Some studies have looked at the age at menarche and risk of Multiple Sclerosis (MS).We aimed to conduct a systematic review and meta-analysis to estimate a pooled odds ratio of developing MS by increasing age at menarche.We searched PubMed, Scopus, EMBASE, CINAHL, Web of Science, Ovid, google scholar and gray literature (references of references, congress abstracts) up to 10th April 2019.The literature search found 312 articles. After eliminating duplicates, reviews, case reports and trials, 18 articles remained. Three articles were ultimately included in the final analysis. Two studies were from Iran, and one from Canada. The pooled odds ratio (OR) for increasing 1 year of age at menarche was 0.88 (95% CI:0.82-0.94), with no significant heterogeneity (IThe result of this systematic review showed that the risk of MS decreases by increasing age at menarche.
De novo drug discovery is a time-consuming and expensive process. Nowadays, drug repositioning is utilized as a common strategy to discover a new drug indication for existing drugs. This strategy is mostly used in cases with a limited number of candidate pairs of drugs and diseases. In other words, they are not scalable to a large number of drugs and diseases. Most of the in-silico methods mainly focus on linear approaches while non-linear models are still scarce for new indication predictions. Therefore, applying non-linear computational approaches can offer an opportunity to predict possible drug repositioning candidates.In this study, we present a non-linear method for drug repositioning. We extract four drug features and two disease features to find the semantic relations between drugs and diseases. We utilize deep learning to extract an efficient representation for each feature. These representations reduce the dimension and heterogeneity of biological data. Then, we assess the performance of different combinations of drug features to introduce a pipeline for drug repositioning. In the available database, there are different numbers of known drug-disease associations corresponding to each combination of drug features. Our assessment shows that as the numbers of drug features increase, the numbers of available drugs decrease. Thus, the proposed method with large numbers of drug features is as accurate as small numbers.Our pipeline predicts new indications for existing drugs systematically, in a more cost-effective way and shorter timeline. We assess the pipeline to discover the potential drug-disease associations based on cross-validation experiments and some clinical trial studies.
The global prevalence of migraine as a primary headache has been estimated as 14.4% in both sexes. Migraine headache has been ranked as the highest contributor to disability in under 50 years old population in the world. Extensive research has been conducted in order to clarify the pathological mechanisms of migraine. Although uncertainties remains, it has been indicated that vascular dysfunction, cortical spreading depression (CSD), activation of the trigeminovascular pathway, pro-inflammatory and oxidative state may play a putative role in migraine pain generation. Knowledge about pathophysiological mechanisms of migraine should be integrated into a multimodal treatment approach to increase quality of life in patients. With respect to this, within the integrative health studies growing interest pertains to dietary interventions. Although the number of studies concerning effects of diet on headache/migraine is not yet very large, the current article will review the available evidence in this area. All publications on headache/migraine and dietary interventions up to May 2019 were included in the present review through a PubMed/MEDLINE and ScienceDirect database search. According to the current findings, Ketogenic diet and modified Atkins diet are thought to play a role in neuroprotection, improving mitochondrial function and energy metabolism, compensating serotoninergic dysfunction, decreasing calcitonin gene-related peptide (CGRP) level and suppressing neuro-inflammation. It can also be speculated that prescription of low glycemic diet may be promising in headache/migraine control through attenuating the inflammatory state. Moreover, obesity and headaches including migraine could be attributed to each other through mechanisms like inflammation, and irregular hypothalamic function. Thereby, applying dietary strategies for weight loss may also ameliorate headache/migraine. Another important dietary intervention that might be effective in headache/migraine improvement is related to balance between the intake of essential fatty acids, omega-6 and omega-3 which also affect inflammatory responses, platelet function and regulation of vascular tone. Regarding elimination diets, it appears that targeted these diets in migraine patients with food sensitivities could be effective in headache/migraine prevention. Taken together, dietary approaches that could be considered as effective strategies in headache/migraine prophylaxis include weight loss diets in obese headache patients, ketogenic and low-calorie diets, reducing omega-6 and increasing omega-3 fatty acid intakes.
This paper presents a method based on neural networks to solve fractional infinite-horizon optimal control problems s(FIHOCP)s, where the dynamic control system depends on Caputo fractional derivatives. First, with the help of an approximation, the Caputo derivative is replaced to integer-order derivative. Using a suitable change of variable, the IHOCP is transformed into a finite-horizon one. According to the Pontryagin minimum principle (PMP) for optimal control problems and by constructing an error function, an unconstrained minimization problem is defined. In the optimization problem, the trial solutions are used for state, costate and control functions where these trial solutions are constructed by using two-layered perceptron neural network. Two numerical results are introduced to explain our main results.
