Search results for: circulating miRNAs

Authors: Chakrit Thapphan, Suteeraporn Chaowattanapanit, Sorutsiri Chareonsudjai, Wisitsak Phoksawat, Supranee Phantanawiboon, Kiatichai Faksri, Steve W. Edwards, Kanin Salao

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Background: Psoriasis is a chronic inflammatory disease of the skin that is mediated by crosstalk between keratinocytes and immune cells, especially CD4+ T helper (Th) cells. To date, psoriasis is established as a T helper 17 (Th17) cell-mediated inflammatory process driven by the over-expression of Th17. However, the role of other CD4+T helper cells is rather controversial. Objective: Our study, thereby, aimed to characterize and analyze T cell subsets in the circulating blood of psoriasis patients and compare them to healthy controls. Methods: Peripheral blood mononuclear cells were isolated from the participants and stained with fluorescent dye-conjugated monoclonal antibodies specific for intracellular cytokines, including interferon-gamma (IFN- γ), interleukin (IL-4), IL-17 and forkhead box P3 (FOXP3), that can be used to define T helper 1 (Th1) cells, T helper 2 (Th2), T helper 17 (Th17) and regulatory T cells (Treg) respectively. Results: We found that the numbers of Th2 (59.6% ± 17.0) and Th17 (4.0% ± 2.0) cells in the circulating blood of psoriasis patients were significantly higher than those of the healthy controls (p= 0.0007 and 0.0013 respectively). In contrast, the numbers of Th1 and Treg cells were not significantly different between psoriasis patients and healthy controls (p= 0.0593 and 0.8518, respectively). Additionally, when adjusting these numbers of Th cells to Treg, we observed a similar trend that the ratio of Th2/Treg and Th17/Treg also elevated (p = 0.0007 and 0.0047, respectively). Conclusion: Taken together, our results suggest an imbalanced T exhibit toward the Th2 and Th17 skewed-immune responses in psoriasis patients.

Keywords: psoriasis, Th cell subsets, Th2 cells, Th17 cells, Treg cells

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Authors: Nisha Sharma, Mili Kaur, Ashutosh Halder, Seema Kaushal, Manoj Kumar, Manish Jain

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Purpose: To investigate microRNAs (miRNA) as an epigenomic etiological factor in idiopathic non-obstructive azoospermia (NOA). In order to achieve the same, an association was seen between occupational exposure to radiation, thermal, and chemical factors and idiopathic cases of non-obstructive azoospermia, and later, testicular differential miRNA expression profiling was done in exposure group NOA cases. Method: It is a prospective study in which 200 apparent idiopathic male factor infertility cases, who have been advised to undergo testicular fine needle aspiration (FNA) evaluation, are recruited. A detailed occupational history was taken to understand the possible type of exposure due to the nature and duration of work. A total of 26 patients were excluded upon XY-FISH and Yq microdeletion tests due to the presence of genetic causes of infertility, 6 hypospermatogeneis (HS), six Sertoli cell-only syndrome (SCOS), and six normospermatogeneis patients testicular FNA samples were used for RNA isolation followed by small RNA sequencing and nCounter miRNA expression analysis. Differential miRNA expression profile of HS and SCOS patients was done. A web-based tool, miRNet, was used to predict the interacting compounds or chemicals using the shortlisted miRNAs with high fold change. The major limitation encountered in this study was the insufficient quantity of testicular FNA sample used for total RNA isolation, which resulted in a low yield and RNA integrity number (RIN) value. Therefore, the number of RNA samples admissible for differential miRNA expression analysis was very small in comparison to the total number of patients recruited. Results: Differential expression analysis revealed 69 down-regulated and 40 up-regulated miRNAs in HS and 66 down-regulated and 33 up-regulated miRNAs in SCOS in comparison to normospermatogenesis controls. The miRNA interaction analysis using the miRNet tool showed that the differential expression profiles of HS and SCOS patients were associated with arsenic trioxide, bisphenol-A, calcium sulphate, lithium, and cadmium. These compounds are reproductive toxins and might be responsible for miRNA-mediated epigenetic deregulation leading to NOA. The association between occupational risk factor exposure and the non-exposure group of NOA patients was not statistically significant, with ꭓ2 (3, N= 178) = 6.70, p= 0.082. The association between individual exposure groups (radiation, thermal, and chemical) and various sub-types of NOA is also not significant, with ꭓ2 (9, N= 178) = 15.06, p= 0.089. Functional analysis of HS and SCOS patients' miRNA profiles revealed some important miR-family members in terms of male fertility. The miR-181 family plays a role in the differentiation of spermatogonia and spermatocytes, as well as the transcriptional regulation of haploid germ cells. The miR-34 family is expressed in spermatocytes and round spermatids and is involved in the regulation of SSCs differentiation. Conclusion: The reproductive toxins might adopt the miRNA-mediated mechanism of disease development in idiopathic cases of NOA. Chemical compound induced; miRNA-mediated epigenetic deregulation can give a future perspective on the etiopathogenesis of the disease.

Keywords: microRNA, non-obstructive azoospermia (NOA), occupational exposure, hypospermatogenesis (HS), Sertoli cell only syndrome (SCOS)

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Authors: Nayera E. Hassan, Sahar A. El-Masry, Mones M. Abu Shady, Rokia A. El Banna, Muhammad Al-Tohamy, Mehrevan M. Abd El-Moniem, Mona Anwar

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Circulating oxidized LDL (ox-LDL) is associated with obesity, insulin resistance (HOMA), metabolic syndrome, and cardiovascular disease in adults. Little is known about relations in children. Aim: To assess association of ox-LDL with fat distribution and insulin resistance in a group of obese Egyptian children. Methods: Study is cross-sectional consisting of 68 obese children, with a mean age of 9.96 ± 1.32. Each underwent a complete physical examination; blood pressure (SBP, DBP) and anthropometric measurements (weight, height, BMI; waist, hip circumferences, waist/hip ratio), biochemical tests of fasting blood glucose (FBS), insulin levels; lipid profile (TC, LDL,HDL, TG) and ox-LDL; calculated HOMA. Sample was classified according to waist/hip ratio into: group I with and group II without central obesity. Results: ox-LDL showed significant positive correlation with LDL and TC in all groups of obesity. After adjustment for age and sex, significant positive correlation was detected between ox-LDL with SBP, DBP, TC, LDL, insulin, and HOMA in group II and with TC and FBS in group I. Insignificant association was detected between ox-LDL and other anthropometric parameters including BMI in any group of obese children (p > 0.05). Conclusions: ox-LDL, as a marker of oxidative stress is not correlated with BMI among all studied obese children (aged 6-12 years). Increased oxidative stress has causal effects on insulin resistance in obese children without central obesity and on fasting blood sugar in those with central obesity. These findings emphasize the importance of obesity during childhood and suggest that the metabolic complications of obesity and body fat distribution are detectable early in life.

