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Elizabeth G Mietlicki-Baase, Kieran Koch-Laskowski, Lauren E McGrath, Joanna Krawczyk, Tram Pham, Rinzin Lhamo, David J Reiner, Matthew R Hayes
Glucagon-like peptide-1 (GLP-1) is an incretin hormone released from intestinal L-cells in response to food entering into the gastrointestinal tract. GLP-1-based pharmaceuticals improve blood glucose regulation and reduce feeding. Specific macronutrients, when ingested, may trigger GLP-1 secretion and enhance the effects of systemic sitagliptin, a pharmacological inhibitor of DPP-IV (an enzyme that rapidly degrades GLP-1). In particular, macronutrient constituents found in dairy foods may act as potent secretagogues for GLP-1, and acute preclinical trials show that ingestion of dairy protein may represent a promising adjunct behavioral therapy in combination with sitagliptin...
August 1, 2017: Physiology & Behavior
Mai-Tram Vo, Seong Hee Choi, Ji-Heon Lee, Chung Hwan Hong, Jong Soo Kim, Unn Hwa Lee, Hyung-Min Chung, Byung Ju Lee, Jeong Woo Park, Wha Ja Cho
Mitochondrial dynamics play critical roles in maintaining mitochondrial functions. Here, we report a novel mechanism for regulation of mitochondrial dynamics mediated by tristetraprolin (TTP), an AU-rich element (ARE)-binding protein. Overexpression of TTP resulted in elongated mitochondria, down-regulation of mitochondrial oxidative phosphorylation, reduced membrane potential, cytochrome c release, and increased apoptotic cell death in cancer cells. TTP overexpression inhibited the expression of α-Synuclein (α-Syn)...
March 30, 2017: Oncotarget
Thi Tram Chau Nguyen, Cuu Khoa Nguyen, Thi Hiep Nguyen, Ngoc Quyen Tran
In the study, four kinds of pluronics (P123, F68, F127 and F108) with varying hydrophilic-lipophilic balance (HLB) values were modified and conjugated on 4th generation of polyamidoamine dendrimer (PAMAM). The obtained results from FT-IR, (1)H NMR and GPC showed that the pluronics effectively conjugated on the dendrimer. The molecular weight of four PAMAM G4.0-Pluronics and its morphologies are in range of 200.15-377.14kDa and around 60-180nm in diameter by TEM, respectively. Loading efficiency and release of hydrophobic fluorouracil (5-FU) anticancer drug were evaluated by HPLC; Interesting that the dendrimer nanocarrier was conjugated with the highly lipophilic pluronic P123 (G4...
January 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
Antonio Espinosa-de-Los-Monteros, Héctor Avendano-Peza, Yuri W Novitsky
Breast reconstruction with a pedicled transverse rectus abdominis muscle (TRAM) flap can result in significant abdominal wall donor-site morbidity. Although the pedicled TRAM flap donor area reinforced with mesh results in decreased rates of postoperative abdominal bulging and hernias, the best technique to accomplish that is yet to be elucidated. We present our novel technique of posterior components separation with transversus abdominis muscle release and retromuscular mesh reinforcement for donor-area closure during pedicled TRAM flap breast reconstruction...
September 2016: Plastic and Reconstructive Surgery. Global Open
Kha Tram, Sepehr Manochehry, Qian Feng, Dingran Chang, Bruno J Salena, Yingfu Li
There are increasing demands for simple but still effective methods that can be used to detect specific pathogens for point-of-care or field applications. Such methods need to be user-friendly and produce reliable results that can be easily interpreted by both specialists and non-professionals. The litmus test for pH is simple, quick, and effective as it reports the pH of a test sample via a simple color change. We have developed an approach to take advantage of the litmus test for bacterial detection. The method exploits a bacterium-specific RNA-cleaving DNAzyme to achieve two functions: recognizing a bacterium of interest and providing a mechanism to control the activity of urease...
