Search results for: pathways

Authors: Lu Yang, Keng Po Lai

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Metformin, a well-known clinical drug against diabetes, is found with potential anti-diabetic and anti-obese benefits, as reported in increasing evidences. However, the current clinical and experimental investigations are not to reveal the detailed mechanisms of metformin-anti-obesity/hypertension. We have used the bioinformatics strategy, including network pharmacology and molecular docking methodology, to uncover the key targets and pathways of bioactive compounds against clinical disorders, such as cancers, coronavirus disease. Thus, in this report, the in-silico approach was utilized to identify the hug targets, pharmacological function, and mechanism of metformin against obesity and hypertension. The networking analysis identified 154 differentially expressed genes of obesity and hypertension, 21 interaction genes, and 6 hug genes of metformin treating hypertensive obesity. As a result, the molecular docking findings indicated the potent binding capability of metformin with the key proteins, including interleukin 6 (IL-6) and chemokine (C-C motif) Ligand 2 (CCL2), in hypertensive obesity. The metformin-exerted anti-hypertensive obesity action involved in metabolic regulation, inflammatory reaction. And the anti-hypertensive obesity mechanisms of metformin were revealed, including regulation of inflammatory and immunological signaling pathways for metabolic homeostasis in tissue and microenvironmental melioration in blood pressure. In conclusion, our identified findings with bioinformatics analysis have demonstrated the detailed hug and pharmacological targets, biological functions, and signaling pathways of metformin treating hypertensive obesity.

Keywords: metformin, obesity, hypertension, bioinformatics findings

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Authors: Samantha Jeffries, Chontit Chuenurah

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Thailand incarcerates the largest number of women and has the highest female incarceration rate in South East Asia. Since the 1990s, there has been a substantial increase in the number, rate and proportion of women imprisoned. Thailand places a high priority on the gender specific contexts out of which offending arises and the different needs of women in the criminal justice system. This is manifested in work undertaken to guide the development of the United Nations Rules for the Treatment of Women Prisoners and Non-Custodial Measures for Women Offenders (the Bangkok Rules); adopted by the United Nations General Assembly in 2010. The Bangkok Rules make a strong statement about Thailand’s recognition of and commitment to the fair and equitable treatment of women throughout their contact with the criminal justice system including at sentencing and in prison. This makes the comparatively high use of imprisonment for women in Thailand particularly concerning and raises questions about the relationship between gender, crime and criminal justice. While there is an extensive body of research in Western jurisdictions exploring women’s pathways to prison, there is a relative dearth of methodologically robust research examining the possible gendered circumstances leading to imprisonment in Thailand. In this presentation, we will report preliminary findings from a qualitative study of women’s pathways to prison in Thailand. Our research aims were to ascertain: 1) the type, frequency, and context of criminal behavior that led to women’s incarceration, 2) women’s experiences of the criminal justice system, 3) the broader life experiences and circumstances that led women to prison in Thailand. In-depth life history interviews (n=77) were utilized to gain a comprehensive understanding of women’s journeys into prison. The interview schedule was open-ended consisting of prisoner responses to broad discussion topics. This approach provided women with the opportunity to describe significant experiences in their lives, to bring together distinct chronologies of events, and to analyze links between their varied life experiences, offending, and incarceration. Analyses showed that women’s journey’s to prison take one of eight pathways which tentatively labelled as follows, the: 1) harmed and harming pathway, 2) domestic/family violence victimization pathway, 3) drug connected pathway, 4) street woman pathway, 5) economically motivated pathway, 6) jealousy anger and/or revenge pathway, 7) naivety pathway, 8) unjust and/or corrupted criminal justice pathway. Each will be fully discussed during the presentation. This research is significant because it is the first in-depth methodologically robust exploration of women’s journeys to prison in Thailand and one of a few studies to explore gendered pathways outside of western contexts. Understanding women’s pathways into Thailand’s prisons is crucial to the development of effective planning, policy and program responses not only while women are in prison but also post-release. To best meet women’s needs in prison and effectively support their reintegration, we must have a comprehensive understanding of who these women are, what offenses they commit, the reasons that trigger their confrontations with the criminal justice system and the impact of the criminal justice system on them.

Keywords: pathways, prison, women, Thailand

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Authors: F. Saleh, F. Lyall, A. Abdulsid, L. Marks

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Background: Labour in human is a complex biological process that involves interactions of neurological, hormonal and inflammatory pathways, with the placenta being a key regulator of these pathways. It is known that uterine contractions and labour pain cause physiological changes in gene expression in maternal and fetal blood, and in placenta during labour. Oxidative and inflammatory stress pathways are implicated in labour and they may cause alteration of placental gene expression. Additionally, in placental tissues, labour increases the expression of genes involved in placental oxidative stress, inflammatory cytokines, angiogenic regulators and apoptosis. Recently, Hydrogen Sulphide (H2S) has been considered as an endogenous gaseous mediator which promotes vasodilation and exhibits cytoprotective anti-inflammatory properties. The endogenous H2S is synthesised predominantly by two enzymes: cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE). As the H2S pathway has anti-oxidative and anti-inflammatory characteristics thus, we hypothesised that the expression of CBS and CSE in placental tissues would alter during labour. Methods: CBS and CSE expressions were examined in placentas using western blotting and RT-PCR in inner, middle and outer placental zones in placentas obtained from healthy non labouring women who delivered by caesarian section. These were compared with the equivalent zone of placentas obtained from women who had uncomplicated labour and delivered vaginally. Results: No differences in CBS and CSE mRNA or protein levels were found between the different sites within placentas in either the labour or non-labour group. There were no significant differences in either CBS or CSE expression between the two groups at the inner site and middle site. However, at the outer site there was a highly significant decrease in CBS protein expression in the labour group when compared to the non-labour group (p = 0.002). Conclusion: To the best of author’s knowledge, this is the first report to suggest that, CBS is expressed in a spatial manner within the human placenta. Further work is needed to clarify the precise function and mechanism of this spatial regulation although it is likely that inflammatory pathways regulation is a complex process in which this plays a role.