Keywords: ox-LDL, obesity, insulin resistance, children

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Authors: Sung Yong Kim, Byung Joo Song

Abstract:

Background: Circulating 25-hydroxyvitamin D (25(OH)D) levels has been considered to be inversely related to breast cancer development, recurrence risk, and mortality. Mean vitamin D levels in Korean population is lower than western countries due to higher incidence of lactose intolerance and lower exposure to sunlight. The purpose of this study was to assess incidence of 25(OH)D deficiency at diagnosis and after adjuvant chemotherapy and to investigate the correlation serum 25(OH)D levels with clinicopathologic features. Methods: From December 2011 to October 2012, 280 breast cancer patients seen at a single tertiary cancer center were enrolled. Serum 25(OH)D was measured at the time of surgery and after completion of adjuvant chemotherapy. Statistical analyses used chi-square test, Fisher's exact test, t-test, and ANOVA. Results: Mean serum 25(OH)D was 18.5 ng/ml. The 25(OH)D levels were deficient (<20 ng/ml) in 190 patients (67.9%), insufficient (20-29 ng/ml) in 51 patients(18.2%), and sufficient (30-150 ng/ml) in 39 patients(13.9%). A notable decrease in 25(OH)D concentration was observed(p<0.001) after chemotherapy but was not related to chemotherapy regimens. It was found significant lower 25(OH)D levels at winter season(from October to March, p=0.030). Subjects with invasive carcinoma (IDC or ILC) had significantly lower circulating levels of 25(OH)D than those with ductal carcinoma in situ(DCIS) (p=0.010). Patients with larger tumor size tends to have lower serum 25(OH)D but there were no statistical significance. Conclusions: Most of the breast cancer patients showed deficient or insufficient serum 25(OH)D concentration. Incidence of vitamin D deficiency was higher in invasive carcinoma than DCIS. Serum 25(OH)D levels were decreased after chemotherapy. Consideration should be given to the supplement of vitamin D to those patients.

Keywords: breast neoplasms, vitamin D, Korean population, breast cancer

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Authors: Antonis Elia, Theo Loizou, Gladys Onambele-Pearson, Matthew Barlow, Georgina Stebbings

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Hypoxic conditions have been reported to enhance red blood cell production in both acclimatised low-landers and altitude adapted populations. This process is mediated by the erythropoietin hormone, which is released predominantly by the hypoxic kidney. A higher haemoglobin concentration was previously reported in elite breath-hold divers when compared to elite-skiers and untrained individuals. Therefore, the present study aimed to investigate whether apnoea induced hypoxia could induce a significant increase in serum erythropoietin concentration in recreational breath-hold divers which would provide an explanation to the higher haemoglobin levels observed in elite breath-hold divers. Identifying whether apnoea induced hypoxia induces a significant increase in serum erythropoietin might suggest that apnoea can be used as an alternative acclimatisation method to high altitude exposure. Seven healthy, recreational male breath-hold divers performed two sets of five 180 second breath-holds with a ten-minute supine rest between each set and a two-minute seated rest between each apnoea. During each breath-hold, participant’s heart rate and peripheral oxygen saturation levels were recorded every subsequent 10 seconds until the end of the 180 second breath-hold. After each 180 second breath-hold a capillary blood sample was collected from the finger to identify circulating haemoglobin levels. Following completion of the apnoeic protocol, three blood samples were collected at 30, 90 and 180 minutes to measure circulating erythropoietin levels. A significant interaction between erythropoietin and time was observed (F(3,18)= 4.72, p < 0.001), with significant increases in erythropoietin evident at 30 (t(6)= -5.035, p < 0.0590 (t(6)= -6.162, p < 0.05) and 180 (t(6)= - 7.232, p < 0.001) minutes post the last apnoea when compared to baseline. Corresponding average increases when compared to baseline were 16% at 30, 23% at 90 and 40% at 180 minutes post the last apnoea. A significant interaction between haemoglobin and time was observed (F(78,84)= 20.814, p < 0.001), with significant increases in haemoglobin evident at the fifth (t(29)= -1.124, p < 0.001), ninth (t(29)= -1.357, p < 0.001) and tenth (t(29)= -1.211, p < 0.05) apnoeas when compared to baseline. A significant interaction between peripheral oxygen saturation and time was observed (F(10,60)= 408.23, p < 0.001). The present study demonstrates that a series of ten 180 second breath-holds is sufficient to induce a significant increase in the circulating erythropoietin concentration of recreational breath hold divers. These observations may suggest that apnoea induced hypoxia may be used as an alternative acclimatisation method to high altitude exposure.

Keywords: apnoea, breath-holding, diving reflex, erythropoietin, haemoglobin

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Authors: Danni Cheng

Abstract:

Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

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Authors: Gwi Hyun Lee, Mun Soo Na

Abstract:

Solar energy has many advantages of infinite and clean source, and also it can be used for reduction of greenhouse gases and environment pollution. Concentrated solar system is a very useful to achieve reasonably high thermal efficiency. Different types of solar concentrating systems have been developed such as parabolic trough and parabolic dish. Conical solar concentrator is one of the most reliable and promising renewable energy systems for higher temperature applications. The objectives of this study were to investigate the influence of flow rate affecting the thermal efficiency of a conical solar collector, which has a double tube absorber placed at focal axis for collecting solar radiation. A conical solar concentrator consists of a conical reflector, which reflects direct solar radiation into an absorber. A double tube absorber was placed at the center of focal axis for collecting the solar radiation reflected from a conical reflector. A dual tracking system consists of a linear actuator and slew drive with driving cycle of 6 seconds. Water was used as circulating fluid, which flows from inlet to outlet of an absorber for collecting solar radiation. Three identical conical solar concentrator systems were installed side by side at the same place for the accurate performance analysis under the same environmental conditions. Performance evaluations were carried out with different volumetric flow rate of 2, 4 and 6 L/min to find the influence of flow rate affecting on thermal efficiency. The results indicated that average thermal efficiency was 73.24%, 81.96%, and 79.78% for each flow rate of 2 L/min, 4 L/min, and 6 L/min. It shows that the flow rate of circulating water has a significant effect on the thermal efficiency of the conical solar concentrator. It is concluded that an optimum flow rate of conical solar concentrator is 6 L/min.

