Search results for: blood cancer
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4427

Search results for: blood cancer

1637 The Stem Cell Transcription Co-factor Znf521 Sustains Mll-af9 Fusion Protein In Acute Myeloid Leukemias By Altering The Gene Expression Landscape

Authors: Emanuela Chiarella, Annamaria Aloisio, Nisticò Clelia, Maria Mesuraca

Abstract:

ZNF521 is a stem cell-associated transcription co-factor, that plays a crucial role in the homeostatic regulation of the stem cell compartment in the hematopoietic, osteo-adipogenic, and neural system. In normal hematopoiesis, primary human CD34+ hematopoietic stem cells display typically a high expression of ZNF521, while its mRNA levels rapidly decrease when these progenitors progress towards erythroid, granulocytic, or B-lymphoid differentiation. However, most acute myeloid leukemias (AMLs) and leukemia-initiating cells keep high ZNF521 expression. In particular, AMLs are often characterized by chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene, which MLL gene includes a variety of fusion oncogenes arisen from genes normally required during hematopoietic development; once they are fused, they promote epigenetic and transcription factor dysregulation. The chromosomal translocation t(9;11)(p21-22;q23), fusing the MLL gene with AF9 gene, results in a monocytic immune phenotype with an aggressive course, frequent relapses, and a short survival time. To better understand the dysfunctional transcriptional networks related to genetic aberrations, AML gene expression profile datasets were queried for ZNF521 expression and its correlations with specific gene rearrangements and mutations. The results showed that ZNF521 mRNA levels are associated with specific genetic aberrations: the highest expression levels were observed in AMLs involving t(11q23) MLL rearrangements in two distinct datasets (MILE and den Boer); elevated ZNF521 mRNA expression levels were also revealed in AMLs with t(7;12) or with internal rearrangements of chromosome 16. On the contrary, relatively low ZNF521 expression levels seemed to be associated with the t(8;21) translocation, that in turn is correlated with the AML1-ETO fusion gene or the t(15;17) translocation and in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. Invitro, we found that the enforced co-expression of ZNF521 in cord blood-derived CD34+ cells induced a significant proliferative advantage, improving MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome profiling of CD34+ cells transduced with either MLL-AF9, ZNF521, or a combination of the two transgenes highlighted specific sets of up- or down-regulated genes that are involved in the leukemic phenotype, including those encoding transcription factors, epigenetic modulators, and cell cycle regulators as well as those engaged in the transport or uptake of nutrients. These data enhance the functional cooperation between ZNF521 and MA9, resulting in the development, maintenance, and clonal expansion of leukemic cells. Finally, silencing of ZNF521 in MLL-AF9-transformed primary CD34+ cells inhibited their proliferation and led to their extinction, as well as ZNF521 silencing in the MLL-AF9+ THP-1 cell line resulted in an impairment of their growth and clonogenicity. Taken together, our data highlight ZNF521 role in the control of self-renewal and in the immature compartment of malignant hematopoiesis, which, by altering the gene expression landscape, contributes to the development and/or maintenance of AML acting in concert with the MLL-AF9 fusion oncogene.

Keywords: AML, human zinc finger protein 521 (hZNF521), mixed lineage leukemia gene (MLL) AF9 (MLLT3 or LTG9), cord blood-derived hematopoietic stem cells (CB-CD34+)

Procedia PDF Downloads 115
1636 Management of Therapeutic Anticancer at Oran Teaching Hospital, Algeria

Authors: S. Boulenouar, M. Sefir, M. Benahmed

Abstract:

All facilities need medication and other pharmaceuticals for their operation. Management and supply is therefore to provide the different services of the facility goods and services in required quantity and quality. The permanent availability of drugs in the facilities is very difficult because most face many difficulties at the inventory management and drug supplies. Therefore, it is necessary for each health facility to know the causes for the malfunction of its management system to cope with them. It is in this context that we have undertaken to conduct this study to know the causes which should be taken into consideration by the concerned authorities to carry out their mission, which is to provide quality health care for the population. In terms of financial resources, the budget for medicines represents a significant part of the budget of the pharmacy. Our study shows that the share of the hospital budget reserved for the drugs procurement represent on average 70% of the budget of the pharmacy. The results show a state of lack of anticancer drugs at Oran teaching hospital. The analysis of the management process allowed us to know the level that the problem of stock-outs of anti-cancer drugs is at. Suggestions were made to that effect to improve the availability for these products and to respond better to the needs of patients.

