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The New Era of Omega-3 Fatty Acids Supplementation: Therapeutic Effects on Dry Age-Related Macular Degeneration. 补充Omega-3脂肪酸的新时代:干性老年性黄斑变性的治疗效果。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2015-01-01
Tassos Georgiou, Ekatherine Prokopiou

One of the major causes of reduced vision over the age of 50 is age-related macular degeneration (AMD). Although such a common pathology, there are no current guidelines for the first-line treatment of dry AMD. The aim of this study is to evaluate the therapeutic effects of high omega-3 fatty acids as anti-inflammatory agents in two sub-groups of dry AMD patients with 1) mild to moderate visual impairment and 2) with severe visual impairment (blindness). The key feature of this investigation is the frequent monitoring of the levels of specific fatty acids in patient's blood in order to adjust the treatment dose within the ideal therapeutic window. Following the positive outcome from our initial observational studies in patients with dry AMD, who demonstrated significant improvement in visual acuity (gain of ≥ 1 line of vision in 4.5 months) when taking a total of 5 g/day eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), additional studies were encouraged. The latest data which is presented in this chapter suggests that the eyes which had the greatest gain in vision (≥ 15 letters gain at 6 months) were from patients with mild to moderate visual impairment, who were taking between 5-7.5 g/day EPA and DHA and had a ratio of arachidonic acid (AA)/EPA < 2. In addition, a sub-group of dry AMD patients with severe visual impairment (< 6/60), showed significant increase in their visual acuity only 3 months following treatment with omega-3 fatty acids. The preliminary results indicate a promising therapeutic regime for dry AMD and perhaps for other types of retinopathies as well. Although initial results are encouraging, further investigations are necessary to establish a better understanding of the mode of action of these supplements and to observe their long-term effects.

50岁以上视力下降的主要原因之一是年龄相关性黄斑变性(AMD)。虽然这是一种常见的病理,但目前还没有针对干性黄斑变性的一线治疗指南。本研究的目的是评估高omega-3脂肪酸作为抗炎剂对两组干性AMD患者的治疗效果,这两组患者分别为1)轻度至中度视力障碍和2)重度视力障碍(失明)。这项研究的主要特点是经常监测患者血液中特定脂肪酸的水平,以便在理想的治疗窗口内调整治疗剂量。根据我们对干性AMD患者的初步观察性研究的积极结果,当总共服用5克/天的二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)时,他们的视力明显改善(在4.5个月内增加≥1条视力),我们鼓励进一步的研究。本章提供的最新数据表明,视力增加最大的眼睛(6个月时视力增加≥15个字母)来自轻度至中度视力障碍患者,每天服用5-7.5 g EPA和DHA,花生四烯酸(AA)/EPA的比例< 2。此外,一组重度视力障碍(< 6/60)的干性AMD患者,在接受omega-3脂肪酸治疗仅3个月后,其视力明显提高。初步结果表明,这是一种治疗干性黄斑变性和其他类型视网膜病变的有希望的疗法。虽然初步结果令人鼓舞,但还需要进一步调查,以更好地了解这些补充剂的作用方式,并观察其长期影响。
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引用次数: 0
Reversal of Methanol-Induced Blindness in Adults by Autologous Bone Marrow-Derived Stem Cells: A Case Series. 自体骨髓干细胞逆转成人甲醇性失明:一个病例系列。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2015-01-01
Himanshu Bansal, Yogesh Chaparia, Anupama Agrawal, Prasad S Koka

Introduction: Methanol ingestion leads to severe damage to visual pathways and permanent loss of vision. Current treatment is aimed at removal of methanol from system and prevention of generation of toxic metabolites along with symptomatic management of patient. Autologous bone marrow mononuclear stem cells (MNC) can be used to rejuvenate the damaged retinal cells and restoration of vision.

Methods: Five patients suffering from methanol induced complete blindness within three months of insult and no known comorbidities during the past 6 months were enrolled to receive autologous bone marrow derived mononuclear cell fraction on compassionate grounds. The visual acuity and visual evoked responses (VER) were done at the time of enrollment and during follow-up visits.

Observations and results: Visual acuity of these patients at the time of enrollment: no perception of light. Improvement in visual acuity was recorded by 7 days which reached maximum at 3 weeks after treatment in three patients and three months in two patients. The patients had acuity of 6/9, finger counting and reading with magnifying glasses with no subsequent improvement till 2 years of follow-up. Visual Evoked Responses demonstrated improvements following treatment. No adverse reactions were noticed during follow-up.

