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Gene therapy pain

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https://www.readbyqxmd.com/read/28212278/the-effect-of-the-human-peptide-ghk-on-gene-expression-relevant-to-nervous-system-function-and-cognitive-decline
#1
Loren Pickart, Jessica Michelle Vasquez-Soltero, Anna Margolina
Neurodegeneration, the progressive death of neurons, loss of brain function, and cognitive decline is an increasing problem for senior populations. Its causes are poorly understood and therapies are largely ineffective. Neurons, with high energy and oxygen requirements, are especially vulnerable to detrimental factors, including age-related dysregulation of biochemical pathways caused by altered expression of multiple genes. GHK (glycyl-l-histidyl-l-lysine) is a human copper-binding peptide with biological actions that appear to counter aging-associated diseases and conditions...
February 15, 2017: Brain Sciences
https://www.readbyqxmd.com/read/28207662/expression-of-mirna-124a-in-cd4-cells-reflects-response-to-a-multidisciplinary-treatment-program-in-patients-with-chronic-low-back-pain
#2
Benjamin Luchting, Jens Heyn, Ludwig Christian Hinske, Shahnaz Christina Azad
STUDY DESIGN: A prospective evaluation of microRNA (miRNA) expression in patients with chronic low back pain (CLBP). OBJECTIVE: The aim of this study was to evaluate whether pain- and T cell-related miRNAs are differentially expressed in CLBP when compared with healthy volunteers and whether these miRNAs may distinguish between responders and nonresponders to a multidisciplinary treatment program. SUMMARY OF BACKGROUND DATA: CLBP is a common health problem worldwide...
February 15, 2017: Spine
https://www.readbyqxmd.com/read/28203345/sweet-s-syndrome-associated-with-clonal-hematopoiesis-of-indeterminate-potential-responsive-to-5-azacitidine
#3
REVIEW
George Yaghmour, Eric Wiedower, Bassam Yaghmour, Sara Nunnery, Eric Duncavage, Mike G Martin
Sweet's syndrome (SS) is a rare condition characterized by the abrupt appearance of painful skin lesions due to neutrophilic dermal infiltration. Hematologic neoplasms, particularly acute myeloid leukemia (AML) and myelodysplastic syndromes (MDSs), have been commonly reported in association with SS. Clonal hematopoiesis of indeterminate potential (CHIP) is an emerging entity that is a precursor state to myeloid neoplasms. CHIP has not been previously associated with SS. We report the case of a 71-year-old man who presented with recurrent, painful edematous and erythematous papules and nodules for 18 months despite treatment with corticosteroids...
February 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28199203/neurogenetics-of-acute-and-chronic-opiate-opioid-abstinence-treating-symptoms-and-the-cause
#4
Kenneth Blum, Mark S Gold, William Jacobs, William Vaughn McCall, Marcelo Febo, David Baron, Kristina Dushaj, Zsolt Demetrovics, Rajendra D Badgaiyan
This review begins with a comprehensive history of opioid dependence and treatment in the United States. The focus is an evidence-based treatment model for opioid/opiate dependent individuals. The role of reward genetic polymorphisms and the epigenetic modifications that lead to vulnerability to use and misuse of opiates/opioid to treat pain are reviewed. The neurochemical mechanisms of acute opiate withdrawal and opiate/opioid reward mechanisms are explored with a goal of identifying specific treatment targets...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28190938/elucidation-of-the-anti-inflammatory-mechanisms-of-bupleuri-and-scutellariae-radix-using-system-pharmacological-analyses
#5
Xia Shen, Zhenyu Zhao, Hao Wang, Zihu Guo, Benxiang Hu, Gang Zhang
Objective. This study was aimed at elucidating the molecular mechanisms underlying the anti-inflammatory effect of the combined application of Bupleuri Radix and Scutellariae Radix and explored the potential therapeutic efficacy of these two drugs on inflammation-related diseases. Methods. After searching the databases, we collected the active ingredients of Bupleuri Radix and Scutellariae Radix and calculated their oral bioavailability (OB) and drug-likeness (DL) based on the absorption-distribution-metabolism-elimination (ADME) model...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28190860/activated-phosphoinositide-3-kinase-%C3%AE-syndrome-presenting-with-gut-associated-t-cell-lymphoproliferative-disease
