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Background Although amyloid beta (Aβ) imaging is widely used for diagnosing and monitoring Alzheimer’s disease in clinical fields, paralleling comparison between 18F-flutemetamol and 18F-florbetaben was rarely attempted in AD mouse model. We performed a comparison of Aβ PET images between 18F-flutemetamol and 18F-florbetaben in a recently developed APPswe mouse model, C57BL/6-Tg (NSE-hAPPsw) Korl. Results After an injection (0.23 mCi) of 18F-flutemetamol and 18F-florbetaben at a time interval of 2–3 days, we compared group difference of SUVR and kinetic parameters between the AD (n = 7) and control (n = 7) mice, as well as between 18F-flutemetamol and 18F-florbetaben image. In addition, bio-distribution and histopathology were conducted. With visual image and VOI-based SUVR analysis, the AD group presented more prominent uptake than did the control group in both the 18F-florbetaben and 18F-flutemetamol images. With kinetic analysis, the 18F-florbetaben images showed differences in K1 and k4 between the AD and control groups, although 18F-flutemetamol images did not show significant difference. 18F-florbetaben images showed more prominent cortical uptake and matched well to the thioflavin S staining images than did the 18F-flutemetamol image. In contrast, 18F-flutemetamol images presented higher K1, k4, K1/k2 values than those of 18F-florbetaben images. Also, 18F-flutemetamol images presented prominent uptake in the bowel and bladder, consistent with higher bio-distribution in kidney, lung, blood and heart. Conclusions Compared with 18F-flutemetamol images, 18F-florbetaben images showed prominent visual uptake intensity, SUVR, and higher correlations with the pathology. In contrast, 18F-flutemetamol was more actively metabolized than was 18F-florbetaben (Son et al. in J Nucl Med 58(Suppl 1):S278, 2017].

Spleen traps malaria-infected red blood cells, thereby leading to splenomegaly. Splenomegaly induces impairment in splenic function, i.e., rupture. Therefore, splenomegaly inhibition is required to protect the spleen. In our previous study, genistein was found to have an influence on malaria-induced splenomegaly. However, the effect of genistein in malaria-induced splenomegaly, especially on the function of spleen, has not been fully investigated. In this study, hematoxylin and eosin (H&E) staining images show that genistein partially prevents malaria-induced architectural disruption of spleen. In addition, genistein decreases transgenic Plasmodium parasites accumulation in the spleen. Genistein treatment can protect splenic function from impairment caused by malaria infection. To examine the functions of malaria-infected spleen, we employed single-photon emission computed tomography/computed tomography (SPECT/CT) technology. Red blood cells are specifically radiolabeled with Technetium-99m pertechnetate (99mTcO4-) and trapped inside the spleen. The standardized uptake values (SUVs) in the spleen of infected mice are higher than those of naive and genistein-treated mice. However, genistein reduces the malaria-induced trapping capacity of spleen for heat-damaged radiolabeled RBCs, while exhibiting a protective effect against malaria. Considering these results, we suggested that genistein could be effectively used in combination therapy for malaria-induced splenic impairment.

A polymer-based coronary drug-eluting stent might induce inflammation and stent thrombosis of the vessel wall due to the presence of the polymer. Therefore, the purpose of this study was to compare synthetic poly lactic–glycolic acid (PLGA)-based tacrolimus (TCL)-eluting stents (PLGA-TES) and polymer-free TCL-eluting stents (PF-TES) in in vitro and in vivo models. The PF-TES was deposited with a TiO2 thin film onto a bare metal stent (BMS) using plasma-enhanced chemical vapor deposition (PECVD). The surface morphologies of the stents were investigated by scanning electron microscopy and energy dispersive X-ray spectroscopy methods. The effect of the drugs released from the stents on smooth muscle cell (SMC) proliferation and platelet adhesion were examined. Animal studies were performed with four study groups; 1) BMS, 2) N-TiO2, 3) PLGA-TES, and 4) PF-TES. Further, after 4 weeks of implantation, the vessels surrounding the stents were isolated and then subjected to various analyses. In this study, the stent was deposited with a very thin and uniform TiO2 film. The platelet adhesion on the TiO2 surfaces was less than that on the BMS surface. The drug was uniformly coated on the stent surface with a concentration of 1.184 μg/mm2. SMC proliferation was significantly inhibited in the TCL-eluting stent group (62.8 %, 42.3 %, n = 7, p

