Sweet Bee Venom Triggers Multiple Cell Death Pathways or Spurs Acute Cell Rupture According to Its Concentration in THP-1 Monocytic Leukemia Cells.

Sweet bee venom (sBV) contains various pharmacologically active components of bee venom (BV), but it is modified via the removal of the harmful substances found in BV. Thus, sBV has been used for pain relief in Oriental medicine but has only recently been applied for the treatment of various diseases. In this study, we examined the pharmacological effects and immunomodulatory functions of sBV in THP-1 monocytic leukemia cells. Growth inhibition and cell death were observed according to the concentration of sBV. However, the rapid collapse of cell cycle distribution was shown at 20 µg/mL sBV treatment, indicating that sBV led to cell death or acute cell rupture according to concentration. sBV administration activated Caspase-9, PARP1, RIPK1, and RIPK3, suggesting that the pharmacological actions of sBV were associated with induction of apoptosis and necroptosis. On the other hand, sBV or LPS administration increased cytokine expression, including IL-1ß, and showed synergistic cell death in combinatory treatment conditions. Moreover, combinatory administration of sBV and LPS induced severe damage or death during egg development. This result implies that sBV exhibits both pharmacological and toxic effects depending on its concentration. Therefore, sBV might be a promising therapeutic approach, but optimal concentration should be considered before treatment.

Regulatory Effect of Cannabidiol (CBD) on Decreased ß-Catenin Expression in Alopecia Models by Testosterone and PMA Treatment in Dermal Papilla Cells.

OBJECTIVES: The hair follicle is composed of more than 20 kinds of cells, and mesoderm derived dermal papilla cells and keratinocytes cooperatively contribute hair growth via Wnt/ß-catenin signaling pathway. We are to investigate ß-catenin expression and regulatory mechanism by CBD in alopecia hair tissues and dermal papilla cells. METHODS: We performed structural and anatomical analyses on alopecia patients derived hair tissues using microscopes. Pharmacological effect of CBD was evaluated by ß-catenin expression using RT-PCR and immunostaining experiment. RESULTS: Morphological deformation and loss of cell numbers in hair shaft were observed in alopecia hair tissues. IHC experiment showed that loss of ß-catenin expression was shown in inner shaft of the alopecia hair tissues, indicating that ß-catenin expression is a key regulatory function during alopecia progression. Consistently, ß-catenin expression was decreased in testosterone or PMA treated dermal papilla cells, suggesting that those treatments are referred as a model on molecular mechanism of alopecia using dermal papilla cells. RT-PCR and immunostaining experiments showed that ß-catenin expression was decreased in RNA level, as well as decreased ß-catenin protein might be resulted from ubiquitination. However, CBD treatment has no changes in gene expression including ß-catenin, but the decreased ß-catenin expression by testosterone or PMA was restored by CBD pretreatment, suggesting that potential regulatory effect on alopecia induction of testosterone and PMA. CONCLUSION: CBD might have a modulating function on alopecia caused by hormonal or excess of signaling pathway, and be a promising application for on alopecia treatment.

Knockout of FosB gene changes drug sensitivity and invasion activity via the regulation of Bcl-2, E-cadherin, ß-catenin, and vimentin expression.

Our previous research suggested the presence of a novel SETDB1-mediated FosB pathway that could be responsible for the regulation of cell proliferation and invasiveness during anticancer treatments. In this study, we prepared FosB knock-out (FosB-KO) A549 human lung cancer cells using the CRISPR/Cas9 system and examined the physiological and molecular changes that caused. Annexin V and TUNEL assays showed that FosB-KO clones were less sensitive to doxorubicin treatment compared to the control A549 cells. Bcl2 expression and mitochondrial membrane potential were also both markedly increased in FosB-KO clones, which suggests the involvement of Bcl2 in the doxorubicin mediated increase in cell viability demonstrated the FosB-KO clones. Moreover, we identified changes in the migration and transforming activities of the FosB-KO clones that coincided with changes in the expression levels of E-cadherin, ß-catenin, and Vimentin. RT-PCR and qPCR analysis showed that the expressions of Bcl2, E-cadherin, ß-catenin, and Vimentin were regulated at the transcriptional level. Importantly, FosB overexpression in FosB-KO clones restored the expression of Bcl2, Akt, E-cad, ß-catenin, and Vimentin, suggesting that those proteins were tightly regulated by FosB. These data suggest that the FosB gene critically regulates both drug sensitivity and invasion related genes, and does so in a manner coordinated with the function of SETDB1. Therefore, we propose that the FosB gene regulates both drug sensitivity and invasion activity related genes, and also shows coordinated function with SETDB1 for the regulation of target proteins.

Identification of Cleaved Haptoglobin in the Serum of Bee Venom-Hypersensitive Patients.