#6
Hideto Teranishi, Masataka Ishimura, Yuuki Koga, Katsuhide Eguchi, Motoshi Sonoda, Tetsuko Kobayashi, Satoru Shiraishi, Kentaro Nakashima, Kouji Ikegami, Murasaki Aman, Hidetaka Yamamoto, Hidetoshi Takada, Shouichi Ohga
A 13-year-old boy was admitted to our hospital because of persistent diarrhea, abdominal pain, and bloody stools. The patient had experienced repeated hospitalizations for the treatment of respiratory infections since early childhood. Colonoscopic and pathological studies led to a diagnosis of gut-associated T-cell lymphoproliferative disease (T-cell LPD). Laboratory data showed T-lymphocytopenia (492/µl), increased serum IgG levels (1,984 mg/dl), and low serum antibody titers for specific pathogens. Combined immunodeficiency accompanied by T-LPD suggested the diagnosis of activated PI3Kδ syndrome (APDS)...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28184053/gastrointestinal-diseases-and-their-oro-dental-manifestations-part-4-peutz-jeghers-syndrome
#7
S E Korsse, M E van Leerdam, E Dekker
Peutz-Jeghers syndrome (PJS) is a rare, autosomal dominant inherited disorder, caused by germline mutations in the LKB1 tumour suppressor gene. It is clinically characterised by distinct perioral mucocutaneous pigmentations, gastrointestinal polyposis and an increased cancer risk in adult life. Hamartomatous polyps can develop already in the first decade of life and may cause various complications, including abdominal pain, bleeding, anaemia, and acute intestinal obstruction. Furthermore, patients have an increased risk for developing cancer, both in the gastrointestinal tract as in other organs...
February 10, 2017: British Dental Journal
https://www.readbyqxmd.com/read/28182354/exploring-the-molecular-mechanism-and-biomarker-of-recurrent-aphthous-stomatitis-based-on-gene-expression-microarray
#8
Shang Dan, Zhang Jinwei, Zhang Qiang, Shang Jianwei, Zhang Weijun
BACKGROUND: Recurrent aphthous stomatitis (RAS) is one of the most common chronic oral diseases with morbidity ranging from 5% to 20%. The pathogenesis is still not fully understood though immune dysregulation and local trauma have been implicated and the curative effect that can be achieved through current therapy is mainly to alleviate the pain. So, the understanding of its molecular mechanisms can allow the prevention and treatment of RAS at the molecular level. METHODS: 14 normal tissues and 14 ulcerated tissues were subjected to Affymetrix Human Genome U133 Plus 2...
February 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28163105/nerve-growth-factor-derivative-ngf61-100-promotes-outgrowth-of-primary-sensory-neurons-with-reduced-signs-of-nociceptive-sensitization
#9
C Severini, P Petrocchi Passeri, M T Ciotti, F Florenzano, C Petrella, F Malerba, B Bruni, M D'Onofrio, I Arisi, R Brandi, R Possenti, P Calissano, A Cattaneo
Nerve Growth Factor (NGF) is being considered as a therapeutic candidate for Alzheimer's disease. However, the development of an NGF-based therapy is limited by its potent pain activity. We have developed a "painless" derivative form of human NGF (NGF61/100), characterized by identical neurotrophic properties but a reduced nociceptive sensitization activity in vivo. Here we characterized the response of rat dorsal root ganglia neurons (DRG) to the NGF derivative NGF61/100, in comparison to that of control NGF (NGF61), analyzing the expression of noxious pro-nociceptive mediators...
February 2, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28162885/genetic-and-familial-predisposition-to-rotator-cuff-disease-a-systematic-review
#10
REVIEW
Dominique I Dabija, Chan Gao, Todd L Edwards, John E Kuhn, Nitin B Jain
BACKGROUND: Rotator cuff disease is a common disorder leading to shoulder pain and loss of function. Its etiology in atraumatic cases is uncertain and is likely to extend beyond repetitive microtrauma or overuse. Our objective was to determine whether there is a genetic or familial predisposition to rotator cuff disease. METHODS: A literature search of PubMed and Embase databases identified 251 citations. After review of the titles, abstracts, and full articles, 7 met our inclusion and exclusion criteria...
