Video1_Triggering cell death in cancers using self-illuminating nanocomposites.MP4

Bioinspired photocatalysis has resulted in efficient solutions for many areas of science and technology spanning from solar cells to medicine. Here we show a new bioinspired semiconductor nanocomposite (nanoTiO2-DOPA-luciferase, TiDoL) capable of converting light energy within cancerous tissues into chemical species that are highly disruptive to cell metabolism and lead to cell death. This localized activity of semiconductor nanocomposites is triggered by cancer-generated activators. Adenosine triphosphate (ATP) is produced in excess in cancer tissues only and activates nearby immobilized TiDoL composites, thereby eliminating its off-target toxicity. The interaction of TiDoL with cancerous cells was probed in situ and in real-time to establish a detailed mechanism of nanoparticle activation, triggering of the apoptotic signaling cascade, and finally, cancer cell death. Activation of TiDoL with non-cancerous cells did not result in cell toxicity. Exploring the activation of antibody-targeted semiconductor conjugates using ATP is a step toward a universal approach to single-cell-targeted medical therapies with more precision, efficacy, and potentially fewer side effects.</p

DataSheet1_Triggering cell death in cancers using self-illuminating nanocomposites.docx

Bioinspired photocatalysis has resulted in efficient solutions for many areas of science and technology spanning from solar cells to medicine. Here we show a new bioinspired semiconductor nanocomposite (nanoTiO2-DOPA-luciferase, TiDoL) capable of converting light energy within cancerous tissues into chemical species that are highly disruptive to cell metabolism and lead to cell death. This localized activity of semiconductor nanocomposites is triggered by cancer-generated activators. Adenosine triphosphate (ATP) is produced in excess in cancer tissues only and activates nearby immobilized TiDoL composites, thereby eliminating its off-target toxicity. The interaction of TiDoL with cancerous cells was probed in situ and in real-time to establish a detailed mechanism of nanoparticle activation, triggering of the apoptotic signaling cascade, and finally, cancer cell death. Activation of TiDoL with non-cancerous cells did not result in cell toxicity. Exploring the activation of antibody-targeted semiconductor conjugates using ATP is a step toward a universal approach to single-cell-targeted medical therapies with more precision, efficacy, and potentially fewer side effects.</p

Video2_Triggering cell death in cancers using self-illuminating nanocomposites.MP4

Bioinspired photocatalysis has resulted in efficient solutions for many areas of science and technology spanning from solar cells to medicine. Here we show a new bioinspired semiconductor nanocomposite (nanoTiO2-DOPA-luciferase, TiDoL) capable of converting light energy within cancerous tissues into chemical species that are highly disruptive to cell metabolism and lead to cell death. This localized activity of semiconductor nanocomposites is triggered by cancer-generated activators. Adenosine triphosphate (ATP) is produced in excess in cancer tissues only and activates nearby immobilized TiDoL composites, thereby eliminating its off-target toxicity. The interaction of TiDoL with cancerous cells was probed in situ and in real-time to establish a detailed mechanism of nanoparticle activation, triggering of the apoptotic signaling cascade, and finally, cancer cell death. Activation of TiDoL with non-cancerous cells did not result in cell toxicity. Exploring the activation of antibody-targeted semiconductor conjugates using ATP is a step toward a universal approach to single-cell-targeted medical therapies with more precision, efficacy, and potentially fewer side effects.</p

Discharge OR comparing seasons within each region as well as geography within each season.

