Search results for: colon cancer
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 2182

Search results for: colon cancer

352 Site-Specific Delivery of Hybrid Upconversion Nanoparticles for Photo-Activated Multimodal Therapies of Glioblastoma

Authors: Yuan-Chung Tsai, Masao Kamimura, Kohei Soga, Hsin-Cheng Chiu

Abstract:

In order to enhance the photodynamic/photothermal therapeutic efficacy on glioblastoma, the functionized upconversion nanoparticles with the capability of converting the deep tissue penetrating near-infrared light into visible wavelength for activating photochemical reaction were developed. The drug-loaded nanoparticles (NPs) were obtained from the self-assembly of oleic acid-coated upconversion nanoparticles along with maleimide-conjugated poly(ethylene glycol)-cholesterol (Mal-PEG-Chol), as the NP stabilizer, and hydrophobic photosensitizers, IR-780 (for photothermal therapy, PTT) and mTHPC (for photodynamic therapy, PDT), in aqueous phase. Both the IR-780 and mTHPC were loaded into the hydrophobic domains within NPs via hydrophobic association. The peptide targeting ligand, angiopep-2, was further conjugated with the maleimide groups at the end of PEG adducts on the NP surfaces, enabling the affinity coupling with the low-density lipoprotein receptor-related protein-1 of tumor endothelial cells and malignant astrocytes. The drug-loaded NPs with the size of ca 80 nm in diameter exhibit a good colloidal stability in physiological conditions. The in vitro data demonstrate the successful targeting delivery of drug-loaded NPs toward the ALTS1C1 cells (murine astrocytoma cells) and the pronounced cytotoxicity elicited by combinational effect of PDT and PTT. The in vivo results show the promising brain orthotopic tumor targeting of drug-loaded NPs and sound efficacy for brain tumor dual-modality treatment. This work shows great potential for improving photodynamic/photothermal therapeutic efficacy of brain cancer.

Keywords: drug delivery, orthotopic brain tumor, photodynamic/photothermal therapies, upconversion nanoparticles

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351 Radon-222 Concentration and Potential Risk to Workers of Al-Jalamid Phosphate Mines, North Province, Saudi Arabia

Authors: El-Said. I. Shabana, Mohammad S. Tayeb, Maher M. T. Qutub, Abdulraheem A. Kinsara

Abstract:

Usually, phosphate deposits contain 238U and 232Th in addition to their decay products. Due to their different pathways in the environment, the 238U/232Th activity concentration ratio usually found to be greater than unity in phosphate sediments. The presence of these radionuclides creates a potential need to control exposure of workers in the mining and processing activities of the phosphate minerals in accordance with IAEA safety standards. The greatest dose to workers comes from exposure to radon, especially 222Rn from the uranium series, and has to be controlled. In this regard, radon (222Rn) was measured in the atmosphere (indoor and outdoor) of Al-Jalamid phosphate-mines working area using a portable radon-measurement instrument RAD7, in a purpose of radiation protection. Radon was measured in 61 sites inside the open phosphate mines, the phosphate upgrading facility (offices and rooms of the workers, and in some open-air sites) and in the dwellings of the workers residence-village that lies at about 3 km from the mines working area. The obtained results indicated that the average indoor radon concentration was about 48.4 Bq/m3. Inside the upgrading facility, the average outdoor concentrations were 10.8 and 9.7 Bq/m3 in the concentrate piles and crushing areas, respectively. It was 12.3 Bq/m3 in the atmosphere of the open mines. These values are comparable with the global average values. Based on the average values, the annual effective dose due to radon inhalation was calculated and risk estimates have been done. The average annual effective dose to workers due to the radon inhalation was estimated by 1.32 mSv. The potential excess risk of lung cancer mortality that could be attributed to radon, when considering the lifetime exposure, was estimated by 53.0x10-4. The results have been discussed in detail.

Keywords: dosimetry, environmental monitoring, phosphate deposits, radiation protection, radon

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350 Night Shift Work as an Oxidative Stressor: A Systematic Review

Authors: Madeline Gibson

Abstract:

Night shift workers make up an essential part of the modern workforce. However, night shift workers have higher incidences of late in life diseases and earlier mortality. Night shift workers are exposed to constant light and experience circadian rhythm disruption. Sleep disruption is thought to increase oxidative stress, defined as an imbalance of excess pro-oxidative factors and reactive oxygen species over anti-oxidative activity. Oxidative stress can damage cells, proteins and DNA and can eventually lead to varied chronic diseases such as cancer, diabetes, cardiovascular disease, Alzheimer’s and dementia. This review aimed to understand whether night shift workers were at greater risk of oxidative stress and to contribute to a consensus on this relationship. Twelve studies published in 2001-2019 examining 2,081 workers were included in the review. Studies compared both the impact of working a single shift and in comparisons between those who regularly work night shifts and only day shifts. All studies had evidence to support this relationship across a range of oxidative stress indicators, including increased DNA damage, reduced DNA repair capacity, increased lipid peroxidation, higher levels of reactive oxygen species, and to a lesser extent, a reduction in antioxidant defense. This research supports the theory that melatonin and the sleep-wake cycle mediate the relationship between shift work and oxidative stress. It is concluded that night shift work increases the risk for oxidative stress and, therefore, future disease. Recommendations are made to promote the long-term health of shift workers considering these findings.

Keywords: night shift work, coxidative stress, circadian rhythm, melatonin, disease, circadian rhythm disruption

Procedia PDF Downloads 266
349 “MaxSALIVA-II” Advancing a Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection, Regeneration and Repair in a Head and Neck Cancer Pre-Clinical Murine Model

Authors: Ziyad S. Haidar

Abstract:

Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

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348 Exploring the Physicochemical and Quality Attributes of Potato Cultivars during Subsequent Storage

Authors: Muhammad Atif Randhawa, Adnan Amjad, Muhammad Nadeem

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Potato (Solanum tuberosum) popularly known as ‘the king of vegetables’, has emerged as fourth most important food crop after rice, wheat and maize. Potato contains carbohydrates, minerals, vitamins and antioxidants. The antioxidants of potatoes especially vitamin C helps in reducing cancer, cardiovascular diseases and high blood pressure by binding free radicals. Physical characteristics and some major chemical properties of potato tubers at fresh and stored stages were investigated. Two varieties of potatoes, Sante (V1) having white colour and Lal moti (V2) with red colour were stored for 3 months and analysis were performed after each month interval. Physical and chemical attributes including weight loss, sprouting, specific gravity, pH, total sugars (reducing and non-reducing sugars) and vitamin C were analyzed before and after storage. Value of weight loss at zero day was null but it increased to 6.45% after 90 days on average in both cultivars and sprouting increased gradually at the end of 90 days. Moreover total sugars were 3.10% at zero day but increased to 9.30% after 90 days. Ascorbic acid was decreased during storage from 17.49(mg/100g) to 3.79. Both varieties of potato were stored at 60C and 120C temperatures with 85% relative humidity in order to prolong their acceptability in the market. The storage conditions influence the potatoes quality and consequently their acceptability to consumer. The data was analyzed statistically and clarifies that total sugars, weight loss, sprouting and specific gravity increase during the storage period while ascorbic acid (Vit-C) and pH decreased. Among both varieties that were stored at 60C and 120C, Sante (V1) was better than Lal moti (V2) due to less physicochemical and quality changes at 60C as compared to store at 120C.

