Preparing and characterizing Fe3O4@cellulose nanocomposites for effective isolation of cellulose-decomposing microorganisms

This study developed Fe3O4@cellulose nanocomposites by co-precipitation synthesis for bacteria capture and isolation. By surface modification with cellulose, the Fe3O4@cellulose nanocomposites have 20 nm average particle size and 3.3–24.9 emu/g saturation magnetization. Living bacteria could be captured by the Fe3O4@cellulose nanocomposites and harvested by magnetic field, with high efficiency (95.1%) and stability (>99.99%). By metabolizing cellulose and destroying the Fe3O4@cellulose@bacteria complex, cellulose-decomposing microorganisms lost the magnetism. They were therefore able to be isolated from the inert microbial community and the separation efficiency achieved over 99.2%. This research opened a door to cultivate the uncultivable cellulose-decomposing microorganisms in situ and further characterize their ecological functions in natural environment

Preformulation Studies of a Stable PTEN-PDZ Lipopeptide Able to Cross an In Vitro Blood-Brain-Barrier Model as a Potential Therapy for Alzheimer's Disease

PurposeAmyloid beta (A beta) drives the accumulation of excess Phosphatase and Tensin Homolog Deleted on Chromosome 10 (PTEN) at synapses, inducing synaptic depression and perturbing memory. This recruitment of PTEN to synapses in response to A beta drives its interaction with PSD95/Disc large/Zonula occludens-1 (PDZ) proteins and, indeed, we previously showed that an oligo lipopeptide (PTEN-PDZ) capable of blocking such PTEN:PDZ interactions rescues the synaptic and cognitive deficits in a mouse model of Alzheimer's disease. Hence, the PTEN:PDZ interaction appears to be crucial for A beta -induced synaptic and cognitive impairment. Here we have evaluated the feasibility of using PTEN-PDZ lipopeptides based on the human/mouse PTEN C-terminal sequence, testing their stability in biological fluids, their cytotoxicity, their ability to self-assemble and their in vitro blood-brain barrier (BBB) permeability. Myristoyl or Lauryl tails were added to the peptides to enhance their cell permeability.MethodsLipopeptides self assembly was assessed using electron microscopy and the thioflavin T assay. Stability studies in mouse plasma (50%), intestinal washing, brain and liver homogenates as well as permeability studies across an all human 2D blood-brain barrier model prepared with human cerebral endothelial cells (hCMEC/D3) and human astrocytes (SC-1800) were undertaken.ResultsThe mouse lauryl peptide displayed enhanced overall stability in plasma, ensuring a longer half-life in circulation that meant there were larger amounts available for transport across the BBB (Papp(0-4h): 6.281.85x10(-6) cm s(-1)).ConclusionThis increased availability, coupled to adequate BBB permeability, makes this peptide a good candidate for therapeutic parenteral (intravenous, intramuscular) administration and nose-to-brain delivery.The authors declare that this study received funding from MemoryPlus Ltd. The funder was not involved in the study design, collection, analysis, and interpretation of data. One of the authors of this article (SK) owns the controlling interest in MemoryPlus Ltd., and has filed an application for a U.S. Patent with respect to the compounds, compositions and methods mentioned in this article. SK was involved in the writing of this article and in the decision to submit it for publication

Receptor Tyrosine Kinase Interaction with the Tumor Microenvironment in Malignant Progression of Human Glioblastoma

Glioblastoma (GBM) is the most malignant brain tumor, characterized with a rapid progression and poor prognosis despite modern therapies. Receptor tyrosine kinase (RTK) is a membrane tyrosine kinase that could be activated by binding ligands with the extracellular domain, and communicating signals according to the tyrosine kinase activity of the intracellular domain. Recent studies revealed that RTKs such as EGFR, PDGFR and MET play key roles in cancer progression through regulation of abundant cellular processes. As transmembrane proteins, RTKs work as a mediator between the extracellular environment and intracellular compartments, translating the tumor microenvironment (TME) signals into the tumor cells. TME is also a critical regulator for the malignant process, lately receiving considerable attention. It is composed of extracellular matrix (ECM), the stromal cells (i.e., endothelial cells, microglia and fibroblasts), secreted factors, and hypoxia environment, etc. Among these, the strong invasion and sustained angiogenesis of GBM are closely related to ECM-receptor interaction and -associated signaling events. In this chapter, we consider the interaction and mechanisms of RTKs and TME in GBM progression, especially the role of ECM-receptor mediated signaling in tumor invasion, hypoxia and angiogenesis, glioma stem cells and tumor metabolism. We then summarize and discuss recent improvements on the approaches of targeting RTK and TME as the therapy in the primary GBM

Preformulation studies of a stable PTEN-PDZ lipopeptide able to cross an in vitro blood-brain-barrier model as a potential therapy for Alzheimer's disease

Purpose: Amyloid β (Aβ) drives the accumulation of excess Phosphatase and Tensin Homolog Deleted on Chromosome 10 (PTEN) at synapses, inducing synaptic depression and perturbing memory. This recruitment of PTEN to synapses in response to Aβ drives its interaction with PSD95/Disc large/Zonula occludens-1 (PDZ) proteins and, indeed, we previously showed that an oligo lipopeptide (PTEN-PDZ) capable of blocking such PTEN:PDZ interactions rescues the synaptic and cognitive deficits in a mouse model of Alzheimer’s disease. Hence, the PTEN:PDZ interaction appears to be crucial for Aβ-induced synaptic and cognitive impairment. Here we have evaluated the feasibility of using PTEN-PDZ lipopeptides based on the human/mouse PTEN C-terminal sequence, testing their stability in biological fluids, their cytotoxicity, their ability to self-assemble and their in vitro blood-brain barrier (BBB) permeability. Myristoyl or Lauryl tails were added to the peptides to enhance their cell permeability. Methods: Lipopeptides self assembly was assessed using electron microscopy and the thioflavin T assay. Stability studies in mouse plasma (50%), intestinal washing, brain and liver homogenates as well as permeability studies across an all human 2D blood-brain barrier model prepared with human cerebral endothelial cells (hCMEC/D3) and human astrocytes (SC-1800) were undertaken. Results: The mouse lauryl peptide displayed enhanced overall stability in plasma, ensuring a longer half-life in circulation that meant there were larger amounts available for transport across the BBB (Papp0-4h: 6.28 ± 1.85 × 10−6 cm s−1). Conclusion: This increased availability, coupled to adequate BBB permeability, makes this peptide a good candidate for therapeutic parenteral (intravenous, intramuscular) administration and nose-to-brain delivery