BACKGROUNDTreatments for Obsessive-Compulsive Disorder (OCD) have greatly improved over time. However, some patients do not respond to current interventions and many are left with residual symptoms even if they are 'responders'. There is increasing evidence that individuals with OCD frequently report delayed bedtimes and are at elevated risk for Delayed Sleep Phase Disorder (DSPD). Therefore, it is logical to ask whether interventions addressing disruptions in sleep timing and circadian rhythms would lead to reductions in OCD symptoms. A prior study from our group showed that behaviorally shifting sleep timing resulted in significant symptom reduction in a treatment resistant OCD patient.OBJECTIVESExtending prior findings, this manuscript presents quantitative data from case studies which tested the use of a pharmacological intervention that targets melatonin receptors. Specifically, the case studies reviewed herein utilized the melatonin analog and melatonergic MT1 and MT2 receptor agonist, Agomelatine.METHODSA literature review revealed 10 cases which have used Agomelatine for OCD.RESULTSSeven of the cases were reported to have sleep and/or circadian disruptions prior to treatment. These cases OCD symptom reductions between 46%-90%. In contrast, three additional cases without pre-treatment sleep and/or circadian disruptions did not respond to the intervention.DISCUSSIONThere is growing evidence that disruptions in sleep and circadian rhythms may contribute to the maintenance of OCD. Further work is warranted.

01 Feb 2016·Stem Cells Translational MedicineQ2 · MEDICINE

Established Stem Cell Model of Spinal Muscular Atrophy Is Applicable in the Evaluation of the Efficacy of Thyrotropin-Releasing Hormone Analog

Q2 · MEDICINE

ArticleOA

Author: Hara, Hideaki ; Kaneko, Hideo ; Ohuchi, Kazuki ; Seki, Junko ; Kato, Zenichiro ; Ono, Yoko ; Tamai, Yuya ; Tsuruma, Kazuhiro ; Ando, Shiori ; Funato, Michinori ; Kawase, Chizuru ; Nagahara, Yuki ; Kameyama, Tsubasa ; Noda, Yasuhiro ; Shimazawa, Masamitsu

AbstractSpinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder characterized by the degeneration of spinal motor neurons. This disease is mainly caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. Currently, no effective treatment is available, and only symptomatic treatment can be provided. Our purpose in the present study was to establish a human SMA-derived induced pluripotent stem cell (SMA-iPSC) disease model and assay a therapeutic drug in preparation for the development of a novel treatment of SMA. We generated iPSCs from the skin fibroblasts of a patient with SMA and confirmed that they were pluripotent and undifferentiated. The neural differentiation of SMA-iPSCs shortened the dendrite and axon length and increased the apoptosis of the spinal motor neurons. In addition, we found activated astrocytes in differentiated SMA-iPSCs. Using this model, we confirmed that treatment with the thyrotropin-releasing hormone (TRH) analog, 5-oxo-l-prolyl-l-histidyl-l-prolinamide, which had marginal effects in clinical trials, increases the SMN protein level. This increase was mediated through the transcriptional activation of the SMN2 gene and inhibition of glycogen synthase kinase-3β activity. Finally, the TRH analog treatment resulted in dendrite and axon development of spinal motor neurons in differentiated SMA-iPSCs. These results suggest that this human in vitro disease model stimulates SMA pathology and reveal the potential efficacy of TRH analog treatment for SMA. Therefore, we can screen novel therapeutic drugs such as TRH for SMA easily and effectively using the human SMA-iPSC model.SignificancePlatelet-derived growth factor (PDGF) has recently been reported to produce the greatest increase in survival motor neuron protein levels by inhibiting glycogen synthase kinase (GSK)-3β; however, motor neurons lack PDGF receptors. A human in vitro spinal muscular atrophy-derived induced pluripotent stem cell model was established, which showed that the thyrotropin releasing hormone (TRH) analog promoted transcriptional activation of the SMN2 gene and inhibition of GSK-3β activity, resulting in the increase and stabilization of the SMN protein and axon elongation of spinal motor neurons. These results reveal the potential efficacy of TRH analog treatment for SMA.

01 Jun 2014·Journal of Surgical ResearchQ4 · MEDICINE

Thyrotropin-releasing hormone and its analogs accelerate wound healing

Q4 · MEDICINE

Article

Author: Dong, Deli ; Yang, Daping ; Zhang, Jiewu ; Nie, Chunlei ; Xu, Jin ; Liu, Nan

BACKGROUNDThyrotropin-releasing hormone (TRH) is a classical hormone that controls thyroid hormone production in the anterior pituitary gland. However, recent evidence suggested that TRH is expressed in nonhypothalamic tissues such as epidermal keratinocytes and dermal fibroblasts, but its function is not clear. This study aimed to investigate the effects of TRH and its analogs on wound healing and explore the underlying mechanisms.MATERIALS AND METHODSA stented excisional wound model was established, and the wound healing among vehicle control, TRH, and TRH analog taltirelin treatment groups was evaluated by macroscopic and histologic analyses. Primary fibroblasts were isolated from rat dermis and treated with vehicle control, TRH or taltirelin, cell migration, and proliferation were examined by scratch migration assay, MTT, and 5-ethynyl-2'- deoxyuridine (EdU) assay. The expression of α-Smooth muscle actin in fibroblasts was detected by Western blot and immunocytochemical analysis.RESULTSTRH or taltirelin-treated wounds exhibited accelerated wound healing with enhanced granulation tissue formation and increased re-epithelialization and tissue formation. Furthermore, TRH or taltirelin promoted the migration and proliferation of fibroblasts and induced the expression of α-Smooth muscle actin in fibroblasts.CONCLUSIONSTRH is important in upregulating the phenotypes of dermal fibroblasts and plays a role in accelerating wound healing.

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