Keywords: physicochemical, potato, quality attributes, storage

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347 The Influence of Amygdalin on Glioblastoma Multiforme Cell Lines

Authors: Sylwia K. Naliwajko, Justyna Moskwa, Patryk Nowakowski, Renata Markiewicz-Zukowska, Krystyna Gromkowska-Kepka, Anna Puscion-Jakubik, Maria H. Borawska

Abstract:

Amygdalin is found in many fruit seeds, including apricot, peach, quince, apples, and almonds. Amygdalin (also named vitamin B17), as well as its sources, are commonly used as an alternative therapy or prevention of cancer. The potential activity of amygdalin is related to its enzymatic degradation to the hydrogen cyanide. Hydrogen cyanide is a toxic substance that causes liver and nerves damage, fever, coma or even death. Amygdalin is much better tolerated after intravenous than oral administration. The aim of this study was to examine the influence of amygdalin on glioblastoma multiforme cell lines. Three glioblastoma multiforme cell lines – U87MG, T98, LN18 were incubated (48 h) with amygdalin in concentrations 100, 250, 500, 1000 and 2000 µg/mL. The MTT (Thiazolyl Blue Tetrazolium Bromide) test and DNA binding test by [3H]-thymidine incorporation were used to determine the anti-proliferative activity of amygdalin. The secretion of metalloproteinases (MMP2 and MMP-9) from U87MG cells was estimated by gelatin zymography. The statistical analysis was performed using Statistica v. 13.0 software. The data was presented as a % of control. Amygdalin did not show significant inhibition of viability of all the glioblastoma cells in concentrations 100, 250, 500, 1000 µg/mL. In 2000 µg/mL there were significant differences compared to the control, but inhibition of viability was less than 20% (more than 80% of control). The average viability of U87MG cells was 92,0±4%, T98G: 85,8±3% and LN18: 94,7±2% of the control. There was no dose-response viability, and IC50 value was not recognized. DNA binding in U87MG cells was not inhibited (109,0±3 % of control). After treatment with amygdalin, we observed significantly increased secretion of MMP2 and MMP9 in U87MG cells (130,3±14% and 112,0±5% of control, respectively). Our results suggest that amygdalin has no anticancer activity in glioblastoma cell lines.

Keywords: amygdalin, anticancer, cell line, glioblastoma

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346 Pros and Cons of Nanoparticles on Health

Authors: Amber Shahi, Ayesha Tazeen, Abdus Samad, Shama Parveen

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Nanoparticles (NPs) are tiny particles. According to the International Organization for Standardization, the size range of NPs is in the nanometer range (1-100 nm). They show distinct properties that are not shown by larger particles of the same material. NPs are currently being used in different fields due to their unique physicochemical nature. NPs are a boon for medical sciences, environmental sciences, electronics, and textile industries. However, there is growing concern about their potential adverse effects on human health. This poster presents a comprehensive review of the current literature on the pros and cons of NPs on human health. The poster will discuss the various types of interactions of NPs with biological systems. There are a number of beneficial uses of NPs in the field of health and environmental welfare. NPs are very useful in disease diagnosis, antimicrobial action, and the treatment of diseases like Alzheimer’s. They can also cross the blood-brain barrier, making them capable of treating brain diseases. Additionally, NPs can target specific tumors and be used for cancer treatment. To treat environmental health, NPs also act as catalytic converters to reduce pollution from the environment. On the other hand, NPs also have some negative impacts on the human body, such as being cytotoxic and genotoxic. They can also affect the reproductive system, such as the testis and ovary, and sexual behavior. The poster will further discuss the routes of exposure of NPs. The poster will conclude with a discussion of the current regulations and guidelines on the use of NPs in various applications. It will highlight the need for further research and the development of standardized toxicity testing methods to ensure the safe use of NPs in various applications. When using NPs in diagnosis and treatment, we should also take into consideration their safe concentration in the body. Overall, this poster aims to provide a comprehensive overview of the pros and cons of NPs on human health and to promote awareness and understanding of the potential risks and benefits associated with their use.

Keywords: disease diagnosis, human health, nanoparticles, toxicity testing

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345 A Rare Case of Metastatic Basal Cell Carcinoma

Authors: Nitesh Kumar, Eoin Twohig, jasparl cheema, Sadiq mawji, Yousif al najjar

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Basal cell carcinoma (BCC) is the commonest cutaneous malignancy affecting humans. Despite this, distant spread is exceptionally rare. Metastatic BCC (mBCC) is estimated to occur in 0.0028 - 0.5%. it aim to illustrate with the aid of histological slides, a case of mBCC occurring in a fit and well 67-year-old. Initial diagnosis of desmoplastic BCC was made in 2006 from a scalp biopsy with the lesion then being excised. Re-excision of local recurrence was undertaken the following year. In 2014 the patient presented with an ipsilateral level 2a mass. Fine Needle Aspiration raised the suspicion of metastatic carcinoma. The patient had excision of two nodes from the left neck alongside pharyngeal tonsillectomy and tongue base biopsies. Histologically, the nodes closely resembled the immunophenotype of the initial scalp lesion. The patient subsequently had a modified radical neck dissection, and residual mBCC was excised from the left Sternocleidomastoid muscle. In 2023 the patient developed haematuria. On further investigation bilateral lung lesions on CT were noted with subsequent biopsy confirming mBCC. Spinal and renal lesions have also been found. Histopathology showed clear resemblance of the lung metastases to both those in the neck and the primary (scalp BCC) – with no squamous differentiation seen. The time span from primary to occurrence of lung metastasis (18 years) affirms the indolent and slow growing nature of BCC.  This case fulfils Lattes and Kessler diagnostic criteria. High risk cases are described as those with advanced local presentation, primary tumour on the Head and Neck and locally recurrent lesions.

