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Thomas W Carion, Abdul Shukkur Ebrahim, David Kracht, Aditya Agrawal, Eliisa Strand, Omar Kaddurah, Cody R McWhirter, Gabriel Sosne, Elizabeth A Berger
With increasing multidrug resistance and contraindication for corticosteroid use, the goal of this study was to develop thymosin beta-4 (Tβ4) as an adjunctive therapy to antibiotics for the treatment of bacterial keratitis that effectively promotes enhanced wound healing, host defense, and inflammation resolution. Disease outcome was assessed by clinical score, slit lamp photography, and histopathology. Cytokine profile, bacterial load, PMN infiltration, and Griess and reactive oxygen species (ROS) levels were determined...
September 20, 2018: Cells
Esperanza Hernández-Carralero, Elisa Cabrera, Ignacio Alonso-de Vega, Santiago Hernández-Pérez, Veronique A J Smits, Raimundo Freire
Eukaryotic cells divide by accomplishing a program of events in which the replication of the genome is a fundamental part. To ensure all cells have an accurate copy of the genome, DNA replication occurs only once per cell cycle and is controlled by numerous pathways. A key step in this process is the initiation of DNA replication in which certain regions of DNA are marked as competent to replicate. Moreover, initiation of DNA replication needs to be coordinated with other cell cycle processes. At the molecular level, initiation of DNA replication relies, among other mechanisms, upon post-translational modifications, including the conjugation and hydrolysis of ubiquitin...
September 20, 2018: Cells
Raghavendra Baregundi Subbarao, Seong-Ho Ok, Soo Hee Lee, Dawon Kang, Eun-Jin Kim, Ji-Yoon Kim, Ju-Tae Sohn
This study aimed to examine the effect of lipid emulsion on the cardiotoxicity induced by doxorubicin in H9c2 rat cardiomyoblasts and elucidates the associated cellular mechanism. The effects of lipid emulsion on cell viability, Bax, cleaved caspase-8, cleaved capase-3, Bcl-XL, apoptosis, reactive oxygen species (ROS), malondialdehyde, superoxide dismutase (SOD), catalase and mitochondrial membrane potential induced by doxorubicin were examined. Treatment with doxorubicin decreased cell viability, whereas pretreatment with lipid emulsion reduced the effect of doxorubicin by increasing cell viability...
September 20, 2018: Cells
Dessy Chan, Yuanyuan Zhou, Chung Hin Chui, Kim Hung Lam, Simon Law, Albert Sun-Chi Chan, Xingshu Li, Alfred King-Yin Lam, Johnny Cheuk On Tang
Cisplatin (CDDP) is one of the front-line chemotherapeutic drugs used in the treatment of esophageal squamous cell carcinoma (ESCC). Occurrence of resistance to CDDP has become one of the main challenges in cancer therapy. In this study, the gene expression profile of CDDP-resistant ESCC cells was investigated and molecular approaches were explored in an attempt to reverse the CDDP resistance. A CDDP-resistant SLMT-1/CDDP1R cell line was established from SLMT-1 cells by subculturing in the medium containing an increasing concentration of CDDP (0...
September 20, 2018: Cells
Flaminia Chellini, Alessia Tani, Larissa Vallone, Daniele Nosi, Paola Pavan, Franco Bambi, Sandra Zecchi Orlandini, Chiara Sassoli
The antifibrotic potential of platelet-rich plasma (PRP) is controversial. This study examined the effects of PRP on in vitro transforming growth factor (TGF)-β1-induced differentiation of fibroblasts into myofibroblasts, the main drivers of fibrosis, and the involvement of vascular endothelial growth factor (VEGF)-A in mediating PRP-induced responses. The impact of PRP alone on fibroblast differentiation was also assessed. Myofibroblastic phenotype was evaluated by confocal fluorescence microscopy and western blotting analyses of α-smooth muscle actin (sma) and type-1 collagen expression, vinculin-rich focal adhesion clustering, and stress fiber assembly...
September 19, 2018: Cells
Maryam Oroujeni, Javad Garousi, Ken G Andersson, John Löfblom, Bogdan Mitran, Anna Orlova, Vladimir Tolmachev
Radionuclide imaging of epidermal growth factor receptor (EGFR) expression in tumors may stratify patients for EGFR-targeting therapies and predict response or resistance to certain treatments. Affibody molecules, which are nonimmunoglobulin scaffold proteins, have a high potential as probes for molecular imaging. In this study, maleimido derivative of desferrioxamine B (DFO) chelator was site-specifically coupled to the C-terminal cysteine of the anti-EGFR affibody molecule ZEGFR:2377, and the DFO-ZEGFR:2377 conjugate was labeled with the generator-produced positron-emitting radionuclide 68 Ga...
