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Circumsporozoite protein suppresses the IFN-gamma-mediated killing of Plasmodium liver stage through enhanced autophagy related proteins ubiquitination [Meeting Abstract]

Zheng, H; Lu, X; Li, K; Zhu, F; Liu, T; Ding, Y; Fu, Y; Zhang, K; Rodriguez, A; Dai, J; Wu, Y; Xu, W
Malaria is still one of the most devastating diseases worldwide, which is caused by infection of the genus Plasmodium. Liver stage is an essential early step of malaria parasite infection, and plasmodium replicates in parasitophorous vacuole (PV) of hepatocytes at this stage. Although encountering with hepatocyte autonomous immunity, exoerythrocytic forms (EEFs) in PV can still survive and successfully complete infection of hepatocytes. The underlying mechanism is largely unknown. Here, we show that sporozoite circumsporozoite protein (CSP) translocates from the parasitophorous vacuole into the hepatocyte cytoplasm to significantly inhibit the killing of exoerythrocytic forms (EEFs) by interferon-gamma (IFN-gamma). Nitric oxide were found to be indispensable for the resistance to IFN-gamma-mediated killing of EEFs by CSP. Attenuation of the IFN-gamma-mediated killing of EEFs by CSP is dependent on its ability to reduce the levels of ATGs in hepatocytes. The ATGs downregulation occurs through its enhanced ubiquitination mediated by E3 ligase NEDD4, an enzyme that is upregulated by CSP when it translocates from the cytoplasm into the nucleus of hepatocytes via its NLS domain. Thus, we have revealed an unrecognized role of CSP in suppressing host autonomous immunity, and shed new light for a prophylaxis strategy against liver-stage infection
ISSN: 1521-4141
CID: 4414712

Released fibroblast growth factor18 from a collagen membrane induces osteoblastic activity involved with downregulation of miR-133a and miR-135a

Imamura, Kentaro; Tachi, Keita; Takayama, Tadahiro; Shohara, Ryutaro; Kasai, Hironori; Dai, Jisen; Yamano, Seiichi
We have developed a unique delivery system of growth factors using collagen membranes (CMs) to induce bone regeneration. We hypothesized that fibroblast growth factor18 (FGF-18), a pleiotropic protein that stimulates proliferation in several tissues, can be a good candidate to use our delivery system for bone regeneration. Cell viability, cell proliferation, alkaline phosphatase activity, mineralization, and marker gene expression of osteoblastic differentiation were evaluated after mouse preosteoblasts were cultured with a CM containing FGF-18, a CM containing platelet-derived growth factor, or a CM alone. Furthermore, expression of microRNA, especially miR-133a and miR-135a involving inhibition of osteogenic factors, was measured in preosteoblasts with CM/FGF-18 or CM alone. A sustained release of FGF-18 from the CM was observed over 21 days. CM/FGF-18 significantly promoted cell proliferation, alkaline phosphatase activity, and mineralization compared to CM alone. Gene expression of type I collagen, runt-related transcription factor 2, osteocalcin, Smad5, and osteopontin was significantly upregulated in CM/FGF-18 compared to CM alone, and similar to CM/platelet-derived growth factor. Additionally, CM/FGF-18 downregulated expression of miR-133a and miR-135a. These results suggested that released FGF-18 from a CM promotes osteoblastic activity involved with downregulation of miR-133a and miR-135a.
PMID: 29544382
ISSN: 1530-8022
CID: 2994272

Dielectric enhanced dipoles for MRI - Approaching the ideal current pattern

Chapter by: Brink, W. M.; Paska, J.; Dai, J.; Van Gemert, J. H.F.; Chen, G.; Wiggins, G. C.; Remis, R. F.; Collins, C. M.; Webb, A. G.
in: Proceedings of the 2017 19th International Conference on Electromagnetics in Advanced Applications, ICEAA 2017 by
[S.l.] : Institute of Electrical and Electronics Engineers Inc., 2017
pp. 1220-1223
ISBN: 9781509044511
CID: 2919822

The potential of stromal cell-derived factor-1 delivery using a collagen membrane for bone regeneration

Takayama, Tadahiro; Dai, Jisen; Tachi, Keita; Shohara, Ryutaro; Kasai, Hironori; Imamura, Kentaro; Yamano, Seiichi
Stromal cell-derived factor-1 (SDF-1) is a cytokine that is important in stem and progenitor cell recruitment in tissue repair after injury. Regenerative procedures using collagen membranes (CMs) are presently well established in periodontal and implant dentistry. The objective of this study is to test the subsequent effects of the released SDF-1 from a CM on bone regeneration compared to platelet-derived growth factor (PDGF) in vitro and in vivo. For in vitro studies, cell proliferation, alkaline phosphatase activity, and osteoblastic differentiation marker genes were assessed after MC3T3-E1 mouse preosteoblasts were cultured with CMs containing factors. In vivo effects were investigated by placement of CMs containing SDF-1 or PDGF using a rat mandibular bone defect model. At 4 weeks after the surgery, the new bone formation was measured using micro-computed tomography (microCT) and histological analysis. The results of in vitro studies revealed that CM delivery of SDF-1 significantly induced cell proliferation, ALP activity, and gene expression of all osteogenic markers compared to the CM alone or control, similar to PDGF. Quantitative and qualitative microCT analysis for volume of new bone formation and the percentage of new bone area showed that SDF-1-treated groups significantly increased and accelerated bone regeneration compared to control and CM alone. The enhancement of bone formation in SDF-1-treated animals was dose-dependent and with levels similar to those measured with PDGF. These results suggest that a CM with SDF-1 may be a great candidate for growth factor delivery that could be a substitute for PDGF in clinical procedures where bone regeneration is necessary.
PMID: 28056602
ISSN: 1530-8022
CID: 2386812

