Presence Of DP Research Articles

Cytarabine and dexamethasone-PAMAM dendrimer di-conjugate sensitizes human acute myeloid leukemia cells to apoptotic cell death

Polyamidoamine (PAMAM) dendrimers are widely used as a part of drug delivery systems (DDS) to improve anticancer drug bioavailability. In the present study, monophosphates of nucleosides, anti-nucleosides (cytarabine, C and fludarabine, F) and synthetic glucocorticoid dexamethasone (D) were attached to the third generation (G3) PAMAM dendrimer via phosphamide pH-sensitive linker. Conjugates were found to be stable at neutral pH, whereas acid-triggered hydrolysis of phosphamide bond was observed at pH 5. The anticancer action of selected biotinylated mono- and di-conjugates, namely CP-, FP-, DP-CP- and DP-FP-PAMAM dendrimers was then compared to cytotoxic activity of free drugs using four cellular models of leukemia in vitro, i.e., K-562, LAMA-84, THP-1 and HL-60 cells. 10 nM DP-CP-conjugate lowered metabolic activity, caused G0/G1 cell cycle arrest and induced apoptotic cell death in HL-60 cells compared to non-cytotoxic and non-cytostatic action of free drugs when used at the same concentration. 10 nM CP-, DP-FP- and FP-conjugates also promoted a decrease in metabolic activity in K-562, LAMA-84, and THP-1 and HL-60 cells, respectively, however, without a sign of cytotoxicity. In conclusion, we show that the anticancer potential of CP and FP in leukemia cells may be enhanced by the conjugation with PAMAM dendrimers, especially in the presence of DP in selected experimental settings.

Periodontal disease severity is associated to pathogenic consortia comprising putative and candidate periodontal pathogens

Based on a holistic concept of polymicrobial etiology, we have hypothesized that putative and candidate periodontal pathogens are more frequently detected in consortia than alone in advanced forms of periodontal diseases (PD). To correlate specific consortia of periodontal pathogens with clinical periodontal status and severity of periodontitis. Subgingival biofilm was obtained from individuals with periodontal health (113, PH), gingivitis (91, G), and periodontitis (209, P). Genomic DNA was purified and the species Aggregatibacter actinomycetemcomitans (Aa), Aa JP2-like strain, Porphyromonas gingivalis (Pg), Dialister pneumosintes (Dp), and Filifactor alocis (Fa) were detected by PCR. Configural frequency and logistic regression analyses were performed to correlate microbial consortia and PD. Aa + Pg in the presence of Dp (phi=0.240; χ2=11.9, p<0.01), as well as Aa JP2 + Dp + Fa (phi=0.186, χ2=4.6, p<0.05) were significantly more associated in advanced stages of P. The consortium Aa + Fa + Dp was strongly associated with deep pocketing and inflammation (p<0.001). The best predictors of disease severity (80% accuracy) included older age (OR 1.11 [95% CI 1.07 - 1.15], p<0.001), Black/African-American ancestry (OR 1.89 [95% CI 1.19 - 2.99], p=0.007), and high frequency of Aa + Pg + Dp (OR 3.04 [95% CI 1.49 - 6.22], p=0.002). Specific microbial consortia of putative and novel periodontal pathogens, associated with demographic parameters, correlate with severe periodontitis, supporting the multifactorial nature of PD.

Vulnerable plaque of the petrous internal carotid artery in embolic stroke of undetermined source.