Conclusion: Treatment with Autologous Bone marrow derived MNC offers a new line of management in patients with loss of vision following methanol ingestion. The efficacy and safety of this line of management needs to be evaluated in controlled clinical trials.

甲醇摄入会导致严重的视觉通路损伤和永久性视力丧失。目前的治疗旨在从系统中去除甲醇,防止有毒代谢物的产生,同时对患者进行症状管理。自体骨髓单个核干细胞(MNC)可用于修复受损视网膜细胞和恢复视力。方法:5例甲醇致完全失明患者在3个月内遭受侮辱,且在过去6个月内无已知合并症,基于同情理由接受自体骨髓来源的单个核细胞分数。在入组时和随访期间进行视敏度和视觉诱发反应(VER)测试。观察结果:患者入组时视力:无光感。视力改善7天,其中3例在治疗后3周达到最大,2例在治疗后3个月达到最大。患者视力为6/9,手指计数和放大镜阅读,随访2年未见改善。视觉诱发反应在治疗后得到改善。随访期间未见不良反应。结论:自体骨髓源性MNC治疗为甲醇摄入后视力丧失的患者提供了一条新的治疗途径。这种治疗方法的有效性和安全性需要在对照临床试验中进行评估。
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引用次数: 0
Stem Cells Cultured on Beta Tricalcium Phosphate (β-TCP) in Combination with Recombinant Human Platelet-Derived Growth Factor - BB (rh-PDGF-BB) for the Treatment of Human Infrabony Defects. β-磷酸三钙(β-TCP)联合重组人血小板衍生生长因子-BB (rh-PDGF-BB)培养干细胞治疗人下骨缺损
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2015-01-01 DOI: jsc.2015.10.4.243
Roshani Dhote, Priti Charde, Manohar Bhongade, Jyotsana Rao

Knowledge gained from the field of tissue engineering, helped to develop a biological substitute that promotes tissue regeneration. The usual biological substitute consists of stem cells, growth factors and an appropriate scaffold. The present randomized controlled clinical and radiographic study was undertaken to evaluate the effectiveness of mesenchymal stem cells cultured on beta tricalcium phosphate (β-TCP) in combination with rh-PDGF-BB in treatment of infrabony defect in humans. A total of 24 infrabony defects in 14 systemically healthy patients were selected for the present study. The selected defects exhibited a probing pocket depth (PPD) of ≥ 5 mm and depth of infrabony component ≥ 3 mm as assessed by clinical and radiographic measurements and later confirmed by intrasurgical measurement. Baseline measurements included were Plaque Index (PI), Papillary Bleeding Index (PBI), Probing Pocket Depth (PPD), Relative gingival marginal level (RGML), Relative Clinical Attachment Level (R-CAL) and Radiographic Defect Depth (DD) and linear bone growth (LBG). 6 weeks after initial therapy, the defects were randomly assigned to either test group or control group. The control group was treated by an open flap debridement (OFD) only, while the test group was treated by a Stem cells cultured on β-TCP in combination with rh-PDGF-BB. All the measurements recorded preoperatively were repeated at 6 months after the surgery. The efficacy of each treatment modality was investigated through statistical analysis. Mean probing pocket depth reduction was significantly greater in test group (4.50 ± 1.08 mm) compared to the OFD group (3.50 ± 0.90 mm). Mean gains in clinical attachment level was 3.91 ± 1.37 mm in the test group and 2.08 ± 0.90 mm in the control group. The mean increase in gingival recession (GR) was less in test group (0.58 ± 0.79 mm) compared to OFD group (1.4 ± 0.66 mm). Radiographic defect depth reduction was greater in the test group (3.50 ± 0.67 mm) with 88.33% defect fill compared to control group (1.83 ± 0.38 mm) with only 52.77% defect fill. Linear bone growth (LBG) was significantly improved by 3.58 mm in test group, while in control group, it was 1.83 mm. Regenerative approach using Stem cells cultured on β-TCP in combination with rh-PDGF-BB for the treatment of human infrabony defects resulted in a significant added benefit in terms of CAL gains, PPD reductions greater radiographic defect fill and improvement in Linear bone growth (LBG) compared to the OFD alone.

