Dendritic Molecule Research Articles

Vitamin C Attenuates Hemorrhagic Hypotension Induced Epithelial-Dendritic Cell Transformation in Rat Intestines by Maintaining GSK-3β Activity and E-Cadherin Expression.

To investigate the roles of epithelial-dendritic cell transformation (EDT) characterized by the expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) in the occurrence of tissue inflammation induced by hemorrhagic hypotension (HH), the protective effect of vitamin C (VitC), and the potential mechanisms. We conducted an in vitro study using the rat intestinal epithelial cells (IEC-6). After hypoxic culture with or without VitC for 2, 6, 24, and 48 h (n = 3 per group), the expression levels of DC-SIGN, E-cadherin, and Glycogen synthase kinase-3β-S9 (GSK-3β-S9) in IEC-6 cells, IL-1β, and IL-6 concentrations in the cell culture medium were measured. To investigate the potential mechanism, we inhibited E-cadherin expression by siRNA and GSK-3β activity by TDZD-8, respectively. The in vivo study was conducted by establishing SD rat HH model. We observed the expression levels and location of DC-SIGN in the intestines. We also showed histological damage, TNF-α and IL-6 concentrations, and organ injury scores at 2, 6, and 24 h after HH (n = 6 per group), with or without VitC pretreatment. Hypoxia-induced DC-SIGN expression in IEC-6 cells in a time-dependent manner and the inflammatory factors were also increased. VitC inhibited all these phenomena. Hypoxia inhibited GSK-3β activity and E-cadherin expression. VitC could ease these inhibitions. The inhibitory effect of VitC on DC-SIGN was diminished when E-cadherin expression was inhibited in advance. TDZD-8 diminished the protective effect of VitC on E-cadherin and abolished inhibitory effect of VitC on DC-SIGN expression. HH-induced DC-SIGN expression in rat intestine epithelial cells and the histological damage scores and pro-inflammatory cytokine levels were also increased. HH induces EDT in rat intestine epithelial cells. VitC maintains GSK-3β activity, attenuates the suppression of E-cadherin caused by hypoxia, and ultimately decreases DC-SIGN expression.

Single molecular tuning of the charge balance in blue-emitting iridium dendrimers for efficient nondoped solution-processed phosphorescent OLEDs

The single molecular tuning of charge balance has been demonstrated here by integrating a p-type dendron, an n-type dendron and a blue emissive Ir core into one dendritic platform. Compared with the commonly used physical blending, not only can the charge balance be well tailored, but also the intrinsic phase separation can be successfully eliminated in such developed single molecular systems (B-TCz2TPO1 and B-TCz1TPO2). As a consequence, their corresponding nondoped solution-processed PhOLEDs achieve more than doubled external quantum efficiencies accompanied by a negligible efficiency roll-off.

Effect of Culture Supernatant Derived from Trichophyton Rubrum Grown in the Nail Medium on the Innate Immunity-related Molecules of HaCaT.

Background:Trichophyton rubrum is superficial fungi characteristically confined to dead keratinized tissues. These observations suggest that the soluble components released by the fungus could influence the host immune response in a cell in contact-free manner. Therefore, this research aimed to analyze whether the culture supernatant derived from T. rubrum grown in the nail medium could elicit the immune response of keratinocyte effectively.Methods:The culture supernatants of two strains (T1a, TXHB) were compared for the β-glucan concentrations and their capacity to impact the innate immunity of keratinocytes. The β-glucan concentrations in the supernatants were determined with the fungal G-test kit and protein concentrations with bicinchoninic acid protein quantitative method, then HaCaT was stimulated with different concentrations of culture supernatants by adopting morphological method to select a suitable dosage. Expressions of host defense genes were assessed by quantitative polymerase chain reaction after the HaCaT was stimulated with the culture supernatants. Data were analyzed with one-way analysis of variance, followed by the least significant difference test.Results:The T. rubrum strains (T1a and TXHB) released β-glucan of 87.530 ± 37.581 pg/ml and 15.747 ± 6.453 pg/ml, respectively into the media. The messenger RNA (mRNA) expressions of toll-like receptor-2 (TLR2), TLR4, and CARD9 were moderately up-regulated in HaCaT within 6-h applications of both supernatants. HaCaT cells were more responsive to T1a than TXHB. The slight increase of dendritic cells-specific intercellular adhesion molecule 3-grabbing nonintegrin expression was faster and stronger, induced by T1a supernatant than TXHB. The moderate decreases of RNase 7, the slight up-regulations of Dectin-1 and interleukin-8 at the mRNA level were detected only in response to T1a rather than TXHB. After a long-time contact, all the elevated defense genes decreased after 24 h.Conclusion:The culture supernatant of T. rubrum could directly and transiently activate the innate immune response of keratinocytes.

