Search results for: Breast cancer genes

Authors: Nabila N. El-Maraghy, Amany Essa, Yousra Abdel–Mottaleb, Nada Ismail

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The use of combination of chemotherapy and natural products to influence the cell death with low doses of chemotherapeutic agents and few side effects has recently emerged as a new method of cancer therapy. Aim: Evaluation the modulatory effect of Thymoquinone on HepG2 cells treated with Sorafenib. Methods: Hepatocellular Carcinoma HepG2 cell line was treated with Sorafenib and TQ individually and in combination. The effect of these treatments on cell viability (MTT assay), apoptosis (Expression of Caspase-3) and oxidative markers (GSH content and extent of lipid peroxidation) was determined. Results: When compared the effect of both agents alone and the combination of the IC50 of Sorafenib and the IC50 TQ, the combination resulted in reduction of cell inhibition and apoptosis and antagonize their actions on GSH content and extent of lipid peroxidation which are increased. This study showed potent anti-tumor activity of both TQ and Sorafenib separately on HepG2 but upon combination surprisingly they interacted and give antagonistic effect. Conclusion: Co-treatment resulted in antagonistic interaction between Sorafenib and Thymoquinone.

Keywords: antagonism, hepatocellular carcinoma, sorafenib, thymoquinone

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Authors: Kiran Datta, Daniella Holland-Hart, Anthony Byrne

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Introduction: Oesophago-gastric (OG) cancers are the fifth commonest in the UK, accounting for over 12,000 deaths each year. Most patients will present at later stages of the disease, with only 21% of patients with stage 4 disease surviving longer than a year. As a result, many patients are unsuitable for curative surgery and instead receive palliative treatment to improve prognosis and symptom burden. However, palliative chemotherapy can result in significant toxicity: almost half of the patients are unable to complete their chemotherapy regimen, with this proportion rising significantly in older and frailer patients. In addition, clinical trials often exclude older and frailer patients due to strict inclusion criteria, meaning there is limited evidence to guide which patients are most likely to benefit from palliative chemotherapy. Inappropriate chemotherapy administration is at odds with the goals of palliative treatment and care, which are to improve quality of life, and this also represents a significant resource expenditure. This literature review aimed to examine and appraise evidence regarding treatment resilience in order to guide clinicians in identifying the most suitable candidates for palliative chemotherapy. Factors influencing treatment resilience were assessed, as measured by completion rates, dose reductions, and toxicities. Methods: This literature review was conducted using rapid review methodology, utilising modified systematic methods. A literature search was performed across the MEDLINE, EMBASE, and Cochrane Library databases, with results limited to papers within the last 15 years and available in English. Key inclusion criteria included: 1) participants with either oesophageal, gastro-oesophageal junction, or gastric cancers; 2) patients treated with palliative chemotherapy; 3) available data evaluating the association between baseline participant characteristics and treatment resilience. Results: Of the 2326 papers returned, 11 reports of 10 studies were included in this review after excluding duplicates and irrelevant papers. Treatment resilience factors that were assessed included: age, performance status, frailty, inflammatory markers, and sarcopenia. Age was generally a poor predictor for how well patients would tolerate chemotherapy, while poor performance status was a better indicator of the need for dose reduction and treatment non-completion. Frailty was assessed across one cohort using multiple screening tools and was an effective marker of the risk of toxicity and the requirement for dose reduction. Inflammatory markers included lymphopenia and the Glasgow Prognostic Score, which assessed inflammation and hypoalbuminaemia. Although quick to obtain and interpret, these findings appeared less reliable due to the inclusion of patients treated with palliative radiotherapy. Sarcopenia and body composition were often associated with chemotherapy toxicity but not the rate of regimen completion. Conclusion: This review demonstrates that there are numerous measures that can estimate the ability of patients with oesophago-gastric cancer to tolerate palliative chemotherapy, and these should be incorporated into clinical assessments to promote personalised decision-making around treatment. Age should not be a barrier to receiving chemotherapy and older and frailer patients should be included in future clinical trials to better represent typical patients with oesophago-gastric cancers. Decisions regarding palliative treatment should be guided by these factors identified as well as patient preference.

Keywords: frailty, oesophago-gastric cancer, palliative chemotherapy, treatment resilience

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Authors: Mohammadreza Hajialigol, Nargues Falahi Charkhabi, Fatemeh Shahryari, Saadat Sarikhani

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BACKGROUND AND OBJECTIVES Iran is the third producer of Persian walnut worldwide. However, its walnut trees have been under threat from decline during last decade. Walnut canker caused by B. nigrifluens and B. rubrifaciens was recorded in multiple regions of Iran. Furthermore, Brenneria rosae subsp. rosae and Gibbsiella quercinecans were recently recognized as responsible for walnut decline in northwestern Iran. This study aimed to identify the causal agent of walnut decline in Kermanshah and Isfahan. MATERIAL AND METHODS Symptomatic samples were collected from affected walnut trees of Kermanshah and Isfahan provinces. The pathogenicity of strains was proved on immature walnut fruits cv. ‘Hartley’ and young green twigs of two-year-old walnut seedling cv. ‘Chandler’. Pathogenic strains were subjected to conventional phenotypic tests. 16S rRNA, gyrB, and infB genes were partially amplified and sequenced. RESULTS Irregular longitudinal cankers and dark lesions were observed in the outer and inner bark, respectively. Twenty-four strains were isolated on EMB-agar media. Fourteen strains were able to cause necrosis and a dark-colored region in the mesocarp and on young green twigs around the inoculation site 14 and 30 days post-inoculation, respectively. Strains were able to hydrolyze Tween 20, Tween 80, gelatin and esculin, however, did not produce indole or urease. Pairwise comparison, the 16S rRNA gene nucleotide sequences of strain I2 were 100% identical with those of Rahnella victoriana FRB 225T. Moreover, a phylogenetic tree reconstructed based on the concatenated sequences of two housekeeping gene fragments, gyrB (601 bp) and infB (615 bp), revealed that the strains I2, I5, and KE6 were clustered with R. victoriana FRB 225T. CONCLUSION To the best of our knowledge, this is the first report of R. victoriana in association with walnut decline. This result is necessary to find resistant genotypes.

