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https://www.readbyqxmd.com/read/28654984/osteoprotegerin-is-a-new-regulator-of-inflammation-and-angiogenesis-in-proliferative-diabetic-retinopathy
#1
Ahmed M Abu El-Asrar, Sofie Struyf, Ghulam Mohammad, Mieke Gouwy, Pieter Rytinx, Mohammad Mairaj Siddiquei, Cristina Hernández, Kaiser Alam, Ahmed Mousa, Gert De Hertogh, Ghislain Opdenakker, Rafael Simó
Purpose: Osteoprotegerin (OPG) is a novel regulator of endothelial cell function, angiogenesis, and vasculogenesis. We correlated expression levels of OPG with those of the angiogenic and inflammatory factors vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1/CCL2) in proliferative diabetic retinopathy (PDR). We also examined expression of OPG in retinas from diabetic rats and diabetic patients and measured production of OPG by human retinal microvascular endothelial cells (HRMEC) and investigated its angiogenic activity...
June 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28654659/environmental-change-drives-accelerated-adaptation-through-stimulated-copy-number-variation
#2
Ryan M Hull, Cristina Cruz, Carmen V Jack, Jonathan Houseley
Copy number variation (CNV) is rife in eukaryotic genomes and has been implicated in many human disorders, particularly cancer, in which CNV promotes both tumorigenesis and chemotherapy resistance. CNVs are considered random mutations but often arise through replication defects; transcription can interfere with replication fork progression and stability, leading to increased mutation rates at highly transcribed loci. Here we investigate whether inducible promoters can stimulate CNV to yield reproducible, environment-specific genetic changes...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28654473/regenerative-rehabilitation-combining-stem-cell-therapies-and-activity-dependent-stimulation
#3
Chet T Moritz, Fabrisia Ambrosio
The number of clinical trials in regenerative medicine is burgeoning, and stem cell/tissue engineering technologies hold the possibility of becoming the standard of care for a multitude of diseases and injuries. Advances in regenerative biology reveal novel molecular and cellular targets, with potential to optimize tissue healing and functional recovery, thereby refining rehabilitation clinical practice. The purpose of this review is to (1) highlight the potential for synergy between the fields of regenerative medicine and rehabilitation, a convergence of disciplines known as regenerative rehabilitation; (2) provide translational examples of regenerative rehabilitation within the context of neuromuscular injuries and diseases; and (3) offer recommendations for ways to leverage activity dependence via combined therapy and technology, with the goal of enhancing long-term recovery...
July 2017: Pediatric Physical Therapy
https://www.readbyqxmd.com/read/28653829/development-and-characterization-of-a-hydroxyl-sulfonamide-analog-5-chloro-n-2-4-hydroxysulfamoyl-phenyl-ethyl-2-methoxy-benzamide-as-a-novel-nlrp3-inflammasome-inhibitor-for-potential-treatment-of-multiple-sclerosis
#4
Chunqing Guo, Jacob W Fulp, Yuqi Jiang, Xia Li, Jeremy Edward Chojnacki, Jingde Wu, Xiang-Yang Wang, Shijun Zhang
In our efforts to develop novel small molecule inhibitors for the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome as potential disease-modifying agents to treat neurological disorders including multiple sclerosis (MS), a hydroxyl sulfonamide analog JC-171 has been rationally designed and biologically characterized both in vitro and in vivo. Our studies established that JC-171 dose dependently inhibited LPS/ATP induced interleukin-1β (IL-1β) release from J774A.1 macrophages with an IC50 of 8...
June 27, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28653423/angiotensin-1-7-inhibits-angiotensin-ii-stimulated-head-and-neck-cancer-progression
#5
E E Hinsley, C E de Oliveira, S Hunt, R D Coletta, D W Lambert
Angiotensin II (Ang II) is the product of the proteolytic action of angiotensin-converting enzyme (ACE) on the precursor peptide, angiotensin I (Ang I). In addition to its vasoactive properties, Ang II is able to stimulate angiogenesis and act as a mitogen, promoting cellular proliferation. Recently, evidence has emerged that Ang II is also able to promote tumour invasion, a key step in the metastatic cascade, although the mechanisms by which it does so remain largely obscure. Here we show that Ang II is able to promote the invasion and migration of head and neck squamous cell carcinoma (HNSCC) cells both in an autocrine manner and by triggering stromal tumour-paracrine interactions...