从组织工程领域获得的知识,有助于开发一种促进组织再生的生物替代品。通常的生物替代品由干细胞、生长因子和合适的支架组成。目前的随机对照临床和放射学研究是为了评估β-磷酸三钙(β-TCP)培养的间充质干细胞联合rh-PDGF-BB治疗人类下骨缺损的有效性。本研究选取了14例全身健康的患者,共24例骨下缺损。所选的缺陷表现为探测袋深度(PPD)≥5mm,下骨成分深度≥3mm,经临床和影像学测量评估,随后经术内测量证实。基线测量包括斑块指数(PI)、乳头状出血指数(PBI)、探测袋深度(PPD)、相对牙龈边缘水平(RGML)、相对临床附着水平(R-CAL)、放射学缺陷深度(DD)和线性骨生长(LBG)。初始治疗6周后,将缺陷随机分为试验组和对照组。对照组采用开放皮瓣清创(OFD)治疗,试验组采用β-TCP培养的干细胞联合rh-PDGF-BB治疗。术前记录的所有测量在术后6个月重复。采用统计学方法对各治疗方式的疗效进行分析。试验组探测袋平均深度减少(4.50±1.08 mm)明显大于OFD组(3.50±0.90 mm)。试验组临床附着水平平均增加3.91±1.37 mm,对照组平均增加2.08±0.90 mm。试验组牙龈退缩(GR)的平均增加(0.58±0.79 mm)小于OFD组(1.4±0.66 mm)。与对照组(1.83±0.38 mm)缺陷充盈率仅为52.77%相比,试验组(3.50±0.67 mm)缺陷深度缩小更大,缺陷充盈率为88.33%。试验组线性骨生长(LBG)显著提高3.58 mm,对照组提高1.83 mm。与单独的OFD相比,利用β-TCP培养的干细胞与rh-PDGF-BB联合治疗人类下骨缺损的再生方法在CAL增益、PPD减少、放射学缺陷填充和线状骨生长(LBG)改善方面取得了显著的额外益处。
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引用次数: 0
Overview of Risk Factors for Age-Related Macular Degeneration (AMD). 年龄相关性黄斑变性(AMD)的危险因素概述。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2015-01-01
Richard A Armstrong, Maryam Mousavi

Age related macular degeneration (AMD) is the leading cause of blindness in individuals older than 65 years of age. It is a multifactorial disorder and identification of risk factors enables individuals to make life style choices that may reduce the risk of disease. This review discusses the role of genetics, sunlight, diet, cardiovascular factors, smoking, and alcohol as possible risk factors for AMD. Genetics plays a more significant role in AMD than previously thought, especially in younger patients, histocompatibility locus antigen (HLA) and complement system genes being the most significant. Whether the risk of AMD is increased by exposure to sunlight, cardiovascular risk factors, and diet is more controversial. Smoking is the risk factor most consistently associated with AMD. Current smokers are exposed to a two to three times higher risk of AMD than non-smokers and the risk increases with intensity of smoking. Moderate alcohol consumption is unlikely to increase the risk of AMD. Optometrists as front-line informers and educators of ocular health play a significant role in increasing public awareness of the risks of AMD. Cessation of smoking, the use of eye protection in high light conditions, dietary changes, and regular use of dietary supplements should all be considered to reduce the lifetime risk of AMD.

年龄相关性黄斑变性(AMD)是65岁以上人群失明的主要原因。它是一种多因素疾病,识别风险因素使个人能够选择可能降低疾病风险的生活方式。这篇综述讨论了遗传、阳光、饮食、心血管因素、吸烟和酒精作为AMD可能的危险因素的作用。遗传在AMD中发挥的作用比以前认为的更重要,特别是在年轻患者中,组织相容性位点抗原(HLA)和补体系统基因是最重要的。黄斑变性的风险是否与暴露在阳光下、心血管危险因素和饮食有关还存在争议。吸烟是与AMD最一致的风险因素。目前吸烟者患黄斑变性的风险是不吸烟者的两到三倍,而且风险随着吸烟的强度而增加。适度饮酒不太可能增加AMD的风险。验光师作为眼科健康的一线信息提供者和教育者,在提高公众对黄斑变性风险的认识方面发挥着重要作用。戒烟、在强光条件下使用护眼、改变饮食习惯和定期使用膳食补充剂都应被视为降低AMD的终生风险。
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引用次数: 0
Effect of Mobile Phone-Induced Electromagnetic Field on Brain Hemodynamics and Human Stem Cell Functioning: Possible Mechanistic Link to Cancer Risk and Early Diagnostic Value of Electronphotonic Imaging. 手机电磁场对大脑血流动力学和人类干细胞功能的影响:与癌症风险的可能机制联系和电子光子成像的早期诊断价值。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2015-01-01 DOI: jsc.2015.10.4.287
Hemant Bhargav, T M Srinivasan, S Varambally, B N Gangadhar, Prasad Koka

