Combined Effects of Tanshinone IIA and an Autophagy Inhibitor on the Apoptosis of Leukemia Cells via p53, Apoptosis-Related Proteins and Oxidative Stress Pathways.

BACKGROUND: Acute myeloid leukemia (AML) is a kind of hematopoietic malignancy with limited response and acquired resistance to therapy. Inducing apoptosis and inhibiting autophagy in tumor cells is a combinational strategy for the development of anticancer therapeutics. Tanshinone IIA (TAIIA) is one of the major ingredients in Salvia miltiorrhiza, which is the most prescribed herb for the treatment of AML in Taiwan. Therefore, this study aimed to delineate the anticancer effects of TAIIA and its effect when combined with an autophagy inhibitor to treat AML. METHODS: The anticancer effects of a combination of TAIIA and the autophagy inhibitor 3-methladenine (3MA) on the human monocytic leukemia cell line THP-1 were explored. The apoptosis and cell cycle of the leukemia cells were examined by Annexin V and propidium iodide staining and analyzed by flow cytometry. The oxidative stress level was determined by a malondialdehyde (MDA) colorimetric assay, nitric oxide colorimetric assay and glutathione peroxidase (GPx) colorimetric assay. The expression of apoptosis-related proteins was determined by western blotting. RESULTS: TAIIA treatment significantly induced apoptosis via increased p53, Bax/Bcl, PARP, and caspase-3 signals and oxidative stress by enhancing MDA and nitrate/nitrite production and reducing GPx activity in THP-1 cells in a dose-dependent and time-dependent manner. The combination of the autophagy inhibitor 3MA enhanced TAIIA-induced apoptosis via the p53, Bax/Bcl, PARP, caspase-3, and oxidative stress pathways in THP-1 cells. CONCLUSION: The results suggest that TAIIA and autophagy inhibitors have combined effects on the apoptosis of leukemia cells, thus representing a novel and effective combination with the potential for application as a clinical therapy for AML.

Targeting glycolysis in Th2 cells by pterostilbene attenuates clinical severities in an asthmatic mouse model and IL-4 production in peripheral blood from asthmatic patients.

Asthma, a major non-communicable disease, affects both adults and children and is associated with high morbidity compared with other chronic diseases. The glycolysis-associated activation of type 2 helper T (Th2) cells is the critical immunopathological mechanism involved in asthma deterioration. Long-term use of steroids as a medical treatment for asthma induces side effects and resistance. Pterostilbene (PS), a stilbenoid compound found in blueberry and vines, exhibits antihyperglycemic and anti-inflammatory properties. Thus, we hypothesized that the modulation of T cell immunity by PS may be an applicable intervention to treat asthma. Airway hyperresponsiveness, interleukin (IL)-4 and IL-13 levels, IgE, IgG, pulmonary infiltrated monocytes and eosinophils, and mucosubstances were measured in house dust mite (HDM)-induced asthmatic mice under PS treatment. Bioenergetic metabolism, PI3K-mTOR signalling, GATA3 expression and histone acetylation in PS-treated Th2 cells were investigated. PS improved HDM-induced pulmonary allergic airway inflammation by inhibiting Th2 cell and eosinophil accumulation in HDM asthmatic mice both in the preventive and therapeutic models. Targeting glycolysis resulted in IL-4 inhibition via the downregulation of mTOR, GATA3 and histone acetylation in PS-treated Th2 cells. Glucose supplementation reversed the inhibitory effect of PS on Th2 cells in vitro. Adoptive transfer with glucose-treated Th2 cells enhanced Th2 activation and eosinophilic accumulation in PS-treated asthmatic mice. Furthermore, PS significantly inhibited IL-4 production of CD4+ T cells from the peripheral blood mononuclear cells of patients with asthma. PS attenuates HDM-induced asthma via the inhibition of the Glut1/mTOR/GATA3 axis in Th2 cells, which supports the potential pharmaceutical application of PS treatment for asthma.

A Standardized Extract of Asparagus officinalis Stem (ETAS®) Ameliorates Cognitive Impairment, Inhibits Amyloid ß Deposition via BACE-1 and Normalizes Circadian Rhythm Signaling via MT1 and MT2.

The prevalence of cognitive impairments and circadian disturbances increases in the elderly and Alzheimer's disease (AD) patients. This study investigated the effects of a standardized extract of Asparagus officinalis stem, ETAS® on cognitive impairments and circadian rhythm status in senescence-accelerated mice prone 8 (SAMP8). ETAS® consists of two major bioactive constituents: 5-hydroxymethyl-2-furfural (HMF), an abundant constituent, and (S)-asfural, a novel constituent, which is a derivative of HMF. Three-month-old SAMP8 male mice were divided into a control, 200 and 1000 mg/kg BW ETAS® groups, while senescence-accelerated resistant mice (SAMR1) were used as the normal control. After 12-week feeding, ETAS® significantly enhanced cognitive performance by an active avoidance test, inhibited the expressions of amyloid-beta precursor protein (APP) and BACE-1 and lowered the accumulation of amyloid ß (Aß) in the brain. ETAS® also significantly increased neuron number in the suprachiasmatic nucleus (SCN) and normalized the expressions of the melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2). In conclusion, ETAS® enhances the cognitive ability, inhibits Aß deposition and normalizes circadian rhythm signaling, suggesting it is beneficial for preventing cognitive impairments and circadian rhythm disturbances in aging.

