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Łukasz Uram, Aleksandra Filipowicz, Maria Misiorek, Natalia Pieńkowska, Joanna Markowicz, Elżbieta Wałajtys-Rode, Stanisław Wołowiec
Tumors still remain one of the main causes of mortality due to the lack of effective anti-cancer therapy. Recently it has been shown, that overexpression of inducible cyclooxygenase-2 (COX-2) and decrease of peroxisome proliferator-activated receptor γ (PPARγ) expression accompany many malignances, therefore, it has been proposed, that COX-2 inhibitors and PPARγ agonists are potential candidates for anticancer therapy and their synergistic, antineoplastic action has been described. In the present study a COX-2 inhibitor (celecoxib) and/or PPARγ agonist (Fmoc-l-Leucine) were conjugated with the biotinylated G3 PAMAM dendrimer to form a three different constructs targeted to cells with increased biotin uptake...
August 14, 2018: European Journal of Pharmaceutical Sciences
Chien-Chi Lin, Murray Korc
Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer mortality in the United States, with a 5-year survival of ∼8%. PDAC is characterized by a dense and hypo-vascularized stroma consisting of proliferating cancer cells, cancer-associated fibroblasts, macrophages and immune cells, as well as excess matrices including collagens, fibronectin, and hyaluronic acid. In addition, PDAC has increased interstitial pressures and a hypoxic/acidic tumor microenvironment (TME) that impedes drug delivery and blocks cancer-directed immune mechanisms...
August 14, 2018: Cancer Letters
Natali Froese, Honghui Wang, Carolin Zwadlo, Yong Wang, Andrea Grund, Anna Gigina, Melanie Hofmann, Katja Kilian, Gesine Scharf, Mortimer Korf-Klingebiel, Anna Melchert, Maria Elena Ricci Signorini, Caroline Halloin, Robert Zweigerdt, Ulrich Martin, Ina Gruh, Kai C Wollert, Robert Geffers, Johann Bauersachs, Joerg Heineke
Maladaptive cardiac remodeling after myocardial infarction (MI) is increasingly contributing to the prevalence of chronic heart failure. Women show less severe remodeling, a reduced mortality and a better systolic function after MI compared to men. Although sex hormones are being made responsible for these differences, it remains currently unknown how this could be translated into therapeutic strategies. Because we had recently demonstrated that inhibition of the conversion of testosterone to its highly active metabolite dihydrotestosterone (DHT) by finasteride effectively reduces cardiac hypertrophy and improves heart function during pressure overload, we asked here whether this strategy could be applied to post-MI remodeling...
August 14, 2018: Journal of Molecular and Cellular Cardiology
Miroslava Didiasova, Lukasz Wujak, Liliana Schaefer, Malgorzata Wygrecka
Factor XII (FXII) is a protease that is mainly produced in the liver and circulates in plasma as a single chain zymogen. Following contact with negatively charged surfaces, FXII is converted into the two-chain active form, FXIIa. FXIIa initiates the intrinsic blood coagulation pathway via activation of factor XI. Furthermore, it converts plasma prekallikrein to kallikrein (PK), which reciprocally activates FXII and liberates bradykinin from high molecular weight kininogen. In addition, FXIIa initiates fibrinolysis via PK-mediated urokinase activation and activates the classical complement pathway...
August 14, 2018: Cellular Signalling
J Cheng, G Jiang, R Tarzemany, H Larjava, L Häkkinen
AIMS: Abundance of connexin 43 (Cx43), a transmembrane protein that forms hemichannels (HCs) and gap junctions (GJs), is dynamically regulated in human gingival fibroblasts (GFBLs) during wound healing. This may be important for fast and scarless gingival wound healing as Cx43 is involved in key cell functions important during this process. Our aim was to uncover the factors that regulate Cx43 expression and abundance in GFBLs. We hypothesized that cytokines and growth factors released during wound healing coordinately regulate Cx43 abundance in GFBLs...
August 14, 2018: Experimental Cell Research
Seong-Wook Seo, Seul-Ki Park, Soo-Jin Oh, Ok Sarah Shin
Exposure to ultraviolet (UV) radiation is a major contributing factor to premature aging (photoaging) and skin cancer. In vitro models of cellular senescence have proven to be very useful for the study of slow and progressive accumulation of damage resulting in the growth arrest of aging skin cells. In this study, we compared UVA-induced cellular responses in non-senescent (NS) vs. senescent (S) human dermal fibroblasts (HDFs). HDFs were irradiated with a single dose of UVA (7.5 J/cm2) and QuantSeq 3' mRNA sequencing was performed to assess differential gene expression...
2018: PloS One
Zhengyi He, Rui Lu, Ting Zhang, Lei Jiang, Minya Zhou, Daijin Wu, Yong Cheng
BACKGROUND: Thromboses is a rapidly growing medical problem worldwide. Low-cost, high-scale production of thrombotic drugs is needed to meet the demand. The production of biomolecules in transgenic animals might help address this issue. To our knowledge, the expression of recombinant human plasminogen activator (rhPA) in goat mammary glands has never been reported before. METHODS: We constructed a mammary gland-specific expression vector, BLC14/rhPA, which encodes only the essential K2 fibrin-binding and P domains of wild-type tPA (deletion mutant of tPA lacking the F, E, and K1 domains), along with the goat β-lactoglobulin gene signal peptide-coding sequence...
