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https://www.readbyqxmd.com/read/29452090/activation-of-calcium-sensing-receptor-mediated-autophagy-in-angiotensinii-induced-cardiac-fibrosis-in-vitro
#1
Jinyu Chi, Lei Wang, Xiaohui Zhang, Yu Fu, Yue Liu, Wenjia Chen, Wenxiu Liu, Zhiyu Shi, Xinhua Yin
Cardiac fibrosis is one of the primary mechanisms of ventricular remodeling, and there is no effective method for reversal. Activation of calcium sensing receptor (CaSR) has been reported to be involved in the development of myocardial fibrosis, but the molecular mechanism for CaSR activation has not yet been clarified and needs to be further explored. Here, we found that AngII induces cardiac fibroblast proliferation and phenotypic transformation in a dose-dependent manner with increased CaSR and autophagy related protein (Beclin1, LC3B) expression...
February 13, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29451701/phase-1b-study-of-pasireotide-everolimus-and-selective-internal-radioembolization-therapy-for-unresectable-neuroendocrine-tumors-with-hepatic-metastases
#2
Hyun S Kim, Walid L Shaib, Chao Zhang, Ganji Purnachandra Nagaraju, Christina Wu, Olatunji B Alese, Zhengjia Chen, Edith Brutcher, Meredith Renfroe, Bassel F El-Rayes
BACKGROUND: Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT. METHODS: This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2...
February 16, 2018: Cancer
https://www.readbyqxmd.com/read/29450149/human-and-mouse-microarrays-guided-expression-analysis-of-membrane-protein-trafficking-related-genes-in-mdck-cells-a-canine-epithelial-model-for-apical-and-basolateral-differential-protein-targeting
#3
Xiaofan Xu, Mingming Pan, Alexis E Gasiewicz, Rongzi Li, Shiu-Ming Kuo
MDCK cells are widely used to study the differential targeting of membrane transporters to apical and basolateral membrane but its canine origin limited the commercial tools available for the analysis of protein trafficking machinery. Because apical and basolateral membranes are only found in differentiated epithelial cells, genes critical for differential targeting may be specifically up-regulated upon MDCK cell differentiation. To search for these genes, a cross-species screening strategy was used. We first analyzed the human microarray data for protein trafficking-related genes that were up-regulated in colon carcinoma Caco2 cells upon differentiation...
June 2017: Biochimie Open
https://www.readbyqxmd.com/read/29449529/gambogenic-acid-inhibits-fibroblast-growth-factor-receptor-signaling-pathway-in-erlotinib-resistant-non-small-cell-lung-cancer-and-suppresses-patient-derived-xenograft-growth
#4
Linfeng Xu, Xiaoxiao Meng, Naihan Xu, Wenwei Fu, Hongsheng Tan, Li Zhang, Qianjun Zhou, Jianan Qian, Shiwei Tu, Xueting Li, Yuanzhi Lao, Hongxi Xu
Erlotinib resistance causes a high degree of lethality in non-small-cell lung cancer (NSCLC) patients. The high expression and activation of several receptor tyrosine kinases, such as JAK/STAT3, c-Met, and EGFR, play important roles in drug resistance. The development of tyrosine kinase inhibitors is urgently required in the clinic. Our previous study found that Gambogenic acid (GNA), a small molecule derived from the traditional Chinese medicine herb gamboge, induced cell death in several NSCLC cell lines through JAK/STAT3 inhibition...
February 15, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29447281/peptidic-inhibitors-of-insulin-degrading-enzyme-with-potential-for-dermatological-applications-discovered-via-phage-display
#5
Caitlin N Suire, Sarah Nainar, Michael Fazio, Adam G Kreutzer, Tara Paymozd-Yazdi, Caitlyn L Topper, Caroline R Thompson, Malcolm A Leissring
Insulin-degrading enzyme (IDE) is an atypical zinc-metalloendopeptidase that hydrolyzes insulin and other intermediate-sized peptide hormones, many of which are implicated in skin health and wound healing. Pharmacological inhibitors of IDE administered internally have been shown to slow the breakdown of insulin and thereby potentiate insulin action. Given the importance of insulin and other IDE substrates for a variety of dermatological processes, pharmacological inhibitors of IDE suitable for topical applications would be expected to hold significant therapeutic and cosmetic potential...