Keywords: emerging pathogens, Iran, juglans regia, MLSA

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Authors: Denise De Fátima Fernandes Barbosa, Tyane Mayara Ferreira Oliveira, Diego Jorge Maia Lima, Paula Renata Amorim Lessa, Ana Karina Bezerra Pinheiro, Cintia Gondim Pereira Calou, Glauberto Da Silva Quirino, Hellen Lívia Oliveira Catunda, Tatiana Gomes Guedes, Nicolau Da Costa

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The aim of this study is to evaluate the use of Digital Cervicography (DC) in the diagnosis of precancerous lesions related to Human Papillomavirus (HPV). Cross-sectional study with a quantitative approach, of evaluative type, held in a health unit linked to the Pro Dean of Extension of the Federal University of Ceará, in the period of July to August 2015 with a sample of 33 women. Data collecting was conducted through interviews with enforcement tool. Franco (2005) standardized the technique used for DC. Polymerase Chain Reaction (PCR) was performed to identify high-risk HPV genotypes. DC were evaluated and classified by 3 judges. The results of DC and PCR were classified as positive, negative or inconclusive. The data of the collecting instruments were compiled and analyzed by the software Statistical Package for Social Sciences (SPSS) with descriptive statistics and cross-references. Sociodemographic, sexual and reproductive variables were analyzed through absolute frequencies (N) and their respective percentage (%). Kappa coefficient (κ) was applied to determine the existence of agreement between the DC of reports among evaluators with PCR and also among the judges about the DC results. The Pearson's chi-square test was used for analysis of sociodemographic, sexual and reproductive variables with the PCR reports. It was considered statistically significant (p<0.05). Ethical aspects of research involving human beings were respected, according to 466/2012 Resolution. Regarding the socio-demographic profile, the most prevalent ages and equally were those belonging to the groups 21-30 and 41-50 years old (24.2%). The brown color was reported in excess (84.8%) and 96.9% out of them had completed primary and secondary school or studying. 51.5% were married, 72.7% Catholic, 54.5% employed and 48.5% with income between one and two minimum wages. As for the sexual and reproductive characteristics, prevailed heterosexual (93.9%) who did not use condoms during sexual intercourse (72.7%). 51.5% had a previous history of Sexually Transmitted Infection (STI), and HPV the most prevalent STI (76.5%). 57.6% did not use contraception, 78.8% underwent examination Cancer Prevention Uterus (PCCU) with shorter time interval or equal to one year, 72.7% had no cases of Cervical Cancer in the family, 63.6% were multiparous and 97% were not vaccinated against HPV. DC identified good level of agreement between raters (κ=0.542), had a specificity of 77.8% and sensitivity of 25% when compared their results with PCR. Only the variable race showed a statistically significant association with CRP (p=0.042). DC had 100% acceptance amongst women in the sample, revealing the possibility of other experiments in using this method so that it proves as a viable technique. The DC positivity criteria were developed by nurses and these professionals also perform PCCU in Brazil, which means that DC can be an important complementary diagnostic method for the appreciation of these professional’s quality of examinations.

Keywords: gynecological examination, human papillomavirus, nursing, papillomavirus infections, uterine lasmsneop

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Authors: Vahid Bayrami Rad

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In recent years, the use of artificial intelligence techniques, tools, and methods in processing medical images and health-related applications has been highlighted and a lot of research has been done in this regard. For example, colonoscopy and diagnosis of colon lesions are some cases in which the process of diagnosis of lesions can be improved by using image processing and artificial intelligence algorithms, which help doctors a lot. Due to the lack of accurate measurements and the variety of injuries in colonoscopy images, the process of diagnosing the type of lesions is a little difficult even for expert doctors. Therefore, by using different software and image processing, doctors can be helped to increase the accuracy of their observations and ultimately improve their diagnosis. Also, by using automatic methods, the process of diagnosing the type of disease can be improved. Therefore, in this paper, a deep learning framework called KCBA is proposed to classify colonoscopy lesions which are composed of several methods such as K-means clustering, a bag of features and deep auto-encoder. Finally, according to the experimental results, the proposed method's performance in classifying colonoscopy images is depicted considering the accuracy criterion.

Keywords: colorectal cancer, colonoscopy, region of interest, narrow band imaging, texture analysis, bag of feature

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Authors: Asma Naseer Cheema, Attya Bhatti, Jabar Ali, John Peter

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Background: High cholesterol levels, endothelial dysfunction, inefficient coagulation cascade and hyper inflammatory response all are the basis of coronary artery disease (CAD). Several studies are carried out to see the genetic influence of these factors on disease outcome. Objective: The objective of our study was to see the association of 10 putative loci with coronary artery disease in our population. Materials & Methods: We screened our population for 10 putative loci of CAD showing significant association (p < 5x10-8) with candidate genes (regulating the cholesterol metabolism, endothelial function, coagulation cascade and inflammatory response of body). Hardy-Weinberg equilibrium and linkage disequilibrium in cases and controls s were estimated separately. Approximately 5-10 ng of dried DNA in 384 well plate format was used to genotype each sample on the Sequenom iPLEX assay at University of Pittsburgh Genomics and Proteomics Core Laboratories. It was built on single-base primer extension with the MALDI-TOF MS detection possessing high sensitivity and specificity. The SNPs were genotyped through Taqman assay. Hardy Weinberg test was applied. The 10 SNPs were selected as genetic markers for this study (rs579459, rs1561198, rs2954029, rs1122608, rs17114036, rs9515203, rs10947789, rs7173743, rs2895811, rs2075650). Results: Mean age of the patient was 52 ± 11 years. Blood pressure and positive family history was found a significant risk factor for CAD. None of the selected SNPs showed significant association with coronary artery disease in our population (p>0.05). Conclusion: rs579459, rs1561198, rs2954029, rs1122608, rs17114036, rs9515203, rs10947789, rs7173743, rs2895811, rs2075650 are not significant genetic markers for CAD in our population.

Keywords: CAD, genetic markers, loci, risk factors

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Authors: Weaam Aldeeban, Majd Aljamali, Lama A. Youssef

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Background & Objective: Warfarin is considered a problematic drug due to its narrow therapeutic window and wide inter-individual response variations, which are attributed to demographic, environmental, and genetic factors, particularly single nucleotide polymorphism (SNPs) in the genes encoding VKORC1 and CYP2C9 involved in warfarin's mechanism of action and metabolism, respectively. CYP2C9*2rs1799853 and CYP2C9*3rs1057910 alleles are linked to reduced enzyme activity, as carriers of either or both alleles are classified as moderate or slow metabolizers, and therefore exhibit higher sensitivity of warfarin compared with wild type (CYP2C9*1*1). Our study aimed to assess the frequency of *1, *2, and *3 alleles in the CYP2C9 gene in a cohort of Syrian patients receiving a maintenance dose of warfarin for different indications, the impact of genotypes on warfarin dosing, and the frequency of adverse effects (i.e., bleedings). Subjects & Methods: This retrospective cohort study encompassed 94 patients treated with warfarin. Patients’ genotypes were identified by sequencing the polymerase chain reaction (PCR) specific products of the gene encoding CYP2C9, and the effects on warfarin therapeutic outcomes were investigated. Results: Sequencing revealed that 43.6% of the study population has the *2 and/or *3 SNPs. The mean weekly maintenance dose of warfarin was 37.42 ± 15.5 mg for patients with the wild-type allele (CYP2C9*1*1), whereas patients with one or both variants (*2 and/or *3) demanded a significantly lower dose (28.59 ±11.58 mg) of warfarin, (P= 0.015). A higher percentage (40.7%) of patients with allele *2 and/or *3 experienced hemorrhagic accidents compared with only 17.9% of patients with the wild type *1*1, (P = 0.04). Conclusions: Our study proves an association between *2 and *3 genotypes and higher sensitivity to warfarin and a tendency to bleed, which necessitates lowering the dose. These findings emphasize the significance of CYP2C9 genotyping prior to commencing warfarin therapy in order to achieve optimal and faster dose control and to ensure effectiveness and safety.

