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3D imaging data necessitate 3D reference atlases for accurate quantitative interpretation. Existing computational methods to generate 3D atlases from 2D-derived atlases result in extensive artifacts, while manual curation approaches are labor-intensive. We present a computational approach for 3D atlas construction that substantially reduces artifacts by identifying anatomical boundaries in the underlying imaging data and using these to guide 3D transformation. Anatomical boundaries also allow extension of atlases to complete edge regions. Applying these methods to the eight developmental stages in the Allen Developing Mouse Brain Atlas (ADMBA) led to more comprehensive and accurate atlases. We generated imaging data from 15 whole mouse brains to validate atlas performance and observed qualitative and quantitative improvement (37% greater alignment between atlas and anatomical boundaries). We provide the pipeline as the MagellanMapper software and the eight 3D reconstructed ADMBA atlases. These resources facilitate whole-organ quantitative analysis between samples and across development., Competing Interests: DY, SF, GS, ZB, DY, MN, LG, JR, WY, SS No competing interests declared, (© 2021, Young et al.)

Objective: Sperm DNA fragmentation and maturation directly interferes with reproductive efficiency. Although there are several methods for assessing sperm DNA integrity, however, many of them are laborious and require high-precision equipment in the clinics. Thus, evaluating economic and reliable methods to prepare suitable sperm for assisted reproductive technologies without DNA damage is critical., Material and Methods: A total of 114 semen samples were collected and analyzed using computer-assisted semen analysis. The DNA fragmentation index (DFI) of all samples was evaluated by two methods of sperm chromatin dispersion (SCD) and sperm chromatin structure assay (SCSA). Besides, chromatin maturation index (CMI) was assessed by three methods including aniline blue (AB)-sperm chromatin maturation assay (SCMA), fluorescence microscopic chromomycin A3 (fmCMA3), and flow cytometric CMA3 (fcCMA3)., Results: The result showed that the DFI had no statistically significant differences (p>0.05) between SCSA (26.98%±1.28%) and SCD (27.88%±1.278%), although SCD demonstrated a strong correlation with DNA maturity (p<0.001), which had not been seen in SCSA. Besides, the CMI demonstrated significant differences (p<0.001) when assessed by AB-SCMA (14.86%±0.65%), fmCMA3 (29.18%±1.01%), and fcCMA3 (22.45%±0.62%). Among these, only the fmCMA3 showed a significant correlation with semen parameters (p<0.01) and embryo development (p<0.001)., Conclusion: It seems that SCD and fmCMA3 were more accessible, affordable, and reliable tests for assessing DFI and CMI. It appeared these two methods may be the best choices for evaluating sperm DNA integrity in clinics.

Background: The three-parent assisted reproductive technique may increase oocyte competence., Objective: In this case-control study, the suitability of germinal vesicle transfer (GVT), synchronous ooplasmic transfer (sOT), asynchronous ooplasmic transfer using cryopreserved MII oocyte (caOT), and asynchronous ooplasmic transfer using waste MII oocyte (waOT) for maturation of the human-aged non-surrounded nucleolus germinal vesicle-stage (NSN-GV) oocyte were investigated., Materials and Methods: NSN-GV oocytes were subjected to four methods: group A (GVT), B (sOT), C (caOT) D (waOT), and E (Control). The fusion rates, MI, MII, ICSI observations and cleavage at 2-cell, 4-cell, and 8-cell stages were compared in the groups., Results: In GVT, none of the oocytes fused. In sOT, all oocytes fused, 20 achieved the MI, 14 progressed to MII, 8 fertilized, 6 cleaved and 5, 4, and 3 achieved the 2-cells, 4-cells and 8-cells, respectively. In caOT, all oocytes fused and achieved the MI, 8 progressed to MII and fertilized, 6 cleaved and 6, 5, and 5 achieved the 2-cells, 4-cells, and 8-cells respectively. In waOT, all oocytes fused, 5 and 3 progressed to MI and MII, respectively, but only one fertilized, cleaved and reached a 4-cells stage. In group E, 6 and 2 oocytes progressed to MI and MII, respectively, and only one fertilized but arrested at the zygote stage. caOT had the highest survival rate when compared to sOT (p = 0.04), waOT (p = 0.002), and control (p = 0.001)., Conclusion: The caOT method was beneficial over sOT, waOT, and GVT in supplementing the developmental capacity of human-aged NSN-GV oocytes., Competing Interests: All authors declare no financial or commercial competing interest., (Copyright © 2020 Darbandi et al.)

