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Adeno-associated virus as a gene therapy vector: strategies to neutralize the neutralizing antibodies
Get PDFAdeno-associated virus (AAV)-derived vectors are currently the most common type of viral vectors used in gene therapy clinical trials. The presence of neutralizing antibodies (NAbs) against wild-type AAVs in the host body is one of the limitations for the successful use of AAV vectors. AAV capsid manipulation, by which recombinant vectors lose their ability to interact with NAbs, can help overcome this obstacle. Various methods can be used for this purpose, including directed evolution as well as conjugation of certain chemical groups to AAV epitopes. The present review concisely explains the use of AAV vectors in the clinic for gene therapy of some diseases, their limitations, and solutions to these limitations. © 2019, Springer Nature Switzerland AG
Comment on long-term outcomes of metabolic and bariatric surgery in adolescents with severe obesity with a follow-up of at least 5 years: a systematic review
Get PDFMeasurement of the contralateral breast photon and neutron dose in breast cancer radiotherapy: A Monte Carlo study
Get PDFIntroduction: This study aimed to calculate the photon and neutron doses received to the contralateral breast (CB) during breast cancer radiotherapy for various field sizes in the presence of a physical wedge. Materials and Methods: Varian 2100 C/D linear accelerator was simulated using a MCNP4C Monte Carlo code. Then, a phantom of real female chest was simulated and the treatment planning was carried out on tumoral breast (left breast). Finally, the received photon and neutron doses to CB (right breast) were calculated in the presence of a physical wedge for 18 MV photon beam energy. These calculations were performed for different field sizes including 11 cm � 13 cm, 11 cm � 17 cm, and 11 cm � 21 cm. Results: The findings showed that the received doses (both of the photon and neutron) to CB in the presence of a physical wedge for 11 cm � 13 cm, 11 cm � 17 cm, and 11 cm � 21 cm field sizes were 9.87, 12.91, and 27.37 of the prescribed dose, respectively. In addition, the results showed that the received photon and neutron doses to CB increased with increment in the field size. Conclusion: From the results of this study, it is concluded that the received photon and neutron doses to CB in the presence of a physical wedge is relatively more, and therefore, they should be reduced to as low as possible. Therefore, using a dynamic wedge instead of a physical wedge or field-in-field technique is suggested. © 2018 Journal of Cancer Research and Therapeutics | Published by Wolters Kluwer - Medknow
The effect of six weeks yoga exercises on quality of life in infertile women with polycystic ovary syndrome (Pcos)
Get PDFIntroduction: Infertility is one of the main concerns of human societies and PCOS is considered as the most common reason of women's infertility due to ovulation disorders. Infertility has been considered as the main cause of psychopathy disorders and reduced quality of life in PCOS patients. Exercise is a non-pharmaceutical method in treatment of PCOS that yoga is a recommended exercise for this disease. This study was performed with aim to determine the effect of 6 weeks yoga on the quality of life in infertile women with PCOS. Methods: This clinical randomized trial was performed on 61 infertile women with PCOS undergoing infertility treatment referred to the Tehran Sarem Hospital in 2015-2015. The qualified subjects were divided to two groups of case and control. Then, all the subjects completed the demographic profile and fertility questionnaires and modified PCOS questionnaire. Then, the case group performed yoga for 6 weeks and the control group did not receive any intervention. After 6 weeks, the questionnaires were again completed. Data were analyzed by SPSS software (version 21) and independent t-test, paired t-test, Mann-Whitney, Chi-square, Mac-Nemar, and Wilcoxon test. P<0.05 was considered statistically significant Results: Yoga exercise for 6 weeks had significant effect on the scores of quality of life and Hirsotism (p=0.001), weight (p= 0.010), Acnea (p= 0.001), infertility (p= 0.001), Emotional (p<0.001), menstrual disorders (p<0.001) and total score (p<0.001). Conclusion: Yoga as a meditation exercise for 6 weeks can improve the score of quality of life in women with PCOS undergoing infertility treatment. Therefore, this exercise as an effective and low-cost method can be used for improvement of life quality in these women. © 2019, Mashhad University of Medical Sciences. All rights reserved