The mobile phones (MP) are low power radio devices which work on electromagnetic fields (EMFs), in the frequency range of 900-1800 MHz. Exposure to MPEMFs may affect brain physiology and lead to various health hazards including brain tumors. Earlier studies with positron emission tomography (PET) have found alterations in cerebral blood flow (CBF) after acute exposure to MPEMFs. It is widely accepted that DNA double-strand breaks (DSBs) and their misrepair in stem cells are critical events in the multistage origination of various leukemia and tumors, including brain tumors such as gliomas. Both significant misbalance in DSB repair and severe stress response have been triggered by MPEMFs and EMFs from cell towers. It has been shown that stem cells are most sensitive to microwave exposure and react to more frequencies than do differentiated cells. This may be important for cancer risk assessment and indicates that stem cells are the most relevant cellular model for validating safe mobile communication signals. Recently developed technology for recording the human bio-electromagnetic (BEM) field using Electron photonic Imaging (EPI) or Gas Discharge Visualisation (GDV) technique provides useful information about the human BEM. Studies have recorded acute effects of Mobile Phone Electromagnetic Fields (MPEMFs) using EPI and found quantifiable effects on human BEM field. Present manuscript reviews evidences of altered brain physiology and stem cell functioning due to mobile phone/cell tower radiations, its association with increased cancer risk and explores early diagnostic value of EPI imaging in detecting EMF induced changes on human BEM.

移动电话(MP)是工作在电磁场(emf)上的低功率无线电设备,频率范围为900- 1800mhz。接触强电磁场可能影响大脑生理,并导致包括脑肿瘤在内的各种健康危害。早期的正电子发射断层扫描(PET)研究发现急性暴露于mmpemfs后脑血流量(CBF)发生改变。干细胞中DNA双链断裂(DSBs)及其错误修复是多种白血病和肿瘤(包括脑肿瘤如胶质瘤)多阶段起源的关键事件,这一观点已被广泛接受。mmpemfs和来自信号塔的EMFs均可触发DSB修复中的显著失衡和严重的应激反应。研究表明,干细胞对微波辐射最敏感,比已分化的细胞对更多频率的微波辐射有反应。这可能对癌症风险评估很重要,并表明干细胞是验证安全移动通信信号最相关的细胞模型。最近发展起来的利用电子光子成像(EPI)或气体放电可视化(GDV)技术记录人体生物电磁(BEM)场的技术提供了有关人体生物电磁(BEM)的有用信息。研究利用EPI记录了手机电磁场的急性效应,并发现了可量化的对人体BEM场的影响。本文综述了移动电话/手机发射塔辐射导致的脑生理和干细胞功能改变的证据,其与癌症风险增加的关系,并探讨了EPI成像在检测电磁场引起的人类BEM变化方面的早期诊断价值。
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引用次数: 0
Overview of Risk Factors for Age-Related Macular Degeneration (AMD). 年龄相关性黄斑变性(AMD)的危险因素概述。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2015-01-01 DOI: 10.1016/B978-0-12-815245-4.00002-8
R. Armstrong, M. Mousavi
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引用次数: 65
Antiaging Effects of an Intensive Mind and Body Therapeutic Program through Enhancement of Telomerase Activity and Adult Stem Cell Counts. 通过增强端粒酶活性和成体干细胞计数的强化身心治疗计划的抗衰老作用。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2015-01-01
Krishna S Rao, Swarup K Chakraharti, Vaishali S Dongare, K Chetana, Christina M Ramirez, Prasad S Koka, Kaushik D Deb

Objective: Key modalities of integrative medicine known to rejuvenate the mind and body are meditation, yoga, and controlled diet. It has been shown previously that intensive or prolonged mind and body therapies (MBT) may have beneficial effects on the well-being of healthy people and in patients. Telomerase activity and levels of peripheral blood adult pluripotent stem cells (PB-APSC) are reliable markers of long-term well-being that are known to decrease with age. The objective of this study is to understand the effect of our MBT program on telomerase activity and stem cells in blood collected from the participants.

Design: Here, we have investigated the effects of an intensive three weeks MBT retreat on telomerase activity and the peripheral blood stem cells in participants before and after the MBT. A total of 108 people were enrolled in the study; 38 men and 70 women (aged 18-90) randomly assigned for the study.