February 2, 2017: Journal of Shoulder and Elbow Surgery
https://www.readbyqxmd.com/read/28159390/sickle-cell-disease
#11
REVIEW
Russell E Ware, Mariane de Montalembert, Léon Tshilolo, Miguel R Abboud
Sickle cell disease is a common and life-threatening haematological disorder that affects millions of people worldwide. Abnormal sickle-shaped erythrocytes disrupt blood flow in small vessels, and this vaso-occlusion leads to distal tissue ischaemia and inflammation, with symptoms defining the acute painful sickle-cell crisis. Repeated sickling and ongoing haemolytic anaemia, even when subclinical, lead to parenchymal injury and chronic organ damage, causing substantial morbidity and early mortality. Currently available treatments are limited to transfusions and hydroxycarbamide, although stem cell transplantation might be a potentially curative therapy...
January 31, 2017: Lancet
https://www.readbyqxmd.com/read/28132712/the-triple-functions-of-d2-silencing-in-treatment-of-periapical-disease
#12
Jie Pan, Jue Wang, Liang Hao, Guochun Zhu, Diep N Nguyen, Qian Li, Yuehua Liu, Zhihe Zhao, Yi-Ping Li, Wei Chen
INTRODUCTION: Dental caries is the most widespread chronic infectious disease. Inflammation in pulp tissues caused by dental caries will lead to periapical granulomas, bone erosion, loss of the tooth, and severe pain. Despite numerous efforts in recent studies to develop effective treatments for dental caries, the need for a potent therapy is still urgent. METHODS: In this study, we applied a gene-based therapy approach by administering recombinant adeno-associated virus (AAV)-mediated Atp6v0d2 (d2) RNA interference knockdown of d2 gene expression to prevent periapical bone loss and suppress periapical inflammation simultaneously...
February 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/28130915/multiscale-modeling-reveals-inhibitory-and-stimulatory-effects-of-caffeine-on-acetaminophen-induced-toxicity-in-humans
#13
C Thiel, H Cordes, V Baier, L M Blank, L Kuepfer
Acetaminophen (APAP) is a widely used analgesic drug that is frequently co-administered with caffeine (CAF) in the treatment of pain. It is well known that APAP may cause severe liver injury after an acute overdose. However, the understanding of whether and to what extent CAF inhibits or stimulates APAP-induced hepatotoxicity in humans is still lacking. Here, a multiscale analysis is presented that quantitatively models the pharmacodynamic (PD) response of APAP during co-medication with CAF. Therefore, drug-drug interaction (DDI) processes were integrated into physiologically based pharmacokinetic (PBPK) models at the organism level, whereas drug-specific PD response data were contextualized at the cellular level...
January 28, 2017: CPT: Pharmacometrics & Systems Pharmacology
https://www.readbyqxmd.com/read/28127509/lentiviral-vector-encoded-microrna-based-shrna-mediated-gene-knockdown-of-n-methyl-d-aspartate-receptors-in-skin-reduces-pain
#14
Chien-Cheng Liu, Jiin-Tsuey Cheng, Kuo-Chuan Hung, Yuan-Yi Chia, Ping-Heng Tan
BACKGROUND AND PURPOSE: RNA polymerase II promoters that drive the expression of rationally designed primary microRNA-based shRNA, for example, shRNAmir, can produce more potent gene knockdown than RNA polymerase III promoters. Antagonists of peripheral N methyl-D-aspartate (NMDA) receptors that do not interfere with central glutamate processing would prevent the development of adverse central nervous system effects. Thus, in this study, we examined the effects of gene silencing and antinociception on formalin- and Complete Freund's adjuvant (CFA)-induced pain in rats by subcutaneously injecting a lentiviral vector encoding a shRNAmir that targets the NR1 subunit of the NMDA receptor...
January 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28125551/o-003-the-brain-as-extraintestinal-ibd-manifestation-are-brain-and-cognitive-differences-in-pediatric-crohn-s-disease-associated-with-immune-gene-expression
#15
Christine Mrakotsky, Dunn W Augustine, Christopher Watson, James Canavan, Michael Rivkin, Scott Snapper
BACKGROUND: Structural brain changes in gray and white matter have been previously found in adults with Crohn's disease (CD). We have recently shown similar effects for pediatric CD in 2 separate studies (Mrakotsky et al., 2012, 2013, 2015), particularly for cortical and subcortical brain regions important for cognition, memory and emotion. Our prior data also revealed serum markers of inflammation and steroid therapy to be negatively associated with cortical thickness, subcortical volume, cognitive and school function, however, associations between brain structure and more detailed inflammatory profiles have not been studied...