Keywords: warfarin, CYP2C9, polymorphisms, Syrian, hemorrhage

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Authors: Suneeta Gireesh Panicker

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Aim: Aminopeptidase P (APP) is an enzyme that has specificity for proline, can specifically cleave Xaa-Proline peptides and is a metallo-aminopeptidase. The bonds nearby to the imino acid proline are tough to cleave by many peptidases, but APP can specifically break peptide bonds engaged with proline. Membrane-bound form and a cytosolic form are the two forms in which this enzyme exists. The exact physiological function of APP remains unclear and hence the present work attempts to determine it. Methods: In the present study, the expression pattern of cytosolic Aminopeptidase P (DAP) was determined in all the embryonic stages and larval stages of wild-type Drosophila by using polyclonal monospecific antibodies. To show the presence of DAP RNA in embryonic and larval stages, RNA in situ hybridization was performed. DAP promoter-LacZ fusion reporter gene vector was used to construct transgenic embryos to study the regulation pattern of DAP. To study the DAP expression profile, a transgenic fly consisting of a DAP promoter with β-gal and GFP reporter genes in front of it was constructed. Results: DAP protein expression was observed in neuroectodermal cells, posterior midgut primordium, proctodeum, ventral neuroblast and primordial stomatogastric nervous system. It was observed in the ventral cord and midgut in stage 12. The completely developed embryos showed the intense occurrence of it in the ventral cord and gut region. The eye-antennal disc, wing disc and leg disc also showed the presence of DAP protein. LacZ expression in transgenic embryos also showed the same pattern. Conclusion: Similar to various known multiple-functional proteins, DAP could be one with different functions at different stages and in different cells. Data presented here designates DAP functions in the early embryonic and imaginal dics differentiation and development, suggesting that it may be required for the metabolism of proteins like neuropeptides and tachykinins.

Keywords: aminopeptidase P, in situ hybridization, transgenic fly, embryonic stages

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Authors: Ahmed Elbeltagy, Francesca Bertolini, Damarius Fleming, Angelica Van Goor, Chris Ashwell, Carl Schmidt, Donald Kugonza, Susan Lamont, Max Rothschild

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The major factor in shaping genomic variation of the African indigenous rural chicken is likely natural selection drives the development genetic footprints in the chicken genomes. To investigate such a hypothesis of a selection footprint, a total of 292 birds were randomly sampled from three indigenous ecotypes from East Africa (Uganda, Rwanda) and North Africa (Egypt) and two registered Egyptian breeds (Fayoumi and Dandarawi), and from the synthetic Kuroiler breed. Samples were genotyped using the Affymetrix 600K Axiom® Array. A total of 526,652 SNPs were utilized in the downstream analysis after quality control measures. The intra-population runs of homozygosity (ROH) that were consensuses in > 50% of individuals of an ecotype or > 75% of a breed were studied. To identify inter-population differentiation due to genetic structure, FST was calculated for North- vs. East- African populations in addition to population-pairwise combinations for overlapping windows (500Kb with an overlap of 250Kb). A total of 28,563 ROH were determined and were classified into three length categories. ROH and Fst detected sweeps were identified on several autosomes. Several genes in these regions are likely to be related to adaptation to local environmental stresses that include high altitude, diseases resistance, poor nutrition, oxidative and heat stresses and were linked to gene ontology terms (GO) related to immune response, oxygen consumption and heme binding, carbohydrate metabolism, oxidation-reduction, and behavior. Results indicated a possible effect of natural selection forces on shaping genomic structure for adaptation to local environmental stresses.

Keywords: African Chicken, runs of homozygosity, FST, selection footprints

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Authors: Vinod Kumar Gupta, Narendrakumar M. Chaudhari, Suchismitha Iskepalli, Chitra Dutta

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Background-The community composition of the human microbiome is known to vary at distinct anatomical niches. But little is known about the nature of variations if any, at the genome/sub-genome levels of a specific microbial community across different niches. The present report aims to explore, as a case study, the variations in gene repertoire of 28 Prevotella reference draft genomes derived from different body-sites of human, as reported earlier by the Human Microbiome Consortium. Results-The analysis reveals the exclusive presence of 11798, 3673, 3348 and 934 gene families and exclusive absence of 17, 221, 115 and 645 gene families in Prevotella genomes derived from the human oral cavity, gastro-intestinal tracts (GIT), urogenital tract (UGT) and skin, respectively. The pan-genome for Prevotella remains “open”. Distribution of various functional COG categories differs appreciably among the habitat-specific genes, within Prevotella pan-genome and between the GIT-derived Bacteroides and Prevotella. The skin and GIT isolates of Prevotella are enriched in singletons involved in Signal transduction mechanisms, while the UGT and oral isolates show higher representation of the Defense mechanisms category. No niche-specific variations could be observed in the distribution of KEGG pathways. Conclusion-Prevotella may have developed distinct genetic strategies for adaptation to different anatomical habitats through selective, niche-specific acquisition and elimination of suitable gene-families. In addition, individual microorganisms tend to develop their own distinctive adaptive stratagems through large repertoires of singletons. Such in situ, habitat-driven refurbishment of the genetic makeup can impart substantial intra-lineage genome diversity within the microbes without perturbing their general taxonomic heritage.