September 18, 2018: Cells
Ruhel Ahmad, Vincenza Sportelli, Michael Ziller, Dietmar Spengler, Anke Hoffmann
Schizophrenia (SCZ) is a devastating mental disorder that is characterized by distortions in thinking, perception, emotion, language, sense of self, and behavior. Epidemiological evidence suggests that subtle perturbations in early neurodevelopment increase later susceptibility for disease, which typically manifests in adolescence to early adulthood. Early perturbations are thought to be significantly mediated through incompletely understood genetic risk factors. The advent of induced pluripotent stem cell (iPSC) technology allows for the in vitro analysis of disease-relevant neuronal cell types from the early stages of human brain development...
September 17, 2018: Cells
Joel K Durand, Qing Zhang, Albert S Baldwin
While primarily studied for their roles in innate immune response, the IκB kinase (IKK)-related kinases TANK-binding kinase 1 (TBK1) and IKKε also promote the oncogenic phenotype in a variety of cancers. Additionally, several substrates of these kinases control proliferation, autophagy, cell survival, and cancer immune responses. Here we review the involvement of TBK1 and IKKε in controlling different cancers and in regulating responses to cancer immunotherapy.
September 15, 2018: Cells
Michaela Dostalova Merkerova, Hana Remesova, Zdenek Krejcik, Nikoleta Loudova, Andrea Hrustincova, Katarina Szikszai, Jaroslav Cermak, Anna Jonasova, Monika Belickova
The DLK1⁻DIO3 region contains a large miRNA cluster, the overexpression of which has previously been associated with myelodysplastic syndromes (MDS). To reveal whether this overexpression is epigenetically regulated, we performed an integrative analysis of miRNA/mRNA expression and DNA methylation of the regulatory sequences in the region (promoter of the MEG3 gene) in CD34+ bone marrow cells from the patients with higher-risk MDS and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC), before and during hypomethylating therapy with azacytidine (AZA)...
September 14, 2018: Cells
Marie Bobowski-Gerard, Francesco Paolo Zummo, Bart Staels, Philippe Lefebvre, Jérôme Eeckhoute
Hepatic stellate cells (HSCs) serve as the main body storage compartment for vitamin A through retinyl ester (RE)-filled lipid droplets (LDs). Upon liver injury, HSCs adopt a myofibroblastic phenotype characterized by an elevated expression of extracellular matrix proteins and a concomitant loss of LDs. On the one hand, LD breakdown has been suggested to provide the energy required for HSC activation into myofibroblast-like cells. On the other hand, this process could mitigate HSC activation following the transformation of released REs into retinoic acids (RAs), ligands for nuclear receptors exerting antifibrotic transcriptional regulatory activities in HSCs...
September 13, 2018: Cells
Martin Kräter, Jiranuwat Sapudom, Nicole Christin Bilz, Tilo Pompe, Jochen Guck, Claudia Claus
The cellular cytoskeleton is central for key cellular functions, and as such is a marker for diseased and infected cell states. Here we analyzed infection with rubella virus (RV) strains with respect to phenotypes in cellular mechanical properties, cell movement, and viral cytopathogenicity. Real-time deformability cytometry (RT-DC), as a high-throughput platform for the assessment of cell mechanics, revealed a correlation of an increase in cortical filamentous-actin (F-actin) with a higher cellular stiffness...
September 13, 2018: Cells
Yue Wang, Xiaochen Meng, Lianqing Zhu
The increased volume and complexity of flow cytometry (FCM) data resulting from the increased throughput greatly boosts the demand for reliable statistical methods for the analysis of multidimensional data. The Support Vector Machines (SVM) model can be used for classification recognition. However, the selection of penalty factor c and kernel parameter g in the model has a great influence on the correctness of clustering. To solve the problem of parameter optimization of the SVM model, a support vector machine algorithm of particle swarm optimization (PSO-SVM) based on adaptive mutation is proposed...
September 12, 2018: Cells
Duy N Do, Pier-Luc Dudemaine, Bridget E Fomenky, Eveline M Ibeagha-Awemu
This study aimed to investigate the potential regulatory roles of miRNAs in calf ileum developmental transition from the pre- to the post-weaning period. For this purpose, ileum tissues were collected from eight calves at the pre-weaning period and another eight calves at the post-weaning period and miRNA expression characterized by miRNA sequencing, followed by functional analyses. A total of 388 miRNAs, including 81 novel miRNAs, were identified. A total of 220 miRNAs were differentially expressed (DE) between the two periods...
September 11, 2018: Cells
Julia Concetti, Caroline L Wilson
Current evidence strongly suggests that aberrant activation of the NF-κB signalling pathway is associated with carcinogenesis. A number of key cellular processes are governed by the effectors of this pathway, including immune responses and apoptosis, both crucial in the development of cancer. Therefore, it is not surprising that dysregulated and chronic NF-κB signalling can have a profound impact on cellular homeostasis. Here we discuss NFKB1 (p105/p50), one of the five subunits of NF-κB, widely implicated in carcinogenesis, in some cases driving cancer progression and in others acting as a tumour-suppressor...