2016: Journal of Visualized Experiments: JoVE
James Chidgey, Paul A Fraser, Philip I Aaronson
There is abundant evidence that H2O2 can act as an endothelium-derived hyperpolarizing factor in the resistance vasculature. However, whilst scavenging H2O2 can abolish endothelial dependent hyperpolarization (EDH) and the associated vascular relaxation in some arteries, EDH-dependent vasorelaxation can often be mimicked only by using relatively high concentrations of H2O2. We have examined the role of H2O2 in EDH-dependent vasodilatation by simultaneously measuring vascular diameter and changes in endothelial cell (EC) [Ca(2+)]i during the application of H2O2 or carbachol, which triggers EDH...
August 2016: Free Radical Biology & Medicine
M Pule Addison, Thakur Uttam Singh, Subhashree Parida, Soumen Choudhury, Jaya Kiran Kasa, Susanth V Sukumaran, Sajad Ahmad Darzi, Kannan Kandasamy, Vishakha Singh, Dinesh Kumar, Santosh Kumar Mishra
BACKGROUND: The aim of the present study was to observe the concomitant activation of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) pathways by TRPV4 channel agonist GSK1016790A in the rat pulmonary artery and explore the mechanism by which NO synthase inhibition attenuates EDHF-mediated relaxation in endothelium-intact rat pulmonary artery. METHODS: Tension experiments were conducted on the pulmonary artery from male Wistar rats. RESULTS: TRPV4 channel agonist GSK1016790A (GSK) caused concentration-dependent relaxation (Emax 86...
June 2016: Pharmacological Reports: PR
Kasper Moller Boje Rasmussen, Thomas Hartig Braunstein, Max Salomonsson, Jens Christian Brasen, Charlotte Mehlin Sorensen
We investigated the mechanisms behind the endothelial-derived hyperpolarization (EDH)-induced renal vasodilation in vivo and in vitro in rats. We assessed the role of Ca(2+)-activated K(+) channels and whether K(+) released from the endothelial cells activates inward rectifier K(+) (Kir) channels and/or the Na(+)/K(+)-ATPase. Also, involvement of renal myoendothelial gap junctions was evaluated in vitro. Isometric tension in rat renal interlobar arteries was measured using a wire myograph. Renal blood flow was measured in isoflurane anesthetized rats...
July 2016: Pflügers Archiv: European Journal of Physiology
Shuang Zhang, Min Yu, Qiang Guo, Rongpeng Li, Guobo Li, Shirui Tan, Xuefeng Li, Yuquan Wei, Min Wu
Lipopolysaccharide (LPS) derived from Gram-negative bacteria activates plasma membrane signaling via Toll-like receptor 4 (TLR4) on host cells and triggers innate inflammatory responses, but the underlying mechanisms remain to be fully elucidated. Here we reveal a role for annexin A2 (AnxA2) in host defense against infection as anxa2(-/-) mice were highly susceptible to Gram-negative bacteria-induced sepsis with enhanced inflammatory responses. Computing analysis and biochemical experiments identified that constitutive AnxA2 expression facilitated TLR4 internalization and its subsequent translocation into early endosomal membranes...
November 3, 2015: Scientific Reports
Cheng-Lung Chen, Jiunn-Wang Liao, Oliver Yoa-Pu Hu, Li-Heng Pao
Tubular cell apoptosis significantly contributes to cisplatin-induced acute kidney injury (AKI) pathogenesis. Although KCa3.1, a calcium-activated potassium channel, participates in apoptosis, its involvement in cisplatin-induced AKI is unknown. Here, we found that cisplatin treatment triggered an early induction of KCa3.1 expression associated with HK-2 cell apoptosis, the development of renal tubular damage, and apoptosis in mice. Treatment with the highly selective KCa3.1 blocker TRAM-34 suppressed cisplatin-induced HK-2 cell apoptosis...
