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Gene therapy pain

Xiaopeng Zhou, Jingkai Wang, Weijing Fang, Yiqing Tao, Tengfei Zhao, Kaishun Xia, Chengzhen Liang, Jianming Hua, Fangcai Li, Qixin Chen
Nucleus pulposus (NP) degeneration is usually the origin of intervertebral disc degeneration and consequent lower back pain. Although adipose-derived stem cell (ADSC)-based therapy is regarded to be promising for the treatment of degenerated NP, there is a lack of viable cell carriers to transplant ADSCs into the NP while maintaining cell function. In this study, we developed a type II collagen/chondroitin sulfate (CS) composite hydrogel-like ADSC (CCSA) delivery system with genipin as the cross-linking agent...
March 16, 2018: Acta Biomaterialia
Xiang Cui, Kun Liu, Dandan Xu, Youyou Zhang, Xun He, Hao Liu, Xinyan Gao, Bing Zhu
Background: Acupuncture therapy plays a pivotal role in pain relief, and increasing evidence demonstrates that mast cells (MCs) may mediate acupuncture analgesia. The present study aims to investigate the role of MCs in acupuncture analgesia using c-kit gene mutant-induced MC-deficient rats. Materials and methods: WsRC-Ws/Ws rats and their wild-type (WT) littermates (WsRC-+/+) were used. The number of MCs in skin of ST36 area was compared in two rats after immunofluorescence labeling...
2018: Journal of Pain Research
Huan Liu, Tianjiao Xia, Fangxia Xu, Zhengliang Ma, Xiaoping Gu
Neuropathic pain is a chronic pain state associated with multiple etiologies that results in considerable social and economic burden. The identification of key genes associated with neuropathic pain is important for the development of novel therapies. Therefore, the present study downloaded the gene expression profile GSE15041 from the Gene Expression Omnibus database. The unverified gene chip was removed and the microarray data was normalized following quality control. The limma package in R was used to screen the differentially expressed genes (DEGs), followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis...
March 9, 2018: Molecular Medicine Reports
S Georgin-Lavialle, I Kone-Paut, J Delaleu, G Sarrabay, G Grateau, I Touitou, V Hentgen
Tumour necrosis receptor associated periodic syndrome (TRAPS) is a rare cosmopolitan dominant autosomal disease that belongs to the group of recurrent autoinflammatory syndromes. TRAPS is characterized by recurrent bouts of fever lasting more than 7 days, with arthralgia, myalgia, abdominal pain, erythematous rash and sometimes ocular symptoms. During flares, raised inflammatory markers are constant. The age of onset may occur during childhood but also during adulthood. TRAPS is caused by mutations in the TNF receptor 1 (TNFRSF1A) gene that may occur in most of the populations over the world...
March 7, 2018: La Revue de Médecine Interne
M Kopáčková, P Beránek, I Bydžovská, R Pytlík, J Soukup, M Mrhalová
OBJECTIVE: Presentation of a rare finding non-Hodgkin´s B-lymphoma of the ovary in a patient during caesarean section. DESIGN: Case report. SETTINGS: Department of Obstetrics and Gynaecology, Regional Hospital Liberec, a.s.; First Internal Clinic - Clinic of Hematology, First Faculty of Medicine and General University Hospital, Charles University in Prague; Department of Pathology and Molecular Medicine, Second Faculty of Medicine, Charles University in Praque and Motol University Hospital...
2018: Ceská Gynekologie
Jan Hoffmann, Andrew Charles
There is substantial evidence indicating a role for glutamate in migraine. Levels of glutamate are higher in the brain and possibly also in the peripheral circulation in migraine patients, particularly during attacks. Altered blood levels of kynurenines, endogenous modulators of glutamate receptors, have been reported in migraine patients. Population genetic studies implicate genes that are involved with glutamate signaling in migraine, and gene mutations responsible for familial hemiplegic migraine and other familial migraine syndromes may influence glutamate signaling...
