assess if the FCGR3A combined genotypes formed by Fc?RIIIa-66L/R/H and Fc?RIIIa-176F/V, as well as copy number variation (CNV), confer risk of developing systemic lupus erythematosus (SLE) and lupus nephritis.
As an important economic insect, Bombyx mori is also a useful model organism for lepidopteran insect. Integrins are evolutionarily conserved from sponges to humans, and play vital roles in many physiological and pathological processes. To explore their diverse functions of integrins in insect, eleven integrins including six ? and five ? subunits were cloned and characterized from silkworm. Our results showed that integrins from silkworm own more family members compared to other invertebrates. Among those ? subunits, integrins ?1, ?2, and the other four subunits belong to PS1, PS2, and PS3 groups, respectively. The ? subunits mainly gather in the insect ?? group except the ?1 subunit which belongs to the insect ? group. Expression profiles demonstrated that the integrins exhibited distinct patterns, but were mainly expressed in hemocytes. ?1 and ?2 subunits are the predominant ones either in the embryogenesis or larva stages. Interestingly, integrins were significantly up-regulated after stimulated by 20-hydroxyecdysone (20-E) in vivo. These results indicate that integrins perform diverse functions in hemocytes of silkworm. Overall, our results provide a new insight into the functional and evolutionary features of integrins.
Using pulsed laser deposition, TiO2 (-) B and its recently discovered variant Ca:TiO2 (-) B (CaTi5O11) are synthesized as highly crystalline thin films for the first time by a completely water-free process. Significant enhancement in the Li-ion battery performance is achieved by manipulating the crystal orientation of the films, used as anodes, with a demonstration of extraordinary structural stability under extreme conditions.
Homotypic cell aggregation plays important roles in physiological and pathological processes, including embryogenesis, immune responses, angiogenesis, tumor cell invasion and metastasis. CD147 has been implicated in most of these phenomena, and it was identified as a T cell activation-associated antigen due to its obvious up-regulation in activated T cells. However, the explicit function and mechanism of CD147 in T cells have not been fully elucidated. In this study, large and compact aggregates were observed in Jurkat T cells after treatment with the specific CD147 monoclonal antibody HAb18 or after the expression of CD147 was silenced by RNA interference, which indicated an inhibitory effect of CD147 in T cell homotypic aggregation. Knocking down CD147 expression resulted in a significant decrease in CD98, along with prominent cell aggregation, similar to that treated by CD98 and CD147 monoclonal antibodies. Furthermore, decreased cell chemotactic activity was observed following CD147- and CD98-mediated cell aggregation, and increased aggregation was correlated with a decrease in the chemotactic ability of the Jurkat T cells, suggesting that CD147- and CD98-mediated homotypic cell aggregation plays a negative role in T cell chemotaxis. Our data also showed that p-ERK, p-ZAP70, p-CD3? and p-LCK were significantly decreased in the CD147- and CD98-knocked down Jurkat T cells, which suggested that decreased CD147- and/or CD98-induced homotypic T cell aggregation and aggregation-inhibited chemotaxis might be associated with these signaling pathways. A role for CD147 in cell aggregation and chemotaxis was further indicated in primary CD4(+) T cells. Similarly, low expression of CD147 in primary T cells induced prominent cell aggregation and this aggregation attenuated primary T cell chemotactic ability in response to CypA. Our results have demonstrated the correlation between homotypic cell aggregation and the chemotactic response of T cells to CypA, and these data indicate that CD147 and CD98 might play important roles in cyclophilin-induced cell migration.
Herein, for the detection of highly explosive 2,4,6-trinitrotoluene (TNT) instantly and on-site, a fluorescence ratiometric probe using a dual-emission nanohybrid has been developed. The nanohybrid comprises blue-colored fluorescent graphene oxide (FGO) being conjugated with red-emitting manganese-doped ZnS nanocrystals (ZnS:Mn NCs), the latter being functionalized with hexamethylenediamine. The blue fluorescence of FGO is insensitive to TNT and is used as an internal reference, whereas the red fluorescence of ZnS:Mn NCs can be selectively quenched by TNT through electron transfer, resulting in a unique red-purple-blue color response as the amount of TNT is increased. Thus, the probe could be used for the quantitative measurement of TNT based on the fluorescence ratiometric method. We demonstrated that the nanohybrid probe exhibited high visual detection sensitivity and reliability in comparison with single-color fluorescence quenching probes. A fluorescence test paper was prepared using the nanohybrid probe and was demonstrated to detect TNT residues directly on various surfaces including rubber, a person's fingers and manila envelopes with a visual detection limit as low as 5.68 ng mm(-2), showing its promising application for security screening.
Population stratification is a growing concern in genetic-association studies. Averaged ancestry at the genome level (global ancestry) is insufficient for detecting the population substructures and correcting population stratifications in association studies. Local and phase stratification are needed for human genetic studies, but current technologies cannot be applied on the entire genome data due to various technical caveats. Here we developed a novel approach (aMAP, ancestry of Modern Admixed Populations) for inferring local phased ancestry. It took about 3 seconds on a desktop computer to finish a local ancestry analysis for each human genome with 1.4-million SNPs. This method also exhibits the scalability to larger datasets with respect to the number of SNPs, the number of samples, and the size of reference panels. It can detect the lack of the proxy of reference panels. The accuracy was 99.4%. The aMAP software has a capacity for analyzing 6-way admixed individuals. As the biomedical community continues to expand its efforts to increase the representation of diverse populations, and as the number of large whole-genome sequence datasets continues to grow rapidly, there is an increasing demand on rapid and accurate local ancestry analysis in genetics, pharmacogenomics, population genetics, and clinical diagnosis.
Circulating endothelial progenitor cells (EPCs) may be a biomarker for vascular function and cardiovascular risk in patients with coronary artery disease (CAD). Dimethylarginine dimethylaminohydrolase 2 (DDAH2) regulates the function of EPCs. This study aimed to examine whether hypermethylation of DDAH2 promoter contributes to impaired function of EPCs in CAD patients.
Rheumatoid arthritis (RA) is a common autoimmune disease that is primarily driven by effector T cells, particularly Th17 cells, which are mainly contained within CD4+CD161+ T cells. Thus, we aimed to explore whether the frequencies of circulating IL-17-producing CD4+CD161+ T cells and CD4+CD161+ T cells were correlated with RA disease activity.
