Modest enhancement of sensory axon regeneration in the sciatic nerve with conditional co-deletion of PTEN and SOCS3 in the dorsal root ganglia of adult mice
Axons within the peripheral nervous system are capable of regeneration, but full functional recovery is rare. Recent work has shown that conditional deletion of two key signaling inhibitors of the PI3K and Jak/Stat pathways—phosphatase and tensin ...
Total knee arthroplasty: improving outcomes with a multidisciplinary approach
Total knee arthroplasty (TKA) is the most commonly performed inpatient surgical procedure within the USA and is estimated to reach 3.48 million procedures annually by 2030. As value-based care initiatives continue to focus on hospital readmission rates ...
Ultrasound-Stimulated Drug Delivery Using Therapeutic Reconstituted High-Density Lipoprotein Nanoparticles
The abnormal tumor vasculature and the resulting abnormal microenvironment are major barriers to optimal chemotherapeutic drug delivery. It is well known that ultrasound (US) can increase the permeability of the tumor vessel walls and enhance the accumulation ...
Yoda1-induced phosphorylation of Akt and ERK1/2 does not require Piezo1 activation
Piezo1 is a mechanosensitive cation channel that is activated by shear stress in endothelial cells (ECs). It has been shown to mediate shear-induced EC responses, including increased calcium influx, and vascular functions, such as vascular tone and blood ...
Effect of Human Myotubes-Derived Media on Glucose-Stimulated Insulin Secretion
Fasting to postprandial transition requires a tight adjustment of insulin secretion to its demand, so tissue (e.g., skeletal muscle) glucose supply is assured while hypo-/hyperglycemia are prevented. High muscle glucose disposal after meals is pivotal ...
The store-operated Ca[2+] entry-associated regulatory factor (SARAF), a protein expressed both in the endoplasmic reticulum and the plasma membrane, has been presented as a STIM1-interacting protein with the ability to modulate intracellular Ca[2+] ...
Blocking the PI3K/AKT pathway enhances mammalian reovirus replication by repressing IFN-stimulated genes
Many host cellular signaling pathways were activated and exploited by virus infection for more efficient replication. The PI3K/Akt pathway has recently attracted considerable interest due to its role in regulating virus replication. This study demonstrated ...
MR-Guided Delivery of Hydrophilic Molecular Imaging Agents Across the Blood-Brain Barrier Through Focused Ultrasound
A wide variety of hydrophilic imaging and therapeutic agents are unable to gain access to the central nervous system (CNS) due to the blood-brain barrier (BBB). In particular, unless a particular transporter exists that may transport the agent across ...
Breaking the Depth Dependency of Phototherapy with Cerenkov Radiation and Low Radiance Responsive Nanophotosensitizers
The combination of light and photosensitizers for phototherapeutic interventions such as photodynamic therapy has transformed medicine and biology. However, the shallow penetration of light in tissues and the reliance on tissue oxygenation to generate ...
Simvastatin Prodrug Micelles Target Fracture and Improve Healing
Simvastatin (SIM), a widely used anti-lipidaemic drug, has been identified as a bone anabolic agent. Its poor water solubility and the lack of distribution to the skeleton, however, have limited its application in the treatment of bone metabolic diseases. ...
Minibody-Indocyanine Green Based Activatable Optical Imaging Probes: The Role of Short Polyethylene Glycol Linkers
Minibodies
show rapider blood clearance than IgGs due to smaller
size that improves target-to-background ratio (TBR) in in vivo imaging.
Additionally, the ability to activate an optical probe after binding
to the target greatly improves the TBR. An optical ...
Ultrasound-stimulated drug delivery for treatment of residual disease following incomplete resection of head and neck cancer
Microbubbles triggered with localized ultrasound (US) can improve tumor drug delivery and retention. Termed US-stimulated drug delivery, this strategy was applied to head and neck cancer (HNC) in a post-surgical tumor resection model. Nude athymic mice ...