March 5, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Keesha L Roach, Patricia E Hershberger, Julienne N Rutherford, Robert E Molokie, Zaijie Jim Wang, Diana J Wilkie
Pain is the quintessential symptom for individuals suffering from sickle cell disease (SCD). Although the degree of suffering and the cost of treatment are staggering, SCD continues to be grossly understudied, including a lack of data for pain-related genes and prevalence of polymorphisms in this population. This lack of data adds to the inadequacy of pain therapy in this population. Pain genetics investigators have recently examined allele frequencies of single-nucleotide polymorphisms from candidate genes in people who have SCD...
March 1, 2018: Pain Management Nursing: Official Journal of the American Society of Pain Management Nurses
E N Gonc, A Ozon, G Buyukyilmaz, A Alikasifoglu, O P Simsek, N Kandemir
Juvenile Paget's disease (JPD) is a rare autosomal recessive osteopathy. There is still a question about the most effective treatment modality in long-term prognosis. A 9-month-old boy who suffered from bone pain and deformities with a very high alkaline phosphatase level was diagnosed as JPD by radiographic findings. Genetic analysis showed a homozygous large deletion in TNFRSF11B gene encoding osteoprotegerin. Clinical improvement was observed with intravenous pamidronate therapy. However, the effect of drug reduced in time so the annual dose per kilogram body weight was increased after 2 years...
March 3, 2018: Osteoporosis International
Min Ho Hwang, Hyeong Guk Son, Jae Won Lee, Chang Min Yoo, Jae Hee Shin, Hyo Geun Nam, Hyun Jung Lim, Seung Min Baek, Jeong Hun Park, Joo Han Kim, Hyuk Choi
The etiology of intervertebral disc (IVD) degeneration accompanied by low back pain (LBP) is largely unknown, and there are no curative therapies. Painful IVD degeneration is associated with infiltrated macrophage-mediated inflammatory response of human nucleus pulposus (NP) cells. The present study aimed to address the hypothesis that pro-inflammatory cytokines derived from macrophages lead to the altered molecular phenotype of human NP cells and to investigate the effects of phototherapy (630, 525, 465 nm with 16, 32, 64 J/cm2 ) on pain-related cytokine interleukin (IL)-6 and chemokine IL-8 under inflammatory conditions in human NP cells...
March 3, 2018: Lasers in Medical Science
Mick Perez-Cruet, Naimisha Beeravolu, Christina McKee, Jared Brougham, Irfan Khan, Shreeya Bakshi, G Rasul Chaudhry
BACKGROUND: Degenerative disc disease (DDD) is a common spinal disorder that manifests with neck and lower back pain caused by the degeneration of intervertebral discs (IVDs). Currently, there is no treatment to cure this debilitating ailment. OBJECTIVE: To investigate the potential of nucleus pulposus (NP)-like cells (NPCs) derived from human umbilical cord mesenchymal stem cells (MSCs) to restore degenerated IVDs using a rabbit DDD model. METHODS: NPCs differentiated from MSCs were characterized using quantitative real-time reverse transcription polymerase chain reaction and immunocytochemical analysis...
February 26, 2018: Neurosurgery
Myung-Ku Kim, Chul-Won Ha, Yong In, Sung-Do Cho, Eui-Sung Choi, Jeong-Ku Ha, Ju-Hong Lee, Jae-Doo Yoo, Seong-Il Bin, Choong-Hyeok Choi, Hee-Soo Kyung, Myung-Chul Lee
OBJECTIVE: To test the clinical efficacy of TissueGene-C (TG-C), a cell and gene therapeutic for osteoarthritis consisting of non-transformed and transduced chondrocytes (3:1), retrovirally transduced to overexpress TGF-β1. DESIGN: We randomly assigned 163 with knee osteoarthritis to receive intra-articular TG-C or placebo in Kellgren-Lawrence grade 3 patients for clinical trial. Primary efficacy measures included criteria for subjective assessment by International Knee Documentation Committee (IKDC) and pain severity by Visual Analog Scale (VAS) for 52 weeks...