Novel point mutations in cyp51A and cyp51B genes associated with itraconazole and posaconazole resistance in aspergillus clavatus isolates
No full textAspergillus clavatus is a common environmental species known to cause occupational allergic disease in grain handlers. We have recently observed azole-resistant isolates of this fungus as a cause of onychomycosis. To further characterize the cause of resistance, the genes encoding 14 α-sterol demethylase enzyme (cyp51A and cyp51B) were characterized and analyzed in 9 ITC-susceptible isolates and 6 isolates with high minimum inhibitory concentrations (MICs) of clinical (nail and sputum) and environmental A. clavatus strains. We found that six isolates with itraconazole MIC >16 mg/L demonstrated nonsynonymous mutations, including V51I, L378P, E483K, and E506G, and synonymous mutations, including F53F, A186A, Q276Q, and H359H. Moreover, P486S was detected in five strains with ITR MIC >16 mg/L. One mutation, F324S, was detected in an isolate with posaconazole MIC >16 mg/L. The effect of E483K and P486S mutations of CYP51A on azole resistance was further investigated using homology modeling and molecular dynamics. We found that E483K and P486S mutations were located near the ligand access channel of CYP51A that could partly lead to narrowing the entry of the ligand access channels. Therefore, we concluded that E483K and P486S mutations may potentially contribute to the limited access of inhibitors to the binding pocket and therefore confer resistance to azole agents. © 2019 Mary Ann Liebert, Inc., publishers
Cancer stem cells as therapeutic targets of pancreatic cancer
No full textThe discovery of stem cells and their potential abilities in self-renewal and differentiation has opened a new horizon in medicine. Scientists have found a small population of stem cells in some types of cancers with the same functions as normal stem cells. There are two models for tumor progression: clonal (stochastic) and cancer stem cell (CSCs) models. According to the first model, all transformed cells in the tumor have carcinogenic potential and are able to proliferate and produce the same cells. The latter model, which has received more attention recently, considers the role of CSCs in drug resistance and tumor metastasis. Following the model, researchers have found that targeting CSCs may be a promising way in cancer therapy. This review describes CSC characteristics in general, while also focusing on CSC properties in the context of pancreatic cancer. © 2019 Société Française de Pharmacologie et de Thérapeutiqu
The Effects of Melatonin Supplementation on Parameters of Mental Health, Glycemic Control, Markers of Cardiometabolic Risk, and Oxidative Stress in Diabetic Hemodialysis Patients: A Randomized, Double-Blind, Placebo-Controlled Trial
Get PDFObjective: This study evaluated the effects of melatonin supplementation on parameters of mental health, glycemic control, markers of cardiometabolic risk, and oxidative stress in diabetic hemodialysis (HD) patients. Design: A randomized, double-blind, placebo-controlled clinical trial was conducted in 60 diabetic HD patients, 18-80 years of age. Participants were randomly divided into 2 groups to take either melatonin (2 x 5mg/day) (n = 30) or placebo (n = 30) 1 hour before bedtime for 12 weeks. The effects of melatonin on mental health, metabolic status, and gene expression related to metabolic status were assessed using multiple linear regression adjusting for age and BMI. Results: Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (P =.007), Beck Depression Inventory index (P =.001), and Beck Anxiety Inventory index (P =.01) compared with the placebo. Additionally, melatonin administration significantly reduced fasting plasma glucose (β = �21.77 mg/dL, 95 CI �33.22 to �10.33, P <.001), serum insulin levels (β = �1.89 μIU/mL, 95 CI �3.34 to �0.45, P =.01), and homeostasis model of assessment-insulin resistance (β = �1.45, 95 CI �2.10 to �0.80, P <.001), and significantly increased the quantitative insulin sensitivity check index (β = 0.01, 95 CI 0.007-0.02, P <.001) compared with placebo treated subjects. In addition, melatonin administration resulted in a significant reduction in serum high sensitivity C-reactive protein (β = �1.92 mg/L, 95 CI �3.02 to �0.83, P =.001) and plasma malondialdehyde (β = �0.21 μmol/L, 95 CI �0.36 to �0.06, P =.005); also, significant rises in plasma total antioxidant capacity (β = 253.87 mmol/L, 95 CI 189.18-318.56, P <.001) and nitric oxide levels (β = 2.99 μmol/L, 95 CI 0.71-5.28, P =.01) were observed compared with the placebo. Conclusion: Overall, melatonin supplementation for 12 weeks to diabetic HD patients had beneficial effects on mental health, glycemic control, inflammatory markers, and oxidative stress. © 2019 National Kidney Foundation, Inc
