Drosophila tweety facilitates autophagy to regulate mitochondrial homeostasis and bioenergetics in Glia.

Mitochondria support the energetic demands of the cells. Autophagic turnover of mitochondria serves as a critical pathway for mitochondrial homeostasis. It is unclear how bioenergetics and autophagy are functionally connected. Here, we identify an endolysosomal membrane protein that facilitates autophagy to regulate ATP production in glia. We determined that Drosophila tweety (tty) is highly expressed in glia and localized to endolysosomes. Diminished fusion between autophagosomes and endolysosomes in tty-deficient glia was rescued by expressing the human Tweety Homolog 1 (TTYH1). Loss of tty in glia attenuated mitochondrial turnover, elevated mitochondrial oxidative stress, and impaired locomotor functions. The cellular and organismal defects were partially reversed by antioxidant treatment. We performed live-cell imaging of genetically encoded metabolite sensors to determine the impact of tty and autophagy deficiencies on glial bioenergetics. We found that tty-deficient glia exhibited reduced mitochondrial pyruvate consumption accompanied by a shift toward glycolysis for ATP production. Likewise, genetic inhibition of autophagy in glia resulted in a similar glycolytic shift in bioenergetics. Furthermore, the survival of mutant flies became more sensitive to starvation, underlining the significance of tty in the crosstalk between autophagy and bioenergetics. Together, our findings uncover the role for tty in mitochondrial homeostasis via facilitating autophagy, which determines bioenergetic balance in glia.

Lycium barbarum extract promotes M2 polarization and reduces oligomeric amyloid-ß-induced inflammatory reactions in microglial cells.

Lycium barbarum (LB) is a traditional Chinese medicine that has been demonstrated to exhibit a wide variety of biological functions, such as antioxidation, neuroprotection, and immune modulation. One of the main mechanisms of Alzheimer's disease is that microglia activated by amyloid beta (Aß) transform from the resting state to an M1 state and release pro-inflammatory cytokines to the surrounding environment. In the present study, immortalized microglial cells were pretreated with L. barbarum extract for 1 hour and then treated with oligomeric Aß for 23 hours. The results showed that LB extract significantly increased the survival of oligomeric Aß-induced microglial cells, downregulated the expression of M1 pro-inflammatory markers (inducible nitric oxide synthase, tumor necrosis factor α, interleukin-6, and interleukin-1ß), and upregulated the expression of M2 anti-inflammatory markers (arginase-1, chitinase-like protein 3, and interleukin-4). LB extract also inhibited the oligomeric Aß-induced secretion of tumor necrosis factor α, interleukin-6, and interleukin-1ß in microglial cells. The results of in vitro cytological experiments suggest that, in microglial cells, LB extract can inhibit oligomeric Aß-induced M1 polarization and concomitant inflammatory reactions, and promote M2 polarization.

Functional but Inefficient Kinesthetic Motor Imagery in Adolescents with Autism Spectrum Disorder.

Whether action representation in individuals with autism spectrum disorder (ASD) is deficient remains controversial, as previous studies of action observation or imitation report conflicting results. Here we investigated the characteristics of action representation in adolescents with ASD through motor imagery (MI) using a hand rotation and an object rotation task. Comparable with the typically-developing group, the individuals with ASD were able to spontaneously use kinesthetic MI to perform the hand rotation task, as manifested by the significant biomechanical effects. However, the ASD group performed significantly slower only in the hand rotation task, but not in the object rotation task. The findings suggest that the adolescents with ASD showed inefficient but functional kinesthetic MI, implicating that their action representation might be preserved.

A Combination of Boron Nitride Nanotubes and Cellulose Nanofibers for the Preparation of a Nanocomposite with High Thermal Conductivity.