Results: Telomerase activity was greater in retreat participants at the end of the MBT retreat. About 45% of people showed more than one-fold increase of telomerase activity after our MBT program. Furthermore, about 27% of people showed more pronounced fold increase (2-fold) in telomerase activity after the MBT. In addition, a substantial percentage of people (about 90%) exhibited increased stem cell counts after the MBT.

Conclusions: The data suggest increased telomerase activity and stem cells count in peripheral blood from MBT retreat participants that may lead to increased longevity and better quality of life at latter age.

目的:已知的使身心恢复活力的综合医学的关键模式是冥想,瑜伽和控制饮食。以前已经表明,密集或长期的身心疗法(MBT)可能对健康人和患者的福祉产生有益影响。端粒酶活性和外周血成体多能干细胞(PB-APSC)水平是长期健康的可靠标志,随着年龄的增长而下降。本研究的目的是了解我们的MBT计划对从参与者收集的血液中端粒酶活性和干细胞的影响。设计:在这里,我们研究了密集的三周MBT退却对MBT前后参与者端粒酶活性和外周血干细胞的影响。共有108人参加了这项研究;38名男性和70名女性(年龄在18-90岁之间)被随机分配到研究中。结果:端粒酶活性在MBT撤退结束时更大的参与者。大约45%的人在我们的MBT项目后端粒酶活性增加了一倍以上。此外,约27%的人在MBT后端粒酶活性明显增加(2倍)。此外,相当大比例的人(约90%)在MBT后表现出增加的干细胞计数。结论:数据表明,MBT撤退参与者外周血端粒酶活性和干细胞计数的增加可能导致晚年寿命延长和生活质量提高。
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引用次数: 0
Differentiation Potential of Mesenchymal Stem Cells from Equine Bone Marrow Cultured on Hyaluronic Acid-Chitosan Polyelectrolyte Multilayer Biofilm. 透明质酸-壳聚糖聚电解质多层生物膜培养马骨髓间充质干细胞的分化潜力。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2015-01-01
Amanda J Listoni, Isadora Arruda, Leandro Maia, Danielle J Barberini, Ian Martins, Fernando C Vasconcellos, Fernanda C Landim-Alvarenga

Nanotechnology techniques have a prominent role in the current technical and scientific scene. The layer-by-layer (LbL) deposition allows obtaining nanostructures with sophisticated multilayer, using a simple, but versatile technique. This procedure, which is used to coat and functionalize surfaces with nanometer- thick films, has applications in bioengineering, medicine, chemistry, materials and chemical engineering among other areas. Chitosan is a biomaterial, coming from the chitin, a very abundant polymer in nature, which has been recently tested as scaffolds. In this experiment we test the hypothesis that the hyaluronic acid-chitosan polyelectrolyte multilayer biofilm would be a good substrate to the adherence of equine mesenchymal stem cells derived from bone marrow. The results showed that these biofilms accelerate the process of cell adhesion on smooth surfaces, allowing a constant cell growth and creating a great option to cover surgical materials.

纳米技术在当前的技术和科学领域具有突出的作用。利用一种简单而通用的技术,逐层沉积可以获得复杂的多层纳米结构。该方法用于在表面涂覆纳米厚薄膜并使其功能化,在生物工程、医学、化学、材料和化学工程等领域都有应用。壳聚糖是一种生物材料,来自于自然界中含量非常丰富的聚合物几丁质,最近已被用作支架进行了测试。本实验验证了透明质酸-壳聚糖聚电解质多层生物膜作为马骨髓间充质干细胞粘附的良好底物的假设。结果表明,这些生物膜加速了细胞在光滑表面上的粘附过程,允许细胞持续生长,并为覆盖手术材料创造了一个很好的选择。
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引用次数: 0
Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Duchenne Muscular Dystrophy: Safety and Feasibility Study in India. 人脐带间充质干细胞治疗杜氏肌营养不良:印度的安全性和可行性研究。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2015-01-01
B S Rajput, Swarup K Chakrabarti, Vaishali S Dongare, Christina M Ramirez, Kaushik D Deb

Objective: Duchenne muscular dystrophy (DMD) is a musculo-degenerative disease characterized by lack of dystrophin production with no definite cure available currently. Discarded umbilical cord is a potential source of mesenchymal stem cells which are non-immunogenic and can be used for transplantation in allogenic set ups. Given the regenerative and anti-inflammatory properties of mesenchymal stem cells (MSCs), here we investigated its role in the cellular therapy of DMD patients.