Keywords: anti-inflammatory, hydrogen sulphide, labour, oxidative stress

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Authors: Anuj Tyagi, Balwinder Singh, Naveen Kumar B. T., Niraj K. Singh

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Characterization of diverse microbial communities in specific environment plays a crucial role in the better understanding of their functional relationship with the ecosystem. It is now well established that gut microbiome of fish is not the simple replication of microbiota of surrounding local habitat, and extensive species, dietary, physiological and metabolic variations in fishes may have a significant impact on its composition. Moreover, overuse of antibiotics in human, veterinary and aquaculture medicine has led to rapid emergence and propagation of antibiotic resistance genes (ARGs) in the aquatic environment. Microbial communities harboring specific ARGs not only get a preferential edge during selective antibiotic exposure but also possess the significant risk of ARGs transfer to other non-resistance bacteria within the confined environments. This phenomenon may lead to the emergence of habitat-specific microbial resistomes and subsequent emergence of virulent antibiotic-resistant pathogens with severe fish and consumer health consequences. In this study, gut microbiota of freshwater carp (Labeo rohita) was investigated by shotgun metagenomics to understand its taxonomic composition and functional capabilities. Metagenomic DNA, extracted from the fish gut, was subjected to sequencing on Illumina NextSeq to generate paired-end (PE) 2 x 150 bp sequencing reads. After the QC of raw sequencing data by Trimmomatic, taxonomic analysis by Kraken2 taxonomic sequence classification system revealed the presence of 36 phyla, 326 families and 985 genera in the fish gut microbiome. At phylum level, Proteobacteria accounted for more than three-fourths of total bacterial populations followed by Actinobacteria (14%) and Cyanobacteria (3%). Commonly used probiotic bacteria (Bacillus, Lactobacillus, Streptococcus, and Lactococcus) were found to be very less prevalent in fish gut. After sequencing data assembly by MEGAHIT v1.1.2 assembler and PROKKA automated analysis pipeline, pathway analysis revealed the presence of 1,608 Metacyc pathways in the fish gut microbiome. Biosynthesis pathways were found to be the most dominant (51%) followed by degradation (39%), energy-metabolism (4%) and fermentation (2%). Almost one-third (33%) of biosynthesis pathways were involved in the synthesis of secondary metabolites. Metabolic pathways for the biosynthesis of 35 antibiotic types were also present, and these accounted for 5% of overall metabolic pathways in the fish gut microbiome. Fifty-one different types of antibiotic resistance genes (ARGs) belonging to 15 antimicrobial resistance (AMR) gene families and conferring resistance against 24 antibiotic types were detected in fish gut. More than 90% ARGs in fish gut microbiome were against beta-lactams (penicillins, cephalosporins, penems, and monobactams). Resistance against tetracycline, macrolides, fluoroquinolones, and phenicols ranged from 0.7% to 1.3%. Some of the ARGs for multi-drug resistance were also found to be located on sequences of plasmid origin. The presence of pathogenic bacteria and ARGs on plasmid sequences suggested the potential risk due to horizontal gene transfer in the confined gut environment.

Keywords: antibiotic resistance, fish gut, metabolic pathways, microbial diversity

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Authors: Latife Merve Oktay, Berrin Tugrul

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Hydroxytyrosol (HT) is a phenolic phytochemical molecule derived from the hydrolysis of oleuropein, which originates during the maturation of the olives. It has recently received particular attention because of its antioxidant, anti-proliferative, pro-apoptotic and anti-inflammatory activities. In this study, we investigated the cytotoxic and apoptotic effects of hydroxytyrosol and its effects on phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase 1/2 (ERK 1/2) signaling pathways in human ovarian cancer cell lines OVCAR-3 and MDAH-2774. XTT cell proliferation kit, Cell Death Detection Elisa Plus Kit (Roche) and Human Apoptosis Array (R&D Systems) were used to determine the cytotoxic and apoptotic effects of HT in OVCAR-3 and MDAH-2774 cell lines at 24, 48, 72, and 96 h. Effect of HT on PI3K/Akt and ERK 1/2 signaling pathways were investigated by using specific inhibitors of these pathways. IC50 values of HT were found to be 102.3 µM in MDAH-2774 cells at 72 h and 51.5 µM in OVCAR-3 cells at 96 h. Apoptotic effect of HT in MDAH-2774 cells was the highest at 50 µM at 72 h, and kept decreasing at 100 and 150 µM concentrations and was not seen at 200 µM and higher concentrations. Highest apoptotic effect was seen at 100 µM concentration in OVCAR-3 cells at 96 h, however apoptotic effect was decreased over 100 µM concentrations. According to antibody microarray results, HT increased the levels of pro-apoptotic molecules Bad, Bax, active caspase-3, Htra2/Omi by 2.0-, 1.4-, 1.2-, 4.2-fold, respectively and also increased the levels of pro-apoptotic death receptors TRAIL R1/DR4, TRAIL R2/DR5, FAS/TNFRSF6 by 2.1-, 1.7-, 1.6-fold, respectively, however, it decreased the level of Survivin by 1.6-fold which is one of the inhibitor of apoptosis protein (IAP) family in MDAH-2774 cells. In OVCAR-3 cells, HT decreased the levels of anti-apoptotic proteins Bcl-2, pro-caspase 3 by 3.1-, 8.2-fold, respectively and IAP family proteins CIAP-1, CIAP-2, XIAP, Livin, Survivin by 6.5-, 6.0-, 3.2-, 2.2-, 2.7-fold, respectively and increased the level of cytochrome-c by 1.2-fold. We have shown that HT shows its cytotoxic and apoptotic effect through inhibiting ERK 1/2 signaling pathway in both OVCAR-3 and MDAH-2774 cells. Further studies are needed to investigate molecular mechanisms and modulatory effects of hydroxytyrosol.

