The protein kinase cascade Raf-MAPKK/MEK-MAPK/ERK connects tyrosine receptors in the membrane with control of transcription factor activity nucleus. We have examined whether Raf is obligatory for activation this and signaling pathway relevant to transformation. By use transient assays epitope-tagged ERK-1 cDNA a dominant inhibitory mutant Raf-1 we found that serum 12-O-tetradecanoylphorbol-13-acetate as well representatives three classes oncogenes (protein kinases abl/src, Ras,...

Two classes of human cDNA encoding the insulin/mitogen-activated p70 S6 kinase have been isolated; two differ only in 5' region, such that longer polypeptide (p70 alpha I; calculated Mr 58,946) consists 525 amino acids, which last 502 residues are identical sequence to entire polypeptides encoded by second II; 56,153). Both predicted these cDNAs present purified from rat liver, and each is thus expressed vivo. Moreover, both a single mRNA transcribed (longer) I through utilization different...

Multifunctional nanoparticles that can provide long circulation and specific accumulation, illuminate the targeted object, intelligently dose pathological zones will enable major advancements in diagnosis therapy. To facilitate a simultaneous tumor-cell imaging adequate local delivery to tumor site, we develop core−shell structured hybrid nanogels (40−80 nm) composed of Ag nanoparticle (NP) as core smart gel poly(N-isopropylacrylamide-co-acrylic acid) shell. The pH-induced shrinkage nanogel...

Multifunctional nanocarriers with good biocompatibility, imaging function, and smart drug delivery ability are crucial for realizing highly efficient imaging-guided chemotherapy in vivo. This paper reports a type of chitosan–carbon dot (CD) hybrid nanogels (CCHNs, ∼65 nm) by integrating pH-sensitive chitosan fluorescent CDs into single nanostructure simultaneous near-infrared (NIR) NIR/pH dual-responsive release to improve therapeutic efficacy. Such CCHNs were synthesized via...

Multifunctional hybrid nanoparticles (NPs, ∼100 nm) that combine magnetic Fe3O4 nanocrystals and fluorescent carbon dots (CDs) in porous (C) were successfully synthesized using a one-pot solvothermal method by simply increasing the H2O2 concentration. The resultant Fe3O4@C-CDs NPs not only demonstrate excellent responsive properties (Ms = 32.5 emu g-1) resonance imaging ability (r 674.4 mM-1 s-1) from nanocrystal core, but also exhibit intriguing photoluminescent (quantum yield ∼6.8%)...

Effective, if dotty: Quantum-dot (QD) emission was modulated through the reversible covalent bonding of glucose to boronic acids on surface QDs (see picture). The highly selective ratiometric probe sensitive in physiologically important concentration range 0.4–20.0 mM and used determine amount within living cells. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted...

The paper demonstrates a class of multifunctional core–shell hybrid nanogels with fluorescent and magnetic properties, which have been successfully developed for simultaneous optical temperature sensing, tumor cell imaging magnetic/NIR-thermally responsive drug carriers.

The paper demonstrates the synthesis of carbon-based responsive hybrid nanogels and their applications including sensing, cell imaging drug delivery.

Glioblastoma (GBM) is a deadly brain tumor with current mean survival of 12–15 months. Despite being potent anti-cancer agent, the turmeric ingredient curcumin (C) has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier strategy involving use two other polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) red grapes at unique, synergistic molar ratio C (C:E:R: 4:1:12.5, termed TriCurin) achieve superior potency against HPV+ tumors...

Curcumin, the primary active ingredient in spice turmeric, was converted to reactive monofunctional derivatives (carboxylic acid/azide/alkyne). The were employed produce a 3 + 2 azide-alkyne "clicked" curcumin dimer and poly(amidoamine) (PAMAM) dendrimer-curcumin conjugate. retain biological activity are efficient for labeling dissolving amyloid fibrils. selectively destroys human neurotumor cells. synthetic methodology developed affords general strategy attaching various macromolecular scaffolds.

Glioblastoma (GBM) is a primary brain tumor with 5-year survival rate of ≤5%. We have shown earlier that GBM-antibody-linked curcumin (CC) and also phytosomal (CCP) rescue 50–60% GBM-bearing mice while repolarizing the tumor-associated microglia/macrophages (TAM) from tumor-promoting M2-type to tumoricidal M1-type. However, systemic application CCP yields only sub-IC50 concentrations CC in plasma, which unlikely kill GBM cells directly. This study investigates role CC-evoked intra-GBM...

The synthesis of a water/plasma soluble, noncytotoxic, "clicked" sugar-derivative curcumin with amplified bioefficacy in modulating amyloid-β and tau peptide aggregation is presented. Curcumin inhibits at micromolar concentrations; the sugar–curcumin conjugate Aβ concentrations as low 8 nM 0.1 nM, respectively. In comparison to curcumin, this conveniently synthesized Alzheimer's drug candidate more powerful antioxidant.

Human papilloma virus (HPV)-induced cervical cancer is one of the most frequent cancers in women residing underdeveloped countries. Natural compounds like polyphenols continue to be scientific interest as non-toxic effective alternative treatments. Our previous work showed efficacy two polyphenols, resveratrol, and pterostilbene on human HeLa cells. Here we explored

Glioblastoma (GBM) is one of the most pernicious forms cancer and currently chances survival from this malady are extremely low. We have used noninvasive strategy intranasal (IN) delivery a glioblastoma-directed adduct curcumin (CC), CC-CD68Ab, into brain mouse GBM GL261-implanted mice to study effect CC on tumor remission phenotype tumor-associated microglial cells (TAMs). The treatment caused in 50% mice. A similar rescue rate was also achieved through intraperitoneal infusion...

Abstract Under a rational design, combining multiple constituents into single nano‐object will not only bridge the unique properties of individual materials to leverage research both fundamentally and practically, but also improve conventional sensing, imaging, therapeutic efficacies. Such (<100 nm) can be constructed by covalently bonding ZnO quantum dots (QDs) nonlinear poly(ethylene glycol)‐based nanogel network chains, followed appropriate growth metallic Au. With polymer gel serving...

The molecule responsible for the enzyme activity plasma membrane (PM) aminophospholipid translocase (APLT), which catalyzes phosphatidylserine (PS) translocation from outer to inner leaflet of membrane, is unknown in mammals. A Caenorhabditis elegans study has shown that ablation transbilayer amphipath transporter-1 (TAT-1), an ortholog a mammalian P-type ATPase, Atp8a1, causes PS externalization germ cells. We demonstrate here hippocampal cells dentate gyrus, and Cornu Ammonis (CA1, CA3)...