​Maf ( c-Maf ) and Mafb transcription factors (TFs) have compensatory roles in repressing somatostatin (SST + ) interneuron (IN) production in medial ganglionic eminence (MGE) secondary progenitors in mice. Maf and Mafb conditional deletion (cDKO) decreases the survival of MGE-derived cortical interneurons (CINs) and changes their physiological properties. Herein, we show that (1) Mef2c and Snap25 are positively regulated by Maf and Mafb to drive IN morphological maturation; (2) Maf and Mafb promote Mef2c expression which specifies parvalbumin (PV + ) INs; (3) Elmo1 , Igfbp4 and Mef2c are candidate markers of immature PV + hippocampal INs (HIN). Furthermore, Maf / Mafb neonatal cDKOs have decreased CINs and increased HINs, that express Pnoc , an HIN specific marker. Our findings not only elucidate key gene targets of Maf and Mafb that control IN development, but also identify for the first time TFs that differentially regulate CIN vs. HIN production., Competing Interests: EP, JC, SF, FC, JC, SL, JC, JP, DV, MP No competing interests declared, JR is cofounder, stockholder, and currently on the scientific board of Neurona, a company studying the potential therapeutic use of interneuron transplantation, (© 2020, Pai et al.)

Tbr1 is a high-confidence autism spectrum disorder (ASD) gene encoding a transcription factor with distinct pre- and postnatal functions. Postnatally, Tbr1 conditional knockout (CKO) mutants and constitutive heterozygotes have immature dendritic spines and reduced synaptic density. Tbr1 regulates expression of several genes that underlie synaptic defects, including a kinesin (Kif1a) and a WNT-signaling ligand (Wnt7b). Furthermore, Tbr1 mutant corticothalamic neurons have reduced thalamic axonal arborization. LiCl and a GSK3β inhibitor, two WNT-signaling agonists, robustly rescue the dendritic spines and the synaptic and axonal defects, suggesting that this could have relevance for therapeutic approaches in some forms of ASD., Competing Interests: Declaration of Interests J.L.R.R. is cofounder and stockholder, and currently on the scientific board, of Neurona, a company studying the potential therapeutic use of interneuron transplantation. A.J.W. is a paid consultant for Daiichi Sankyo. M.W.S. is a consultant to BlackThorn and ArRett Pharmaceuticals. All other authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Studies showed a decrease of the semen analysis parameters and an increase in the average age of first-time fathers over the past several decades. The aim of the present study was to assess the influence of paternal age on semen quality and fertilization outcomes in men with normal sperm DNA fragmentation and chromatin maturation index (DFI and CMI), reactive oxygen species (ROS), and total antioxidant capacity (TAC) levels., Material and Methods: The study was performed on 70 men with their wife's age ≤38 years and normal sperm DFI, CMI, ROS, and TAC levels. None of the couples had a history of genital inflammation, chronic diseases, endocrine abnormality, chromosomal aberrations, Y chromosome microdeletion, azoospermia, and leukocytospermia. These men were separated into 2 groups according to their age (group A: age <45 years and group B: age ≥45 years). Semen analysis and fertilization outcome after using the intracytoplasmic sperm injection were assessed in both groups., Result: Sperm concentration showed a significant reduction in group B (p=0.04). Although semen volume, sperm normal morphology, and progressive motility were decreased in group B, the reduction was not significant when compared with group A (p=0.09, p=0.47, and p=0.77, respectively). In addition, the differences of embryo quality with grades A, B, and C and 8-cell embryo formation were not statistically significant between the 2 groups., Conclusion: These results demonstrated that in men with normal sperm DFI, CMI, ROS, and TAC levels, there were no significant changes in semen parameters and fertilization outcomes with an increasing age.

Kelch-like ECH-associated protein 1 (keap1)-nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway is one of the master regulators of cellular defence against oxidative stress. Epigenetic alterations like hypermethylation of keap1 gene impair keap1-Nrf2 system in several oxidative stress-associated diseases. The objective of this study was to evaluate the epigenetic status of keap1 in sperm DNA of normozoospermic subjects, having different levels of reactive oxygen species (ROS) in seminal plasma. Semen samples were obtained from 151 apparently healthy male partners of couples who attended the Avicenna infertility clinic. Samples were categorised into four groups according to their ROS levels: group A (n = 39, ROS < 20 RLU/s per 10 6 spermatozoa), group B (n = 38, 20 ≤ ROS < 40 RLU/s per 10 6 spermatozoa), group C (n = 31, 40 ≤ ROS < 60 RLU/s per 10 6 spermatozoa) and group D; (n = 43, ROS ≥ 60 RLU/s per 10 6 spermatozoa). Keap1 methylation status was assessed using methylation-specific PCR along with seminal total antioxidant capacity. The results showed no significant alterations in keap1 methylation in any groups, whereas the total antioxidant capacity enhanced with increasing levels of ROS exposure. These results indicate that keap1 was not methylated during ROS elevation and oxidative stress, suggesting that the cells have adopted other mechanisms to elevate antioxidant level., (© 2018 Blackwell Verlag GmbH.)

