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In JoVE (1)
Other Publications (14)
- Journal of Immunology (Baltimore, Md. : 1950)
- Acta Crystallographica. Section C, Crystal Structure Communications
- Annals of Plastic Surgery
- Acta Crystallographica. Section C, Crystal Structure Communications
- The Journal of Clinical Investigation
- Wound Repair and Regeneration : Official Publication of the Wound Healing Society [and] the European Tissue Repair Society
- AIDS and Behavior
- Addiction (Abingdon, England)
- Reproductive Biology and Endocrinology : RB&E
- Biochemical Pharmacology
- Sexually Transmitted Diseases
- PloS One
- Bioorganic & Medicinal Chemistry Letters
- The Biochemical Journal
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Articles by Jian Luo in JoVE
JoVE Applied Physics
Строительство и испытания монет клетки литий-ионных батарей
1School of Materials Science and Engineering, Clemson University, 2Center for Optical Materials Science and Engineering Technologies, Clemson University
Протокол для построения и тестирования монеты клетки литий-ионных батарей описан. Конкретные процедуры принятия рабочего электрода, подготовке контр электрод, монтаж ячейки внутри перчаточного ящика и тестирования ячейки представлены.
Other articles by Jian Luo on PubMed
Global Analysis of Smad2/3-dependent TGF-beta Signaling in Living Mice Reveals Prominent Tissue-specific Responses to Injury
Smad2 and Smad3 (Smad2/3) proteins are key signaling molecules for TGF-beta and some related family members regulating the transcription of several hundred genes. TGF-beta have key roles in development, tissue homeostasis, and the pathogenesis of many human diseases, including cancer, fibrotic disorders, developmental defects, and neurodegeneration. To study the temporal and spatial patterns of Smad2/3-dependent signaling in normal and pathological conditions in the living organism, we engineered transgenic mice with a Smad-responsive luciferase reporter construct (SBE-luc mice). Using bioluminescent imaging, we assessed Smad2/3 signaling activity noninvasively in living mice. At baseline, this activity was highest in brain, intestine, heart, and skin, and correlated with biochemical measurements of reporter activity. Primary astrocytes cultured from SBE-luc mice showed specific activation of the reporter in response to Smad2/3-activating TGF-beta family members. Treatment of mice with the endotoxin LPS resulted in a fast and vigorous, but transient activation of the reporter in the intestine. Although the response was similarly rapid in brain, it remained increased, indicating important but different cellular responses to endotoxin challenge in these organs. Traumatic brain injury with a needle stab resulted in local activation of Smad2/3-dependent genes and a severalfold increase in bioluminescence in living mice. SBE-luc mice can therefore be used to study temporal, tissue-specific activation of Smad2/3-dependent signaling in living mice in normal or pathological conditions as well as for the identification of endogenous or synthetic modulators of this pathway.
Two Pseudo-polymorphic Copper-benzene-1,2,4,5-tetracarboxylate Complexes
Two pseudo-polymorphic polymers, poly[ethylenediammonium [[aquacopper(II)]-micro(4)-benzene-1,2,4,5-tetracarboxylato] dihydrate], [(C(2)H(10)N(2))[Cu(C(10)H(2)O(8))(H(2)O)].2H(2)O](n), (I), and poly[ethylenediammonium [copper(II)-micro(4)-benzene-1,2,4,5-tetracarboxylato] 2.5-hydrate], [(C(2)H(10)N(2))[Cu(C(10)H(2)O(8))].2.5H(2)O](n), (II), contain two-dimensional anionic layers, ethylenediammonium (H(2)en) cations acting as counter-ions and free water molecules. Although the topological structures of the two anionic layers are homologous, the coordination environments of the Cu(II) centres are different. In (I), the Cu(II) centre, sitting on a general position, has a square-pyramidal environment. The two independent benzene-1,2,4,5-tetracarboxylate (btc) anions rest on centres of inversion. The Cu(II) cation in (II) is located on a twofold axis in a square-planar coordination. The H(2)en cation is on an inversion centre and the btc ligand is split by a mirror plane. Extensive hydrogen-bonding interactions between the complexes, H(2)en cations and water molecules lead to the formation of three-dimensional supramolecular structures.
In Vitro Analysis of Transforming Growth Factor-beta1 Inhibition in Novel Transgenic SBE-luciferase Mice
Transforming growth factor beta1 (TGF-beta1) expression correlates with scarring. A novel transgenic mouse model with a Smad2/3-responsive luciferase reporter construct (SBE-luc) has been developed. We hypothesized that bioluminescence in SBE-luc dermal fibroblasts could be measured to assess TGF-beta1 inhibition.