Keywords: BCC, metastasis, rare, skin cancer

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344 3D Dentofacial Surgery Full Planning Procedures

Authors: Oliveira M., Gonçalves L., Francisco I., Caramelo F., Vale F., Sanz D., Domingues M., Lopes M., Moreia D., Lopes T., Santos T., Cardoso H.

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The ARTHUR project consists of a platform that allows the virtual performance of maxillofacial surgeries, offering, in a photorealistic concept, the possibility for the patient to have an idea of the surgical changes before they are performed on their face. For this, the system brings together several image formats, dicoms and objs that, after loading, will generate the bone volume, soft tissues and hard tissues. The system also incorporates the patient's stereophotogrammetry, in addition to their data and clinical history. After loading and inserting data, the clinician can virtually perform the surgical operation and present the final result to the patient, generating a new facial surface that contemplates the changes made in the bone and tissues of the maxillary area. This tool acts in different situations that require facial reconstruction, however this project focuses specifically on two types of use cases: bone congenital disfigurement and acquired disfiguration such as oral cancer with bone attainment. Being developed a cloud based solution, with mobile support, the tool aims to reduce the decision time window of patient. Because the current simulations are not realistic or, if realistic, need time due to the need of building plaster models, patient rates on decision, rely on a long time window (1,2 months), because they don’t identify themselves with the presented surgical outcome. On the other hand, this planning was performed time based on average estimated values of the position of the maxilla and mandible. The team was based on averages of the facial measurements of the population, without specifying racial variability, so the proposed solution was not adjusted to the real individual physiognomic needs.

Keywords: 3D computing, image processing, image registry, image reconstruction

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343 Increased Cytolytic Activity of Effector T-Cells against Cholangiocarcinoma Cells by Self-Differentiated Dendritic Cells with Down-Regulation of Interleukin-10 and Transforming Growth Factor-β Receptors

Authors: Chutamas Thepmalee, Aussara Panya, Mutita Junking, Jatuporn Sujjitjoon, Nunghathai Sawasdee, Pa-Thai Yenchitsomanus

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Cholangiocarcinoma (CCA) is an aggressive malignancy of bile duct epithelial cells in which the standard treatments, including surgery, radiotherapy, chemotherapy, and targeted therapy are partially effective. Many solid tumors including CCA escape host immune responses by creating tumor microenvironment and generating immunosuppressive cytokines such as interleukin-10 (IL-10) and transforming growth factor-β (TGF-β). These cytokines can inhibit dendritic cell (DC) differentiation and function, leading to decreased activation and response of effector CD4+ and CD8+ T cells for cancer cell elimination. To overcome the effects of these immunosuppressive cytokines and to increase ability of DC to activate effector CD4+ and CD8+ T cells, we generated self-differentiated DCs (SD-DCs) with down-regulation of IL-10 and TGF-β receptors for activation of effector CD4+ and CD8+ T cells. Human peripheral blood monocytes were initially transduced with lentiviral particles containing the genes encoding GM-CSF and IL-4 and then secondly transduced with lentiviral particles containing short-hairpin RNAs (shRNAs) to knock-down mRNAs of IL-10 and TGF-β receptors. The generated SD-DCs showed up-regulation of MHC class II (HLA-DR) and co-stimulatory molecules (CD40 and CD86), comparable to those of DCs generated by convention method. Suppression of IL-10 and TGF-β receptors on SD-DCs by specific shRNAs significantly increased levels of IFN-γ and also increased cytolytic activity of DC-activated effector T cells against CCA cell lines (KKU-213 and KKU-100), but it had little effect to immortalized cholangiocytes (MMNK-1). Thus, SD-DCs with down-regulation of IL-10 and TGF-β receptors increased activation of effector T cells, which is a recommended method to improve DC function for the preparation of DC-activated effector T cells for adoptive T-cell therapy.

Keywords: cholangiocarcinoma, IL-10 receptor, self-differentiated dendritic cells, TGF-β receptor

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342 An Unbiased Profiling of Immune Repertoire via Sequencing and Analyzing T-Cell Receptor Genes

Authors: Yi-Lin Chen, Sheng-Jou Hung, Tsunglin Liu

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Adaptive immune system recognizes a wide range of antigens via expressing a large number of structurally distinct T cell and B cell receptor genes. The distinct receptor genes arise from complex rearrangements called V(D)J recombination, and constitute the immune repertoire. A common method of profiling immune repertoire is via amplifying recombined receptor genes using multiple primers and high-throughput sequencing. This multiplex-PCR approach is efficient; however, the resulting repertoire can be distorted because of primer bias. To eliminate primer bias, 5’ RACE is an alternative amplification approach. However, the application of RACE approach is limited by its low efficiency (i.e., the majority of data are non-regular receptor sequences, e.g., containing intronic segments) and lack of the convenient tool for analysis. We propose a computational tool that can correctly identify non-regular receptor sequences in RACE data via aligning receptor sequences against the whole gene instead of only the exon regions as done in all other tools. Using our tool, the remaining regular data allow for an accurate profiling of immune repertoire. In addition, a RACE approach is improved to yield a higher fraction of regular T-cell receptor sequences. Finally, we quantify the degree of primer bias of a multiplex-PCR approach via comparing it to the RACE approach. The results reveal significant differences in frequency of VJ combination by the two approaches. Together, we provide a new experimental and computation pipeline for an unbiased profiling of immune repertoire. As immune repertoire profiling has many applications, e.g., tracing bacterial and viral infection, detection of T cell lymphoma and minimal residual disease, monitoring cancer immunotherapy, etc., our work should benefit scientists who are interested in the applications.

Keywords: immune repertoire, T-cell receptor, 5' RACE, high-throughput sequencing, sequence alignment

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341 Assessment of Cardioprotective Effect of Deferiprone on Doxorubicin-Induced Cardiac Toxicity in a Rat Model