June 27, 2017: European Journal of Oral Sciences
https://www.readbyqxmd.com/read/28653289/histamine-h4-receptor-signalling-in-tongue-cancer-and-its-potential-role-in-oral-carcinogenesis%C3%A2-a-short-report
#6
Abdelhakim Salem, Rabeia Almahmoudi, Dyah Listyarifah, Maria Siponen, Katariina Maaninka, Ahmed Al-Samadi, Tuula Salo, Kari K Eklund
PURPOSE: Recent reports indicate that histamine and its novel, high-affinity histamine H4 receptor (H4R) play a role in carcinogenesis, and thus H4R signalling has become a focus of increasing interest in the pathogenesis of many cancers. The roles of H4R in oral epithelial dysplasia (OED) and oral tongue squamous cell carcinoma (OTSCC) are unknown. The purpose of this study was to assess H4R expression in OTSCC patients and in OTSCC-derived cell lines. METHODS: Biopsies taken from OED, OTSCC and healthy oral mucosa were studied by immunostaining...
June 26, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28653285/innate-defense-regulator-idr-1018-activates-human-mast-cells-through-g-protein-phospholipase-c-mapk-and-nf-%C3%A4-b-sensitive-pathways
#7
Kensuke Yanashima, Panjit Chieosilapatham, Eri Yoshimoto, Ko Okumura, Hideoki Ogawa, François Niyonsaba
Host defense (antimicrobial) peptides not only display antimicrobial activities against numerous pathogens but also exert a broader spectrum of immune-modulating functions. Innate defense regulators (IDRs) are a class of host defense peptides synthetically developed from natural or endogenous cationic host defense peptides. Of the IDRs developed to date, IDR-1018 is more efficient not only in killing bacteria but also in regulating the various functions of macrophages and neutrophils and accelerating the wound healing process...
June 26, 2017: Immunologic Research
https://www.readbyqxmd.com/read/28653164/should-dbs-for-psychiatric-disorders-be-considered-a-form-of-psychosurgery-ethical-and-legal-considerations
#8
Devan Stahl, Laura Cabrera, Tyler Gibb
Deep brain stimulation (DBS), a surgical procedure involving the implantation of electrodes in the brain, has rekindled the medical community's interest in psychosurgery. Whereas many researchers argue DBS is substantially different from psychosurgery, we argue psychiatric DBS-though a much more precise and refined treatment than its predecessors-is nevertheless a form of psychosurgery, which raises both old and new ethical and legal concerns that have not been given proper attention. Learning from the ethical and regulatory failures of older forms of psychosurgery can help shed light on how to address the regulatory gaps that exist currently in DBS research...
June 26, 2017: Science and Engineering Ethics
https://www.readbyqxmd.com/read/28652963/switching-from-sildenafil-to-riociguat-for-the-treatment-of-pah-and-inoperable-cteph-real-life-experiences
#9
Asger Andersen, Kasper Korsholm, Søren Mellemkjær, Jens Erik Nielsen-Kudsk
Riociguat is a novel soluble guanylate cyclase stimulator that is approved for the treatment of patients with pulmonary arterial hypertension (PAH) and patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) or persistent/recurrent CTEPH after pulmonary endarterectomy (PEA). As riociguat is a relatively new drug, experience of its use in clinical practice is limited, especially in patients who would not have met the inclusion criteria for the pivotal Phase III clinical trials, PATENT-1 and CHEST-1...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28652624/serum-hepcidin-may-be-a-novel-uremic-toxin-which-might-be-related-to-erythropoietin-resistance
#10
Sung Woo Lee, Jeong Min Kim, Hye Jin Lim, Young-Hwan Hwang, Soo Wan Kim, Wookyung Chung, Kook-Hwan Oh, Curie Ahn, Kyu-Beck Lee, Su Ah Sung
The clinical importance of serum hepcidin in non-dialysis chronic kidney disease (CKD) patients is unclear. The database of a large-scale multicentre prospective study in Korea of 2238 patients enrolled from 2011-2016 was analysed. After excluding patients with missing serum hepcidin (n = 125) and haemoglobin (n = 23) levels, the study included 2090 non-dialysis CKD patients. Markers of inflammation and iron status were positively associated with serum hepcidin level, regardless of CKD stage. However, estimated glomerular filtration rate was inversely associated with serum hepcidin level, particularly in patients with CKD stages 3b-5 but not in those with CKD stages 1-3a...