Keywords: anticancer drugs, health care facility, budget, hospital pharmacist, hospital service

Procedia PDF Downloads 450
1635 Core-Shell Structured Magnetic Nanoparticles for Efficient Hyperthermia Cancer Treatment

Authors: M. R. Phadatare, J. V. Meshram, S. H. Pawar

Abstract:

Conversion of electromagnetic energy into heat by nanoparticles (NPs) has the potential to be a powerful, non-invasive technique for biomedical applications such as magnetic fluid hyperthermia, drug release, disease treatment and remote control of single cell functions, but poor conversion efficiencies have hindered practical applications so far. In this paper, an attempt has been made to increase the efficiency of magnetic, thermal induction by NPs. To increase the efficiency of magnetic, thermal induction by NPs, one can take advantage of the exchange coupling between a magnetically hard core and magnetically soft shell to tune the magnetic properties of the NP and maximize the specific absorption rate, which is the gauge of conversion efficiency. In order to examine the tunability of magnetocrystalline anisotropy and its magnetic heating power, a representative magnetically hard material (CoFe₂O₄) has been coupled to a soft material (Ni₀.₅Zn₀.₅Fe₂O₄). The synthesized NPs show specific absorption rates that are of an order of magnitude larger than the conventional one.

Keywords: magnetic nanoparticles, surface functionalization of magnetic nanoparticles, magnetic fluid hyperthermia, specific absorption rate

Procedia PDF Downloads 325
1634 Urban Landscape for Walkability

Authors: Sara Khalifa, Dina Salem

Abstract:

Cities have become overly automobile-oriented which clearly accommodates driving at the expense of walking in an age of global concerns about emerging health issues (obesity, cancer, heart disease) and environmental disasters (global warming, depletion of resources) which makes sustainable solutions a necessity not an option. One of these sustainable solutions is creating walkable communities. Walking is a distinctive and fundamental human activity that plays an important role in achieving urban sustainability and yields incredible benefits to people and environment with its influence on transportation infrastructure, public health, economic development, and social equity. Considerable research supports the idea that the presence of green, natural settings and quality urban landscapes can enhance walking and other physical activity and travel behaviour. Stepping towards a sustainable future, requires rethinking our communities in terms of walkability enhancement for this purpose, this paper starts with defining walkable communities and their characteristics, benefits and related concepts then discusses the contribution of urban landscape quality in promoting walkability.

Keywords: walkability, walkable community, liveable communities, urban landscape qualities

Procedia PDF Downloads 509
1633 Preparation of Novel Antimicrobial Meat Packaging Using Chitosan-Arginine

Authors: R. A. Lahmer, A. P. Williams, S. Townsend, S. Baker, D. L. Jones

Abstract:

Chitosan-arginine (Ch-arg) has been proposed as an anti-microbial agent to reduce the proliferation of spoilage and pathogenic bacteria within meat products destined for human consumption. In the current experiment its use as an antimicrobial packaging material was examined. Two different concentrations of chitosan-arginine (0.05 and 0.15 % w/w) were blended into a cellulose film (Ch-arg film). When placed in contact with chicken and beef juice inoculated with a lux-marked strain of E. coli O157, the film incorporating the highest Ch-arg concentration resulted in a small reduction of E. coli O157 in chicken juice; however, there was no effect of the Ch-arg film on E. coli O157 in beef juice. The lack of observed effect in the beef juice experiment we ascribe to insufficient surface-to-surface contact between the film and the bacteria in the beef juice and the greater presence of other Ch-arg reactive components in the juice (e.g. fats, blood cells). Results suggest that, in combination with other anti microbials, Ch-arg packaging may offers some potential for limiting the growth of pathogenic bacteria in foodstuffs; however, further research is needed to enhance their anti-microbial performance.