Purpose: This study was conducted in order to investigate the effects of reactive oxygen species (ROS) levels on the seminal plasma (SP) metabolite milieu and sperm dysfunction., Methods: Semen specimens of 151 normozoospermic men were analyzed for ROS by chemiluminescence and classified according to seminal ROS levels [in relative light units (RLU)/s/10 6 sperm]: group 1 (n = 39): low (ROS < 20), group 2 (n = 38): mild (20 ≤ ROS < 40), group 3 (n = 31): moderate (40 ≤ ROS < 60), and group 4 (n = 43): high (ROS ≥ 60). A comprehensive analysis of SP and semen parameters, including conventional semen characteristics, measurement of total antioxidant capacity (TAC), sperm DNA fragmentation index (DFI), chromatin maturation index (CMI), H19-Igf2 methylation status, and untargeted seminal metabolic profiling using nuclear magnetic resonance spectroscopy (1H-NMR), was carried out., Result(s): The methylation status of H19 and Igf2 was significantly different in specimens with high ROS (P < 0.005). Metabolic fingerprinting of these SP samples showed upregulation of trimethylamine N-oxide (P < 0.001) and downregulations of tryptophan (P < 0.05) and tyrosine/tyrosol (P < 0.01). High ROS significantly reduced total sperm motility (P < 0.05), sperm concentration (P < 0.001), and seminal TAC (P < 0.001) but increased CMI and DFI (P < 0.005). ROS levels have a positive correlation with Igf2 methylation (r = 0.19, P < 0.05), DFI (r = 0.40, P < 0.001), CMI (r = 0.39, P < 0.001), and trimethylamine N-oxide (r = 0.45, P < 0.05) and a negative correlation with H19 methylation (r = - 0.20, P < 0.05), tryptophan (r = - 0.45, P < 0.05), sperm motility (r = - 0.20, P < 0.05), sperm viability (r = - 0.23, P < 0.01), and sperm concentration (r = - 0.30, P < 0.001)., Conclusion(s): Results showed significant correlation between ROS levels and H19-Igf2 gene methylation as well as semen parameters. These findings are critical to identify idiopathic male infertility and its management through assisted reproduction technology (ART).

Mafb and c-Maf transcription factor (TF) expression is enriched in medial ganglionic eminence (MGE) lineages, beginning in late-secondary progenitors and continuing into mature parvalbumin (PV + ) and somatostatin (SST + ) interneurons. However, the functions of Maf TFs in MGE development remain to be elucidated. Herein, Mafb and c-Maf were conditionally deleted, alone and together, in the MGE and its lineages. Analyses of Maf mutant mice revealed redundant functions of Mafb and c-Maf in secondary MGE progenitors, where they repress the generation of SST + cortical and hippocampal interneurons. By contrast, Mafb and c-Maf have distinct roles in postnatal cortical interneuron (CIN) morphological maturation, synaptogenesis, and cortical circuit integration. Thus, Mafb and c-Maf have redundant and opposing functions at different steps in CIN development., (Copyright © 2019 UCSF. Published by Elsevier Inc. All rights reserved.)

Objective: Fibronectin (FN) is a multifunctional diametric glycoprotein on the surface of the sperm that plays an important role in the sperm-oocyte interaction and fertilization process. The aim of the present study was to assess the FN levels as a sperm surface biomarker for sperm selection in assisted reproductive technology., Material and Methods: Polyclonal antibody against human FN was produced in rabbit. Its quality, purity, and immune reactivity were assessed by SDS-PAGE and western blot. In addition, the presence of FN on the sperm surface was assessed through immunocytochemistry and flow cytometry. The amount of FN and the sperm quality were assessed in normozoospermia (N) (42 men) and asthenoteratozoospermia (AT) (72 men) groups through sperm chromatin dispersion (SCD), sperm chromatin structure assay (SCSA), and chromatin maturation index (CMI)., Results: The results showed the distribution of FN protein on the equatorial region of the human sperm surface. In addition, the FN levels were found to have a significant difference between the two groups with 24.64±9.08% in N and 16.90±7.27% in AT (p≤0.0001). In addition, FN level negatively correlated with SCD (p≤0.0001), SCSA (p≤0.0001), and CMI (p≤0.001). Threshold values of FN level and DNA fragmentation index (DFI) percentage were 16 and 30 and were identified as cut-off values to determine the N group with a specificity of 83.3% and 81.0% and a sensitivity of 16.8% and 19.0%, respectively. The specificity and sensitivity of FN-DFI were 91.2% and 8.8%, respectively., Conclusion: It appears that FN can be used for the selection of sperm with suitable quality, although future studies are recommended.