June 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28652540/the-study-of-ghrelin-secretion-and-acyl-modification-using-mice-and-ghrelinoma-cell-lines
#11
Ichiro Sakata, Zhi Gong, Chika Ikenoya, Shota Takemi, Takafumi Sakai
Ghrelin is a peptide hormone with a unique structure comprising a medium chain fatty acid modification. Ghrelin cells are known to be abundantly localized in the gastric mucosa and are released into the blood stream to exert their multifunctional physiological effects. To elucidate the regulatory mechanisms of ghrelin secretion and acyl-modification, we developed novel ghrelin-producing cell lines. Using ghrelinoma cell lines, we focused on the mechanisms of ghrelin secretion and found that several GPCRs were highly expressed in ghrelin cells...
2017: Endocrine Journal
https://www.readbyqxmd.com/read/28652399/c-rel-and-i%C3%AE%C2%BAbns-govern-common-and-independent-steps-of-regulatory-t-cell-development-from-novel-cd122-expressing-pre-precursors
#12
Marc Schuster, Carlos Plaza-Sirvent, Anne-Marie Matthies, Ulrike Heise, Andreas Jeron, Dunja Bruder, Alexander Visekruna, Jochen Huehn, Ingo Schmitz
Foxp3-expressing regulatory T cells (Tregs) are essential regulators of immune homeostasis and, thus, are prime targets for therapeutic interventions of diseases such as cancer and autoimmunity. c-REL and IκBNS are important regulators of Foxp3 induction in Treg precursors upon γ-chain cytokine stimulation. In c-REL/IκBNS double-deficient mice, Treg numbers were dramatically reduced, indicating that together, c-REL and IκBNS are pivotal for Treg development. However, despite the highly reduced Treg compartment, double-deficient mice did not develop autoimmunity even when aged to more than 1 y, suggesting that c-REL and IκBNS are required for T cell effector function as well...
June 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28652114/antibiotic-innovation-for-future-public-health-needs
#13
REVIEW
Ursula Theuretzbacher
BACKGROUND: The public health threat of antibiotic resistance has gained attention at the highest political levels globally, and recommendations on how to respond are being considered for implementation. Among the recommended responses being explored for their feasibility is the introduction of economic incentives to promote research and development (R&D) of new antibiotics. There is broad agreement that public investment should stimulate innovation and be linked to policies promoting sustainable and equitable access to antibiotics...
June 23, 2017: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/28651891/neuroanatomical-alterations-and-synaptic-plasticity-impairment-in-the-perirhinal-cortex-of-the-ts65dn-mouse-model-of-down-syndrome
#14
Vincenzo Roncacé, Costanza Burattini, Fiorenza Stagni, Sandra Guidi, Andrea Giacomini, Marco Emili, Giorgio Aicardi, Renata Bartesaghi
Down syndrome (DS), a genetic condition due to triplication of Chromosome 21, is characterized by numerous neurodevelopmental alterations and intellectual disability. Individuals with DS and DS mouse models are impaired in several memory domains, including hippocampus-dependent declarative (spatial, in rodents) memory and visual recognition memory, a form of memory in which the perirhinal cortex (PRC) plays a fundamental role. The anatomo-functional substrates of hippocampus-dependent memory impairment have been largely elucidated in the Ts65Dn mouse model of DS...
June 23, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28650457/fibroblast-growth-factor-19-regulates-skeletal-muscle-mass-and-ameliorates-muscle-wasting-in-mice
#15
Bérengère Benoit, Emmanuelle Meugnier, Martina Castelli, Stéphanie Chanon, Aurélie Vieille-Marchiset, Christine Durand, Nadia Bendridi, Sandra Pesenti, Pierre-Axel Monternier, Anne-Cécile Durieux, Damien Freyssenet, Jennifer Rieusset, Etienne Lefai, Hubert Vidal, Jérôme Ruzzin
The endocrine-derived hormone fibroblast growth factor (FGF) 19 has recently emerged as a potential target for treating metabolic disease. Given that skeletal muscle is a key metabolic organ, we explored the role of FGF19 in that tissue. Here we report a novel function of FGF19 in regulating skeletal muscle mass through enlargement of muscle fiber size, and in protecting muscle from atrophy. Treatment with FGF19 causes skeletal muscle hypertrophy in mice, while physiological and pharmacological doses of FGF19 substantially increase the size of human myotubes in vitro...