Keywords: cross-contamination, foodborne pathogen, polymer film, shelf life

Procedia PDF Downloads 413
1632 N₂O₂ Salphen-Like Ligand and Its Pd(II), Ag(I) and Cu(II) Complexes as Potentially Anticancer Agents: Design, Synthesis, Antimicrobial, CT-DNA Binding and Molecular Docking

Authors: Laila H. Abdel-Rahman, Mohamed Shaker S. Adam, Ahmed M. Abu-Dief, Hanan El-Sayed Ahmed

Abstract:

In this investigation, Cu(II), Pd(II) and Ag(I) complexes with the tetra-dentate DSPH Schiff base ligand were synthesized. The DSPH Schiff base and its complexes were characterized by using different physicochemical and spectral analysis. The results revealed that the metal ions coordinated with DSPH ligand through azomethine nitrogen and phenolic oxygen. Cu(II), Pd(II) and Ag(I) complexes are present in a 1:1 molar ratio. Pd(II) and Ag(I) complexes have square planar geometries while, Cu(II) has a distorted octahedral (Oh) geometry. All investigated complexes are nonelectrolytes. The investigated compounds were tested against different strains of bacteria and fungi. Both prepared compounds showed good results of inhibition against the selected pathogenic microorganism. Moreover, the interaction of investigated complexes with CT-DNA was studied via various techniques and the binding modes are mainly intercalative and grooving modes. Operating Environment MOE package was used to do docking studies for the investigated complexes to explore the potential binding mode and energy. Furthermore, the growth inhibitory effect of the investigated compounds was examined on some cancer cells lines.

Keywords: tetradentate, antimicrobial, CT-DNA interaction, docking, anticancer

Procedia PDF Downloads 247
1631 The Effect of Thymoquinone and Sorafenib Combination on Hepatocellular Carcinoma Cell Line

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

Abstract:

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

Procedia PDF Downloads 558
1630 Factors Affecting Treatment Resilience in Patients with Oesophago-Gastric Cancers Undergoing Palliative Chemotherapy: A Literature Review

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

Abstract:

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

Procedia PDF Downloads 80
1629 Pre-Cancerigene Injuries Related to Human Papillomavirus: Importance of Cervicography as a Complementary Diagnosis Method

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

Abstract:

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

Procedia PDF Downloads 304
1628 KCBA, A Method for Feature Extraction of Colonoscopy Images

Authors: Vahid Bayrami Rad

Abstract:

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

Procedia PDF Downloads 59
1627 A Case of Severe Iatrogenic Cushing’s Syndrome Followed by Adrenal Crisis, Multifocal Pneumonia, Sepsis, Pulmonary Embolism and Prolonged Adrenal Insufficiency

Authors: Jelena Maletkovic

Abstract:

Background: Endogenous Cushing’s syndrome is a rare disease, but iatrogenic or drug related Cushing syndrome from glucocorticoid products is commonly seen in clinical practice. With high dose and long term use of glucocorticoids, patients can develop isolated hypothalamic-pituitary-adrenal (HPA) suppression, or HPA axis suppression can be accompanied by overt iatrogenic Cushing’s syndrome. This is a rare case where severe Cushing’s syndrome developed from an unknown medication and was followed by severe and prolonged adrenal insufficiency and multiple potentially fatal complications. Case: This is a 37-year-old woman who is presented to Emergency Room (ER) with shortness of breath and chest pain. Four months prior to this presentation the patient was a generally healthy woman who was looking for improvement in her appearance and visited local Rejuvenation Clinic. After initial consultation with a nurse, she was contacted by a physician over the phone and was advised to start taking multiple injectable medications that will arrive by mail. Medications without any labels on bottles were delivered and the patient started daily intramuscular injections. Over the next two months, she noticed rounding of her face and swelling around her eyes. She gained 20 pounds, mostly abdominal fat and became extremely fatigued. Her muscles on legs were visibly decreasing in size and she felt significant muscle weakness. Unexplained bruising occurred. She started growing hair on face and developed secondary amenorrhea. New severe back pain started. She developed depression and headaches. Finally, over a few days, a number of red-purple stretch marks that were sensitive and painful appeared over her abdomen, upper part of arms and legs. She then became suspicious that these dramatic symptoms are caused by injectable medication and she discontinued injections. Over the next few days she presented to ER with low blood pressure and oxygen saturation of 75%. Studies revealed extensive pneumonia as well as multiple pulmonary emboli. Her white blood count was elevated with 32 000 and she also had acute kidney failure on admission. She was treated for sepsis and was also given stress dose steroids. Steroids were tapered over 48 hours and discontinued. After being discharged to home, on her first visit to endocrinology clinic she had undetectable ACTH of < 2pg/mL and undetectable 8am cortisol of < 0.2mcg/dL. She did not respond to an intramuscular injection of cosyntropin 250mcg and her repeated cortisol after 60 minutes was only 1mcg/dL. The patient was diagnosed with adrenal insufficiency and was started on hydrocortisone 20mg+10mg. It took close to 2 years of slow tapering for recovery of this patient’s HPA axis and resolve all the sequelae from Cushing’s syndrome. Conclusion: Misuse and abuse of glucocorticoids have been present almost since these medications were discovered. This is a rare case where not only severe Cushing’s syndrome in full clinical picture developed but also the patient suffered multiple potentially fatal complications and prolonged adrenal insufficiency. Visits to herbal, rejuvenation, esthetic, and similar clinics are becoming more and more popular and physicians need to be aware of possible non-benign nature of medications that their patients may be using.