Ex vivo nonviral gene delivery of mu-opioid receptor to attenuate cancer-induced pain

Yamano, Seiichi; Viet, Chi T; Dang, Dongmin; Dai, Jisen; Hanatani, Shigeru; Takayama, Tadahiro; Kasai, Hironori; Imamura, Kentaro; Campbell, Ron; Ye, Yi; Dolan, John C; Kwon, William Myung; Schneider, Stefan D; Schmidt, Brian L
Virus-mediated gene delivery shows promise for the treatment of chronic pain. However, viral vectors have cytotoxicity. To avoid toxicities and limitations of virus-mediated gene delivery, we developed a novel nonviral hybrid vector: HIV-1 Tat peptide sequence modified with histidine and cysteine residues combined with a cationic lipid. The vector has high transfection efficiency with little cytotoxicity in cancer cell lines including HSC-3 (human tongue squamous cell carcinoma) and exhibits differential expression in HSC-3 ( approximately 45-fold) relative to HGF-1 (human gingival fibroblasts) cells. We used the nonviral vector to transfect cancer with OPRM1, the mu-opioid receptor gene, as a novel method for treating cancer-induced pain. After HSC-3 cells were transfected with OPRM1, a cancer mouse model was created by inoculating the transfected HSC-3 cells into the hind paw or tongue of athymic mice to determine the analgesic potential of OPRM1 transfection. Mice with HSC-3 tumors expressing OPRM1 demonstrated significant antinociception compared with control mice. The effect was reversible with local naloxone administration. We quantified beta-endorphin secretion from HSC-3 cells and showed that HSC-3 cells transfected with OPRM1 secreted significantly more beta-endorphin than control HSC-3 cells. These findings indicate that nonviral delivery of the OPRM1 gene targeted to the cancer microenvironment has an analgesic effect in a preclinical cancer model, and nonviral gene delivery is a potential treatment for cancer pain.
PMID: 28092646
ISSN: 1872-6623
CID: 2412132

Gene delivery from supercharged coiled-coil protein and cationic lipid hybrid complex

More, Haresh T; Frezzo, Joseph A; Dai, Jisen; Yamano, Seiichi; Montclare, Jin K
A lipoproteoplex comprised of an engineered supercharged coiled-coil protein (CSP) bearing multiple arginines and the cationic lipid formulation FuGENE HD (FG) was developed for effective condensation and delivery of nucleic acids. The CSP was able to maintain helical structure and self-assembly properties while exhibiting binding to plasmid DNA. The ternary CSP.DNA(8:1).FG lipoproteoplex complex demonstrated enhanced transfection of beta-galactosidase DNA into MC3T3-E1 mouse preosteoblasts. The lipoproteoplexes showed significant increases in transfection efficiency when compared to conventional FG and an mTat.FG lipopolyplex with a 6- and 2.5-fold increase in transfection, respectively. The CSP.DNA(8:1).FG lipoproteoplex assembled into spherical particles with a net positive surface charge, enabling efficient gene delivery. These results support the application of lipoproteoplexes with protein engineered CSP for non-viral gene delivery.
PMID: 24875765
ISSN: 0142-9612
CID: 1019062

Efficient in vivo gene delivery using modified Tat peptide with cationic lipids

Yamano, Seiichi; Dai, Jisen; Hanatani, Shigeru; Haku, Ken; Yamanaka, Takuto; Ishioka, Mika; Takayama, Tadahiro; Moursi, Amr M
A combination of modified HIV-1 Tat (mTat) peptide and cationic lipids, FuGENE HD (FH), dramatically enhanced transfection efficiency across a range of cell lines when compared to mTat or FH alone (Biomaterials 35:1705-1715 2014). The efficiency of this Tat peptide combination was significantly higher than many commercial non-viral vectors. In this present study, we tested the feasibility of this non-viral vector, mTat/FH, in vivo using plasmid DNA encoding a luciferase gene. The results of the in vivo studies showed that animals administered mTat/FH/DNA intramuscularly had significantly higher and longer luciferase expression ( approximately 7 months) than those with mTat/DNA, FH/DNA, or DNA alone. Histological evaluation showed little immune response in the muscles, livers, and kidneys of mice administered with the mTat/FH. The combination of mTat with FH could significantly improve transfection efficiency, expanding the potential use of non-viral gene vectors in vivo.
PMID: 24573442
ISSN: 0141-5492
CID: 820962

