Applications of Genome-Wide Screening and Systems Biology Approaches in Drug Repositioning

Simple Summary Drug repurposing is an accelerated route for drug development and a promising approach for finding medications for orphan and common diseases. Here, we compiled databases that comprise both computationally- or experimentally-derived data, and categorized them based on quiddity and origin of data, further focusing on those that present high throughput omic data or drug screens. These databases were then contextualized with genome-wide screening methods such as CRISPR/Cas9 and RNA interference, as well as state of art systems biology approaches that enable systematic characterizations of multi-omic data to find new indications for approved drugs or those that reached the latest phases of clinical trials. Modern drug discovery through de novo drug discovery entails high financial costs, low success rates, and lengthy trial periods. Drug repositioning presents a suitable approach for overcoming these issues by re-evaluating biological targets and modes of action of approved drugs. Coupling high-throughput technologies with genome-wide essentiality screens, network analysis, genome-scale metabolic modeling, and machine learning techniques enables the proposal of new drug-target signatures and uncovers unanticipated modes of action for available drugs. Here, we discuss the current issues associated with drug repositioning in light of curated high-throughput multi-omic databases, genome-wide screening technologies, and their application in systems biology/medicine approaches

Metabolic effects of fasting in adolescents with diabetes type 1

Type I diabetes mellitus is a common chronic disease in adolescents. According to statistics, 12,243 diabetic Muslims fast in thirteen Islamic countries, 43% of whom have type I diabetes. This longitudinal study was conducted on volunteer adolescents with type I diabetes aged 13-18 years for 15 days using the census method. Three days before Ramadan and during the last three days of the study period, changes in the insulin dose, HbA1C, lipid profile, and body mass index (BMI) were evaluated. Among 10 volunteer patients, eight individuals could complete Ramadan fasting. Blood glucose analysis indicated a significant difference between the reported blood glucose levels (

IMPACT OF ENVIRONMENTAL FACTORS OF SHOPPING CENTER FOR ARCHITECTURE DESIGN

ABSTRACT Purchasing process in shopping centers, are among the main issues in design and management of shopping centers, therefore the following research that is intended to determine the buyer 's needs and changes in space to meet the needs, has been developed. In this research , we accessed the person in the environment by using a experimental laboritical method and as a result to 155 people who centered in this place a question air and a form to report was given to record their opinions , which in them people tell their reason for shopping and the required conditions to purchase. By analyzing these issues , it is inferred that different factors will inference to process of purchasing which among them are feeling of security, calmness, anxiety. Therefore we could use the findings from the present research to increase the rate of purchase and transforming them to a full trading center for designing these shopping centers. By assuming that study of behaviors. In the users of these spaces , could offer approaches in design of shopping centers, these questions have been answered. By considering to the results from histograms, rate off effect of effective environmental factors on the purchasing process and also that much these factors are effective , was determined in this study. In this research , it was found that people have a large inclination to the their shopping at night , because in this time the existing environmental factors have the most influence on the shopping , singularly and recognize this process as a part of luxury , they wanted the auxiliary space beside shopping centers . so they can do other things such as eating. In this regard , these shopping centers did not have favorable environmental space and conditions and this is one of the weaknesses in this centers. For this purpose in designing the shopping centers we must consider to environmental factors such as security , attractiveness of space , environmental variations, and also in design of shopping centers, they allocate faces for doing those auxiliary activities. to these consumers. In the other word all of these groups were interred in these centers. The reason for this is having more free time because of industrialization and mechanizing and raising the level of incomes. Also the modern consumption, instead of considering to the needs, focuses on the wishes and therefore the main entity of consumption, would be on the social and cultural aspects instead of economical aspects. These shopping centers are a place for supply and demand to be in contact .increasing changes in technology, appearance of new products and their variation , and lack of familiarity of consumers, together with severe competition and unfavorable of producers are some of the reasons for forming these new shopping centers. These centers could offer any kind of information's such as cultural, artistic, economical, technological and scientific information . those people with these information's and goods are gathered in a specific place to help each other by offering their own abilities to each other and to the consumers by intend of development and promotion of job opportunities and discovering the new grounds of jobs. These information's could be one the Old streets and bazaars which in one time industries craft men were supplying and offering their goods, now is becoming a place for shopping from various shops including boutiques, dress shops, restaurants, coffees, whole sale stores, agencies for big and famous manufactures of cameras and computers, banks and travel agencies. At the same time of industrial change and transitions, type of bazaars were formed and civic life was expanded and a result the big stores. Were established to serve to these consumers and also to better distribute the KEYWORDS

Finite difference time domain simulation of arbitrary shapes quantum dots

Utilizing the finite difference time domain (FDTD) method, energy eigenvalues of spherical, cylindrical, pyramidal and cone-like quantum dots are calculated. To do this, by the imaginary time transformation, we transform the schrödinger equation into a diffusion equation. Then, the FDTD algorithm is hired to solve this equation. We calculate four lowest energy eigenvalues of these QDs and then compared the simulation results with analytical ones. Our results clearly show that simulation results are in very good agreement with analytical results. Therefore, we can use the FDTD method to find accurate results for the Schrödinger equation

Evaluation the Correlation between Turbidity and Total Suspended Solids with other Chemical Parameters in Yazd Wastewater Treatment Effluent Plant