2018: PloS One
https://www.readbyqxmd.com/read/29447206/multiplex-crispr-cas9-system-impairs-hcmv-replication-by-excising-an-essential-viral-gene
#6
Janina Gergen, Flora Coulon, Alison Creneguy, Nathan Elain-Duret, Alejandra Gutierrez, Olaf Pinkenburg, Els Verhoeyen, Ignacio Anegon, Tuan Huy Nguyen, Franck Albert Halary, Fabienne Haspot
Anti-HCMV treatments used in immunosuppressed patients reduce viral replication, but resistant viral strains can emerge. Moreover, these drugs do not target latently infected cells. We designed two anti-viral CRISPR/Cas9 strategies to target the UL122/123 gene, a key regulator of lytic replication and reactivation from latency. The singleplex strategy contains one gRNA to target the start codon. The multiplex strategy contains three gRNAs to excise the complete UL122/123 gene. Primary fibroblasts and U-251 MG cells were transduced with lentiviral vectors encoding Cas9 and one or three gRNAs...
2018: PloS One
https://www.readbyqxmd.com/read/29446095/orobanche-cernua-loefling-attenuates-ultraviolet-b-mediated-photoaging-in-human-dermal-fibroblasts
#7
Wei Gao, Yu-Shuai Wang, Zheng-Yi Qu, Eunson Hwang, Hien T T Ngo, Ying-Ping Wang, Jahyun Bae, Tae-Hoo Yi
UV radiation is the primary cause of skin photoaging, which results in an increase in matrix metalloproteinases and degradation of collagen. Developing new natural antioxidant as photoprotective agents have become a popular area of research. Orobanche cernua Loefling is a parasitic plant that is rich in phenylethanoid glycosides (PhGs). This study investigated the photoprotective effects of the ethanolic extract of Orobanche cernua Loefling (OC) and its principal component acteoside on UVB-induced photoaging as well as their underlying molecular mechanisms in normal human dermal fibroblasts (NHDFs)...
February 15, 2018: Photochemistry and Photobiology
https://www.readbyqxmd.com/read/29446010/phosphaturic-mesenchymal-tumors-what-an-endocrinologist-should-know
#8
REVIEW
J M Boland, P J Tebben, A L Folpe
Tumor-induced osteomalacia (TIO), also known as "oncogenic osteomalacia", is a rare cause of osteomalacia. TIO often has an insidious onset characterized clinically by progressive muscle weakness and bone pain with fractures. The hallmark biochemical finding is a persistent low serum phosphorus concentration due to renal phosphate wasting. The vast majority of cases of TIO result from production of the phosphaturic hormone fibroblast growth factor 23 (FGF23) by a histologically distinctive mesenchymal tumor, termed "phosphaturic mesenchymal tumor" (PMT)...
February 14, 2018: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29445421/evidence-for-a-pre-malignant-cell-line-in-a-skin-biopsy-from-a-patient-with-nijmegen-breakage-syndrome
#9
Raneem Habib, Heidemarie Neitzel, Aurelie Ernst, John K L Wong, Bozenna Goryluk-Kozakiewicz, Antje Gerlach, Ilja Demuth, Karl Sperling, Krystyna Chrzanowska
Background: Nijmegen breakage syndrome is an autosomal recessive disorder characterized by microcephaly, immunodeficiency, hypersensitivity to X-irradiation, and a high predisposition to cancer. Nibrin, the product of the NBN gene, is part of the MRE11/RAD50 (MRN) complex that is involved in the repair of DNA double strand breaks (DSBs), and plays a critical role in the processing of DSBs in immune gene rearrangements, telomere maintenance, and meiotic recombination. NBS skin fibroblasts grow slowly in culture and enter early into senescence...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29445083/fibroblast-growth-factor-21-prevents-diabetic-cardiomyopathy-via-ampk-mediated-antioxidation-and-lipid-lowering-effects-in-the-heart
#10
Hong Yang, Anyun Feng, Sundong Lin, Lechu Yu, Xiufei Lin, Xiaoqing Yan, Xuemian Lu, Chi Zhang
Our previous studies showed that both exogenous and endogenous FGF21 inhibited cardiac apoptosis at the early stage of type 1 diabetes. Whether FGF21 induces preventive effect on type 2 diabetes-induced cardiomyopathy was investigated in the present study. High-fat-diet/streptozotocin-induced type 2 diabetes was established in both wild-type (WT) and FGF21-knockout (FGF21-KO) mice followed by treating with FGF21 for 4 months. Diabetic cardiomyopathy (DCM) was diagnosed by significant cardiac dysfunction, remodeling, and cardiac lipid accumulation associated with increased apoptosis, inflammation, and oxidative stress, which was aggravated in FGF21-KO mice...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29444177/kidney-differentiated-cells-derived-from-lowe-syndrome-patient-s-ipscs-show-ciliogenesis-defects-and-six2-retention-at-the-golgi-complex
#11
Wen-Chieh Hsieh, Swetha Ramadesikan, Donna Fekete, Ruben Claudio Aguilar
Lowe syndrome is an X-linked condition characterized by congenital cataracts, neurological abnormalities and kidney malfunction. This lethal disease is caused by mutations in the OCRL1 gene, which encodes for the phosphatidylinositol 5-phosphatase Ocrl1. While in the past decade we witnessed substantial progress in the identification and characterization of LS patient cellular phenotypes, many of these studies have been performed in knocked-down cell lines or patient's cells from accessible cell types such as skin fibroblasts, and not from the organs affected...
