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Caroline Wilson
The spread of breast cancer cells to bone and survival in this new metastatic environment is influenced not only by the genetic signature of the cells, but also multiple host cells and soluble factors produced locally (paracrine) or from distant sites (endocrine). Disrupting this metastatic process has been evaluated in clinical trials of the bone targeted agents bisphosphonates and denosumab and have shown that these agents reduce the recurrence of breast cancer in postmenopausal women only, suggesting the efficacy of the drugs are influenced by levels of reproductive endocrine hormones...
September 2016: Journal of Bone Oncology
E C Martino, G Misso, P Pastina, S Costantini, F Vanni, C Gandolfo, C Botta, F Capone, A Lombardi, L Pirtoli, P Tassone, C Ulivieri, P Tagliaferri, M G Cusi, M Caraglia, P Correale
The mPEBev is an anticancer regimen which combines a chemotherapy doublet, based on cisplatin and oral etoposide (mPE), with bevacizumab (mPEBev), a mAb targeting the vasculo-endothelial growth factor (VEGF). In previous studies, this regimen showed powerful anti-angiogenetic effects and significant antitumor activity in metastatic non-small-cell lung cancer (mNSCLC) patients. We also recorded the best benefit in patients exhibiting low-systemic inflammatory profile at baseline. On these bases, we hypothesized that mPEBev antitumor activity could be partially related to bevacizumab-associated immunological effects...
2016: Cell Death Discovery
Gang Li, Qing-Shan Li, Wen-Bin Li, Jian Wei, Wen-Kai Chang, Zhi Chen, Hu-Yun Qiao, Ying-Wei Jia, Jiang-Hua Tian, Bing-Sheng Liang
Denervation often results in skeletal muscle atrophy. Different mechanisms seem to be involved in the determination between denervated slow and fast skeletal muscle atrophy. At the epigenetic level, miRNAs are thought to be highly involved in the pathophysiological progress of denervated muscles. We used miRNA microarrays to determine miRNA expression profiles from a typical slow muscle (soleus muscle) and a typical fast muscle (tibialis anterior muscle) at an early denervation stage in a rat model. Results showed that miR-206, miR-195, miR-23a, and miR-30e might be key factors in the transformation process from slow to fast muscle in denervated slow muscles...
August 2016: Neural Regeneration Research
Qun Wei, Haiyan Liu, Miao Liu, Chunyan Yang, Jie Yang, Zhonghui Liu, Ping Yang
Prior studies have shown that overexpression of ACT A can lead to ventricular remodeling in rat models of heart failure. Furthermore, recently work studying demonstrated that stimulation of activin An expression in rat aortic smooth muscle (RASM) cells by angiotensin II (Ang II). Ramipril is a recently developed angiotensin converting enzyme (ACE) inhibitor. To investigate the effects of Ramipril on expression of ACT A-FS, we established the rat model of heart failure after myocardial infarction (MI), and divided into either a sham operation (SO), MI, or MI-Ramipril group...
2016: Scientific Reports
Andrew P Hinck, Thomas D Mueller, Timothy A Springer
We review the evolution and structure of members of the transforming growth factor β (TGF-β) family, antagonistic or agonistic modulators, and receptors that regulate TGF-β signaling in extracellular environments. The growth factor (GF) domain common to all family members and many of their antagonists evolved from a common cystine knot growth factor (CKGF) domain. The CKGF superfamily comprises six distinct families in primitive metazoans, including the TGF-β and Dan families. Compared with Wnt/Frizzled and Notch/Delta families that also specify body axes, cell fate, tissues, and other families that contain CKGF domains that evolved in parallel, the TGF-β family was the most fruitful in evolution...
September 16, 2016: Cold Spring Harbor Perspectives in Biology
Gaetano Leto, Lorena Incorvaia, Carla Flandina, Chiara Ancona, Fabio Fulfaro, Marilena Crescimanno, Maria Vittoria Sepporta, Giuseppe Badalamenti
This study was directed to assess the clinical impact of the circulating cathepsin L, cystatin C, activin A, and follistatin in breast cancer patients. The serum concentrations of these molecules were determined by immunoenzymatic assays, and their association with some clinico-pathological parameters of breast cancer progression was evaluated. Our results identified cystatin C and activin A as predictive markers for the presence of breast cancer and bone metastasis, respectively. Therefore, these proteins may have a clinical role as circulating biomarkers in the diagnosis and therapeutic monitoring of breast cancer patients...
