65 research outputs found

    Low-Molecular-Weight Organo- and Hydrogelators Based on Cyclo(l‑Lys‑l‑Glu)

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    Four cyclo­(l-Lys-l-Glu) derivatives (<b>3</b>–<b>6</b>) were synthesized from the coupling reaction of protecting l-lysine with l-glutamic acid followed by the cyclization, deprotection, and protection reactions. They can efficiently gelate a wide variety of organic solvents or water. Interestingly, a spontaneous chemical reaction proceeded in the organogel obtained from <b>3</b> in acetone exhibiting not only visual color alteration but also increasing mechanical strength with the progress of time due to the formation of Schiff base. Moreover, <b>6</b> bearing a carboxylic acid and Fmoc group displayed a robust hydrogelation capability in PBS solution. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) revealed the characteristic gelation morphologies of 3D fibrous network structures in the resulting organo- and hydrogels. FT-IR and fluorescence analyses indicated that the hydrogen bonding and π–π stacking play as major driving forces for the self-assembly of these cyclic dipeptides as low-molecular-weight gelators. X-ray diffraction (XRD) measurements and computer modeling provided information on the molecular packing model in the hydrogelation state of <b>6</b>. A spontaneous chemical reaction proceeded in the organogel obtained from <b>3</b> in acetone exhibiting visual color alteration and increasing mechanical strength. <b>6</b> bearing an optimized balance of hydrophilicity to lipophilicity gave rise to a hydrogel in PBS with MGC at 1 mg/mL

    Biomimetic Hemostatic Powder Derived from Coacervate-Immobilized Thermogelling Copolymers

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    Intrinsic hemostasis is an innate body response to prevent bleeding based on the sol–gel transition of blood. However, it is often inadequate for exceptional situations, such as acute injury and coagulation disorders, which typically require immediate medical intervention. Herein, we report the preparation of an efficient hemostatic powder, composed of tannic acid (TA), poly(ethylene glycol) (PEG), and poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide) triblock copolymer (TB), for biomimetic hemostasis at the bleeding sites. TA has a high affinity for biomolecules and cells and can form coacervates with PEG driven by hydrogen bonding. TB enhances the mechanical strength and provides thermoresponsiveness. The hemostatic powder can rapidly transit into a physical and biodegradable seal on wet substrates under physiological conditions, demonstrating its promise for the generation of instant artificial clots. Importantly, this process is independent of the innate blood clotting process, which could benefit those with blood clotting disorders. This biomimetic hemostatic powder is an adaptive topical sealing agent for noncompressible and irregular wounds, which is promising for biomedical applications

    Biologically Derived Nanoarchitectonic Coatings for the Engineering of Hemostatic Needles

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    Bleeding after venipuncture could cause blood loss, hematoma, bruising, hemorrhagic shock, and even death. Herein, a hemostatic needle with antibacterial property is developed via coating of biologically derived carboxymethyl chitosan (CMCS) and Cirsium setosum extract (CsE). The rapid transition from films of the coatings to hydrogels under a wet environment provides an opportunity to detach the coatings from needles and subsequently seal the punctured site. The hydrogels do not significantly influence the healing process of the puncture site. After hemostasis, the coatings on hemostatic needles degrade in 72 h without inducing a systemic immune response. The composition of CMCS can inhibit bacteria of Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus by destroying the membrane of bacteria. The hemostatic needle with good hemostasis efficacy, antibacterial property, and safety is promising for the prevention of bleeding-associated complications in practical applications

    Additional file 1 of Nanoarchitectonics of tannic acid based injectable hydrogel regulate the microglial phenotype to enhance neuroplasticity for poststroke rehabilitation

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    Additional file 1: Fig. S1. Chemical reaction equation of TA and CMCS. Fig. S2. Immunofluorescence images of N2a cells by live/dead assay. Fig. S3. Immunofluorescence images of CD16 and CD206 staining in BV2 cells after OGD. Fig. S4. Chemical reaction equation of Cy5-NHS and CMCS. Fig. S5. Immunofluorescence spectrum of CMCS-Cy5. Fig. S6. SEM image of immunofluorescent TA gel formed by TA and CMCS-Cy5. Fig. S7. Standard curve of TA in aqueous solution. Fig. S8. The rheological curves of the mouse’s brain

    Image3_Artemis inhibition as a therapeutic strategy for acute lymphoblastic leukemia.jpeg