2018: PloS One
https://www.readbyqxmd.com/read/29444077/peculiar-combinations-of-individually-non-pathogenic-missense-mitochondrial-dna-variants-cause-low-penetrance-leber-s-hereditary-optic-neuropathy
#12
Leonardo Caporali, Luisa Iommarini, Chiara La Morgia, Anna Olivieri, Alessandro Achilli, Alessandra Maresca, Maria Lucia Valentino, Mariantonietta Capristo, Francesca Tagliavini, Valentina Del Dotto, Claudia Zanna, Rocco Liguori, Piero Barboni, Michele Carbonelli, Veronica Cocetta, Monica Montopoli, Andrea Martinuzzi, Giovanna Cenacchi, Giuseppe De Michele, Francesco Testa, Anna Nesti, Francesca Simonelli, Anna Maria Porcelli, Antonio Torroni, Valerio Carelli
We here report on the existence of Leber's hereditary optic neuropathy (LHON) associated with peculiar combinations of individually non-pathogenic missense mitochondrial DNA (mtDNA) variants, affecting the MT-ND4, MT-ND4L and MT-ND6 subunit genes of Complex I. The pathogenic potential of these mtDNA haplotypes is supported by multiple evidences: first, the LHON phenotype is strictly inherited along the maternal line in one very large family; second, the combinations of mtDNA variants are unique to the two maternal lineages that are characterized by recurrence of LHON; third, the Complex I-dependent respiratory and oxidative phosphorylation defect is co-transferred from the proband's fibroblasts into the cybrid cell model...
February 14, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29442539/platelets-in-wound-healing-and-regenerative-medicine
#13
Julia Etulain
Although platelets are widely recognized as having a critical role in primary hemostasis and thrombosis, increasing experimental and clinical evidence identifies these enucleated cells as relevant modulators of other physiopathological processes including inflammation and tissue regeneration. These phenomena are mediated through the release of growth factors, cytokines, and extracellular matrix modulators that sequentially promote (i) revascularization of damaged tissue through the induction of migration, proliferation, differentiation, and stabilization of endothelial cells in new blood vessels; (ii) restoration of damaged connective tissue through migration, proliferation, and activation of fibroblasts; and (iii) proliferation and differentiation of mesenchymal stem cells into tissue-specific cell types...
February 14, 2018: Platelets
https://www.readbyqxmd.com/read/29441570/inhibition-of-nox4-dependent-ros-signaling-attenuates-prostate-fibroblast-activation-and-abrogates-stromal-mediated-pro-tumorigenic-interactions
#14
Natalie Sampson, Elena Brunner, Anja Weber, Martin Puhr, Georg Schäfer, Cedric Szyndralewiez, Helmut Klocker
Carcinoma-associated fibroblasts (CAFs) play a key onco-supportive role during prostate cancer (PCa) development and progression. We previously reported that the reactive oxygen species (ROS)-producing enzyme NADPH oxidase 4 (Nox4) is essential for TGFβ1-mediated activation of primary prostate human fibroblasts to a CAF-like phenotype. This study aimed to further investigate the functional relevance of prostatic Nox4 and determine whether pharmacological inhibition of stromal Nox4 abrogates paracrine-mediated PCa-relevant processes...
February 14, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29440885/annexin-a1-is-elevated-in-patients-with-copd-and-affects-lung-fibroblast-function
#15
Tianwen Lai, Yanyu Li, Zongjiong Mai, Xiaoxia Wen, Yingying Lv, Zhanqing Xie, Quanchao Lv, Min Chen, Dong Wu, Bin Wu
Purpose: Fibrosis in peripheral airways is responsible for airflow limitation in chronic obstructive pulmonary disease (COPD). Annexin A1 modulates several key biological events during inflammation. However, little is known about its role in airway fibrosis in COPD. We investigated whether levels of Annexin A1 were upregulated in patients with COPD, and whether it promoted airway fibrosis. Methods: We quantified serum Annexin A1 levels in never-smokers (n=12), smokers without COPD (n=11), and smokers with COPD (n=22)...