With the current development of modern electronics toward miniaturization, high-degree integration and multifunctionalization, considerable heat is accumulated, which results in the thermal failure or even explosion of modern electronics. The thermal conductivity of materials has thus attracted much attention in modern electronics. Although polymer composites with enhanced thermal conductivity are expected to address this issue, achieving higher thermal conductivity (above 10 W m-1 K-1) at filler loadings below 50.0 wt % remains challenging. Here, we report a nanocomposite consisting of boron nitride nanotubes and cellulose nanofibers that exhibits high thermal conductivity (21.39 W m-1 K-1) at 25.0 wt % boron nitride nanotubes. Such high thermal conductivity is attributed to the high intrinsic thermal conductivity of boron nitride nanotubes and cellulose nanofibers, the one-dimensional structure of boron nitride nanotubes, and the reduced interfacial thermal resistance due to the strong interaction between the boron nitride nanotubes and cellulose nanofibers. Using the as-prepared nanocomposite as a flexible printed circuit board, we demonstrate its potential usefulness in electronic device-cooling applications. This thermally conductive nanocomposite has promising applications in thermal interface materials, printed circuit boards or organic substrates in electronics and could supplement conventional polymer-based materials.

Nanocrystalline calcium sulfate/hydroxyapatite biphasic compound as a TGF-ß1/VEGF reservoir for vital pulp therapy.

OBJECTIVES: Vital pulp therapy aims to treat reversible pulpal injuries via protective dentinogenesis and to preserve more tooth structure. Mineral trioxide aggregate (MTA)-based capping materials demonstrate prolonged setting time increases the risk of pulpal infection during multi-visit treatment. Their non-degradable property occupies pulp space and limits dentin-pulp regeneration. This study reports an inorganic degradable biomaterial that presents a short initial setting time and acts as a growth factor reservoir to promote reparative dentinogenesis. METHODS: We synthesize nanocrystalline calcium sulfate hemihydrate (nCS), hydroxyapatite (HAp) and calcium sulfate hemihydrate (CS) as a reservoir to which transforming growth factor-beta 1 (TGF-ß1) and vascular endothelial growth factor (VEGF) are added (denoted as nCS/HAp/CS/TGF-ß1/VEGF). In vitro biocompatibility and mineralization (the activity and expression of alkaline phosphatase, ALP) were evaluated. Rat animal model was created to test in vivo efficacy. RESULTS: Cultured human dental pulp cells (HDPCs) showed that nCS/HAp/CS/TGF-ß1/VEGF cement has excellent biocompatibility and the potential to elevate the activity and expression of ALP. The in vivo efficacy (rat animal model) indicates protective dentin by micro-computed tomography (µ-CT) measurements and histological analyses. The 3D µ-CT non-destructive analysis also determines volume changes during pulpotomy, suggesting that the degraded space of the nCS/HAp/CS/TGF-ß1/VEGF cement is repaired by the formation of dentin-pulp tissue. SIGNIFICANCE: These findings demonstrate that nCS/HAp/CS cement acts as a potent reservoir for the sustained release of growth factors, and that nCS/HAp/CS/TGF-ß1/VEGF cement has a high potential to form the reparative dentinogenesis in vivo.

Mosquitocidal and Oviposition Repellent Activities of the Extracts of Seaweed Bryopsis pennata on Aedes aegypti and Aedes albopictus.

The ever-increasing threat from infectious diseases and the development of insecticide resistance in mosquito populations drive the global search for new natural insecticides. The aims of this study were to evaluate the mosquitocidal activity of the extracts of seaweed Bryopsis pennata against dengue vectors Aedes aegypti and Aedes albopictus, and determine the seaweed's toxic effect on brine shrimp nauplii (as a non-target organism). In addition, the chemical compositions of the active larvicidal extract and fraction were analyzed by using liquid chromatography-mass spectrometry (LC-MS). Chloroform extract exhibited strong ovicidal activity (with LC50 values of 229.3 and 250.5 µg/mL) and larvicidal activity against Ae. aegypti and Ae. albopictus. The larvicidal potential of chloroform extract was further ascertained when its A7 fraction exhibited strong toxic effect against Ae. aegypti (LC50 = 4.7 µg/mL) and Ae. albopictus (LC50 = 5.3 µg/mL). LC-MS analysis of the chloroform extract gave a tentative identification of 13 compounds; Bis-(3-oxoundecyl) tetrasulfide was identified as the major compound in A7 fraction. Methanol extract showed strong repellent effect against female oviposition, along with weak adulticidal activity against mosquito and weak toxicity against brine shrimp nauplii. The mosquitocidal results of B. pennata suggest further investigation for the development of effective insecticide.

Engaging traditional medicine providers in colorectal cancer screening education in a chinese american community: a pilot study.

