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Manipulation therapy

Marcos de Lima, Betul Oran, Richard E Champlin, Esperanza B Papadopoulos, Sergio A Giralt, Bart L Scott, Basem M William, Joel Hetzer, Eric Laille, Becky Hubbell, Barry S Skikne, Charles Craddock
BACKGROUND: Relapse is the main cause of treatment failure after allogeneic stem cell transplant (alloSCT) in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Injectable azacitidine can improve posttransplant outcomes but presents challenges with exposure and compliance. Oral CC-486 allows extended dosing to prolong azacitidine activity. We investigated use of CC-486 maintenance therapy post-alloSCT. METHODS: Adults with MDS or AML in morphological complete remission at CC-486 initiation (42-84 days post-alloSCT) were included...
June 19, 2018: Biology of Blood and Marrow Transplantation
Kobi Perl, Ron Shamir, Karen B Avraham
BACKGROUND: Hearing loss is a major cause of disability worldwide, impairing communication, health, and quality of life. Emerging methods of gene therapy aim to address this morbidity, which can be employed to fix a genetic problem causing hair cell dysfunction and to promote the proliferation of supporting cells in the cochlea and their transdifferentiation into hair cells. In order to extend the applicability of gene therapy, the scientific community is focusing on discovery of additional deafness genes, identifying new genetic variants associated with hearing loss, and revealing new factors that can be manipulated in a coordinated manner to improve hair cell regeneration...
June 22, 2018: Human Genomics
Katherine E MacDuffie, Jeff MacInnes, Kathryn C Dickerson, Kari M Eddington, Timothy J Strauman, R Alison Adcock
To benefit from cognitive behavioral therapy (CBT), individuals must not only learn new skills but also strategically implement them outside of session. Here, we tested a novel technique for personalizing CBT skills and facilitating their generalization to daily life. We hypothesized that showing participants the impact of specific CBT strategies on their own brain function using real-time functional magnetic imaging (rt-fMRI) neurofeedback would increase their metacognitive awareness, help them identify effective strategies, and motivate real-world use...
2018: NeuroImage: Clinical
Gaurav Agrahari, Shyam Kishor Sah, Tae-Yoon Kim
Therapeutic applications of mesenchymal stem cells (MSCs) are limited due to their early death within the first few days of transplantation. Therefore, to improve the efficacy of cell-based therapies, it is necessary to manipulate MSCs so that they can resist various stresses imposed by the microenvironment. Moreover, the role of superoxide dismutase 3 (SOD3) in regulating such survival under different stress conditions remain elusive. In this study, we overexpressed SOD3 in MSCs (SOD3-MSCs) and evaluated its effect under serum starvation conditions...
June 20, 2018: BMB Reports
Ling-Yan Zhou, Zhi-Yao He, Ting Xu, Yu-Quan Wei
Small activating RNAs (saRNAs) are small double-stranded RNAs that could mediate the target-specific gene expression by targeting selected sequences in gene promoters at both the transcriptional and epigenetic levels. This phenomenon of gene manipulation is known as RNA activation (RNAa), which opens up a new pathway for RNA-based gene therapeutics in contrast to RNA interference. Although the exact molecular mechanism of RNAa mediated by saRNAs still remains foggy, some reports have provided the possible ones to explain it...
June 19, 2018: Current Gene Therapy
Jingjing Gan, Yunyan Dou, Yurong Li, Zhenzhen Wang, Lintao Wang, Shang Liu, Qiu Li, Heran Yu, Chunyan Liu, Congwei Han, Zhen Huang, Junfeng Zhang, Chunming Wang, Lei Dong
Macrophages are highly plastic cells that can either mediate or suppress inflammation, depending on their cellular phenotype and cytokine secretion. Inducing macrophages from an inflammatory ('M1') to anti-inflammatory ('M2') phenotype has significant implications for the treatment of inflammatory diseases and regeneration of injured tissues. Although certain cytokines, such as interleukin-4 and -13, are known to induce this phenotypic switch, their therapeutic use in vivo has both safety and efficacy concerns...
