Exploring the Role of Molecular Dynamics Simulations in Most Recent Cancer Research: Insights into Treatment Strategies

Cancer is a complex disease that is characterized by uncontrolled growth and division of cells. It involves a complex interplay between genetic and environmental factors that lead to the initiation and progression of tumors. Recent advances in molecular dynamics simulations have revolutionized our understanding of the molecular mechanisms underlying cancer initiation and progression. Molecular dynamics simulations enable researchers to study the behavior of biomolecules at an atomic level, providing insights into the dynamics and interactions of proteins, nucleic acids, and other molecules involved in cancer development. In this review paper, we provide an overview of the latest advances in molecular dynamics simulations of cancer cells. We will discuss the principles of molecular dynamics simulations and their applications in cancer research. We also explore the role of molecular dynamics simulations in understanding the interactions between cancer cells and their microenvironment, including signaling pathways, proteinprotein interactions, and other molecular processes involved in tumor initiation and progression. In addition, we highlight the current challenges and opportunities in this field and discuss the potential for developing more accurate and personalized simulations. Overall, this review paper aims to provide a comprehensive overview of the current state of molecular dynamics simulations in cancer research, with a focus on the molecular mechanisms underlying cancer initiation and progression.Comment: 49 pages, 2 figure

The Effect of Reproductive Factors on Coronary Artery Disease in Women

Abstract Introduction: There is a sex discrepancy in cardiovascular physiology. In this study, we aimed to investigate the effect of female reproductive factors on coronary artery disease (CAD) beyond the known CAD risk factors. Methods: In a case-control study, women referred to Tehran Heart Center for coronary artery angiography from 2012 to 2014 were enrolled. Of these, 80 premenopausal and 100 postmenopausal females with CAD in angiography were randomly selected as cases and 80 premenopausal and 100 postmenopausal females without CAD in angiography were selected as controls. A questionnaire including reproductive history and known CAD risk factors was filled for every subject. Analysis was performed separately for pre and postmenopausal women and a final adjustment for coronary artery disease risk factors was done. Results: Among reproductive factors, oligomenorrhea (OR= 6.72) was a significant risk factor for CAD in premenopausal women and history of oral contraceptive (OCP) use had a protective effect on CAD in pre and postmenopausal woman (OR= 0.24 and 0.20, respectively). Conclusions: Since oligomenorrhea has a strong association with insulin resistance and diabetes, a conventional risk factor of CAD, women with oligomenorrhea should be treated not only for cyclic irregularity but also for prevention of CAD

Relationship between the Presence of the nalC Mutation and Multidrug Resistance in Pseudomonas aeruginosa

Objectives. The current study was conducted to determine the relationship between the presences of significant multidrug resistance in Pseudomonas aeruginosa (P. aeruginosa) having intact mexR genes (nalC) to different antibiotics. Methods. In order to identify nalC, fifty strains of P. aeruginosa were obtained. All isolates were found in urinary tract infections. They were evaluated against different antibiotics. The nalC mutant was identified by PCR. Results. The 50 clinical isolates of P. aeruginosa originated from two hospitals in Iran, in which 32 isolates were found in Milad hospital, and 18 isolates were collected in the Ilam Hospital. The results in Milad hospital of nalC revealed that all P. aeruginosa resistant to oxacillin showed the presence of nalC. In Ilam hospital only three (16.6%) isolates were resistant to oxacilin and aztreonam, and among these three isolates only one isolate revealed resistance to ceftazidime and amikacin. The resistant isolates showed the presence of both OXA-10 and nalC. Conclusion. Our results showed that the presence of nalC was observed among P. aeruginosa resistance to oxacilin. Thus, the finding suggested relationship between oxacilin resistance and presence of nalC and consequently overproduction of the MexABOprM efflux system

The Prevalence of ESBLs Producing Klebsiella pneumoniae Isolates in Some Major Hospitals, Iran