An understanding of how heterozygous loss-of-function mutations in autism spectrum disorder (ASD) risk genes, such as TBR1, contribute to ASD remains elusive. Conditional Tbr1 deletion during late mouse gestation in cortical layer 6 neurons (Tbr1 layer6 mutants) provides novel insights into its function, including dendritic patterning, synaptogenesis, and cell-intrinsic physiology. These phenotypes occur in heterozygotes, providing insights into mechanisms that may underlie ASD pathophysiology. Restoring expression of Wnt7b largely rescues the synaptic deficit in Tbr1 layer6 mutant neurons. Furthermore, Tbr1 layer6 heterozygotes have increased anxiety-like behavior, a phenotype seen ASD. Integrating TBR1 chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) data from layer 6 neurons and activity of TBR1-bound candidate enhancers provides evidence for how TBR1 regulates layer 6 properties. Moreover, several putative TBR1 targets are ASD risk genes, placing TBR1 in a central position both for ASD risk and for regulating transcriptional circuits that control multiple steps in layer 6 development essential for the assembly of neural circuits., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: The selection of sperm with good genomic integrity and surface antigens is suggested for improving assisted reproductive technology (ART) outcome. The aim of this study was evaluating the heat shock protein (HSPA2), Dj-1 and serum amyloid P compound (SAP) three sperm surface proteomes as biomarkers for this purpose., Methods: In this study, semen samples were obtained from 114 men who presented at Avicenna Fertility Clinic for their treatment. The semen characteristics, DNA fragmentation Index (DFI), chromatin maturation index (CMI), biomarker levels, and their embryo quality were considered. The paired-samples t-test and independent-samples t-test were used for analyzing the data and p-values<0.05 were considered significant., Results: Outcomes exhibited the major reduction in HSPA2, DJ-1 and SAP following reduction in sperm quality and DNA integrity (p<0.001) with cut-off value of 14% (HSPA2), 12% (DJ-1) and 10% (SAP). The specificity of these three biomarkers was 95.2, 73.8 and 88.1%, respectively. Also, DFI (p<0.001), CMI (p<0.05), cleavage (p<0.05), and embryos quality (p<0.001) decreased significantly in abnormal spermiogram (ANS) group in compared with normal spermiogram (NS) group. It was shown that DFI was 97.1% in HSPA2, 76.5% in DJ-1 and 94.1% in SAP, and CMI was 95.0%, 75.50% and 87.5%, respectively. The significant correlation was found between of the three biomarkers and CMI (p<0.001), DFI (p<0.001) and embryos quality (p<0.001)., Conclusion: By comparing the efficiency of these three biomarkers for selecting sperm with the lowest level of chromatin damages, it seems that selection based on HSPA2 has significance over others., Competing Interests: Conflict of Interest The authors declare that they have no competing interests.

Reports of the increasing incidence of male infertility paired with decreasing semen quality have triggered studies on the effects of lifestyle and environmental factors on the male reproductive potential. There are numerous exogenous and endogenous factors that are able to induce excessive production of reactive oxygen species (ROS) beyond that of cellular antioxidant capacity, thus causing oxidative stress. In turn, oxidative stress negatively affects male reproductive functions and may induce infertility either directly or indirectly by affecting the hypothalamus-pituitary-gonadal (HPG) axis and/or disrupting its crosstalk with other hormonal axes. This review discusses the important exogenous and endogenous factors leading to the generation of ROS in different parts of the male reproductive tract. It also highlights the negative impact of oxidative stress on the regulation and cross-talk between the reproductive hormones. It further describes the mechanism of ROS-induced derangement of male reproductive hormonal profiles that could ultimately lead to male infertility. An understanding of the disruptive effects of ROS on male reproductive hormones would encourage further investigations directed towards the prevention of ROS-mediated hormonal imbalances, which in turn could help in the management of male infertility.