Keywords: iatrogenic, Cushing's syndrome, adrenal crisis, steroid abuse

Procedia PDF Downloads 173
1626 PMEL Marker Identification of Dark and Light Feather Colours in Local Canary

Authors: Mudawamah Mudawamah, Muhammad Z. Fadli, Gatot Ciptadi, Aulanni’am

Abstract:

Canary breeders have spread throughout Indonesian regions for the low-middle society and become an income source for them. The interesting phenomenon of the canary market is the feather colours become one of determining factor for the price. The advantages of this research were contributed to the molecular database as a base of selection and mating for the Indonesia canary breeder. The research method was experiment with the genome obtained from canary blood isolation. The genome did the PCR amplification with PMEL marker followed by sequencing. Canaries were used 24 heads of light and dark colour feathers. Research data analyses used BioEdit and Network 4.6.0.0 software. The results showed that all samples were amplification with PMEL gene with 500 bp fragment length. In base sequence of 40 was found Cytosine(C) in the light colour canaries, while the dark colour canaries was obtained Thymine (T) in same base sequence. Sequence results had 286-415 bp fragment and 10 haplotypes. The conclusions were the PMEL gene (gene of white pigment) was likely to be used PMEL gene to detect molecular genetic variation of dark and light colour feather.

Keywords: canary, haplotype, PMEL, sequence

Procedia PDF Downloads 241
1625 Recent Developments in E-waste Management in India

Authors: Rajkumar Ghosh, Bhabani Prasad Mukhopadhay, Ananya Mukhopadhyay, Harendra Nath Bhattacharya

Abstract:

This study investigates the global issue of electronic waste (e-waste), focusing on its prevalence in India and other regions. E-waste has emerged as a significant worldwide problem, with India contributing a substantial share of annual e-waste generation. The primary sources of e-waste in India are computer equipment and mobile phones. Many developed nations utilize India as a dumping ground for their e-waste, with major contributions from the United States, China, Europe, Taiwan, South Korea, and Japan. The study identifies Maharashtra, Tamil Nadu, Mumbai, and Delhi as prominent contributors to India's e-waste crisis. This issue is contextualized within the broader framework of the United Nations' 2030 Agenda for Sustainable Development, which encompasses 17 Sustainable Development Goals (SDGs) and 169 associated targets to address poverty, environmental preservation, and universal prosperity. The study underscores the interconnectedness of e-waste management with several SDGs, including health, clean water, economic growth, sustainable cities, responsible consumption, and ocean conservation. Central Pollution Control Board (CPCB) data reveals that e-waste generation surpasses that of plastic waste, increasing annually at a rate of 31%. However, only 20% of electronic waste is recycled through organized and regulated methods in underdeveloped nations. In Europe, efficient e-waste management stands at just 35%. E-waste pollution poses serious threats to soil, groundwater, and public health due to toxic components such as mercury, lead, bromine, and arsenic. Long-term exposure to these toxins, notably arsenic in microchips, has been linked to severe health issues, including cancer, neurological damage, and skin disorders. Lead exposure, particularly concerning for children, can result in brain damage, kidney problems, and blood disorders. The study highlights the problematic transboundary movement of e-waste, with approximately 352,474 metric tonnes of electronic waste illegally shipped from Europe to developing nations annually, mainly to Africa, including Nigeria, Ghana, and Tanzania. Effective e-waste management, underpinned by appropriate infrastructure, regulations, and policies, offers opportunities for job creation and aligns with the objectives of the 2030 Agenda for SDGs, especially in the realms of decent work, economic growth, and responsible production and consumption. E-waste represents hazardous pollutants and valuable secondary resources, making it a focal point for anthropogenic resource exploitation. The United Nations estimates that e-waste holds potential secondary raw materials worth around 55 billion Euros. The study also identifies numerous challenges in e-waste management, encompassing the sheer volume of e-waste, child labor, inadequate legislation, insufficient infrastructure, health concerns, lack of incentive schemes, limited awareness, e-waste imports, high costs associated with recycling plant establishment, and more. To mitigate these issues, the study offers several solutions, such as providing tax incentives for scrap dealers, implementing reward and reprimand systems for e-waste management compliance, offering training on e-waste handling, promoting responsible e-waste disposal, advancing recycling technologies, regulating e-waste imports, and ensuring the safe disposal of domestic e-waste. A mechanism, Buy-Back programs, will compensate customers in cash when they deposit unwanted digital products. This E-waste could contain any portable electronic device, such as cell phones, computers, tablets, etc. Addressing the e-waste predicament necessitates a multi-faceted approach involving government regulations, industry initiatives, public awareness campaigns, and international cooperation to minimize environmental and health repercussions while harnessing the economic potential of recycling and responsible management.