June 14, 2018: Biomaterials
Simon McKenzie-Nickson, Jacky Chan, Keyla Perez, Lin W Hung, Lesley Cheng, Amelia Sedjahtera, Lydia Gunawan, Paul A Adlard, David J Hayne, Lachlan E Mcinnes, Paul S Donnelly, David I Finkelstein, Professor Andrew Hill, Kevin J Barnham
Alzheimer's disease (AD) is the leading cause of dementia worldwide accounting around 70% of all cases. There is currently no treatment for AD beyond symptom management and attempts at developing disease-modifying therapies have yielded very little. These strategies have traditionally targeted the peptide Aβ which is thought to drive pathology. However, the lack of clinical translation of these Aβ-centric strategies underscores the need for diverse treatment strategies targeting other aspects of the disease...
June 19, 2018: ACS Chemical Neuroscience
Konstantin Igorevich Novikov, Koushik Narayan Subramanyam, Sergey V Kolesnikov, Oleg K Chegurov, Elina S Kolesnikova, Abhishek V Mundargi
Ilizarov is an accepted technique for lengthening short amputation stumps to improve prosthetic function and rehabilitation. The relation of stump lengthening and phantom limb pain (PLP) has not been reported in literature. We present here a case report of a transfemoral amputee who had a flare up of PLP following stump lengthening. He responded well to a combination of pharmacological therapy and soft tissue manipulative techniques and desired length was achieved. This report alerts the possibility of aggravation of PLP following stump lengthening and discusses its management...
May 2018: Archives of Bone and Joint Surgery
Huihui Sun, Fanfan Li, Jie Liu, Fayu Yang, Zhenhai Zeng, Xiujuan Lv, Mengjun Tu, Yeqing Liu, Xianglian Ge, Changbao Liu, Junzhao Zhao, Zongduan Zhang, Jia Qu, Zongming Song, Feng Gu
Cpf1 has been harnessed as a tool for genome manipulation in various species because of its simplicity and high efficiency. Our recent study demonstrated that FnCpf1 could be utilized for human genome editing with notable advantages for target sequence selection due to the flexibility of the protospacer adjacent motif (PAM) sequence. Multiplex genome editing provides a powerful tool for targeting members of multigene families, dissecting gene networks, modeling multigenic disorders in vivo, and applying gene therapy...
June 15, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Mitra Amoli-Diva, Rasoul Sadighi-Bonabi, Kamyar Pourghazi
New dual light/temperature-responsive nanocarriers were synthesized using bimetallic plasmonic Au-Ag and Ag-Au nanoparticles (NPs) as cores of vehicles which subsequently functionalized with a UCST-based poly acrylamide-co-acrylonitrile using reversible addition-fragmentation chain transfer for spatiotemporally controlled chemo-photothermal synergistic cancer therapy. The bimetallic cores were assigned to sense wavelengths close to the localized SPR of monometallic NP shell to produce heat which not only can increase the surrounding temperature over the UCST of polymer to open the its valves and promote drug diffusion, but also can kill cancerous cells through photothermal effects with increasing in environment temperature nearly 18 °C after about 5 min radiation...
June 14, 2018: Journal of Pharmaceutical Sciences
Shenara Musthaq, Anna Mazuy, Jeannette Jakus
The skin supports a delicate ecosystem of microbial elements. Although the skin typically acts as a barrier, these microbes interact with the internal body environment and imbalances from the "healthy" state that have been linked to several dermatologic diseases. Understanding the changes in microbial flora in disease states allows for the potential to treat by restoring equilibrium. With the rising popularity of holistic and natural consumerism, prebiotics, probiotics, symbiotic, and other therapies are under study to find alternative treatments to these skin disorders through manipulation or supplementation of the microbiome...
May 2018: Clinics in Dermatology
Kazushige Kawai, Keisuke Hata, Toshiaki Tanaka, Takeshi Nishikawa, Kensuke Otani, Koji Murono, Kazuhito Sasaki, Manabu Kaneko, Shigenobu Emoto, Hiroaki Nozawa
OBJECTIVE: This study aimed to assess the learning curve of robotic rectal surgery, a procedure that has gained increasing focus in recent years because it is expected that the advanced devices used in this approach provide advantages resulting in a shorter learning curve than that of laparoscopic surgery. However, no studies have assessed the learning curve of robotic rectal surgery, especially when lateral lymph node dissection is required. DESIGN: This was a nonrandomized, retrospective study from a single institution...
June 12, 2018: Journal of Surgical Education
Robert H Scannevin
Neurodegenerative diseases can arise from a multitude of different pathological drivers, however protein misfolding appears to be a common molecular feature central to several disorders. Protein folding, and attainment of correct secondary and tertiary structure, is essential for proper protein function. Protein misfolding gives rise to structural perturbations that can result in loss of protein function or a gain of toxic function, such as through aggregation, either of which can initiate and propagate biological responses that are deleterious to cells...