Design: This is a single-blinded study conducted in various hospitals of India situated in Mumbai, Delhi, and Lucknow. Inclusion criteria for enrolling the patients in the study were boys aged between 5 to 18 years, absence of dystrophin in the immunohistochemistry of muscle biopsy and mutation in dystrophin gene in cytogenetic analysis. The exclusion criteria were presence of dystrophin in the muscle biopsy, patients on corticosteroids etc. UC-MSCs (2 millions/kg body weight) were administered through IV and IM injection. Muscle power in muscles of proximal upper limb, distal upper limb, proximal lower limb, distal lower limb, hip flexors, hip extensors, hip abductors, and paraspinal muscles were measured in 11 DMD patients after UC-MSCs transplantation and were followed for up to 3 years (average follow up 1.5 years). 5 DMD patients did not receive any UC-MSCs transplantation and served as the control group.

Results: The treatment group (N = 11 at baseline) had a pretransplantation strength of 3.45 ± 1.0357 and 4.090 ± 0.8312 in muscles of proximal upper limb and distal upper limb respectively. After 1 year (N = 9) these strengths remained stable with an average of 3.78 (1.03) and 4.22 (0.83). In contrast, the control group (N = 5) has a pre-transplantation strength of 3.6 (0.54) and 4 (1) in the proximal and distal upper limb respectively. After 1 year, (N = 5) 3/5 subjects had a slight but not statistically significant decrease in the proximal upper limb, mean 3.0 (1.0) and 5/5 had a lunit decrease in strength, mean 3.0 (1.0). The treatment group had a pre-transplantation strength of 2.0909 ± 0.8312 and 3.1181 ± 0.8738 in muscles of distal and proximal lower limbs respectively. At 1 year (N = 9), 4/9 subjects had a 1 unit increase in strength in the distal lower limb (mean 3.78 (0.97)) and 8/9 subjects had a lunit increase in strength in the proximal lower limb, mean 3.11 (1.05). The control group has a mean of 3.41 (0.54) and 3.0 (1.0) at baseline in the distal and proximal lower limb respectively. By 1 year, 3/5 subjects had a 1 unit decrease (mean 2.8 (0.45)) and 5/5 had a lunit decrease, mean 2.0 (1.0) in distal and proximal lower limb strength. Stability in muscle function was also achieved in muscles of hip flexors, hip extensors, hip abductors, and paraspinal muscles at one year as compared to untreated group.