Keywords: e-waste management, sustainable development goal, e-waste disposal, recycling technology, buy-back policy

Procedia PDF Downloads 93
1624 Attitudes of Nurses towards End-of-Life Care for Themselves

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

Abstract:

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

Procedia PDF Downloads 522
1623 The Use of Ensiled Sweet Potato Vines as Feed for Growing Rabbits

Authors: O. John Makinde

Abstract:

A total of 60 crossbred weaned rabbits with an average initial body weight of 650 ±2.00 g were used to study the effects of dietary inclusion of graded levels of Ensiled sweet potato vines (ESPV) based diets on growth performance. Four experimental diets were formulated such that ESPV was included at the graded levels of 0, 10, 20 and 30 % in diets 1, 2, 3 and 4 respectively. The rabbits were randomly assigned into 4 treatments with 15 rabbits per treatment; each treatment was replicated thrice (5 rabbits per replicate) in a completely randomised design. The rabbits were managed based on standard experimental procedures. Feed and water were given ad libitum. Results of growth performance were not significantly different (p > 0.05) for final weight, total weight gain, total feed intake, feed conversion ratio and mortality. Carcass characteristics were not significantly (p > 0.05) affected by the treatments. The economics of production showed that diet with 30 % ESPV had the least cost/kg diets. It was concluded that ESPV can be included up to 30 % in growing rabbit diets without adverse effect on their performance, blood indices and cost of production.

Keywords: ensiled, sweet potato vines, performance, rabbits, Oryctolagus cuniculus

Procedia PDF Downloads 258
1622 Biological Activity of Hibiscus sabdariffa Extract

Authors: Chanasit Chaocharoenphat

Abstract:

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

Procedia PDF Downloads 254
1621 Glucose Monitoring System Using Machine Learning Algorithms

Authors: Sangeeta Palekar, Neeraj Rangwani, Akash Poddar, Jayu Kalambe

Abstract:

The bio-medical analysis is an indispensable procedure for identifying health-related diseases like diabetes. Monitoring the glucose level in our body regularly helps us identify hyperglycemia and hypoglycemia, which can cause severe medical problems like nerve damage or kidney diseases. This paper presents a method for predicting the glucose concentration in blood samples using image processing and machine learning algorithms. The glucose solution is prepared by the glucose oxidase (GOD) and peroxidase (POD) method. An experimental database is generated based on the colorimetric technique. The image of the glucose solution is captured by the raspberry pi camera and analyzed using image processing by extracting the RGB, HSV, LUX color space values. Regression algorithms like multiple linear regression, decision tree, RandomForest, and XGBoost were used to predict the unknown glucose concentration. The multiple linear regression algorithm predicts the results with 97% accuracy. The image processing and machine learning-based approach reduce the hardware complexities of existing platforms.