Keywords: body niche adaptation, human microbiome, pangenome, Prevotella

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Authors: H. N. S. Silva, S. N. Silva

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Introduction: 88.3% of physicians decided to choose a ‘no-code’ or a DNR order if hospitalized and would choose to die less aggressively at home. However, their wishes were mostly over ridden. Objective: To assess the attitudes of nurses towards the end-of-the-life care they would like to receive for themselves and their attitudes towards terminal illnesses. Methods: A mixed method approach was used. A closed and open-ended questionnaire was administered to 73 participants and 5 registered nurses, who have more than 10 years of experience, working in hospitals both in Sri Lanka and abroad, were interviewed. Results: 94.1% of the participants stated that they would like to die at home, spending their last hours at home surrounded by their loved ones and engaging in religious activities but 57.7% of unmarried nurse said they would agree on euthanasia if they had a terminal disease, and also 66.2% of them stated they would agree in DNR order if they happen to be admitted to the ICU, but 82.5% wanted to diagnose if they had a terminal illness or cancer but did not agree on euthanasia. Qualitative analysis confirmed the findings and revealed that despite having adequate confidence about the hospital care, nurses would choose to die at home, surrounded by their loved once and engaging in religious activities. Euthanasia was believed to be inappropriate as it is religiously incorrect and as death is a natural process. Conclusion: The perception of death among nurses depends on their religious belief.

Keywords: death, do not resuscitate, euthanasia, nurses

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Authors: V. Konjik, J. Schwartz, R. Sandhoff, M. Mack

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The rising number of multi-resistant pathogens demands the development of new antibiotics in order to reduce the lethal risk of infections. Here, we investigate roseoflavin, a vitamin B2 analogue which is produced by Streptomyces davawensis and Streptomyces cinnabarinus. We consider roseoflavin to be a 'Trojan horse' compound. Its chemical structure is very similar to riboflavin but in fact it is a toxin. Furthermore, it is a clever strategy with regard to the delivery of an antibiotic to its site of action but also with regard to the production of this chemical: The producer cell has only to convert a vitamin (which is already present in the cytoplasm) into a vitamin analog. Roseoflavin inhibits the activity of Flavin depending proteins, which makes up to 3.5 % of predicted proteins in organisms sequenced so far. We sequentially knocked out gene clusters and later on single genes in order to find the ones which are involved in the roseoflavin biosynthesis. Consequently, we identified the gene rosB, coding for the protein carrying out the first step of roseoflavin biosynthesis, starting form Flavin mononucleotide. Here we show, that the protein RosB has so far unknown features. It is per se an oxidoreductase, a decarboxylase and an aminotransferase, all rolled into one enzyme. A screen of cofactors revealed needs of oxygen, NAD+, thiamine and glutamic acid to carry out its function. Surprisingly, thiamine is not only needed for the decaboxylation step, but also for the oxidation of 8-demethyl-8-formyl Flavin mononucleotide. We had managed to isolate three different Flavin intermediates with different oxidation states, which gave us a mechanistic insight of RosB functionality. Our work points to a so far new function of thiamine in Streptomyces davawensis. Additionally, RosB could be extremely useful for chemical synthesis. Careful engineering of RosB may allow the site-specific replacement of methyl groups by amino groups in polyaromatic compounds of commercial interest. Finally, the complete clarification of the roseoflavin biosynthesis opens the possibility of engineering cost-effective roseoflavin producing strains.

Keywords: antibiotic, flavin analogue, roseoflavin biosynthesis, vitamin B2

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Authors: Chanasit Chaocharoenphat

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Hibiscus sabdariffa is a herbal plant that is commonly used for home remedies in Thailand. This study aims to determine the antioxidant activity of polyphenols, as oxidative stress plays a vital role in the development of cancer, and H. sabdariffa was used in this study. The total flavonoids content was determined using the aluminium chloride colourimetric method and expressed as quercetin equivalents (QE)/g and the antioxidant capacity of the flavonoids using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging capacity assays. The IC50 values of H. sabdariffa extract were 167.14 μg/mL ± 0.843 and 77.59 μg/mL ± 0.798, respectively. In the DPPH assay, vitamin C was used as a positive control, whereas Trolox was used as a positive control in the ABTS assay. To summarise, H. sabdariffa extract contains a high concentration of total flavonoids and exhibits potent antioxidant activity. However, additional antioxidant activity assays such as superoxide dismutase (SOD), reactive oxygen species (ROS), and reactive nitrogen species (RNS) scavenging assays and in vitro antioxidant experiments should be carried out to investigate the molecular mechanism of the compound.

Keywords: ABTS assay, antioxidant activity, Gracilaria fisheri, DPPH assays, total flavonoid content

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Authors: Cliff Shunsheng Han

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Identifying the direct allergy cause that can be easily mitigated is the foundation to stop the allergy epidemic that has been started in the seventies. It has confirmed that the personal and social hygiene practices are associated with the allergy prevalence. But direct causes have been found, and proposed translational measures have not been effective. This study, assisted by a particular case of allergies, has seen the direct cause of allergies, developed a valid test resulted in lasting relief for allergies, and constructed theory describing general relationship between microbiota and host immune system. Saliva samples were collected from a subject for three years during which time the person experienced yearlong allergy, seasonal allergy, and remission of allergy symptoms. Bacterial DNA was extracted and 16S rRNA genes were profiled with Illumina sequencing technology. The analyzing results indicate that the possible direct cause of allergy is the lacking probiotic bacteria in the oral cavity, such as genera Streptococcus and Veilonella, that can produce metabolites to pacify immune system. Targeted promotion of those bacteria with a compound designed for them, has led to lasting remissions of allergic rhinitis. During the development of the translational measure, the subject's oral biofilm was completely destructed by a moderate fever due to an unrelated respiratory infection. The incident not only facilitated the development of the heat based microbiota reseeding procedure but also indicated a possible natural switch that subsequently increases the efficacy of the immune system previously restrained by metabolites from microbiota. These results lead to the proposal of a Theory of Negative Trigger (TNT) to describe the relationship between oral probiotics and immune system, in which probiotics are the negative trigger that will release the power of immune system when removed by fever or modern lifestyles. This study could open doors leading to further understanding of how the immune system functions under the influence of microbiota as well as validate simple traditional practices for healthy living.

