Embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), which are collectively called pluripotent stem cells (PSCs), have emerged as a promising source for regenerative medicine. Particularly, human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) have shown robust potential for regenerating injured heart. Over the past two decades, protocols to differentiate hPSCs into CMs at high efficiency have been developed, opening the door for clinical application. Studies further demonstrated therapeutic effects of hPSC-CMs in small and large animal models and the underlying mechanisms of cardiac repair. However, gaps remain in explanations of the therapeutic effects of engrafted hPSC-CMs. In addition, bioengineering technologies improved survival and therapeutic effects of hPSC-CMs in vivo. While most of the original concerns associated with the use of hPSCs have been addressed, several issues remain to be resolved such as immaturity of transplanted cells, lack of electrical integration leading to arrhythmogenic risk, and tumorigenicity. Cell therapy with hPSC-CMs has shown great potential for biological therapy of injured heart; however, more studies are needed to ensure the therapeutic effects, underlying mechanisms, and safety, before this technology can be applied clinically.
Levodopa (L-DOPA) therapy is normally practised to treat motor pattern associated with Parkinson disease (PD). Additionally, several inhibitory drugs such as Entacapone and Opicapone are also cosupplemented to protect peripheral inactivation of exogenous L-DOPA (~80%) that occurs due to metabolic activity of the enzyme catechol-O-methyltransferase (COMT). Although, both Entacapone and Opicapone have U.S. Food and Drug Administration approval but regular use of these drugs is associated with high risk of side effects. Thus, authors have focused on in silico discovery of phytochemicals and evaluation of their effectiveness against human soluble COMT using virtual screening, molecular docking, drug-like property prediction, generation of pharmacophoric property, and molecular dynamics simulation. Overall, study proposed, nine phytochemicals (withaphysalin D, withaphysalin N, withaferin A, withacnistin, withaphysalin C, withaphysalin O, withanolide B, withasomnine, and withaphysalin F) of plant Withania somnifera have strong binding efficiency against human COMT in comparison to both of the drugs i.e., Opicapone and Entacapone, thus may be used as putative bioenhancer in L-DOPA therapy. The present study needs further experimental validation to be used as an adjuvant in PD treatment.
Jae-Sung Park;Min Ju Lee;Seong Bin Jo;Young Ae Joe
Biomolecules & Therapeutics
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v.31
no.1
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pp.1-15
/
2023
Autophagy is a process of eliminating damaged or unnecessary proteins and organelles, thereby maintaining intracellular homeostasis. Deregulation of autophagy is associated with several diseases including cancer. Contradictory dual roles of autophagy have been well established in cancer. Cytoprotective mechanism of autophagy has been extensively investigated for overcoming resistance to cancer therapies including radiotherapy, targeted therapy, immunotherapy, and chemotherapy. Selective autophagy inhibitors that directly target autophagic process have been developed for cancer treatment. Efficacies of autophagy inhibitors have been tested in various pre-clinical cancer animal models. Combination therapies of autophagy inhibitors with chemotherapeutics are being evaluated in clinal trials. In this review, we will focus on genetical and pharmacological perturbations of autophagy-related proteins in different steps of autophagic process and their therapeutic benefits. We will also summarize combination therapies of autophagy inhibitors with chemotherapies and their outcomes in pre-clinical and clinical studies. Understanding of current knowledge of development, progress, and application of cytoprotective autophagy inhibitors in combination therapies will open new possibilities for overcoming drug resistance and improving clinical outcomes.
Kim Sehee;Hong Ji Young;Joo So Yeon;Kim Jae Hwan;Moon Shin Yong;Yoon Hyun Soo;Kim Doo Han;Chung Hyung Min;Choi Seong-Jun
Reproductive and Developmental Biology
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v.28
no.4
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pp.247-252
/
2004
Human embryonic stem (ES) cells are derived from the inner cell mass of the preimplantation embryo. Human ES cells have the capacity to differentiate into various types of cells in the body. Human ES cells are indefinite source of cells for cell therapy in various degenerative disorders including neuronal disorders. Directed differentiation of human ES cells is a prerequisite for their clinical application. The objective of this study is to develop the culture condition for the derivation of neural precursor cells from human ES cells. Neural precursor cells were derived from human ES cells in a stepwise culture condition. Neural precursor cells in the form of neural rosette structures developed into neurospheres when cultured in suspension. Suspension culture of neurospheres has been maintained over 4 months. Expressions of nestin, soxl, sox2, pax3 and pax6 transcripts were upregulated during differentiation into neural precursor cells by RT-PCR analysis. In contrast, expression of oct4 was dramatically downregulated in neural precursor cells. Immunocytochemical analyses of neural precursor cells demonstrated expression of nestin and SOX1. When induced to differentiate on an adhesive substrate, neuro-spheres were able to differentiate into three lineages of neural systems, including neurons, astrocytes and oligo-dendrocytes. Transcripts of sox1 and pax6 were downregulated during differentiation of neural precursor cells into neurons. In contrast, expression of map2ab was elevated in the differentiated cells, relative to those in neural precursor cells. Neurons derived from neural precursor cells expressed NCAM, Tuj1, MAP2ab, NeuN and NF200 in immunocytochemical analyses. Presence of astrocytes was confirmed by expression of GFAP immuno-cytochemically. Oligodendrocytes were also observed by positive immuno-reactivities against oligodendrocyte marker O1. Results of this study demonstrate that a stepwise culture condition is developed for the derivation of neural precursor cells from human ES cells.