The IL1RL1, which encodes at least three isoforms by alternative splicing, has been identified to be involved in the initiation and perpetuation of inflammation. In spite of being a main contributor of maternal and perinatal mortality, the mechanism responsible for the pathophysiology of preeclampsia has not yet been well addressed. To investigate the relationship between IL1RL1 polymorphisms and preeclampsia risk, we identified the correlation between three tag SNPs (rs13017455, rs1420103 and rs17027006) in IL1RL1 with preeclampsia risk in a case-control study. A total of 214 cases and 208 controls were recruited to participate in this study. Genotypes of the three SNPs were determined with the use of polymerase chain reaction-restriction fragment length polymorphism assay. Significantly reduced preeclampsia risk was found to be associated with the CT genotype of rs13017455 (p = 0. 032, OR = 0. 66, 95% CI = 0.45-0.97) in overdominant model. Differences were particularly significant in the severe preeclampsia subgroup (p = 0.045, OR = 0.66, 95% CI = 0.44-0.99) and the early-onset severe preeclampsia subgroup (p = 0.0097, OR = 0.47, 95% CI = 0.26-0.84). Significantly increased mild preeclampsia risk was observed associated with GG genotype of rs1420103 polymorphisms (p = 0.029, OR = 2.18, 95% CI = 1.09-4.34), while reducing late-onset severe preeclampsia susceptibility was associated with TT genotype of rs1420103 (p = 0.02, OR = 0.49, 95% CI = 0.26-0.92).
Lung interstitial fibrosis is a chronic lung disease, and few effective therapies are available to halt or reverse the progression of the disease. In murine and human lung fibrosis, the expression of CD147 is increased. However, the role of CD147 in lung fibrosis has not been identified, and it remains to be determined whether lung fibrosis would be improved by decreasing the expression of CD147. A murine bleomycin-induced lung interstitial fibrosis model was used in the experiments, and HAb18 mAbs and CsA were administered during the induction of lung fibrosis. In our study, we found that the HAb18 mAbs markedly reduced the collagen score and down-regulated M1 macrophages and Th17 cells. In vitro, flow cytometry analysis showed that M1 macrophages induced higher Th17 differentiation than M2 macrophages. After treatment with HAb18 mAbs or after reducing the expression of CD147 by lentivirus interference in M1 macrophages, the level of Th17 cells were significantly inhibited. In conclusion, HAb18 mAbs or CsA treatment ameliorates lung interstitial fibrosis. CD147 promoted M1 macrophage and induced the differentiation of Th17 cells in lung interstitial fibrosis, perhaps by regulating some cytokines such as IL-6, IL-1?, IL-12 and IL-23. These results indicated that CD147 may play an important role in the development of lung interstitial fibrosis.
Osteosarcoma occurs most commonly in children and young adults, with a historic second incidence peak in the elderly. Most studies have focused on those occurring in adolescence. Detailed information on descriptive features and prognostic factors in patients of different age groups is lacking. We analyzed 381 osteosarcomas diagnosed between 1973 and 2012 to identify factors significantly associated with survival in various age groups. The peak incidence was seen in patients age <25, followed by a steady incidence rate thereafter until the sixth decade, when it started to decline. In the early onset diseases, significant factors for recurrence-free survival (RFS) were tumor site and size; whereas those for overall survival (OS) were gender, tumor site, type, grade and size. In patients age 25 to 54, tumor type and grade were significant for RFS, and the pathologic type was significant for OS. In those age ?55, race and tumor size were significant for RFS; tumor site and size were significant for OS. In multivariate analysis, tumor size remained significant for RFS; gender, tumor site and size maintained their significance for OS in patients age <25. While no independent factor was identified in patients age 25 to 54, tumor size remained significant for RFS in those age ?55. Chemotherapy-induced tumor necrosis was a prognosticator for RFS in patients age 25 to 54 by univariate analysis, but not as an independent factor in any stratified age group. Our data indicate that the distinctive prognostic factors differed significantly among different age groups, thus providing a rationale for age-based management strategies.
Klebsiella pneumoniae is a frequent nosocomial pathogen, with the multidrug-resistant (MDR) K. pneumoniae being a major public health concern, frequently causing difficult-to-treat infections worldwide. The aim of this study was to investigate the molecular characterization of clinical MDR Klebsiella pneumoniae isolates.
Objectives Gender norms, especially among men, can reduce the effectiveness of HIV prevention programs. We sought to assess the association between attitudes towards gender norms and risky sexual behaviours, and identify sociodemographic factors that predict gender-inequitable and masculinity norms among men in western Jamaica. Methods: A cross-sectional, survey of 549 men aged 19-54 years was conducted. Attitudes towards gender norms were measured using the Gender Equitable Men and Macho scales. Logistic regression and general linear models were used to assess associations between gender norms and multiple sexual partners, and to identify the associated sociodemographic factors. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) are presented. Results: Fifty-four percent of the participants (mean age=32.4 years) reported multiple sex partners and 22% reported unprotected sex with non-regular partner in the past 12 months. Men with moderate (AOR=2.2; 95% CI=1.4-3.3) and high (AOR=4.2; 95% CI=2.0-8.5) support for inequitable gender norms, and moderate (AOR=1.7; 95% CI=1.1-2.7) and high (AOR=2.5; 95% CI=1.5-4.3) support for masculinity norms were more likely to report multiple sex partners. Similarly, men with moderate (AOR=2.4; 95% CI=1.3-4.3) and high (AOR=2.5; 95% CI=1.2-5.2) support for inequitable gender norms were more likely to report unprotected sex with a nonregular partner. Conclusion: A high proportion of Jamaican men engage in risky sexual behaviours. These results highlight the need for behaviour change interventions addressing gender norms targeting Jamaican men.
Trastuzumab resistance is a challenging problem in ErbB2/HER2-positive breast cancers. Multiple mechanisms of resistance have been proposed and, thus, may require the development of more personalized therapies. In this study, we report the establishment of a mouse mammary cancer cell line, designated MT104T, obtained from spontaneous tumors in genetically engineered FVB/N-ErbB2/Neu-positive-PTEN-deficient mice. The critical molecular phenotype of MT104T cells was confirmed by genotyping and western blot analysis. This cell line was tumorigenic in immunologically intact syngeneic mice, forming tumors of generally similar histology as its origin. PTEN loss led to hyperactivation of Akt and conferred resistance to anti-ErbB2/Neu antibody treatment in MT104T cells. Addition of the Akt inhibitor triciribine (TCN) inhibited the viability of MT104T cells in a dose- and time-dependent manner as evaluated by MTT assay. ErbB2/Neu antibody and TCN combination treatment greatly induced apoptosis of MT104T cells as indicated by Annexin V-FITC staining. Moreover, this combination treatment also significantly reduced both Akt and Erk activities, which are responsible for the inhibitory effect on MT104T cells. Therefore, MT104T cells could represent an alternative model system to investigate the nature of ErbB2?positive breast cancer and for the experimental therapeutics studies of this disease. Our findings also suggest that combination of TCN may be a potential strategy for the treatment of trastu-zumab-resistant breast cancer mediated by PTEN loss or PI3K hyperactivation, which may facilitate the development of more personalized therapies for breast cancer patients.