Authors: Sadaf Kalhori

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Introduction: Doxorubicin (DOX)-induced cardiotoxicity is widely known as the most severe complication of anthracycline-based chemotherapy in patients with cancer. It is unknown whether Deferiprone (DFP), could reduce the severity of DOX-induced cardiotoxicity by inhibiting free radical reactions. Thus, this study was performed to assess the protective effect of Deferiprone on DOX-induced cardiotoxicity in a rat model. Methods: The rats were divided into five groups. Group one was a control group. Group 2 was DOX (2 mg/kg/day, every other day for 12 days), and Group three to five which receiving DOX as in group 2 and DFP 75,100 and 150 mg/kg/day, for 19 days, respectively. DFP was starting 5 days prior to the first DOX injection and two days after the last DOX injection throughout the study. Electrocardiographic and hemodynamic studies, along with histopathological examination, were conducted. In addition, serum sample was taken and total cholesterol, Malone dialdehyde, triglyceride, albumin, AST, ALT, total protein, lactate dehydrogenase, total anti-oxidant and creatine kinase were assessed. Result: Our results showed the normal structure of endocardial, myocardial and pericardial in the control group. Pathologic data such as edema, hyperemia, bleeding, endocarditis, myocarditis and pericarditis, hyaline degeneration, cardiomyocyte necrosis, myofilament degeneration and nuclear chromatin changes were assessed in all groups. In the DOX group, all pathologic data was seen with mean grade of 2±1.25. In the DFP group with a dose of 75 and 100 mg, the mean grade was 1.41± 0.31 and 1±.23, respectively. In DFP group with a dose of 150, the pathologic data showed a milder change in comparison with other groups with e mean grade of 0.45 ±0.19. Most pathologic data in DFP groups showed significant changes in comparison with the DOX group (p < 0.001). Discussion: The results also showed that DFP treatment significantly improved DOX-induced heart damage, structural changes in the myocardium, and ventricular function. Our data confirm that DFP is protective against cardiovascular-related disorders induced by DOX. Clinical studies are needed to be involved to examine these findings in humans.

Keywords: cardiomyopathy, deferiprone, doxorubicin, rat

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340 Oxidative Antioxidative Status and DNA Damage Profile Induced by Chemotherapy in Algerian Children with Lymphoma

Authors: Assia Galleze, Abdurrahim Kocyigit, Nacira Cherif, Nidel Benhalilou, Nabila Attal, Chafia Touil Boukkoffa, Rachida Raache

Abstract:

Introduction and aims: Chemotherapeutic agents used to inhibit cell division and reduce tumor growth, increase reactive oxygen species levels, which contributes to their genotoxicity [1]. The comet assay is an inexpensive and rapid method to detect the damage at cellular levels and has been used in various cancer populations undergoing chemotherapy [2,3]. The present study aim to assess the oxidative stress and the genotoxicity induced by chemotherapy by the determination of plasma malondialdehyde (MDA) level, protein carbonyl (PC) content, superoxide dismutase (SOD) activity and lymphocyte DNA damage in Algerian children with lymphoma. Materials and Methods: For our study, we selected thirty children with lymphoma treated in university hospital of Beni Messous, Algeria, and fifty unrelated subjects as controls, after obtaining the informed consent in accordance with the Declaration of Helsinki (1964). Plasma levels of MDA, PC and SOD activity were spectrophotometrically measured, while DNA damage was assessed by alkaline comet assay in peripheral blood leukocytes. Results and Discussion: Plasma MDA, PC levels and lymphocyte DNA damage, were found to be significantly higher in lymphoma patients than in controls (p < 0.001). Whereas, SOD activity in lymphoma patients was significantly lower than in healthy controls (p < 0.001). There were significant positive correlations between DNA damage, MDA and PC in patients (r = 0.96, p < 0.001, r = 0.97, p < 0.001, respectively), and negative correlation with SOD (r = 0.87, p < 0.01). Conclusion and Perspective: Our results indicated that, leukocytes DNA damage and oxidative stress were significantly higher in lymphoma patients, suggesting that the direct effect of chemotherapy and the alteration of the redox balance may influence oxidative/antioxidative status.

Keywords: chemotherapy, comet assay, DNA damage, lymphoma

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339 Core-Shell Type Magnetic Nanoparticles for Targeted Drug Delivery

Authors: Yogita Patil-Sen

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Magnetic nanoparticles such as those made of iron oxide have been widely explored as biocatalysts, contrast agents, and drug delivery systems. However, some of the challenges associated with these particles are agglomeration and biocompatibility, which lead to concern of toxicity of the particles, especially for drug delivery applications. Coating the particles with biocompatible materials such as lipids and peptides have shown to improve the mentioned issues. Thus, these core-shell type nanoparticles are emerging as the new class of nanomaterials for targeted drug delivery applications. In this study, various types of core-shell magnetic nanoparticles are prepared and characterized using techniques, such as Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), Vibrating Sample Magnetometer (VSM) and Thermogravimetric Analysis (TGA). The heating ability of nanoparticles is tested under oscillating magnetic field. The efficacy of the nanoparticles as drug carrier is also investigated. The loading of an anticancer drug, Doxorubicin at 18 °C is measured up to 48 hours using UV-visible spectrophotometer. The drug release profile is obtained under thermal incubation condition at 37 °C and compared with that under the influence of oscillating field. The results suggest that the core-shell nanoparticles exhibit superparamagnetic behaviour, although, coating reduces the magnetic properties of the particles. Both the uncoated and coated particles show good heating ability, again it is observed that coating decreases the heating behaviour of the particles. However, coated particles show higher drug loading efficiency than the uncoated particles and the drug release is much more controlled under the oscillating magnetic field. Thus, the results strongly indicate the suitability of the prepared core-shell type nanoparticles as drug delivery vehicles and their potential in magnetic hyperthermia applications and for hyperthermia cancer therapy.

Keywords: core-shell, hyperthermia, magnetic nanoparticles, targeted drug delivery

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338 Lymphomas as Estrogen-Regulated Cancers

Authors: M. S. Hasni, J. Guan, K. Yakimchuk, M. Berglund, B. Sander, G. Enblad, R. M. Amini, S. Okret

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Lymphomas are generally not considered as endocrine-related cancers. However, most lymphoid malignancies show gender differences in incidence and show prognosis with males being more affected. Furthermore, some epidemiological data indicate a protective role of estrogens against Non-Hodgkin lymphomas. Recent studies have demonstrated estrogen receptor β (ERβ) to be the major ER expressed in normal and malignant cells of lymphoid origin. We have analyzed the effects of estradiol and selective ERα and ERβ agonists on lymphoma growth in culture and in vivo. Treating lymphoma cells with estradiol or ERα selective agonist had minor or no effect on cell growth while selective ERβ agonist treatment showed an antiproliferative effect. When grafting mice with murine T lymphoma cells, male mice developed larger tumors compared to female mice, a difference that was abolished following ovariectomy, demonstrating estrogen-dependent growth in vivo. When subcutaneously grafting lymphoma cells to mice, so far growth of all tested human B lymphoma tumors (Raji and Ramos Burkitt lymphoma, SU.DHL4 (GC) and U2932 (ABC) DLBCL, Granta-519, Maver1 and Z138 MCL cells), were reduced following treatment with ERβ selective agonist (ref. 2 and unpublished). Moreover, the number and size of liver foci of disseminating Raji cells was reduced. We have identified target genes and mechanism that could explain the above effects of ERβ agonists. This included effects on angio and lymphangiogenesis. Now we have further analyzed effects of ERβ agonists on Ibrutinib-sensitive and -insensitive MCL cells in xenograft experiments as well as ERβ expression in primary lymphoma material (DLBCL). Preliminary statistical analysis has been done correlating ERβ expression to other biomarkers and clinical data.