Context: Depending on the cause of the infertility, nonsurgical or surgical treatments may be used to treat men and women with infertility. Despite improved outcomes due to medical advances, assisted reproductive technology (ART) for couples with infertility is sometimes unsuccessful. Success may be affected by the patient's social, psychological, and physical status., Objective: The study examined the effects of yoga-including asanas (yoga poses), pranayama (proper breathing), shavasana, and meditation-on male and female fertility and ART outcomes., Design: The research team performed a literature review, electronically searching for articles published between January 1978 and January 2016 in the PubMed, Scopus, ScienceDirect, and Google Scholar databases., Setting: The study took place at the Reproductive Biotechnology Research Center at the Avicenna Research Institute at the Academic Center for Education, Culture, and Research (Tehran, Iran)., Participants: Participants were couples with infertility taking part in 87 reviewed studies., Intervention: Yoga was the intervention., Outcome Measures: The outcome measures comprised fertility factors in males and females, fertility rate, and ART success rate., Results: The reviewed studies showed that yoga can provide stress management for patients with infertility, with beneficial effects on fertility, helping couples give birth. They found that yoga also could reduce pain; decrease depression, anxiety, and stress; reduce the rate of assisted vaginal delivery; and improve fetal outcomes., Conclusions: Yoga can help couples overcome infertility and increase the ART success rate by improving the physiological and psychological states of both men and women.

Context: People are increasingly exposed to low frequency (LF) electromagnetic fields (EMFs), mainly from electricity distribution networks and electronic devices. Critics of this widespread exposure believe that it can have detrimental effects on the human body. On the other hand, many in vivo and in vitro studies have claimed that low frequency electromagnetic therapy can function as a form of alternative medicine and that therapists can treat disease by applying electromagnetic radiation or pulsed EMFs to the body or cells. It is not yet entirely clear, however, whether LF-EMF is beneficial or harmful., Objectives: This study aimed to examine the effects of LF-EMFs on men's reproductive functions, according to the types of waveform and the frequency and duration of exposure., Design: The study reviewed all available research, both human and animal, on the effects of LF-EMFs on male reproductive functions, covering the literature from January 1978 to June 2016. The documents were obtained from PubMed, Science Direct, and Google Scholar, and any article that was irrelevant or a duplicate was excluded. A total of 61 articles were found, and 27 articles were reviewed., Setting: This project was performed at the Avicenna Research Center (Tehran, Iran)., Participants: Literature included human and animal studies conducted on rabbits, mice, rats, and boars., Intervention: Among these studies, any article that was irrelevant, a duplicate, or published with duplicate data was excluded. At the end, 27 articles were checked., Outcome Measures: Outcome measures included testing related to reproductive organ weights, reproductive endocrinal hormones, fetal development, and spermatogenesis as well as sperm motility, morphology, and vitality., Results: The reviewed studies provided contradictory results that were highly dependent on the exposure parameters, such as the shape and frequency of wave, intensity, duration, and timing of the exposure., Conclusions: LF-EMF at 15 Hz with a peak intensity of 8 Gauss, with a square waveform of 50 Hz frequency and a duration of a few hours or less can have a positive effect on sperm quality, motility, and fertility. Exposures at other frequencies either had no effects on the sperm's performance and quality or held biological hazard for cells. It appears that there is still little understanding of how EMF affects cellular functions. Therefore, more standardized and controlled studies should be carried out to understand the effects of EMF on the body.

Background: Non-obstructive azoospermia (NOA) occurs in approximately 10% of infertile men. Retrieval of the spermatozoa from the testicle of NOA patients is an invasive approach. Seminal plasma is an excellent source for exploring to find the biomarkers for presence of spermatozoa in testicular tissue. The present discovery phase study aimed to use metabolic fingerprinting to detect spermatogenesis from seminal plasma in NOA patients as a non-invasive method., Methods: In this study, 20 men with NOA were identified based on histological analysis who had their first testicular biopsy in 2015 at Avicenna Fertility Center, Tehran, Iran. They were divided into two groups, a positive testicular sperm extraction (TESE(+)) and a negative testicular sperm extraction (TESE(-)). Seminal plasma of NOA patients was collected before they underwent testicular sperm extraction (TESE) operation. The metabolomic fingerprinting was evaluated by Raman spectrometer. Principal component analysis (PCA) and an unsupervised statistical method, was used to detect outliers and find the structure of the data. The PCA was analyzed by MATLAB software., Results: Metabolic fingerprinting of seminal plasma from NOA showed that TESE (+) versus TESE(-) patients were classified by PCA. Furthermore, a possible subdivision of TESE(-) group was observed. Additionally, TESE(-) patients were in extreme oxidative imbalance compared to TESE(+) patients., Conclusion: Metabolic fingerprinting of seminal plasma can be considered as a breakthrough, an easy and cheap method for prediction presence of spermatogenesis in NOA., Competing Interests: Conflict of Interest The authors declare no conflict of interest.