Accumulating evidence supports that genetic factors are another risk factors for lung cancer. Previously, we used whole exome sequencing with sanger sequencing to search for genetic-related mutations in one of four individuals from a pedigree with lung cancer history. Then, we used PCR-RFLP and direct-sequence in the sample size of 318 individuals with lung cancer (cases) and 272 controls. Recently, we detected two new genes including CRTC2 (CREB regulated transcription coactivator 2) and PROM1(human prominin-1,CD133). We investigated the CRTC2 mutation and PROM1 mutation of surgically resected NSCLC tissues (n=200). The presence or absence of CRTC2 and PROM1 mutation was analyzed by direct sequencing. The expression of CRTC2 and PROM1 was studied by western blot and immunohistochemical analysis of the lung cancer tissues which had the mutation of the two genes(cases), the samples without mutations(controls) and the normal lung tissue(controls). CRTC2 and PROM1 mutations in 5 NSCLC tissues and 3 NSCLC tissues out of the samples were identified. The positive results were closely correlated with clinicopathological features, such as male gender, adenocarcinoma, smoker status, and older age (?55). We found that the CRTC2 and PROM1 expression were significantly higher in tissues of NSCLS with mutations than that without mutations and the normal lung tissue. The results imply that the high expression of CRTC2 and PROM1 may play an important role in the development and hereditary of NSCLC.
Escherichia coli is an important pathogen involved in community-acquired urinary tract infections (CA-UTIs). In this study, we analyzed the prevalence of frequently occurring genes and the distribution of integrons in 51 multidrug-resistant (MDR) E. coli isolates associated with CA-UTIs. The clonality of these strains was investigated by phylogrouping, multi-locus sequence typing, and pulsed-field gel electrophoresis (PFGE). All these strains were found to produce two or more resistance determinants, ceftazidime-hydrolyzing CTX-M-type extended-spectrum ?-lactamases (ESBLs) and plasmid-mediated quinolone resistance determinants were the most prevalent (92.2% and 51.0%, respectively). A sulfhydryl variable-61-producing E. coli strain was identified for the first time in China. The prevalence of class 1 integrons was 54.9%, class 2 integrons were detected in three isolates but no isolate contained a class 3 integron. Phylogenetic group D was the dominant, observed in 70.6% of the isolates. PFGE analysis revealed a high level of diversity. Twenty-four distinctive sequence types (STs) including four major STs (ST648, ST224, ST38, and ST405) were identified. To our knowledge, this is the first report on the characterization of MDR E. coli isolates associated with CA-UTIs in China; our results suggest that an MDR D-ST648 clone producing CTX-M-ESBLs has emerged as a major clone in the community setting.
Programmed cell death 6 (PDCD6) has recently been found dysregulated in tumors of various origin. The aim of this study is to explore the association between PDCD6 genetic polymorphisms and susceptibility to bladder cancer and survival of patients with bladder cancer. Two tag SNPs of PDCD6, rs3756712 and rs4957014, were genotyped in 332 patients with bladder cancer and 509 controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and correlated with patients' survival. The frequencies of G allele and GG genotype of rs3756712 in patients were significantly lower than that of controls (P?=?0.001, odds ratio [OR]?=?0.68 for G allele; P?=?0.024, OR?=?0.53 for GG genotype in the recessive genetic model, respectively). The GT genotype of rs4957014 was associated with decreased susceptibility to bladder cancer in the overdominant genetic model (P?=?0.023, OR?=?0.72). Kaplan-Meier curves revealed a significant higher risk for death in superficial bladder cancer patients harboring GG homozygous of rs3756712 (P?0.001), and an increased risk for recurrence in invasive bladder cancer patients carrying GT heterozygous of rs4957014 (P?=?0.04). Multiple Cox regression analysis identified rs3756712 GG genotype as an independent prognostic factor for death in superficial bladder cancer patients (hazard ratio [HR]?=?5.11, P?=?0.01), and rs4957014 GT genotype as an independent prognostic factor for recurrence in invasive bladder cancer patients (HR?=?1.93, P?=?0.03). PDCD6 may represent a biomarker candidate gene that could help to identify a group of patients at high risk for recurrence and death.
Recent studies have demonstrated the protective effect of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in cardiovascular diseases. Increased levels of the potential ALDH2 substrate 4-hydroxynonenal (4-HNE) are involved in myocardial/cerebral ischemia accompanied by a high level of oxidative stress. In this investigation, we first performed a case-control study to explore the potential association of ALDH2 rs671 polymorphism and post-stroke epilepsy (PSE). Then, we performed an in vitro study to determine whether the overexpression of ALDH2 could decrease the level of oxidative stress and the apoptosis ratio induced by 4-HNE. There was a significant difference in the distribution of the allele and genotype frequencies of the rs671 polymorphism between PSE patients and ischemic stroke (IS) patients. Individuals with the rs671 A allele showed significantly higher levels of plasma 4-HNE. The overexpression of ALDH2 partially blocked the increased levels of malondialdehyde (MDA), reactive oxygen species (ROS) and apoptosis ratio induced by 4-HNE and also partially restored the ALDH2 activity in PC12 cells; these effects were reversed in the presence of ?V1-2. Our results suggest that the ALDH2 rs671 polymorphism is associated with PSE susceptibility and affects the 4-HNE levels. Targeting ALDH2 might be a useful strategy for the treatment or prevention of PSE.
In this paper, based on the coupled social networks (CSN), we propose a hybrid algorithm to nonlinearly integrate both social and behavior information of online users. Filtering algorithm, based on the coupled social networks, considers the effects of both social similarity and personalized preference. Experimental results based on two real datasets, Epinions and Friendfeed, show that the hybrid pattern can not only provide more accurate recommendations, but also enlarge the recommendation coverage while adopting global metric. Further empirical analyses demonstrate that the mutual reinforcement and rich-club phenomenon can also be found in coupled social networks where the identical individuals occupy the core position of the online system. This work may shed some light on the in-depth understanding of the structure and function of coupled social networks.
The influenza A H7N9 virus outbreak in Eastern China in the spring of 2013 represented a novel, emerging avian influenza transmission to humans. While clinical and microbiological features of H7N9 infection have been reported in the literature, the current study investigated acute cytokine and antibody responses in acute H7N9 infection. Between March 27, 2013 and April 23, 2013, six patients with confirmed H7N9 influenza infection were admitted to Drum Tower Hospital, Nanjing, China. Acute phase serum cytokine profiles were determined using a high-throughput multiplex assay. Daily H7 hemagglutinin (HA)-specific IgG, IgM, and IgA responses were monitored by ELISA. Neutralizing antibodies specific for H7N9 viruses were determined against a pseudotyped virus expressing the novel H7 subtype HA antigen. Five cytokines (IL-6, IP-10, IL-10, IFN?, and TNF?) were significantly elevated in H7N9-infected patients when compared to healthy volunteers. Serum H7 HA-specific IgG, as well as IgM and IgA responses, were detected within 8 days of disease onset and increased in a similar pattern during acute infection. Neutralizing antibodies developed shortly after the appearance of binding antibody responses and showed similar kinetics as a fraction of the total H7 HA-specific IgG responses. H7N9 infection resulted in hallmark serum cytokine increases, which correlated with fever and disease persistence. The novel finding of simultaneous development of IgG, IgM, and IgA responses in acute H7N9 infection points to the potential for live influenza viruses to elicit fast and potent protective antibodies to limit the infection.