Keywords: lymphomas, estrogen receptors, cancer, liver foci

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337 Sensitive Electrochemical Sensor for Simultaneous Detection of Endocrine Disruptors, Bisphenol A and 4- Nitrophenol Using La₂Cu₂O₅ Modified Glassy Carbon Electrode

Authors: S. B. Mayil Vealan, C. Sekar

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Bisphenol A (BIS A) and 4 Nitrophenol (4N) are the most prevalent environmental endocrine-disrupting chemicals which mimic hormones and have a direct relationship to the development and growth of animal and human reproductive systems. Moreover, intensive exposure to the compound is related to prostate and breast cancer, infertility, obesity, and diabetes. Hence, accurate and reliable determination techniques are crucial for preventing human exposure to these harmful chemicals. Lanthanum Copper Oxide (La₂Cu₂O₅) nanoparticles were synthesized and investigated through various techniques such as scanning electron microscopy, high-resolution transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and electrochemical impedance spectroscopy. Cyclic voltammetry and square wave voltammetry techniques are employed to evaluate the electrochemical behavior of as-synthesized samples toward the electrochemical detection of Bisphenol A and 4-Nitrophenol. Under the optimal conditions, the oxidation current increased linearly with increasing the concentration of BIS A and 4-N in the range of 0.01 to 600 μM with a detection limit of 2.44 nM and 3.8 nM. These are the lowest limits of detection and the widest linear ranges in the literature for this determination. The method was applied to the simultaneous determination of BIS A and 4-N in real samples (food packing materials and river water) with excellent recovery values ranging from 95% to 99%. Better stability, sensitivity, selectivity and reproducibility, fast response, and ease of preparation made the sensor well-suitable for the simultaneous determination of bisphenol and 4 Nitrophenol. To the best of our knowledge, this is the first report in which La₂Cu₂O₅ nano particles were used as efficient electron mediators for the fabrication of endocrine disruptor (BIS A and 4N) chemical sensors.

Keywords: endocrine disruptors, electrochemical sensor, Food contacting materials, lanthanum cuprates, nanomaterials

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336 Ameliorative Effects of Ganoderma lucidum Extracts on Testosterone Induced Prostatic Hyperplasia in Rats

Authors: Alok Nahata

Abstract:

Introduction: Nowadays, androgen-mediated diseases such as prostate cancer, hirsutism, acne, androgenic alopecia and benign prostatic hyperplasia (BPH) have become serious problems. The aim of the present study was to find out whether Ganoderma lucidum (GL) can be used as a clinically effective medicine for the management of prostatic hyperplasia. Methodology: In vitro studies were conducted to assess the 5α-reductase inhibitory potential of GL. Testosterone (3 mg/kg s.c.) was administered to the rats along with the test extracts (10, 20 and 50 mg/kg p.o for a period of 28 days. Finasteride was used as a positive control (1 mg/kg p.o.). Major Findings: GL extracts attenuated the increase in the prostate/body weight ratio (P/BW) induced by testosterone. Most of the values were significant when compared to testosterone-treated group and finasteride treated groups. Petroleum ether extract (50 mg/kg p.o.) exhibited the best activity (P < 0.01). Ethanolic extract (20 and 50 mg/kg p.o.) also exhibited significant activity (P < 0.01). The urine output also improved significantly (P < 0.01 in all groups as compared to standard finasteride), which emphasize the clinical implications of the study. Testosterone levels measured weekly and prostate-specific antigen (PSA) levels measured at the end of the study also support the findings. Histological studies suggested improvement in prostatic histoarchitecture in extract-treated groups as compared to the testosterone-treated group. Conclusion: Study clearly reflects the utility of extracts in BPH. Because of conversion of testosterone to dihydrotestosterone, the prostate size is increased, thereby causing obstruction in urinary output. The observed effect that extracts do not allow the increase as reflected by urinary output, P/BW ratios and histoarchitecture showed that activity of administered testosterone was blocked by the extract and resulted in recovery.

Keywords: benign prostatic hyperplasia, Ganoderma lucidum, prostate-specific antigen, 5α-reductase, testosterone

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335 Extraskeletal Ewing Sarcoma- Experience in a Tertiary Cancer Care Centre of India

Authors: Himanshu Rohela

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BACKGROUND: Ewing sarcoma can arise in either bone or soft tissue. Extraskeletal Ewing sarcoma (EES) is an uncommon primary tumor of the soft tissues, accounting for 20 30% of all reported cases of ES. AIM: Was to investigate demographic distribution, survival analysis and factors affecting the survival and recurrence in patients of EES. METHODS: Retrospective study of 19 biopsy-proven EES was performed. Overall survival (OS) using log-rank test and factors affecting OS and local recurrence (LR) were evaluated for the entire cohort. RESULTS: Patients with EES had a mean age of 19.5 and it was more commonly seen in males (63%). Axial location (58%) and solitary presentation (84%) were more common. The average size was 11 cm, 3 of 19 were metastatic at presentation, with the lung beings the most common site for metastasis. 17 received NACT, 16 with VAC-IE regimen and 1 underwent a second line with GEM/DOCE regimen. Unplanned surgery was done in 2 of 19. 3 patients received definitive RT and 13 underwent surgical-wide local excision. 2 of 13 showed good response to NACT. 10 patients required readmission out of which 6 patients had chemotherapy-related complications, 2 had surgical site complications and one patient developed secondary AML post-completion of treatment. A total of 4 patients had a recurrence. One had local recurrence alone, one had distant recurrence alone and 2 patients had a distant and local recurrence both. Tumor size >10 cm, axial location, and previous unplanned surgery was associated with higher LR rate. The mean overall survival was 32 months (2.66 years), with higher rates seen in non-metastatic and non-recurrent settings. CONCLUSIONS: Early and accurate diagnosis is the key to the management of EES, with promising results seen via NACT and RO resection regimens. But further studies with larger study groups are needed to standardize the treatment protocol and evaluate its efficacy.