Background: Ooplasmic transfer (OT) technique or cytoplasmic transfer is an emerging technique with relative success, having a significant status in assisted reproduction. This technique had effectively paved the way to about 30 healthy births worldwide. Though OT has long been invented, proper evaluation of the efficacy and risks associated with this critical technique has not been explored properly until today. This review thereby put emphasis upon the applications, efficacy and adverse effects of OT techniques in human., Main Body: Available reports published between January 1982 and August 2017 has been reviewed and the impact of OT on assisted reproduction was evaluated. The results consisted of an update on the efficacy and concerns of OT, the debate on mitochondrial heteroplasmy, apoptosis, and risk of genetic and epigenetic alteration., Short Conclusion: The application of OT technique in humans demands more clarity and further development of this technique may successfully prove its utility as an effective treatment for oocyte incompetence.

Nuclear transfer procedures have been recently applied for clinical and research targets as a novel assisted reproductive technique and were used for increasing the oocyte activity during its growth and maturation. In this review, we summarized the nuclear transfer technique for germinal vesicle stage oocytes to reconstruct the maturation of them. Our study covered publications between 1966 and August 2017. In result utilized germinal vesicle transfer techniques, fusion, and fertilization survival rate on five different mammalian species are discussed, regarding their potential clinical application. It seems that with a study on this method, there is real hope for effective treatments of old oocytes or oocytes containing mitochondrial problems in the near future.

Introduction: Hypertension is an important risk factor of cardiovascular disease (CVD), which is associated with premature death, myocardial infarction, stroke, peripheral vascular disease, and renal disease. The goal of the present study was to use a randomized controlled clinical trial to explore and compare the effectiveness of abdominal and auricular acupuncture on blood pressure in 440 subjects with and without obesity., Methods: Four hundred participants were recruited and randomized to one of four groups: cases and controls receiving auricular acupuncture (204 subjects) and cases and controls receiving abdominal electroacupuncture (196 subjects). Blood pressure and anthropometric parameters were measured before and after the intervention period. In order to match the initial diet of the groups, participants were required to follow an isocaloric diet for two weeks before the trial, and a low-calorie diet for 6 weeks during the intervention period., Results: We observed a significant time dependent improvement in the systolic blood pressure measurements in the abdominal intervention group, although this improvement was more pronounce in the first period of study. Of note, in the auricular intervention group, a significant increasing in the level of SBP was detected. Importantly no statistically significant changes were found in the corresponding sham groups., Conclusions: Our findings demonstrated that abdominal electro-acupuncture for 6 weeks reduced both systolic and diastolic blood pressure and auricular acupuncture had a short-term adverse effect on both SBP and DBP., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Purpose: The mitochondrial complement is critical in sustaining the earliest stages of life. To improve the Assisted Reproductive Technology (ART), current methods of interest were evaluated for increasing the activity and copy number of mitochondria in the oocyte cell., Methods: This covered the researches from 1966 to September 2015., Results: The results provided ten methods that can be studied individually or simultaneously., Conclusion: Though the use of these techniques generated great concern about heteroplasmy observation in humans, it seems that with study on these suggested methods there is real hope for effective treatments of old oocyte or oocytes containing mitochondrial problems in the near future., (Copyright © 2016 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

Alzheimer᾽s disease is characterized by cognitive deficits, impaired long-term potentiation of learning and memory. A progressive reduction in cholinergic neurons in some areas of the brain such as cortex and hippocampus is related to the deficits in memory and cognitive function in Alzheimer's disease (AD). In the current project a new series of phthalimide derivatives were synthesized. Phthalic anhydride was reacted with 4-aminobenzoic acid in the presence of triethylamine under reflux condition. Then, the obtained acidic derivative was utilized for preparation of final compounds via an amidation reaction through a carbodiimde coupling reaction. Anti-acetylcholinesterase activity of synthesized derivatives was assessed by Ellman᾽s test. Compound 4g in this series exhibited the highest inhibitory potency (IC 50 = 1.1 ± 0.25 µM) compared to donepezil (IC 50 = 0.41 ± 0.12 µM) as reference drug.