Purpose: The study to pulsed ultrasound effects of diabetes mellitus fracture model in rat. Methods: We used 36 Sprague-Dawely rats which were divided into 3 groups; the animals were divided into group of 4 rats each 4th, 14th and 28th days. All animal was induced diabetes mellitus model to used streptozotocin with 45 mg/kg. Pulsed wave were divided into $50\;mW/cm^2$ and $100\;mW/cm^2$. Results: T-ALP value was significantly change from group II, III on 14th, 28th days (p<0.05). Especially T-ALP value to between groups was significantly change from group II on 14th days (p<0.05). Osteocalcin value was significantly change from group II on 28th days(p<0.05). At fracture site, osteoblast, osteoclast expression was observed from 4th days after treatment and it reached its maximum intensity at 28th days. At fracture site, $TGF-{\beta}_1$ expression was observed from 4th days after treatment and it reached maximum intensity at 14th days. Conclusion: According to this study, diabetes mellitus fracture model to the more effective is divided into $50m\;W/cm^2$ pulsed ultrasound.
This study was performed to identify the effect of constant direct current and to give us methods which can be applied easily in clinic. Six rabbits was used at this experiment. After each animal was fractured at left fibula, divided into experimental group(n=3) and central group(n=3). Experiment duration of electrical stimulation on experimental rabbits was 35 days. Direct current from fifteen microampere to twenty microampere was passed continously through the placed electrode between fracture area and thigh. Negative electrode was placed at fracture area and positive at thigh. Roentgenography was used to observe bone-healing progression wet three times-at 15days, 25days and 35days after electrical stimulation. The results obtained are as followings: 1. Both experimental group and control group do not obtain callus formation on the first roentgenography(15 days after ES). 2. On the second roentgenography(25 days after ES), experimental group achieves above $70\%$ on fracture-healing, but control group achieves about $20-30\%$ on fracture healing. 3. On the third roentgenegraphy(35 nays after ES), experimental group achieves above $85-95\%$ on fracture healing and control group achieves about $60-70\%$ of bone union. Thus, statistically significance(independent t-test) was occured ie the second and third roentgenography between experimental group and control group.
Jo, Dae Hyun;Baatarkhuyag, Ariunchimeg;Jo, Ye Eun;Lee, Sang Hoon;Lee, Jae Dong
Journal of Acupuncture Research
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v.33
no.1
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pp.79-93
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2016
Objectives : The purpose of this study is to explore research trends in gold implantation therapy performed on the animal and human body, through a review of clinical studies focused on gold thread, gold needle and gold bead. Methods : Medical databases, including Pubmed, CENTRAL, MEDLINE, EMBASE, RISS4u, KISTI, OASIS and KTKP, were searched for relevant articles published from their launch to December 31, 2015 using the key word 'gold' with '$thread^*$', '$needle^*$', '$acupuncture^*$', '$wire^*$', '$bead^*$', '$embed^*$', '$implant^*$', or '$insert^*$'. The results were classified into in vivo studies, clinical trials and clinical reports. Analysis of the results was conducted in several research areas, from the identity of studies such as nationality and published year, to the gold preparations-features and implanted locations and to the outcomes that reflect the clinically favorable or adverse effect of gold implantation therapy. Results : A total of 30 studies including 11 in vivo studies, 4 clinical trials and 15 case reports, were found in the search. We observed certain research trends according to the research time, nationality and target indication of the studies. The studies primarily revealed a chronic local inflammatory response which could be a useful mechanism for pain-relief in musculoskeletal diseases and facial rejuvenation. Researches concerning long-term reactions or adverse effects were rare. Conclusion : The results show that the efforts to discover the level of clinical efficacy of gold implantation therapy were steady and worldwide. However, further researches on the longterm effect, and more importantly, the safety of gold implantation therapy are required.
