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Thanh D Do, Joseph F Ellis, Elizabeth K Neumann, Troy J Comi, Emily G Tillmaand, Ashley E Lenhart, Stanislav S Rubakhin, Jonathan Sweedler
The mammalian dorsal root ganglia (DRG) are located on the dorsal roots of the spinal nerves and contain cell bodies of primary sensory neurons. DRG cells have been classified into subpopulations based on their size, morphology, intracellular markers, response to stimuli, and neuropeptides. To understand the connections between DRG chemical heterogeneity and cellular function, we performed optically guided, high-throughput single cell profiling using sequential matrix-assisted laser desorption/ionization mass spectrometry (MS) to detect lipids, peptides, and several proteins in individual DRG cells...
March 15, 2018: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
Tomoyuki Hatano, Salvatore Alioto, Emanuele Roscioli, Saravanan Palani, Scott T Clarke, Anton Kamnev, Juan Ramon Hernandez-Fernaud, Lavanya Sivashanmugam, Bernardo Chapa-Y-Lazo, Alexandra M E Jones, Robert C Robinson, Karuna Sampath, Masanori Mishima, Andrew D McAinsh, Bruce L Goode, Mohan K Balasubramanian
Actins are major eukaryotic cytoskeletal proteins, which perform many important cell functions, including cell division, cell polarity, wound healing, and muscle contraction. Despite obvious drawbacks, muscle actin, which is easily purified, is used extensively presently for biochemical studies of actin cytoskeleton from other organisms / cell types. Here we report a rapid and cost-effective method to purify heterologous actins expressed in the yeast Pichia pastoris Actin is expressed as a fusion with the actin-binding protein thymosin β4 and purified using an affinity tag introduced in the fusion...
March 13, 2018: Journal of Cell Science
Jun Won Park, Min-Sik Kim, Dominic C Voon, Su-Jin Kim, Jingi Bae, Dong-Gi Mun, Seung-Ik Ko, Hark Kyun Kim, Sang-Won Lee, Dae-Yong Kim
The molecular mechanisms underlying the pathogenesis of diffuse-type gastric cancer (DGC) have not been adequately explored due to a scarcity of appropriate animal models. A recently developed tool well suited for this line of investigation is the Pdx-1-Cre;Cdh1F/+ ;Trp53F/F ;Smad4F/F (pChe PS) mouse model that spontaneously develops metastatic DGC showing nearly complete E-cadherin loss. Here, we performed a proteogenomic analysis to uncover the molecular changes induced by the concurrent targeting of E-cadherin, p53, and Smad4 loss...
March 12, 2018: Molecular Carcinogenesis
Justin B Belsky, Emanuel P Rivers, Michael R Filbin, Patty J Lee, Daniel C Morris
Sepsis is the dysregulated host response to an infection resulting in life-threatening organ damage. Thymosin Beta 4 is an actin binding protein that inhibits the polymerization of G-actin into F-actin and improves mortality when administered intravenously to septic rats. Thymosin Beta 4 decreases inflammatory mediators, lowers reactive oxygen species, up-regulates anti-oxidative enzymes, anti-inflammatory genes, and anti-apoptotic enzymes making it an interesting protein to study in sepsis. Areas covered: The authors summarize the current knowledge of actin and Thymosin Beta 4 as it relates to sepsis via a comprehensive literature search...
March 6, 2018: Expert Opinion on Biological Therapy
Warren Ky Tan, Kristy Purnamawati, Leroy S Pakkiri, Sock Hwee Tan, Xiaoxun Yang, Mark Y Chan, Chester L Drum
Thymosin beta-4 (TB4) is an endogenous peptide with protective and regenerative effects in models of cellular and organ injury. TB4 is increasingly measured as a potential plasma or serum biomarker in human cardiovascular, liver, infectious, and autoimmune disease. Areas Covered: The focus of this review is the quantification of TB4 in clinical cohort studies and whether reported TB4 concentrations differ with respect to method of sample preparation. We survey current literature for studies measuring TB4 in human serum or plasma and compare reported concentrations in healthy controls...
March 3, 2018: Expert Opinion on Biological Therapy
Rinky Kapoor, Debraj Shome
BACKGROUND: Research has shown the efficacy of hair growth factors in hair regrowth. We describe the intradermal injections of a recombinant, bioengineered hair formulation, containing growth factors, into the scalp skin, for enhancement of hair regrowth and evaluate its efficacy. OBJECTIVES: The objective of this study was to assess the efficacy and safety of the hair growth factor formulation in reducing hair loss and enhancing hair growth. MATERIALS AND METHODS: This was an open-label, prospective, single-arm interventional pilot study in which 1000 patients were given intradermal injections of a hair formulation into the scalp skin...