Delivery of antigen to nasal-associated lymphoid tissue microfold cells through secretory IgA targeting local dendritic cells confers protective immunity

Transmission of mucosal pathogens relies on their ability to bind to the surfaces of epithelial cells, to cross this thin barrier, and to gain access to target cells and tissues, leading to systemic infection. This implies that pathogen-specific immunity at mucosal sites is critical for the control of infectious agents using these routes to enter the body. Although mucosal delivery would ensure the best onset of protective immunity, most of the candidate vaccines are administered through the parenteral route. The present study evaluates the feasibility of delivering the chemically bound p24gag (referred to as p24 in the text) HIV antigen through secretory IgA (SIgA) in nasal mucosae in mice. We show that SIgA interacts specifically with mucosal microfold cells present in the nasal-associated lymphoid tissue. p24-SIgA complexes are quickly taken up in the nasal cavity and selectively engulfed by mucosal dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin-positive dendritic cells. Nasal immunization with p24-SIgA elicits both a strong humoral and cellular immune response against p24 at the systemic and mucosal levels. This ensures effective protection against intranasal challenge with recombinant vaccinia virus encoding p24. This study represents the first example that underscores the remarkable potential of SIgA to serve as a carrier for a protein antigen in a mucosal vaccine approach targeting the nasal environment.

Association of DC-SIGNR Expression in Peripheral Blood Mononuclear Cells with DC-SIGNR Genotypes in HIV-1 Infection.

Dendritic cell-specific intracellular adhesion molecule 3 grabbing nonintegrin related molecule (DC-SIGNR) is a C-type lectin, calcium-dependent carbohydrate-binding protein, which can act as a cell-adhesion and pathogen recognition receptor. DC-SIGNR is known to be highly expressed on liver sinusoidal cells and in the lymph nodes. However, its expression in peripheral blood mononuclear cells (PBMCs) in HIV-1 infection has not been addressed. Therefore, this study determined the expression of DC-SIGNR in PBMCs of HIV-1-infected patients and healthy seronegative individuals by real-time polymerase chain reaction and assessed its correlation with CD4+ T cell counts and DC-SIGNR genotypes. A significantly higher expression of DC-SIGNR was observed in the PBMCs of HIV-1-infected patients compared with healthy seronegative individuals. Further, there was a negative correlation between DC-SIGNR expression and CD4+ T cell counts and positive with viral load, with higher DC-SIGNR expression in the PBMCs of HIV-1-infected patients with a CD4+ T cell count <200 cells/μL than those with >200 cells/μL. This is the first study to report the expression of DC-SIGNR in PBMCs of HIV-1-infected patients. A salient finding of this study is that the DC-SIGNR expression was higher in HIV-1-infected patients, and its positive correlation with viral load and negative with CD4+ T cells counts suggesting a potential role of DC-SIGNR in HIV-1 infection.

Modification of regenerated cellulose membrane based on thiol dendrimer

This work describes the modification of a highly swollen commercial regenerated cellulose (RC) membrane with a dendritic molecule (thiol DAB dendrimer of generation 3) by the dip coating method, and its possible use in electrochemical systems with saline solutions fluxes. Moreover, cellulosic membrane modification with dendrimer covered-CdSe quantum dot was also performed, since it allows dendrimer assortment by fluorescence. Changes in electrical, mechanical and diffusive membrane parameters were determined by impedance spectroscopy, elasticity curves and diffusional permeability measurements. The results indicate a reduction in the free volume of the RC chains in the original membrane associated with the thiol dendrimer inclusion, which reduces diffusive permeability. This demonstrates the possibility of using the thiol dendrimer-modified membrane in low/medium concentration level (0.001M/0.01M) devices with NaCl and PbCl2 solutions.