Many studies have shown that low sex hormone-binding globulin (SHBG) is associated with insulin resistance, but only few studies have examined how serum SHBG is regulated by insulin in humans. This interventional study aimed to investigate the effect of insulin therapy (IT) on serum SHBG levels in newly diagnosed type 2 diabetic patients.
This work presented a novel strategy for the synthesis of the hybrid structure silica/CdTe/molecularly imprinted polymer (Si-NP/CdTe/MIP) to recognize and detect the template bovine hemoglobin (BHb). First, amino-functionalized silica nanoparticles (Si-NP) and carboxyl-terminated CdTe quantum dots (QDs) were assembled into composite nanoparticles (Si-NP/CdTe) using the EDC (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) chemistry. Next, Si-NP/CdTe/MIP was synthesized by anchoring molecularly imprinted polymer (MIP) layer on the surface of Si-NP/CdTe through the sol-gel technique and surface imprinting technique. The hybrid structure possessed the selectivity of molecular imprinting technique and the sensitivity of CdTe QDs as well as well-defined morphology. The binding experiment and fluorescence method demonstrated its special recognition performance toward the template BHb. Under the optimized conditions, the fluorescence intensity of the Si-NP/CdTe/MIP decreased linearly with the increase of BHb in the concentration range 0.02-2.1 ?M, and the detection limit was 9.4 nM. Moreover, the reusability and reproducibility and the successful applications in practical samples indicated the synthesis of Si-NP/CdTe/MIP provided an alternative solution for special recognition and determination of protein from real samples.
Suppressor of cytokine signaling (SOCS) proteins are inhibitors of cytokine signaling pathway involved in negative feedback loops. Although SOCS1 is an important intracellular suppressor of apoptosis in a variety of cell types, its role in cytokine-induced pancreatic ?-cell apoptosis remains unclear. The present study investigated potential effects of SOCS1 on the cytokine-induced pancreatic ?-cell apoptosis.
Our previous study showed that hypermethylation of dimethylarginine dimethylaminohydrolase 2 contributes to homocysteine-induced apoptosis of human umbilical vein endothelial cells. Epigallocatechin-3-gallate is a green tea-derived phenol which has been proved beneficial on atherosclerosis. It was demonstrated that epigallocatechin-3-gallate inhibits DNA methyltransferase activity and reactivates methylation-silenced genes in cancer cells. The aim of this study was to address whether epigallocatechin-3-gallate could induce DNA demethylation of the dimethylarginine dimethylaminohydrolase 2 gene, contributing to prevent endothelial cells from apoptosis induced by homocysteine. Human umbilical vein endothelial cells (ATCC, CRL-2480) were treated with homocysteine (1?mM) for 48 hours with or without epigallocatechin-3-gallate (20?µM) or 5-Aza (DNA methyltransferase inhibitor, 5?µM). Apoptosis rate of human umbilical vein endothelial cells was assayed by flow cytometry with an annexin V-FITC apoptosis detection kit. The mRNA and protein expression level of dimethylarginine dimethylaminohydrolase 2 and DNA methyltransferase 1 were detected by real-time PCR and Western blot, respectively. DNA methylation level of dimethylarginine dimethylaminohydrolase 2 was assayed by methylation specific PCR. The binding level of DNA methyltransferase 1 in the promoter of dimethylarginine dimethylaminohydrolase 2 was determined by chromatin immunoprecipitation-quantitative real-time PCR. It was shown that the apoptosis rate was decreased significantly in human umbilical vein endothelial cells treated with homocysteine compared with the control. Furthermore, the mRNA and protein level of dimethylarginine dimethylaminohydrolase 2 were downregulated, the dimethylarginine dimethylaminohydrolase 2 gene promoter was hypermethylated, and the DNA methyltransferase 1 mRNA and protein level were increased in human umbilical vein endothelial cells treated with homocysteine. Chromatin immunoprecipitation-quantitative real-time PCR revealed that homocysteine-induced binding of DNA methyltransferase 1 to the dimethylarginine dimethylaminohydrolase 2 promoter was increased. Pretreatment with epigallocatechin-3-gallate or 5-Aza inhibited such effects of homocysteine. In conclusion, epigallocatechin-3-gallate exerted protective effects on homocysteine-induced apoptosis in human umbilical vein endothelial cells by inhibiting promoter hypermethylation of the dimethylarginine dimethylaminohydrolase 2 gene and inducing dimethylarginine dimethylaminohydrolase 2 expression. These effects may be due to the decreased DNA methyltransferase 1 expression and binding of DNA methyltransferase 1 to the dimethylarginine dimethylaminohydrolase 2 promoter induced by epigallocatechin-3-gallate. This research suggests that modulating the epigenetic processes might be a novel plausible way for treatment of atherosclerosis.
Nicotinamide phosphoribosyltransferase (Nampt) was served as a useful biomarker for tumorigenesis and for the prediction of cancer survival. In the present study, we analyzed the SNPs of the NAMPT gene and their impact on the susceptibility and prognosis for patients with bladder cancer (BC). The rs61330082, rs2505568 and rs9034 were selected and genotyped by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method in 407 patients with bladder cancer and 316 ethnicity-matched healthy control subjects. The genotyping method was confirmed by the DNA sequencing analysis. Statistically significant increased bladder cancer risk was found to be associated with the C allele and CC genotype of rs61330082; nevertheless, decreased bladder cancer risk was revealed to be associated with A allele and AT genotype of rs2505568. Stratified analyses revealed the rs61330082 to be statistically associated with increased bladder cancer risk in smokers and increased invasiveness of bladder cancer. The AT heterozygote of rs2505568 may prevent the recurrence of bladder cancer. Kaplan-Meier curves revealed a statistically significant association of rs2505568 with recurrence-free survival for total bladder cancer patients and non-muscle-invasive bladder cancer patients, and a statistically significant association of rs9034 with recurrence-free survival for muscle-invasive bladder cancer patients. Multiple Cox regression analysis identified the rs2505568 as a possible independent prognostic factor for recurrence-free survival in total bladder cancer patients. Our results suggested an important role for NAMPT in the pathogenesis of bladder cancer and SNPs of NAMPT gene might be a novel genetic biomarker for the prognosis of bladder cancer.