Keywords: oral microbiome, allergy, immune system, infection

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Authors: Maryam Monazzah, Ronak Samadpour, Mehdi Nasr-esfahani, Fatemeh Qalavand, Marziye Motamedi

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Bipolaris sorokiniana, and Heterodera filipjevi, are important wheat diseases that lead to yield losses worldwide. Identifying novel resistant sources helps us combat these devastating diseases. In this study, we studied the role of Cre3 gene and antioxidant enzymes in the immune responses of wheat genotypes to H. filipjevi and B. sorokiniana. Therefore, real-time PCR analysis using Cre3 gene marker, a resistant gene to cereal cyst nematodes, was conducted on leaves and roots, along with changes ‎in the activity of antioxidant enzymes, peroxidase, and catalase. Enzyme activity assay was performed on roots attacked by nematode and in leaves infected with Bipolaris. Wheat accessions including “Bam” (resistant), “Parsi” (moderately-resistant), “Azar2”, “Ohadi”, “Homa” (highly-susceptible) were previously screened against both stresses under greenhouse and field conditions. Results showed that Cre3 expression against cyst nematodes was significantly higher in resistant cultivars compared to susceptible cultivars. Cre3 was used in marker-assisted selection programs to identify genotypes carrying resistant genes to cyst nematodes. Interestingly, Cre3 was also up-regulated in both tissues of resistant cultivars to B. sorokiniana. Therefore, Cre3 in wheat similarly modulates immunity against B. sorokiniana and might be one of the central components of the induced immune system in wheat. The activity of antioxidant enzymes also indicated the highest increase in resistant genotypes upon both stresses that subsequently neutralize oxidative stress in tissues and decrease damage. Further studies on these resistance components may help us gain insight into the molecular basis of resistance and shed new light on the interaction and overlap between different forms of stress.

Keywords: Bipolaris sorokiniana, Heterodera filipjevi, resistant gene expression, wheat

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Authors: E.A. Kuchma

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Photodynamic therapy (PDT) is considered an alternative and minimally invasive cancer treatment modality compared to chemotherapy and radiation therapy. PDT includes three main components: a photosensitizer (PS), oxygen, and a light source. PS is injected into the patient's body and then selectively accumulates in the tumor. However, the light used in PDT (spectral range 400–700 nm) is limited to superficial lesions, and the light penetration depth does not exceed a few cm. The problem of PDT (poor visible light transmission) can be solved by using X-rays. The penetration depth of X-rays is ten times greater than that of visible light. Therefore, X-ray radiation easily penetrates through the tissues of the body. The aim of this work is to develop universal nanocomposites for X-ray photodynamic therapy of deep and superficial tumors using scintillation nanoparticles of gadolinium fluoride (GdF3), doped with Tb3+, coated with a biocompatible coating (PEG) and photosensitizer RB (Rose Bengal). PEG@GdF3:Tb3+(15%) – RB could be used as an effective X-ray, UV, and photoluminescent mediator to excite a photosensitizer for generating reactive oxygen species (ROS) to kill tumor cells via photodynamic therapy. GdF3 nanoparticles can also be used as contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI).

Keywords: X-ray induced photodynamic therapy, scintillating nanoparticle, radiosensitizer, photosensitizer

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Authors: Mindaye Teshome, Nesibu Yahya, Carlos Moreira Miquelino Eleto Torres, Pedro Manuel Villaa, Mehari Alebachew

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Arbagugu forest is one of the remnant dry Afromontane forests under severe anthropogenic disturbances in central Ethiopia. Despite this fact, up-to-date information is lacking about the status of the forest and its role in climate change mitigation. In this study, we evaluated the woody species composition, structure, biomass, and carbon stock in this forest. We employed a systematic random sampling design and established fifty-three sample plots (20 × 100 m) to collect the vegetation data. A total of 37 woody species belonging to 25 families were recorded. The density of seedlings, saplings, and matured trees were 1174, 101, and 84 stems ha-1, respectively. The total basal area of trees with DBH (diameter at breast height) ≥ 2 cm was 21.3 m2 ha-1. The characteristic trees of dry Afromontane Forest such as Podocarpus falcatus, Juniperus procera, and Olea europaea subsp. cuspidata exhibited a fair regeneration status. On the contrary, the least abundant species Lepidotrichilia volkensii, Canthium oligocarpum, Dovyalis verrucosa, Calpurnia aurea, and Maesa lanceolata exhibited good regeneration status. Some tree species such as Polyscias fulva, Schefflera abyssinica, Erythrina brucei, and Apodytes dimidiata lack regeneration. The total carbon stored in the forest ranged between 6.3 Mg C ha-1 and 835.6 Mg C ha-1. This value is equivalent to 639.6 Mg C ha-1. The forest had a very low number of woody species composition and diversity. The regeneration study also revealed that a significant number of tree species had unsatisfactory regeneration status. Besides, the forest had a lower carbon stock density compared with other dry Afromontane forests. This implies the urgent need for forest conservation and restoration activities by the local government, conservation practitioners, and other concerned bodies to maintain the forest and sustain the various ecosystem goods and services provided by the Arbagugu forest.

Keywords: aboveground biomass, forest regeneration, climate change, biodiversity conservation, restoration

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Authors: Zahia Kabouche, Ouissem Gherboudj, Naima Boutaghane, Ahmed Kabouche, Laurence Voutquenne-Nazabadioko

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Chrysanthemum herbs (Asteraceae) are extensively used as food additives and in folk medicine. Anti-cancer, anti-human immunodeficiency virus type 1 (HIV-1), anti-inflammatory, antinociceptive and antiproliferative activities as well as antioxidant effects have been reported for Chrysanthemum species. We report the isolation and identification of flavonoids and new and known terpenoids from the endemic species, C. macrocarpum and C. deserticolum “guertoufa”, used in Algerian Sahara as tea drinks and in “couscous” and soups “Chorba”. Structures of the isolated compounds were established by 1-D and 2-D homo and hetero-nuclear NMR (1H, 13C, COSY, HSQC, HMBC, and NOESY), mass spectrometry, UV and comparison with literature data. C. deserticolum extracts were tested by four methods to identify the antioxidant activity namely, ABTS•+, DPPH• scavenging, CUPRAC and ferrous-ions chelating activity methods. Anti-inflammatory, antinociceptive, antiproliferative and antioxidant activities of C. macrocarpum extracts and isolated compounds are also reported here.

Keywords: Chrysanthemum macrocarpum, C. deserticolum, flavonoids, terpenoids, antioxidant, anti-inflammatory, anti-proliferative

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Authors: Kyriaki Hatziagapiou, Konstantinos Bethanis, Olti Nikola, Elias Christoforides, Eleni Koniari, Eleni Kakouri, George Lambrou, Christina Kanaka-Gantenbein