Keywords: Ewings, sarcoma, extraskeletal, chemotherapy

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334 Associations of Vitamin D Receptor Polymorphisms with Coronary Artery Diseases

Authors: Elham Sharif, Nasser Rizk, Sirin Abu Aqel, Ofelia Masoud

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Background: Previous studies have investigated the association of rs1544410, rs7975232 and rs731236 polymorphisms in vitamin D receptor gene and its impact on diseases such as cancer, diabetes and hypertension in different ethnic backgrounds. Aim: The aim of this study is to investigate the association between VDR polymorphisms using three SNP’s (rs1544410, rs7975232 and rs731236) and the severity of the significant lesion in coronary arteries among angiographically diagnosed CAD. Methods: A prospective-retrospective study was conducted on 192 CAD patients enrolled from the cardiology department-Heart Hospital HMC, grouped in 96 subjects with significant stenosis and 96 with non-significant stenosis with a mean age between 30 and 75 years old. Genotyping was performed for the following SNPs rs1544410, rs7975232 and rs731236 using TaqMan assay by the Real Time PCR, ABI 7500 in Health Sciences Labs at Qatar University Biomedical Research Center. Results: The results showed that both groups have matched age and gender distribution but patients with the significant stenosis have significantly higher; BMI (p=0.047); smoking status (p=0.039); FBS (p= 0.031); CK-MB (p=0.025) and Troponin (p=0.002) than the patients with non–significant lesion. Among the traditional risk factors, smoking increases the odds of the severe stenotic lesion in CAD patients by 1.984, with 95% CI between 1.024 – 7.063, with p= 0.042.HWE showed deviations of the rs1544410 and rs731236 among the study subjects. The most frequent genotype in distribution of rs7975232 is the AA among the significant stenosis patients, while the heterozygous AC was the frequent genotype in distribution among the non-significant stenosis group. The carriers of CC genotype in rs7975232 increased the risk of having significant coronary arteries stenotic lesion by 1.83 with 95% CI (1.020 – 3.280), p=0.043. No association was found between the rs7975232 with vitamin D and VDBP. Conclusion: There is a significant association between rs7975232 and the severity of CAD lesion. The carrier of CC genotype in rs7975232 increased the risk of having significant coronary arteries atherosclerotic lesion especially in patients with smoking history independent of vitamin D.

Keywords: vitamin D, vitamin D receptor, polymorphism, coronary harat disease

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333 Levels of Microcystin in the Coastal Waters of Nigeria

Authors: Medina Kadiri

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Blue-green otherwise called cyanobacteria, produce an array of biotoxins grouped into five categories notably hapatotoxins, neurotoxins, cytotoxins, dermatotoxins, and irritant toxins. Microcystins which are examples of hepatotoxins produced by blue-green algae Microcystins comprise the most common group of the cyanobacterial toxins. Blue-green algae flourish in aquatic environments, whether marine, brackish or freshwater, producing blooms in different forms such as microscopic, mats, or unsightly odoriferous scums. Microcystins biotoxins cause a plethora of animal and human hazards such as liver damage/cirrhosis and cancer, kidney damage, dermatitis, tinnitus, gastroenteritis, sore throat, nausea, myalgia, neurological problems, respiratory irritation and death. Water samples were collected from coastal regions of Nigeria in March 2014, June 2014, October 2014 and January 2015 and analyzed with Enzyme Linked Immunosorbent Assay (ELISA) kits. Microcystin biotoxin was recorded in all sites both during dry and wet seasons. The range of microcystins found was 0.000041-There was a seasonal trend of increasing microcystin concentrations from March till Octobers and a decrease thereafter. Generally in the oceanic waters, microcystin levels were highest at Cross Rivers in March and January, Barbeach in June and Lekki in October. In the adjoining riverine ecosystems, on the other hand, the highest concentrations of microcystin were observed at Akwa Ibom in March, June and October and in Bayelsa in January. Continuous monitoring and screening of coastal water bodies is suggested to minimize the health risks of cyanobacterial biotoxins to coastal communities of Nigeria.

Keywords: biotoxins, harmful algae, marine, microcystin, Nigeria

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332 Suggested Role for Neutrophil Extracellular Traps Formation in Ewing Sarcoma Immune Microenvironment

Authors: Rachel Shukrun, Szilvia Baron, Victoria Fidel, Anna Shusterman, Osnat Sher, Netanya Kollender, Dror Levin, Yair Peled, Yair Gortzak, Yoav Ben-Shahar, Revital Caspi, Sagi Gordon, Michal Manisterski, Ronit Elhasid

Abstract:

Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescent. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared to those with local disease. High NETs formation at diagnosis predicted poor response to neo-adjuvant chemotherapy, relapse, and death from disease (P < .05). NETs formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared to pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NETs formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Keywords: Ewing sarcoma, tumor microenvironment, neutrophil, neutrophil extracellular traps (NETs), prognosis

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331 Community Pharmacist's Perceptions, Attitude and Role in Oral Health Promotion and Diseases Prevention

Authors: Bushra Alghamdi, Alla Alsharif, Hamzah Aljohani, Saba Kassim

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Introduction: Collaborative work has always been acknowledged as a fundamental concept in delivering oral health care. Aim: This study aimed to assess the perception and attitude of pharmacists in oral health promotion and to determine the confident levels of pharmacists in delivering advice on oral health problems. Methods: An observational cross-sectional survey, using self-administered anonymous questionnaires, was conducted between March and April 2017. The study recruited a convenience sample of registered community pharmacists who were working in local private pharmaceutical stores in the urban area of Madinah, Kingdom of Saudi Arabia (KSA). A preliminary descriptive analysis was performed. Results: Thirty-five pharmacists have completed the surveys. All participants were males, with a mean age of 35.5 ( ± 6.92) years. Eighty-six percent of the participants reported that pharmacists should have a role in oral health promotion. Eighty percent have reported adequate level of confident when giving advice on most of the common oral health problems that include; oral health related risk behaviors such as tobacco cessation (46%), bleeding gums (63%) and sensitive teeth (60%). However, higher percentages of pharmacists have reported low confident levels when giving advice in relation to specific domain of dentistry, such as lost dental fillings (57%), loose crowns (60%), trauma to teeth (40%), denture-related problems (51%) and oral cancer (6.9%). Conclusion: Community pharmacists recognized their potential role in promoting oral health in KSA. Community pharmacists had varying levels of ability and confidence to offer support for oral health. The study highlighted that inner professional collaboration between pharmacists and dental care healthcare should be enhanced.