Background: Traditional medicines with anti-diabetic effects are considered suitable supplements to treat diabetes. Among medicinal herbs, Stevia Rebaudiana Bertoni is famous for its sweet taste and beneficial effect in regulation of glucose. However, little is known about the exact mechanism of stevia in pancreatic tissue. Therefore, this study investigated the possible effects of stevia on pancreas in managing hyperglycemia seen in streptozotocin-induced Sprague-Dawley rats., Methods: Sprague-Dawley rats were divided into four groups including normoglycemic, diabetic and two more diabetic groups in which, one was treated with aquatic extract of stevia (400 mg/kg) and the other with pioglitazone (10 mg/kg) for the period of 28 days. After completion of the experimental duration, rats were dissected; blood samples and pancreas were further used for detecting biochemical and histopathological changes. FBS, TG, cholestrol, HDL, LDL, ALT and AST levels were measured in sera. Moreover, MDA (malondialdehyde) level, catalase activity, levels of insulin and PPARγ mRNA expression were also measured in pancreatic tissue., Results: Aquatic extract of stevia significantly reduced the FBS, triglycerides, MDA, ALT, AST levels and normalized catalase activity in treated rats compared with diabetic rats (p<0.05). In addition to this, stevia surprisingly, increased PPARγ and insulin mRNA levels in treated rats (p<0.05). Furthermore, stevia compensated for the histopathological damage in diabetic rats., Conclusion: It is concluded that stevia acts on pancreatic tissue to elevate the insulin level and exerts beneficial anti-hyperglycemic effects through the PPARγ-dependent mechanism and stevia's antioxidant properties.

Background: The prevalence of abdominal obesity is on the rise worldwide. Previous studies have indicated the higher diagnostic value of body fat distribution pattern compared with general body in abdominal obesity assessments. Several non-pharmacological methods have been suggested for obesity management, of which acupuncture has gained a great deal of research interest with promising results. This study aimed to comparatively evaluate the effects of conventional auricular and body electroacupuncture on abdominal fat mass in obese men., Methods: The volunteers were randomly divided into four groups, including 2 interventions and 2 controls. This study was conducted on 80 obese volunteer men with Body Mass Index (BMI) range of 30-40 kg/m2.The intervention groups including real body electroacupuncture (A), real auricular acupuncture (C) and the control groups containing sham body electroacupuncture (B), and sham auricular acupuncture (D). All groups were in combination with a low-calorie diet for 6 weeks. BMI, Trunk Fat Mass (TFM), Waist Circumference (WC), and Hip Circumference (HC) were measured pre- and post-intervention., Results: In group A, respectively a significant reduction was shown in BMI (P < 0.005), TFM (P < 0.005), WC (P < 0.05, P < 0.005) and HC (P < 0.005) when compared with controls (Groups B and D). Interestingly, group C had significant decreases in BMI (P < 0.005), TFM (P < 0.01, P < 0.005), WC (P < 0.005) and HC (P < 0.001) after comparison with the sham. Likewise, WC (P < 0.05) and HC (P < 0.05) were significantly reduced post- intervention when compared with two treatment groups., Conclusions: In our study, acupuncture treatment (body or auricular) seemed to have an effect on reducing BMI, TFM, WC and HC. Comparison of the two types of treatment (body and auricular acupuncture) suggests that the two types of acupuncture had similar effects on reducing BMI and TFM, but body electroacupuncture is more effective in reducing WC and auricular in HC. It seems that both auricular and body electro-acupuncture combined with a low-calorie diet are efficient, simple and painless methods to reduce respectively the HC and WC fat in obese men, compared with conventional techniques., Trial Registration: IRCT201201127117N2.

Background: The prevalence of obesity, a major public health problem, is increasing in many countries, including Iran. Leptin, a peptide hormone that is released from adipocytes, is a major factor in appetite regulation. Levels of plasma leptin increase with increased body fat mass (BFM). Research has found acupuncture to be effective both in weight loss and suppression of appetite. Although a few studies have reported the effect of body and ear acupuncture on leptin levels, researchers have performed few studies on the effect of body electroacupuncture in humans., Objective: The research team examined the effects of body electroacupuncture and a low-calorie diet on plasma leptin in obese and overweight individuals with an excess (phlegm-dampness or phlegm-heat) or deficiency (spleen/stomach qi deficiency or primary qi deficiency) pattern according to Chinese medicine., Design: The research team randomly assigned participants to one of two groups, intervention or control., Setting: This study occurred in the nutritional clinic at Ghaem Hospital in Mashhad, Iran., Participants: Participants were individuals (N = 86) between 18 and 65 years of age with body mass indexes (BMI) between 25 and 45 kg/m2., Intervention: The intervention group (n = 47) received actual electroacupuncture, and the control group (n = 47) received sham acupuncture. Both groups consumed a low-calorie diet for 6 weeks., Outcome Measures: The research team measured plasma leptin, BFM, body weight (BW), and BMI before and after treatment., Results: For participants in the intervention group with both the excess and the deficiency patterns, the research team found a significant reduction in plasma leptin (24.96%, P = .001) and BFM (8.29%, P = .001). In the control group, the team found a less significant reduction in leptin and BFM. The difference between the two groups was significant for leptin (P = .03) but not for BFM (P = .8)., Conclusions: While body electroacupuncture with a low-calorie diet can reduce plasma leptin concentration, the mechanism will require further clarification.