Keywords: conical solar concentrator, performance evaluation, solar energy, solar energy system

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Authors: Leander Van Neste, Kirk Wojno

Abstract:

The innate immune system reacts to foreign insult in several unique ways, one of which is phagocytosis of perceived threats such as cancer, bacteria, and viruses. The goal of this study was to look for evidence of phagocytosed RNA from tumor cells in circulating monocytes. While all monocytes possess phagocytic capabilities, the non-classical CD14+/FCGR3A+ monocytes and the intermediate CD14++/FCGR3A+ monocytes most actively remove threatening ‘external’ cellular materials. Purified CD14-positive monocyte samples from fourteen patients recently diagnosed with clinically localized prostate cancer (PCa) were investigated by single-cell RNA sequencing using the 10X Genomics protocol followed by paired-end sequencing on Illumina’s NovaSeq. Similarly, samples were processed and used as controls, i.e., one patient underwent biopsy but was found not to harbor prostate cancer (benign), three young, healthy men, and three men previously diagnosed with prostate cancer that recently underwent (curative) radical prostatectomy (post-RP). Sequencing data were mapped using 10X Genomics’ CellRanger software and viable cells were subsequently identified using CellBender, removing technical artifacts such as doublets and non-cellular RNA. Next, data analysis was performed in R, using the Seurat package. Because the main goal was to identify differences between PCa patients and ‘control’ patients, rather than exploring differences between individual subjects, the individual Seurat objects of all 21 patients were merged into one Seurat object per Seurat’s recommendation. Finally, the single-cell dataset was normalized as a whole prior to further analysis. Cell identity was assessed using the SingleR and cell dex packages. The Monaco Immune Data was selected as the reference dataset, consisting of bulk RNA-seq data of sorted human immune cells. The Monaco classification was supplemented with normalized PCa data obtained from The Cancer Genome Atlas (TCGA), which consists of bulk RNA sequencing data from 499 prostate tumor tissues (including 1 metastatic) and 52 (adjacent) normal prostate tissues. SingleR was subsequently run on the combined immune cell and PCa datasets. As expected, the vast majority of cells were labeled as having a monocytic origin (~90%), with the most noticeable difference being the larger number of intermediate monocytes in the PCa patients (13.6% versus 7.1%; p<.001). In men harboring PCa, 0.60% of all purified monocytes were classified as harboring PCa signals when the TCGA data were included. This was 3-fold, 7.5-fold, and 4-fold higher compared to post-RP, benign, and young men, respectively (all p<.001). In addition, with 7.91%, the number of unclassified cells, i.e., cells with pruned labels due to high uncertainty of the assigned label, was also highest in men with PCa, compared to 3.51%, 2.67%, and 5.51% of cells in post-RP, benign, and young men, respectively (all p<.001). It can be postulated that actively phagocytosing cells are hardest to classify due to their dual immune cell and foreign cell nature. Hence, the higher number of unclassified cells and intermediate monocytes in PCa patients might reflect higher phagocytic activity due to tumor burden. This also illustrates that small numbers (~1%) of circulating peripheral blood monocytes that have interacted with tumor cells might still possess detectable phagocytosed tumor RNA.

Keywords: circulating monocytes, phagocytic cells, prostate cancer, tumor immune response

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Authors: Daniela E. Marin, Cornelia Braicu, Gina C. Pistol, Roxana Cojocneanu-Petric, Ioana Berindan Neagoe, Mihail A. Gras, Ionelia Taranu

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Aristolochic acid (AA) is a carcinogenic, mutagenic, and nephrotoxic compound commonly found in the Aristolochiaceae family of plants. AA is frequently associated with urothelial carcinoma of the upper urinary tract in human and animals and is considered as being responsible for Balkan Endemic Nephropathy. The pig provides a good animal model because the porcine urological system is very similar to that of humans, both in aspects of physiology and anatomy. MicroRNA (miRNA) are small non-coding RNAs that have an impact on a wide range of biological processes by regulating gene expression at post-transcriptional level. The objective of this study was to analyze the miRNA profiling in the kidneys of AA intoxicated swine. For this purpose, ten TOPIGS-40 crossbred weaned piglets, 4-week-old, male and females with an initial average body weight of 9.83 ± 0.5 kg were studied for 28 days. They were given ad libitum access to water and feed and randomly allotted to one of the following groups: control group (C) or aristolochic acid group (AA). They were fed a maize-soybean-meal-based diet contaminated or not with 0.25mgAA/kg. To profile miRNA in the kidneys of pigs, microarrays and bioinformatics approaches were applied to analyze the miRNA in the kidney of control and AA intoxicated pigs. After normalization, our results have shown that a total of 5 known miRNAs and 4 novel miRNAs had different profiling in the kidney of intoxicated animals versus control ones. Expression of miR-32-5p, miR-497-5p, miR-423-3p, miR-218-5p, miR-128-3p were up-regulated by 0.25mgAA/kg feed, while the expression of miR-9793-5p, miR-9835-3p, miR-9840-3p, miR-4334-5p was down-regulated. The microRNA profiling in kidney of intoxicated animals was associated with modified expression of target genes as: RICTOR, LASP1, SFRP2, DKK2, BMI1, RAF1, IGF1R, MAP2K1, WEE1, HDGF, BCL2, EIF4E etc, involved in cell division cycle, apoptosis, cell differentiation and cell migration, cell signaling, cancer etc. In conclusion, this study provides new data concerning the microRNA profiling in kidney after aristolochic acid intoxications with important implications for human and animal health.

Keywords: aristolochic acid, kidney, microRNA, swine

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Authors: Andi Fallahi, Bona Ryan Situmeang

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The Construction Industry is notoriously risky. Much of the preparatory paperwork that precedes construction project can be viewed as the formulation of risk allocation between the owner and the Contractor. The Owner is taking the risk that his project will not get built on the schedule that it will not get built for what he has budgeted and that it will not be of the quality he expected. The Contractor Face a multitude of risk. One of them is an unforeseen condition at the construction site. The Owner usually has the upper hand here if the unforeseen condition occurred. Site data contained in Ground Investigation report is often of significant contractual importance in disputes related to the unforeseen ground condition. A ground investigation can never fully disclose all the details of the underground condition (Risk of an unknown ground condition can never be 100% eliminated). Adipala Coal Fired Steam Power Plant (CSFPP) 1 x 660 project is one of the large CSFPP project in Indonesia based on Engineering, Procurement, and Construction (EPC) Contract. Unforeseen Ground Condition it’s responsible by the Contractor has stipulated in the clausal of Contract. In the implementation, there’s indicated unforeseen ground condition at Circulating Water Pump House (CWPH) area which caused the Contractor should be changed the Method of Work that give big impact against Time of Completion and Cost Project. This paper tries to analyze the best way for allocating the risk between The Owner and The Contractor. All parties that allocating of sharing risk fairly can ultimately save time and money for all parties, and get the job done on schedule for the least overall cost.