Previous studies have identified several single nucleotide polymorphisms (SNPs) of Fc receptor-like 3 (FCRL3), an excellent susceptibility gene, as predisposing factors for human autoimmune diseases (ADs). However, the results remain inconclusive. To assess the effect of four selected SNPs (rs7528684, rs11264799, rs945635 and rs3761959), we conducted a meta-analysis with 34 case-control studies. Summary odd ratios (ORs) and 95% confidence intervals (95% CIs) for the polymorphisms in FCRL3 and ADs risk were evaluated. Furthermore, this meta-analysis was performed by using allele comparisons, as well as stratified analyses by ethnicity and disease phenotypes under different genetic models. Our data showed that the TC, TT?+?TC genotypes of rs7528684 contributed to a lower risk of ADs, compared with the CC carriers (OR?=?0.91, 95% CI?=?0.85-0.97; OR?=?0.91, 95% CI?=?0.85-0.98). In comparison with rs7528684 TC genotype, the TT?+?CC carriers were significantly associated with higher ADs risk (OR?=?1.03, 95% CI?=?1.00-1.07). In terms of stratified analyses by ethnicity and disease phenotypes, there were significant associations of rs7528684 polymorphism both with ADs in Asians and Europeans, and with rheumatoid arthritis, Graves disease, type-1 diabetes, and other ADs under different genetic models. Moreover, significant associations were also found to be correlated with ADs risk for the SNP rs11264799 in mixed subgroup, for rs945635 in Europeans, North Americans and mixed group, and for rs3761959 in North Americans. These findings indicate that the polymorphisms in FCRL3 may play a role in the pathogenesis of ADs.
It has been suggested that the rs2910164 and rs3746444 polymorphisms of pre-miRNA are significantly associated with the risk of autoimmune diseases (ADs), described as candidate susceptibility factors, whereas results have yield conflicting findings. We conducted this meta-analysis to investigate whether these two polymorphisms contribute to susceptibility to ADs by using allele comparison and different genetic models, and we also performed stratified analyses by ethnicity and disease phenotype. Our meta-analysis demonstrated that increased risk of ADs was significantly associated with GC genotype in Asians for SNP rs2910164 in the stratified analyses by ethnicity; there was increased OR for GC genotype compared with that for GG?+?CC genotype in other disease subgroup, respectively (OR?=?0.89, 95% CI?=?0.79-0.99; OR?=?0.84, 95% CI?=?0.75-0.95, respectively). Moreover, elevated AD risk was found to be associated with CC genotype of rs3746444 in contrast to TT and TT?+?TC carriers, respectively (OR?=?0.55, 95% CI?=?0.34-0.90; OR?=?0.59, 95% CI?=?0.36-0.97, respectively). Taken together, these findings indicated that the rs2910164 and rs3746444 polymorphisms may play potential roles in the pathogenesis of ADs.
Syndecan-1 expression is decreased in diverse tumor types but remains controversial in breast carcinomas. The goal of the study was to examine syndecan-1 expression in breast carcinoma and its prognostic significance.
This study investigated the association between IL-27 gene polymorphisms and susceptibility to epithelial ovarian cancer in a Chinese population and discusses the risk factors associated with survival time. We collected data on 229 patients diagnosed with epithelial ovarian cancer, from 15 to 77 years of age with a long clinical follow-up period. Polymerase chain reaction-restriction fragment length polymorphism was performed to determine the genotype of IL-27 gene polymorphisms. Ovarian cancer-specific survival (OCSS) according to genotype of IL-27 gene polymorphisms was explored by Kaplan-Meier analysis and Cox proportional hazards modeling. Significant differences for genotype frequencies of both SNP sites were found between cases and controls. Both allele G frequencies were significantly greater among the cases (rs153109: 0.404 vs. 0.303, P = 0.001, odds ratio [OR]?=?1.333, 95% confidence interval [CI]?=?1.133-1.567; rs17855750: 0.146 vs. 0.083, P = 0.001, OR?=?1.766, 95% CI?=?1.258-2.481). Haplotype analysis showed haplotypes AG, GT and GG were associated with increased ovarian cancer susceptibility while AT was a protective haplotype. Advanced FIGO stage (stages III?+?IV) and non-optimal cytoreductive surgery (residual tumor ?1 cm) were poor prognostic factors in the univariate analysis (P = 0.003, P = 0.049). However, FIGO stage was found to be the only independent significant prognostic factor by Cox proportional hazards analysis (P = 0.042). IL-27p28 mRNA expression was significantly decreased in ovarian cancer patients (P?0.0001), while no significant relationship was found between IL-27p28 mRNA expression and polymorphism of rs153109 and rs17855750 (P?=?0.193 and P?=?0.146, respectively). Our study suggests that IL-27 gene polymorphisms may be involved in the susceptibility to epithelial ovarian cancer, but not in survival in a clinic-based Chinese population. Haplotype analysis of these two SNPs seems to be an important mark to predict the disease susceptibility. Advanced FIGO stage, as the only significant, independent risk factor, predicts poor clinical outcomes for patients diagnosed with epithelial ovarian cancer. The decreased expression of IL-27p28 mRNA in ovarian cancer might indicate the antitumor activities of this novel cytokine.
We have developed a robust, nanobiotechnology-based electrochemical cytosensing approach with high sensitivity, selectivity, and reproducibility toward the simultaneous multiplex detection and classification of both acute myeloid leukemia and acute lymphocytic leukemia cells. The construction of the electrochemical cytosensor involves the hierarchical assembly of dual aptamer-functionalized, multilayered graphene-Au nanoparticle electrode interface and the utilization of hybrid electrochemical nanoprobes co-functionalized with redox tags, horseradish peroxidase, and cell-targeting nucleic acid aptamers. The hybrid nanoprobes are multifunctional, capable of specifically targeting the cells of interest, amplifying the electrochemical signals, and generating distinguishable signals for multiplex cytosensing. The as-assembled electrode interface not only greatly facilitates the interfacial electron transfer process due to its high conductivity and surface area but also exhibits excellent biocompatibility and specificity for cell recognition and adhesion. A superstructured sandwich-type sensor geometry is adopted for electrochemical cytosensing, with the cells of interest sandwiched between the nanoprobes and the electrode interface. Such an electrochemical sensing strategy allows for ultrasensitive, multiplex acute leukemia cytosensing with a detection limit as low as ~350 cells per mL and a wide linear response range from 5 × 10(2) to 1 × 10(7) cells per mL for HL-60 and CEM cells, with minimal cross-reactivity and interference from non-targeting cells. This electrochemical cytosensing approach holds great promise as a new point-of-care diagnostic tool for early detection and classification of human acute leukemia and may be readily expanded to multiplex cytosensing of other cancer cells.
The ability to respond properly to Toll-like receptor (TLR) ligands may be impaired by polymorphisms within the TLR family of genes, which results in an altered susceptibility to cancers. However, the results of epidemiological studies remained inconsistent. To assess the effect of four selected polymorphisms (rs5743708, -196 to -174 del polymorphism, rs3804099, and rs3804100) in TLR-2 on cancer, we conducted a meta-analysis, up to November 2012; 20 case-control studies were available. Summary odds ratios (OR) and corresponding 95% confidence intervals (CIs) for polymorphisms in TLR-2 and cancer risk were estimated. Our meta-analysis identified that elevated cancer risk was statistically associated with -196 to -174 del allele in -196 to -174 del polymorphism (OR=1.63, 95% CI=1.10-2.41 for allele comparison; OR=1.64, 95% CI=1.05-2.57 for dominant model; OR=2.26, 95% CI=1.24-4.12 for recessive model; OR=2.57, 95% CI=1.30-5.08 for DD vs. II and OR=1.53, 95% CI=1.01-2.32 for ID vs. II in codominant model); whereas rs3804099 in TLR-2 was associated with decreased cancer risk. Moreover, in terms of stratified analyses by cancer type for -196 to -174 del polymorphism, significantly elevated risk was observed to be associated with -196 to -174 del allele in "other cancers." These findings indicate that polymorphisms in TLR-2 may play a role, although modest, in cancer development.