Leukemia-derived exosomes: Bringing oncogenic signals to blood cells
No full textLeukemia is a cancer, which is derived from leukocytes and precursors of leukocytes in the bone marrow. A large number of pivotal biological processes are linked to leukemia pathogenesis. More insights into these mechanisms can provide a better developing pharmacological platform for patients with leukemia. Among the different players in leukemia pathogenesis, exosomes have appeared as a new biological vehicle, which can transfer oncogenic signals to blood cells. Exosomes are nano-carriers, which enable transferring numerous cargos such as DNA fragments, RNAs, messenger RNAs, microRNAs, long noncoding RNA, and proteins. Targeting the contents of exosomes leads to the alteration of host cell behavior. Increasing evidence has indicated that leukemia-derived exosomes could be utilized as prognostic, diagnostic, and therapeutic biomarkers for individuals suffering from leukemia. In this regard, the importance of exosomes in terms of initiation and progression of leukemia was underlined in this study. © 2019 Wiley Periodicals, Inc
N-3 fatty acids as preventive and therapeutic agents in attenuating pcos complications
Get PDFTo our knowledge, in spite of several trials exploring the beneficial effect of n-3 polyunsaturated fatty acids (PUFA) on polycystic ovary syndrome (PCOS), no comprehensive evidence has investigated the effects of n-3 PUFA consumption on PCOS complications. Therefore, our aim was to conduct a review to investigate the possible effect and related mechanisms. A comprehensive systematic search was conducted in Embase, MED-LINE/PubMed, Google Scholar, and SCOPUS, to identify studies investigating n-3 fatty acids as a preventative or therapeutic agent for the attenuation of PCOS complications. Subsequently, the impact of omega-3 on PCOS, omega-3 and inflammation, omega-3 and insulin resistance, omega-3 and adipokines, omega-3 and lipid metabolism, omega-3 and endothelial function and omega-3 and hormonal factors were discussed. There are multiple mechanisms by which n-3 PUFAs may exert their beneficial effects on PCOS, including anti-obesity, glycemic and hormonal hemostasis, anti-inflammatory, regulation of adipokine production and enhancement of endothelial function. N-3 PUFAs are a promising agent in relieving complications associated with PCOS. Although most of the studies in patients with PCOS reported an improvement in most complications after administration of omega-3 supplements, there is a distinct dearth of studies investigating the dietary intake of these types of fatty acids. Moreover, favorable effects regarding the improvement of dyslipidemia, regulation of adipokines, regulation of hormonal factors and enhancement of endothelial function are limited. Therefore, more trials are warranted to investigate palatable mechanisms for clarifying the metabolic and hormonal effects of these agents in PCOS. © 2019, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved
Melatonin: A new inhibitor agent for cervical cancer treatment
No full textCervical cancer is one of the most common cancers between women and is known as the third leading cause of female cancer related deaths annually. Its detection in early stages allows it to be a preventable and generally treatable disease. Increasing evidence revealed, a variety of internal and external factors are associated with initiation and progression of cervical cancer pathogenesis. Human papilloma virus infection is found as a major cause of cervical cancer. Other molecular and biochemical alterations as well as genetic and epigenetic changes are related cervical cancer progression. Current treatment options often have severe side effects and toxicities thus, new adjuvant agents having synergistic effects and ability to decrease different side effects and toxicities are needed. Melatonin is an indolamine compound secreted from the pineal gland which shows wide range anticancer activities. A large amount of studies indicated inhibitory effects of melatonin against various types of cancers. In addition, experimental evidence reports inhibitory effects of melatonin as an adjuvant therapy on cervical cancer by targeting a sequence of different molecular mechanisms. Herein, for first time, we summarized anticervical cancer effects of melatonin and its underlying molecular mechanisms. © 2019 Wiley Periodicals, Inc