Keywords: apoptosis, cytotoxicity, hydroxytyrosol, ovarian cancer

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Authors: Hyun Ji Hyun, Hyo Sun Suh, Min Kook Kim, Yong Chan Kwon, Byung-Mu Lee

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Scope: This study is focused on the effect of myristic acid on LPS-induced inflammation in RAW 264.7 macrophage cells. Methods and results: For the experiment, RAW 264.7 mouse macrophage cell line was used. Results showed that treatment with myristic acid can attenuate LPS-induced inflammation. Moreover, myristic acid significantly suppressed expression of inflammatory mediators and down-regulating UVB-induced intracellular ROS generation. Furthermore, myristic acid reduced the expression of NF-κB by inhibiting degradation of IκB-α and ERK, JNK, and p38 pathways by inhibiting phosphorylation in RAW 264.7 macrophage cells. Conclusion: Overall, these data suggest that the myristic acid could reduce LPS-induced inflammation. Acknowledgment: This research was supported by the Ministry of Trade, Industry & Energy(MOTIE), Korea Institute for Advancement of Technology(KIAT) through the Encouragement Program for The Industries of Economic Cooperation Region

Keywords: anti-inflammation, myristic acid, ROS, ultraviolet light

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Authors: M. Dehestani, F. Kamali, M. Klantari Pour, L. Zeidabadi-Nejad

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Chemical bonding between polyethylene glycol (PEG) with pharmaceutical proteins called pegylation is one of the most effective methods of improving the pharmacological properties. The covalent attachment of polyethylene glycol (PEG) to proteins will increase their pharmacologic properties. For the formation of a combination of pegylated protein should first be activated PEG and connected to the protein. Interferons(IFNs) are a family of cytokines which show antiviral effects in front of the biological and are responsible for setting safety system. In this study, the nature and properties of the interaction between active positions of IFNs and polyethylene glycol have been investigated using molecular dynamics simulation. The main aspect of this theoretical work focuses on the achievement of valuable data on the reaction pathways of PEG-IFNs and the transition state energy. Our results provide a new perspective on the interactions, chemical properties and reaction pathways between IFNs and PEG.

Keywords: interaction, interferons, molecular dynamics simulation, polyethylene glycol

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Authors: Azizah M. Nahari, Peter Doerner

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Phosphate (Pi) is one of the essential macronutrients in plant growth and development, and it plays a central role in metabolic processes in plants, particularly photosynthesis and respiration. Limitation of crop productivity by Pi is widespread and is likely to increase in the future. Applications of Pi fertilizers have improved soil Pi fertility and crop production; however, they have also caused environmental damage. Therefore, in order to reduce dependence on unsustainable Pi fertilizers, a better understanding of phosphate use efficiency (PUE) is required for engineering nutrient-efficient crop plants. Enhanced Pi efficiency can be achieved by improved productivity per unit Pi taken up. We aim to identify, by using association mapping, general features of the most important loci that contribute to increased PUE to allow us to delineate the physiological pathways involved in defining this trait in the model plant Arabidopsis. As PUE is in part determined by the efficiency of uptake, we designed a hydroponic system to avoid confounding effects due to differences in root system architecture leading to differences in Pi uptake. In this system, 18 parental lines and 217 lines of the MAGIC population (a Multiparent Advanced Generation Inter-Cross) grown in high and low Pi availability conditions. The results showed revealed a large variation of PUE in the parental lines, indicating that the MAGIC population was well suited to identify PUE loci and pathways. 2 of 18 parental lines had the highest PUE in low Pi while some lines responded strongly and increased PUE with increased Pi. Having examined the 217 MAGIC population, considerable variance in PUE was found. A general feature was the trend of most lines to exhibit higher PUE when grown in low Pi conditions. Association mapping is currently in progress, but initial observations indicate that a wide variety of physiological processes are involved in influencing PUE in Arabidopsis. The combination of hydroponic growth methods and genome-wide association mapping is a powerful tool to identify the physiological pathways underpinning complex quantitative traits in plants.

Keywords: hydroponic system growth, phosphate use efficiency (PUE), Genome-wide association mapping, MAGIC population

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Authors: Shamill Amedot Udonwa, Phyllis S. Y. Chong, Lim S. L. Julia, Wee-Joo Chng

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In this paper, we investigated how PRL-3 expression in H929 and U266 cells affects the efficacy of drug treatment. H929 and U266 cells were treated with Bortezomib (BTZ) of different concentrations, and it was observed that H929 cells were resistant to BTZ, while U266 cells were not viable. Investigations into how BTZ targets these cells were conducted, and it was observed that BTZ affects the PARP-Caspase3 pathway as well as PRL-3-Leo1 pathways. These pathways regulate cell proliferation and cell cycle, respectively. Hence, we are able to show the mechanism of how BTZ affects cells and also the role PRL-3 plays on downstream oncogenes such as cyclin-D1 and c-MYC. More importantly, this investigation into PRL-3 in BTZ resistance will be highly applicable in the future as the first clinical trials of PRL-3 antibody (PRL3-zumab) are ongoing at the National University Hospital, Singapore (NUHS). This would mean that understanding the mechanism of resistance through PRL-3, which has yet to be studied, will demonstrate the potential of PRL-3 in developing novel strategies to improve the treatment of MM.

Keywords: drug resistance, hematology, multiple myeloma, oncogene

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Authors: Ehsan Motamedian

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Finding all optimal flux distributions of a metabolic model is an important challenge in systems biology. In this paper, a new algorithm is introduced to identify all alternate optimal solutions of a large scale metabolic network. The algorithm reduces the model to decrease computations for finding optimal solutions. The algorithm was implemented on the Escherichia coli metabolic model to find all optimal solutions for lactate and acetate production. There were more optimal flux distributions when acetate production was optimized. The model was reduced from 1076 to 80 variable fluxes for lactate while it was reduced to 91 variable fluxes for acetate. These 11 more variable fluxes resulted in about three times more optimal flux distributions. Variable fluxes were from 12 various metabolic pathways and most of them belonged to nucleotide salvage and extra cellular transport pathways.

Keywords: flux variability, metabolic network, mixed-integer linear programming, multiple optimal solutions

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Authors: Mustafa Mabruk

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Groups such as Al-Shabaab have managed to radicalize many individuals abroad, including the first American citizen to ever be radicalized. Yet the pathways of radicalization for these foreign individuals are understudied. Moreover, current measures to prevent foreign radicalization are ineffective, with privacy, screening and profiling implications that render current counter-radicalization efforts counterproductive. Such measures exhibit strictness, political bias, and harshness. As confirmed by recent studies, such counter-radicalization issues exacerbate existing grievances and channel fresh recruits to Al-Shabaab. Addressing these challenges is paramount, requiring alternative strategies to effectively reduce radicalization without triggering further harm. The development of counter-narratives emerges as a potential measure with minimal risk of exacerbating grievances, yet the development of such counter-narratives necessitates a thorough understanding of the radicalization pathways of foreign individuals that are understudied. This study investigates the success of Al-Shabaab in recruiting individuals abroad by analyzing their propaganda in conjunction with analyzing identity-focused theories of radicalization, including Framing Theory and Social Identity Theory. Qualitative content analysis is used to analyze various propaganda material, including tweets, speeches, and webpages. The analysis reveals that issues of identity are of major significance in the radicalization patterns identified and that grievances of Muslims worldwide are used to exploit identity-related grievances. Based on these findings, the paper argues that such evidence enhances our understanding of potential deradicalization pathways and present counter-narratives based on Islamic scripture.