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Glioblastoma multiforme (GBM) remains a serious health challenge, as current therapeutic modalities continue to yield unsatisfactory results, with the average survival rarely exceeding 1-2 years. Natural compounds still provide some of the most promising approaches for discovering new drugs. The non-psychotropic cannabidiol (CBD) deriving from Cannabis sativa L. provides such promise. CBD is endowed with anticancer, antioxidant, and genoprotective properties as established in vitro and in in vivo experiments. CBD’s selectivity towards cancer cells and its safe profile suggest its usage in cancer therapies. However, the bioavailability of oral CBD is low due to poor aqueous solubility, erratic gastrointestinal absorption, and significant first-pass metabolism, hampering its therapeutic potential and resulting in a variable pharmacokinetic profile. In this context, CBD can take great advantage of nanomedicine-based formulation strategies. Cyclodextrins (CDs) are cyclic oligosaccharides used in the pharmaceutical industry to incorporate apolar molecules inside their hydrophobic cavity, increasing their stability, water solubility, and bioavailability or decreasing their side effects. CBD-inclusion complexes with CDs could be a good strategy to improve its properties, like solubility and stability to harness its full therapeutic potential. The current research aims to study the potential cytotoxic effect of CBD and CBD-CDs complexes CBD-RMβCD (randomly methylated β-cyclodextrin) and CBD-HPβCD (hydroxypropyl-b-CD) on the A172 glioblastoma cell line. CBD is diluted in 10% DMSO, and CBD/CDs solutions are prepared by mixing solid CBD, solid CDs, and dH2O. For the biological assays, A172 cells are incubated at a range of concentrations of CBD, CBD-RMβCD and CBD-HPβCD, RMβCD, and HPβCD (0,03125-4 mg/ml) at 24, 48, and 72 hours. Analysis of cell viability after incubation with the compounds is performed with Alamar Blue viability assay. CBD’s dilution to DMSO 10% was inadequate, as crystals are observed; thus cytotoxicity experiments are not assessed. CBD’s solubility is enhanced in the presence of both CDs. CBD/CDs exert significant cytotoxicity in a dose and time-dependent manner (p < 0.005 for exposed cells to any concentration at 48, 72, and 96 hours versus cells not exposed); as their concentration and time of exposure increases, the reduction of resazurin to resofurin decreases, indicating a reduction in cell viability. The cytotoxic effect is more pronounced in cells exposed to CBD-HPβCD for all concentrations and time-points. RMβCD and HPβCD at the highest concentration of 4 mg/ml also exerted antitumor action per se since manifesting cell growth inhibition. The results of our study could afford the basis of research regarding the use of natural products and their inclusion complexes as anticancer agents and the shift to targeted therapy with higher efficacy and limited toxicity. Acknowledgments: The research is partly funded by ΙΚΥ (State Scholarships Foundation) – Post-doc Scholarships-Partnership Agreement 2014-2020.

Keywords: cannabidiol, cyclodextrins, glioblastoma, hydroxypropyl-b-Cyclodextrin, randomly-methylated-β-cyclodextrin

Procedia PDF Downloads 158

Authors: Choonoh Lee, Seyeon Park, Dongyun Kang, Jaehyeong Choi, Soojee Kim, Younggeun Kim

Abstract:

Market Kurly is the first South Korean online grocery retailer that guarantees same-day, overnight shipping. More than 1.6 million customers place an average of 4.7 million orders and add 3 to 14 products into a cart per month. The company has sold almost 30,000 kinds of various products in the past 6 months, including food items, cosmetics, kitchenware, toys for kids/pets, and even flowers. The company is operating and expanding multiple dry, cold, and frozen fulfillment centers in order to store and ship these products. Due to the scale and complexity of the fulfillment, pick-pack-ship processes are planned and operated in batches, and thus, the planning that decides the batch of the customers’ orders is a critical factor in overall productivity. This paper introduces a metaheuristic optimization method that reduces the complexity of batch processing in a fulfillment center. The method is an iterative genetic algorithm with heuristic creation and evolution strategies; it aims to group similar orders into pick-pack-ship batches to minimize the total number of distinct products. With a well-designed approach to create initial genes, the method produces streamlined plans, up to 13.5% less complex than the actual plans carried out in the company’s fulfillment centers in the previous months. Furthermore, our digital-twin simulations show that the optimized plans can reduce 3% of operation time for packing, which is the most complex and time-consuming task in the process. The optimization method implements a multithreading design on the Spring framework to support the company’s warehouse management systems in near real-time, finding a solution for 4,000 orders within 5 to 7 seconds on an AWS c5.2xlarge instance.

Keywords: fulfillment planning, genetic algorithm, online grocery retail, optimization

Procedia PDF Downloads 71

Authors: J. U. Santhosh Kumar, V. Krishna, Sebin Sebastian, G. S. Seethapathy, G. Ravikanth, R. Uma Shaanker

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Food is one of the basic needs of human beings. It requires the normal function of the body part and a healthy growth. Recently, food adulteration increases day by day to increase the quantity and make more benefit. Animal source foods can provide a variety of micronutrients that are difficult to obtain in adequate quantities from plant source foods alone. Particularly in the meat industry, products from animals are susceptible targets for fraudulent labeling due to the economic profit that results from selling cheaper meat as meat from more profitable and desirable species. This work presents an overview of the main PCR-based techniques applied to date to verify the authenticity of beef meat and meat products from beef species. We were analyzed 25 market beef samples in South India. We examined PCR methods based on the sequence of the cytochrome b gene for source species identification. We found all sample were sold as beef meat as Bos Taurus. However, interestingly Male meats are more valuable high price compare to female meat, due to this reason most of the markets samples are susceptible. We were used sex determination gene of cattle like TSPY(Y-encoded, testis-specific protein TSPY is a Y-specific gene). TSPY homologs exist in several mammalian species, including humans, horses, and cattle. This gene is Y coded testis protein genes, which only amplify the male. We used multiple PCR products form species-specific “fingerprints” on gel electrophoresis, which may be useful for meat authentication. Amplicons were obtained only by the Cattle -specific PCR. We found 13 market meat samples sold as female beef samples. These results suggest that the species-specific PCR methods established in this study would be useful for simple and easy detection of adulteration of meat products.

Keywords: authentication, meat products, species-specific, TSPY

Procedia PDF Downloads 361

Authors: Sabahattin Comertpay, Sandra Pastorino, Rosanna Mezzapelle, Mika Tanji, Oriana Strianese, Andrea Napolitano, Tracey Weigel, Joseph Friedberg, Paul Sugarbaker, Thomas Krausz, Ena Wang, Amy Powers, Giovanni Gaudino, Harvey I. Pass, Fatmagul Ozcelik, Barbara L. Parsons, Haining Yang, Michele Carbone

Abstract:

Tumors are thought to be monoclonal in origin. This paradigm arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas. The clonal origin of malignant mesothelioma (MM), a deadly cancer resistant to the current therapies, has not been investigated. Examination of the pleura from patients with MM shows often the presence of multiple pleural nodules, raising the question of whether they represent independent or metastatic growth processes. To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 14 sporadic and 2 familial Malignant Mesotheliomas (MM). Of 16 specimens studied, 15 were informative and 14/15 revealed two electrophoretically distinct methylated HUMARA alleles, indicating a polyclonal origin for these tumors. This discovery has important clinical implications, because an accurate assessment of tumor clonality is key to the design of novel molecular strategies for the treatment of MM.