Keywords: community, oral health, promotion, pharmacist

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330 Nanomaterial Based Electrochemical Sensors for Endocrine Disrupting Compounds

Authors: Gaurav Bhanjana, Ganga Ram Chaudhary, Sandeep Kumar, Neeraj Dilbaghi

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Main sources of endocrine disrupting compounds in the ecosystem are hormones, pesticides, phthalates, flame retardants, dioxins, personal-care products, coplanar polychlorinated biphenyls (PCBs), bisphenol A, and parabens. These endocrine disrupting compounds are responsible for learning disabilities, brain development problems, deformations of the body, cancer, reproductive abnormalities in females and decreased sperm count in human males. Although discharge of these chemical compounds into the environment cannot be stopped, yet their amount can be retarded through proper evaluation and detection techniques. The available techniques for determination of these endocrine disrupting compounds mainly include high performance liquid chromatography (HPLC), mass spectroscopy (MS) and gas chromatography-mass spectrometry (GC–MS). These techniques are accurate and reliable but have certain limitations like need of skilled personnel, time consuming, interference and requirement of pretreatment steps. Moreover, these techniques are laboratory bound and sample is required in large amount for analysis. In view of above facts, new methods for detection of endocrine disrupting compounds should be devised that promise high specificity, ultra sensitivity, cost effective, efficient and easy-to-operate procedure. Nowadays, electrochemical sensors/biosensors modified with nanomaterials are gaining high attention among researchers. Bioelement present in this system makes the developed sensors selective towards analyte of interest. Nanomaterials provide large surface area, high electron communication feature, enhanced catalytic activity and possibilities of chemical modifications. In most of the cases, nanomaterials also serve as an electron mediator or electrocatalyst for some analytes.

Keywords: electrochemical, endocrine disruptors, microscopy, nanoparticles, sensors

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329 Free Radical Scavenging Activity and Total Phenolic Assessment of Drug Repurposed Medicinal Plant Metabolites: Promising Tools against Post COVID-19 Syndromes and Non-Communicable Diseases in Botswana

Authors: D. Motlhanka, M. Mine, T. Bagaketse, T. Ngakane

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There is a plethora of evidence from numerous sources that highlights the triumph of naturally derived medicinal plant metabolites with antioxidant capability for repurposed therapeutics. As post-COVID-19 syndromes and non-communicable diseases are on the rise, there is an urgent need to come up with new therapeutic strategies to address the problem. Non-communicable diseases and Post COVID-19 syndromes are classified as socio-economic diseases and are ranked high among threats to health security due to the economic burden they pose to any government budget commitment. Research has shown a strong link between accumulation of free radicals and oxidative stress critical for pathogenesis of non-communicable diseases and COVID-19 syndromes. Botswana has embarked on a robust programme derived from ethno-pharmacognosy and drug repurposing to address these threats to health security. In the current approach, a number of medicinally active plant-derived polyphenolics are repurposed and combined into new medicinal tools to target diabetes, Hypertension, Prostate Cancer and oxidative stress induced Post COVID 19 syndromes such as “brain fog”. All four formulants demonstrated Free Radical scavenging capacities above 95% at 200µg/ml using the diphenylpicryalhydrazyl free radical scavenging assay and the total phenolic contents between 6899-15000GAE(g/L) using the folin-ciocalteau assay respectively. These repurposed medicinal tools offer new hope and potential in the fight against emerging health threats driven by hyper-inflammation and free radical-induced oxidative stress.

Keywords: drug repurposed plant polyphenolics, free radical damage, non-communicable diseases, post COVID 19 syndromes

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328 Phenolic Composition and Antioxidant Property of Honey with Dried Apricots

Authors: Jasna Čanadanović-Brunet, Gordana Ćetković, Sonja Djilas, Vesna Tumbas-Šaponjac, Jelena Vulić, Sladjana Stajčić

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Honey, produced by the honeybee, is a natural saturated sugar solution, which is mainly composed of a complex mixture of carbohydrates. Besides this, it also contains certain minor constituents, proteins, enzymes, amino and organic acids, lipids, vitamins, phenolic acids, flavonoids and carotenoids. Honey serves as a source of natural antioxidants, which are effective in reducing the risk of heart disease, cancer, immune-system decline, cataracts, and different inflammatory processes. Honey is consumed in its natural form alone, but also in combination with nuts and various kinds of dried fruits (plums, figs, cranberries, apricots etc.). The aim of this research was to investigate the contribution of dried apricot addition to polyphenols and flavonoids contents and antioxidant activities of honey. Some individual phenolic compounds in Serbian polyfloral honey (PH), linden honey (LH) and also in their mixtures with dried apricot, in 40% mass concentrations (PH40; LH40), were identified and quantified by HPLC. The most dominant phenolic compound was: gallic acid in LH (11.14 mg/100g), LH40 (42.65 mg/100g), PH (7.24 mg/100g) and catehin in PH40 (11.83 mg/100g). The antioxidant activity of PH, LH, PH40 and LH40 was tested by measuring their ability to scavenge hydroxyl radicals (OH) by electron spin resonance spectroscopy (ESR). Honey samples with 40% dried apricot exhibited better antioxidant activity measured by hydroxyl radical scavenging activity. The EC50 values, the amount of antioxidant necessary to decrease the initial concentration of OH radicals by 50%, were: EC50PH=3.36 mg/ml, EC50LH=13.36 mg/ml, EC50PH40=2.29 mg/ml, EC50 LH40=7.78 mg/ml. Our results indicate that supplementation of polyfloral honey and linden honey with dried apricots improves antioxidant activity of honey by enriching the phenolic composition.

Keywords: honey, dried apricot, HPLC, hydroxyl radical

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327 Crystalline Silica Exposure in Tunnelling: Identifying Barriers to Safe Practices

Authors: Frederick Anlimah, Vinod Gopaldasani, Catherine MacPhail, Brian Davies

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The construction industry, particularly tunnel construction, exposes workers to respirable crystalline silica (RCS), which can cause incurable illnesses such as silicosis and lung cancer. Despite various control measures, exposures remain inadequately controlled. This research aimed to identify the barriers and challenges hindering the implementation of effective controls and the adoption of safe work practices to protect workers from RCS exposure in tunnelling. A mixed-method approach was employed for this research. Tunnel construction workers were observed, surveyed and interviewed to gauge their knowledge and attitudes and understand their challenges in reducing RCS exposure. The preliminary analysis of the data reveals a diverse array of sociotechnical factors interacting to influence RCS exposure. It is noteworthy that participants consistently emphasised the project as the most exemplary one they have been involved in, although there is room for improvement. While there is a commendable level of knowledge about RCS exposure and control in tunnelling, there is a striking lack of perceived satisfaction regarding dust control. Several factors were identified as interacting to prevent the effective management of dust. These include perceived time pressure, absence of on-tool dust controls, low risk perceptions among workers, and inadequate enforcement of controls. Moreover, participants highlighted communication and heat-related challenges as hindrances to the continuous wear of respirators. This research highlights the need for a paradigm shift in tunnel construction to address the barriers associated with RCS exposure reduction. It emphasises the importance of collaboration among various stakeholders, advocating for more effective controls and enforcement strategies and enhanced worker education through knowledge sharing.