A robust, nanobiotechnology-based electrochemical cytosensing platform for the detection of acute leukemia cells was developed with high sensitivity, selectivity, acceptable rapidity and excellent extensibility. It utilized the competitive binding of cell-specific aptamers to acute leukemia cells and subsequent voltammetric quantification of the metal signature. Greatly enhanced sensitivity was achieved with dual signal amplification by using Fe3O4 magnetic nanoparticles (MNPs) as carriers to load a large amount of gold nanoparticles (AuNPs) and AuNP-catalyzed silver deposition. The proposed competitive cytosensor showed high sensitivity with a detection limit down to 10 cells. This simple and low-cost electrochemical cytosensing approach offers great promise to extend its application to early detection of human leukemia and possibly to other cancer cells.
This study aimed to investigate factors that influence antenatal care utilization and their association with adverse pregnancy outcomes (defined as low birth weight, stillbirth, preterm delivery or small for gestational age) among pregnant women in Kumasi. A quantitative cross-sectional study was conducted of 643 women aged 19-48 years who presented for delivery at selected public hospitals and private traditional birth attendants from July-November 2011. Participants information and factors influencing antenatal attendance were collected using a structured questionnaire and antenatal records. Associations between these factors and adverse pregnancy outcomes were assessed using chi-square and logistic regression. Nineteen percent of the women experienced an adverse pregnancy outcome. For 49% of the women, cost influenced their antenatal attendance. Cost was associated with increased likelihood of a woman experiencing an adverse outcome (adjusted OR=2.15; 95% CI=1.16-3.99; p=0.016). Also, women with >5 births had an increased likelihood of an adverse outcome compared with women with single deliveries (adjusted OR=3.77; 95% CI=1.50-9.53; p=0.005). The prevalence of adverse outcomes was lower than previously reported (44.6 versus 19%). Cost and distance were associated with adverse outcomes after adjusting for confounders. Cost and distance could be minimized through a wider application of the Ghana National Health Insurance Scheme.
A novel epitope molecularly imprinted polymer (EMIP) for specific recognition and direct fluorescent quantification of the target protein bovine serum albumin (BSA) was demonstrated where polymerization was performed on the surface of silica nanospheres embedded CdTe quantum dots (QDs). The synthetic peptide derived from the surface-exposed C-terminus of bovine serum albumin (BSA, residues 599-607) was selected as the template molecule. The resulting EMIP film was able to selectively capture the template peptide and the corresponding target protein BSA via the recognition cavities. Based on the fluorescence quenching, the EMIP-coated QDs (molecular imprinted polymer coating CdTe QDs using epitope as the template) nanospheres were successfully applied to the direct fluorescence quantification of BSA. Compared with BMIP-coated QDs (molecular imprinted polymer coating CdTe QDs using BSA as the template), the imprinting factor and adsorption capacity of EMIP-coated QDs were greatly increased. The prepared EMIP-coated QDs can also discriminate even one mismatched sequences from the original sequences of the epitope of the BSA. The practical analytical performance of the EMIP-coated QDs was examined by evaluating the detection of BSA in the bovine calf serum sample with satisfactory results. In addition, the resulting EMIP-coated QDs nanospheres were also successfully applied to separating BSA from the bovine blood sample.
Hidden Markov model, based on Li and Stephens model that takes into account chromosome sharing of multiple individuals, results in mainstream haplotype phasing algorithms for genotyping arrays and next-generation sequencing (NGS) data. However, existing methods based on this model assume that the allele count data are independently observed at individual sites and do not consider haplotype informative reads, i.e. reads that cover multiple heterozygous sites, which carry useful haplotype information. In our previous work, we developed a new hidden Markov model to incorporate a two-site joint emission term that captures the haplotype information across two adjacent sites. Although our model improves the accuracy of genotype calling and haplotype phasing, haplotype information in reads covering non-adjacent sites and/or more than two adjacent sites is not used because of the severe computational burden.
Objectives. To verify the relationship between Egr-1 and vein graft restenosis and investigate the related mechanisms. Methods. Mouse vein graft models were established in Egr-1 knockout (KO) and wild-type (WT) mice. The vein grafts in the mice were taken for pathological examination and immunohistochemical analysis. The endothelial cells (ECs) were stimulated by using a computer-controlled cyclic stress unit. BrdU staining and PCR were used to detect ECs proliferation activity and Egr-1 and ICAM-1 mRNA expression, respectively. Western-blot analysis was also used to detect expression of Egr-1 and intercellular adhesion molecule-1 (ICAM-1) proteins. Results. The lumens of vein grafts in Egr-1 KO mice were wider than in WT mice. ECs proliferation after mechanical stretch stimulation was suppressed by Egr-1 knockout (P < 0.05). Both in vein grafts and ECs from WT mice after mechanical stretch stimulation, mRNA expression and protein of Egr-1 and ICAM-1 showed increases (P < 0.05). However, ICAM-1 expression was significantly suppressed in ECs from Egr-1 knockout mice (P < 0.05). Conclusions. Egr-1 may promote ECs proliferation and result in vein graft restenosis by upregulating the expression of ICAM-1. As a key factor of vein graft restenosis, it could be a target for the prevention of restenosis after CABG surgery.
We have developed a robust enzymatic peptide cleavage-based assay for the ultrasensitive dual-channel detection of matrix metalloproteinase-2 (MMP-2) in human serum using gold-quantum dot (Au-QD) core-satellite nanoprobes.
Protein-imprinted polymers with hollow cores that have a super-high imprinting factor were prepared by etching the core of the surface-imprinted polymers that used silica particles as the support. Lysozyme as template was modified onto the surface of silica particles by a covalent method, and after polymerization and the removal of template molecules, channels through the polymer layer were formed, which allowed a single-protein molecule to come into the hollow core and attach to the binding sites inside the polymer layer. The adsorption experiments demonstrated that the hollow imprinted polymers had an extremely high binding capacity and selectivity, and thus a super-high imprinting factor was obtained. The as-prepared imprinted polymers were used to separate the template lysozyme from egg white successfully, indicating its high selectivity and potential application in the field of separation of protein from real samples.