Keywords: unforeseen ground condition, coal fired steam power plant, circulating water pump house, Indonesia

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Authors: Leona Ondrejikova, Martin Hill, Antonin Parizek

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The incidence of gestational diabetes mellitus (GDM) is higher in women predisposed to developing intrahepatic cholestasis of pregnancy (ICP). Both diseases are associated with altered steroidogenesis when compared with none-ICP controls. However, the effect of GDM on circulating steroids in ICP patients remains unclear. The question remains, whether the levels of circulating steroids differ between ICP patients with and without GDM. In total 10 ICP patients without GDM (ICP+GDM-), 7 ICP patients with GDM (ICP+GDM+), and 15 controls (ICP-GDM-) were monitored during late gestation, at labor, and during three periods postpartum (day 5, week 3, and week 6 postpartum) (Šimják et al., 2018). The relationships between steroid profiles and patients’ status were evaluated using the ANOVA model consisting of subject factor, between-subject factors Group (ICP+GDM+, ICP+GDM-, ICP-GDM-), gestational age at the diagnosis of ICP and gestational age at labor, and within-subject factor Stage and ICP × Stage interaction. The levels of the C21 and C19 Δ5 steroids and 5α/β-reduced C19 steroids were highest in ICP+GDM+, while those for the ICP-GDM-, and ICP+GDM- groups were lower. In the C21 Δ4 steroids and their 5α/β-reduced metabolites, the steroid levels were highest in the ICP+GDM-, intermediate in the ICP-GDM- and lowest in the ICP+GDM+ group. This higher concentration in ICP+GDM- group may be of importance as the 5α-pregnane-3α,20α-diol disulfate, is considered as the substance inducing ICP. In general, these data show that the comorbidity with GDM substantially changes the steroidome in ICP patients towards the higher activity of steroid CYP17A1 lyase step in adrenal zona reticularis reduced CYP17A1 hydroxylase step in zona fasciculata. This is consistent with our previously published hypothesis about the critical role of maternal zona reticularis in the pathophysiology of ICP. Our present data also indicate that the comorbidity with GDM might moderate the gravity of the ICP in this way.

Keywords: CYP17A1, GC-MS, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy

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Authors: F. Clara Fang, Hernan Castaneda

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The Connecticut Department of Transportation (ConnDOT) has constructed four roundabouts in the State of Connecticut within the past ten years. VISSIM traffic simulation software was utilized to analyze these roundabouts during their design phase. The queue length and level of service observed in the field appear to be better than predicted by the VISSIM model. The objectives of this project are to: identify VISSIM input variables most critical to accurate modeling; recommend VISSIM calibration factors; and, provide other recommendations for roundabout traffic operations modeling. Traffic data were collected at these roundabouts using Miovision Technologies. Cameras were set up to capture vehicle circulating activity and entry behavior for two weekdays. A large sample size of filed data was analyzed to achieve accurate and statistically significant results. The data extracted from the videos include: vehicle circulating speed; critical gap estimated by Maximum Likelihood Method; peak hour volume; follow-up headway; travel time; and, vehicle queue length. A VISSIM simulation of existing roundabouts was built to compare both queue length and travel time predicted from simulation with measured in the field. The research investigated a variety of simulation parameters as calibration factors for describing driver behaviors at roundabouts. Among them, critical gap is the most effective calibration variable in roundabout simulation. It has a significant impact to queue length, particularly when the volume is higher. The results will improve the design of future roundabouts in Connecticut and provide decision makers with insights on the relationship between various choices and future performance.

Keywords: driver critical gap, roundabout analysis, simulation, VISSIM modeling

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Authors: B. Gonzalez-Yebra, H. Barajas, P. Palomares, M. Hernandez, O. Torres, M. Ayala, A. L. González, G. Vazquez-Ortiz, M. L. Guzman

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Leukemia arises by molecular alterations of the normal hematopoietic stem cell (HSC) transforming it into a leukemic stem cell (LSC) with high cell proliferation, self-renewal, and cell differentiation. Chronic myeloid leukemia (CML) originates from an LSC-leading to elevated proliferation of myeloid cells and acute lymphoblastic leukemia (ALL) originates from an LSC development leading to elevated proliferation of lymphoid cells. In both cases, LSC can be identified by multicolor flow cytometry using several antibodies. However, to date, LSC levels in peripheral blood (PB) are not established well enough in ALL and CML patients. On the other hand, the detection of the minimal residue disease (MRD) in leukemia is mainly based on the identification of the mRNA bcr-abl gene in CML patients and some other genes in ALL patients. There is no a properly biomarker to detect MDR in both types of leukemia. The objective of this study was to determine mRNA bcr-abl and the percentage of LSC in peripheral blood of patients with CML and ALL and identify a possible association between the amount of LSC in PB and clinical data. We included in this study 19 patients with Leukemia. A PB sample was collected per patient and leukocytes were obtained by Ficoll gradient. The immunophenotype for LSC CD34+ was done by flow cytometry analysis with CD33, CD2, CD14, CD16, CD64, HLA-DR, CD13, CD15, CD19, CD10, CD20, CD34, CD38, CD71, CD90, CD117, CD123 monoclonal antibodies. In addition, to identify the presence of the mRNA bcr-abl by RT-PCR, the RNA was isolated using TRIZOL reagent. Molecular (presence of mRNA bcr-abl and LSC CD34+) and clinical results were analyzed with descriptive statistics and a multiple regression analysis was performed to determine statistically significant association. In total, 19 patients (8 patients with ALL and 11 patients with CML) were analyzed, 9 patients with de novo leukemia (ALL = 6 and CML = 3) and 10 under treatment (ALL = 5 and CML = 5). The overall frequency of mRNA bcr-abl was 31% (6/19), and it was negative in ALL patients and positive in 80% in CML patients. On the other hand, LSC was determined in 16/19 leukemia patients (%LSC= 0.02-17.3). The Novo patients had higher percentage of LSC (0.26 to 17.3%) than patients under treatment (0 to 5.93%). The amount of LSC was significantly associated with the amount of LSC were: absence of treatment, the absence of splenomegaly, and a lower number of leukocytes, negative association for the clinical variables age, sex, blasts, and mRNA bcr-abl. In conclusion, patients with de novo leukemia had a higher percentage of circulating LSC than patients under treatment, and it was associated with clinical parameters as lack of treatment, absence of splenomegaly and a lower number of leukocytes. The mRNA bcr-abl detection was only possible in the series of patients with CML, and molecular detection of LSC could be identified in the peripheral blood of all leukemia patients, we believe the identification of circulating LSC may be used as biomarker for the detection of the MRD in leukemia patients.

Keywords: stem cells, leukemia, biomarkers, flow cytometry

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Authors: Sumera, Sanila Amber, Fatima Javed Mirza, Amjad Ali, Saadia Zahid

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Glioblastoma multiforme (GBM) is a widely spread and fatal primary brain tumor with an increased risk of relapse in spite of aggressive treatment. The current procedures for GBM diagnosis include invasive procedures i.e. resection or biopsy, to acquire tumor mass. Implementation of negligibly invasive tests as a potential diagnostic technique and biofluid-based monitoring of GBM stresses on discovering biomarkers in CSF and blood. Therefore, we performed a comprehensive in silico analysis to identify potential circulating biomarkers for GBM. Initially, six gene and protein databases were utilized to mine brain-specific proteins. The resulting proteins were filtered using a channel of five tools to predict the secretory proteins. Subsequently, the expression profile of the secreted proteins was verified in the brain and blood using two databases. Additional verification of the resulting proteins was done using Plasma Proteome Database (PPD) to confirm their presence in blood. The final set of proteins was searched in literature for their relationship with GBM, keeping a special emphasis on secretome proteome. 2145 proteins were firstly mined as brain-specific, out of which 69 proteins were identified as secretory in nature. Verification of expression profile in brain and blood eliminated 58 proteins from the 69 proteins, providing a final list of 11 proteins. Further verification of these 11 proteins further eliminated 2 proteins, giving a final set of nine secretory proteins i.e. OPCML, NPTX1, LGI1, CNTN2, LY6H, SLIT1, CREG2, GDF1 and SERPINI1. Out of these 9 proteins, 7 were found to be linked to GBM, whereas 2 proteins are not investigated in GBM so far. We propose that these secretory proteins can serve as potential circulating biomarker signatures of GBM and will facilitate the development of minimally invasive diagnostic methods and novel therapeutic interventions for GBM.