Chemically reactive supramolecular hydrogel coupled with a signal amplification system for enhanced analyte sensitivity.

Multicomponent supramolecular hydrogels are constructed for sensitive, naked-eye detection of small-molecule biomarkers. A dendritic self-immolative molecule and the corresponding enzyme as a signal amplification system were stably embedded in a hydrogen peroxide (H2O2)-responsive supramolecular hydrogel (BPmoc-F3), together with other enzymes. The nanostructure and mechanical strength of the hybrid BPmoc-F3 gel were not substantially diminished by incorporation of these multiple components in the absence of target biomarkers, but could be destroyed by addition of the biomarker through the multiple enzymatic and chemical cascade reactions operating in combination within the gel matrix. The sensitivity to biomarkers such as H2O2, glucose, and uric acid, detected by gel-sol transition, was significantly enhanced by the signal amplification system. An array chip consisting of these multicomponent hydrogels enabled the detection of the level of hyperuricemia disease in human plasma samples.

“Moonlighting” GAPDH Protein Localizes with AMPA Receptor GluA2 and L1 Axonal Cell Adhesion Molecule at Fiber Cell Borders in the Lens

Purpose: The canonical role of glyceraldehyde phosphate dehydrogenase (GAPDH) is as an enzyme in glycolysis. GAPDH is also a principal “moonlighting” protein with additional roles at diverse sites in a variety of cells. Surface GAPDH on mammalian, yeast, and bacterial cells acts as a receptor and also mediates cell contacts. In neurons, extracellular GAPDH localizes at synapses. Two GAPDH binding partners at synapses are α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor (AMPA) GluA2 subunit at dendritic spines and L1 cell adhesion molecule at pre-synaptic membranes, and both proteins are also expressed in lenses. Fiber cell membrane protrusions and dendritic spines have similar size, shape, and spacing, contain F-actin, and express clathrin/AP-2 Adaptor at their surfaces linked with Tyr-phosphatase STEP-regulated endocytosis of AMPA/GluA2 receptors. AMPA receptors work with NMDA (N-methyl-d-aspartate) and GABA (γ-aminobutyric acid) receptors, calcium calmodulin kinase II (CaMKIIα), channel proteins, STEP, and ephrin receptors, which are also expressed in lenses. In neurons, coordinate AMPA/GluA2 receptor endocytosis with GAPDH is linked with disease. GAPDH was previously characterized as a fiber cell membrane protein and shown to decrease substantially in interior fiber cells in human age-related cataract. Here, we examined GAPDH spatial expression in healthy lenses in two vertebrate species.Methods: In situ methods were used to examine GAPDH expression in lenses of healthy young adult rabbits and chickens. Immunoblots were used to detect L1 in lenses.Results: The present study demonstrated that GAPDH is present at fiber cell borders in adult rabbit and chicken lenses with evidence of focal concentrations along the fiber cell perimeter, and overlapped with detection of p-Tyr-GluA2, L1, STEP, actin and clathrin. We observed that L1-140 kDa was the prominent form in lens.Conclusions: Our findings indicate investigations into GAPDH “moonlighting” activities similar to its role in cell–cell interactions at neuron surfaces are warranted in the lens.

Early transcriptional response of human monocyte-like THP-1 cells in response to Trichosporon asahii infection.