February 26, 2018: Journal of Cosmetic and Laser Therapy: Official Publication of the European Society for Laser Dermatology
Gailen D Marshall
No abstract text is available yet for this article.
February 23, 2018: Expert Opinion on Biological Therapy
Christoffer Stark, Pekka Taimen, Timo Savunen, Juha Koskenvuo
OBJECTIVE: We wanted to determine the impact of different doses of a pegylated and liposomal formulation of the cardiotoxic drug doxorubicin on cardiac function, fibrosis and survival in mice. The drug causes myocardial damage by producing reactive oxygen species, mitochondrial damage and lipid peroxidation. Thymosin beta 4 is a peptide with cardioprotective, anti-oxidant and anti-fibrotic properties and we further investigated whether the peptide could attenuate this drug-induced injury by measuring cardiac function and fibrosis...
February 21, 2018: BMC Research Notes
Baik-Dong Choi, Do-Seon Lim, Seung-Yeon Lee, Tae-Hee Nho, Soon-Jeong Jeong, Yeong-Mu Ko, Sung-Nam Gang, Young-Joon Kim, Xing-Hui Piao, Moon-Jin Jeong
Thymosin β4 (Tβ4) is known to inhibit an inflammatory response and to increase the survival of osteoblasts on titanium (Ti) surfaces. Ti is the most widely used graft material in dentistry; however, an inflammatory response induced following implant placement results in the generation of reactive oxygen species (ROS). The oxidative stress from the production of ROS such as nitric oxide (NO) and hydrogen peroxide (H2O2) can damage surrounding cells, resulting in implant failure by decreasing cell viability...
February 1, 2018: Journal of Nanoscience and Nanotechnology
Dong-Li Li, Xue-Jiao Chang, Xiao-Lu Xie, Shu-Cheng Zheng, Qiu-Xia Zhang, Shu-Ao Jia, Ke-Jian Wang, Hai-Peng Liu
The β-thymosins are a group of structurally related, highly conserved intracellular small peptides in vertebrates with various biological functions, including cytoskeletal remodeling, neuronal development, cell migration, cell survival, tissue repair and inhibition of inflammation. In contrast to vertebrates, the function of β-thymosin is not fully understood in crustaceans. Previously, we found that a thymosin-repeated protein1 (CqTRP1) gene was up-regulated after white spot syndrome virus (WSSV) challenge in haematopoietic tissue (Hpt) cells from the red claw crayfish Cherax quadricarinatus...
February 8, 2018: Developmental and Comparative Immunology
Valeria Tomati, Emanuela Caci, Loretta Ferrera, Emanuela Pesce, Elvira Sondo, Deborah M Cholon, Nancy L Quinney, Susan E Boyles, Andrea Armirotti, Roberto Ravazzolo, Luis Jv Galietta, Martina Gentzsch, Nicoletta Pedemonte
In cystic fibrosis (CF), deletion of phenylalanine 508 (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel causes misfolding and premature degradation. Considering the numerous effects of the F508del mutation on the assembly and processing of CFTR protein, combination therapy with several pharmacological correctors is likely to be required to treat CF patients. Recently, it has been reported that thymosin α-1 (Tα-1) has multiple beneficial effects that could lead to a single-molecule-based therapy for CF patients with F508del...
February 8, 2018: JCI Insight
Jinxu Liao, Chen Zhang, Wenjuan Ru, Dan Wang, Wenping Zhang
Previous study showed that exogenously applied recombinant thymosin from Bombyx mori (BmTHY) reduces B. mori nucleopolyhedrovirus (BmNPV) proliferation in silkworm. Which stands to reason that BmTHY in B. mori is crucial for the defense against BmNPV. However, little is known about the effect of endogenously overexpressed or repressed BmTHY on B. mori resistance to virus infection. To study this issue, we constructed an overexpression and inhibited expression systems of BmTHY in BmN cells. The viral titer and the analysis from the quantitative real-time polymerase chain reaction (PCR) revealed that overexpression of BmTHY decreased the copies of BmNPV gene gp41, which goes over to inhibit the proliferation of BmNPV in BmN cells, while the inhibited expression of BmTHY significantly enhanced viral proliferation in infected BmN cells...
January 29, 2018: Archives of Insect Biochemistry and Physiology
Tsuyoshi Morita, Kenichiro Hayashi
Although enhanced thymosin beta-ß4 (TMSBX4/Tß4) expression is associated with tumor progression and metastasis, its tumor-promoting functions remain largely unknown. Here it is demonstrated that transforming growth factor beta (TGFß) facilitates Tß4 expression and leads to the activation of myocardin-related transcription factors (MRTFs), which are co-activators of serum response factor (SRF) and regulate the expression of genes critical for the epithelial-mesenchymal transition (EMT) and tumor metastasis...