Keywords: glioblastoma multiforme, secretory proteins, brain secretome, biomarkers

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Authors: Vasishtha Avadhani Upadrasta, Mradul Kumar Daga, Smita Kaushik

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Background: Caffeine consumption has skyrocketed in the recent decades as we try to match pace with the machines. Studies have been conducted on animals and a few on humans, mainly on the acute effects of high-dose caffeine intake. Almost none have been conducted on the chronic effects of caffeine consumption. This study involved Medical professionals as case subjects, who consumed caffeine daily. Methods: This study, over a period of 3 months, involved 96 volunteers (chosen randomly w.r.t. gender and field in medical fraternity), including people who drank >500mg of caffeine a day to people who consumed none. People with any co-morbidities at all were excluded straight away. Two sets of blood samples were drawn and assessed. Three groups were created, Group 1 (>200mg caffeine/day) and Group 2 (15-200 mg caffeine/day) and Group 3 (<200mg Caffeine/day). Results: The result of the study found that exposure to caffeine at doses >200mg/day for more than 6 months leads to a significant difference in circulating free T3 [(-0.96 pmol/L ± 0.07) = (-18.5%), CI 95%, p = .000024] and Cortisol [(-123 nmol/L ± 9.8) = (-46.8%), CI 95%, p = .00029] hormones but shows an insignificant effect on circulating TSH [0.4 mIU/L, CI 95%, p=.37] and ACTH [(-3.2 pg/ml ± 0.3), CI 95%, p = .53) hormones, which stay within normal physiological ranges, irrespective of the daily dose of consumption. Results also highlight that women are more susceptible to decrement in fT3 than men (Relative Risk =1.58, ANOVA F-static = 7.15, p = 0.0105). Conclusions: Caffeine consumption in excess of 200mg/day, for more than or equal to 6 months, causes significant derangement in basal fT3 and Cortisol hormone levels, without affecting the TSH and ACTH (regulatory) hormone levels, indicating disturbance of action at the peripheral and/or cellular levels, possibly via the Paraventricular Nucleus –Leptin-CAR-Adenosine interactions. Women are more susceptible to decrement in fT3 levels than men (at same dose of caffeine).

Keywords: ACTH, adrenals, caffeine, cortisol, thyroid, thyroxin, TSH

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Authors: Miao Zhang, Limin Liu, Feng Zhi, Panpan Niu, Mengya Yang, Xuemei Zhu, Ying Diao, Jun Wang, Ying Zhao

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Background and Aims: Clinical studies have demonstrated that serum semicarbazide-sensitive amine oxidase (SSAO) activities positively correlate with the progression of atherosclerosis. The aim of the present study is to investigate the effect of SSAO inactivation on the development of atherosclerosis. Methods: Female LDLr knockout (KO) mice were given the Western-type diet for 6 and 9 weeks to induce the formation of early and advanced lesions, and semicarbazide (SCZ, 0.125%) was added into the drinking water to inactivate SSAO in vivo. Results: Despite no impact on plasma total cholesterol levels, abrogation of SSAO by SCZ not only resulted in the enlargement of both early (1.5-fold, p=0.0043) and advanced (1.8-fold, p=0.0013) atherosclerotic lesions, but also led to reduced/increased lesion contents of macrophages/smooth muscle cells (SMCs) (macrophage: ~0.74-fold, p=0.0002(early)/0.0016(advanced); SMC: ~1.55-fold, p=0.0003(early) /0.0001(advanced)), respectively. Moreover, SSAO inactivation inhibited the migration of circulating monocytes into peripheral tissues and reduced the amount of circulating Ly6Chigh monocytes (0.7-fold, p=0.0001), which may account for the reduced macrophage content in lesions. In contrast, the increased number of SMCs in lesions of SCZ-treated mice is attributed to an augmented synthetic vascular SMC phenotype switch as evidenced by the increased proliferation of SMCs and accumulation of collagens in vivo. Conclusion: SSAO inactivation by SCZ promotes the phenotypic switch of SMCs and the development of atherosclerosis. The enzymatic activity of SSAO may thus represent a potential target in the prevention and/or treatment of atherosclerosis.

Keywords: atherosclerosis, phenotype switch of smooth muscle cells, SSAO/VAP-1, semicarbazide

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Authors: Bahar Tunctan, Sefika Pinar Kucukkavruk, Meryem Temiz-Resitoglu, Demet Sinem Guden, Ayse Nihal Sari, Seyhan Sahan-Firat

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We hypothesized that rexinoids such as bexarotene, a selective retinoid X receptor α (RXRα) agonist, may be beneficial for preventing mortality due to inflammation associated with increased expression/activity of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS). Therefore, we investigated effects of bexarotene on the changes in circulating protein levels of iNOS (an index for systemic iNOS expression), myeloperoxidase (MPO) (an index for systemic inflammation), and lactate dehydrogenase (LDH) (an index for systemic tissue injury) in LPS-induced systemic inflammation model resulting in septic shock in rats. Rats were injected with saline (4 ml/kg; i.p.), LPS (10 mg/kg; i.p.), dimethylsulphoxide (4 ml/kg, 0.1%; s.c.) at time 0. Mean arterial blood pressure and heart rate were measured using a tail-cuff device. Bexarotene (0.03, 0.1, 0.3, and 1 mg/kg; s.c.) was administered to separate groups of rats 1 h after injection of saline or LPS. The rats were sacrificed 4 h after saline or LPS injection and blood was collected for measurement of serum iNOS, MPO, and LDH protein levels. Blood pressure decreased by 31 mmHg and heart rate increased by 63 bpm in the LPS-treated rats. Bexarotene at 0.3 and 1 mg/kg doses caused 20% mortality 4 h after LPS injection. In the LPS-treated rats, serum iNOS, MPO, and LDH protein levels were increased. Bexarotene only at 0.1 mg/kg dose prevented the LPS-induced hypotension and increased in iNOS, MPO, and LDH protein levels. These data are consistent with the view that a decrease in systemic iNOS levels contributes to the beneficial effect of bexarotene to prevent the hypotension associated with inflammation and tissue injury during rat endotoxemia. [This work was financially supported by The Scientific and Technological Research Council of Turkey (SBAG-109S121)].