Aims of this study were to investigate on antibiotic resistance and molecular epidemiology of K.pneumoniae producing ESBLs isolates of respiratory tract infections in some major hospitals in Iran. K.pneumonaie were obtained of patients with RTI. K. pneumoniae producing ESBLs detected by screening, confirming and PCR methods. During the 12-month period, a total of one hundred and thirteen of K.pneumoniae were found from RTI in three cities in different region of Iran which Sixty seven strains (59.2%) were ESBLs producer. In Ilam hospitals, seventeen strains (43.6%), in Milad hospital, thirty-seven strains (74%) and in Emam Reza hospital, thirteen strains (54.2%) were ESBLs producer. The findings showed that among sixty-seven K.pneumoniae producing ESBLs, Sixty-three strains (94%) were positive for blaSHV, eleven strains (16.4%) contained blaTEM and sixteen strains (23.9%) harbored blaCTX-M. Imipenem was found as an effectiveness antibiotic. In the current study, Majority of the ESBLs production had occurred in Milad hospital in Tehran (74%). In conclusion, spreading ESBL-producing strains is a concern, as it causes limitations to the antimicrobial agents for optimal treatment of patients

Detecting structural damage in Timoshenko beams based on optimization via simulation (OVS)

Considering easy determination of natural frequency in structures leads researchers to focus on detecting the damage through the dynamic parameters using combination of various artificial intelligence algorithms. The main contribution of this research is to detect damage in structures (including its depth and location) for the deep beams with Timoshenko behavior using optimization via simulation (OVS). This method is established based on the first three natural frequencies of the deep or semi-deep beams. The finite element method (FEM) is conducted to obtain essential inputs parameters for OVS. The exact location and depth of the structural damage are determined, using combination of multi-objective optimization algorithms, multi-objective genetic algorithm (MOGA), and modified multi-objective genetic algorithm (MMOGA). This research also remarkably concerns about detecting the location of the defect in the beams with several cracks. In order to verify the results obtained from numerical analysis, several experimental specimens are presented. The dynamics parameters of the beams are experimentally identified using modal hammer. The responses obtained from the numerical method, proposed in this research, are also compared with the results obtained from previous studies. Practically, a beam with real dimensions is examined for different boundary conditions. In addition, the results obtained from MOGA and MMOGA are compared with the other researchers’ achievements. Finally, it was observed that the proposed method, (OVS), can be satisfyingly determined the exact location and depth of damage with the high accuracy

Up-to-date Treatments of Primary Hyperhidrosis with Focus on Sympathectomy and Sympathicotomy; a Narrative Review

Background: Primary hyperhidrosis (PH) refers to excessive sweating, beyond normal physiological levels, in specific sites of the body for unknown reasons. It is usually bilateral and is most prominent in the palms, axillae, feet, and face. PH prevalence is estimated to be 0%-6.1% in different populations. It usually begins in childhood and is more frequent in women. In 57% of cases, there is a positive family history. It is an autosomal dominant disorder with variable penetration in chromosomes 5, 14, or both. Objective: The aim of this study was to illustrate current treatments of PH while focusing on surgical therapies through a narrative review. Methods: A complete search of online articles from 2007 to 2014 in PubMed, Scopus, and the Cochrane Library was performed. A free search and a search in the MeSH database for the study’s keywords were also done. More than 600 relevant articles were found, of which 51 were chosen for this study. This article is based on those articles. Results: Surgery is the best and more permanent therapy for PH. The most common consequences of surgery are compensatory sweating and gustatory sweating. There is controversy concerning whether lowering the level and limiting the number of ganglia on which surgery is performed reduces compensatory sweating. Conclusion: It seems that ramicotomy (selective division of the sympathetic postganglionic fibers) reduces compensatory sweating, but this theory should be confirmed with more studies

Evaluation of SD-208, a TGF-β-RI kinase inhibitor, as an anticancer agent in retinoblastoma