Keywords: counter-narratives, foreign radicalization, identity grievances, propaganda analysis

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Authors: Nahid H. Hajrah, Jamal S. M. Sabir, Neil Hall

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The jasmonic pathway is ubiquitous in plants and is crucial to plant development. It Is involved in fertility, ripening, and sex determination as well as in response to environmental stresses such as herbivory, pathogen drought or temperature shock. Essentially the jasmonic pathway acts to shut down growth in order to induce defence pathways. These pathways include the production of secondary metabolites which have evolved to defend against herbivores and pathogens but are of increasing interest due to their roll in medicine and biotechnology. Here we describe the transcriptional response of Rhazia stricta (a poisonous shrub widely used in traditional medicine) to jasmonic acid, in order to better characterize the genes involved in secondary metabolite production and its response to stress. We observe coordinated upregulation of flavonoid biosynthesis pathway leading to flavonols, flavones and anthocyanins but no similar coordination of the monoterpene indole alkaloid pathway.

Keywords: medicinal plants, Rhazia stricta, jasmonic acid, transcriptional analysis

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Authors: Ankita Shukla, Tiratha Raj Singh

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Colorectal cancer (CRC) imposes serious mortality burden worldwide and it has been increasing for past consecutive years. Continuous efforts have been made so far to diagnose the disease condition and to identify the root cause for it. In this study, we performed the pathway level as well as the differential gene expression studies for CRC. We analyzed the gene expression profile GSE24514 from Gene Expression Omnibus (GEO) along with the gene pathways involved in the CRC. This analysis helps us to understand the behavior of the genes that have shown differential expression through their targeted pathways. Pathway analysis for the targeted genes covers the wider area which therefore decreases the possibility to miss the significant ones. This will prove to be beneficial to expose the ones that have not been given attention so far. Through this analysis, we attempt to understand the various neighboring genes that have close relationship to the targeted one and thus proved to be significantly controlling the CRC. It is anticipated that the identified hub and neighboring genes will provide new directions to look at the pathway level differently and will be crucial for the regulatory processes of the disease.

Keywords: mismatch repair, microsatellite instability, carcinogenesis, morbidity

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Authors: Chanya Inprasit, Ching-Liang Hsieh, Yi-Wen Lin

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Obesity (OB) is a hazardous global health problem that has been increasing in prevalence, more severely in last decade. It is the mainly resultant from the imbalance between food consumption and energy expenditure, which is concordant with a modern lifestyle, implying an increase in calories with poorer quality of food intake accompanied by a decrease in physical activities. Obesity does not concern the appearance only but is also a major factor contributing to poor physiology, psychology, society and economic issues. Moreover, OB induces low-grade inflammation in the body through the regulatory effect it enacts on the adipocyte function. Various alternative treatments were investigated for body weight control, including Acupoint Catgut Embedding (ACE). ACE is the implantation of absorbable catgut sutures at specific acupoints, displaying durable and potent stimulation and thereby reducing the treatment frequency. Our study utilized a mouse model to exclude any psychological factors of OB and ACE treatment. High-fat diet and body weight were measured once a week before subjects in ACE and Sham group received the ACE treatment or placebo treatment. We hypothesized that ACE can control body weight through the interaction of the TRPV1 pathways, as TRPV1 accordingly responds to inflammatory factors. The results of body weight variation show a significant decrease in body weight in ACE group compared with the baseline of control and Sham group. Meanwhile, converse results were explored in TRPV1 knockout mice, where a significant maintenance of normal body weight throughout the experiment period was observed. There was no significant difference in food consumption of each group. These finding indicated that TRPV1 pathways and its associated pathways may be involved in the maintenance of body weight, which can be controlled by ACE treatment of genetic manipulation.

Keywords: acupoint catgut embedding, obesity, hypothalamus, TRPV1

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Authors: Sahar El Shair, Laura Greco, William Reay, Murray Cairns

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Background: Rheumatoid arthritis (RA) is a chronic, systematic, inflammatory, autoimmune disease that involves damages to joints and erosions to the associated bones and cartilage, resulting in reduced physical function and disability. RA is a multifactorial disorder influenced by heterogenous genetic and environmental factors. Whilst different medications have proven successful in reducing inflammation associated with RA, they often come with significant side effects and limited efficacy. To address this, the novel pharmagenic enrichment score (PES) algorithm was tested in self-reported RA patients from the UK Biobank (UKBB), which is a cohort of predominantly European ancestry, and identified individuals with a high genetic risk in clinically actionable biological pathways to identify novel opportunities for precision interventions and drug repurposing to treat RA. Methods and materials: Genetic association data for rheumatoid arthritis was derived from publicly available genome-wide association studies (GWAS) summary statistics (N=97173). The PES framework exploits competitive gene set enrichment to identify pathways that are associated with RA to explore novel treatment opportunities. This data is then integrated into WebGestalt, Drug Interaction database (DGIdb) and DrugBank databases to identify existing compounds with existing use or potential for repurposed use. The PES for each of these candidates was then profiled in individuals with RA in the UKBB (Ncases = 3,719, Ncontrols = 333,160). Results A total of 209 pathways with known drug targets after multiple testing correction were identified. Several pathways, including interferon gamma signaling and TID pathway (which relates to a chaperone that modulates interferon signaling), were significantly associated with self-reported RA in the UKBB when adjusting for age, sex, assessment centre month and location, RA polygenic risk and 10 principal components. These pathways have a major role in RA pathogenesis, including autoimmune attacks against certain citrullinated proteins, synovial inflammation, and bone loss. Encouragingly, many also relate to the mechanism of action of existing RA medications. The analyses also revealed statistically significant association between RA polygenic scores and self-reported RA with individual PES scorings, highlighting the potential utility of the PES algorithm in uncovering additional genetic insights that could aid in the identification of individuals at risk for RA and provide opportunities for more targeted interventions. Conclusions In this study, pharmacologically annotated genetic risk was explored through the PES framework to overcome inter-individual heterogeneity and enable precision drug repurposing in RA. The results showed a statistically significant association between RA polygenic scores and self-reported RA and individual PES scorings for 3,719 RA patients. Interestingly, several enriched PES pathways were targeted by already approved RA drugs. In addition, the analysis revealed genetically supported drug repurposing opportunities for future treatment of RA with a relatively safe profile.