The association between nonstenotic plaque at the petrous internal carotid artery (ICA) and embolic stroke of undetermined source (ESUS) remains unknown. We aimed to test the hypothesis that the presence of a larger build-up of petrous plaque is more prevalent in the ipsilateral versus the contralateral side among ESUS patients without plaque in the intracranial and proximal ICA. From a total of 243 patients with ESUS and 160 patients with small-vessel disease (SVD) without proximal ICA plaque, we enrolled 88 ESUS and 103 SVD patients without ipsilateral nonstenotic intracranial and proximal ICA plaque in the present study. Targeting the petrous segment of the ICA on two sides, plaque burden including plaque thickness, lumen area, vessel area, wall area, and percentage of luminal stenosis, and composition features (presence/absence of the ruptured fibrous cap, ulcer plaque, thrombus, discontinuity of plaque surface [DPS], intraplaque hemorrhage and complicated plaque) were assessed by high-resolution magnetic resonance imaging. We found a higher prevalence of petrous plaque thickness ≥3.5 mm ipsilateral versus contralateral to the stroke (25/88 [28.4%] vs. 12/88 [13.6%], odds ratio [OR] 3.60, 95% confidence interval [CI] 1.34-9.70), but this imbalance was not seen in SVD. In patients with plaque thickness ≥3.5 mm, the presence of DPS (OR 4.05, 95% CI 1.11-14.78) and complicated plaque (OR 5.00, 95% CI 1.10-22.82) was more closely related to an index ESUS, a finding that was not evident in the subgroup with petrous plaque <3.5 mm (p for interaction=0.027). The present study provided the first evidence supporting a potential etiological role of vulnerable petrous plaque in ESUS.

Pengaruh Kinerja Keuangan dan Good Corporate Governance terhadap Potensi Kebangkrutan Bank Muamalat Indonesia

This study aims to examine the effect of financial performance and GCG variables represented by the presence of the Sharia Supervisory Board on the potential for bankruptcy of Bank Muamalat Indonesia. The type of data used is secondary data sourced from financial statements and corporate GCG reports using multiple linear analysis data analysis methods with data processing tools using EViews 10 software. The results of this study indicate that NPF has a significant negative effect, FDR has a significant negative effect, and CAR has a significant negative effect. significant positive on the potential for bankruptcy of Bank Muamalat Indonesia, then the presence of DPS also has a significant effect. positive effect in reducing the risk of bankruptcy.

Effect of Dermatophagoides pteronyssinus extract on the expression of genes involved in inflammation and tissue remodeling by peripheral blood mononuclear cells of allergic asthma patients

PurposeHouse dust mite allergy constitutes a risk factor for asthma development and is associated with a faster decline of lung function in allergic asthmatics (AAs).To evaluate the effect of Dermatophagoides pteronyssinus (Dp) allergens on the expression of genes involved in inflammation and tissue remodeling by peripheral blood mononuclear cells (PBMCs) isolated from the blood of AAs. Materials and methodsThe cells from AAs, allergic rhinitis without asthma patients (ARs), and healthy controls (HCs) were cultured in the presence of Dp, lipopolysaccharide (LPS), or without any stimulation. The expression of 84 genes was evaluated using a low-density microarray whereas, the quantitative expression analysis of selected genes was performed using a real-time polymerase chain reaction. The concentration of selected proteins in the cell culture supernatants was assessed using ELISA. ResultsStimulation of PBMCs with Dp and LPS resulted in a significant upregulation of 8 and 15 among 84 studied genes, respectively. The greatest upregulation was observed for CCL2 and CCL3 using Dp and LPS, respectively. In comparison with HCs, in AAs, significantly increased upregulation of CCL2 in response to Dp was found. The secretion of CCL2 and CCL3 by PBMCs reflected the pattern of gene expression at the mRNA level. The mean Dp-stimulated secretion of CCL2 by PBMCs of ARs was less than in AAs (p ​< ​0.01), both being notably greater than in the HCs (p ​< ​0.01). ConclusionRapid and potent upregulation of CCL2 expression by PBMCs in response to Dp may constitute an important contribution to the development of allergic asthma.

CD4+ CD8αα+ T cells in the gastric epithelium mediate chronic inflammation induced by Helicobacter felis

CD4+ CD8αα+ double-positive intraepithelial T lymphocytes (DP T cells), a newly characterized subset of intraepithelial T cells, are reported to contribute to local immunosuppression. However, the presence of DP T cells in Helicobacter. pylori -induced gastritis and their relationship with disease prognosis has yet to be elucidated. In this study, a chronic gastritis model was established by infecting mice with Helicobacter felis. Gastric-infiltrating lymphocytes were isolated from these mice and analyzed by flow cytometry. The frequency of DP T cells in H. felis-induced gastritis mice was higher than that in uninfected mice. The gastric DP T cells were derived from lamina propria cells but were predominantly distributed in the gastric epithelial layer. These gastric DP T cells also exhibited anti-inflammatory functions, and they inhibited the maturation of dendritic cells and proliferation of CD4+ T lymphocytes in vitro. Elimination of DP T cells simultaneously resulted in severe gastritis and a reduction of H. felis load in vivo. Finally, vaccine mixed with different adjuvants was used to explore the relationship between vaccine efficacy and DP cells. Silk fibroin as the vaccine delivery system enhanced vaccine efficacy by reducing the number of DP T cells. This study demonstrated that DP T cells perform an immunosuppressive role in Helicobacter felis-induced gastritis, and consequently, DP T cells may affect disease prognosis and vaccine efficacy.