Keywords: artificial intelligence glucose detection, glucose oxidase, peroxidase, image processing, machine learning

Procedia PDF Downloads 209
1620 Effect of Fenugreek Seed with Aerobic Exercise Training on Insulin Resistance in Women with Type 2 Diabetes

Authors: M. Nasiri

Abstract:

Aim: Considering the hypoglisimic ad hipolipidimic effect of the fenugreek seed and aerobic exercise training, this study was conducted to evaluate the effect of fenugreek and aerobic exercise training on insulin resistance in women with type 2 diabetes. Methodology: 32 patients with type II diabetes were selected and randomly divided into four groups: control, fenugreek, training and fenugreek - training. Fenugreek groups used 10 grams of fenugreek seeds daily for eight weeks on two occasions before noon and evening meal. Training of groups is also performed a regular program of aerobic exercise 65-55% of maximum heart rate (4 days per week).Two days before and after the training period, blood samples were taken from their brachial veins in a fasting state (12 hours prior to the test) in a sitting position. The data was analyzed used of t-independent and ANOVA at a significance level of α < 0.05. Results: Intra-group changes in all experimental groups showed that significant decrease insulin resistance, and the difference between groups showed significant difference between the groups of fenugreek - training than other groups there. Conclusions: According to the research findings to fenugreek combined with aerobic exercise more beneficial effect on the inhibition of insulin resistance in women with diabetes are recommended to them.

Keywords: fenugreek, training, insulin resistance, diabetes

Procedia PDF Downloads 449
1619 Peg@GDF3:TB3+ – Rb Nanocomposites for Deep-Seated X-Ray Induced Photodynamic Therapy in Oncology

Authors: E.A. Kuchma

Abstract:

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

Procedia PDF Downloads 84
1618 Antiprotozoal Activity of Peganum harmala against Babesiosis in Cattle

Authors: Muhammad Mustafa Jafar, Syed Ashar Mahfooz, Muhammad Ejaz Saleem, Muhammad Asif Raza, Asghar Abbas, Rao Zahid Abbas, Muhammad Kasib Khan, Hafiz Muhammad Ishaq

Abstract:

The Babesia gradually attained resistance against the synthetic medicines. To overcome the drug resistance, herbal therapy has gained more attention as compared to allopathic therapy. Peganumharmala (harmal) is a plant which has shown effective results against various protozoal diseases. Therefore, the present study was planned to monitor the efficacy of Peganumharmala (aqueous extract) against Babesiosis in cattle. For this purpose, a total of forty (n=40) infected animals were randomly divided into four equal groups (A, B, C, and D). Group A was treated with aqueous extract of Peganum harmala at 7.5 mg/kg, group B at 10 mg/kg and group C at 12.5 mg/kg of body weight. Group D served as a control group (normal). It was observed that there was a stabilization in hematological parameters (white and red blood cells, hemoglobin and Packed cell volume) in infected animals treated with Peganum harmala at different doses. Results of this study hence indicated that Peganum harmala extract at 12.5mg/kg BW is more effective against Babesiosis than lower doses.

Keywords: Babesiosis, cattle, control, Peganum harmala

Procedia PDF Downloads 292
1617 New Bioactive Compounds from Two Chrysanthemum Saharian Species (Asteraceae) Growing in Algeria

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

Abstract:

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

Procedia PDF Downloads 342
1616 Endoscopic Depiction and Treatment Evaluation of Spirocerca lupi in Dogs

Authors: ELdessouky Sheta, Sayed Elzomor, Haithem Farghali, Kawkab A. Ahmed, Naglaa A. Abd Elkader

Abstract:

The present investigation has been dealt with Spirocerca (S.) lupi infested mongrel dogs. This parasitic disease is highly infective to human beings and carnivores. The diagnosis march has been comprised the lateral contrast thoracic radiographs, fecal examination, blood profile, endoscopic examination and histopathological sections of deep seated pinch biopsies. These infested dogs have been put under an adopted treatment with Ivermectin injection combined with oral prednisolone. The obtained results reveal an absence of the pessimistic recognitions particularly after 3 weeks from the onset of treatment. Endoscopically the presented esophageal nodules are marked out in the distal third of infested dogs' esophagus as masses assigned into the esophageal lumen and fundus of stomach. The endoscopic outlook of Spirocerca lupi lesions has been considered an integral procedure of the diagnostic march and for evaluation of treatment follow up. The diagnostic procedures and the recommended treatment are the vet's guidance to care for Spirocerca lupi in dogs, hoping in future to prevent this disease from being spread among human beings and other carnivores.