Methamphetamine (METH) is an illicit dopaminergic neurotoxin and is an extremely addictive psychostimulant drug that influences monoamine neurotransmitter system of the brain and is responsible for enhancing energy and satisfaction and feelings of alertness. Long-lasting exposure to METH causes psychosis and increases the risk of Parkinson's disease. Studies have revealed that obestatin (OB) is a novel endogenous ligand, which may have neuroprotective effects. Hence, we hypothesized that OB might appropriately limit METH-induced neurotoxicity via the control of apoptotis and autophagy. In the current study, PC12 cells were exposed to both METH (0.5, 1, 2, 3, 4, and 6 mmol/L) and pretreatment OB (1, 10, 100, and 200 nmol/L) in vitro for 24 h to determine appropriate dose, and then downstream pathways were measured to investigate apoptosis and autophagy. The results have shown that OB reduced the apoptotic response post-METH exposure in PC12 cells by developing cell viability and diminishing apoptotic rates. Furthermore, the study has exhibited OB decreased gene expression of Beclin-1 by real-time polymerase chain reaction and LC3-II by Western blotting in METH-induced PC12 cells, which demonstrated that autophagy is reduced. The study is proposed that OB is useful in reducing oxidative stress, which may also play an essential role in the regulation of METH-triggered apoptotic response. So these data indicate that OB could potentially alleviate METH-induced neurotoxicity via the reduction of apoptotic and autophagy responses.
There is limited information about pesticide contamination in Iran's agricultural land, particularly in plains producing exportable fruits. The aim of this investigation was to evaluate the concentration of organochlorine pesticides (OCPs) including hexachlorocyclohexane (HCH), heptachlor, dichloro-diphenyl-trichloroethane (DDT), chlordane (CHL), and their isomers compounds in agricultural soils of southern Iran. A total of 28 topsoil samples were collected from agricultural lands of Dalaki and Shabankare areas, Bushehr, Iran. In Dalaki area, the mean value of ΣHCH (α, β, γ, δ), ΣDDT (o,p-DDE, o,p-DDD, o,p-DDT, p,p-DDE, p,p-DDD, p,p-DDT, and DDT), and ΣCHL (Trans-chlordane, Cis-chlordane, Heptachlor-exo-epoxide, and Heptachlor) was found to be 0.411 ng/g (dry weight, dw), 4.37 ng/g dw, and 2.04 ng/g dw, respectively. In Shabankare area the mean value of ΣHCH, ΣDDT, and ΣCHL was measured to be 1.38 ng/g dw, 11.99 ng/g dw, and 1.62 ng/g dw, respectively. The concentration trend of pesticides in both areas was as follows: DDT > CHL > HCH. Source identification indicated recent usage of HCH and DDT in the studied areas. Obtaining a cis-chlordane/trans-chlordane ratio greater than one in Shabankare farmlands showed that chlordane was not used recently. The health risk assessment showed that children and adults groups in both areas are exposed to negligible cancer risk. More serious attempts are necessary to reduce usage of OCPs during the agricultural process and the protection of soil and human health in the studied areas.
Trace elements play an important role in tuberculosis infection because their deficiencies can be associated with impaired immunity. Blood samples were collected from a total of 320 active pulmonary tuberculosis patients and healthy individuals. The serum concentrations of Zinc, Iron, Copper, Calcium, lead, Arsenic and Selenium were analyzed by atomic absorption spectrometry. The levels of trace elements were measured after 2, 4 and 6 months of anti-TB treatment initiation in TB infected groups. Compared to the control group, the concentrations of Zinc, Selenium, and Iron were significantly lower (P < 0.001) in tuberculosis patients; however, that of Arsenic, Lead, and copper was significantly higher (P < 0.001) in the serum of patients. Cu/Zn and Cu/Se ratios were also significantly higher (P < 0.001) in TB patients compared to the control group. In addition, serum concentration calcium was similar in both TB patients and healthy controls. Our results indicated that trace elements concentrations in tuberculosis patients are related to each element role in immune system. Wherever the element is essential for the pathogenesis of bacteria, its concentration will remain low; and contrariwise, when the element is toxic for the bacteria, its level will be regulated up to provide a perfect condition for bacterial growth.