Trichosporon asahii is the major cause of invasive trichosporonosis, but little is known about the host immune response to this pathogen. In this study, the early transcriptional response of human monocyte-like THP-1 cells to T. asahii infection was evaluated using cDNA microarray and 1,315 differentially expressed genes were identified. The up-regulated genes were mostly involved in both innate and adaptive immune responses, as well as apoptosis and anti-apoptosis processes. Genes encoding the pro-inflammatory cytokines TNF-α, IL-1β, IL18 and IL-23α, along with the both C-C motif and C-X-C motif chemokines were strongly up-regulated, suggesting that THP-1 cells can mount a powerful inflammatory response to T. asahii infection. Genes encoding pattern recognition receptors were found up-regulated, such as dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin, cluster of differentiation 36 and the long pentraxin 3. Genes encoding members of the dual-spasticity phosphates family were up-regulated, and these genes were considered as a negative feedback mechanism to prevent excessive inflammatory response. The down-regulated genes in T. asahii-infected THP-1 cells were predominantly associated with cell cycle, mitosis, cell division and DNA repair. Thus, our study defines the early transcriptional response of monocyte-like THP-1 cells to T. asahii infection and provides a foundation for further investigations into the pathogenesis of T. asahii infection.

Hydrophobic cavity formed by oligopeptide for doxorubicin delivery based on dendritic poly(L-lysine)

To deliver anti-cancer drugs to tumors, a hydrophobic cavity was prepared in the dendritic molecule, dendritic poly(L-lysine) of sixth generation (KG6), which was used as a drug carrier. The dendritic molecule was modified with polyethylene glycol (PEG)-linked hydrophobic penta-phenylalanine or penta-alanine. The hydrophobic cavity was formed between the KG6 and PEG chains. The penta-phenylalanine peptide was better in encapsulating doxorubicin (DOX) in the cavity compared with penta-alanine. The loaded DOX was slowly released from the cavity, and it depended on pH. After intravenous injection, the DOX-loaded dendrimers accumulated in the tumor by the enhanced permeability and retention effect, and showed significant suppression of tumor growth without loss of body weight. These results indicate that hydrophobic oligopeptides can be used for forming a hydrophobic cavity in a dendritic molecule for delivery of anti-cancer drugs to tumor sites.

A “breathing” dendritic molecule—conformational fluctuation induced by external stimuli

A series of PAMAM dendrimers peripherally modified with tetraphenylethylene (TPE), a typical chromophore with emission enhancement in aggregate, were synthesized (D0–D4). The dendrimers are molecularly dissolved in toluene, a selective solvent. The intramolecular rotation of TPE is depressed by the restrained conformation caused by the congested packing periphery in higher generation dendrimers (D2–D4), which results in a remarkable emission enhancement. The fluorescence quantum yield increases more than 10-fold in D3 and D4 dendrimers compared with a model compound. Furthermore, the emission intensity of dendrimers can be tuned by changing the temperature or solvent conditions, which alters the conformational confinement. Unimolecular spheres with multiple chromophores and conformation-controlled emission are reminiscent of proteins with modulated sizes and photofunctions. Developing these dendritic systems will promote the research of multi-functionalized chromophores and lead to their potential applications in biomimics and sensors.

Elucidating factors leading to acidolytic degradation of sterically strained oligoether dendrons.

While steric hindrance can be particularly large in dendritic molecules, it is usually implicated with difficulties in the synthesis of higher generation structures and restricted access of reagents, including bond-cleaving agents, to the dendritic interior. A different situation, where the steric hindrance is translated into a steric strain within the dendritic molecule and, consequently, causes enhanced decomposition of the dendron-containing structure, has only occasionally been reported and exclusively for dendronized polymers. In this work we describe post-synthetic cleavage of sterically congested third-generation oligoether dendrons from solid supports, followed by their disassembly into monomeric building blocks under acidic conditions. This disassembly was monitored by H NMR, revealing the intermediate fragment structures and the exact order of bond cleavage within the dendritic molecule. These conclusions were supported by MS analysis of the cleavage mixtures. Though distinguishing between steric and electronic reasons of molecular disassembly can be a challenging task, we were able to analyze these factors separately by monitoring the dendron disassembly and comparing the rates of "decay" of parent dendrons and their fragments. This comparison reveals that while the electron donation of the steric congestion-inducing alkyl substituents is a prerequisite for the disassembly of the structures, this disassembly is very strongly accelerated in the sterically crowded dendrons and intermediates, where both steric and electronic factors contribute in a synergistic way to the disassembly phenomenon.