Conclusion: UC-MSCs administration not only resulted in the s

目的:杜氏肌营养不良症(DMD)是一种以肌营养不良蛋白缺乏为特征的肌肉退行性疾病,目前尚无明确的治疗方法。废弃脐带是非免疫原性间充质干细胞的潜在来源,可用于同种异体移植。鉴于间充质干细胞(MSCs)的再生和抗炎特性,我们在这里研究了它在DMD患者细胞治疗中的作用。设计:这是一项在印度孟买、德里和勒克瑙的多家医院进行的单盲研究。纳入研究患者的标准是年龄在5 - 18岁之间的男孩,肌肉活检的免疫组化检查中没有肌营养不良蛋白,细胞遗传学分析中有肌营养不良蛋白基因突变。排除标准为肌肉活检中存在肌营养不良蛋白,患者使用皮质类固醇等。UC-MSCs(200万个/kg体重)通过静脉注射和IM注射给药。对11例UC-MSCs移植后的DMD患者的上肢近端、上肢远端、下肢近端、下肢远端、髋关节屈肌、髋关节伸肌、髋关节外展肌和棘旁肌的肌力进行了测量,随访时间长达3年(平均随访时间为1.5年)。5例DMD患者未接受UC-MSCs移植,作为对照组。结果:治疗组(基线时N = 11)上肢近端和远端肌肉移植前强度分别为3.45±1.0357和4.090±0.8312。1年后(N = 9),这些优势保持稳定,平均为3.78(1.03)和4.22(0.83)。对照组(N = 5)的上肢近端和远端移植前强度分别为3.6(0.54)和4(1)。1年后,(N = 5) 3/5的受试者上肢近端有轻微但无统计学意义的下降,平均3.0(1.0),5/5的受试者力量下降,平均3.0(1.0)。治疗组移植前下肢远端和近端肌肉强度分别为2.0909±0.8312和3.1181±0.8738。1年后(N = 9), 4/9的受试者下肢远端力量增加了1个单位(平均3.78(0.97)),8/9的受试者下肢近端力量增加了1个单位,平均3.11(1.05)。对照组下肢远端和近端基线平均值分别为3.41(0.54)和3.0(1.0)。1年后,3/5的受试者下肢远端和近端强度下降1个单位(平均2.8(0.45)),5/5的受试者下肢远端和近端强度下降1个单位,平均2.0(1.0)。与未治疗组相比,髋关节屈肌、髋关节伸肌、髋关节外展肌和棘旁肌的肌肉功能在一年内也实现了稳定。结论:UC-MSCs给药不仅导致肌肉力量的稳定,而且没有显示出GVHD或对患者的任何有害影响,因此与对照组相比,可能被认为是治疗DMD的安全选择,尽管需要进一步的更大规模的双盲研究。
{"title":"Human Umbilical Cord Mesenchymal Stem Cells in the Treatment of Duchenne Muscular Dystrophy: Safety and Feasibility Study in India.","authors":"B S Rajput,&nbsp;Swarup K Chakrabarti,&nbsp;Vaishali S Dongare,&nbsp;Christina M Ramirez,&nbsp;Kaushik D Deb","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objective: </strong>Duchenne muscular dystrophy (DMD) is a musculo-degenerative disease characterized by lack of dystrophin production with no definite cure available currently. Discarded umbilical cord is a potential source of mesenchymal stem cells which are non-immunogenic and can be used for transplantation in allogenic set ups. Given the regenerative and anti-inflammatory properties of mesenchymal stem cells (MSCs), here we investigated its role in the cellular therapy of DMD patients.</p><p><strong>Design: </strong>This is a single-blinded study conducted in various hospitals of India situated in Mumbai, Delhi, and Lucknow. Inclusion criteria for enrolling the patients in the study were boys aged between 5 to 18 years, absence of dystrophin in the immunohistochemistry of muscle biopsy and mutation in dystrophin gene in cytogenetic analysis. The exclusion criteria were presence of dystrophin in the muscle biopsy, patients on corticosteroids etc. UC-MSCs (2 millions/kg body weight) were administered through IV and IM injection. Muscle power in muscles of proximal upper limb, distal upper limb, proximal lower limb, distal lower limb, hip flexors, hip extensors, hip abductors, and paraspinal muscles were measured in 11 DMD patients after UC-MSCs transplantation and were followed for up to 3 years (average follow up 1.5 years). 5 DMD patients did not receive any UC-MSCs transplantation and served as the control group.</p><p><strong>Results: </strong>The treatment group (N = 11 at baseline) had a pretransplantation strength of 3.45 ± 1.0357 and 4.090 ± 0.8312 in muscles of proximal upper limb and distal upper limb respectively. After 1 year (N = 9) these strengths remained stable with an average of 3.78 (1.03) and 4.22 (0.83). In contrast, the control group (N = 5) has a pre-transplantation strength of 3.6 (0.54) and 4 (1) in the proximal and distal upper limb respectively. After 1 year, (N = 5) 3/5 subjects had a slight but not statistically significant decrease in the proximal upper limb, mean 3.0 (1.0) and 5/5 had a lunit decrease in strength, mean 3.0 (1.0). The treatment group had a pre-transplantation strength of 2.0909 ± 0.8312 and 3.1181 ± 0.8738 in muscles of distal and proximal lower limbs respectively. At 1 year (N = 9), 4/9 subjects had a 1 unit increase in strength in the distal lower limb (mean 3.78 (0.97)) and 8/9 subjects had a lunit increase in strength in the proximal lower limb, mean 3.11 (1.05). The control group has a mean of 3.41 (0.54) and 3.0 (1.0) at baseline in the distal and proximal lower limb respectively. By 1 year, 3/5 subjects had a 1 unit decrease (mean 2.8 (0.45)) and 5/5 had a lunit decrease, mean 2.0 (1.0) in distal and proximal lower limb strength. Stability in muscle function was also achieved in muscles of hip flexors, hip extensors, hip abductors, and paraspinal muscles at one year as compared to untreated group.</p><p><strong>Conclusion: </strong>UC-MSCs administration not only resulted in the s","PeriodicalId":53626,"journal":{"name":"Journal of Stem Cells","volume":"10 2","pages":"141-56"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34439704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Cancer Stem Cells and Chemoresistance in Glioblastoma Multiform: A Review Article. 多形性胶质母细胞瘤的肿瘤干细胞和化疗耐药研究综述。
Q4 Biochemistry, Genetics and Molecular Biology Pub Date : 2015-01-01 DOI: jsc.2015.10.4.271
Mojdeh Safari, Alireza Khoshnevisan