Retinoblastoma is the most common intraocular tumor in children resulting from genetic alterations and transformation of mature retinal cells. The objective of this study was to investigate the effects of SD-208, TGF-β-RI kinase inhibitor, on the expression of some miRNAs including a miR-17/92 cluster in retinoblastoma cells. Prior to initiate this work, the cell proliferation was studied by Methyl Thiazolyl Tetrazolium (MTT) and bromo-2′-deoxyuridine (BrdU) assays. Then, the expression patterns of four miRNAs (18a, 20a, 22, and 34a) were investigated in the treated SD-208 (0.0, 1, 2 and 3 μM) and untreated Y-79 cells. A remarkable inhibition of the cell proliferation was found in Y-79 cells treated with SD-208 versus untreated cells. Also, the expression changes were observed in miRNAs 18a, 20a, 22 and 34a in response to SD-208 treatment (P<0.05). The findings of the present study suggest that the anti-cancer effect of SD-208 may be exerted due to the regulation of specific miRNAs, at least in this particular retinoblastoma cell line. To the best of the researchers’ knowledge, this is the first report demonstrating that the SD-208 could alter the expression of tumor suppressive miRNAs as well as oncomiRs in vitro. In conclusion, the present data suggest that SD-208 could be an alternative agent in retinoblastoma treatment. © 2016 Tehran University of Medical Sciences. All rights reserved

Differential between multi-drug resistance pattern of extended spectrum b- Lactamases producing E. coli and K. pneumoniae

The current study aimed to determine the prevalence of Extended-Spectrum b-Lactamases (ESBLs) in Escherichia coli (E. coli) and Klebsiella pneumoniae (K. pneumoniae) strains isolated from patients with Urinary Tract Infections (UTIs), to study the association between presence of ESBL enzyme and multi-drug resistance strains and finally, and to investigate the predominant ESBL gene in E. coli and K. pneumoniae. The strains were examined for the presence of ESBL as a Clinical Laboratory Standards Institute (CLSI) guideline. Among 284 clinical isolates, 52.8% (n = 150) and 47.2% (n =134) were E. coli and K. pneumoniae, respectively, and 110 strains were ESBL producer, which 68 strains were K. pneumoniae and 42 strains were E. coli. Significant difference observed between the TEM gene and ciprofloxacin resistant in E. coli (P ? 0.05) while no significant difference observed between CTX-M, SHV genes and the other multi-drug resistant E. coli. No significant difference observed between CTX-M, TEM, and SHV genes and multi-drug resistant K. pneumoniae. In conclusion, spreading of ESBL-producing strains is a concern, as it causes limitations to the antimicrobial agents for optimal treatment of patients. Prevalence of ESBLs was more observed in K. pneumoniae than E. coli. In addition, TEM gene was more prevalent in E. coli and resistance to ciprofloxacin was predominant in E. coli

Transforming Growth Factor Beta-Induced Factor 2-Linked X (TGIF2LX) Regulates Two Morphogenesis Genes, Nir1 and Nir2 in Human Colorectal

Abstract- A member of homeodomain protein namely TGIF2LX has been implicated as a tumor suppressor gene in human malignancy as well as in spermatogenesis. However, to our knowledge, dynamic functional evidence of the TGIF2LX has not yet been provided. The aim of the present study was to investigate the human TGIF2LX target gene(s) using a cDNA-AFLP as a differential display method. A pEGFP-TGIF2LX construct containing the wild-type TGIF2LX cDNA was stably transfected into SW48 cells. UV microscopic analysis and Real-time RT-PCR were used to confirm TGIF2LX expression. The mRNA expressions of TGIF2LX in transfected SW48 cells, the cells containing empty vector (pEGFP-N), and untransfected cells were compared. Also, a Real-time PCR technique was applied to validate cDNA-AFLP results. The results revealed a significant down-regulation and up-regulationby TGIF2LX of Nir1 and Nir2 genes, respectively. The genes are engaged in the cell morphogenesis process. Our findings may provide new insight into the complex molecular pathways underlying colorectal cancer development