Keywords: malignant mesothelioma, clonal origin, HUMARA, sarcomas

Procedia PDF Downloads 445

Authors: Maysam Mard-Soltani, Mohamad Javad Rasaee, Saeed Khalili, Abdol Karim Sheikhi, Mehdi Hedayati

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Production of specific antibody responses against hTSH is a cumbersome process due to the high identity between the hTSH and the other members of the glycoprotein hormone family (FSH, LH and HCG) and the high identity between the human hTSH and host animals for antibody production. Therefore, two polyclonal antibodies were purified against two recombinant proteins. Four possible ELISA tests were designed based on these antibodies. These ELISA tests were checked against hTSH and other glycoprotein hormones, and their sensitivity and specificity were assessed. Bioinformatics tools were used to analyze the immunological properties. After the immunogen region selection from hTSH protein, c terminal of B hTSH was selected and applied. Two recombinant genes, with these cut pieces (first: two repeats of C terminal of B hTSH, second: tetanous toxin+B hTSH C terminal), were designed and sub-cloned into the pET32a expression vector. Standard methods were used for protein expression, purification, and verification. Thereafter, immunizations of the white New Zealand rabbits were performed and the serums of them were used for antibody titration, purification and characterization. Then, four ELISA tests based on two antibodies were employed to assess the hTSH and other glycoprotein hormones. The results of these assessments were compared with standard amounts. The obtained results indicated that the desired antigens were successfully designed, sub-cloned, expressed, confirmed and used for in vivo immunization. The raised antibodies were capable of specific and sensitive hTSH detection, while the cross reactivity with the other members of the glycoprotein hormone family was minimum. Among the four designed tests, the test in which the antibody against first protein was used as capture antibody, and the antibody against second protein was used as detector antibody did not show any hook effect up to 50 miu/l. Both proteins have the ability to induce highly sensitive and specific antibody responses against the hTSH. One of the antibody combinations of these antibodies has the highest sensitivity and specificity in hTSH detection.

Keywords: hTSH, bioinformatics, protein expression, cross reactivity

Procedia PDF Downloads 177

Authors: Hailemariam Solomon, Taye Tadesse, Daniel Nadew, Firezer Girma

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Sorghum is an important crop in semi-arid regions and has shown resilience to drought stress. However, recurrent drought is affecting its productivity. Therefore, it is necessary to explore genes that contribute to drought stress adaptation to increase sorghum productivity. The aim of this study is to evaluate and determine the effect of root system traits, specifically root angle, on drought stress adaptation and grain yield performance in sorghum genotypes. A total of 428 sorghum genotypes from the Ethiopian breeding program were evaluated in three drought-stress environments. Field trials were conducted using a row-column design with three replications. Root system traits were phenotyped using a high-throughput phenotyping platform and analyzed using a row-column design with two replications. Data analysis was performed using R software and regression analysis. The study found significant variations in root system architecture among the sorghum genotypes. Non-stay-green genotypes had a grain yield ranging from 1.63 to 3.1 tons/ha, while stay-green genotypes had a grain yield ranging from 2.4 to 2.9 tons/ha. The analysis of root angle showed that non-stay-green genotypes had an angle ranging from 8.0 to 30.5 degrees, while stay-green genotypes had an angle ranging from 12.0 to 29.0 degrees. Improved varieties exhibited angles between 14.04 and 19.50 degrees. Positive and significant correlations were observed between leaf areas and shoot dry weight, as well as between leaf width and shoot dry weight. Negative correlations were observed between root angle and leaf area, as well as between root angle and root length. This research highlights the importance of root system architecture, particularly root angle traits, in enhancing grain yield production in drought-stressed conditions. It also establishes an association between root angle and grain yield traits for maximizing sorghum productivity.

Keywords: roor sysytem architecture, root angle, narrow root angle, wider root angle, drought

Procedia PDF Downloads 61

Authors: Komala Arsi, Terrel Spencer, Casey M. Owens, Dan J. Donoghue, Ann M. Donoghue

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Organic poultry production is becoming increasingly popular in the United States with approximately 17% increase in the sales of organic meat and poultry in 2016. As per the National Organic Program (NOP), organic poultry production system should operate according to specific standards, including access to outdoors. In the United States, organic poultry farmers are raising both fast growing and slow growing genotypes for alternative productive systems. Even though heritage breed birds grow much slower compared to commercial breeds, many free range producers believe that they are better suited for outdoor production systems. We conducted an on-farm trial on a working pasture poultry farm to compare the performance and meat quality characteristics of a slow-growing heritage breed (Freedom Rangers, FR), and two commonly used fast growing types of chickens (Cornish cross, CC and Naked Neck, NN), raised on pasture, in side by side pens segregated by breed (n=70/breed). CC and NN group birds were reared for eight weeks whereas FR group birds were reared for 10 weeks and all the birds were commercially processed. By the end of the rearing period, the final body weight of FR group birds was significantly lower than both the fast growing genotypes (CC and NN). Both CC and NN birds showed significantly higher live weight, carcass weight as well as fillet, tender and leg yield (P < 0.05). There was no difference in the wing and rack yield among the different groups. Color of the meat was measured using CEILAB method and expressed as lightness (L), redness (a*) and yellowness (b*). The breast meat from FR birds was much redder (higher a* values) and less yellow (lesser b* values) compared to both the fast growing type of chickens (P < 0.05). Overall, fast growing genotypes produced higher carcass weight and meat yield compared to slow growing genotypes and appear to be an economical option for alternative production systems.

Keywords: fast growing chickens, meat quality, pasture, slow growing chickens

Procedia PDF Downloads 372

Authors: Ankush M. Dewle, Suditi Bhattacharya, Prachi R. Abhang, Savita Datar, Ajay J. Jog, Rupesh K. Srivastava, Geetanjali Tomar

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Objectives: The aim of this study was to investigate the quality of mesenchymal stem cells (MSCs) obtained from ageing gingival tissues, in order to suggest their potential role in autologous stem cell therapy for old individuals. Methods: MSCs were isolated from gingival tissues of young (18-45 years) and old (above 45 years) donors by enzymatic digestion. MSCs were analysed for cfu-f, surface marker expression by flow-cytometry and multilineage differentiation potential. The angiogenic potential was compared in a chick embryo yolk sac membrane model. The aging and differentiation markers including SA-β-galactosidase and p21 respectively were analysed by staining and flow-cytometry analysis. Additionally, osteogenic markers such as glucocorticoid receptor (GR), vitamin D receptor (VDR) were measured by flow-cytometry and RT-qPCR was performed for quantification of osteogenic gene expression. Alizarin Red S and alkaline phosphatase (ALP) activity were also quantitated. Results: Gingival MSCs (GMSCs) from both the age groups were similar in their morphology and displayed cfu-f. They had similar expression of MSC surface markers and p21, comparable rate of proliferation and differentiated to all the four lineages. GMSCs from young donors had a higher adipogenic differentiation potential as compared to the old GMSCs. Moreover, these cells did not display a significant difference in ALP activity probably due to comparable expression of GR, VDR, and osteogenic genes. Conclusions: Ageing of GMSCs occurs at a much slower rate than stem cells from other sources. Thus we suggest GMSCs as an excellent candidate for autologous stem cell therapy in degenerative diseases of elderly individuals. Clinical Significance: GMSCs could help overcome the setbacks in clinical implementation of autologous stem cell therapy for regenerative medicine in all age group of patient.

