Peptide-based inhibitors and nanoparticles: Emerging therapeutics for Alzheimer's disease.

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder characterized by memory loss, cognitive decline, and behavioral changes, impacting millions of individuals worldwide. Despite significant research into its cellular and molecular mechanisms, no cure has been found to treat AD to date. For over two decades, research aimed at treating AD has focused on targeting amyloid-β (Aβ); however, these strategies have not demonstrated substantial effectiveness.

Standardized evaluation of CAR-T cells using acellular artificial target particles.

The horizon of immunotherapy using CAR-T cells is continuously extending to treat solid tumors beyond the success in the treatment of liquid tumors. Precise evaluations of CAR-T cells for their phenotypes, quantity and quality of activation in various tumor microenvironments including different antigen densities, and the resulting effector functions are critical for the successful development of CAR-T therapies and safe translation to clinics. Unfortunately, the development of methods and tools to accommodate these needs have been lagging behind.

Contextual reprogramming of CAR-T cells for treatment of HER2 cancers.

Background: Adoptive transfer of chimeric antigen receptor (CAR)-engineered T cells combined with checkpoint inhibition may prevent T cell exhaustion and improve clinical outcomes. However, the approach is limited by cumulative costs and toxicities.

Methods: To overcome this drawback, we created a CAR-T (RB-340-1) that unites in one product the two modalities: a CRISPR interference-(CRISPRi) circuit prevents programmed cell death protein 1 (PD-1) expression upon antigen-encounter.

Targeted Association and Intracellular Delivery of Nanocargoes into Primary T Lymphocytes via Interleukin-2 Receptor-Mediated Endocytosis.

Despite the tremendous progress in immunotherapy regimens using T cells, efforts to modulate the functions of T cells are still significantly hampered by the lack of reliable methods to deliver various cargoes into the T cells. This ongoing challenge originates from the intrinsic resistance of T cells in taking up exogenous materials. Here, we strategically aimed to hijack the natural endocytosis of Interleukin-2 (IL2) by the activated T cells for the targeted association and intracellular delivery of cargoes in varying sizes.

Calcium signaling on Jurkat T cells induced by microbeads coated with novel peptide ligands specific to human CD3ε.

CD3ε is expressed on T lymphocytes as a part of the T cell receptor (TCR)-CD3 complex. Together with other CD3 molecules, CD3ε is responsible for the activation of T cells via transducing the event of antigen recognition by the TCR into intracellular signaling cascades. The present study first aims to identify a novel peptide ligand that binds to human CD3ε in a specific manner and to perform an initial evaluation of its biological efficacy on the human T cell line, Jurkat cells.

Calcium enhances polyplex-mediated transfection efficiency of plasmid DNA in Jurkat cells.

Jurkat, an immortalized cell line derived from human leukemic T lymphocytes, has been employed as an excellent surrogate model of human primary T-cells for the advancement of T-cell biology and their applications in medicine. However, presumably due to its T-cell origin, Jurkat cells are very difficult to transfect. Thus, for the genetic modification of Jurkat cells, expensive and time-consuming viral vectors are normally required.

Oxime Cross-Linked Alginate Hydrogels with Tunable Stress Relaxation.

Stress relaxation is an important design parameter of biomaterials that can provide an artificial microenvironment mimicking natural extracellular matrix (ECM). Here, we report a novel hydrogel platform based on sodium alginate (NaAlg) with tunable stress relaxation. We first developed a new synthesis route to introduce alkoxyamine functional groups into the alginate polymer backbone.

Artificial Methods for T Cell Activation: Critical Tools in T Cell Biology and T Cell Immunotherapy.

Antigen-specific immunity conferred by T lymphocytes is a result of complex molecular interactions at the immunological synapse. A variety of biomimetic approaches have been devised to artificially induce T cell activation either to study the T cell biology or to expand and prime the therapeutic T cell populations. Here we first briefly review the molecular and cellular, structural and phenotypical bases that are involved in T cell activation.

A synthetic stroma-free germinal center niche for efficient generation of humoral immunity ex vivo.