Association of CD209 and CD209L polymorphisms with tuberculosis infection in a Northeastern Brazilian population.

Tuberculosis (TB) caused by Mycobacterium tuberculosis, is major cause of morbidity and mortality worldwide. So far, many candidate genes have been investigated for their possible association with TB. Dendritic cell-specific intercellular adhesion molecule 3 (ICAM-3) grabbing non-integrin (DC-SIGN) and Liver/lymph node-specific intercellular adhesion molecule-grabbing non-integrin (L-SIGN), encoded by CD209 and CD209L genes respectively, are known for binding to M. tuberculosis on human dendritic cells and macrophages. We screened 4 single nucleotide polymorphisms (SNPs) in the promoter region of CD209, namely -939G>A (rs735240), -871A>G (rs735239), -336A>G (rs4804803) and -139G>A (rs2287886) and tandem repeat polymorphisms in exon 4 of CD209 and CD209L genes looking for association with TB in a Northeastern Brazilian population (295 subjects, 131TB patients and 164 healthy controls). The -139G>A and -939G>A SNPs were associated with susceptibility to TB, and in particular with pulmonary and extra-pulmonary forms respectively. The -871A>G and -336A>G SNPs were associated, the first with protection to both pulmonary and extra-pulmonary TB, the latter only with the pulmonary form. An association between GGAG haplotype and protection to TB infection was also found. Also tandem repeat polymorphism in CD209L exon 4 was associated with TB infection. This study provides evidence of an association between CD209 and CD209L polymorphisms and TB development in a Brazilian population, suggesting that variations in these genes may influence the protection and susceptibility to infection caused by M. tuberculosis.

A systematic study of peripherally multiple aromatic ester-functionalized poly(benzyl ether) dendrons for the fabrication of organogels: structure-property relationships and thixotropic property.

A new class of peripherally multiple aromatic ester-functionalized poly(benzyl ether) dendrons and/or dendrimers with different focal point substituents, surface groups, interior structures, as well as different generations have been synthesized and their structure-property relationships with respect to their gelation ability have been investigated systematically. Most of these dendrons are able to gel organic solvents over a wide polarity range. Evident dendritic effects were observed not only in gelation capability but also in thermotropic, morphological, and rheological characterizations. It was disclosed that subtle changes in peripheral ester functionalities and interior dendritic structures affected the gelation behavior of the dendrons significantly. Among all the dendrons studied, the second- and third-generation dendrons G0G2-Me and G0G3-Me with dimethyl isophthalates (DMIP) as peripheral groups exhibited the best capability in gelation, and stable gels were formed in more than 22 aromatic and polar organic solvents. The lowest critical gelation concentration (CGC) reached 2.0 mg mL(-1), indicating that approximately 1.35×10(4) solvent molecules could be entrapped by one dendritic molecule. Further study on driving forces in gel formation was carried out by using a combination of single-crystal/powder X-ray diffraction (XRD) analysis and concentration-dependent (CD)/temperature-dependent (TD) (1)H NMR spectroscopy. The results obtained from these experiments revealed that the multiple π-π stacking of extended π-systems due to the peripheral DMIP rings, cooperatively assisted by non-conventional hydrogen-bonding, is the key contributor in the formation of the highly ordered supramolecular and fibrillar network. In addition, these dendritic organogels exhibited unexpected thixotropic-responsive properties, which make them promising candidates with potential applications in the field of intelligent soft materials.

Arylethynyl‐Substituted Tristriazolotriazines: Synthesis, Optical Properties, and Thermotropic Behavior

AbstractThe synthesis of C3‐symmetrical tristriazolotriazines with conjugated arms and lateral alkoxy side chains was performed by a threefold condensation of cyanuric chloride with tetrazoles. Conjugated π segments include phenyl, tolane, and its phenylethynyl‐elongated homologue. Disclike and a dendritic molecule have been obtained, and two compounds with a 3,4,5‐tris(octyloxy) substitution form broad thermotropic mesophases. The linear optical properties, solvatochromism of the fluorescence, acidochromism, and the two‐photon absorption efficiency of selected compounds are reported.