June 26, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28650429/acetate-mediated-novel-survival-strategy-against-drought-in-plants
#16
Jong-Myong Kim, Taiko Kim To, Akihiro Matsui, Keitaro Tanoi, Natsuko I Kobayashi, Fumio Matsuda, Yoshiki Habu, Daisuke Ogawa, Takuya Sakamoto, Sachihiro Matsunaga, Khurram Bashir, Sultana Rasheed, Marina Ando, Hiroko Takeda, Kanako Kawaura, Miyako Kusano, Atsushi Fukushima, Takaho A Endo, Takashi Kuromori, Junko Ishida, Taeko Morosawa, Maho Tanaka, Chieko Torii, Yumiko Takebayashi, Hitoshi Sakakibara, Yasunari Ogihara, Kazuki Saito, Kazuo Shinozaki, Alessandra Devoto, Motoaki Seki
Water deficit caused by global climate changes seriously endangers the survival of organisms and crop productivity, and increases environmental deterioration(1,2). Plants' resistance to drought involves global reprogramming of transcription, cellular metabolism, hormone signalling and chromatin modification(3-8). However, how these regulatory responses are coordinated via the various pathways, and the underlying mechanisms, are largely unknown. Herein, we report an essential drought-responsive network in which plants trigger a dynamic metabolic flux conversion from glycolysis into acetate synthesis to stimulate the jasmonate (JA) signalling pathway to confer drought tolerance...
June 26, 2017: Nature Plants
https://www.readbyqxmd.com/read/28649750/vasopressin-physiology-assessment-and-osmosentation
#17
Lise Bankir, Daniel G Bichet, Nils G Morgenthaler
Vasopressin (AVP) plays a major role in the regulation of water and sodium homeostasis by its antidiuretic action on the kidney, mediated by V2 receptors. AVP secretion is stimulated by a rise in plasma osmolality, a decline in blood volume, or stress. V1a receptors are expressed in vascular smooth muscle cells but the role of vasopressin in blood pressure regulation is still a matter of debate. AVP may also play a role in some metabolic pathways, including gluconeogenesis, through its action on V1a receptors expressed in the liver...
June 25, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28649604/combined-immunotherapy-with-anti-insulin-resistance-therapy-as-a-novel-therapeutic-strategy-against-neurodegenerative-diseases
#18
Yoshiki Takamatsu, Gilbert Ho, Wakako Koike, Shuei Sugama, Takato Takenouchi, Masaaki Waragai, Jianshe Wei, Kazunari Sekiyama, Makoto Hashimoto
Protein aggregation is a pathological hallmark of and may play a central role in the neurotoxicity in age-associated neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Accordingly, inhibiting aggregation of amyloidogenic proteins, including amyloid β and α-synuclein, has been a main therapeutic target for these disorders. Among various strategies, amyloid β immunotherapy has been extensively investigated in Alzheimer's disease, followed by similar studies of α-synuclein in Parkinson's disease...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28649090/mirna-143-mediates-the-proliferative-signaling-pathway-of-fsh-and-regulates-estradiol-production
#19
Li Zhang, XiaoXin Zhang, Xuejing Zhang, Yu Lu, Lei Li, Sheng Cui
MicroRNAs (MiRNAs) play important regulatory roles in many cellular processes. MiR-143 is highly enriched in the mouse ovary, but its roles and underlying mechanisms are not well understood. In the current study, we show that miR-143 is located in granulosa cells of primary, secondary and antral follicles. To explore the specific functions of miR-143, we transfected miR-143 inhibitor into primary cultured granulosa cells to study the loss of function of miR-143 and the results showed that miR-143 silencing significantly increased estradiol production and steroidogenesis-related gene expression...
July 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/28648843/identification-of-regulators-of-germ-stem-cell-enwrapment-by-its-niche-in-c-elegans
#20
Lara M Linden, Kacy L Gordon, Ariel M Pani, Sara G Payne, Aastha Garde, Dane Burkholder, Qiuyi Chi, Bob Goldstein, David R Sherwood
Many stem cell niches contain support cells that increase contact with stem cells by enwrapping them in cellular processes. One example is the germ stem cell niche in C. elegans, which is composed of a single niche cell termed the distal tip cell (DTC) that extends cellular processes, constructing an elaborate plexus that enwraps germ stem cells. To identify genes required for plexus formation and to explore the function of this specialized enwrapping behavior, a series of targeted and tissue-specific RNAi screens were performed...
June 22, 2017: Developmental Biology
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