Keywords: rheumatoid arthritis, precision medicine, drug repurposing, system biology, bioinformatics

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Authors: Ruqia Nazir, Robin Perutz

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Collision-induced dissociation (CID) can be used to study the intrinsic properties of ions in the gas phase.1 Decay pathways of transition metal difluoride complexes of titanium, zirconium, hafnium, and ruthenium were studied by CID in an ESI-Ion trap mass spectrometer. Furthermore, the decay pathways of multiply charged anions (MCAs) of titanium and zirconium were also studied. The CID results are illustrated by the behaviour of (Cp*)₂TiF₂, which initially forms the ions [M-F-]⁺, [M+Na]⁺, and [M+K]⁺. The [(Cp*₂)TiF⁺ ion decays on resonant excitation to lose HF forming [Cp*(C₅Me₄CH₂)Ti]⁺ (Figure). The other major ion, [(Cp*)₂TiF₂+Na]⁺, decays on resonant excitation with production of [(Cp*)₂TiF₂]⁺ and [C₅Me₄CH₂]⁺. We also report the behaviour of Cp₂MF₂ (M = Zr, Hf) and Ru(PMe₃)₄F₂. The decay pathway of the multiply charged anions (MCAs), notably TiF₆²⁻ and ZrF₆²⁻ was concluded to be ionic fragmentation with loss of F⁻ rather than electron detachment.

Keywords: collision induced dissociation, transition metal difluoride comolexes, multiply charged anions, mass spectrometry

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Authors: Edward Poluyi, Eghosa Morgan, Charles Poluyi, Chibuikem Ikwuegbuenyi, Grace Imaguezegie

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Background: Current epidemiological studies have examined the associations between moderate and severe traumatic brain injury (TBI) and their risks of developing neurodegenerative diseases. Concussion, also known as mild TBI (mTBI), is however quite distinct from moderate or severe TBIs. Only few studies in this burgeoning area have examined concussion—especially repetitive episodes—and neurodegenerative diseases. Thus, no definite relationship has been established between them. Objectives : This review will discuss the available literature linking concussion and amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). Materials and Methods: Given the complexity of this subject, a realistic review methodology was selected which includes clarifying the scope and developing a theoretical framework, developing a search strategy, selection and appraisal, data extraction, and synthesis. A detailed literature matrix was set out in order to get relevant and recent findings on this topic. Results: Presently, there is no objective clinical test for the diagnosis of concussion because the features are less obvious on physical examination. Absence of an objective test in diagnosing concussion sometimes leads to skepticism when confirming the presence or absence of concussion. Intriguingly, several possible explanations have been proposed in the pathological mechanisms that lead to the development of some neurodegenerative disorders (such as ALS and AD) and concussion but the two major events are deposition of tau proteins (abnormal microtubule proteins) and neuroinflammation, which ranges from glutamate excitotoxicity pathways and inflammatory pathways (which leads to a rise in the metabolic demands of microglia cells and neurons), to mitochondrial function via the oxidative pathways.

Keywords: amyotrophic lateral sclerosis, Alzheimer's disease, mild traumatic brain injury, neurodegeneration

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Authors: Farideh Halakou, Emel Sen, Attila Gursoy, Ozlem Keskin

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Protein–Protein Interactions (PPIs) mediate major biological processes in living cells. The study of PPIs as networks and analyze the network properties contribute to the identification of genes and proteins associated with diseases. In this study, we have created the sub-networks of brain and lung metastasis from primary tumor in breast cancer. To do so, we used seed genes known to cause metastasis, and produced their interactions through a network-topology based prioritization method named GUILDify. In order to have the experimental support for the sub-networks, we further curated them using STRING database. We proceeded by modeling structures for the interactions lacking complex forms in Protein Data Bank (PDB). The functional enrichment analysis shows that KEGG pathways associated with the immune system and infectious diseases, particularly the chemokine signaling pathway, are important for lung metastasis. On the other hand, pathways related to genetic information processing are more involved in brain metastasis. The structural analyses of the sub-networks vividly demonstrated their difference in terms of using specific interfaces in lung and brain metastasis. Furthermore, the topological analysis identified genes such as RPL5, MMP2, CCR5 and DPP4, which are already known to be associated with lung or brain metastasis. Additionally, we found 6 and 9 putative genes that are specific for lung and brain metastasis, respectively. Our analysis suggests that variations in genes and pathways contributing to these different breast metastasis types may arise due to change in tissue microenvironment. To show the benefits of using structural PPI networks instead of traditional node and edge presentation, we inspect two case studies showing the mutual exclusiveness of interactions and effects of mutations on protein conformation which lead to different signaling.

Keywords: breast cancer, metastasis, PPI networks, protein conformational changes

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Authors: Charalabos Antonatos, Mariza Panoutsopoulou, Georgios K. Georgakilas, Evangelos Evangelou, Yiannis Vasilopoulos