INTRODUCTION: Although colorectal cancer (CRC) screening is effective in preventing colon cancer, it remains underused by Asian Americans. Because Chinese Americans often use traditional Chinese medicine (TCM), we conducted a pilot study to explore the feasibility and acceptability of having TCM providers deliver education about CRC screening. METHODS: Four TCM providers (2 herbalists and 2 acupuncturists) were trained to deliver small-group educational sessions to promote CRC screening. Each provider recruited 15 participants aged 50 to 75. Participants completed a baseline survey on CRC-related knowledge, attitudes, and behaviors and then attended one 2-hour educational session delivered by the providers in Cantonese or Mandarin. Three months later, participants completed a postintervention survey. RESULTS: Sixty participants were recruited from the San Francisco Chinatown neighborhood. The average age was 62.4 years. Most participants had limited English proficiency (96.7%), annual household income less than $20,000 per year (60%), and low educational attainment (65.1% < high school education). At postintervention (n = 57), significant increases were found in having heard of CRC (from 52.6% to 79.0%, P < .001) and colon polyps (from 64.9% to 84.2%, P < .001). Knowledge regarding screening frequency recommendations also increased significantly. The rate of ever having received any CRC screening test increased from 71.9% to 82.5% (P <.001). The rate of up-to-date screening increased from 70.2% to 79.0% (P = .04). CONCLUSION: The findings suggest that TCM providers can be trained to deliver culturally and linguistically appropriate outreach on CRC screening within their community. Participants reached by TCM providers increased CRC knowledge and self-reported CRC screening.

Understanding and use of nicotine replacement therapy and nonpharmacologic smoking cessation strategies among Chinese and Vietnamese smokers and their families.

INTRODUCTION: Population-based studies have reported high rates of smoking prevalence among Chinese and Vietnamese American men. Although nicotine replacement therapy (NRT) is effective, recommended, and accessible without prescription, these populations underuse NRT for smoking cessation. The aim of this study was to assess understanding and use of NRT and nonpharmacologic treatments among Chinese and Vietnamese American male smokers and their families. METHODS: In-depth qualitative interviews were conducted with 13 smoker-family pairs, followed by individual interviews with each participant. A total of 39 interviews were conducted in Vietnamese or Chinese, recorded, translated, and transcribed into English for analysis. RESULTS: Four themes were identified: use and understanding of NRT, nonpharmacologic strategies, familial and religious approaches, and willpower. Both smokers and their family members believed strongly in willpower and a sense of personal responsibility as the primary drivers for stopping smoking. Lack of these 2 qualities keeps many Chinese and Vietnamese men from using NRT to quit smoking. Those who do use NRT often use it incorrectly, following their own preferences rather than product instructions. CONCLUSION: Our findings indicate the importance of culturally appropriate patient education about NRT. It may be necessary to teach smokers and their families at an individual level about NRT as a complementary approach that can strengthen their resolve to quit smoking. At a community level, public health education on the indication and appropriate use of evidence-based smoking cessation resources, such as NRT, would be an important component of effective tobacco control.

Exploring a Culturally Relevant Model of Cancer Prevention Involving Traditional Chinese Medicine Providers in a Chinese American Community.

INTRODUCTION: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in all racial and ethnic groups. Although CRC screening is very cost-effective, screening rates are low among most ethnic groups, including Asian Americans. Given the high use of traditional Chinese medicine (TCM) among Chinese Americans one potentially useful approach to promote CRC screening in these communities could involve TCM providers in outreach efforts. METHODS: A two-phase study was conducted. The perceived suitability of TCM providers in CRC prevention was explored in Phase 1. Guided by Phase 1 findings, in Phase 2, a 38-page integrative educational flipchart was developed and tested. Focus groups and observations were conducted with TCM providers (acupuncturists and herbalists) and with limited English proficient Chinese American immigrants living in San Francisco, California. RESULTS: In Phase 1, the role of TCM providers as CRC screening educators was deemed acceptable by both providers and community members, although some providers had reservations about engaging in CRC outreach activities due to lack of expertise. The majority of providers were not aware of regular CRC screening as a preventive measure, and most were not up-to-date in their own screening. In Phase 2, the integrative CRC education flipchart was perceived as culturally appropriate based on stakeholder input and feedback. CONCLUSION: This study shows that TCM providers have the potential to be a valuable and culturally appropriate community resource for providing information on CRC screening. It suggests a potential role for traditional healers as change agents in the immigrant community health network.

