Efficient Combination Chemo-Sonodynamic Cancer Therapy Using Mitochondria-Targeting Sonosensitizer-Loaded Polysorbate-Based Micelles.

Sonodynamic therapy (SDT), utilizing ultrasound (US) and sonosensitizers, holds immense potential as a noninvasive and targeted treatment for a variety of deep-seated tumors. However, the clinical translation of SDT is hampered by several key limitations in sonosensitizers, especially their low aqueous stability and poor cellular uptake. In this study, non-ionic polysorbate (Tween 80, T80) was adopted to formulate effective nanocarriers for the safe and efficient delivery of sonosensitizers to cancer cells. Mitochondria-targeting triphenylphosphonium (TPP)-conjugated chlorin e6 (Ce6) sonosensitizer was loaded into T80-based micelles for efficient SDT. Pro-oxidant piperlongumine (PL) was co-encapsulated with TPP-conjugated Ce6 (T-Ce6) in T80 micelles to enable combination chemo-SDT. T80 micelles substantially enhanced the cellular internalization of T-Ce6. As a result, T80 micelles loaded with T-Ce6 and PL [T80(T-Ce6/PL)] significantly elevated intracellular reactive oxygen species (ROS) generation in MCF-7 human breast cancer cells upon US exposure. Moreover, T-Ce6 exhibited selective accumulation within the mitochondria, leading to efficient cell death under US irradiation. Importantly, T80(T-Ce6/PL) micelles caused cancer-specific cell death by selectively triggering apoptosis in cancer cells through PL. This study demonstrated the feasibility of using T80(T-Ce6/PL) micelles for efficient and cancer-specific combination chemo-SDT.

Effects of dynamic neuromuscular stabilization on diaphragm movement, postural control, balance and gait performance in cerebral palsy.

PURPOSE: To determine the effects of a novel dynamic neuromuscular stabilization (DNS) technique on gross motor function, diaphragm movement, and activation of the external oblique (EO) and internal oblique (IO)/transversus abdominal (TrA) muscles in participants with cerebral palsy (CP). METHOD: Fifteen participants with CP (7 females) underwent DNS intervention for 30 minutes/day, 3 days a week for 4 weeks. Gross motor function, diaphragm movement, and muscle activation were determined using a gross motor function measure (GMFM-88), ultrasound, and electromyography measurements, respectively, before and after the DNS core stabilization intervention. Paired t-tests were used at p < 0.05. DESIGN: A single-arm, pretest-posttest clinical trial. RESULTS: GMFM scores for standing, walking, and jumping domains were significantly improved after the intervention (P < 0.05). Diaphragm descending movement (P = 0.0001) and activation of the internal oblique and transversus abdominals were initially undetectable, but remarkably increased after the intervention (P = 0.012). CONCLUSIONS: DNS is a promising, effective intervention for facilitating deep core muscle activation of the underactive muscle chain comprising the diaphragm, internal oblique, and transversus abdominals, thereby improving age-appropriate standing, walking, and jumping in participants with spastic diplegic CP.

Hydrogen sensing under ambient conditions using SnO2 nanowires: synergetic effect of Pd/Sn codeposition.

Semiconducting SnO2 nanowires deposited with Pd and Sn nanoparticles on their surface are shown to be a highly sensitive hydrogen sensor with fast response time at room temperature. Compared with the SnO2 nanowire deposited with Pd or Sn nanoparticles alone, the Pd/Sn-deposited SnO2 nanowire exhibits a significant improvement in the sensitivity and reversibility of sensing hydrogen gas in the air at room temperature. Our investigation indicates that two factors are responsible for the synergistic effect of Pd/Sn codeposition on SnO2 nanowires. One is that in the presence of Pd the oxidation of Sn nanoparticles on the surface of the SnO2 nanowire is incomplete leading only to suboxides SnOx (1 ≤ x < 2), and the other is that the surface of the Pd/Sn-deposited SnO2 nanowire is almost perfectly hydrophobic.

Expression and mutation analysis of TIG1 (tazarotene-induced gene 1) in human gastric cancer.

Tazarotene-induced gene 1 (TIG1) has been known to function as a cell adhesion molecule, which leads to better cell to cell contact and reduced proliferation. We investigated expression and mutation status of TIG1 in primary gastric tumors and cell lines to explore the candidacy of the gene as a tumor suppressor. A total of 172 gastric tissue specimes, including 80 primary adenocarcinomas, 12 benign tumors, and 80 adjacent normal mucosa, and 15 gastric cancer cell lines were used. TIG1 expression was analyzed by semiquantitative RT-PCR and immunoblot analysis. To screen for the presence of somatic mutations, RT-PCR-SSCP analysis was carried out. The effect of 5-aza-2'-deoxycytidine treatment was examined to elicit whether TIG1 reduction is associated with abnormal DNA hypermethylation. Compared to noncancerous tissues, a substantial reduction of TIG1 expression was observed in 73.3% (11115) cancer cell lines, and seven of these exhibited nearly undetectable levels of expression. Decreased expression of TIG1 was also found in 62 (77.5%) primary carcinoma tissues compared to adjacent noncancerous tissues, indicating a tumor-specific reduction of TIG1. Expression levels of TIG1 were significantly low in primary carcinomas and cancer cell lines compared to those of normal tissues. Moreover, loss or reduction of TIG1 was significantly high in advanced tumors compared to early tumors and more frequent in poorly differentiated tumors than well or moderately differentiated tumors. TIG1 expression was reactivated or its level was elevated following 5-aza-2'-deoxycytidine treatment, indicating that TIG1 expression is transcriptionally silenced in these cancer cells by abnormal DNA hypermethylation. These data indicate that TIG1 undergoes frequent epigenetic inactivation due to aberrant DNA hypermethylation in gastric cancers, and its altered expression is associated with the malignant progression of tumors.

Templated carbon nanofiber with mesoporosity and semiconductivity.

We have newly fabricated a long one-dimensional (1D) mesoporous carbon nanofiber by using a mesoporous silica nanofiber template. The resulting mesoporous carbon nanofiber shows the unique mesoporous structure of circularly wound nanochannel alignment perpendicular to the long fiber axis and the high gas sorption property, which interestingly presents the p-type semiconducting behavior.