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The extended tissue damage and severe clinical outcomes of autoimmune diseases, accompanied by the high annual costs to the overall health care system, highlight the need for an efficient therapy. Increasing knowledge over the pathophysiology of specific chronic inflammatory diseases, namely Psoriasis (PsO), Inflammatory Bowel Diseases (IBD) consisting of Crohn’s disease (CD) and Ulcerative colitis (UC), and Rheumatoid Arthritis (RA), has provided insights into the underlying mechanisms that lead to the maintenance of the inflammation, such as Tumor Necrosis Factor alpha (TNF-α). Hence, the anti-TNFα biological agents pose as an ideal therapeutic approach. Despite the efficacy of anti-TNFα agents, several clinical trials have shown that 20-40% of patients do not respond to treatment. Nowadays, high-throughput technologies have been recruited in order to elucidate the complex interactions in multifactorial phenotypes, with the most ubiquitous ones referring to transcriptome quantification analyses. In this context, a random effects meta-analysis of available gene expression cDNA microarray datasets was performed between responders and non-responders to anti-TNFα therapy in patients with IBD, PsO, and RA. Publicly available datasets were systematically searched from inception to 10th of November 2020 and selected for further analysis if they assessed the response to anti-TNFα therapy with clinical score indexes from inflamed biopsies. Specifically, 4 IBD (79 responders/72 non-responders), 3 PsO (40 responders/11 non-responders) and 2 RA (16 responders/6 non-responders) datasetswere selected. After the separate pre-processing of each dataset, 4 separate meta-analyses were conducted; three disease-specific and a single combined meta-analysis on the disease-specific results. The MetaVolcano R package (v.1.8.0) was utilized for a random-effects meta-analysis through theRestricted Maximum Likelihood (RELM) method. The top 1% of the most consistently perturbed genes in the included datasets was highlighted through the TopConfects approach while maintaining a 5% False Discovery Rate (FDR). Genes were considered as Differentialy Expressed (DEGs) as those with P ≤ 0.05, |log2(FC)| ≥ log2(1.25) and perturbed in at least 75% of the included datasets. Over-representation analysis was performed using Gene Ontology and Reactome Pathways for both up- and down-regulated genes in all 4 performed meta-analyses. Protein-Protein interaction networks were also incorporated in the subsequentanalyses with STRING v11.5 and Cytoscape v3.9. Disease-specific meta-analyses detected multiple distinct pro-inflammatory and immune-related down-regulated genes for each disease, such asNFKBIA, IL36, and IRAK1, respectively. Pathway analyses revealed unique and shared pathways between each disease, such as Neutrophil Degranulation and Signaling by Interleukins. The combined meta-analysis unveiled 436 DEGs, 86 out of which were up- and 350 down-regulated, confirming the aforementioned shared pathways and genes, as well as uncovering genes that participate in anti-inflammatory pathways, namely IL-10 signaling. The identification of key biological pathways and regulatory elements is imperative for the accurate prediction of the patient’s response to biological drugs. Meta-analysis of such gene expression data could aid the challenging approach to unravel the complex interactions implicated in the response to anti-TNFα therapy in patients with PsO, IBD, and RA, as well as distinguish gene clusters and pathways that are altered through this heterogeneous phenotype.

Keywords: anti-TNFα, autoimmune, meta-analysis, microarrays

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Authors: Evar C. Umeozor, Experience I. Nduagu, Ian D. Gates

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The energy requirements of carbon dioxide utilization (CDU) technologies/processes are diverse, so also are their environmental footprints. This paper explores the energy and environmental impacts of systems for CO₂ conversion to fuels, chemicals, and materials. Energy needs of the technologies and processes deployable in CO₂ conversion systems are met by one or combinations of hydrogen (chemical), electricity, heat, and light. Likewise, the environmental footprint of any CO₂ utilization pathway depends on the systems involved. So far, evaluation of CDU systems has been constrained to particular energy source/type or a subset of the overall system needed to make CDU possible. This introduces limitations to the general understanding of the energy and environmental implications of CDU, which has led to various pitfalls in past studies. A CDU system has an energy source, CO₂ supply, and conversion units. We apply a holistic approach to consider the impacts of all components in the process, including various sources of energy, CO₂ feedstock, and conversion technologies. The electricity sources include nuclear power, renewables (wind and solar PV), gas turbine, and coal. Heat is supplied from either electricity or natural gas, and hydrogen is produced from either steam methane reforming or electrolysis. The CO₂ capture unit uses either direct air capture or post-combustion capture via amine scrubbing, where applicable, integrated configurations of the CDU system are explored. We demonstrate how the overall energy and environmental impacts of each utilization pathway are obtained by aggregating the values for all components involved. Proper accounting of the energy and emission intensities of CDU must incorporate total balances for the utilization process and differences in timescales between alternative conversion pathways. Our results highlight opportunities for the use of clean energy sources, direct air capture, and a number of promising CO₂ conversion pathways for producing methanol, ethanol, synfuel, urea, and polymer materials.

Keywords: carbon dioxide utilization, processes, energy options, environmental impacts

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Authors: Alexander de Tomás, Miquel Sierra, Stefan Pfenninger, Francesco Lombardi, Ines Campos, Cristina Madrid

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Environmental parameters are key in the definition of sustainable energy systems yet excluded from most energy system optimization models. Still, decision-making may be misleading without considering them. Environmental analyses of the energy transition are a key part of industrial ecology but often are performed without any input from the users of the information. This work assesses the systemic impacts of energy transition pathways in Portugal. Using the Calliope energy modeling framework, 250+ optimized energy system pathways are generated. A Delphi study helps to identify the relevant criteria for the stakeholders as regards the environmental assessment, which is performed with ENBIOS, a python package that integrates life cycle assessment (LCA) with a metabolic analysis based on complex relations. Furthermore, this study focuses on how the uncertainty propagates through the model’s consortium. With the aim of doing so, a soft link between the Calliope/ENBIOS cascade and Brightway’s data capabilities is built to perform Monte Carlo simulations. These findings highlight the relevance of including uncertainty analysis as a range of values rather than informing energy transition results with a single value.

Keywords: energy transition, energy modeling, uncertainty, sustainability

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Authors: Manish Khanra, Shashank Prabhu

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The decarbonization of hard-to-abate sectors is currently high on the agenda in the EU and its member states, as these sectors have substantial shares in overall GHG emissions while it is facing serious challenges to decarbonize. In particular, the aviation sector accounts for 2.8% of global anthropogenic CO₂ emissions. These emissions are anticipated to grow dramatically unless immediate mitigating efforts are implemented. Hydrogen and its derivatives based on renewable electricity can have a key role in the transition towards CO₂-neutral flights. The substantial shares of energy carriers in the form of drop-in fuel, direct combustion and Hydrogen-to-Electric are promising in most scenarios towards 2050. For creating appropriate policies to ramp up the production and utilisation of hydrogen commodities in the German aviation sector, a detailed analysis of the spatial distribution of supply-demand sites is essential. The objective of this research work is to assess the demand for hydrogen-based alternative fuels in the German aviation sector to achieve the perceived goal of the ‘Net Zero’ scenario by 2050. Here, the analysis of the technological pathways for the production and utilisation of these fuels in various aircraft options is conducted for reaching mitigation targets. Our method is based on data-driven bottom-up assessment, considering production and demand sites and their spatial distribution. The resulting energy demand and its spatial distribution with consideration of technology diffusion lead to a possible transition pathway of the aviation sector to meet short-term and long-term mitigation targets. Additionally, to achieve mitigation targets in this sector, costs and policy aspects are discussed, which would support decision-makers from airline industries, policymakers and the producers of energy commodities.