Herein, we synthesized a novel core-satellite CdTe/Silica/Au NCs hybrid sphere by covalently linking the separately synthesized highly fluorescent bovine serum albumin (BSA) stabilized gold nanoclusters (Au@BSA NCs) to the surface of the amino functionalized CdTe@SiO2 spheres by using the EDC chemistry. Numerous "satellites" of Au NCs were linked on the surface of the CdTe@SiO2 by the way of amide bonding. The synthesized dual-emission hybrid spheres were further characterized by the transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), UV-vis absorption spectroscopy, Fourier transform infrared (FTIR) spectroscopy, photoluminescence (PL), etc. Finally, the CdTe/Silica/Au NCs hybrid spheres were developed as ratiometric fluorescence probe for the determination of Cu(2+) with high sensitivity and selectivity. The fluorescence intensity ratio (F545 nm/F655 nm) of the probe against the concentration of Cu(2+) showed a good linear relationship from 6.0×10(-7) mol L(-1) to 100.0×10(-7) mol L(-1). It showed an excellent reproducibility (0.67% relative standard deviation for 10 replicate measurements of Cu(2+) at 40.0×10(-7) mol L(-1)) and low detection limit (4.1×10(-7) mol L(-1)). Furthermore, the ratiometric fluorescent probe was successfully applied in the determination of Cu(2+) in vegetable samples with satisfactory results.
Of various chemosensory protocols, the color change observed by the naked eye is considered to be a conceivable and on-site way to indicate the presence of an analyte. We herein designed a ratiometric fluorescence probe by hybridizing dual-emission quantum dots (QDs) and demonstrated its efficiency for on-site visual determination of copper ions. The hybrid probe comprises two sizes of cadmium telluride QDs emitting red and green fluorescence, respectively, in which the red-emitting ones are embedded in silica nanoparticles and the green-emitting ones are covalently linked onto the surface. The fluorescence of the embedded QDs is insensitive to the analyte, whereas the green emissive QDs are functionalized to be selectively quenched by the analyte. Upon exposure to different amounts of copper ions, the variations of the dual emission intensity ratios display continuous color changes from green to red, which can be clearly observed by the naked eye. The limit of detection for copper is estimated to be 1.1 nM, much lower than the allowable level of copper (~20 ?M) in drinking water set by U.S. Environmental Protection Agency. The probe is demonstrated for the determination of copper ions in lake water and mineral water samples, especially for visually monitoring copper residues on herb leaves. This prototype ratiometric probe is simple, fully self-contained, and thus potentially attractive for visual identification without the need for elaborate equipment.
A new cyclodextrin-derived chiral stationary phase (denoted as CDA-CSP) was synthesized by immobilizing mono(6(A)-azido-6(A)-deoxy)-per(p-chlorophenyl carbamoylated) ?-cyclodextrin derivative to alkynyl modified silica via click chemistry. This newly prepared CSP shows good enantioseparation performance for six chiral compounds (1-6), such as 4-phenyl-oxazolidine-2-thione, two kinds of aryl alcohols, substituted flavonoids and benzoin, in which baseline separation of Analytes 1-4 was achieved under the experimental conditions. The effects of column temperature, mobile phase pH and content of methanol on the enantioseparation characteristics of CDA-CSP were investigated in detail. Retention factor and resolution for Compound 3 gradually reduced with an increase of column temperature, and a good linear relationship was shown between napierian logarithm of selectivity factor and reciprocal of column temperature. In the pH range from 3.56 to 5.50, a change in pH hardly affected the resolution of Analyte 2. In addition, increasing methanol in the mobile phase resulted in rapid eluting of the analytes from the column in reversed-phase mode. The retention factors for Analytes 1 and 3 significantly decreased and their resolution showed different trends.
Homocysteine (Hcy) could induce apoptosis of endothelial cells (ECs). Dimethylarginine dimethylaminohydrolase 2 (DDAH2) is recognized as a protective factor to improve the endothelial function. Defect of DDAH2 has been confirmed to be involved in the Hcy-induced dysfunction of endothelial NO system. This study was to determine whether Hcy could inhibit DDAH2 expression and induce apoptosis of ECs via increasing DNA methylation level of DDAH2 promoter and whether DNA methylation inhibitor 5-azacytidine (5-aza) could attenuate the effect of Hcy on ECs. Firstly, human umbilical vein endothelial cells (HUVECs) were treated by Hcy with or without 5-aza for 48 h. MTT assay showed that Hcy reduced the viability of HUVECs in a dose-dependent manner. The level of asymmetric dimethylarginine (ADMA) and the apoptosis rate of HUVECs treated with Hcy at 1.0 mM were increased significantly compared with that of control. Moreover, we found that mRNA level of DDAH2 was down-regulated and DNA methylation level of DDAH2 promoter was increased significantly in HUVECs treated with Hcy, in concomitance with up-regulated protein level of DNA methyltransferase 1 (DNMT1). Furthermore, we also found that 5-aza could neutralize the effect of Hcy on ECs through up-regulating mRNA level of DDAH2 and inducing demethylation of DDAH2 promoter. In conclusion, hypermethylation of DDAH2 contributes to Hcy induced apoptosis of ECs. Modulating DNA methylation status of DDAH2 promoter may be a potential strategy for treatment of endothelial dysfunction.
Our aim is to screen miRNAs and genes related to tetralogy of Fallot and construct a co-expression network based on integrating miRNA and gene microarrays. We downloaded the gene expression profile GSE35490 (miRNA) and GSE35776 (mRNA) of tetralogy of Fallot from the Gene Expression Omnibus database, which includes eight normal and 15 disease samples from infants, and screened differentially expressed miRNAs and genes between normal and disease samples (cut-off: p < 0.05; FDR < 0.05; and log FC > 2 or log FC < -2); in addition, we downloaded human miRNA and their targets, which were collected in the miRNA targets prediction database TargetScan, and selected ones that also appeared in our differentially expressed miRNAs and their predicted targets (score >0.9) and then made a relationship of diff_miRNAs and diff_genes of our results. Finally, we uploaded all the diff_target genes into String, constructed a co-expression network regulated by diff_miRNAs, and performed functional analysis with the software DAVID. Comparing normal and disease lesion tissue, we got 32 and 875 differentially expressed miRNAs and genes, respectively, and found hsa-miR-124 with 34 diff_target genes and hsa-miR-138 with two diff_target genes. Then we constructed a co-expression network that contains 231 pairs of genes. Genes in the network were enriched into 14 function clusters, and the most significant one is protein localisation. We screened the tetralogy of Fallot-related hsa-miR-124 and hsa-miR-138 with their direct and indirect differentially expressed target genes, and found that protein localisation is the significant cause affecting tetralogy of Fallot. Our approach may provide the groundwork for a new therapy approach to treating tetralogy of Fallot.
For most complex diseases, the fraction of heritability that can be explained by the variants discovered from genome-wide association studies is minor. Although the so-called "rare variants" (minor allele frequency [MAF] < 1%) have attracted increasing attention, they are unlikely to account for much of the "missing heritability" because very few people may carry these rare variants. The genetic variants that are likely to fill in the "missing heritability" include uncommon causal variants (MAF < 5%), which are generally untyped in association studies using tagging single-nucleotide polymorphisms (SNPs) or commercial SNP arrays. Developing powerful statistical methods can help to identify chromosomal regions harboring uncommon causal variants, while bypassing the genome-wide or exome-wide next-generation sequencing. In this work, we propose a haplotype kernel association test (HKAT) that is equivalent to testing the variance component of random effects for distinct haplotypes. With an appropriate weighting scheme given to haplotypes, we can further enhance the ability of HKAT to detect uncommon causal variants. With scenarios simulated according to the population genetics theory, HKAT is shown to be a powerful method for detecting chromosomal regions harboring uncommon causal variants.