Digital pitting scars are associated with a severe disease course and death in systemic sclerosis: a study from the EUSTAR cohort.

Digital pitting scars (DPS) are frequent, but little studied in SSc to date. An analysis of SSc patients enrolled in the EUSTAR database. Primary objectives were to (i) examine DPS prevalence; (ii) examine whether DPS are associated with digital ulcers (DUs) and active digital ischaemia (DUs or gangrene); and (iii) describe other associations with DPS including internal organ complications. Secondary objectives were whether DPS are associated with (i) functional impairment; (ii) structural microvascular disease; and (iii) mortality. Descriptive statistics and parametric/non-parametric tests were used. Binary logistic regression was used to examine the association between DPS and DUs, active digital ischaemia and mortality. A total of 9671 patients were included with reported DPS at any time point (n = 4924) or 'never' DPS (n = 4747). The majority (86.9%) were female and mean age was 55.7 years. DPS were associated with longer disease and Raynaud's duration (both P ≤ 0.001). DPS were associated with interstitial lung disease, pulmonary hypertension, conduction blocks, telangiectases, calcinosis (all P ≤ 0.001) and joint synovitis (P = 0.021). Patients were more likely to have more severe capillaroscopic abnormality and greater hand functional impairment. Multivariable logistic regression analyses showed that DPS were associated (odds ratio) with DUs: 22.03 (19.51-24.87), active digital ischaemia: 6.30 (5.34-7.42) and death: 1.86 (1.48-2.36). DPS are associated with a severe disease course including death. The impact of DPS on hand function and ischaemia is significant. The presence of DPS should alert the clinician to a poor prognosis and need to optimize the therapeutic strategy.

DNA-binding protein from starvation cells traps intracellular free-divalent iron and plays an important role in oxidative stress resistance in Acetobacter pasteurianus NBRC 3283

Acetobacter pasteurianus accumulates reactive oxygen species (ROS). ROS are produced by electron and oxygen coupling in the electron transport chain in the intracellular environment during the stationary and in the acetic acid over-oxidation phases in the presence of ethanol, thereby exposing cell to oxidative stress. In this study, to reveal the resistance mechanism to oxidative stress in A.pasteurianus, we focused on DNA-binding protein from starvation cells (Dps) and analyzed the function of Dps against oxidative stress. When Dps under the copresence of plasmid DNA was exposed to H2O2 and divalent iron, plasmid DNA fragmentation was suppressed under the presence of Dps; however, DNA binding was not observed, revealing a defensive activity for oxidative damage. In addition, this finding revealed that Dps incorporates a divalent iron intracellularly, forming a ferroxidase center. Moreover, levels of hydroxyl radicals produced by Fenton reaction under the presence of H2O2 and divalent iron were decreased by the addition of Dps, resulting in the suppression of the Fenton reaction. Through fluorescence microscopy using a divalent-iron-specific fluorescent probe, we found that, in dps gene disruptants, the accumulation of the divalent iron increased, and the dps gene disruptants showed higher sensitivity to H2O2 than the wild-type. These result strongly suggested that Dps traps intracellular free-divalent iron and plays an important role in the oxidative stress resistance of A.pasteurianus NBRC 3283 after the acetic acid fermentation phase.