Keywords: the aviation sector, hard-to-abate sectors, hydrogen demand, alternative fuels, technological pathways, data-driven approach

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Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

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Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

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Authors: Mohammadjavad Sotoudeheian

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Heart failure (HF) prevalence, as a global cardiovascular problem, is increasing gradually. A variety of molecular mechanisms contribute to HF. Proteins involved in cardiac contractility regulation, such as ion channels and calcium handling proteins, are altered. Additionally, epigenetic modifications and gene expression can lead to altered cardiac function. Moreover, inflammation and oxidative stress contribute to HF. The progression of HF can be attributed to mitochondrial dysfunction that impairs energy production and increases apoptosis. Molecular mechanisms such as these contribute to the development of cardiomyocyte defects and HF and can be therapeutically targeted. The heart's contractile function is controlled by cardiomyocytes. Calpain, and its related molecules, including Bax, VEGF, and AMPK, are among the proteins involved in regulating cardiomyocyte function. Apoptosis is facilitated by Bax. Cardiomyocyte apoptosis is regulated by this protein. Furthermore, cardiomyocyte survival, contractility, wound healing, and proliferation are all regulated by VEGF, which is produced by cardiomyocytes during inflammation and cytokine stress. Cardiomyocyte proliferation and survival are also influenced by AMPK, an enzyme that plays an active role in energy metabolism. They all play key roles in apoptosis, angiogenesis, hypertrophy, and metabolism during myocardial inflammation. The role of calpains has been linked to several molecular pathways. The calpain pathway plays an important role in signal transduction and apoptosis, as well as autophagy, endocytosis, and exocytosis. Cell death and survival are regulated by these calcium-dependent cysteine proteases that cleave proteins. As a result, protein fragments can be used for various cellular functions. By cleaving adhesion and motility proteins, calcium proteins also contribute to cell migration. HF may be brought about by calpain-mediated pathways. Many physiological processes are mediated by the calpain molecular pathways. Signal transduction, cell death, and cell migration are all regulated by these molecular pathways. Calpain is activated by calcium binding to calmodulin. In the presence of calcium, calmodulin activates calpain. Calpains are stimulated by calcium, which increases matrix metalloproteinases (MMPs). In order to develop novel treatments for these diseases, we must understand how this pathway works. A variety of myocardial remodeling processes involve calpains, including remodeling of the extracellular matrix and hypertrophy of cardiomyocytes. Calpains also play a role in maintaining cardiac homeostasis through apoptosis and autophagy. The development of HF may be in part due to calpain-mediated pathways promoting cardiomyocyte death. Numerous studies have suggested the importance of the Ca2+ -dependent protease calpain in cardiac physiology and pathology. Therefore, it is important to consider this pathway to develop and test therapeutic options in humans that targets calpain in HF. Apoptosis, autophagy, endocytosis, exocytosis, signal transduction, and disease progression all involve calpain molecular pathways. Therefore, it is conceivable that calpain inhibitors might have therapeutic potential as they have been investigated in preclinical models of several conditions in which the enzyme has been implicated that might be treated with them. Ca 2+ - dependent proteases and calpains contribute to adverse ventricular remodeling and HF in multiple experimental models. In this manuscript, we will discuss the calpain molecular pathway's important roles in HF development.

Keywords: calpain, heart failure, autophagy, apoptosis, cardiomyocyte

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Authors: Swati Kundu, Seemi Farhat Basir, Luqman A. Khan

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Acute and chronic exposure to arsenic and mercury is known to produce vasoconstriction. Pathways involved in this hypercontraction and their relative contribution are not understood. In this study, we measure agonist-induced contraction of isolated rat aorta exposed to arsenic and mercury aorta and delineate pathways mediating this effect. PE-induced hypercontraction of 37% and 32% was obtained with 25 µM As(III) and 6 nM Hg(II), respectively. Isometric contraction measurements in the presence of apocynin, verapamil and sodium nitroprusside indicates that the major cause of increased contraction is reactive oxygen species and depletion of nitric oxide. Calcium influx plays a minor role in both arsenic and mercury caused hypercontraction. In the unexposed aorta, eugenol causes relaxation by inhibiting ROS and elevating NO, linalool by blocking voltage dependent calcium channel (VDCC) and elevating NO, and carvone by blocking calcium influx through VDDC. Since arsenic and mercury caused hypercontraction is mediated by increased ROS and depletion of nitric oxide, we hypothesize that molecules which neutralize ROS or elevate NO will be better ameliorators. In line with this argument, we find eugenol to be the best ameliorator of arsenic and mercury hypercontraction followed by linalool and carvone.

Keywords: carvone, eugenol, linalool, mercury

Procedia PDF Downloads 299

Authors: Jessica Leigh Thornton

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The South African Constitution outlines provisions for every detainee and sentenced prisoner in relation to the human rights recognized in the country since 1994; but currently, across the country, prisons have yet to meet many of these criteria. Consequently, their day-to-day lives are marked by extreme lack of privacy, high rates of infection, poor nutrition, and deleterious living conditions, which steadily erode prisoners’ mental and physical capacities rather than rehabilitating inmates so that they can effectively reintegrate into society. Even more so, policy reform, advocacy, security, and rehabilitation programs continue to be based on research and theories that were developed to explain the experiences of men, while female offenders are seen as the “special category” of inmates. Yet, the experiences of women and their pathways to incarceration are remarkably different from those of male offenders. Consequently, little is known about the profile, nature and contributing factors and experiences of female offenders which has impeded a comprehensive and integrated understanding of the subject of female criminality. The number of women globally in correctional centers has more than doubled over the past fifteen years (these increases vary from prison to prison and country to country). Yet, female offenders have largely been ignored in research even though the minority status of female offenders is a phenomenon that is not peculiar to South Africa as the number of women incarcerated has increased by 68% within the decade. Within South Africa, there have been minimal studies conducted on the gendered experience of offenders. While some studies have explored the pathways to female offending, gender-sensitive correctional programming for women that respond to their needs has been overlooked. This often leads to a neglect of the needs of female offenders, not only in terms of programs and services delivery to this minority group but also from a research perspective. In response, the aim of the proposed research is twofold: Firstly, the lived experiences and views of rehabilitation and reintegration of female offenders will be explored. Secondly, the various pathways into and out of recidivism amongst female offenders will be investigated regarding their inclusion in educational rehabilitation.