Keywords: bexarotene, inflammation, iNOS, lipopolisaccharide, RXRa

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Authors: Grace McCambridge, Alanna Keady, Madhur Agrawal, Dequina Nicholas Alvarado, Barbara Nikolajczyk, Leena Panneerseelan-Bharath

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Age is a non-modifiable risk factor for the inflammation that underlies pathologies such as type 2 diabetes mellitus (T2DM). Inflammation, as indicated by circulating cytokines, rises in aging, but mechanisms that promote this ‘inflammaging’ remain poorly defined. Furthermore, downstream consequences of inflammaging, including the development of an inflammatory profile that predicts comorbidities like T2DM, remain speculative. We tested the possibility that natural aging-associated changes in autophagy, a process that is compromised in both aging and T2DM, regulates inflammatory profiles in older subjects. Our data showed that circulating CD4⁺ T cells from older compared to younger subjects have (i) defects in autophagy; (ii) higher mitochondria accumulation; (iii) a failure to metabolically shift from oxidative phosphorylation to anaerobic glycolysis upon αCD3/CD28 activation; (iv) more reactive oxygen species (ROS) accumulation; and (v) a cytokine profile that recapitulates the Th17 profile that predicts T2DM. ROS scavenging in cells from older subjects restored mitochondrial mass and membrane potential (indicators of improved autophagy) and reduced Th17 cytokines to amounts made by T cells from younger subjects. Knock-down of the autophagy protein Atg3 in T cells from younger subjects increased mitochondrial accumulation and Th17 cytokines. To begin translating these findings to clinical practice, we showed that physiological concentrations of the diabetes drug metformin (100 µM) added in vitro enhanced autophagy, prevented mitochondria and ROS accumulation, increased anaerobic glycolysis, and decreased Th17 cytokines in activated CD4⁺ T cells from older subjects. Metformin therefore improves autophagy and multiple downstream pro-inflammatory mechanisms CD4⁺ T cells from older subjects. We conclude that autophagy improvement ameliorates the development of a T2DM-predictive Th17 profile in aging, and thus holds promise for delay or prevention of aging-associated metabolic decline.

Keywords: autophagy, mitochondrial turnover, ROS, glycolysis

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Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li

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Determinants of growth and metastasis in cancer remain of great interest to define. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. Here, we report the definition of miR-346 as an oncogenic microRNA that facilitates non-small cell lung cancer (NSCLC) cell growth and metastasis. XPC, an important DNA damage recognition factor in nucleotide excision repair was defined as a target for down-regulation by miR-346, functioning through direct interaction with the 3'-UTR of XPC mRNA. Blocking miR-346 by an antagomiR was sufficient to inhibit NSCLC cell growth and metastasis, an effect that could be phenol-copied by RNAi-mediated silencing of XPC. In vivo studies established that miR-346 overexpression was sufficient to promote tumor growth by A549 cells in xenografts mice, relative to control cells. Overall, our results defined miR-346 as an oncogenic miRNA in NSCLC, the levels of which contributed to tumor growth and invasive aggressiveness.

Keywords: microRNA-346, miR-346, XPC, non-small cell lung cancer, oncogenesis

Procedia PDF Downloads 278

Authors: Gabriela C. Caldas, Fernanda C. Jacome, Arthur da C. Rasinhas, Ortrud M. Barth, Flavia B. dos Santos, Priscila C. G. Nunes, Yuli R. M. de Souza, Pedro Paulo de A. Manso, Marcelo P. Machado, Debora F. Barreto-Vieira

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The establishment of animal models for studies of DENV infections has been challenging, since circulating epidemic viruses do not naturally infect nonhuman species. Such studies are of great relevance to the various areas of dengue research, including immunopathogenesis, drug development and vaccines. In this scenario, the main objective of this study is to verify possible morphological changes, as well as the presence of antigens and viral RNA in lung samples from BALB/c mice experimentally infected with an epidemic and non-neuroadapted DENV-3 strain. Male BALB/c mice, 2 months old, were inoculated with DENV-3 by intravenous route. After 72 hours of infection, the animals were euthanized and the lungs were collected. Part of the samples was processed by standard technique for analysis by light and transmission electronic microscopies and another part was processed for real-time PCR analysis. Morphological analyzes of lungs from uninfected mice showed preserved tissue areas. In mice infected with DENV-3, the analyzes revealed interalveolar septum thickening with presence of inflammatory infiltrate, foci of alveolar atelectasis and hyperventilation, bleeding foci in the interalveolar septum and bronchioles, peripheral capillary congestion, accumulation of fluid in the blood capillary, signs of interstitial cell necrosis presence of platelets and mononuclear inflammatory cells circulating in the capillaries and/or adhered to the endothelium. In addition, activation of endothelial cells, platelets, mononuclear inflammatory cell and neutrophil-type polymorphonuclear inflammatory cell evidenced by the emission of cytoplasmic membrane prolongation was observed. DEN-like particles were seen in the cytoplasm of endothelial cells. The viral genome was recovered from 3 in 12 lung samples. These results demonstrate that the BALB / c mouse represents a suitable model for the study of the histopathological changes induced by DENV infection in the lung, with tissue alterations similar to those observed in human cases of DEN.

Keywords: BALB/c mice, dengue, histopathology, lung, ultrastructure

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Authors: Amir Seyfoori, Ehsan Samiei, Mohsen Akbari

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The use of microtechnology for detection and high yield isolation of circulating tumor cells (CTCs) has shown enormous promise as an indication of clinical metastasis prognosis and cancer treatment monitoring. The Immunomagnetic assay has been also coupled to microtechnology to improve the selectivity and efficiency of the current methods of cancer biomarker isolation. In this way, generation and configuration of the local high gradient magnetic field play essential roles in such assay. Additionally, considering the intrinsic heterogeneity of cancer cells, real-time analysis of isolated cells is necessary to characterize their responses to therapy. Totally, on-chip isolation and monitoring of the specific tumor cells is considered as a pressing need in the way of modified cancer therapy. To address these challenges, we have developed a bi-layer magnetic-based microfluidic chip for enhanced CTC detection and capturing. Micromagnet arrays at the bottom layer of the chip were fabricated using a new method of magnetic nanoparticle paste deposition so that they were arranged at the center of the chain microchannel with the lowest fluid velocity zone. Breast cancer cells labelled with EPCAM-conjugated smart microgels were immobilized on the tip of the micromagnets with greater localized magnetic field and stronger cell-micromagnet interaction. Considering different magnetic nano-powder usage (MnFe2O4 & gamma-Fe2O3) and micromagnet shapes (ellipsoidal & arrow), the capture efficiency of the systems was adjusted while the higher CTC capture efficiency was acquired for MnFe2O4 arrow micromagnet as around 95.5%. As a proof of concept of on-chip tumor cell monitoring, magnetic smart microgels made of thermo-responsive poly N-isopropylacrylamide-co-acrylic acid (PNIPAM-AA) composition were used for both purposes of targeted cell capturing as well as cell monitoring using antibody conjugation and fluorescent dye loading at the same time. In this regard, magnetic microgels were successfully used as cell tracker after isolation process so that by raising the temperature up to 37⁰ C, they released the contained dye and stained the targeted cell just after capturing. This microfluidic device was able to provide a platform for detection, isolation and efficient real-time analysis of specific CTCs in the liquid biopsy of breast cancer patients.