Improving flame retardancy of in-situ silica-epoxy nanocomposites cured with aliphatic hardener: Combined effect of DOPO-based flame-retardant and melamine

Silica-epoxy nanocomposites were prepared via an “in-situ” sol-gel synthesis process and a phosphorus (P) flame-retardant i.e. 6H-dibenz[c,e][1,2]oxaphosphorin,6-[(1-oxido-2,6,7-trioxa-1-phosphabicyclo[2.2.2]oct-4-yl)methoxy]-, 6-oxide (DP) and melamine (Mel) were further added to the matrix to improve its fire performance. The main components of epoxy resin were bisphenol A diglycidyl ether (DGEBA) and isophorone diamine (IPDA) hardener. The addition of DP as well as silica alone into the epoxy system stopped the melt dripping phenomena in the vertical fire test (UL 94), however, the addition of melamine was crucial for achieving the highest fire classification (UL 94-V0 rating). The presence of DP and Mel in the silica-epoxy nanocomposite promoted a large reduction (ranging from 53% up to 80%) in the heat release rate (HRR) and a delay (up to 31%) in the ignition time in the cone calorimetry experiments. Improved fire performance of the epoxy system was attributed to i) a condensed phase activity of silica, DP and melamine to form a protective thermal barrier during combustion and ii) a minor gas phase flame inhibition activity of DOPO component of DP. The mechanical characterization of the epoxy nanocomposites through tensile tests showed that the addition of DP increases the stiffness of the epoxy resin, resulting in a strong increase of Young modulus (up to 32%) and in a slight decrease of fracture strength, elongation at break and toughness. An increased glass transition temperature (up to 8%) of the epoxy system possibly due to hydrogen bonds and polar interactions of DP with the matrix was also observed.

Dental problems and chronic diseases in mentally ill homeless adults: a cross-sectional study

BackgroundDental problems (DPs) and physical chronic diseases (CDs) are highly prevalent and incident in people with low socioeconomic status such as homeless individuals. Yet, evidence on the association between DPs and physical CDs in this population is limited. In the present study, we assessed the association between DPs and type and number of CDs in individuals experienced chronic homelessness and serious mental health problems.MethodsWe analyzed cross-sectional baseline data from 575 homeless adults with serious mental health problems participating in the Toronto site of the At Home/Chez Soi randomized controlled trial. Chronic DPs (lasting at least 6 months) were the primary exposure variable. Presence of self-reported CDs, including heart disease, effect of stroke, hypertension, diabetes, asthma, chronic bronchitis/emphysema, stomach or intestinal ulcer, inflammatory bowel disease, migraine, thyroid problems, arthritis, kidney/bladder problems, liver disease (other than hepatitis), and iron-deficiency anemia, were the primary outcomes. The total number of CDs was also analyzed as a secondary outcome.Logistic regression models were used to assess the association between DPs with each of the studied CDs, and negative binomial regression was used to test the association between DPs with the number of CDs.ResultsIn our 575 homeless participants (68.5% males) with mean age 40.3 (11.8) years, a high proportion had DPs (42.5%). The presence of DPs was positively associated with heart disease (adjusted odds ratio (AOR):4.19,1.67–10.52), diabetes (AOR:2.17,1.13–4.17), chronic bronchitis (AOR:2.34,1.28–4.29), stomach or intestinal ulcer (AOR:3.48,1.80–6.73), inflammatory bowel disease (AOR:2.52,1.38–4.60), migraine (AOR:1.80,1.20–2.72), arthritis (AOR:2.71,1.71–4.29), kidney/bladder problems (AOR:2.43,1.30–4.54), and iron-deficiency anemia (AOR:3.28,1.90–5.65). DPs were also associated with a higher number of CDs (IRR: 1.62,1.38–1.90).ConclusionDental health problems in homeless individuals with serious mental disorders are associated with several CDs. Dental care should be better integrated into existing social and health programs serving this population to improve their overall health status.The AH/CS study is registered with the International Standard Randomized Control Trial Number Register (ISRCTN42520374).

Mechanism of Nucleoid Collapse in E. coli

All living cells must organize their DNA into dynamic three-dimensional architectures that are compatible with essential cellular processes such as transcription, translation, and DNA repair. Recently it has been shown that DNA is able to condense into a crystalline lattice in bacterial cells exposed to stressful conditions due to the action of a single gene. The protein responsible for creating these DNA ‘biocrystals’ is Dps (DNA-binding protein from starved cells) and it is essential in helping cells survive conditions ranging from starvation to antibiotic exposure. When present at sufficiently high concentrations, Dps drives the condensation of DNA into a biocrystal both in vitro and in vivo. We investigate the cooperative transition that allows Dps to rearrange the genome using a variety of techniques. We have developed a novel single molecule assay to probe the physical interactions between fluorescently tagged Dps and DNA. We find that Dps induced collapse is rate limited by a slow nucleation event but then proceeds extremely rapidly (< 100 ms). We also used magnetic tweezers to apply loads to DNA in the presence of Dps and determined collapse is much more concerted than previously assumed. We find that Dps binding to DNA displays the qualitative features of an Ising system and we have developed a mean field model that captures important features of the collapse. We look at nucleoid dynamics in single cells to test this model.

