In utero exposure to electronic-cigarette aerosols decreases lung fibrillar collagen content, increases Newtonian resistance and induces sex-specific molecular signatures in neonatal mice

Approximately 7% of pregnant women in the United States use electronic-cigarette (e-cig) devices during pregnancy. There is, however, no scientific evidence to support e-cig use as being \u27safe\u27 during pregnancy. Little is known about the effects of fetal exposures to e-cig aerosols on lung alveologenesis. In the present study, we tested the hypothesis that in utero exposure to e-cig aerosol impairs lung alveologenesis and pulmonary function in neonates. Pregnant BALB/c mice were exposed 2 h a day for 20 consecutive days during gestation to either filtered air or cinnamon-flavored e-cig aerosol (36 mg/mL of nicotine). Lung tissue was collected in offspring during lung alveologenesis on postnatal day (PND) 5 and PND11. Lung function was measured at PND11. Exposure to e-cig aerosol in utero led to a significant decrease in body weights at birth which was sustained through PND5. At PND5, in utero e-cig exposures dysregulated genes related to signaling and epigenetic modifications in both females (~ 120 genes) and males (40 genes). These alterations were accompanied by reduced lung fibrillar collagen content at PND5-a time point when collagen content is close to its peak to support alveoli formation. In utero exposure to e-cig aerosol also increased the Newtonian resistance of offspring at PND11, suggesting a narrowing of the conducting airways. At PND11, in females, transcriptomic dysregulation associated with epigenetic alterations was sustained (17 genes), while signaling dysregulation was largely resolved (10 genes). In males, at PND11, the expression of only 4 genes associated with epigenetics was dysregulated, while 16 related-genes were altered. These data demonstrate that in utero exposures to cinnamon-flavored e-cig aerosols alter lung structure and function and induce sex-specific molecular signatures during lung alveologenesis in neonatal mice. This may reflect epigenetic programming affecting lung disease development later in life

Ultrahigh Throughput Silicon Nanomanufacturing by Simultaneous Reactive Ion Synthesis and Etching

One-dimensional nanostructures, such as nanowhisker, nanorod, nanowire, nanopillar, nanocone, nanotip, nanoneedle, have attracted significant attentions in the past decades owing to their numerous applications in electronics, photonics, energy conversion and storage, and interfacing with biomolecules and living cells. The manufacturing of nanostructured devices relies on either bottom-up approaches such as synthesis or growth process or top-down approaches such as lithography or etching process. Here we report a unique, synchronized, and simultaneous top-down and bottom-up nanofabrication approach called simultaneous plasma enhanced reactive ion synthesis and etching (SPERISE). For the first time the atomic addition and subtraction of nanomaterials are concurrently observed and precisely controlled in a single-step process permitting ultrahigh-throughput, lithography-less, wafer-scale, and room-temperature nanomanufacturing. Rapid low-cost manufacturing of high-density, high-uniformity, light-trapping nanocone arrays was demonstrated on single crystalline and polycrystalline silicon wafers, as well as amorphous silicon thin films. The proposed nanofabrication mechanisms also provide a general guideline to designing new SPERISE methods for other solid-state materials besides silicon

Electrically Induced Conformational Change of Peptides on Metallic Nanosurfaces

Surface immobilized biomolecular probes are used in many areas of biomedical research, such as genomics, proteomics, immunology, and pathology. Although the structural conformations of small DNA and peptide molecules in free solution are well studied both theoretically and experimentally, the conformation of small biomolecules bound on surfaces, especially under the influence of external electric fields, is poorly understood. Using a combination of molecular dynamics simulation and surface-enhanced Raman spectroscopy, we study the external electric field-induced conformational change of dodecapeptide probes tethered to a nanostructured metallic surface. Surface-tethered peptides with and without phosphorylated tyrosine residues are compared to show that peptide conformational change under electric field is sensitive to biochemical modification. Our study proposes a highly sensitive <i>in vitro</i> nanoscale electro-optical detection and manipulation method for biomolecule conformation and charge at bio–nano interfaces

Electrically Induced Conformational Change of Peptides on Metallic Nanosurfaces

Surface immobilized biomolecular probes are used in many areas of biomedical research, such as genomics, proteomics, immunology, and pathology. Although the structural conformations of small DNA and peptide molecules in free solution are well studied both theoretically and experimentally, the conformation of small biomolecules bound on surfaces, especially under the influence of external electric fields, is poorly understood. Using a combination of molecular dynamics simulation and surface-enhanced Raman spectroscopy, we study the external electric field-induced conformational change of dodecapeptide probes tethered to a nanostructured metallic surface. Surface-tethered peptides with and without phosphorylated tyrosine residues are compared to show that peptide conformational change under electric field is sensitive to biochemical modification. Our study proposes a highly sensitive <i>in vitro</i> nanoscale electro-optical detection and manipulation method for biomolecule conformation and charge at bio–nano interfaces

Docetaxel radiosensitizes castration resistant prostate cancer by downregulating CAV-1

Purpose: Docetaxel (dox), a noted radiosensitizer, is one of the few chemotherapy drugs approved for castration-resistant prostate cancer (CRPC), though only a fraction of CRPCs respond to it. CAV-1, a critical regulator of radioresistance, has been known to modulate dox and radiation effects. Combining dox with radiotherapy may create a synergistic anticancer effect through CAV-1 and improve CRPC patients' response to therapy. Here, we investigate the effectiveness and molecular characteristics of dox and radiation combination therapy in vitro. Materials and Methods: We used live/dead assays to determine the IC50 of dox for PC3, DU-145, and TRAMP-C1 cells. Colony formation assay was used to determine the radioresponse of the same cells treated with radiation with/without IC50 dox (4, 8, 12 Gy). We performed gene expression analysis on public transcriptomic data collected from human-derived prostate cancer cell lines (C4-2, PC3, DU-145, LNCaP) treated with dox for 8, 16, and 72 hours. Cell cycle arrest and protein expression were assessed using flow cytometry and western blot, respectively. Results: Compared to radiation alone, combination therapy with dox significantly increased CRPC death in PC3 (1.48-fold, p  Conclusions: Our results suggest that dox sensitizes CRPC cells to radiation by downregulating CAV-1. Dox + radiation combination therapy may be effective at treating CRPC, especially subtypes associated with high CAV-1 expression, and should be studied further. </p

Trimodal Therapy: Combining Hyperthermia with Repurposed Bexarotene and Ultrasound for Treating Liver Cancer

Repurposing of existing cancer drugs to overcome their physical limitations, such as insolubility, represents an attractive strategy to achieve enhanced therapeutic efficacy and broaden the range of clinical applications. Such an approach also promises to offer substantial cost savings in drug development efforts. Here we repurposed FDA-approved topical agent bexarotene (Targretin), currently in limited use for cutaneous manifestations of T-cell lymphomas, and re-engineer it for use in solid tumor applications by forming self-assembling nanobubbles. Physico-chemical characterization studies of the novel prodrug nanobubbles demonstrated their stability, enhanced target cell internalization capability, and highly controlled release profile in response to application of focused ultrasound energy. Using an <i>in vitro</i> model of hepatocellular carcinoma and an <i>in vivo</i> large animal model of liver ablation, we demonstrate the effectiveness of bexarotene prodrug nanobubbles when used in conjunction with catheter-based ultrasound, thereby highlighting the therapeutic promise of this trimodal approach