Introduction: Expensive chemical tests are usually applied to control the efficiency of wastewater treatment plants. However, the cost of measuring these parameters is one of the challenges of the wastewater treatment plants. Using statistical methods has been evaluated for possibility of calculating expensive parameters by measuring the inexpensive parameters in this study. Materials and Methods: Initial sample number in this study was 87 cases that were collected from SBR effluent treatment plants of Yazd as a routine sampling for two years in March 2013 to March 2015. Total suspended solids (TSS) and turbidity parameters were defined as independent variables and twelve parameters including BOD5, COD, TKN, NH3+, NO3-, NO2-, TP, TH, Ca2+, Mn2+, alkalinity, and color were the dependent variables. Spearman test was used to investigate the significant relationship between independent and dependent variables. Linear regression analysis was used to determine the linear equation between TSS and turbidity as independent variables with BOD5, COD, TKN, NH3-, NO2-, TP and color as dependent variables. Results: The results of the regression equations in relation to turbidity and TSS with independent variables showed that the R value for color, TKN, NH3+, BOD5, COD, TP, and NO2- were 0.942 , 0.931 , 0.91 , 0.905 , 0.874 , 0. 872 and 0.86 respectively from the highest to the lowest. Conclusion: The measured values of BOD5, COD, TKN, TP, NO2-, NH3+, and color in laboratory were very close to those predicted through regression equations. Therefore, regression equations created in this study can be used to calculate expensive parameters

Current Status of COVID-19 Therapies and Drug Repositioning Applications

The rapid and global spread of a new human coronavirus (SARS-CoV-2) has produced an immediate urgency to discover promising targets for the treatment of COVID-19. Drug repositioning is an attractive approach that can facilitate the drug discovery process by repurposing existing pharmaceuticals to treat illnesses other than their primary indications. Here, we review current information concerning the global health issue of COVID-19 including promising approved drugs and ongoing clinical trials for prospective treatment options. In addition, we describe computational approaches to be used in drug repurposing and highlight examples of in silico studies of drug development efforts against SARS-CoV-2

Drug repositioning for immunotherapy in breast cancer using single-cell analysis.

Acknowledgements: The research received no funding.Immunomodulatory peptides, while exhibiting potential antimicrobial, antifungal, and/or antiviral properties, can play a role in stimulating or suppressing the immune system, especially in pathological conditions like breast cancer (BC). Thus, deregulation of these peptides may serve as an immunotherapeutic strategy to enhance the immune response. In this meta-analysis, we utilized single-cell RNA sequencing data and known therapeutic peptides to investigate the deregulation of these peptides in malignant versus normal human breast epithelial cells. We corroborated our findings at the chromatin level using ATAC-seq. Additionally, we assessed the protein levels in various BC cell lines. Moreover, our in-house drug repositioning approach was employed to identify potential drugs that could positively impact the relapse-free survival of BC patients. Considering significantly deregulated therapeutic peptides and their role in BC pathology, our approach aims to downregulate B2M and SLPI, while upregulating PIGR, DEFB1, LTF, CLU, S100A7, and SCGB2A1 in BC epithelial cells through our drug repositioning pipeline. Leveraging the LINCS L1000 database, we propose BRD-A06641369 for B2M downregulation and ST-4070043 and BRD-K97926541 for SLPI downregulation without negatively affecting the MHC complex as a significantly correlated pathway with these two genes. Furthermore, we have compiled a comprehensive list of drugs for the upregulation of other selected immunomodulatory peptides. Employing an immunotherapeutic approach by integrating our drug repositioning pipeline with single-cell analysis, we proposed potential drugs and drug targets to fortify the immune system against BC

Additional file 1 of Effect of soluble fiber on blood pressure in adults: a systematic review and dose–response meta-analysis of randomized controlled trials

Additional file 1: Table S1. Search strategies including the key terms and the queries for each database. Table S2. Reason for exclusion of retrieved articles. Table S3. Characteristics of eligible studies examining the effect of soluble fiber supplementation on blood pressure parameters. Table S4. Sensitivity analyses of the use of correlation coefficients of 0.25 and 0.75. Table S5. Result of subgroup analysis of included studies in meta-analysis. Table S6. Risk of bias assessment in randomised controlled trials. Table S7. The GRADE evidence quality for each outcome

Size matters : the impact of nucleus size on results from spatial transcriptomics

Background: Visium Spatial Gene Expression (ST) is a method combining histological spatial information with transcriptomics profiles directly from tissue sections. The use of spatial information has made it possible to discover new modes of gene expression regulations. However, in the ST experiment, the nucleus size of cells may exceed the thickness of a tissue slice. This may, in turn, negatively affect comprehensive capturing the transcriptomics profile in a single slice, especially for tissues having large differences in the size of nuclei. Methods: Here, we defined the effect of Consecutive Slices Data Integration (CSDI) on unveiling accurate spot clustering and deconvolution of spatial transcriptomic spots in human postmortem brains. By considering the histological information as reference, we assessed the improvement of unsupervised clustering and single nuclei RNA-seq and ST data integration before and after CSDI. Results: Apart from the escalated number of defined clusters representing neuronal layers, the pattern of clusters in consecutive sections was concordant only after CSDI. Besides, the assigned cell labels to spots matches the histological pattern of tissue sections after CSDI. Conclusion: CSDI can be applied to investigate consecutive sections studied with ST in the human cerebral cortex, avoiding misinterpretation of spot clustering and annotation, increasing accuracy of cell recognition as well as improvement in uncovering the layers of grey matter in the human brain