September 2016: Archives of Toxicology
Satish N Nadig, Suraj K Dixit, Natalie Levey, Scott Esckilsen, Kayla Miller, William Dennis, Carl Atkinson, Ann-Marie Broome
In this study, we developed a stable, nontoxic novel micelle nanoparticle to attenuate responses of endothelial cell (EC) inflammation when subjected to oxidative stress, such as observed in organ transplantation. Targeted Rapamycin Micelles (TRaM) were synthesized using PEG-PE-amine and N-palmitoyl homocysteine (PHC) with further tailoring of the micelle using targeting peptides (cRGD) and labeling with far-red fluorescent dye for tracking during cellular uptake studies. Our results revealed that the TRaM was approximately 10 nm in diameter and underwent successful internalization in Human Umbilical Vein EC (HUVEC) lines...
2015: RSC Advances
Dom Guillaume, Thi Ngoc Tram Huynh, Clément Denhez, Kim Phi Phung Nguyen, Azzaq Belaaouaj
Neutrophile elastase has the capacity to degrade elastin, a protein found in the connective tissue of the lungs. Unchecked elastase leads to pulmonary pathologies. Therefore, the development of elastase inhibitors is currently actively pursued in the therapeutic field. Several triterpenoids have been reported as inhibitors against elastase or its release. Such compounds could be valuable for the design of new drugs. This review is aimed at giving a comprehensive insight into the recent work performed in the field of triterpenoid-induced elastase inhibition...
January 2015: Natural Product Communications
Nadra J Nilsen, Gregory I Vladimer, Jørgen Stenvik, M Pontus A Orning, Maria V Zeid-Kilani, Marit Bugge, Bjarte Bergstroem, Joseph Conlon, Harald Husebye, Amy G Hise, Katherine A Fitzgerald, Terje Espevik, Egil Lien
Toll-like receptors (TLRs) are involved in sensing invading microbes by host innate immunity. TLR2 recognizes bacterial lipoproteins/lipopeptides, and lipopolysaccharide activates TLR4. TLR2 and TLR4 signal via the Toll/interleukin-1 receptor adaptors MyD88 and MAL, leading to NF-κB activation. TLR4 also utilizes the adaptors TRAM and TRIF, resulting in activation of interferon regulatory factor (IRF) 3. Here, we report a new role for TRAM and TRIF in TLR2 regulation and signaling. Interestingly, we observed that TLR2-mediated induction of the chemokine Ccl5 was impaired in TRAM or TRIF deficient macrophages...
February 6, 2015: Journal of Biological Chemistry
Fabiano E Xavier, Javier Blanco-Rivero, Esther Sastre, Laura Caracuel, María Callejo, Gloria Balfagón
BACKGROUND AND PURPOSE: Tranilast, in addition to its capacity to inhibit mast cell degranulation, has other biological effects, including inhibition of reactive oxygen species, cytokines, leukotrienes and prostaglandin release. In the current study, we analyzed whether tranilast could alter endothelial function in rat mesenteric resistance arteries (MRA). EXPERIMENTAL APPROACH: Acetylcholine-induced relaxation was analyzed in MRA (untreated and 1-hour tranilast treatment) from 6 month-old Wistar rats...
2014: PloS One
Heyang Xu, Wei Lai, Yang Zhang, Lu Liu, Xingxi Luo, Yujie Zeng, Heng Wu, Qiusheng Lan, Zhonghua Chu
BACKGROUND: Tumor-associated macrophages (TAMs) are known to promote cancer progression and metastasis through the release of a variety of cytokines. Phosphatase of regenerating liver (PRL-3) has been considered as a marker of colorectal cancer (CRC) liver metastasis. Our previous research suggests that PRL-3 can enhance the metastasis of CRC through the up-regulation of intermediate-conductance Ca2+-activated K+ (KCNN4) channel, which is dependent on the autocrine secretion of tumor necrosis factor-alpha (TNF-α)...