Like other members of the ?-herpesvirus family, human herpes virus 8, the etiologic agent of classic and HIV-related Kaposis sarcoma (HIV-KS) acquired and evolved several human genes with key immune modulatory and cellular growth control functions. The encoded viral homologs substitute for their human counterparts but escape cellular regulation, leading to uncontrolled cell proliferation. We postulated that DNA variants in the human homologs of viral genes that potentially alter the expression or the binding of the encoded factors controlling the antiviral response may facilitate viral interference. To test whether cellular homologs are candidate susceptibility genes, we evaluated the association of DNA variants in 92 immune-related genes including seven cellular homologs with the risk for HIV-KS in a matched case and control study nested in the Multicenter AIDS Cohort Study. Low- and high-risk gene-by-gene interactions were estimated by multifactor dimensionality reduction and used as predictors in conditional logistic models. Among the most significant gene interactions at risk (OR?=?2.84-3.92; Bonferroni- adjusted p?=?9.9 × 10(-3) - 2.6 × 10(-4) ), three comprised human homologs of two latently expressed viral genes, cyclin D1 (CCND1) and interleukin-6 (IL-6), in conjunction with angiogenic genes (VEGF, EDN-1 and EDNRB). At lower significance thresholds (adjusted p < 0.05), human homologs related to apoptosis (CFLAR) and chemotaxis (CCL2) emerged as candidates. This "proof of concept" study identified human homologs involved in the regulation of type I interferon-induced signaling, cell cycle and apoptosis potentially as important determinants of HIV-KS.
Programmed cell death 6 (PDCD6) participates in T cell receptor, Fas, and glucocorticoid-induced programmed cell death. To test the relationship between PDCD6 polymorphisms and uterine leiomyomas (UL) risk, we investigated the association of two SNPs (rs4957014 and rs3756712) in PDCD6 with UL risk in a case-control study of 295 unrelated premenopausal UL patients and 436 healthy postmenopausal control subjects in a population of China. Genotypes of the two SNPs were determined with the use of PCR-restriction fragment length polymorphism assay. Significantly increased UL risks were found to be associated with the T allele of rs4957014 and the T allele of rs3756712 (p=0.016, odds ratio [OR]=1.325, 95% confidence intervals [CI]=1.053-1.668 for rs4957014; p<0.0001, OR=1.898, 95% CI=1.457-2.474 for rs3756712, respectively). Increased UL risks were associated with them in different genetic models. The present study provided evidence that rs4957014 and rs3756712 are associated with UL risk, the results indicated that genetic polymorphisms in PDCD6 may contribute to the development of UL.
OBJECTIVE: Rheumatoid arthritis (RA) is a common autoimmune disease that is primarily driven by effector T cells, particularly Th17 cells, which are mainly contained within CD4+CD161+ T cells. Thus, we aimed to explore whether the frequencies of circulating IL-17-producing CD4+CD161+ T cells and CD4+CD161+ T cells were correlated with RA disease activity. METHODS: The surface phenotype and cytokine production of blood were analyzed by flow cytometry in 52 RA patients and 17 healthy controls. The disease activity was evaluated by the 28-joint disease activity score. RESULTS: The frequencies of circulating IL-17-producing CD4+CD161+ T cells and CD4+CD161+ T cells were increased in RA patients, and they were elevated in patients with active disease status compared to patients with low disease status. Furthermore, their frequencies were positively correlated with disease activity parameters. Receiver operating characteristic curve analysis revealed that IL-17-producing CD4+CD161+ T cell levels were able to distinguish disease activity with 60.7 % sensitivity and 87.5 % specificity, while CD4+CD161+ T cell levels showed 92.9 % sensitivity and 66.7 % specificity. CONCLUSION: These results support the hypothesis that Th17 cells are involved in the pathogenesis of RA and suggest that circulating CD4+CD161+ T cells are a potential biomarker of RA disease activity.
Hemocytes play multiple important roles during insect growth and development. Five types of hemocytes have been identified in the silkworm, Bombyx mori: prohemocyte, plasmatocyte, granulocyte, spherulocyte, and oenocytoid. We used the S-phase marker bromodeoxyuridine (BrdU) antibody along with the mitosis marker phosphohistone H3 (PHH3) antibody to monitor proliferation of hemocytes in vivo. The results indicate that silkworm hematopoiesis not only occurs in the circulatory system but also in hematopoietic organs (HPOs). During the 5th instar, the hemocyte proliferation in the circulatory system reaches a peak at the pre-wandering stage. Following infection by Escherichia coli, circulating hemocytes increase their cell divisions as demanded by the cellular immune response. All hemocytes, except spherulocytes, have the capacity to multiply in vivo. The BrdU label-retaining assay shows that a small portion of cells from the circulatory system and the HPOs are continuously labelled up to 9days and 4days respectively. A small number of long-term label retaining cells (LRCs) quiescently locate in circulatory system. All results indicate that there are a few quiescent stem cells or some progenitors in the larval circulatory system and HPO that produce new hemocytes and continuously release them into the circulating system.
The study of the composition, morphology, and surface structure of carbon dots (Cdots) is critical to understanding their effect on the photo- and electrochemiluminescence (PL and ECL) of Cdots in selected applications. Herein, two kinds of Cdots were prepared with 3-(3,4-dihydroxyphenyl)-L-alanine (L-DOPA) as precursor. The Cdots prepared by using a carbonization-extraction strategy have a low oxidation level and are denoted as reduced Cdots (r-Cdots). The Cdots obtained with a carbonization-oxidation process are highly oxidized and are denoted as oxidized Cdots (o-Cdots). The o-Cdots have a carbon core and oxygen-containing loose shell, but the r-Cdots consist mainly of the carbon core. Whereas r-Cdots have a strong blue PL but no apparent ECL response, o-Cdots exhibit a relatively weak PL and strong ECL emission. These properties allow for selected applications of the Cdots. The r-Cdots were used in cell imaging with their high PL emission. The o-Cdots, with their high ECL efficiencies, were selected to sense Cu(2+) with Cu(2+) -inducing ECL quenching in the o-Cdots/K2 S2 O8 system. This work provides the possibility to control the composition of Cdots for selected applications and shows a good way to characterize surface traps of Cdots because ECL is characterized by the surface-state and PL is mainly related to the core-state in Cdots.
Tacrolimus is used clinically for the long-term treatment of antirejection of transplanted organs in liver and kidney transplant recipients, although dose optimization is poorly managed. The aim of this study was to examine the association between tacrolimus pharmacokinetic variability and CYP3A4 and CYP3A5 genotypes by a population pharmacokinetic analysis based on routine drug monitoring data in adult renal transplant recipients.
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