Mer-Bis(1,4-dibenzoylthiosemicarbazidato-kappa3O,N,O')cobalt(II)
The title complex, [Co(C(15)H(12)N(3)O(2)S)(2)], consists of an octahedrally coordinated Co(II) ion, with two crystallographically independent 1,4-dibenzoylthiosemicarbazidate ligands in a tridentate mer coordination [Co-O = 2.064 (3)-2.132 (3) A and Co-N = 2.037 (3)-2.043 (3) A]. There are intermolecular N-H...S hydrogen bonds involving one ligand and strong pi-pi stacking interactions involving the other ligand, resulting in a three-dimensional supramolecular framework. The hydrogen bonds and pi-pi interactions, as well as different intramolecular aryl-benzamide H-C...H(-N) distances, give rise to a difference in conformation between the two ligands.
Glia-dependent TGF-beta Signaling, Acting Independently of the TH17 Pathway, is Critical for Initiation of Murine Autoimmune Encephalomyelitis
Autoimmune encephalomyelitis, a mouse model for multiple sclerosis, is characterized by the activation of immune cells, demyelination of axons in the CNS, and paralysis. We found that TGF-beta1 synthesis in glial cells and TGF-beta-induced signaling in the CNS were activated several days before the onset of paralysis in mice with autoimmune encephalomyelitis. While early production of TGF-beta1 was observed in glial cells TGF-beta signaling was activated in neurons and later in infiltrating T cells in inflammatory lesions. Systemic treatment with a pharmacological inhibitor of TGF-beta signaling ameliorated the paralytic disease and reduced the accumulation of pathogenic T cells and expression of IL-6 in the CNS. Priming of peripheral T cells was not altered, nor was the generation of TH17 cells, indicating that this effect was directed within the brain, yet affected the immune system. These results suggest that early production of TGF-beta1 in the CNS creates a permissive and dangerous environment for the initiation of autoimmune inflammation, providing a rare example of the brain modulating the immune system. Importantly, inhibition of TGF-beta signaling may have benefits in the treatment of the acute phase of autoimmune CNS inflammation.
Live Imaging of Smad2/3 Signaling in Mouse Skin Wound Healing
Biophotonics and real-time imaging are novel technologies that can greatly enhance the study of complex biological processes. We applied this technology in a transgenic mouse with a luciferase reporter gene fused to a transforming growth factor-beta (TGF-beta) responsive Smad2/3-binding element to study bioluminescence after skin wounding. Two dorsal midline excisional skin wounds were made using a biopsy punch. One wound was randomized to suture closure and the other allowed to heal by secondary intention (n=8 each wound). Bioluminescence was measured at fixed time points following surgery. Phospho-Smad2/3 immunohistochemistry was performed to localize expression in skin wound samples. In vivo bioluminescence increased following skin wounding. Peak activity occurred on day 17 and was fourfold that of baseline (p<0.05). Subgroup analysis of primary and secondary healing showed that primarily sutured wounds had peak activities earlier than those with secondary healing, although this did not reach statistical significance. Intense phospho-Smad2/3 staining was found in the hair follicles. In vivo bioluminescence tracks Smad2/3-dependent TGF-beta signaling in the in vivo wound healing process. Our findings suggest that signaling increases after wound healing, which contrasts with other studies that show raised TGF-beta signaling in the initial days following wounding.
Role of Social Network Dimensions in the Transition to Injection Drug Use: Actions Speak Louder Than Words
The objective of this study was to examine the influences of social network factors, particularly social support and norms, in the transition from non-injection heroin and/or opiate use to heroin-injection, which is one of the leading causes of the spread of HIV/AIDS in China. Respondent-driven sampling was used to recruit young heroin and/or opiate users in an egocentric network study in Yunnan, China. Multivariate logistic regression using hierarchical combinations of candidate variables was used to analyze network factors for the injection transition. A total of 3,121 social network alters were reported by 403 egos with an average network size of eight. Fifty-eight percent of egos transitioned to heroin-injection from non-injection. This transition was associated with having a larger sex network size, a larger number of heroin injectors in one's network, and a higher network density. The findings enhance our understanding of the influence of social network dimensions on the transition to injection drug use. Accordingly, the development of interventions for heroin and/or opiate users in China should consider social network characteristics.
Sexual Transmissibility of HIV Among Opiate Users with Concurrent Sexual Partnerships: an Egocentric Network Study in Yunnan, China
To investigate the patterns of concurrent sexual partnerships among young opiate users and sexual transmissibility of human immunodeficiency virus (HIV) in concurrent sexual partnerships in drug-use and sexual networks.
Effect of Estradiol on Proliferation and Differentiation of Side Population Stem/progenitor Cells from Murine Endometrium
In our previous study, endometrium side population cells (SP cells) were isolated from postpartum murine uterus, and characterized by a heterogeneous population of stem/progenitor cells. In this study, we investigated the effect of estrogen on the proliferation and differentiation of SP cells.