October 20, 2016: Cancer Investigation
Ayse Yasemin Karageyim Karsidag, Yunus Emre Purut, Esra Esim Buyukbayrak, Asuman Orçun, Mehmet Menke
PURPOSE: To determine whether the first trimester maternal serum levels of follistatin like 3 (FSTL3) are altered in patients who develop gestational diabetes mellitus (GDM). METHODS: This is a prospective nested case-control study that included 170 singleton pregnant women recruited in their first trimester. All women were followed up until the delivery and 144 of them completed the study. The maternal serum levels of FSTL3 were measured at 11-14 weeks of gestation...
September 14, 2016: Journal of Maternal-fetal & Neonatal Medicine
Stergios A Polyzos, Jannis Kountouras, Athanasios D Anastasilakis, Georgios Α Triantafyllou, Christos S Mantzoros
OBJECTIVE: There are limited data on the role of activin A and its binding protein, follistatin, in nonalcoholic fatty liver disease (NAFLD). The main aim was the evaluation of serum activin A and follistatin levels in patients with biopsy-proven NAFLD vs. METHODS: This was a case-control study. Fifteen patients with nonalcoholic simple steatosis (SS), 16 with steatohepatitis (NASH), and 52 (24 lean and 28 obese) controls were recruited. Activin A and follistatin were measured using ELISA...
October 2016: Metabolism: Clinical and Experimental
Athanasios D Anastasilakis, Stergios A Polyzos, Elpida C Skouvaklidou, Georgios Kynigopoulos, Zacharias G Saridakis, Aggeliki Apostolou, Georgios A Triantafyllou, Thomai Karagiozoglou-Lampoudi, Christos S Mantzoros
PURPOSE: Follistatin may affect lean and fat mass and be implicated in metabolic diseases. We aimed to elucidate physiological predictors of circulating follistatin variation in healthy young humans. PROCEDURES: This was an observational, cross-sectional study with two additional prospective observational arms (circadian, seasonal sub-studies) and one prospective interventional arm (mixed meal sub-study). Healthy, young individuals of both sexes (n=122) were subjected to anthropometric and body composition measurements and their eating and exercise behavior profiles were assessed by validated questionnaires...
October 2016: Metabolism: Clinical and Experimental
David J Sharkey, Kelton P Tremellen, Nancy E Briggs, Gustaaf A Dekker, Sarah A Robertson
STUDY QUESTION: Do seminal plasma transforming growth factor-β (TGFB) cytokines vary within individuals over time, and does this relate to sperm parameters, age or prior abstinence? SUMMARY ANSWER: Activin A and follistatin, and to a lesser extent TGFB1, TGFB2 and TGFB3, vary within individuals over time, in association with duration of abstinence. WHAT IS ALREADY KNOWN: Seminal plasma TGFB cytokines can influence sperm function and reproductive success through interactions with the female reproductive tract after coitus...
October 2016: Human Reproduction
Shigeo Otake, Min Kyun Park
Gonadal sex differentiation proceeds by interplay of various genes including the transcription factors and secretory factors in a complex network. The sex-differentiating genes are expressed not only during early sex differentiation but also throughout the gonadal development, and even in the adult gonads. In addition, the evidence that they actually function in the adult gonads have been accumulated from the studies using the conditional knockout mice. However, many previous studies were focused on one single gene though those genes function in a network...
August 31, 2016: Reproduction: the Official Journal of the Society for the Study of Fertility
Hiroshi Kaji
The links between muscle and bone have been recently examined because of the increasing number of patients with osteoporosis and sarcopenia. Myokines are skeletal muscle-derived humoral cytokines and growth factors, which exert physiological and pathological functions in various distant organs, including the regulation of glucose, energy and bone metabolism. Myostatin is a crucial myokine, the expression of which is mainly limited to muscle tissues. The inhibition of myostatin signaling increases bone remodeling, bone mass and muscle mass, and it may provide a target for the treatment of both sarcopenia and osteoporosis...
2016: BoneKEy Reports
Junxia Guo, Wanqian Liang, Jianhua Li, Jingning Long
Activation of inflammation by oxidized low-density lipoprotein (oxLDL) has been implicated in the development of atherosclerosis. Follistatin-like protein 1 (FSTL1) play a central role in the inflammation process and modulate cardiovascular disorders. However, little is known about the effects of FSTL1 on the inflammation induced by oxLDL. The aim of this study was to evaluate the anti-inflammatory effect of FSTL1 and investigate potential mechanisms in cultured endothelial cells. A model of oxLDL-induced injury in human coronary artery endothelial cells (HCAECs) was established to evaluate the protective role of FSTL1...
September 30, 2016: Biochemical and Biophysical Research Communications
QuanYong Zhou, MingChun Wan, QiPeng Wei, QiongLi Song, LiGen Xiong, JunHong Huo, JiangNan Huang
Proliferation, differentiation, and estrogen secretion of granulosa cells are the key factors affecting the estrous after weaning in sows. The objective of this study was to evaluate the expression of Follistatin (FST) in the ovary of Xiushui Hang and Duroc sows at weaning and estrus, the effect of FSH on transcript abundance of FST gene in granulosa cells and the role of FST gene in the weaning to estrus using siRNAs targeted to FST gene. In the present study, expression of the FST mRNA was evaluated by real time PCR...