Background: Bee venom has been used as a therapeutic compound for various human diseases in oriental medicine; however, it can induce anaphylaxis in hypersensitive patients during treatment. Anaphylaxis is an acute allergic reaction that occurs after allergen exposure. IgE is released from immune-related cells such as mast cells and basophils during anaphylaxis. Various inflammatory mediators are also released into the bloodstream during the acute response. Objectives: We aimed to identify specific proteins from bee venom-hypersensitive patients. Methods: We analyzed the blood serum of control and bee venom-hypersensitive patients using two-dimensional (2D) electrophoresis. Results: An interesting protein spot with a molecular size of 10 kDa was identified at an isoelectric point (p.I.) of 5.5. Spots detected both before and after sweet bee venom therapy were not proteins induced by sweet bee venom. The 10 kDa protein was identified as the cleaved form of haptoglobin through liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Statistical analysis indicated that the presence of the spot was highly significant in the bee venom-hypersensitive group. Conclusion: The findings suggest that cleaved haptoglobin may be a significant diagnostic protein for anaphylaxis. In addition, a high incidence of bee venom hypersensitivity may be associated with the haptoglobin genotype.

Synthesis and Electroluminescence Property of Green Fluorescent Dopant Including Anthracene and Diphenylamine Moiety.

We have synthesized green fluorescent emitters of N9,N9,N10,N10-tetraphenylanthracene-9,10-diamine (TAD) and N9,N9,N10,N10-tetra-o-tolylanthracene-9,10-diamine (oMe-TAD) including anthracene and diphenylamine moiety and evaluated properties of compounds. The methyl groups were introduced to the diphenylamine to prevent molecular aggregation of the dopant and reduce self-quenching through steric hindrance of molecular structure. In solution state, photoluminescence (PL) maximum wavelength is 508 nm for TAD and 519 nm for oMe-TAD. In film state, PL maximum wavelength is 518 nm for TAD and 527 nm for oMe-TAD. In electroluminescence (EL) spectra, EL maximum wavelength of TAD is 508 nm and EL maximum wavelength of oMe-TAD is 522 nm. The doped device using TAD as green fluorescent dopant exhibited CE of 17.7 cd/A, PE of 7.74 lm/W, and EQE of 6.11%. The doped device using oMe-TAD as dopant exhibited CE of 19.8 cd/A, PE of 7.23 lm/W, and EQE of 5.97%.

Synthesis and Electroluminescent Properties of New Dibenzo-Diazocine Derivatives.

AK-1NA and AK-2NA based on dibenzo-diazocine and anthracene moieties were designed and synthesized. Normalized UV-visible spectra of AK-1NA and AK-2NA in film state showed maximum absorption wavelength of 394 and 393 nm. PL spectra of AK-1NA and AK-2NA showed maximum emission wavelength of 429 and 444 nm. At a current density of 10 mA/cm2, OLED devices of AK-1NA and AK-2NA exhibited luminance efficiency of 2.39 and 1.50 cd/A, power efficiency of 1.01 and 0.81 lm/W. Also, OLED devices of AK-1NA and AK-2NA devices exhibited CIE(x, y ) of (0.16, 0.22) and (0.23, 0.42).

Relationships between Pathological Patterns and Quality of Life: Pathway Analysis.

Purpose. The purpose of our study was to examine the relationships between pathological patterns and self-rated quality of life (QoL). Methods. A total of 426 Korean subjects participated in this study (male : female = 154 : 272). The subjects were asked to complete Yin Deficiency (YD), Qi Deficiency (QD), Food Stagnation (FS), Blood Stasis (BS), Phlegm, and Seven Emotions Impairment (SEI) pattern Questionnaires and the General Health Questionnaire (GHQ). We formed a pathway model consisting of pathological patterns and QoL questionnaire scores and examined which pathological patterns resulted in decreased QoL using path analysis. Results. Our pathway model had satisfactory fitness levels (GFI = 0.975, NFI = 0.984, and CFI = 0.984) and showed that Phlegm and SEI patterns directly resulted in decreased QoL, whereas QD, YD, FD, and BS indirectly resulted in decreased QoL. The pathway model suggested that the severity or stage of decreased QoL may be estimated by pathological patterns: QD and YD patterns are associated with the early stage; FS and BS patterns are associated with the middle stage; Phlegm and SEI are associated with the later stage of decreased QoL. Conclusion. Our results suggest that pathological patterns directly or indirectly affect decreases in QoL.

Effect of pre-existing oxide film on the electrochemical fabrication of nanoporous alumina film.

Different thickness of barrier-type oxide film was intentionally grown on the Al metal surface and the effect of barrier film on the formation of nanoporous aluminum oxide film during anodization was investigated to control the nanopore structure. Analysis of potential transients during anodization indicated that anodic oxide film is initially overlaid on the barrier film but the anodic film is more facile to dissolve than barrier film. As the thickness of barrier film increases, both nanopore diameter and density decrease but the pore length is irrespective of barrier-film thickness.

Electrochemical fabrication of SrTiO3 nanowires with nanoporous alumina template.

Strontium titanate nanowires were electrochemically synthesized with nanoporous alumina template. Both chemical and electrical variables such as electrolyte pH, temperature, and current waveform were modulated to investigate the synthesis process of SrTiO3 nanowires. Superimposed cathodic pulse and diffusion time accelerated the growth of SrTiO3 nanowires, which suggested that the concentration of H+ and Sr2+ ion inside alumina template had a strong influence on the formation of SrTiO3 nanowires. Morphology and crystallinity of SrTiO3 nanowires were investigated with scanning electron microscope, X-ray diffractometer and energy dispersive X-ray spectroscopy.