Most of the introduced susceptibility methods of
Most of the introduced susceptibility methods of
Decellularized tissue scaffolds provide an extracellular matrix to control stem cells differentiation toward specific lineages. The application of mesenchymal stem cells for artificial ovary production may enhance In this experimental study, three methods were used for cellular seeding including rotational (spinner flask) and static (conventional and injection) seeding cultures. OVECs were evaluated with Hematoxylin and Eosin staining and viability analyses for the seeded PMSCs. Then, immunohistochemistry analysis was performed using the best method of cellular seeding for primordial germ cell-like cells, mesenchymal stem cells and proliferation markers. Stereology analysis was also performed for the number of penetrated cells into the OVECs.Our results showed that rotational seeding increases the permeability of PMSCs into the scaffold and survival rate of the seeded PMSCs, comparing to the other methods. On the other hand, rotationally seeded PMSCs had a more favorable capability of proliferation with Ki67 expression and differentiation to ovarian specific cells with expression of primordial germ cell line markers without mesenchymal stem cells markers production. Furthermore, stereology showed a more favorable distribution of PMSCs along the outer surfaces of the OVEC with further distribution at the central part of the scaffold. The average total cell values were determined 2142187 cells/mmThe rotational seeding method is a more favorable approach to cell seeding into ovarian decellularized tissue than static seeding.
We present a four-branch model of the dielectrophoresis (DEP) method that takes into consideration the inherent properties of particles, including size, electrical conductivity, and permittivity coefficient. By using this model, bioparticles can be continuously separated by the application of only a one-stage separation process.In this numerical study, we based the separation process on the differences in the particle sizes. We used the various negative DEP forces on the particles caused by the electrodes to separate them with a high efficiency. The particle separator could separate blood cells because of their different sizes.Blood cells greater than 12 μm were guided to a special branch, which improved separation efficiency because it prevented the deposition of particles in other branches. The designed device had the capability to separate blood cells with diameters of 2.0 μm, 6.2 μm, 10.0 μm, and greater than 12.0 μm. The applied voltage to the electrodes was 50 V with a frequency of 100 kHz.The proposed device is a simple, efficient DEP-based continuous cell separator. This capability makes it ideal for use in various biomedical applications, including cell therapy and cell separation, and results in a throughput increment of microfluidics devices.
Platelet (PLT) storage at 4˚C has several benefits, however, it is accompanied by increased clearance of PLTs after transfusion. In this study, we evaluated the potential of sodium octanoate (SO) for reducing apoptosis and clearance rate of PLTs after long-term storage in cold.In this experimental study, PLT concentrates (PCs) were stored for 5 days under the following three conditions: 20-24˚C, 4˚C, and 4˚C in the presence of SO. To measure the viability of PLTs, the water-soluble tetrazolium salt (WST-1) assay was performed. Phosphatidylserine (PS) exposure was determined on PLTs using flow cytometry technique. The amount of human active caspase-3 was determined in PLTs using an enzyme-linked immunosorbent assay. Additionally, the amount of PLT ingestion or clearance was determined by using HepG2 cell line.The viability was higher in the SO-treated PLTs compared to the other groups. The level of PS exposure on PLTs was lower in the SO-treated PLTs compared to the other groups. The amount of active caspase-3 increased in all groups during 5-day storage. The highest increase in the amount of caspase-3 levels was observed at cold temperature. However, PLTs kept at 4˚C in the presence of SO had a lower amount of active caspase-3 compared to PLTs kept at 4˚C. The amount of PLTs removal by HepG2 cells was increased for 4˚C-kept PLTs but it was lower for PLTs kept at 4˚C in the presence of SO but, the differences were not significant (P>0.05).SO could partially moderate the effects of cold temperature on apoptosis and viability of platelets. It also decreases the ingestion rate of long-time refrigerated PLTs in vitro. Further studies using higher numbers of samples are required to demonstrate the effect of SO on reducing the clearance rate of PLTs.