Glioblastomamultiforme (GBM) is the most common malignant and aggressive primary tumor of the brain in adults and characterized by a heterogeneous population of cells that are genetically unstable, highly infiltrative, angiogenic, and resistant to chemotherapy. Considerable efforts being devoted to identifying the molecular basis of resistance in GBM and exploring novel therapeutic targets that may improve overall survival. Several independent DNA repair mechanisms that normally safeguard genome integrity can facilitate drug resistance and cancer cell survival by removing chemotherapy- induced adducts. The recent data suggest that the most important mechanism of resistance to alkylating agents is the DNA repair enzyme O6-methylguanine methyltransferase (MGMT). Although, the treatment failure is a result of a number of causes, but currently, it has been demonstrated that a highly tumorigenic subpopulation of cancer cells called glioblastoma stem cells (GSCs) display relative resistance to radiation and chemotherapy. In fact, GBM stem cells express high levels of MGMT and this may account for GBM resistance following chemotherapy. GSCs also contribute to tumor growth through the stimulation of angiogenesis, which has been shown to be a useful therapeutic target in the treatment of recurrent or progressive malignant gliomas. In this review, we summarize the chemoresistance mechanisms of GBMs (to alkylating agents), with a special focus on the role of cancer stem cells.

多形性胶质母细胞瘤(GBM)是成人中最常见的恶性和侵袭性原发性脑肿瘤,其特点是细胞群异质性,遗传不稳定,高度浸润,血管生成,耐化疗。在确定GBM耐药的分子基础和探索可能提高总生存率的新治疗靶点方面,人们付出了相当大的努力。一些独立的DNA修复机制通常保护基因组完整性,可通过去除化疗诱导的加合物促进耐药和癌细胞存活。最近的数据表明,对烷基化剂的抗性最重要的机制是DNA修复酶o6 -甲基鸟嘌呤甲基转移酶(MGMT)。虽然治疗失败是由多种原因造成的,但目前已经证明,一种称为胶质母细胞瘤干细胞(GSCs)的高度致瘤性癌细胞亚群对放疗和化疗表现出相对的抗性。事实上,GBM干细胞表达高水平的MGMT,这可能是化疗后GBM耐药的原因。GSCs还通过刺激血管生成促进肿瘤生长,这已被证明是治疗复发或进展性恶性胶质瘤的有用治疗靶点。在这篇综述中,我们总结了GBMs(对烷基化剂)的化学耐药机制,特别关注癌症干细胞的作用。
{"title":"Cancer Stem Cells and Chemoresistance in Glioblastoma Multiform: A Review Article.","authors":"Mojdeh Safari,&nbsp;Alireza Khoshnevisan","doi":"jsc.2015.10.4.271","DOIUrl":"https://doi.org/jsc.2015.10.4.271","url":null,"abstract":"<p><p>Glioblastomamultiforme (GBM) is the most common malignant and aggressive primary tumor of the brain in adults and characterized by a heterogeneous population of cells that are genetically unstable, highly infiltrative, angiogenic, and resistant to chemotherapy. Considerable efforts being devoted to identifying the molecular basis of resistance in GBM and exploring novel therapeutic targets that may improve overall survival. Several independent DNA repair mechanisms that normally safeguard genome integrity can facilitate drug resistance and cancer cell survival by removing chemotherapy- induced adducts. The recent data suggest that the most important mechanism of resistance to alkylating agents is the DNA repair enzyme O6-methylguanine methyltransferase (MGMT). Although, the treatment failure is a result of a number of causes, but currently, it has been demonstrated that a highly tumorigenic subpopulation of cancer cells called glioblastoma stem cells (GSCs) display relative resistance to radiation and chemotherapy. In fact, GBM stem cells express high levels of MGMT and this may account for GBM resistance following chemotherapy. GSCs also contribute to tumor growth through the stimulation of angiogenesis, which has been shown to be a useful therapeutic target in the treatment of recurrent or progressive malignant gliomas. In this review, we summarize the chemoresistance mechanisms of GBMs (to alkylating agents), with a special focus on the role of cancer stem cells.</p>","PeriodicalId":53626,"journal":{"name":"Journal of Stem Cells","volume":"10 4","pages":"271-85"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34454923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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Journal of Stem Cells
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