A viologen phosphorus dendritic molecule as a carrier of ATP and Mant-ATP: spectrofluorimetric and NMR studies

A viologen phosphorus dendritic molecule is able to create non-covalent interactions with model molecules of drugs belonging to the group of nucleoside analogues.

Work Function Maps and Surface Topography Characterization of Nitroaromatic-Ended Dendron Films on Graphite

Surface topography and work function maps were simultaneously obtained for carbon surfaces modified by a dendritic molecule: 3,5-Bis (3,5-dinitrobenzoylamino) benzoic acid. The dendrons were spontaneously assembled onto highly ordered pyrolytic graphite samples, exhibiting an increase in the surface potential. This fact is consistent with the incorporation of an electron-acceptor functional group that remains electroactive on the surface.

Enhancement of photovoltaic performance in dye-sensitized solar cells fabricated with dendritic photosensitizer containing site-isolated chromophores

We designed and synthesized a series of phenothiazine-based donor–acceptor type molecules which consist of different numbers of chromophores in a molecule for use as photosensitizers for dye-sensitized solar cells (DSSCs). Intriguingly, a dendritic molecule containing three chromophores not only gave a new possibility to modify the three dimensional structure, but also reduced aggregation between chromophores inducing dipole–dipole interaction. The DSSCs made of a dendritic photosensitizer system exhibited much higher cell efficiencies than those with the single- or double-chromophoric photosensitizers due to efficient electron extraction pathways in the dendritic molecule which lead to a significantly reduce recombination rate of electrons from the TiO2 to the electrolyte when the same numbers of chromophores were loaded on the TiO2 surface. In particular, the DSSC based on the dendritic molecule exhibited improved open-circuit voltage than that of the single- or double-chromophoric photosensitizers. This can be attributed to strong adsorption properties of the TiO2 electrode and a screening effect to the electrolyte ions provided by the network structure of the dendritic photosensitizer. The different behavior of these DSSCs was explained by comparing the results of electrochemical impedance spectroscopy and measurement of open-circuit voltage decay.

One-step preparation of novel conjugated porous polymer with tubular structure

A shape-persistent dendritic molecule, tris(4-(2,7-dibromo-9-phenyl-9-fluoren-9-yl)phenyl)amine (TF-6Br), has been readily synthesized in high yield through a concise Friedel-Crafts reaction from triphenylamine and 2,7-dibromo(9-phenyl-fluoren-9-ol). It was further employed as the key building block to achieve the synthesis of conjugated porous polymer via Sonogashira coupling with 1,4-diethynylbenzene. Under experimental reaction conditions, the resulting porous polymer shows exceptionally nanotubular morphology, which further allows for a template-free synthesis of porous carbon nanotubes via thermal treatment at high temperature. The obtained nitrogen-doped carbon nanotubes feature with an improved porosity and high surface area.

Association of promoter region polymorphisms of CD209 gene with clinical outcomes of dengue virus infection in Western India

Dendritic cell specific intercellular adhesion molecule 3 grabbing non-integrin, coded by the CD209 gene, acts as an entry receptor for dengue virus. Polymorphisms in the promoter region of CD209 gene (rs735239, rs4804803, rs2287886) were investigated in 112 hospitalized cases of dengue (DEN) and 104 healthy controls to find out whether they are associated with dengue in a Western Indian population. Results revealed a significantly higher frequency of ‘G’ allele and ‘G/G’ genotype of rs2287886 and A-A-G haplotype of CD209 gene in DEN compared to healthy controls [For ‘G/G’ genotype, P=0.0072, Odds ratio (OR) 2.43; For A-A-G haplotype, P=0.0033, OR 2]. The frequency of A/A genotype of rs735239 was higher in DEN cases with thrombocytopenia compared to cases without thrombocytopenia (P=0.026). The results suggest that rs2287886 G/G genotype of CD209 gene is associated with development of dengue requiring hospitalization while A/A genotype of rs735239 is associated with thrombocytopenia in dengue cases.