Keywords: circulating tumor cells, microfluidic, immunomagnetic, cell isolation

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Authors: Angelica Corcoran, Fredrik Lind, Pavleta Knutsson, Henrik Thunman

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Solid waste volumes are at current predominately deposited on landfill. Furthermore, the impending climate change requires new solutions for a sustainable future energy mix. Currently, solid waste is globally utilized to small extent as fuel during combustion for heat and power production. Due to its variable composition and size, solid waste is considered difficult to combust and requires a technology with high fuel flexibility. One of the commercial technologies used for combustion of such difficult fuels is circulating fluidized beds (CFB). In a CFB boiler, fine particles of a solid material are used as 'bed material', which is accelerated by the incoming combustion air that causes the bed material to fluidize. The chosen bed material has conventionally been silica sand with the main purpose of being a heat carrier, as it transfers heat released by the combustion to the heat-transfer surfaces. However, the release of volatile compounds occurs rapidly in comparison with the lateral mixing in the combustion chamber. To ensure complete combustion a surplus of air is introduced, which decreases the total efficiency of the boiler. In recent years, the concept of partly or entirely replacing the silica sand with an oxygen carrier as bed material has been developed. By introducing an oxygen carrier to the combustion chamber, combustion can be spread out both temporally and spatially in the boiler. Specifically, the oxygen carrier can take up oxygen from the combustion air where it is in abundance and release it to combustible gases where oxygen is in deficit. The concept is referred to as oxygen carrier aided combustion (OCAC) where the natural ore ilmenite (FeTiO3) has been the oxygen carrier used. The authors have validated the oxygen buffering ability of ilmenite during combustion of biomass in Chalmers 12-MWth CFB boiler in previous publications. Furthermore, the concept has been demonstrated on full industrial scale during combustion of municipal solid waste (MSW) in E.ON’s 75 MWth CFB boiler. The experimental campaigns have showed increased mass transfer of oxygen inside the boiler when combustion both biomass and MSW. As a result, a higher degree of burnout is achieved inside the combustion chamber and the plant can be operated at a lower surplus of air. Moreover, the buffer of oxygen provided by the oxygen carrier makes the system less sensitive to disruptions in operation. In conclusion, combusting difficult fuels with OCAC results in higher operation stability and an increase in boiler efficiency.

Keywords: OCAC, ilmenite, combustion, CFB

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Authors: Henry Memczak, Marc Hovestaedt, Bernhard Ay, Sandra Saenger, Thorsten Wolff, Frank F. Bier

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The influenza viruses cause flu epidemics every year and serious pandemics in larger time intervals. The only cost-effective protection against influenza is vaccination. Due to rapid mutation continuously new subtypes appear, what requires annual reimmunization. For a correct vaccination recommendation, the circulating influenza strains had to be detected promptly and exactly and characterized due to their antigenic properties. During the flu season 2016/17, a wrong vaccination recommendation has been given because of the great time interval between identification of the relevant influenza vaccine strains and outbreak of the flu epidemic during the following winter. Due to such recurring incidents of vaccine mismatches, there is a great need to speed up the process chain from identifying the right vaccine strains to their administration. The monitoring of subtypes as part of this process chain is carried out by national reference laboratories within the WHO Global Influenza Surveillance and Response System (GISRS). To this end, thousands of viruses from patient samples (e.g., throat smears) are isolated and analyzed each year. Currently, this analysis involves complex and time-intensive (several weeks) animal experiments to produce specific hyperimmune sera in ferrets, which are necessary for the determination of the antigen profiles of circulating virus strains. These tests also bear difficulties in standardization and reproducibility, which restricts the significance of the results. To replace this test a peptide-based assay for influenza virus subtyping from corresponding virus samples was developed. The differentiation of the viruses takes place by a set of specifically designed peptidic recognition molecules which interact differently with the different influenza virus subtypes. The differentiation of influenza subtypes is performed by pattern recognition guided by machine learning algorithms, without any animal experiments. Synthetic peptides are immobilized in multiplex format on various platforms (e.g., 96-well microtiter plate, microarray). Afterwards, the viruses are incubated and analyzed comparing different signaling mechanisms and a variety of assay conditions. Differentiation of a range of influenza subtypes, including H1N1, H3N2, H5N1, as well as fine differentiation of single strains within these subtypes is possible using the peptide-based subtyping platform. Thereby, the platform could be capable of replacing the current antigenic characterization of influenza strains using ferret hyperimmune sera.

Keywords: antigenic characterization, influenza-binding peptides, influenza subtyping, influenza surveillance

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Authors: Farah Diab, Mohamad Khalil, Francesca Storace, Francesca Baldini, Piero Portincasaa, Giulio Lupidi, Laura Vergani

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Thymbra spicata is a thyme-like plant belonging to the Lamiaceae family that shows a global distribution, especially in the eastern Mediterranean region. Leaves of T. spicata contain large amounts of phenols such as phenolic acids (rosmarinic acid), phenolic monoterpenes (carvacrol), and flavonoids. In Lebanon, T. spicata is currently used as a culinary herb in salad and infusion, as well as for traditional medicinal purposes. Carvacrol (5-isopropyl-2-methyl phenol), the most abundant polyphenol in the organic extract and essential oils, has a great array of pharmacological properties. In fact, carvacrol is largely employed as a food additive and neutraceutical agent. Our aim is to investigate the beneficial effects of T. spicata ethanolic extract (TE) and its main component, carvacrol, using in vitro models of hepatic steatosis and endothelial dysfunction. As a further point, we focused on investigating if and how the binding of carvacrol to albumin, the physiological transporter for drugs in the blood, might be altered by the presence of high levels of fatty acids (FAs), thus impairing the carvacrol bio-distribution in vivo. For that reason, hepatic FaO cells treated with exogenous FAs such as oleate and palmitate mimic hepatosteatosis; endothelial HECV cells exposed to hydrogen peroxide are a model of endothelial dysfunction. In these models, we measured lipid accumulation, free radical production, lipoperoxidation, and nitric oxide release before and after treatment with carvacrol. The carvacrol binding to albumin with/without high levels of long-chain FAs was assessed by absorption and emission spectroscopies. Our findings show that both TE and carvacrol (i) counteracted lipid accumulation in hepatocytes by decreasing the intracellular and extracellular lipid contents in steatotic FaO cells; (ii) decreased oxidative stress in endothelial cells by significantly reducing lipoperoxidation and free radical production, as well as, attenuating the nitric oxide release; (ii) high levels of circulating FAs reduced the binding of carvacrol to albumin. The beneficial effects of TE and carvacrol on both hepatic and endothelial cells point to a nutraceutical potential. However, high levels of circulating FAs, such as those occurring in metabolic disorders, might hinder the carvacrol transport, bio-distribution, and pharmacodynamics.