Prostate-Specific Antigen-Retargeted Recombinant Newcastle Disease Virus for Prostate Cancer Virotherapy
Oncolytic virus (OV) therapies of cancer are based on the use of replication-competent, tumor-selective viruses with limited toxicity. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising OV and is inherently tumor selective and cytotoxic ...
Sortase-Tag Expressed Protein Ligation (STEPL): combining protein purification and site-specific bioconjugation into a single step
Efficient labeling of protein-based targeting ligands with various cargos (drugs, imaging agents, nanoparticles, etc.) is essential to the fields of molecular imaging and targeted therapeutics. Many common bioconjugation techniques, however, are inefficient, ...
The Effects of Psychostimulant Drugs on Blood Brain Barrier Function and Neuroinflammation
The blood brain barrier (BBB) is a highly dynamic interface between the central nervous system (CNS) and periphery. The BBB is comprised of a number of components and is part of the larger neuro(glio)vascular unit. Current literature suggests that psychostimulant ...
The Soluble Guanylate Cyclase Stimulator BAY 41-2272 Inhibits Vascular Smooth Muscle Growth through the cAMP-Dependent Protein Kinase and cGMP-Dependent Protein Kinase Pathways
Vascular smooth muscle (VSM) proliferation and migration are key components in vessel remodeling. Cyclic nucleotide signaling is protective and has long-served as a therapeutic target against undesired VSM growth. The present work analyzed the effects ...
Mechanical signals control SOX-9, VEGF, and c-Myc expression and cell proliferation during inflammation via integrin-linked kinase, B-Raf, and ERK1/2-dependent signaling in articular chondrocytes
The importance of mechanical signals in normal and inflamed cartilage is well established. Chondrocytes respond to changes in the levels of proinflammatory cytokines and mechanical signals during inflammation. Cytokines like interleukin (IL)-1β ...
Soleimavis Liu presented this paper at the recent E-Leader conference held by Fudan University and Chinese American Scholars Association in Shanghai, January 5-7, 2015. Recent years, the words “mind control abuse and torture” and “target individual” appears frequently online.
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Cocaine Hijacks σ1 Receptor to Initiate Induction of Activated Leukocyte Cell Adhesion Molecule: Implication for Increased Monocyte Adhesion and Migration in the CNS | Journal of Neuroscience
Human immunodeficiency virus (HIV)-associated increase in monocyte adhesion and trafficking is exacerbated by cocaine abuse. The underlying mechanisms involve cocaine-mediated upregulation of adhesion molecules with subsequent disruption of the blood–brain barrier (BBB). Recently, a novel activated leukocyte cell adhesion molecule (ALCAM) has been implicated in leukocyte transmigration across the endothelium. We now show that upregulation of ALCAM in the brain endothelium seen in HIV+/cocaine drug abusers paralleled increased CD68 immunostaining compared with HIV+/no cocaine or uninfected controls, suggesting the important role of ALCAM in promoting leukocyte infiltration across the BBB. Furthermore, ALCAM expression was increased in cocaine-treated mice with concomitant increase in monocyte adhesion and transmigration in vivo , which was ameliorated by pretreating with the neutralizing antibody to ALCAM, lending additional support to the role of ALCAM. This new concept was further confirmed by in vitro experiments. Cocaine-mediated induction of ALCAM in human brain microvascular endothelial cells through the translocation of σ receptor to the plasma membrane, followed by phosphorylation of PDGF-β (platelet-derived growth factor-β) receptor. Downstream activation of mitogen-activated protein kinases, Akt, and NF-κB (nuclear factor-κB) pathways resulted in induced expression of ALCAM. Functional implication of upregulated ALCAM was confirmed using cell adhesion and transmigration assays. Neutralizing antibody to ALCAM ameliorated this effect. Together, these findings implicate cocaine-mediated induction of ALCAM as a mediator of increased monocyte adhesion/transmigration into the CNS.