2014: BMC Cancer
Christian Freise, Uwe Querfeld
Vascular calcifications are a hallmark of advanced cardiovascular disease in patients with chronic kidney disease. A key event is the transition of contractile vascular smooth muscle cells (VSMC) into an osteoblast-like phenotype, promoting a coordinated process of vascular remodeling resembling bone mineralization. Intermediate-conductance calcium-activated potassium channels (KCa3.1) are expressed in various tissues including VSMC. Aiming for novel therapeutic targets in vascular calcification, we here studied effects of KCa3...
July 2014: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Tram T K Pham, Brittany Stinson, Nethaji Thiyagarajan, Michelle Lizotte-Waniewski, Keith Brew, K Ravi Acharya
Mammalian members of glycosyltransferase family 6 (GT6) of the CAZy database have a GT-A fold containing a conserved Asp-X-Asp (DXD) sequence that binds an essential metal cofactor. Bacteroides ovatus GT6a represents a GT6 clade found in more than 30 Gram-negative bacteria that is similar in sequence to the catalytic domains of mammalian GT6, but has an Asn(95)-Ala-Asn(97) (NXN) sequence substituted for the DXD motif and metal-independent catalytic activity. Co-crystals of a low activity mutant of BoGT6a (E192Q) with UDP-GalNAc contained protein complexes with intact UDP-GalNAc and two forms with hydrolysis products (UDP plus GalNAc) representing an initial closed complex and later open form primed for product release...
March 21, 2014: Journal of Biological Chemistry
Jun Li, Jingzhi Sun, Li Yang, Jing Zhao, Zhenglun Wang, Lei Yang
OBJECTIVE: To investigate the role of calcium activated-potassium channels (KCa) in the injury to rat alveolar macrophages induced by quartz. METHODS: The experiments were conducted on a rat alveolar macrophage cell line (NR8383) in vitro, where crystal silica (100 üg/ml) and amorphous silica (100 üg/ml) were used as the test substances and the cells without any treatment as negative controls. At first the effects of two kinds of quartz were compared. Then KCa special inhibitors (Paxilline for BK, Tram-34 for IK, Apamin for SK) were added in different doses to the in vitro test system with 100 üg/ml crystal quartz as matrix, to observe the function of such channels...
January 2014: Chinese Journal of Industrial Hygiene and Occupational Diseases
Ameet A Chimote, Peter Hajdu, Vladimir Kucher, Nina Boiko, Zerrin Kuras, Orsolya Szilagyi, Yeo-Heung Yun, Laura Conforti
Adenosine, a purine nucleoside, is present at high concentrations in tumors, where it contributes to the failure of immune cells to eliminate cancer cells. The mechanisms responsible for the immunosuppressive properties of adenosine are not fully understood. We tested the hypothesis that adenosine's immunosuppressive functions in human T lymphocytes are in part mediated via modulation of ion channels. The activity of T lymphocytes relies on ion channels. KCa3.1 and Kv1.3 channels control cytokine release and, together with TRPM7, regulate T cell motility...
December 15, 2013: Journal of Immunology: Official Journal of the American Association of Immunologists
Owain Llŷr Roberts, Tomoko Kamishima, Richard Barrett-Jolley, John M Quayle, Caroline Dart
Vasodilator-induced elevation of intracellular cyclic AMP (cAMP) is a central mechanism governing arterial relaxation but is incompletely understood due to the diversity of cAMP effectors. Here we investigate the role of the novel cAMP effector exchange protein directly activated by cAMP (Epac) in mediating vasorelaxation in rat mesenteric arteries. In myography experiments, the Epac-selective cAMP analogue 8-pCPT-2-O-Me-cAMP-AM (5 μM, subsequently referred to as 8-pCPT-AM) elicited a 77.6 ± 7.1% relaxation of phenylephrine-contracted arteries over a 5 min period (mean ± SEM; n = 6)...
October 15, 2013: Journal of Physiology
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