Cudratricusxanthone G Inhibits Human Colorectal Carcinoma Cell Invasion by MMP-2 Down-regulation Through Suppressing Activator Protein-1 Activity
Cudratricusxanthone G (CTXG), a natural bioactive cudratricusxanthone extracted from C. tricuspidata, has shown anti-cancer properties. However, the function and mechanism of CTXG in tumor invasion have not been elucidated to date. In this study, we investigated the inhibitory effect of CTXG on the proliferation, migration and invasion of SW620 cells. We found that MMP-2, a pivotal factor in tumor invasion, was suppressed in both expression and activation by CTXG in a dose-dependent manner. The suppression of MMP-2 expression by CTXG led to an inhibition of SW620 cells invasion and migration by inactivating Rac1 and Cdc42 but not RhoA GTPase. Furthermore, CTXG also inhibited the transcriptional activity of AP-1 (activator protein-1). In conclusion, our data demonstrate that CTXG exerted anti-invasion action in SW620 cells by targeting MMP-2 though regulating the activities of Rac1, Cdc42 and their downstream transcriptional factor AP-1. These results are the first to reveal the novel functions of CTXG in cancer cell invasion and its molecular basis for the anti-cancer action.
Role of Sexual Transmission of HIV Among Young Noninjection and Injection Opiate Users: a Respondent-driven Sampling Study
Sexual transmissibility of HIV among young drug users in China has been investigated in few studies. The objective of this study was to examine the role of sexual transmission on HIV infection among injection drug users (IDUs) and noninjection drug users (NIDUs).
AMG 837: a Novel GPR40/FFA1 Agonist That Enhances Insulin Secretion and Lowers Glucose Levels in Rodents
Agonists of GPR40 (FFA1) have been proposed as a means to treat type 2 diabetes. Through lead optimization of a high throughput screening hit, we have identified a novel GPR40 agonist called AMG 837. The objective of these studies was to understand the preclinical pharmacological properties of AMG 837. The activity of AMG 837 on GPR40 was characterized through GTPγS binding, inositol phosphate accumulation and Ca(2+) flux assays. Activity of AMG 837 on insulin release was assessed on isolated primary mouse islets. To determine the anti-diabetic activity of AMG 837 in vivo, we tested AMG 837 using a glucose tolerance test in normal Sprague-Dawley rats and obese Zucker fatty rats. AMG 837 was a potent partial agonist in the calcium flux assay on the GPR40 receptor and potentiated glucose stimulated insulin secretion in vitro and in vivo. Acute administration of AMG 837 lowered glucose excursions and increased glucose stimulated insulin secretion during glucose tolerance tests in both normal and Zucker fatty rats. The improvement in glucose excursions persisted following daily dosing of AMG 837 for 21-days in Zucker fatty rats. Preclinical studies demonstrated that AMG 837 was a potent GPR40 partial agonist which lowered post-prandial glucose levels. These studies support the potential utility of AMG 837 for the treatment of type 2 diabetes.
AMG 837: A Potent, Orally Bioavailable GPR40 Agonist
The discovery that certain long chain fatty acids potentiate glucose stimulated insulin secretion through the previously orphan receptor GPR40 sparked interest in GPR40 agonists as potential antidiabetic agents. Optimization of a series of β-substituted phenylpropanoic acids led to the identification of (S)-3-(4-((4'-(trifluoromethyl)biphenyl-3-yl)methoxy)phenyl)hex-4-ynoic acid (AMG 837) as a potent GPR40 agonist with a superior pharmacokinetic profile and robust glucose-dependent stimulation of insulin secretion in rodents.
Ubiquitin-specific Protease 4 (USP4) Targets TRAF2 and TRAF6 for Deubiquitination and Inhibits TNFα-induced Cancer Cell Migration
TRAF [TNF (tumour necrosis factor)-receptor-associated factor] 2 and 6 are essential adaptor proteins for the NF-κB (nuclear factor κB) signalling pathway, which play important roles in inflammation and immune response. Polyubiquitination of TRAF2 and TRAF6 is critical to their activities and functions in TNFα- and IL (interleukin)-1β-induced NF-κB activation. However, the regulation of TRAF2 and TRAF6 by deubiquitination remains incompletely understood. In the present study, we identified USP (ubiquitin-specific protease) 4 as a novel deubiquitinase targeting TRAF2 and TRAF6 for deubiquitination. We found that USP4 specifically interacts with TRAF2 and TRAF6, but not TRAF3. Moreover, USP4 associates with TRAF6 both in vitro and in vivo, independent of its deubiquitinase activity. The USP domain is responsible for USP4 to interact with TRAF6. Ectopic expression of USP4 inhibits the TRAF2- and TRAF6-stimulated NF-κB reporter gene and negatively regulates the TNFα-induced IκBα (inhibitor of NF-κBα) degradation and NF-κB activation. Knockdown of USP4 significantly increased TNFα-induced cytokine expression. Furthermore, we found that USP4 deubiquitinates both TRAF2 and TRAF6 in vivo and in vitro in a deubiquitinase activity-dependent manner. Importantly, the results of the present study showed that USP4 is a negative regulator of TNFα- and IL-1β-induced cancer cell migration. Taken together, the present study provides a novel insight into the regulation of the NF-κB signalling pathway and uncovers a previously unknown function of USP4 in cancer.