B cells play a major role in the adaptive immune response by producing antigen-specific antibodies against pathogens and imparting immunological memory. Following infection or vaccination, antibody-secreting B cells and memory B cells are generated in specialized regions of lymph nodes and spleens, called germinal centers. Here, we report a fully synthetic ex-vivo system that recapitulates the generation of antigen-specific germinal-center (GC) like B cells using material-surface driven polyvalent signaling.

Engineering approaches for regeneration of T lymphopoiesis.

T cells play a central role in immune-homeostasis; specifically in the induction of antigen-specific adaptive immunity against pathogens and mutated self with immunological memory. The thymus is the unique organ where T cells are generated. In this review, first the complex structures and functions of various thymic microcompartments are briefly discussed to identify critical engineering targets for regeneration of thymic functions in vitro and in vivo.

Biomanufacturing of Therapeutic Cells: State of the Art, Current Challenges, and Future Perspectives.

Stem cells and other functionally defined therapeutic cells (e.g., T cells) are promising to bring hope of a permanent cure for diseases and disorders that currently cannot be cured by conventional drugs or biological molecules.

In Vitro Synergistic Effects of Antimicrobial Combinations on Extensively Drug-Resistant Pseudomonas aeruginosa and Acinetobacter baumannii Isolates.

Background: Extensively drug-resistant (XDR) Pseudomonas aeruginosa and Acinetobacter baumannii are a threat to hospitalized patients. We evaluated the effects of antimicrobial combinations on XDR P. aeruginosa and A.

The coreceptor CD4 is expressed in distinct nanoclusters and does not colocalize with T-cell receptor and active protein tyrosine kinase p56lck.

CD4 molecules on the surface of T lymphocytes greatly augment the sensitivity and activation process of these cells, but how it functions is not fully understood. Here we studied the spatial organization of CD4, and its relationship to T-cell antigen receptor (TCR) and the active form of Src kinase p56lck (Lck) using single and dual-color photoactivated localization microscopy (PALM) and direct stochastic optical reconstruction microscopy (dSTORM). In nonactivated T cells, CD4 molecules are clustered in small protein islands, as are TCR and Lck.

An initial and rapid step of lytic granule secretion precedes microtubule organizing center polarization at the cytotoxic T lymphocyte/target cell synapse.

It is presently assumed that lethal hit delivery by cytotoxic T lymphocytes (CTLs) is mechanistically linked to centrosome polarization toward target cells, leading to dedicated release of lytic granules within a confined secretory domain. Here we provide three lines of evidence showing that this mechanism might not apply as a general paradigm for lethal hit delivery. First, in CTLs stimulated with immobilized peptide-MHC complexes, lytic granules and microtubule organizing center localization into synaptic areas are spatio-temporally dissociated, as detected by total internal reflection fluorescence microscopy.

Anisotropic hybrid particles based on electrohydrodynamic co-jetting of nanoparticle suspensions.

Electrohydrodynamic co-jetting of two different nanocrystal suspensions can result in anisotropic nanocomposite particles. Using this approach, we are able to prepare submicron-sized, spherical Janus particles (464 ± 242 nm), which are not only comprised of two chemically distinct compartments, but are also morphologically anisotropic. Specifically, multifunctional hybrid particles have been derived, which are composed of a crosslinked copolymer, poly(acrylamide-co-acrylic acid) (p(AAm-co-AA)), and compartmentalized with respect to two metal oxides, i.

Structurally Controlled Bio-hybrid Materials Based on Unidirectional Association of Anisotropic Microparticles with Human Endothelial Cells.

Biocompatible anisotropic polymer particles with bipolar affinity towards human endothelial cells are a novel type of building blocks for microstructured bio-hybrid materials. Functional polarity due to two biologically distinct hemispheres has been achieved by synthesis of anisotropic particles via electro-hydrodynamic co-jetting of two different polymer solutions and subsequent selective surface modification.

Biocompatible Polymers: Structurally Controlled Bio-hybrid Materials Based on Unidirectional Association of Anisotropic Microparticles with Human Endothelial Cells (Adv. Mater. 48/2009).

Biocompatible anisotropic polymer particles with bipolar affinity towards human endothelial cells are a novel type of building blocks for microstructured biohybrid materials, report Joerg Lahann and co-workers on p. 4920. Functional polarity due to two biologically distinct hemispheres has been achieved by synthesis of anisotropic particles via electro-hydrodynamic co-jetting of two different polymer solutions and subsequent selective surface modification.