Keywords: endoscopy, esophagus, stomach spirocercosis, dogs

Procedia PDF Downloads 396
1615 Integrating Non-Psychoactive Phytocannabinoids and Their Cyclodextrin Inclusion Complexes into the Treatment of Glioblastoma

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

Abstract:

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 185
1614 The Effect of Acute Creatine Supplementation on Physiological Variables of Continuous and Intermittent Soccer Activities of Men Soccer Players

Authors: Abdolrasoul Daneshjoo

Abstract:

The aim of this study was studying the effect of acute creatine supplementation on physiological variables of continuous and intermittent soccer activities of men soccer players. 32 soccer players from Tarbiat Moalem University aged (22/3+-1/6) volunteered for this research and were divided into two groups randomly. Both experimental and control groups after 6 days taking supplementation were tested. For measuring height and weight meter and balance were used. Questionnaire for health background, lactate electro, heart beat measuring polar electro, continuous and intermittent training program and time recorder were used for data collection. For data analysis descriptive statistical techniques, two-way ANOVA and F test were used. The result of this study showed increased significantly in heart rate in control group. For control group heart beat was (71/6 +- 3/5) and for experimental group it was (75/3 +- 4/9). No significant differences were observed in players weight after taking creatine.

Keywords: heartbeat, lactate Blood, creatine, soccer players of Tarbiat Moalem University

Procedia PDF Downloads 384
1613 An Inverse Heat Transfer Algorithm for Predicting the Thermal Properties of Tumors during Cryosurgery

Authors: Mohamed Hafid, Marcel Lacroix

Abstract:

This study aimed at developing an inverse heat transfer approach for predicting the time-varying freezing front and the temperature distribution of tumors during cryosurgery. Using a temperature probe pressed against the layer of tumor, the inverse approach is able to predict simultaneously the metabolic heat generation and the blood perfusion rate of the tumor. Once these parameters are predicted, the temperature-field and time-varying freezing fronts are determined with the direct model. The direct model rests on one-dimensional Pennes bioheat equation. The phase change problem is handled with the enthalpy method. The Levenberg-Marquardt Method (LMM) combined to the Broyden Method (BM) is used to solve the inverse model. The effect (a) of the thermal properties of the diseased tissues; (b) of the initial guesses for the unknown thermal properties; (c) of the data capture frequency; and (d) of the noise on the recorded temperatures is examined. It is shown that the proposed inverse approach remains accurate for all the cases investigated.

Keywords: cryosurgery, inverse heat transfer, Levenberg-Marquardt method, thermal properties, Pennes model, enthalpy method

Procedia PDF Downloads 203
1612 Colloid-Based Biodetection at Aqueous Electrical Interfaces Using Fluidic Dielectrophoresis

Authors: Francesca Crivellari, Nicholas Mavrogiannis, Zachary Gagnon

Abstract:

Portable diagnostic methods have become increasingly important for a number of different purposes: point-of-care screening in developing nations, environmental contamination studies, bio/chemical warfare agent detection, and end-user use for commercial health monitoring. The cheapest and most portable methods currently available are paper-based – lateral flow and dipstick methods are widely available in drug stores for use in pregnancy detection and blood glucose monitoring. These tests are successful because they are cheap to produce, easy to use, and require minimally invasive sampling. While adequate for their intended uses, in the realm of blood-borne pathogens and numerous cancers, these paper-based methods become unreliable, as they lack the nM/pM sensitivity currently achieved by clinical diagnostic methods. Clinical diagnostics, however, utilize techniques involving surface plasmon resonance (SPR) and enzyme-linked immunosorbent assays (ELISAs), which are expensive and unfeasible in terms of portability. To develop a better, competitive biosensor, we must reduce the cost of one, or increase the sensitivity of the other. Electric fields are commonly utilized in microfluidic devices to manipulate particles, biomolecules, and cells. Applications in this area, however, are primarily limited to interfaces formed between immiscible interfaces. Miscible, liquid-liquid interfaces are common in microfluidic devices, and are easily reproduced with simple geometries. Here, we demonstrate the use of electrical fields at liquid-liquid electrical interfaces, known as fluidic dielectrophoresis, (fDEP) for biodetection in a microfluidic device. In this work, we apply an AC electric field across concurrent laminar streams with differing conductivities and permittivities to polarize the interface and induce a discernible, near-immediate, frequency-dependent interfacial tilt. We design this aqueous electrical interface, which becomes the biosensing “substrate,” to be intelligent – it “moves” only when a target of interest is present. This motion requires neither labels nor expensive electrical equipment, so the biosensor is inexpensive and portable, yet still capable of sensitive detection. Nanoparticles, due to their high surface-area-to-volume ratio, are often incorporated to enhance detection capabilities of schemes like SPR and fluorimetric assays. Most studies currently investigate binding at an immobilized solid-liquid or solid-gas interface, where particles are adsorbed onto a planar surface, functionalized with a receptor to create a reactive substrate, and subsequently flushed with a fluid or gas with the relevant analyte. These typically involve many preparation and rinsing steps, and are susceptible to surface fouling. Our microfluidic device is continuously flowing and renewing the “substrate,” and is thus not subject to fouling. In this work, we demonstrate the ability to electrokinetically detect biomolecules binding to functionalized nanoparticles at liquid-liquid interfaces using fDEP. In biotin-streptavidin experiments, we report binding detection limits on the order of 1-10 pM, without amplifying signals or concentrating samples. We also demonstrate the ability to detect this interfacial motion, and thus the presence of binding, using impedance spectroscopy, allowing this scheme to become non-optical, in addition to being label-free.

Keywords: biodetection, dielectrophoresis, microfluidics, nanoparticles

Procedia PDF Downloads 389
1611 Evaluation Rabbit Serum of the Immunodominant Proteins of Mycobacterium avium Paratuberculosis Extracts

Authors: Maryam Hashemi, Nematollah Razmi, Rasool Madani

Abstract:

M. paratuberculosis is a slow growing mycobactin dependent mycobacterial species known to be the causative agent of Johne’s disease in all species of domestic ruminants worldwide. JD is characterized by gradual weight loss; decreased milk production. Excretion of the organism may occur for prolonged periods (1 to 2.5 years) before the onset of clinical disease. In recent years, researchers focus on identification a specific antigen of MAP to use in diagnosis test and preparation of effective vaccine. In this paper, for production of polyclonal antibody against proteins of Mycobacterium avium paratuberculosis cell wall a rabbit immunization at a certain time period with antigen. After immunization of the animal, blood samples were collected from the rabbit for producing enriched serum. Antibodies were purified with ion exchange chromatography. For exact measurement of interaction, western blotting test was used and as it is demonstrated in the study, sharp bands appear in nitrocellulose paper and specific bands were 50 and 150 KD molecular weight. These were indicating immunodominant proteins.

Keywords: immunodominant, paratuberculosis, Western blotting, cell wall proteins, protein purification

Procedia PDF Downloads 258
1610 Clonal Evaluation of Malignant Mesothelioma

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 465
1609 Acute Oral Toxicity Study of Mystroxylon aethiopicum Root Bark Aqueous Extract in Albino Mice

Authors: Mhuji Kilonzo

Abstract:

Acute oral toxicity of Mystroxylon aethiopicum root bark aqueous was evaluated in albino mice of either sex. In this study, five groups of mice were orally treated with doses of 1000, 2000, 3000, 4000 and 5000 mg/kg body weight of the crude extract. The mortality, signs of toxicity and body weights were observed individually for two weeks. At the end of the two weeks study, all animals were sacrificed, and the hematological and biochemical parameters, as well as organ weights relative to body weight of each animal, were determined. No mortality, signs of toxicity and abnormalities in vital organs were observed in the entire period of study for both treated and control groups of mice. Additionally, there were no significant changes (p > 0.05) in the blood hematology and biochemical analysis. However, the body weights of all mice increased significantly. The Mystroxylon aethiopicum root bark aqueous extract were found to have a high safe margin when administered orally. Hence, the extract can be utilized for pharmaceutical formulations.

Keywords: acute oral toxicity, albino mice, Mystroxylon aethiopicum, safety

Procedia PDF Downloads 291
1608 A Computational Investigation of Potential Drugs for Cholesterol Regulation to Treat Alzheimer’s Disease

Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

Abstract:

Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

Procedia PDF Downloads 79