2018: PloS One
Alex Dobzanski, Syed Muaz Khalil, Andrew P Lane
BACKGROUND: While essential to the normal differentiation of ciliated airway epithelial cells, upregulated Wnt signaling in chronic rhinosinusitis with nasal polyps (CRSwNP) has been proposed to result in abnormal epithelial morphology and dysfunctional mucociliary clearance. The mechanism of epithelial Wnt signaling dysregulation in CRSwNP is unknown, and importantly cellular sources of Wnt ligands in CRSwNP have not yet been investigated. METHODS: Human sinonasal epithelial cells (hSNECs) and human sinonasal fibroblasts (hSNFs) were collected from 34 human subjects (25 control and 9 CRSwNP) and differentiated as primary air-liquid interface (ALI) and organoid co-cultures...
August 17, 2018: International Forum of Allergy & Rhinology
Corrie L Gallant-Behm, Joseph Piper, Brent A Dickinson, Christina M Dalby, Linda A Pestano, Aimee L Jackson
There is a strong unmet need for new therapeutics to accelerate wound healing across both chronic and acute indications. It is well established that local tissue hypoxia, vascular insufficiency and/or insufficient angiogenesis contribute to inadequate wound repair in the context of diabetic foot ulcers as well as to other chronic wounds such as venous stasis and pressure ulcers. microRNA-92a-3p (miR-92a) is a potent anti-angiogenic miRNA whose inhibition has led to increases in angiogenesis in multiple organ systems, resulting in an improvement in function following myocardial infarction, limb ischemia, vascular injury and bone fracture...
August 17, 2018: Wound Repair and Regeneration
Riccardo Ricci, Maria Cristina Giustiniani, Marco Gessi, Paola Lanza, Federica Castri, Alberto Biondi, Roberto Persiani, Fabio M Vecchio, Mauro Risio
PDGFRA mutations in the gastrointestinal (GI) tract can cause GI stromal tumour (GIST) and inflammatory fibroid polyp (IFP). Hitherto no cell type has been identified as a physiological counterpart of the latter, while interstitial Cajal cells (ICC) are considered the precursor of the former. However, ICC hyperplasia (ICCH), which strongly supports the ICC role in GIST pathogenesis, has been identified in germline KIT-mutant settings but not in PDGFRA-mutant ones, challenging the precursor role of ICC for PDGFRA-driven GISTs...
August 17, 2018: Journal of Cellular and Molecular Medicine
Guang Dong Hu, Ke Xing Hao, Tao Huang, Wei Bin Zeng, Xin Li Gu, Jing Wang
piggyBac (PB) is a DNA transposon that mediates transposition in various animal cells. As an efficient tool, PB transposons are applied to various transgenic research and optimized for different species, which is an essential means to enhance its versatility. To construct a universal PB transposase (PBase) vector for ovine transgene manipulation, the gene expression box of PBase with optimized bias for sheep codons was inserted into the pBNW-TP1 vector. The vector pBNW-TP2 with a single plasmid was successfully constructed...
August 16, 2018: Yi Chuan, Hereditas
Barbara Hernando, Viki B Swope, Steven Guard, Renny J Starner, Kevin Choi, Ayesha Anwar, Pamela Cassidy, Sancy Leachman, Ana Luisa Kadekaro, Dorothy C Bennett, Zalfa A Abdel-Malek
Co-inheritance of germline mutation in cyclin-dependent kinase inhibitor 2A (CDKN2A) and loss-of-function (LOF) melanocortin 1 receptor (MC1R) variants is clinically associated with exaggerated risk for melanoma. To understand the combined impact of these mutations, we established and tested primary human melanocyte cultures from different CDKN2A mutation carriers, expressing either wild-type MC1R or MC1R LOF variant(s). These cultures expressed the CDKN2A product p16 (INK4A) and functional MC1R. Except for 32ins24 mutant melanocytes, the remaining cultures showed no detectable aberrations in proliferation or capacity for replicative senescence...
August 16, 2018: Pigment Cell & Melanoma Research
Luiz H Lima, Michel E Farah, Glenwood Gum, Pamela Ko, Ricardo A de Carvalho
Background: To evaluate the efficacy of selective episcleral delivery of celecoxib formulated in a sustained-release episcleral exoplant on a model of retinal and choroidal neovascularization induced in rabbits by subretinal injection of matrigel combined with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Methods: Nine New Zealand white rabbits were randomly assigned to three groups (episcleral celecoxib exoplant, intravitreal bevacizumab injection and control group)...