SAT0530 The Useful of us in Diagnosis of Carpal Tunnel Syndrome in Diabetics: a Proposal for New Reference Values.

BackgroundCarpal Tunnel Syndrome (CTS) is a neural affection that in diabetic patients can be associated with polyneuropathy (DP). In rheumatologists’s practice, ultrasonography represents a useful tool in the study of...

Dynamic state of DNA topology is essential for genome condensation in bacteria

In bacteria, Dps is one of the critical proteins to build up a condensed nucleoid in response to the environmental stresses. In this study, we found that the expression of Dps and the nucleoid condensation was not simply correlated in Escherichia coli, and that Fis, which is an E. coli (gamma-Proteobacteria)-specific nucleoid protein, interfered with the Dps-dependent nucleoid condensation. Atomic force microscopy and Northern blot analyses indicated that the inhibitory effect of Fis was due to the repression of the expression of Topoismerase I (Topo I) and DNA gyrase. In the Deltafis strain, both topA and gyrA/B genes were found to be upregulated. Overexpression of Topo I and DNA gyrase enhanced the nucleoid condensation in the presence of Dps. DNA-topology assays using the cell extract showed that the extracts from the Deltafis and Topo I-/DNA gyrase-overexpressing strains, but not the wild-type extract, shifted the population toward relaxed forms. These results indicate that the topology of DNA is dynamically transmutable and that the topology control is important for Dps-induced nucleoid condensation.

Synthesis of Morphiceptin (Tyr-Pro-Phe-Pro-NH2) by Dipeptidyl Aminopeptidase IV Derived from Aspergillus oryzae

Morphiceptin (Tyr-Pro-Phe-Pro-NH(2)), tetrapeptide, was synthesized using dipeptidyl aminopeptidase IV (DP IV, EC 3.4.14.5) derived from Aspergillus oryzae RIB 915 as a catalyst. Tyr-Pro-OEt was incubated with Phe-Pro-NH(2) in the presence of DP IV under various conditions of temperature, concentrations of ethylene glycol, pH, reaction time, and others. Morphiceptin was obtained at 40% yield under the optimal reaction conditions: substrate, 4 mM Tyr-Pro-OEt.HCl and 20 mM Phe-Pro-NH(2).HCl; enzyme, DP IV, 0.275 nkat; solvent, 60% ethylene glycol containing 20 mM phosphate buffer at pH 7.0; amine, 4.2 mM diisopropylamine at 4 degrees C for 24 h. Amino group protection was unnecessary for synthesis of morphiceptin by DP IV.

Wild-isolated Neurospora crassa strains that increase fertility of crosses with segmental aneuploids used to establish that a large duplication suppresses RIP in a smaller duplication

Crosses involving strains bearing large segmental duplications are characteristically barren and produce only very few viable ascospores. We report here that the productivity of duplication x euploid crosses can be influenced by the euploid parent. The yield of ascospores was exceptionally low in crosses with the wild-isolated strains Golikro (FGSC# 4830) and Costa Rica (FGSC# 852) and exceptionally high in crosses with Lahore-1 (FGSC #1824), Dagguluru-1 (FGSC #3360), Okeechobee (FGSC # 3968), and Tiassale (FGSC # 4825). The four strains that increased productivity were used in crosses with strains bearing the duplication Dp(IBj5) together with a small (1.3 kb) duplication of the erg-3 gene. This made it possible to obtain sufficient numbers of progeny to establish that presence of Dp(IBj5) suppresses RIP in erg-3.