Background: Human leptin is a peptide hormone that is released from white adipocytes. The absence of leptin or its receptor leads to uncontrolled food intake, leading to obesity. In the present work, the effects of auricular acupressure combined with low-calorie diet on the leptin hormone level were investigated., Methods: Volunteers (n=86) with body mass indices (BMI) between 25 and 45 kg/m² were randomised into a case (n=43) or a control (n=43) group. Participants in each group received a low-calorie diet for 6 weeks. The case group was treated with auricular acupressure and the control group received a sham procedure. Plasma leptin levels, body fat mass, body weight and BMI were measured before and after treatment., Results: Participants who received auricular acupressure showed significant reductions in their plasma leptin levels (18.57%, p<0.01) as well as in their body fat mass (4%, p<0.05). These changes were not observed in the control group. The reduction in leptin was significantly greater in the acupressure group than the controls., Conclusions: Auricular acupressure combined with a low-calorie diet significantly reduced plasma levels of leptin. However, the mechanism of this reduction is not clear.

Objectives: A randomized controlled clinical trial was performed to examine the effectiveness of auricular acupuncture on body weight loss and its impact on lipid profile, and immunologic and inflammatory markers in obese subjects., Methods: Participants (n=204) were randomized to therapeutic acupuncture and control groups. Subjects received authentic (cases) or sham (controls) acupuncture for 6 weeks (first period) in combination with a low-calorie diet. In the next 6 weeks (second period), the low-calorie diet was used on its own. Subjects were assessed at the beginning and 6 and 12 weeks later. In addition to anthropometric and lipid parameters, serum anti-heat shock protein (Hsp)-27, 60, 65, 70 and high sensitive C-reactive protein (hs-CRP) levels were assessed., Results: In the first period, anthropometric parameters and hs-CRP changed significantly in both groups, while significant changes in anti-Hsp antibodies were only observed in case subjects. In the second period, which shows the sustainable effects of acupuncture, changes in anthropometric parameters were more prominent in controls, while significant reductions in the group receiving authentic acupuncture were maintained for anti-Hsp antibodies. A comparison between the first and second period in both groups showed that the changes for most of the parameters were more significant in the first period. Comparison between cases and controls showed that authentic acupuncture was more effective in reducing the levels of anthropometric factors and anti-Hsp antibodies but not hs-CRP., Conclusions: Auricular acupuncture in combination with diet restriction was effective for weight loss and dyslipidemia. Moreover, it was found that it has immunomodulatory but not anti-inflammatory effects on the immune system by regulation of the levels of anti-Hsp antibodies.

A randomized controlled clinical trial in 196 obese subjects was performed to examine the effectiveness of body acupuncture on body weight loss, lipid profile and immunogenic and inflammatory markers. Subjects received authentic (cases) or sham (controls) acupuncture for 6 weeks in combination with a low-calorie diet. In the following 6 weeks, they received the low-calorie diet alone. Subjects were assessed at the beginning, 6 and 12 weeks later. Heat shock protein (Hsps)-27, 60, 65, 70 antibody titers and high sensitivity C-reactive protein (hs-CRP) levels were also assessed. A significant reduction in measures of adiposity and improvement in lipid profile were observed in both groups, but the levels of anti-Hsp-antibodies decreased in cases only. A reduction in anthropometric and lipid profile in cases were sustained in the second period, however, only changes in lipid profile were observed in the control group. Anti-Hsp-antibodies and hs-CRP levels continued to be reduced in cases but in controls only the reduction in hs-CRP remained. Changes in anthropometric parameters, lipid profile, and anti-Hsp-antibodies were more evident in cases. Body acupuncture in combination with diet restriction was effective in enhancing weight loss and improving dyslipidemia.

Ryanodine receptors (RyRs) are large homotetrameric protein complexes that mediate the release of intracellular stores of calcium. Mammals possess three gene copies, RyR1, RyR2, and RyR3 that are expressed in a variety of tissue types. Teleost fish express RyR1a and RyR1b genes that are expressed in slow twitch skeletal muscle and fast twitch skeletal muscles respectively. Here we report the results of a survey of the genome of bichir (Polypterus ornatipinnis), considered the most basal ray-finned fish, for its RyR genes. The bichir genome encodes four RyR genes, RyR1a, RyR1b, RyR2, and RyR3 that phylogenetically cluster with their vertebrate orthologs. Quantitative real time PCR shows fibre type-specific expression of the RyR1a and RyR1b genes. The RyR3 gene, however, is down regulated in bichir in contrast to derived teleosts including zebrafish in which the RyR1 and RyR3 genes are co-expressed at equivalent levels.