October 2016: Animal Biotechnology
Yue Xi, Da-Wei Gong, Zhenjun Tian
Exercise training has been reported to ameliorate heart dysfunction in both humans and animals after myocardial infarction (MI), but the underlying mechanisms are poorly understood. Follistatin-like1 (FSTL1) is a cardioprotective factor against ischemic injury and is induced in cardiomyocytes and skeletal muscle in ischemic and hypoxic conditions. To test the hypothesis that FSTL1 may be a molecular link between exercise and improved heart function post MI, we subjected MI-rats, induced by left coronary artery ligation, to two modes of exercise: intermittent aerobic exercise (IAE) or mechanical vibration training (MVT), for four weeks and examined the relevance of FSTL1 to exercise-mediated cardiac effects...
2016: Scientific Reports
David P L Toews, Scott A Taylor, Rachel Vallender, Alan Brelsford, Bronwyn G Butcher, Philipp W Messer, Irby J Lovette
When related taxa hybridize extensively, their genomes may become increasingly homogenized over time. This mixing via hybridization creates conservation challenges when it reduces genetic or phenotypic diversity and when it endangers previously distinct species via genetic swamping [1]. However, hybridization also facilitates admixture mapping of traits that distinguish each species and the associated genes that maintain distinctiveness despite ongoing gene flow [2]. We address these dual aspects of hybridization in the golden-winged/blue-winged warbler complex, two phenotypically divergent warblers that are indistinguishable using traditional molecular markers and that draw substantial conservation attention [3-5]...
September 12, 2016: Current Biology: CB
Der-Sheng Han, Ming-Yen Hsiao, Tyng-Guey Wang, Ssu-Yuan Chen, Wei-Shiung Yang
BACKGROUND: Patients with spinal cord injury (SCI) have a higher prevalence of cardiovascular diseases compared to the healthy population. Aerobic exercise training is one of the recommended treatments. However, literature regarding the effect of aerobic training on patients with SCI is scarce. This study evaluated changes in parameters of exercise physiology and serum myokines immediately after exercise and after a training program among patients with SCI. METHODS: Male patients with SCI and age- and sex-matched healthy individuals were recruited...
2016: BMC Neurology
Jens Vanselow, Andreas Vernunft, Dirk Koczan, Marion Spitschak, Björn Kuhla
High environmental temperatures induce detrimental effects on various reproductive processes in cattle. According to the predicted global warming the number of days with unfavorable ambient temperatures will further increase. The objective of this study was to investigate effects of acute heat stress during the late pre-ovulatory phase on morphological, physiological and molecular parameters of dominant follicles in cycling cows during lactation. Eight German Holstein cows in established lactation were exposed to heat stress (28°C) or thermoneutral conditions (15°C) with pair-feeding for four days...
2016: PloS One
Kristof Nolan, Chandramohan Kattamuri, Scott A Rankin, Randy J Read, Aaron M Zorn, Thomas B Thompson
The DAN family, including Gremlin-1 and Gremlin-2 (Grem1 and Grem2), represents a large family of secreted BMP (bone morphogenetic protein) antagonists. However, how DAN proteins specifically inhibit BMP signaling has remained elusive. Here, we report the structure of Grem2 bound to GDF5 at 2.9-Å resolution. The structure reveals two Grem2 dimers binding perpendicularly to each GDF5 monomer, resembling an H-like structure. Comparison to the unbound Grem2 structure reveals a dynamic N terminus that undergoes significant transition upon complex formation, leading to simultaneous interaction with the type I and type II receptor motifs on GDF5...
August 23, 2016: Cell Reports
Dzmitry Matsiukevich, Giovanna Piraino, Lindsey R Klingbeil, Paul W Hake, Vivian Wolfe, Michael O'Connor, Basilia Zingarelli
The development of myocardial dysfunction in patients with hemorrhagic shock is significantly impacted by the patient age. AMP-activated protein kinase (AMPK) is a pivotal orchestrator of energy homeostasis, which coordinates metabolic recovery after cellular stress. We investigated whether AMPK-regulated pathways are age-dependent in hemorrhage-induced myocardial injury and whether AMPK activation by 5-amino-4-imidazole carboxamide riboside (AICAR) affords cardioprotective effects. Anesthetized C57/BL6 young (3-5 months old) and mature male mice (9-12 months old) were subjected to hemorrhagic shock by blood withdrawing followed by resuscitation with shed blood and Lactated Ringer's solution...
August 10, 2016: Shock
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