Epidemiology and control of an outbreak of vancomycin-resistant enterococci in the intensive care units.

Purpose: This study was aimed to describe a vancomycin-resistant enterococci (VRE) outbreak across three intensive care units (ICUs) of a Korean hospital from September 2006 to January 2007 and the subsequent control strategies.

Materials And Methods: We simultaneously implemented multifaceted interventions to control the outbreak, including establishing a VRE cohort ward, active rectal surveillance cultures, daily extensive cleaning of environmental surfaces and environmental cultures, antibiotic restriction, and education of hospital staff. We measured weekly VRE prevalence and rectal acquisition rates and characterized the VRE isolates by polymerase chain reaction (PCR) of the vanA gene and Sma1-pulsed-field gel electrophoresis (PFGE).

Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device.

The enumeration of rare circulating epithelial cells (CEpCs) in the peripheral blood of metastatic cancer patients has shown promise for improved cancer prognosis. Moving beyond enumeration, molecular analysis of CEpCs may provide candidate surrogate endpoints to diagnose, treat, and monitor malignancy directly from the blood samples. Thorough molecular analysis of CEpCs requires the development of new sample preparation methods that yield easily accessible and purified CEpCs for downstream biochemical assays.

Water-stable biphasic nanocolloids with potential use as anisotropic imaging probes.

Electrified co-jetting of two aqueous polymer solutions followed by a thermal cross-linking step was used to create water-stable biphasic nanocolloids. For this purpose, aqueous solution mixtures of poly(acrylamide-co-acrylic acid) and poly(acrylic acid) were employed as jetting solutions. When the biphasic nanocolloids created by side-by-side electrified co-jetting were thermally treated, a cross-linking reaction occurred between amide groups and carboxylic groups to form stable imide groups.

Short-term biocompatibility of biphasic nanocolloids with potential use as anisotropic imaging probes.

Advances in nanotechnology, in particular the development of novel types of nanoparticles, will result in advanced tools for biomedical research and clinical practice. One exciting aspect of future nanomaterial research will be the possibility to combine therapy and imaging in multifunctional nanoparticle designs. In this context, anisotropic particles with subcellular dimensions may offer so far unattainable capabilities, because they could provide access to directional information with respect to nanoparticle-cell interactions.

Triphasic nanocolloids.

Triphasic nanocolloids, that is, nanocolloids with three distinct compartments, were successfully produced by use of electrified co-jetting. Simultaneous manipulation of the three parallel liquid with laminar flows yielded a liquid droplet with three interfaces between the jetting liquids. Under a high electric potential, a single liquid jet was produced from the triple point of the droplet.

The effect of chitosan bead encapsulating calcium sulfate as an injectable bone substitute on consolidation in the mandibular distraction osteogenesis of a dog model.

Purpose: The purpose of this project was to study the effect of chitosan bead encapsulating calcium sulfate, which provides a sustained release of chitosan and calcium sulfate after implantation, on early bony consolidation in distraction osteogenesis of a dog model.

Materials And Methods: Forty-five dogs were used for this study. An external distraction device was applied to the mandibular body after a vertical osteotomy and mandibular distraction was initiated 5 days after the operation at a rate of 1 mm/day up to a 10-mm distraction.

Biphasic Janus particles with nanoscale anisotropy.

Advances in the field of nanotechnology have fuelled the vision of future devices spawned from tiny functional components that are able to assemble according to a master blueprint. In this concept, the controlled distribution of matter or 'patchiness' is important for creating anisotropic building blocks and introduces an extra design parameter--beyond size and shape. Although the reliable and efficient fabrication of building blocks with controllable material distributions will be of interest for many applications in research and technology, their synthesis has been addressed only in a few specialized cases.

Effect of calcium sulfate-chitosan composite: pellet on bone formation in bone defect.

The purpose of this experiment was to study the effects of chitosan, calcium sulfate, and calcium sulfate-chitosan composite pellet on the osteogenesis of defective tibia in rabbits. Eighty New Zealand white rabbits, each weighing approximately 3 to 3.5 kg, were used for this study.