The analgesic effect of thermal therapy after total knee arthroplasty.

OBJECTIVES: Pain induced by surgery is a dynamic symptom, which may be quite variable even in the same surgical procedures. The purpose of this study was to investigate the analgesic effect of far infrared rays on the patients during the postoperative period of total knee arthroplasty (TKA). The selection and application of analgesic methods after the orthopedic surgery are therefore valuable for advanced studies. DESIGN: The quasi-experimental design with a total five consecutive days of far infrared ray (FIR) thermal therapy was employed in this study. SUBJECTS: The study involved 41 participants assigned by register code entry on computer to either the intervention or the control group. INTERVENTION: The FIR pads were applied on the acupoints of ST37 (Shang Chu Hsu), ST38 (Tiao Kou), ST39 (Hsia Chu Hsu), and ST40 (Feng Lung) of the patients involved in the experimental group from the third day to the fifth day after the TKA. OUTCOME MEASURES: The analgesic effect was evaluated via the pain intensity of the numeric rating scale (NRS) level and serum concentration of interleukin-6 (IL-6) and endothelin-1 (ET-1). RESULTS: The FIR showed that the significant effects are on relieving pain and lowering the levels of IL-6 and ET-1. The results cannot only be the reference for the postoperative pain relief of TKA, but it can also be the database of another clinical application. CONCLUSIONS: This study demonstrated that the FIR can lower the NRS of pain and thus reduce the discomfort experienced by the patient. Findings indicated that effective application of FIR decreased the serum level of IL-6 and ET-1, which represent the subjective indicator of pain.

[Synergistic antileukemic effect of phytoestrogens and chemotherapeutic drugs on leukemic cell lines in vitro].

Natural phytoestrogens such as the isoflavones genistein and daidzein, and the flavones quercetin exhibit anti-cancer properties. This study was purpose to investigate the anti-proliferative effect of phytoestrogens on acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) cells, and their synergistic antileukemic effect in combination with chemotherapeutic drugs. Optimal dosage of genistein, quercetin and in combination with chemicals for leukemia cells were determined by experiments. Cell viability, apoptosis induction and cell cycle arrest were detected by trypan blue staining, MTT assay, optical microscopy, flow cytometry (FCM). The schedule treatment of combination of genistein and chemicals was determined. The results showed that genistein exhibited a dose- and time-dependent inhibitory effect on cell proliferation in NB4 and HL-60 cells, induced apoptosis and cell cycle arrest in G2/M phase. Quercetin had evident inhibitory effect on the proliferation of K562 and K562/A cells. The combination of genistein and chemicals exerted a synergistic effect on cell growth inhibition. In conclusion, this study demonstrated the synergistic antileukemic effect of genistein with chemotherapeutic drugs on leukemic cells. This combination appears to be a new idea for the clinical novel treatment of leukemia.

Improved tumor vascular function following high-dose epidermal growth factor receptor tyrosine kinase inhibitor therapy.

PURPOSE: To determine if inhibitors of the human growth factor receptor (HER) family can be used to enhance tumor vascular permeability and perfusion and optimize the efficacy of cytotoxic chemotherapeutics. Poor tumor vascular function limits the delivery and efficacy of cancer chemotherapeutics and HER family tyrosine kinases mediate tumor-endothelial signaling in both of these compartments. MATERIALS AND METHODS: BT474 human breast cancer tumors were established in mice and the biologic effects of the HER tyrosine kinase inhibitor (TKI) gefitinib on tumor vascular function was determined by dynamic contrast-enhanced MRI (DCE-MRI), and on tumor vascular architecture and perfusion by immunofluorescence microscopy. RESULTS: A brief dose of gefitinib enhances the antitumor activity of paclitaxel in vivo but not in cell culture, suggesting that its chemoenhancing activity involves the in vivo microenvironment. A brief high dose of gefitinib induces a decrease in endothelial transfer constant (Kps) and a concomitant increase in tumor fractional plasma volume (fPV). These changes are accompanied by a rapid reduction in tumor volume, likely due to decreased tumor edema, and modestly improved tumor vascular architecture and perfusion on microscopy. CONCLUSION: These data suggest that HER family TKIs have the potential to optimize the tumor microenvironment for delivery of cytotoxic chemotherapeutics.