DNA methylation, a major epigenetic reprogramming mechanism, contributes to the increased prevalence of type 2 diabetes mellitus (T2DM). Based on genome-wide association studies, polymorphisms in In this experimental study, we delineated DNA methylation patterns, mRNA transcription and protein expression level of Our results demonstrated that hypomethylation of CpG sites in the vicinity of We postulate that GDM is likely to exert its adverse effects on pancreatic β-cells of offspring through hypomethylation of the
Autophagy and apoptosis play key roles in cancer survival and pathogenesis and are governed by specific genes which have a dual role in both cell death and survival. Arsenic trioxide (ATO) and thalidomide (THAL) are used for treatment of many types of hematologic malignancies. ATO prevents the proliferation of cells and induces apoptosis in some cancer cells. Moreover, THAL has immunomodulatory and antiangiogenic effects in malignant cells. The aim of present study was to examine the effects of ATO and THAL on U937 and KG-1 cells, and evaluation of mRNA expression level of VEGFs genes, PI3K genes and some of autophagy genes.In this ATO/THAL combination enhanced cell apoptosis in a dose-dependent manner. Also, ATO/THAL induced SubG1/ G1 phase arrest. mRNA expression levels of Combined treatment with ATO and THAL can inhibit proliferation and invasion of AML cells by down-regulating
Mutations of In this case-control study, blood sample of 622 participants, including 308 breast cancer cases and 314 controls were collected. Genotyping for rs1042522 was conducted by Allele Specific polymerase chain reaction (AS-PCR). In order to set a meta-analysis study, PubMed, Scopus and ISI Web of Knowledge and Persian databases were searched to explore relevant studies, published up to September 2018, containing information on All retrieved available data as well as the results of our current study were consisted of 1965 breast cancer cases and 1999 healthy controls. No significant difference was observed in allele frequencies between groups (P=0.90) in our study. The cumulative results did not also show any association between rs1042522 and breast cancer risk on the dominant (P=0.61) and recessive (P=0.89) models.These findings cannot support contribution of rs1042522 polymorphism to breast cancer risk in an Iranian population. Future larger studies may help confirm this finding with a greater power.
Recent data suggest that increased levels of the In this experimental study, expression level of The results of present study demonstrated no signiﬁcant difference in the expression of This study demonstrated that expression of
We aimed to examine the expression levels of the VASA gene and protein in testis sections of neonate and adult mice as well as testicular cell cultures.In this experimental study, in order to investigate the expression of this germ cell marker gene in more detail, we analyzed the expression of VASA by immunocytochemistry, immunohistochemistry and fluidigm reverse transcription-polymerase chain reaction (RT-PCR).The immunohistochemical assays showed that the VASA protein was exclusively expressed in germ cells in the seminiferous tubules of the neonate and adult testis and not in somatic cells. VASA was not detectable in PLZF positive spermatogonial stem cells (SSCs), was weakly expressed in proliferating spermatogonia, and became abundant in spermatocytes and round spermatozoa. Counting VASA-positive cells in the seminiferous tubules of the neonate and adult testis depicted significant higher expression (P<0.05) of VASA in the adult testis in comparison to its neonate counterpart. SSC colonies were established The VASA protein is, therefore, an extremely specific marker of testicular germ cell differentiation
Multiple sclerosis (MS) is a chronic disorder involving both inflammatory and neurodegenerative responses. Long non-coding RNAs (lncRNAs) have been had an emerging role as the biomarkers of different disorders, including autoimmune diseases. Previous studies have shown that NR_003531.3 (MEG3a), AC000061.1_201, and AC007182.6 play a role in the pathogenesis of human autoimmune diseases. However, the potential significance of these lncRNAs, as the diagnostic biomarkers of MS, has not been studied yet. We aimed to quantitatively evaluate the expression levels of NR_003531.3, AC000061.1_201, and AC007182.6 in peripheral blood samples of MS patients in comparison with healthy controls.In this case-control study, the blood samples from 20 MS patients and 10 healthy controls were collected. Total RNA was extracted, and the expression levels of three selected lncRNAs were quantitatively measured using the quantitative real time-polymerase chain reaction (qRT-PCR) method.We detected a significant down-regulation in the expression of NR_003531.3 in MS patients, while no marked changes were observed in the expression of AC000061.1_201 and AC007182.6 in patients compared with controls. Based on the receiver operating characteristic (ROC) curve analysis, NR_003531.3 could discriminate MS patients from healthy subjects effectively. Regarding the prognosis of MS patients, NR_003531.3 is significantly and inversely correlated with the expanded disability status scale (EDSS).The potential role of NR_003531.3 lncRNA as a diagnostic biomarker to distinguish MS patients is proposed. Prognostically, NR_003531.3 correlates with lower disability rates in MS patients.
Transforming growth factor beta/single mothers against decapentaplegic (TGFβ/SMAD) signaling pathway plays important roles in various biological processes. It acts as a tumor suppressor during the early stages of cancer progression. Discovering the regulators of this pathway provides important options for therapeutic strategies. Here, we searched for candidate microRNAs (miRNAs) that potentially target the critical components of the TGFβ signaling pathway.In the current experimental study, we first predicted miRNAs that target TGFβ components using a bioinformatics software. After that, quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of miR-587, Multiple miRNA responsive elements (MREs) were predicted for Altogether, our data revealed an important role for