2018: International Journal of Retina and Vitreous
Jing Jing Liu, Li Meng
The 8p11 myeloproliferative syndrome (EMS), a rare myeloproliferative disease, generally progresses rapidly and is characterized by chromosomal translocations of the fibroblast growth factor receptor 1 (FGFR1) gene. The FGFR1 gene is located at chromosome 8p11 and may fuse with distinct partner genes. The breakpoint cluster region gene located at chromosome 22 is one of these partner genes. The patients' clinical phenotype is primarily dependant on the partner gene that translocates with FGFR1. Of all the available examinations, determination of the chromosome karyotype is most essential for the diagnosis of EMS...
August 2018: Experimental and Therapeutic Medicine
Chengfang Xu, Zhenyan Han, Ping Li, Xuejiao Li
Gestational diabetes mellitus (GDM) is a metabolic disease with symptoms of hyperglycemia, insulin resistance and fetal maldevelopment. Evidence has indicated that fibroblast growth factor (FGF)-21 is a multifunctional protein and exhibits potential therapeutic value for metabolic diseases. The present study investigated the diagnostic value of FGF-21 serum levels in patients with GDM (n=50) and age-matched healthy individuals (n=50). It was demonstrated that the gene and protein expression levels of FGF-21 were downregulated in adipose cells in patients with GDM compared with those in healthy individuals...
August 2018: Experimental and Therapeutic Medicine
Sun-Young Lee, Sery Lim, Dong-Hyu Cho
A 16-year-old female with Ewing sarcoma, a very rare disease with poor prognosis in women, was admitted to the hospital with abdominal pain. Diagnostic laparotomy revealed the Ewing sarcoma originating from the extramural uterus. Histological examination yielded positive test results for CD99, vimentin, S-100, eosin 5-maleimide and periodic acid-Shiff. EWS-FLI1 type 1 translocation was confirmed. Fibroblast growth factor receptor (FGFR) 4 (c.1162G> A) and HRas proto-oncogene (HRAS; c.182A> G) mutations were also detected...
August 2018: Experimental and Therapeutic Medicine
Qi Chen, Tianlan Zhao, Xiaoming Xie, Daojiang Yu, Lijun Wu, Wenyuan Yu, Wei Sun
The present study determined the expression of microRNA (miR)-663 in hypertrophic scar (HS) tissues and investigate the regulatory mechanisms of miR-663 in HS. A total of 51 patients diagnosed with HS between December 2013 and February 2016 were included in the present study. HS tissues (experimental group) and HS-adjacent tissues (control group) were collected. Primary fibroblasts were obtained from HS tissue and transfected with small-interfering RNA against transforming growth factor (TGF)-β1 or miR-663 mimics...
August 2018: Experimental and Therapeutic Medicine
Dan Wang, Xinhao Jiang, Aiqing Lu, Min Tu, Wei Huang, Ping Huang
Bone marrow mesenchymal stem cells (BMSCs) are pluripotent cells, which have the capacity to differentiate into various types of mesenchymal cell phenotypes, including osteoblasts, chondroblasts, myoblasts and tendon fibroblasts (TFs). The molecular mechanism for tenogenic differentiation of BMSCs is still unknown. The present study investigated the effects of bone morphogenetic protein (BMP) 14 on BMSC differentiation in vitro . It was revealed that BMP14 significantly increased the expression of tendon markers (scleraxis and tenomodulin) at the mRNA and protein level, which led to the upregulation of sirtuin 1 (Sirt1) expression...
August 2018: Experimental and Therapeutic Medicine
Ya-Lin Lu, Andrew S Yoo
The use of transcriptional factors as cell fate regulators are often the primary focus in the direct reprogramming of somatic cells into neurons. However, in human adult fibroblasts, deriving functionally mature neurons with high efficiency requires additional neurogenic factors such as microRNAs (miRNAs) to evoke a neuronal state permissive to transcription factors to exert their reprogramming activities. As such, increasing evidence suggests brain-enriched miRNAs, miR-9/9∗ and miR-124, as potent neurogenic molecules through simultaneously targeting of anti-neurogenic effectors while allowing additional transcription factors to generate specific subtypes of human neurons...
2018: Frontiers in Neuroscience
Bin Zhu, Li-Na Jin, Jian-Qin Shen, Jin-Feng Liu, Ri-Yue Jiang, Ling Yang, Jie Zhang, Ai-Lin Luo, Li-Ying Miao, Chun Yang
Studies suggest that hemodialysis patients are at a higher risk for cognitive decline than healthy individuals; however, underlying mechanisms have not been fully elucidated. We aimed to investigate the roles of serum biomarkers, such as brain-derived neurotrophic factor (BDNF), inflammatory cytokines, fibroblast growth factor (FGF)-23 and its co-receptor α-klotho and platelet (PLT) count in mild cognitive decline (MCD) of patients undergoing hemodialysis in this prospective cohort study. Serum levels of BDNF, tumour necrosis factor (TNF)-α, interleukin (IL)-6 and the number of PLT were significantly altered in the MCD group compared with those in healthy controls (HCs) or those with normal cognitive function (NCF)...
August 16, 2018: Scientific Reports
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