February 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28104732/iatrogenic-cushing-s-syndrome-due-to-topical-ocular-glucocorticoid-treatment
#16
Daisuke Fukuhara, Toshihiko Takiura, Hiroshi Keino, Annabelle A Okada, Kunimasa Yan
Iatrogenic Cushing's syndrome (CS) is a severe adverse effect of systemic glucocorticoid (GC) therapy in children, but is extremely rare in the setting of topical ocular GC therapy. In this article, we report the case of a 9-year-old girl suffering from idiopathic uveitis who developed CS due to topical ocular GC treatment. She was referred to the ophthalmology department with a complaint of painful eyes, at which time she was diagnosed with bilateral iridocyclitis and started on a treatment of betamethasone sodium phosphate eye drops...
February 2017: Pediatrics
https://www.readbyqxmd.com/read/28094851/blood-transfusion-for-preventing-primary-and-secondary-stroke-in-people-with-sickle-cell-disease
#17
REVIEW
Lise J Estcourt, Patricia M Fortin, Sally Hopewell, Marialena Trivella, Winfred C Wang
BACKGROUND: Sickle cell disease is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. Sickle cell disease can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Stroke affects around 10% of children with sickle cell anaemia (HbSS). Chronic blood transfusions may reduce the risk of vaso-occlusion and stroke by diluting the proportion of sickled cells in the circulation...
January 17, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28093873/diagnostic-and-management-challenges-from-childhood-puberty-through-to-transition-in-severe-insulin-resistance-due-to-insulin-receptor-mutations
#18
Christina Wei, Christine P Burren
Two Caucasian girls, both of normal weight and body mass indices, were diagnosed with type A insulin resistance (IR) in childhood. Case 1 presented with premature adrenarche aged 7 years, then by age 12 years had hirsutism, acne, acanthosis nigricans, and asymptomatic diabetes. Subsequent investigation revealed raised adiponectin (15.3 mg/L) and heterozygous p.Pro1205Leu mutation in the INSR gene encoding the insulin receptor. She experienced postprandial hypoglycaemia on metformin; acarbose was trialled and discontinued aged 16 years, as she became normoglycaemic...
January 17, 2017: Pediatric Diabetes
https://www.readbyqxmd.com/read/28079752/changes-in-dorsal-root-ganglion-gene-expression-in-response-to-spinal-cord-stimulation
#19
Dana M Tilley, David L Cedeño, Courtney A Kelley, Margaret DeMaegd, Ramsin Benyamin, Ricardo Vallejo
BACKGROUND AND OBJECTIVES: Spinal cord stimulation (SCS) has been shown to influence pain-related genes in the spinal cord directly under the stimulating electrodes. There is limited information regarding changes occurring at the dorsal root ganglion (DRG). This study evaluates gene expression in the DRG in response to SCS therapy. METHODS: Rats were randomized into experimental or control groups (n = 6 per group). Experimental animals underwent spared-nerve injury, implantation of lead, and continuous SCS (72 hours)...
March 2017: Regional Anesthesia and Pain Medicine
https://www.readbyqxmd.com/read/28058943/genome-wide-analysis-of-blood-gene-expression-in-migraine-implicates-immune-inflammatory-pathways
#20
Zachary F Gerring, Joseph E Powell, Grant W Montgomery, Dale R Nyholt
Background Typical migraine is a frequent, debilitating and painful headache disorder with an estimated heritability of about 50%. Although genome-wide association (GWA) studies have identified over 40 single nucleotide polymorphisms associated with migraine, further research is required to determine their biological role in migraine susceptibility. Therefore, we performed a study of genome-wide gene expression in a large sample of 83 migraine cases and 83 non-migraine controls to determine whether altered expression levels of genes and pathways could provide insights into the biological mechanisms underlying migraine...
January 1, 2017: Cephalalgia: An International Journal of Headache
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