Violet Laser Diode Enables Lighting Communication.

Violet laser diode (VLD) based white-light source with high color rendering index (CRI) for lighting communication is implemented by covering with Y3Al5O12:Ce3+ (YAG:Ce) or Lu3Al5O12:Ce3+/CaAlSiN3:Eu2+ (LuAG:Ce/CASN:Eu) phosphorous diffuser plates. After passing the beam of VLD biased at 70 mA (~2I th ) through the YAG:Ce phosphorous diffuser, a daylight with a correlated color temperature (CCT) of 5068 K and a CRI of 65 is acquired to provide a forward error correction (FEC) certified data rate of 4.4 Gbit/s. By using the VLD biased at 122 mA (~3.5I th ) to excite the LuAG:Ce/CASN:Eu phosphorous diffuser with 0.85-mm thickness, a warm white-light source with a CCT of 2700 K and a CRI of 87.9 is obtained at a cost of decreasing transmission capacity to 2.4 Gbit/s. Thinning the phosphor thickness to 0.75 mm effectively reduces the required bias current by 32 mA to achieve the same CCT for the delivered white light, which offers an enlarged CRI of 89.1 and an increased data rate of 4.4 Gbit/s. Further enlarging the bias current to 105 mA remains the white-light transmission capacity at 4.4 Gbit/s but reveals an increased CCT of 3023 K and an upgraded CRI of 91.5.

Tricolor R/G/B Laser Diode Based Eye-Safe White Lighting Communication Beyond 8 Gbit/s.

White light generation by mixing red, green, and blue laser diodes (RGB LDs) was demonstrated with Commission International de l'Eclairage coordinates of (0.2928, 0.2981), a correlated color temperature of 8382 K, and a color rendering index of 54.4 to provide a maximal illuminance of 7540 lux. All the white lights generated using RGB LDs were set within the risk group-1 criterion to avoid the blue-light hazard to human eyes. In addition, the RGB-LD mixed white light was diffused using a frosted glass to avoid optical aberration and to improve the performance of the lighting source. In addition, visible light communication (VLC) by using RGB-LD mixed white-light carriers and a point-to-point scheme over 1 m was performed in the directly modulated 16-QAM OFDM data format. In back-to-back transmission, the maximal allowable data rate at 10.8, 10.4, and 8 Gbps was determined for R, G, and B LDs, respectively. Moreover, the RGB-LD mixed white light-based indoor wavelength-division multiplexing (WDM)-VLC system yielded a total allowable transmission data rate of 8.8 Gbps over 0.5 m in free space. Such a high-speed RGB-LD mixed WDM-VLC system without any channel interference can be used to simultaneously provide data transmission and white lighting in an indoor environment.

Blue Laser Diode Enables Underwater Communication at 12.4 Gbps.

To enable high-speed underwater wireless optical communication (UWOC) in tap-water and seawater environments over long distances, a 450-nm blue GaN laser diode (LD) directly modulated by pre-leveled 16-quadrature amplitude modulation (QAM) orthogonal frequency division multiplexing (OFDM) data was employed to implement its maximal transmission capacity of up to 10 Gbps. The proposed UWOC in tap water provided a maximal allowable communication bit rate increase from 5.2 to 12.4 Gbps with the corresponding underwater transmission distance significantly reduced from 10.2 to 1.7 m, exhibiting a bit rate/distance decaying slope of -0.847 Gbps/m. When conducting the same type of UWOC in seawater, light scattering induced by impurities attenuated the blue laser power, thereby degrading the transmission with a slightly higher decay ratio of 0.941 Gbps/m. The blue LD based UWOC enables a 16-QAM OFDM bit rate of up to 7.2 Gbps for transmission in seawater more than 6.8 m.

Poly-silicon nanowire sensor for sodium chloride concentration measurement.

In this paper, the poly-Si nanowire sensor was fabricated by top-down technique for sodium chloride concentration measurement. The results showed that the smallest threshold voltage and the best resolution were 1.65 V and 0.41 µM, respectively. Furthermore, the sensor can be reused more than 50 times which maintained acceptable performance and showed good linearity of the calibration within wide range of the concentration. Based on these results, it can be concluded that the proposed sensor has great potential to be used for measuring complicated sample with suitable modification on the surface of nanowires.