February 27, 2018: Human Gene Therapy. Clinical Development
Lucienne A Vonk, Sanne F J van Dooremalen, Nalan Liv, Judith Klumperman, Paul J Coffer, Daniël B F Saris, Magdalena J Lorenowicz
Osteoarthritis (OA) is a rheumatic disease leading to chronic pain and disability with no effective treatment available. Recently, allogeneic human mesenchymal stromal/stem cells (MSC) entered clinical trials as a novel therapy for OA. Increasing evidence suggests that therapeutic efficacy of MSC depends on paracrine signalling. Here we investigated the role of extracellular vesicles (EVs) secreted by human bone marrow derived MSC (BMMSC) in human OA cartilage repair. METHODS: To test the effect of BMMSC-EVs on OA cartilage inflammation, TNF-alpha-stimulated OA chondrocyte monolayer cultures were treated with BMMSC-EVs and pro-inflammatory gene expression was measured by qRT-PCR after 48 h...
2018: Theranostics
Lara Al-Olabi, Satyamaanasa Polubothu, Katherine Dowsett, Katrina A Andrews, Paulina Stadnik, Agnel P Joseph, Rachel Knox, Alan Pittman, Graeme Clark, William Baird, Neil Bulstrode, Mary Glover, Kristiana Gordon, Darren Hargrave, Susan M Huson, Thomas S Jacques, Gregory James, Hannah Kondolf, Loshan Kangesu, Kim M Keppler-Noreuil, Amjad Khan, Marjorie J Lindhurst, Mark Lipson, Sahar Mansour, Justine O'Hara, Caroline Mahon, Anda Mosica, Celia Moss, Aditi Murthy, Juling Ong, Victoria E Parker, Jean-Baptiste Rivière, Julie C Sapp, Neil J Sebire, Rahul Shah, Branavan Sivakumar, Anna Thomas, Alex Virasami, Regula Waelchli, Zhiqiang Zeng, Leslie G Biesecker, Alex Barnacle, Maya Topf, Robert K Semple, E Elizabeth Patton, Veronica A Kinsler
BACKGROUND: Sporadic vascular malformations (VMs) are complex congenital anomalies of blood vessels that lead to stroke, life-threatening bleeds, disfigurement, overgrowth, and/or pain. Therapeutic options are severely limited and multi-disciplinary management remains challenging, particularly for high-flow arteriovenous malformations (AVM). METHODS: To investigate the pathogenesis of sporadic intracranial and extracranial VMs in 160 children in which known genetic causes had been excluded, we sequenced DNA from affected tissue and optimised analysis for detection of low mutant allele frequency...
February 20, 2018: Journal of Clinical Investigation
Ivano Di Meo, Valeria Tiranti
Brain iron accumulation is the hallmark of a group of seriously invalidating and progressive rare diseases collectively denominated Neurodegeneration with Brain Iron Accumulation (NBIA), characterized by movement disorder, painful dystonia, parkinsonism, mental disability and early death. Currently there is no established therapy available to slow down or reverse the progression of these conditions. Several genes have been identified as responsible for NBIA but only two encode for proteins playing a direct role in iron metabolism...
March 2018: European Journal of Paediatric Neurology: EJPN
Tianqi Tao, Yiqiu Jiang, Wang Li, Yang Li, Jing Du, Jianchao Gui
BACKGROUND: This study aimed to identify the relationship between the vitamin D receptor (VDR) BsmI gene polymorphism and risk factors, surgical outcome and prognosis of hallux valgus (HV). METHODS: A case-control study was performed on a cohort of 236 HV patients and 236 controls in a Chinese Han population. Detection of the VDR BsmI/G2A polymorphism was performed using restriction fragment length polymorphism-polymerase chain reaction. RESULTS: We detected a statistically significant difference in the allele distribution of the BsmI polymorphism between cases and controls (p<0...