Changes in onion root development induced by the inhibition of peptidyl-prolyl hydroxylase and influence of the ascorbate system on cell division and elongation

Post-translational hydroxylation of peptide-bound proline residues, catalyzed by peptidyl-prolyl-4 hydroxylase (EC 1.14.11.2) using ascorbate as co-substrate, is a key event in the maturation of a number of cell wall-associated hydroxyproline-rich glycoproteins (HRGPs), including extensins and arabinogalactan-proteins, which are involved in the processes of wall stiffening, signalling and cell proliferation. Allium cepa L. roots treated with 3, 4-DL-dehydroproline (DP), a specific inhibitor of peptidyl-prolyl hydroxylase, showed a 56% decrease in the hydroxyproline content of HRGP. Administration of DP strongly affected the organization of specialized zones of root development, with a marked reduction of the post-mitotic isodiametric growth zone, early extension of cells leaving the meristematic zone and a huge increase in cell size. Electron-microscopy analysis showed dramatic alterations both to the organization of newly formed cell walls and to the adhesion of the plasma membranes to the cell walls. Moreover, DP administration inhibited cell cycle progression. Root tips grown in the presence of DP also showed an increase both in ascorbate content (+53%) and ascorbate-specific peroxidase activity in the cytosol (+72%), and a decrease in extracellular "secretory" peroxidase activity (-73%). The possible interaction between HRGPs and the ascorbate system in the regulation of both cell division and extension is discussed.

The mechanism of mutation induction by a hydrogen bond ambivalent, bicyclic N4-oxy-2'-deoxycytidine in Escherichia coli.

The triphosphate of the nucleoside deoxyribosyl dihydropyrimido[4,5-c][1,2]oxazin-7-one (dP) is known to be incorporated into DNA efficiently by Taq polymerase and is a useful tool for polymerase-mediated in vitro mutagenesis. It is shown here that dP is a potent mutagen in Escherichia coli and Salmonella typhimurium . In E.coli , this deoxycytidine analog induces both GC-->AT and AT-->GC transitions. No induced transversions are observed. It is highly mutagenic in wild-type E.coli, but this is much reduced in a strain lacking thymidine kinase. Mutagenesis induced by dP is efficiently inhibited by the addition of thymidine. Partially purified thymidine kinase from E.coli catalyzes phosphorylation of dP to its 5'-monophosphate. When E.coli was grown in the presence of dP, the nucleoside analog was incorporated into its DNA. The content of dP in DNA was dependent on the concentration of dP added to the medium. The incorporation characteristics of the 5'-triphosphate of dP (dPTP) were also studied using E.coli DNA polymerase I large fragment. The results confirm that this triphosphate can be incorporated opposite A and G in the template with similar efficiencies. This indicates that dP is metabolized as a thymidine analog and that the resulting triphosphate induces a high rate of mutagenesis through replicational errors.

Tumor necrosis factor production by human T-cells stimulated with bacterial superantigens

Tumor necrosis factor (TNF) production from T-cells stimulated with superantigenic exotoxins, staphylococcal enterotoxin B and streptococcal pyrogenic exotoxin A was investigated in the presence of cells bearing distinct isotypes of HLA class II molecules. The main T-cell subset for TNF production was investigated in parallel. Similarly high levels of TNF production were induced upon stimulation with the toxins in the presence of DR + or DQ + cells, but only marginal levels of TNF production were induced in the presence of DP + cells. Although both CD4 + T-cells and CD8 + T-cells produced TNF-α and TNF-β in response to toxin stimulation in the presence of HLA class II + cells, the former T-cell subset was the major source of producers of TNF-α and TNF-β.

Inhibition of lymphoproliferation by dipyridamole

Dipyridamole (DP, Persantin) was examined for its effects on the proliferation of mitogen-stimulated murine splenocytes and L1210 leukemia cells. In keeping with its reported activity as an inhibitor of nucleoside transport, DP inhibited incorporation by lymphoid cells of labeled thymidine and uridine into macromolecules. That this inhibition resulted from activities in addition to suppression of nucleoside transport was verified by measured decreases of cellular DNA and viable cell numbers. In addition, protein synthesis was also decreased as indicated by labeled valine incorporation and total protein content of the cells. The rapid accumulation of cAMP in phytohemagglutinin-stimulated splenocytes in the presence of DP may provide an explanation for the anti-proliferative effect of DP on lymphoid cells.