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    As effective therapies for relapse and refractory B-cell acute lymphoblastic leukemia (B-ALL) remain problematic, novel therapeutic strategies are needed. Artemis is a key endonuclease in V(D)J recombination and nonhomologous end joining (NHEJ) of DNA double-strand break (DSB) repair. Inhibition of Artemis would cause chromosome breaks during maturation of RAG-expressing T- and B-cells. Though this would block generation of new B- and T-cells temporarily, it could be oncologically beneficial for reducing the proliferation of B-ALL and T-ALL cells by causing chromosome breaks in these RAG-expressing tumor cells. Currently, pharmacological inhibition is not available for Artemis. According to gene expression analyses from 207 children with high-risk pre-B acute lymphoblastic leukemias high Artemis expression is correlated with poor outcome. Therefore, we evaluated four compounds (827171, 827032, 826941, and 825226), previously generated from a large Artemis targeted drug screen. A biochemical assay using a purified Artemis:DNA-PKcs complex shows that the Artemis inhibitors 827171, 827032, 826941, 825226 have nanomolar IC50 values for Artemis inhibition. We compared these 4 compounds to a DNA-PK inhibitor (AZD7648) in three patient-derived B-ALL cell lines (LAX56, BLQ5 and LAX7R) and in two mature B-cell lines (3301015 and 5680001) as controls. We found that pharmacological Artemis inhibition substantially decreases proliferation of B-ALL cell lines while normal mature B-cell lines are not markedly affected. Inhibition of DNA-PKcs (which regulates Artemis) using the DNA-PK inhibitor AZD7648 had minor effects on these same primary patient-derived ALL lines, indicating that inhibition of V(D)J hairpin opening requires direct inhibition of Artemis, rather than indirect suppression of the kinase that regulates Artemis. Our data provides a basis for further evaluation of pharmacological Artemis inhibition of proliferation of B- and T-ALL.</p

    Supplemental Methods and Results from Global Promoter Methylation Analysis Reveals Novel Candidate Tumor Suppressor Genes in Natural Killer Cell Lymphoma

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    Supplemental Methods and Results. Supplemental file including methods for GEP, RRBS, pyrosequencing, q-RT-PCR, western blot, functional assays, additional statistical methods and results describing the enrichment of tumor suppressor genes among epigenetically silenced genes</p

    DataSheet1_Artemis inhibition as a therapeutic strategy for acute lymphoblastic leukemia.pdf

    No full text
    As effective therapies for relapse and refractory B-cell acute lymphoblastic leukemia (B-ALL) remain problematic, novel therapeutic strategies are needed. Artemis is a key endonuclease in V(D)J recombination and nonhomologous end joining (NHEJ) of DNA double-strand break (DSB) repair. Inhibition of Artemis would cause chromosome breaks during maturation of RAG-expressing T- and B-cells. Though this would block generation of new B- and T-cells temporarily, it could be oncologically beneficial for reducing the proliferation of B-ALL and T-ALL cells by causing chromosome breaks in these RAG-expressing tumor cells. Currently, pharmacological inhibition is not available for Artemis. According to gene expression analyses from 207 children with high-risk pre-B acute lymphoblastic leukemias high Artemis expression is correlated with poor outcome. Therefore, we evaluated four compounds (827171, 827032, 826941, and 825226), previously generated from a large Artemis targeted drug screen. A biochemical assay using a purified Artemis:DNA-PKcs complex shows that the Artemis inhibitors 827171, 827032, 826941, 825226 have nanomolar IC50 values for Artemis inhibition. We compared these 4 compounds to a DNA-PK inhibitor (AZD7648) in three patient-derived B-ALL cell lines (LAX56, BLQ5 and LAX7R) and in two mature B-cell lines (3301015 and 5680001) as controls. We found that pharmacological Artemis inhibition substantially decreases proliferation of B-ALL cell lines while normal mature B-cell lines are not markedly affected. Inhibition of DNA-PKcs (which regulates Artemis) using the DNA-PK inhibitor AZD7648 had minor effects on these same primary patient-derived ALL lines, indicating that inhibition of V(D)J hairpin opening requires direct inhibition of Artemis, rather than indirect suppression of the kinase that regulates Artemis. Our data provides a basis for further evaluation of pharmacological Artemis inhibition of proliferation of B- and T-ALL.</p

    Supplemental Figures 1-12 from Global Promoter Methylation Analysis Reveals Novel Candidate Tumor Suppressor Genes in Natural Killer Cell Lymphoma

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    Supplemental Figures 1-12. Fig.1: The distribution of mappable HpaII sites(MSCC cut sites) and the distribution of MSCC reads in normal NK cells; Fig.2: Mean log2 cut counts per site for promoters and bodies of genes with differing normal NK expression levels; Fig.3: Correlation of promoter hypermethylation and gene expression of candidate genes in malignant NK samples; Fig.4: Genome-wide comparisons of MSCC and RRBS methodologies on detection of promoter methylation levels; Fig.5: Hypermethylated candidate tumor suppressor genes have low expression in malignant NK-cell lines.; Fig.6: BIM protein is silenced in NK-cell lines; Fig.7: Comparison of MSCC with locus-specific pyrosequencing; Fig.8: Pyrosequencing analysis of BIM, ASNS and DAPK1 promoters in NK-cell lines and normal NK-cells cross-validates MSCC results; Fig.9: Validation of BIM and ASNS promoter methylation with locus-specific q-MSP in malignant NK samples; Fig.10: BIM protein is induced after Decitabine treatment; Fig.11: Ectopic expression of BIM in NKYS cells 2 days post-transduction; Fig.12: Ectopic expression of SOCS6 in NK-cell lines</p
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