Background Although amyloid beta (Aβ) imaging is widely used for diagnosing and monitoring Alzheimer’s disease in clinical fields, paralleling comparison between 18F-flutemetamol and 18F-florbetaben was rarely attempted in AD mouse model. We performed a comparison of Aβ PET images between 18F-flutemetamol and 18F-florbetaben in a recently developed APPswe mouse model, C57BL/6-Tg (NSE-hAPPsw) Korl. Results After an injection (0.23 mCi) of 18F-flutemetamol and 18F-florbetaben at a time interval of 2–3 days, we compared group difference of SUVR and kinetic parameters between the AD (n = 7) and control (n = 7) mice, as well as between 18F-flutemetamol and 18F-florbetaben image. In addition, bio-distribution and histopathology were conducted. With visual image and VOI-based SUVR analysis, the AD group presented more prominent uptake than did the control group in both the 18F-florbetaben and 18F-flutemetamol images. With kinetic analysis, the 18F-florbetaben images showed differences in K1 and k4 between the AD and control groups, although 18F-flutemetamol images did not show significant difference. 18F-florbetaben images showed more prominent cortical uptake and matched well to the thioflavin S staining images than did the 18F-flutemetamol image. In contrast, 18F-flutemetamol images presented higher K1, k4, K1/k2 values than those of 18F-florbetaben images. Also, 18F-flutemetamol images presented prominent uptake in the bowel and bladder, consistent with higher bio-distribution in kidney, lung, blood and heart. Conclusions Compared with 18F-flutemetamol images, 18F-florbetaben images showed prominent visual uptake intensity, SUVR, and higher correlations with the pathology. In contrast, 18F-flutemetamol was more actively metabolized than was 18F-florbetaben (Son et al. in J Nucl Med 58(Suppl 1):S278, 2017]. Electronic supplementary material The online version of this article (10.1186/s12868-018-0447-7) contains supplementary material, which is available to authorized users.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the abnormal accumulation of β-amyloid (Aβ). Multiple Aβ-aggregated species have been identified, and neurotoxicity appears to be correlated with the amount of non-fibrillar oligomers. Potent inhibitors of Aβ oligomer formation or Aβ-induced cell toxicity have emerged as attractive means of therapeutic intervention. Eremochloa ophiuroide Hack. (Poaceae), also known as centipedegrass (CG), originates from China and South America and is reported to contain several C-glycosyl flavones and phenolic constituents.We investigated whether CG could suppress Aβ aggregation, BACE1 activity, and toxicity at neuronal cell.The inhibitory effect of CG extracts toward aggregation of Aβ42 was investigated in the absence and presence of 50 µg/mL CG. We investigated the inhibitory effects of CG (0-5 µg/mL) on BACE1 using fluorescence resonance energy transfer (FRET)-based assay. The effects of CG (0-75 µg/mL) on Aβ42-induced neurotoxicity were examined in PC12 cells in the presence or absence of maysin and its derivatives of CG.We isolated EA-CG fraction (70% MeOH fraction from EtOAc extracts) from methanol extracts of CG, which contained approximately 60% maysin and its derivatives. In the present studies, we found that several Aβ oligomeric forms such as the monomer, dimer, trimer, and highly aggregated oligomeric forms were remarkably inhibited in the presence of 50 µg/mL of EA-CG. EA-CG also inhibited BACE1 enzyme activity in a dose-dependent manner. EA-CG treatment generated approximately 50% or 85% inhibition to the control at the tested concentrations of 1 or 5 µg/mL, respectively. Moreover, the neurotoxicity induced by Aβ42 was significantly reduced by treatment of EA-CG, and the 75 µg/mL EA-CG treatment significantly increased cell viability up to 82.5%.These results suggested that the anti-Alzheimer's effects of CG occurred through inhibition of neuronal cell death by intervening with oligomeric Aβ formation and reducing BACE1 activity. Maysin in CG could be an excellent therapeutic candidate for the prevention of AD.