January 12, 2018: Molecular Cancer Research: MCR
Hua Ji, Linhao Xu, Zheng Wang, Xinli Fan, Lihui Wu
Cerebral ischemia causes severe brain injury and results in selective neuronal death through programmed cell death mechanisms, including apoptosis and autophagy. Minimizing neuronal injury has been considered a hot topic among clinicians. The present study elucidated the effect of thymosin β4 (Tβ4) on neuronal death induced by cerebral ischemia/reperfusion in PC12 cells that were subjected to oxygen‑glucose deprivation and reoxygenation (OGD/R). The survival, apoptotic and autophagy rates of PC12 cells were investigated...
January 9, 2018: International Journal of Molecular Medicine
Kristen Skruber, Tracy-Ann Read, Eric A Vitriol
Globular (G)-actin, the actin monomer, assembles into polarized filaments that form networks that can provide structural support, generate force and organize the cell. Many of these structures are highly dynamic and to maintain them, the cell relies on a large reserve of monomers. Classically, the G-actin pool has been thought of as homogenous. However, recent work has shown that actin monomers can exist in distinct groups that can be targeted to specific networks, where they drive and modify filament assembly in ways that can have profound effects on cellular behavior...
January 10, 2018: Journal of Cell Science
Marcel Schmidt, Ana Toplak, Henriëtte J Rozeboom, Hein J Wijma, Peter J L M Quaedflieg, Jan H van Maarseveen, Dick B Janssen, Timo Nuijens
The synthesis of thymosin-α1, an acetylated 28 amino acid long therapeutic peptide, via conventional chemical methods is exceptionally challenging. The enzymatic coupling of unprotected peptide segments in water offers great potential for a more efficient synthesis of peptides that are difficult to synthesize. Based on the design of a highly engineered peptide ligase, we developed a fully convergent chemo-enzymatic peptide synthesis (CEPS) process for the production of thymosin-α1via a 14-mer + 14-mer segment condensation strategy...
January 4, 2018: Organic & Biomolecular Chemistry
Mónika Bokor, Ágnes Tantos, Attila Mészáros, Bence Jenei, Réka Haminda, Péter Tompa, Kálmán Tompa
Wide-line 1H NMR measurements were extended and all results were reinterpreted in a thermodynamics based new approach on aqueous solutions of thymosin-β4 (Tβ4), stabilin C-terminal domain (CTD) and their 1:1 complex. The energy distributions of the potential barriers, which control motion of protein-bound water molecules, were determined. Heterogeneous and homo-geneous regions were found in the protein-water interface. The measure of heterogeneity give quantitative value for the portion of disordered parts in the protein...
December 23, 2017: Chemphyschem: a European Journal of Chemical Physics and Physical Chemistry
Elena V Navolotskaya, Vladimir B Sadovnikov, Valery M Lipkin, Vladimir P Zav'yalov
We have prepared 125I-labeled cholera toxin B subunit (125I-labeled CT-B, a specific activity of 98Ci/mmol) and found that it binds to rat IEC-6 and human Caco-2 intestinal epithelial cells with high affinity (Kd 3.6 and 3.7nM, respectively). The binding of labeled protein was completely inhibited by unlabeled thymosin-α1 (TM-α1), interferon-α2 (IFN-α2), and the synthetic peptide LKEKK that corresponds to residues 16-20 in TM-α1 and 131-135 in IFN-α2, but was not inhibited by the synthetic peptide KKEKL with inverted amino acid sequence (Ki>10μM)...
December 17, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Xiaoming Chen, Fangjie Wo, Jiang Chen, Jie Tan, Tao Wang, Xiao Liang, Jianmin Wu
This study proposed an easy-to-use method for cell identification and quantitation by ratiometric matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Two pairs of MS peaks in the molecular fingerprint of cells were selected as intracellular dual-biomarkers due to the stability and specificity of their ratio values in different types of hepatocellular cancer (HCC) cell lines. Five types of HCC cells can be thereafter differentiated based on these two pairs of intracellular peptides/proteins...
December 12, 2017: Scientific Reports
Jing Chen, Haibin Li, Tao Wang, Shuyang Sun, Jia Liu, Jianhua Chen
Thymosin alpha 1 (Tα1) is an important immunomodulating agent with various clinical applications. The natural form of Tα1 is Nα -acetylated, which was supposed to be related to in vivo stability of the hormone. In this study, fusion protein Tα1-HSA was constructed and expressed in Pichia pastoris . RimJ, a Nα -acetyltransferase from E.coli , was also overexpressed and purified to homogeneity. In vitro acetylation of Tα1-HSA in the presence of RimJ and acetyl coenzyme A resulted in Nα -acetyl Tα1-HSA...
November 10, 2017: Oncotarget
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