2018: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/29439343/overactive-brca1-affects-presenilin-1-in-induced-pluripotent-stem-cell-derived-neurons-in-alzheimer-s-disease
#16
Michalina Wezyk, Aleksandra Szybinska, Joanna Wojsiat, Marcelina Szczerba, Kelly Day, Harriet Ronnholm, Malin Kele, Mariusz Berdynski, Beata Peplonska, Jakub Piotr Fichna, Jan Ilkowski, Maria Styczynska, Anna Barczak, Marzena Zboch, Anna Filipek-Gliszczynska, Krzysztof Bojakowski, Magdalena Skrzypczak, Krzysztof Ginalski, Michal Kabza, Izabela Makalowska, Maria Barcikowska-Kotowicz, Urszula Wojda, Anna Falk, Cezary Zekanowski
 The BRCA1 protein, one of the major players responsible for DNA damage response has recently been linked to Alzheimer's disease (AD). Using primary fibroblasts and neurons reprogrammed from induced pluripotent stem cells (iPSC) derived from familial AD (FAD) patients, we studied the role of the BRCA1 protein underlying molecular neurodegeneration. By whole-transcriptome approach, we have found wide range of disturbances in cell cycle and DNA damage response in FAD fibroblasts. This was manifested by significantly increased content of BRCA1 phosphorylated on Ser1524 and abnormal ubiquitination and subcellular distribution of presenilin 1 (PS1)...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29436696/cxcr4-receptor-blockage-reduces-the-contribution-of-tumor-and-stromal-cells-to-the-metastatic-growth-in-the-liver
#17
Aitor Benedicto, Irene Romayor, Beatriz Arteta
The liver is a common site for the metastatic spread of primary malignancies including colorectal cancer, and liver metastasis is a main cause of death in cancer patients. This is due to the complexity of the interactions taking place in the liver between tumor and stromal cells. In fact, cancer‑associated fibroblasts (CAFs) have been shown to support tumor growth through the CXCL12/CXCR4 axis. However, along with cancer cells, myeloid‑derived suppressor cells (MDSCs), immature dendritic cells with immunosuppressive potential, also express CXCR4...
February 8, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29436393/therapeutically-targeting-tumor-microenvironment-mediated-drug-resistance-in-estrogen-receptor-positive-breast-cancer
#18
Kevin Shee, Wei Yang, John W Hinds, Riley A Hampsch, Frederick S Varn, Nicole A Traphagen, Kishan Patel, Chao Cheng, Nicole P Jenkins, Arminja N Kettenbach, Eugene Demidenko, Philip Owens, Anthony C Faber, Todd R Golub, Ravid Straussman, Todd W Miller
Drug resistance to approved systemic therapies in estrogen receptor-positive (ER+) breast cancer remains common. We hypothesized that factors present in the human tumor microenvironment (TME) drive drug resistance. Screening of a library of recombinant secreted microenvironmental proteins revealed fibroblast growth factor 2 (FGF2) as a potent mediator of resistance to anti-estrogens, mTORC1 inhibition, and phosphatidylinositol 3-kinase inhibition in ER+ breast cancer. Phosphoproteomic analyses identified ERK1/2 as a major output of FGF2 signaling via FGF receptors (FGFRs), with consequent up-regulation of Cyclin D1 and down-regulation of Bim as mediators of drug resistance...
February 7, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29435158/osteopontin-integrin-engagement-induces-hif-1%C3%AE-tcf12-mediated-endothelial-mesenchymal-transition-to-exacerbate-colorectal-cancer
#19
Chi-Shuan Fan, Wei-Shone Chen, Li-Li Chen, Chia-Chi Chen, Yu-Ting Hsu, Kee Voon Chua, Horng-Dar Wang, Tze-Sing Huang
Osteopontin (OPN) is a multi-functional phospho-glycoprotein that can stimulate angiogenesis through acting on endothelial cells. As angiogenic sprouting involves endothelial-to-mesenchymal transition (EndoMT), we are intrigued to know whether OPN exerts an effect on EndoMT. Clinically, we indeed detected EndoMT-derived cells next to OPN-expressing cells in colorectal cancer tissues. Furthermore, we treated OPN to primary cultures of endothelial cells to investigate the EndoMT-inducing activity and the underlying mechanisms...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29434868/cytotoxic-effect-of-efavirenz-in-bxpc-3-pancreatic-cancer-cells-is-based-on-oxidative-stress-and-is-synergistic-with-ionizing-radiation
#20
Markus Hecht, Thomas Harrer, Verena Körber, Eric O Sarpong, Fabian Moser, Nora Fiebig, Manuela Schwegler, Michael Stürzl, Rainer Fietkau, Luitpold V Distel
The non-nucleoside reverse transcriptase inhibitor (NNRTI) Efavirenz is frequently used in human immunodeficiency virus treatment, but also efficient against cancer in mouse models. Its radiosensitizing effect makes it a promising drug for combination with radiotherapy. The efficacy of Efavirenz combined with irradiation was assessed with immunostaining of DNA-damage markers and colony formation assays in BxPC-3 pancreatic cancer cells. Gene expression and protein phosphorylation of the Efavirenz-sensitive BxPC-3 cells was compared to the resistant primary fibroblasts SBL-5...
February 2018: Oncology Letters
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