The effect of a bioactive collagen membrane releasing PDGF or GDF-5 on bone regeneration

Yamano, Seiichi; Haku, Ken; Yamanaka, Takuto; Dai, Jisen; Takayama, Tadahiro; Shohara, Ryutaro; Tachi, Keita; Ishioka, Mika; Hanatani, Shigeru; Karunagaran, Sanjay; Wada, Keisuke; Moursi, Amr M
Regenerative procedures using barrier membrane technology are presently well established in periodontal/endodontic surgery. The objective of this study was to compare the subsequent effects of the released platelet-derived growth factor (PDGF) and growth/differentiation factor 5 (GDF-5) from collagen membranes (CMs) on bone regeneration in vitro and in vivo. In vitro studies were conducted using MC3T3-E1 mouse preosteoblasts cultured with or without factors. Cell viability, cell proliferation, alkaline phosphatase (ALP) activity and bone marker gene expression were then measured. In vivo studies were conducted by placing CMs with low or high dose PDGF or GDF-5 in rat mandibular defects. At 4 weeks after surgery new bone formation was measured using muCT and histological analysis. The results of in vitro studies showed that CM/GDF-5 significantly increased ALP and cell proliferation activities without cytotoxicity in MC3T3-E1 cells when compared to CM/PDGF or CM alone. Gene expression analysis revealed that Runx2 and Osteocalcin were significantly increased in CM/GDF-5 compared to CM/PDGF or control. Quantitative and qualitative muCT and histological analysis for new bone formation revealed that although CM/PDGF significantly enhanced bone regeneration compared to CM alone or control, CM/GDF-5 significantly accelerated bone regeneration to an even greater extent than CM/PDGF. The results also showed that GDF-5 induced new bone formation in a dose-dependent manner. These results suggest that this strategy, using a CM carrying GDF-5, might lead to an improvement in the current clinical treatment of bone defects for periodontal and implant therapy.
PMID: 24388383
ISSN: 0142-9612
CID: 720432

Long-term efficient gene delivery using polyethylenimine with modified Tat peptide

Yamano, Seiichi; Dai, Jisen; Hanatani, Shigeru; Haku, Ken; Yamanaka, Takuto; Ishioka, Mika; Takayama, Tadahiro; Yuvienco, Carlo; Khapli, Sachin; Moursi, Amr M; Montclare, Jin K
Polyethylenimine (PEI), a cationic polymer, has been widely studied and shown great promise as an efficient gene delivery vehicle. Likewise, the HIV-1 Tat peptide, a cell-permeable peptide, has been successfully used for intracellular gene delivery. To improve the favorable properties of these two vectors, we combine PEI with the modified Tat peptide sequence bearing histidine and cysteine residues (mTat). In vitro mTat/PEI-mediated transfection was evaluated by luciferase expression plasmid in two cell types. mTat/PEI produced significant improvement ( approximately 5-fold) in transfection efficiency of both cell lines with little cytotoxicity when compared to mTat alone, PEI alone, or four commercial reagents. The particle size of mTat/PEI/DNA complex was significantly smaller than mTat or PEI alone, and it was correlated with higher transfection efficiency. Filipin III, an inhibitor of caveolae-mediated endocytosis, significantly inhibited mTat/PEI transfection. In contrast, chlorpromazine, an inhibitor of clathrin-mediated endocytosis, did not. This suggested caveolae-mediated endocytosis as the transfection mechanism. Furthermore, the results of in vivo studies showed that animals administered mTat/PEI/DNA intramuscularly had significantly higher and longer luciferase expression ( approximately 7 months) than those with mTat/DNA, PEI/DNA, or DNA alone, without any associated toxicity. The combination of mTat with PEI could significantly improve transfection efficiency, expanding the potential use as a non-viral gene vector both in vitro and in vivo.
PMID: 24268201
ISSN: 0142-9612
CID: 652082

Menopause increases the iron storage protein ferritin in skin

Pelle, Edward; Jian, Jinlong; Zhang, Qi; Muizzuddin, Neelam; Yang, Qing; Dai, Jisen; Maes, Daniel; Pernodet, Nadine; Yarosh, Daniel B; Frenkel, Krystyna; Huang, Xi
Menstruation and desquamation are important routes for humans to excrete iron. Because menstruation is no longer available in postmenopausal women, in the present study, we examined whether iron accumulates more in postmenopausal skin than in premenopausal skin. Skin biopsy samples were obtained from six pre- and six postmenopausal Caucasian women. Iron levels in the form of ferritin were 42% higher, but vascular endothelial growth factor and total antioxidant capacity were 45% and 34% lower in postmenopausal skin (58.8 +/- 1.3 years old) than in premenopausal skin (41.6 +/- 1.7 years old), respectively. Moreover, in vitro cultured normal human epidermal keratinocytes had surprisingly high levels of ferritin when compared to immortalized human breast epithelial MCF-10A cells or human liver HepG2 cancer cells. Our results indicate that skin is a cellular repository of iron and that menopause increases iron in skin and, thus, may contribute to the manifestation of accelerated skin aging and photo aging after menopause.
PMID: 23752032
ISSN: 1525-7886
CID: 438832