The neurotransmitter dopamine (DA) regulates various physiological and psychological functions, such as movement, motivation, behavior, and learning. DA exerts its function through DA receptors and a series of studies have reported the role of DAergic receptors in preventing DAergic neuronal degeneration. Here, we studied the DA receptor-mediated neuroprotective effect of the D2-like receptor agonists against 6-hydroxydopamine (6-OHDA)-induced DAergic neurodegeneration. D2-like receptor agonists were administered in the substantia nigra in vivo and to primary cultured neurons. Treatment of 6-OHDA decreased tyrosine hydroxylase (TH) and paraplegin (mitochondrial regulation protein) immunoreactivity, whereas pretreatment with quinpirole (a full D2-like receptor agonist) preserved TH and paraplegin reactivity. This led us to test which DA receptors were necessary for the neuroprotective effect and whether paraplegin can be regulated by D2 or D3 receptor agonists. Pretreatment with the D2 receptor selective agonist, sumanirole, did not preserve TH and paraplegin reactivity from 6-OHDA. However, the D3 receptor agonist, pramipexole, protected TH reactivity and restored paraplegin expression to the control level in the presence of 6-OHDA. Interestingly, pretreatment with the D3 receptor antagonist GR103691 reduced TH and paraplegin expression levels. These results suggest that the D3 receptor agonist may protect DA neurons from the effect of 6-OHDA through the modulation of the mitochondrial regulation protein paraplegin.

Grifola frondosa (GF), distributed widely in far east Asia including Korea, is popularly used as traditional medicines and health supplementary foods, especially for enhancing the immune functions of the body. To extend the application of GF polysaccharides (GFP) for atopic dermatitis (AD), we investigated the effects of GFP on the 2,4-dinitrochlorobenzene-induced AD-like skin lesion in NC/Nga mice. GFP treatment significantly reduced the dorsa skin dermatitis score and combination treatment with GFP, and dexamethasone has a synergistic effect in AD-like skin lesion by reduced Serum IgE, mast cells infiltration, and cytokines expression. These results indicate that GFP suppressed the AD-like skin lesions by controlling the Th-1/Th-2-type cytokines in NC/Nga mice. These findings strongly suggest that GFP can be useful for AD patients as a novel therapeutic agent and might be used for corticosteroids replacement or supplement agent.

Hesperidin, a natural flavonoid abundantly present in Citrus is known for its anti-cancer, anti-oxidant and anti-inflammatory properties. In this study we examined the effect of hesperidin on HepG2 cells. HepG2 cells treated with various concentration of hesperidin undergo a distinct type of programed cell death. Cytoplasmic vacuolization, mitochondria and endoplasmic reticulum swelling and uncondensed chromatin were observed in hesperidin treated cells. DNA electrophoresis show lack of DNA fragmentation and western blot analysis demonstrates lack of caspase activation and PARP cleavage. It was observed that hesperidin induced cell death is nonautophagic and also activate mitogen activated protein kinase ERK1/2. Taken together, the data indicate that hesperidin induces paraptosis like cell death in HepG2 cells with the activation of ERK1/2. Thus our finding suggests that hesperidin inducing paraptosis may offer an alternative tool in human liver carcinoma therapy.

Unlike most other mammals, human bodies do not have the ability to synthesize vitamin C inside of their own bodies. Therefore, humans must obtain vitamin C through daily diet. Gulo(-/-) mice strain is known with deficiency, in which vitamin C intake can be controlled by diet like human, and would be valuable for investigating the molecular mechanism of various diseases. In the present study, we established Gulo(-/-) mice model and investigated the differentially expressed proteins in stomach tissue of Gulo(-)(/-) mice after Helicobacter pylori-infected, and followed by DENA, using immunohistochemistry and proteomic approach. The results of immunohistochemistry analysis of stomach tissue showed that the tumor suppressor, p53 protein, expression was significantly decreased (p0.05) but not messenger RNA (mRNA) transcriptional level, and 14-3-3 ε, 14-3-3 δ, Ki-67 and cleaved caspase 3 expressions were significantly increased (p0.05) by H. Pylori infection, and followed by DENA treatment in Gulo(-/-) mice. Moreover, knockdown of 14-3-3 isoforms (14-3-3 ε, 14-3-3 σ, 14-3-3 ζ and 14-3-3 η) were significantly increased sub-G1 phase (characteristics of apoptosis) in AGS cells and, phenotypic changes like cell shrinkage, density and cleaved nuclei were also observed. Proteome analyses showed that 14-3-3 σ, 14-3-3 η, and tropomyosin alpha-1 chain were down-regulated, and Hspd1 protein and HSC70 were up-regulated after H. Pylori-infection, and followed by DENA. The combined results of immunohistochemistry and proteomic analysis suggest that H. pylori altered the p53 and 14-3-3 isoforms expression and DENA further enhanced the H. pylori effect, which might be involved in carcinogenesis and metastasis of gastric cancer on Gulo(-/-) mice.