June 11, 2018: Current Opinion in Chemical Biology
Xiaojing Wang, Guowei Wang, Sarah Zingales, Baodong Zhao
Repairing bone defects poses a major orthopedic challenge because current treatments are constrained by the limited regenerative capacity of human bone tissue. Novel therapeutic strategies, such as stem cell therapy and tissue engineering, have the potential to enhance bone healing and regeneration, and hence may improve quality of life for millions of people. However, the ex vivo expansion of stem cells and their in vivo delivery pose technical difficulties that hamper clinical translation and commercial development...
June 13, 2018: Tissue Engineering. Part B, Reviews
Radka Graf, Jami L Longo, Zoë A Hughes
Deficits in hippocampal-mediated pattern separation are one aspect of cognitive function affected in schizophrenia (SZ) or Alzheimer's disease (AD). To develop novel therapies, it is beneficial to explore this specific aspect of cognition preclinically. The location discrimination reversal (LDR) task is a hippocampal-dependent operant paradigm that evaluates spatial learning and cognitive flexibility using touchscreens. Here we assessed baseline performance as well as multimodal disease-relevant manipulations in mice...
June 1, 2018: Journal of Psychopharmacology
Nigel Farrow, Patricia Cmielewski, Martin Donnelley, Nathan Rout-Pitt, Yuben Moodley, Ivan Bertoncello, David Parsons
BACKGROUND: Airway disease is a primary cause of morbidity and early mortality for patients with cystic fibrosis (CF). Cell transplantation therapy has proven successful for treating immune disorders and may have the potential to correct the airway disease phenotype associated with CF. Since in vivo cell delivery into unconditioned mouse airways leads to inefficient engraftment, we hypothesised that disrupting the epithelial cell layer using the agent polidocanol (PDOC) would facilitate effective transplantation of cultured stem cells in mouse nasal airways...
June 13, 2018: Stem Cell Research & Therapy
Yinglu Feng, Zifei Yin, Daniel Zhang, Arun Srivastava, Chen Ling
The success of gene and cell therapy in clinic during the past two decades as well as our expanding ability to manipulate these biomaterials are leading to new therapeutic options for a wide range of inherited and acquired diseases. Combining conventional therapies with this emerging field is a promising strategy to treat those previously-thought untreatable diseases. Traditional Chinese medicine (TCM) has evolved for thousands of years in China and still plays an important role in human health. As part of the active ingredients of TCM, proteins and peptides have attracted long-term enthusiasm of researchers...
June 11, 2018: Current Protein & Peptide Science
Hong Chen, Hai-Xiang Shen, Yi-Wei Lin, Ye-Qing Mao, Ben Liu, Li-Ping Xie
Small RNAs play an important role in gene regulatory networks. The gene suppressive effect of small RNAs was previously the dominant focus of studies, but during the recent decade, small RNA-induced gene activation has been reported and has become a notable gene manipulation technique. In this study, a putative tumor suppressor, INTS6, was activated by introducing a promoter-targeted small RNA (dsRNA-915) into castration-resistant prostate cancer (CRPC) cells. Unique dynamics associated with the gene upregulation phenomenon was observed...
June 12, 2018: Cell Cycle
Amina Dahmani, Jean-Sébastien Delisle
Transforming Growth Factor beta (TGF-β) is a pleiotropic cytokine produced in large amounts within cancer microenvironments that will ultimately promote neoplastic progression, notably by suppressing the host’s T-cell immunosurveillance. This effect is mostly due to the well-known inhibitory effect of TGF-β on T cell proliferation, activation, and effector functions. Moreover, TGF-β subverts T cell immunity by favoring regulatory T-cell differentiation, further reinforcing immunosuppression within tumor microenvironments...
June 11, 2018: Cancers
Hidehiko Okamoto
Neurophysiological and neuroimaging data suggest that the brains of not only children but also adults are reorganized based on sensory inputs and behaviors. Plastic changes in the brain are generally beneficial; however, maladaptive cortical reorganization in the auditory cortex may lead to hearing disorders such as tinnitus and hyperacusis. Recent studies attempted to noninvasively visualize pathological neural activity in the living human brain and reverse maladaptive cortical reorganization by the suitable manipulation of auditory inputs in order to alleviate detrimental auditory symptoms...
2018: Neural Plasticity
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