September 7, 2018: Cells
Erik W Martin, Myong-Hee Sung
Technological advances are continually improving our ability to obtain more accurate views about the inner workings of biological systems. One such rapidly evolving area is single cell biology, and in particular gene expression and its regulation by transcription factors in response to intrinsic and extrinsic factors. Regarding the study of transcription factors, we discuss some of the promises and pitfalls associated with investigating how individual cells regulate gene expression through modulation of transcription factor activities...
September 7, 2018: Cells
Estefania Carrasco-Garcia, Isabel Martinez-Lacaci, Leticia Mayor-López, Elena Tristante, Mar Carballo-Santana, Pilar García-Morales, Maria Paz Ventero Martin, Maria Fuentes-Baile, Álvaro Rodriguez-Lescure, Miguel Saceda
Glioblastomas are highly resistant to radiation and chemotherapy. Currently, there are no effective therapies for this type of tumor. Signaling mechanisms initiated by PDGFR and IGF-1R are important in glioblastoma, and inhibition of the signal transduction pathways initiated by these receptors could be a useful alternative strategy for glioblastoma treatment. We have studied the effects of the PDGFR inhibitor JNJ-10198409 (JNJ) and the IGF-1R inhibitor picropodophyllin (PPP) in glioblastoma cell lines as well as in primary cultures derived from patients affected by this type of tumor...
September 6, 2018: Cells
Mohamed A Elmonem, Sante Princiero Berlingerio, Lambertus P van den Heuvel, Peter A de Witte, Martin Lowe, Elena N Levtchenko
The structural and functional similarity of the larval zebrafish pronephros to the human nephron, together with the recent development of easier and more precise techniques to manipulate the zebrafish genome have motivated many researchers to model human renal diseases in the zebrafish. Over the last few years, great advances have been made, not only in the modeling techniques of genetic diseases in the zebrafish, but also in how to validate and exploit these models, crossing the bridge towards more informative explanations of disease pathophysiology and better designed therapeutic interventions in a cost-effective in vivo system...
September 1, 2018: Cells
Jasmina Makarević, Jochen Rutz, Eva Juengel, Sebastian Maxeiner, Jens Mani, Stefan Vallo, Igor Tsaur, Frederik Roos, Felix K-H Chun, Roman A Blaheta
This study was designed to investigate whether epigenetic modulation by histone deacetylase (HDAC) inhibition might circumvent resistance towards the mechanistic target of rapamycin (mTOR) inhibitor temsirolimus in a prostate cancer cell model. Parental (par) and temsirolimus-resistant (res) PC3 prostate cancer cells were exposed to the HDAC inhibitor valproic acid (VPA), and tumor cell adhesion, chemotaxis, migration, and invasion were evaluated. Temsirolimus resistance was characterized by reduced binding of PC3res cells to endothelium, immobilized collagen, and fibronectin, but increased adhesion to laminin, as compared to the parental cells...
September 1, 2018: Cells
Natsuko Miura, Mitsuyoshi Ueda
Development of proteome analysis of extracellular proteins has revealed that a wide variety of proteins, including fungal allergens are present outside the cell. These secreted allergens often do not contain known secretion signal sequences. Recent research progress shows that some fungal allergens are secreted by unconventional secretion pathways, including autophagy- and extracellular-vesicle-dependent pathways. However, secretion pathways remain unknown for the majority of extracellular proteins. This review summarizes recent data on unconventional protein secretion in Saccharomyces cerevisiae and other fungi...
August 31, 2018: Cells
Andrea Aparecida de Aro, Giane Daniela Carneiro, Luis Felipe R Teodoro, Fernanda Cristina da Veiga, Danilo Lopes Ferrucci, Gustavo Ferreira Simões, Priscyla Waleska Simões, Lúcia Elvira Alvares, Alexandre Leite R de Oliveira, Cristina Pontes Vicente, Caio Perez Gomes, João Bosco Pesquero, Marcelo Augusto M Esquisatto, Benedicto de Campos Vidal, Edson Rosa Pimentel
Tendon injuries represent a clinical challenge in regenerative medicine because their natural repair process is complex and inefficient. The high incidence of tendon injuries is frequently associated with sports practice, aging, tendinopathies, hypertension, diabetes mellitus, and the use of corticosteroids. The growing interest of scientists in using adipose-derived mesenchymal stem cells (ADMSC) in repair processes seems to be mostly due to their paracrine and immunomodulatory effects in stimulating specific cellular events...
August 31, 2018: Cells
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