Keywords: bone regeneration, cell therapy, senescence, stem cell

Procedia PDF Downloads 170

Authors: Mahsa Falahatpour

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Introduction: This study aims to explore how inter-observer variability in manual tumor segmentation impacts the reliability of radiomic features in non–small cell lung cancer (NSCLC). Methods: The study included twenty-three NSCLC tumors. Each patient had three tumor segmentations (VOL1, VOL2, VOL3) contoured on PET/CT scans by three radiation oncologists. Dice coefficients (DCS) were used to measure the segmentation variability. Radiomic features were extracted with 3D-slicer software, consisting of 66 features: first-order (n=15), second-order (GLCM, GLDM, GLRLM, and GLSZM) (n=33). The inter-observer variability of radiomic features was assessed using the intraclass correlation coefficient (ICC). An ICC > 0.8 indicates good stability. Results: The mean DSC of VOL1, VOL2, and VOL3 was 0.80 ± 0.04, 0.85 ± 0.03, and 0.76 ± 0.06, respectively. 92% of all extracted radiomic features were found to be stable (ICC > 0.8). The GLCM texture features had the highest stability (96%), followed by GLRLM features (90%) and GLSZM features (87%). The DSC was found to be highly correlated with the stability of radiomic features. Conclusion: The variability in inter-observer segmentation significantly impacts radiomics analysis, leading to a reduction in the number of appropriate radiomic features.

Keywords: PET/CT, radiomics, radiotherapy, segmentation, NSCLC

Procedia PDF Downloads 20

Authors: Hadeer Hegazy, Wael Ewieda, Ranin Soliman, Samah Elway, Asmaa Tawfik, Ragaa Sayed, Sahar Mousa

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The current healthcare system is facing major challenges in terms of cost, quality of care, and access to services. In response, the concept of value-based healthcare has emerged as a new approach to healthcare delivery. This concept puts the focus on patient values rather than on the traditional medical model of care. To achieve this, healthcare organizations must be agile and able to anticipate and respond quickly to changing needs. Agile management is essential for healthcare organizations to achieve value-based care, as it allows them to rapidly adjust their strategies to changing circumstances. Additionally, it is argued that agile management can help healthcare organizations gain a better understanding of the needs of their patients and develop better care delivery models. Besides, it can help healthcare organizations develop new services, innovate, and become more efficient. The authors provide evidence to support their argument, drawing on examples from successful value-based healthcare initiatives at children’s cancer hospital Egypt-57357. The paper offers insight into how agile management can be used to facilitate the shift towards value-based healthcare and how it can be used to maximize value in the healthcare system.

Keywords: value-based healthcare, agility in healthcare, nursing department, patients outcomes

Procedia PDF Downloads 753

Authors: James Ladzekpo

Abstract:

Background: The urgent need to identify new pharmacological targets for diabetes treatment and prevention has been amplified by the disease's extensive impact on individuals and healthcare systems. A deeper insight into the biological underpinnings of diabetes is crucial for the creation of therapeutic strategies aimed at these biological processes. Current predictive models based on genetic variations fall short of accurately forecasting diabetes. Objectives: Our study aims to pinpoint key epigenetic factors that predispose individuals to diabetes. These factors will inform the development of an advanced predictive model that estimates diabetes risk from genetic profiles, utilizing state-of-the-art statistical and data mining methods. Methodology: We have implemented a recursive feature elimination with cross-validation using the support vector machine (SVM) approach for refined feature selection. Building on this, we developed six machine learning models, including logistic regression, k-Nearest Neighbors (k-NN), Naive Bayes, Random Forest, Gradient Boosting, and Multilayer Perceptron Neural Network, to evaluate their performance. Findings: The Gradient Boosting Classifier excelled, achieving a median recall of 92.17% and outstanding metrics such as area under the receiver operating characteristics curve (AUC) with a median of 68%, alongside median accuracy and precision scores of 76%. Through our machine learning analysis, we identified 31 genes significantly associated with diabetes traits, highlighting their potential as biomarkers and targets for diabetes management strategies. Conclusion: Particularly noteworthy were the Gradient Boosting Classifier and Multilayer Perceptron Neural Network, which demonstrated potential in diabetes outcome prediction. We recommend future investigations to incorporate larger cohorts and a wider array of predictive variables to enhance the models' predictive capabilities.

Keywords: diabetes, machine learning, prediction, biomarkers

Procedia PDF Downloads 44

Authors: Mehran Fadaeinasab, Hamed Karimian, Najihah Mohd Hashim, Hapipah Mohd Ali

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In this study, three indole alkaloids namely; rauvolfine B, macusine B, and isoreserpiline have been isolated from the dichloromethane crude extract of Rauvolfia reflexa bark (Apocynaceae). The structural elucidation of the isolated compounds has been performed using spectral methods such as UV, IR, MS, 1D, and 2D NMR. Rauvolfine B showed anti proliferation activity on HCT-116 cancer cell line, its cytotoxicity induction was observed using MTT assay in eight different cell lines. Annexin-V is serving as a marker for apoptotic cells and the Annexin-V-FITC assay was carried out to observe the detection of cell-surface Phosphatidylserine (PS). Apoptosis was confirmed by using caspase-8 and -9 assays. Cell cycle arrest was also investigated using flowcytometric analysis. rauvolfine B had exhibited significantly higher cytotoxicity against HCT-116 cell line. The treatment significantly arrested HCT-116 cells in the S phase. Together, the results presented in this study demonstrated that rauvolfine B inhibited the proliferation of HCT-116 cells and programmed cell death followed by cell cycle arrest.

Keywords: apocynacea, indole alkaloid, apoptosis, cell cycle arrest

Procedia PDF Downloads 323