Keywords: female incarceration, educational rehabilitation, exclusion, experiences of female offenders

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Authors: Ejoke U. P., Smitha Dev., Madwuke Ann, DuPlessis E. D.

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The study examines the relationship between psychological capital (PsyCap) and social well-being among international faculty members in the United Arab Emirates (UAE). The UAE has become a significant destination for global academic talent, yet challenges related to social integration, acceptance, and overall well-being persist among its international faculty. The study focuses on the predictive role of PsyCap, encompassing hope, efficacy, resilience, and optimism, in determining various dimensions of social well-being, including social integration, acceptance, contribution, actualization, and coherence. Additionally, the research investigates the potential moderating or mediating effects of institutional support and Faculty Job-Status position on the relationship between PsyCap and social well-being. Through structural equation modeling, we found that institutional support mediated the positive relationship between PsyCap and SWB and the permanent Faculty job-status position type strengthens the relationship between PsyCap and SWB. Our findings uncover the pathways through which PsyCap influences the social well-being outcomes of international faculty in the UAE. The findings will contribute to the development of tailored interventions and support systems aimed at enhancing the integration experiences and overall well-being of international faculty within the UAE academic community. Thus, fostering a more inclusive and thriving academic environment in the UAE.

Keywords: faculty job-status, institutional-faculty, psychological capital, social well-being, UAE

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Authors: Su Bin Wang, Jin Hee Ahn, Tong-Shin Chang

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The peroxisome proliferator-activated receptors (PPARs) are member of nuclear receptor superfamily that act as a ligand-activated transcription factors. Although platelets lack a nucleus, previous studies have shown that PPARγ agonists, rosiglitazone, inhibited platelet activation induced by collagen. In this study, we investigated the inhibitory effects of KR-62980, a newly synthesized PPARγ agonist, on collagen receptor-stimulated platelet activation. The specific tyrosine phosphorylations of key components (Syk, Vav1, Btk and PLCγ2) for collagen receptor signaling pathways were suppressed by KR-62980. KR-62980 also attenuated downstream responses including cytosolic calcium elevation, P-selectin surface exposure, and integrin αIIbβ3 activation. PPARγ was found to associate with multiple proteins within the LAT signaling complex in collagen-stimulated platelets. This association was prevented by KR-62980, indicating a potential mechanism for PPARγ function in collagen-stimulated platelet activation. Furthermore, KR-62980 inhibited platelet aggregation and adhesion in response to collagen in vitro and prolonged in vivo thrombotic response in carotid arteries of mice. Collectively, these data suggest that KR-62980 inhibits collagen-stimulated platelet activation and thrombus formation through modulating the collagen receptor signaling pathways.

Keywords: KR-62980, PPARγ, antiplatelet, thrombosis

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Authors: Mohammad Hossein Habibi, Atena Sadat Hosseini

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Colorectal cancer is the third leading cause of cancer-related death in the world. Colorectal cancer screening, early detection, and treatment programs could benefit from the most up-to-date information on the disease's burden, given the present worldwide trend of increasing colorectal cancer incidence. Tumor recurrence and resistance are exacerbated by the presence of chemotherapy-resistant cancer stem cells that can generate rapidly proliferating tumor cells. In addition, tumor cells can evolve chemoresistance through adaptation mechanisms. In this work, we used in silico analysis to select suitable GEO datasets. In this study, we compared slow-growing cancer stem cells with high-growth colorectal cancer-derived cancer stem cells. We then evaluated the signal pathways, transcription factors, and kinases associated with these two types of cancer stem cells. A total of 980 upregulated genes and 870 downregulated genes were clustered. MAPK signaling pathway, AGE-RAGE signaling pathway in diabetic complications, Fc gamma R-mediated phagocytosis, and Steroid biosynthesis signaling pathways were observed in upregulated genes. Also, caffeine metabolism, amino sugar and nucleotide sugar metabolism, TNF signaling pathway, and cytosolic DNA-sensing pathway were involved in downregulated genes. In the next step, we evaluated the best transcription factors and kinases in two types of cancer stem cells. In this regard, NR2F2, ZEB2, HEY1, and HDGF as transcription factors and PRDM5, SMAD, CBP, and KDM2B as critical kinases in upregulated genes. On the other hand, IRF1, SPDEF, NCOA1, and STAT1 transcription factors and CTNNB1 and CDH7 kinases were regulated low expression genes. Using bioinformatics analysis in the present study, we conducted an in-depth study of colorectal cancer stem cells at low and high growth rates so that we could take further steps to detect and even target these cells. Naturally, more additional tests are needed in this direction.

Keywords: colorectal cancer, bioinformatics analysis, transcription factor, kinases, cancer stem cells

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Authors: Chanya Inprasit, Yi-Wen Lin

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Motion sickness (MS) is an acute disorder that occurs in healthy persons without considering gender, age or ethnicity worldwide. All signs and symptoms of MS are the results of confliction and mismatch among neural signal inputs. It is known that no singular remedy works for everybody, and electroacupuncture (EA) is one of the popular alternative therapies used for MS. Our study utilized a mouse model in order to exclude any psychological factors of MS and EA. Mice lack an emetic reflex. Therefore pica behavior, which is a normal consumption of non-nutritive substances, was found to measure the response of MS in mice. In the laboratory, Kaolin was used as a non-nutrient food substance instead of natural substances lacking nutritional value such as wood, cloth, charcoal, soil or grass. It was hypothesized that EA treatment could reduce the symptoms of MS through the TRPV1 pathways. The results of pica behavior showed a significantly increased intake of kaolin in the MS group throughout the experiment period. Moreover, the Kaolin intake of the EA group decreased to the average baseline of the control group. There was no recorded difference in the food and water intake of each group. The results indicated an increase of the TRPV1, pERK, pJNK and pmTOR protein levels in the thalamus after MS stimulation, and a significant decrease in the EA group compared with that of the control group. These findings suggest that TRPV1 pathways are associated in MS mechanisms and can be reduced by EA.

Keywords: electroacupuncture, motion sickness, Thalamus, TRPV1

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