October 28, 2017: Foot and Ankle Surgery: Official Journal of the European Society of Foot and Ankle Surgeons
Shaman Rajindrajith, Judith Zeevenhooven, Niranga Manjuri Devanarayana, Bonaventure Jayasiri Crispus Perera, Marc A Benninga
Chronic abdominal pain is a common problem in pediatric practice. The majority of cases fulfill the Rome IV criteria for functional abdominal pain disorders (FAPDs). At times, these disorders may lead to rather serious repercussions. Area covered: We have attempted to cover current knowledge on epidemiology, pathophysiology, risk factors related to pathophysiology, clinical evaluation and management of children with FAPDs. Expert commentary: FAPDs are a worldwide problem with a pooled prevalence of 13.5%. There are a number of predisposing factors and pathophysiological mechanisms including stressful events, child maltreatment, visceral hypersensitivity, altered gastrointestinal motility and change in intestinal microbiota...
February 16, 2018: Expert Review of Gastroenterology & Hepatology
Fernando J Martinez, MeiLan K Han, James P Allinson, R Graham Barr, Richard C Boucher, Peter Calverley, Bartolome R Celli, Stephanie A Christenson, Ronald G Crystal, Malin Fagerås, Christine M Freeman, Lars Groenke, Eric A Hoffman, Mehmet Kesimer, Konstantinos Kostikas, Robert Paine Iii, Shahin Rafii, Stephen I Rennard, Leopoldo N Segal, Renat Shaykhiev, Christopher Stevenson, Ruth Tal-Singer, Jørgen Vestbo, Prescott G Woodruff, Jeffrey L Curtis, Jadwiga A Wedzicha
Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder with varying presentations and progression, but limited disease-modifying therapies. Trajectories of lung function decline in COPD differ significantly between individuals, with differences detectable in young adulthood. "Early disease" (initial manifestations in young individuals) should be distinguished from "late mild disease" (disease of mild severity in older individuals potentially present for decades). For research purposes, we propose an operational definition of early COPD: ever-smokers (≥10 pack-years) younger than 50 years with any of these abnormalities: (1) FEV1/FVC< lower limit of normal; (2) compatible CT abnormalities (airway abnormality and/or emphysema); or (3) FEV1 decline (≥60 mL/year)...
February 6, 2018: American Journal of Respiratory and Critical Care Medicine
A Rothenbuhler, A Linglart
Hypophosphatasia (HPP) is a rare genetic disease due to loss of function mutations in the gene that encodes for Alkaline Phosphatase-Liver (ALPL) that encodes for tissue non-specific alkaline phosphatase (TNSALP) or ALP. Juvenile HPP is, by definition, diagnosed between 6 months of age and adulthood. The clinical signs and symptoms of juvenile HPP are very heterogeneous in their presentation, severity and course. The bone (impaired bone mineralization, leg deformations, pain, rickets, growth abnormalities) and dental (premature loss of deciduous teeth) abnormalities are the best known...
May 2017: Archives de Pédiatrie: Organe Officiel de la Sociéte Française de Pédiatrie
Deng Xiang, Jiannan He, Hongmei Wang, Fangfang Xiong, Hao Cheng, Junhua Ai, Renfeng Shan, Renhua Wan, Lunli Zhang, Jun Shi
RATIONALE: Progressive familial intrahepatic cholestasis (PFIC) type 3, characterized by high gamma glutamyl transferase (GGT), is an autosomal recessive genetic disease. It often occurs in patients' first years of age. However, high GGT type PFIC is still rare. PATIENT CONCERNS: The present study reports a case of liver transplantation for decompensated liver cirrhosis caused by PFIC type 3. An 18-year-old male presented with a history of abdominal distension and jaundice for 2 months...
December 2017: Medicine (Baltimore)
Yan Song, Kui Jiang, Shuai Su, Bangmao Wang, Guangxia Chen
The current study aimed to summarize the clinical manifestations and identify the epigenetic mechanisms of gastric mucosa associated lymphoid tissue (MALT) lymphoma, as well as evaluate the long-term effects of Helicobacter pylori (H. pylori) eradication. A total of 122 patients with marginal zone B-cell lymphoma of primary gastric MALT lymphoma were enrolled in the present study. The clinical manifestations of gastric MALT lymphoma, including symptoms, H. pylori state and endoscopic type, were summarized. The response to therapy was evaluated in patients that underwent H...
January 2018: Experimental and Therapeutic Medicine
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