<p>For each year, the OR were calculated for all IBD, UC only, and CD only.</p

Northern Latitude but Not Season Is Associated with Increased Rates of Hospitalizations Related to Inflammatory Bowel Disease: Results of a Multi-Year Analysis of a National Cohort

<div><p>Background and Aims</p><p>There is growing evidence that the incidence and severity of inflammatory bowel disease (IBD) may be geographically and seasonally related. Why these associations are observed remains unclear. We assessed the impact of geographic location, season, and exposure to ultraviolet light on disease severity by measuring national hospital IBD-related discharge rates.</p><p>Methods</p><p>Utilizing the Nationwide Inpatient Sample (NIS), we identified all patients with IBD-related discharges from 2001–2007. Patients were included if they were discharged from states above the 40^th parallel (north) or at or below the 35^th parallel (south); and their discharge fell within the winter (January, February, and March) or summer (July, August, and September). Groups of patients were assessed comparing north to south within each season, and summer to winter within each region. UV index was recorded from the National Weather Service data and compared to monthly discharge rates.</p><p>Results</p><p>There was a consistent pattern of increased IBD-related hospitalization rates in northern states compared to southern states for both ulcerative colitis and Crohn’s disease. Differences in IBD-related hospitalization rates by season, however, were not uniform across the years studied. UV index was significantly inversely associated although not proportional to discharge rates for both Crohn’s disease and ulcerative colitis.</p><p>Conclusions</p><p>In the US, there is a significant increased rate of IBD-related hospitalizations in the northern compared to southern states, which not fully explained by differences in UV exposure.</p></div

Monthly discharge rates with associated mean UV index values for 2001–2004 for included northern and southern states.

<p>(a) Discharge rates for all IBD (p<0.001), (b) discharge rates for UC only (p<0.001), (c) discharge rates for CD only (p = 0.018).</p

Multivariate analysis comparing south versus north.

<p>Variables included in the multivariate analysis included race, age, and payer status.</p

TU-100 (Daikenchuto) and Ginger Ameliorate Anti-CD3 Antibody Induced T Cell-Mediated Murine Enteritis: Microbe-Independent Effects Involving Akt and NF-κB Suppression

<div><p>The Japanese traditional medicine daikenchuto (TU-100) has anti-inflammatory activities, but the mechanisms remain incompletely understood. TU-100 includes ginger, ginseng, and Japanese pepper, each component possessing bioactive properties. The effects of TU-100 and individual components were investigated in a model of intestinal T lymphocyte activation using anti-CD3 antibody. To determine contribution of intestinal bacteria, specific pathogen free (SPF) and germ free (GF) mice were used. TU-100 or its components were delivered by diet or by gavage. Anti-CD3 antibody increased jejunal accumulation of fluid, increased TNFα, and induced intestinal epithelial apoptosis in both SPF and GF mice, which was blocked by either TU-100 or ginger, but not by ginseng or Japanese pepper. TU-100 and ginger also blocked anti-CD3-stimulated Akt and NF-κB activation. A co-culture system of colonic Caco2BBE and Jurkat-1 cells was used to examine T-lymphocyte/epithelial cells interactions. Jurkat-1 cells were stimulated with anti-CD3 to produce TNFα that activates epithelial cell NF-κB. TU-100 and ginger blocked anti-CD3 antibody activation of Akt in Jurkat cells, decreasing their TNFα production. Additionally, TU-100 and ginger alone blocked direct TNFα stimulation of Caco2BBE cells and decreased activation of caspase-3 and polyADP ribose. The present studies demonstrate a new anti-inflammatory action of TU-100 that is microbe-independent and due to its ginger component.</p></div

TU-100 blocks activation of jejunal mucosal Akt and IκB stimulated by anti-CD3.

<p>(A) Mice were sacrificed at varying times after anti-CD3 antibody injection. Blots are representative of three separate mice. (B) Mice were gavaged daily for 3 days and one hr before anti-CD3 antibody treatment with TU-100 or components. Mice were sacrificed 3 hrs after anti-CD3 antibody injection. Blots are representative of two mice for each group, and a total of 6 mice were analyzed.</p

TU-100 blocks TNFα activation of IκBα, caspase 3 and PARP in Caco2BBE cells.

<p>Caco2BBE cells were treated overnight with IFNγ to increase TNF receptor expression and then stimulated with TNFα (100 ng/ml). Cells were harvested at 3 hrs for IκBα determinations and 6 hours for caspase 3 and PARP. Blots shown are representative of four separate experiments.</p