Journal of Physiology & Pathology in Korean Medicine
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v.26
no.6
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pp.842-848
/
2012
This study was performed to investigate the acupuncture & moxibustion therapy of the Wei symptom(痿證) in order to find out the clinical possibility. We investigated the acupuncture & moxibustion therapy of Wei symptom through six books published after 1993, searched sites as like 'Oasis', 'Pubmed', 'RISS', 'KISS', 'NDSL' and 'Google scholar'. Acupuncture & moxibustion prescriptions recorded in the orietal medicine literatures that were published before and after 1993 had a similar basis. Since 2000, in the clinical papers on the wei symptom searched from domestic journal, sa-am and dong's acupuncture therapy were mainly applied, but papers were confined in a case study. Since the mid-2000s, the clinical effectiveness of bee venom and electroacupuncture therapy on the wei symptom were uncovered, but the researches about the chracteristics in accordance with acupoints are more required. Since 2010, the mechanism of the bee venom and electroacupuncture on the wei symptom was revealed in animal experiments. On this basis, the systematic clinical studies beyond case paer or pilot study is(are) needed. The development of various treatment implements as like electroacupuncture, pharmacopuncture was required to access the incurable disease like wei syptom, and the efforts of providing evidence through systemic clinical trials are needed.
Kim Nam-soo;Lee Cheol-ho;Lee Jong-il;Park Young-jae;Lee Byung-gon;Choi In-hyuk
Journal of Veterinary Clinics
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v.21
no.4
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pp.380-383
/
2004
Two dogs with hindlimb paralysis were referred to the Teaching Animal Hospital of Chonbuk National University. We performed an acupuncture in two cases. Case No.1 was a 5-year-old, 3kg intact mixed breed female dog presented with hindlimb paralysis during last 3 days. Physical examinations, CBC, serum chemistry, urinalysis and radiography carried out. The diagnosis was the thoracolumbar disk disease of Tl2-Tl3 on the basis of above these tests. Acupoints selected were Lumbosacral point, GV-5(Xuan Shu), GV-20(Bai Hui), GB-30(Huan Tiao), GB-31(Feng Shi), ST-36(Zu San Li) and GB-34(Yang Ling Quan). we performed an acupuncture therapy five times at 2 days intervals for 15 minutes each time. Case No.2 was 7-year-old, 6.0kg, mixed breed male dog which was presented with the history of hindlimb paralysis since 2 months. The medical history of the patient revealed that the condition did not respond to medicinal therapy. The diagnosis was the thoracolumbar disk disease of Tl3-Ll and left patellar luxation (one or two grade). We decided to perform acupuncture in this case also and the Lumbosacral point, GV-5(Xuan Shu), GV6(Ji Zhong), GV-7(Zhong She), GB-30(Huan Tiao), GB-31(Feng Shi), ST-36(Zu San Li), GB-34(Yang Ling Quan) were used. We performed acupuncture therapy at day 3, 6, 8 and 10 for 15 minutes each time. The response to an acupuncture therapy in two patients was good and the patients were almost recovered from hindlimb paralysis.
The purpose of this study was to investigate the effects of nutrition counseling on diabetes management by determining changes in anthropometry and blood components as well as knowledge and practice of diet therapy and nutrient intake in 34 (male 11, female 23) type 2 diabetes patients. The knowledge and the practice of diet therapy, drinking, smoking and exercise were analyzed by questionnaires. Dietary nutrient intake were obtained from the patients by the 1 day 24-hr recall. Blood glucose level and blood pressure were measured before and 3 months after the treatment. The results are summarized as follows: Average weight (p<0.05) and body mass index (p<0.05) were significantly lower post-counseling. Fasting blood glucose levels (p<0.01) and postprandial-2hour blood glucose levels (p<0.01) were also significantly lower post-counseling. In lifestyle changes for self-management the patients showed significantly higher exercise habits post-counseling (p<0.01). Regarding their level of diet knowledge, they showed significantly higher levels post-counseling in six items such as importance of diet therapy for diabetes (p<0.001), principles of diet therapy (p<0.001), nutrient composition of foods (p<0.01), carbohydrate composition of foods (p<0.001), the prescribed calories (p<0.001) understanding food item and exchange units of cereals, grains (p<0.001) and fruits, juices (p<0.001). Regarding their diet practices, the patients showed significantly higher levels of practice post-counseling in keeping within permitted meal size (p<0.001), using food exchange lists (p<0.001), keeping exact meal times (p<0.01), and controling sweet foods (p<0.001). Protein (p<0.05), animal lipid (p<0.05), and vitamin C (p<0.05) intakes were significantly higher post-counseling.
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