Keywords: carvacrol, endothelial dysfunction, fatty acids, non-alcoholic fatty liver diseases, serum albumin

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Authors: Jae-Soo Do, Kyoung-Seok Kim

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The crisis theory of Samsung Electronics is becoming a hot topic today. Due to its performance deterioration, the share of Samsung Electronics lost its driving power. Considering the public opinion about the bad rumors circulating within the company, it is quite probable that the company is currently facing crisis. Then, what company has challenged the stronghold of Samsung Electronics? At the core of the crisis is 'Xiaomi' who snatched the first place of the market share, pushing Samsung Electronics aside in the Chinese market. In June 2010, Xiaomi, established by eight co-founders, has been showing a miraculous growth as the smart device manufacturer, taking the first place in the Chinese market and coming in fifth worldwide in just four years after its establishment. How did Xiaomi instantaneously achieve enough growth to overtake Samsung? Thus, we have conducted a comparative analysis on the competitive strategies of Samsung and Xiaomi.

Keywords: Samsung, Xiaomi, industrial attractiveness, VIRO

Procedia PDF Downloads 355

Authors: Xi Chen, King-Yip Cheng

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Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

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Authors: Antonio Pratelli, Lorenzo Brocchini, Reginald Roy Souleyrette

Abstract:

A rotary is a traffic circle intersection where vehicles entering from branches give priority to circulating flow. Vehicles entering the intersection from converging roads move around the central island and weave out of the circle into their desired exiting branch. This creates merging and diverging conflicts among any entry and its successive exit, i.e., a section. Therefore, rotary capacity models are usually based on the weaving of the different movements in any section of the circle, and the maximum rate of flow value is then related to each weaving section of the rotary. Nevertheless, the single-section capacity value does not lead to the typical performance characteristics of the intersection, such as the entry average delay which is directly linked to its level of service. From another point of view, modern roundabout capacity models are based on the limitation of the flow entering from the single entrance due to the amount of flow circulating in front of the entrance itself. Modern roundabouts capacity models generally lead also to a performance evaluation. This paper aims to incorporate a modern roundabout capacity model into an old rotary capacity method to obtain from the latter the single input capacity and ultimately achieve the related performance indicators. Put simply; the main objective is to calculate the average delay of each single roundabout entrance to apply the most common Highway Capacity Manual, or HCM, criteria. The paper is organized as follows: firstly, the rotary and roundabout capacity models are sketched, and it has made a brief introduction to the model combination technique with some practical instances. The successive section is deserved to summarize the TRRL old rotary capacity model and the most recent HCM-7th modern roundabout capacity model. Then, the two models are combined through an iteration-based algorithm, especially set-up and linked to the concept of roundabout total capacity, i.e., the value reached due to a traffic flow pattern leading to the simultaneous congestion of all roundabout entrances. The solution is the average delay for each entrance of the rotary, by which is estimated its respective level of service. In view of further experimental applications, at this research stage, a collection of existing rotary intersections operating with the priority-to-circle rule has already started, both in the US and in Italy. The rotaries have been selected by direct inspection of aerial photos through a map viewer, namely Google Earth. Each instance has been recorded by location, general urban or rural, and its main geometrical patterns. Finally, conclusion remarks are drawn, and a discussion on some further research developments has opened.

Keywords: mixed methods, old rotary and modern roundabout capacity models, total capacity algorithm, level of service estimation

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Authors: Önder M. Özdem

Abstract:

Producing and circulating films of professional standards have become technically easier with the development and widespread use of digital recording and distribution technologies. Additionally, film festivals on common platforms have rapidly increased in numbers and diversity. On the one hand, no-charge applications result in excessive submissions; thus, it complicates the evaluation and selection process. On the other hand, festival’s high submission fees may make the distribution of films with a limited budget very difficult. Inspired by the author’s engagement with the film industry as both a pre-jury member of an international film festival and an applicant to many festivals, this study discusses the causes and consequences of the increasing commercialization of film festivals. The author’s double identity, both as a jury and an applicant, provides a comparative perspective through which one can unfold the different dimensions and dynamics in the film production and distribution processes.

Keywords: commercialization, film distribution, film festivals, film production

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Authors: Mahdi Rahaie

Abstract:

MicroRNAs are a novel class of small RNAs which regulate gene expression by translational repression or degradation of messenger RNAs. To produce sensitive, simple and cost-effective assays for microRNAs, detection is in urgent demand due to important role of these biomolecules in progression of human disease such as Alzheimer’s, Multiple sclerosis, and some other neurodegenerative diseases. Herein, we report several novel, sensitive and specific microRNA nanobiosensors which were designed based on colorimetric and fluorescence detection of nanoparticles and hybridization chain reaction amplification as an enzyme-free amplification. These new strategies eliminate the need for enzymatic reactions, chemical changes, separation processes and sophisticated equipment whereas less limit of detection with most specify are acceptable. The important features of these methods are high sensitivity and specificity to differentiate between perfectly matched, mismatched and non-complementary target microRNAs and also decent response in the real sample analysis with blood plasma. These nanobiosensors can clinically be used not only for the early detection of neuro diseases but also for every sickness related to miRNAs by direct detection of the plasma microRNAs in real clinical samples, without a need for sample preparation, RNA extraction and/or amplification.

Keywords: hybridization chain reaction, microRNA, nanobiosensor, neurodegenerative diseases

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Authors: Zahra Solgi, Hossein Rassi

Abstract:

Colorectal cancer (CRC) is a multi-step disease, and chronic gastric infection with H. pylori could play a role in one or more of the steps in this pathogenic process. Polymorphisms in several miRNAs are considered to increase the risk for the development of CRC by controlling proliferation, apoptosis and H. pylori pathogenesis. Therefore, the aim of this study was to investigate miRNA146a rs2910164 polymorphism and Helicobacter pylori infection in CRC. A total of 65 patients with CRC were divided into 2 groups: 28 patients < 50 years of age and 37 patients ≥ 50 years of age. DNA was extracted from all samples by a standard method and H. pylori cagA and miRNA146a rs2910164 genotypes were determined by PCR method. The results show that there was no significant difference in the frequency of H. pylori cagA gene between the two groups but there was a significant difference in the distribution of rs2910164 genotypes in patients < 50 years of age with the p-value of 0.05 and odds ratio equal to 2.69. On other hand, patients < 50 years of age with genotype CC of miRNA146a showed a significant difference in CRC risk. Furthermore, there was a significant correlation between rs2910164 CC genotype with Helicobacter pylori infection in patients < 50 years of age. The present study suggests that the CC genotype of miRNA146a in combination with H. pylori infection can be effective as risk factors and molecular markers for early diagnosis and treatment of CRC.

Keywords: colorectal cancer, Helicobacter pylori, miRNA146a, rs2910164 polymorphism

Procedia PDF Downloads 124