Nicotine alters mucin rheological properties.

Tobacco smoke exposure, the major cause of chronic obstructive pulmonary disease (COPD), instigates a dysfunctional clearance of thick obstructive mucus. However, the mechanism underlying the formation of abnormally viscous mucus remains elusive. We investigated whether nicotine can directly alter the rheological properties of mucin by examining its physicochemical interactions with human airway mucin gels secreted from A549 lung epithelial cells. Swelling kinetics and multiple particle tracking were utilized to assess mucin gel viscosity change when exposed to nicotine. Herein we show that nicotine (≤50 nM) significantly hindered postexocytotic swelling and hydration of released mucins, leading to higher viscosity, possibly by electrostatic and hydrophobic interactions. Moreover, the close association of nicotine and mucins allows airway mucus to function as a reservoir for prolonged nicotine release, leading to correlated pathogenic effects. Our results provide a novel explanation for the maltransport of poorly hydrated mucus in smokers. More importantly, this study further indicates that even low-concentration nicotine can profoundly increase mucus viscosity and thus highlights the health risks of secondhand smoke exposure.

Activated charcoal composite biomaterial promotes human embryonic stem cell differentiation toward neuronal lineage.

Transplantation of biomaterial scaffolds encasing human embryonic stem cells (hESCs) has been proposed as a clinical therapy for various neurological lesions and disorders. In light of recent developments, artificially synthesized carbon-based biomaterials such as carbon nanotubes and graphene have demonstrated feasibility in supporting stem cell attachment and differentiation. However, the applicability is significantly hampered by evidence of nanotoxic effects on multiple cell types. Thus, an emergent drive for an innovative carbonaceous biomaterial calls for a safer platform with comparable advantageous characteristics. Here, we showed for the first time, a natural coal-based activated charcoal (AC) composite biosubstrate can support and promote neuronal differentiation in hESCs. The bio-friendly AC composite biomatrices resulted in more matured neuron-like cells. Both of axonal length and density were at least twice as long and abundant, respectively, when compared with control groups. A functional assay demonstrated that the derived neuron-like cells responded to depolarization-dependent synaptic recycling and may contain active synapses. In addition, the AC composite substrate can serve to concentrate growth factors and cell adhesion proteins, further encouraging attachment and hESC differentiation. Moreover, the AC composite biomaterial can potentially be economically manufactured as implantable three-dimensional bioscaffolds, facilitating the regeneration of damaged neural and other tissues.

A mixture of anatase and rutile TiO2 nanoparticles induces histamine secretion in mast cells.

BACKGROUND: Histamine released from mast cells, through complex interactions involving the binding of IgE to FcεRI receptors and the subsequent intracellular Ca²âº signaling, can mediate many allergic/inflammatory responses. The possibility of titanium dioxide nanoparticles (TiO2 NPs), a nanomaterial pervasively used in nanotechnology and pharmaceutical industries, to directly induce histamine secretion without prior allergen sensitization has remained uncertain. RESULTS: TiO2 NP exposure increased both histamine secretion and cytosolic Ca²âº concentration ([Ca²âº]C) in a dose dependent manner in rat RBL-2H3 mast cells. The increase in intracellular Ca²âº levels resulted primarily from an extracellular Ca²âº influx via membrane L-type Ca²âº channels. Unspecific Ca²âº entry via TiO2 NP-instigated membrane disruption was demonstrated with the intracellular leakage of a fluorescent calcein dye. Oxidative stress induced by TiO2 NPs also contributed to cytosolic Ca²âº signaling. The PLC-IP3-IP3 receptor pathways and endoplasmic reticulum (ER) were responsible for the sustained elevation of [Ca²âº]C and histamine secretion. CONCLUSION: Our data suggests that systemic circulation of NPs may prompt histamine release at different locales causing abnormal inflammatory diseases. This study provides a novel mechanistic link between environmental TiO2 NP exposure and allergen-independent histamine release that can exacerbate manifestations of multiple allergic responses.

Clinical implications of contralateral axillary sentinel lymph nodes.

Extra-axillary sentinel lymph nodes can only be detected if radioactive tracer is used and pre-operative scans are carried out. The presence of metastatic sentinel lymph nodes in most extra-axillary sites will upstage patients if the ipsilateral axillary sentinel lymph node is normal. Paradoxically, the presence of metastatic sentinel lymph nodes in the contralateral axilla has the potential to prevent upstaging to stage IV, but only if detected as a sentinel node at the initial surgery rather than as a systemic recurrence at some later time. We describe a case of bilateral axillary sentinel lymph nodes detected by pre-operative lymphoscintigraphy in a patient with a medial quadrant breast cancer and discuss the possible implications of such a finding.