Keywords: respirable crystalline silica, dust control, worker practices, exposure prevention, silicosis

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326 FWGE Production From Wheat Germ Using Co-culture of Saccharomyces cerevisiae and Lactobacillus plantarum

Authors: Valiollah Babaeipour, Mahdi Rahaie

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food supplements are rich in specific nutrients and bioactive compounds that eliminate free radicals and improve cellular metabolism. The major bioactive compounds are found in bran and cereal sprouts. Secondary metabolites of these microorganisms have antioxidant properties that can be used alone or in combination with chemotherapy and radiation therapy to treat cancer. Biologically active compounds such as benzoquinone derivatives extracted from fermented wheat germ extract (FWGE) have several positive effects on the overall state of human health and strengthen the immune system. The present work describes the discontinuous fermentation of raw wheat germ for FWGE production through the simultaneous culture process using the probiotic strains of Saccharomyces cerevisiae, Lactobacillus plantarum, and the possibility of using solid waste. To increase production efficiency, first to select important factors in the optimization of each fermentation process, using a factorial statistical scheme of stirring fraction (120 to 200 rpm), dilution of solids to solvent (1 to 8-12), fermentation time (16 to 24 hours) and strain to wheat germ ratio (20% to 50%) were studied and then simultaneous culture was performed to increase the yields of 2 and 6 dimethoxybenzoquinone (2,6-DMBQ). Since 2 and 6 dimethoxy benzoquinone were fermented as the main biologically active compound in wheat germ extract, UV-Vis analysis was performed to confirm the presence of 2 and 6 dimethoxy benzoquinone in the final product. In addition, 2,6-DMBQ of some products was isolated in a non-polar C-18 column and quantified using high performance liquid chromatography (HPLC). Based on our findings, it can be concluded that the increase of 2 and 6 dimethoxybenzoquinone in the simultaneous culture of Saccharomyces cerevisiae - Lactobacillus plantarum compared to pure culture of Saccharomyces cerevisiae (from 1.89 mg / g) to 28.9% (2.66 mg / g) Increased.

Keywords: wheat germ, FWGE, saccharomyces cerevisiae, lactobacillus plantarum, co-culture, 2, 6-DMBQ

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325 Free Energy Computation of A G-Quadruplex-Ligand Structure: A Classical Molecular Dynamics and Metadynamics Simulation Study

Authors: Juan Antonio Mondragon Sanchez, Ruben Santamaria

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The DNA G-quadruplex is a four-stranded DNA structure formed by stacked planes of four base paired guanines (G-quartet). Guanine rich DNA sequences appear in many sites of genomic DNA and can potential form G-quadruplexes, such as those occurring at 3'-terminus of the human telomeric DNA. The formation and stabilization of a G-quadruplex by small ligands at the telomeric region can inhibit the telomerase activity. In turn, the ligands can be used to down regulate oncogene expression making G-quadruplex an attractive target for anticancer therapy. Many G-quadruplex ligands have been proposed with a planar core to facilitate the pi–pi stacking and electrostatic interactions with the G-quartets. However, many drug candidates are impossibilitated to discriminate a G-quadruplex from a double helix DNA structure. In this context, it is important to investigate the site topology for the interaction of a G-quadruplex with a ligand. In this work, we determine the free energy surface of a G-quadruplex-ligand to study the binding modes of the G-quadruplex (TG4T) with the daunomycin (DM) drug. The complex TG4T-DM is studied using classical molecular dynamics in combination with metadynamics simulations. The metadynamics simulations permit an enhanced sampling of the conformational space with a modest computational cost and obtain free energy surfaces in terms of the collective variables (CV). The free energy surfaces of TG4T-DM exhibit other local minima, indicating the presence of additional binding modes of daunomycin that are not observed in short MD simulations without the metadynamics approach. The results are compared with similar calculations on a different structure (the mutated mu-G4T-DM where the 5' thymines on TG4T-DM have been deleted). The results should be of help to design new G-quadruplex drugs, and understand the differences in the recognition topology sites of the duplex and quadruplex DNA structures in their interaction with ligands.

Keywords: g-quadruplex, cancer, molecular dynamics, metadynamics

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324 Design and Implementation of Smart Watch Textile Antenna for Wi-Fi Bio-Medical Applications in Millimetric Wave Band

Authors: M. G. Ghanem, A. M. M. A. Allam, Diaa E. Fawzy, Mehmet Faruk Cengiz

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This paper is devoted to the design and implementation of a smartwatch textile antenna for Wi-Fi bio-medical applications in millimetric wave bands. The antenna is implemented on a leather textile-based substrate to be embedded in a smartwatch. It enables the watch to pick Wi-Fi signals without the need to be connected to a mobile through Bluetooth. It operates at 60 GHz or WiGig (Wireless Gigabit Alliance) band with a wide band for higher rate applications. It also could be implemented over many stratified layers of the body organisms to be used in the diagnosis of many diseases like diabetes and cancer. The structure is designed and simulated using CST (Studio Suite) program. The wearable patch antenna has an octagon shape, and it is implemented on leather material that acts as a flexible substrate with a size of 5.632 x 6.4 x 2 mm3, a relative permittivity of 2.95, and a loss tangent of 0.006. The feeding is carried out using differential feed (discrete port in CST). The work provides five antenna implementations; antenna without ground, a ground is added at the back of the antenna in order to increase the antenna gain, the substrate dimensions are increased to 15 x 30 mm2 to resemble the real hand watch size, layers of skin and fat are added under the ground of the antenna to study the effect of human body tissues human on the antenna performance. Finally, the whole structure is bent. It is found that the antenna can achieve a simulated peak realized gain in dB of 5.68, 7.28, 6.15, 3.03, and 4.37 for antenna without ground, antenna with the ground, antenna with larger substrate dimensions, antenna with skin and fat, and bent structure, respectively. The antenna with ground exhibits high gain; while adding the human organisms absorption, the gain is degraded because of human absorption. The bent structure contributes to higher gain.

Keywords: bio medical engineering, millimetric wave, smart watch, textile antennas, Wi-Fi

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323 Uterine Cervical Cancer; Early Treatment Assessment with T2- And Diffusion-Weighted MRI

Authors: Susanne Fridsten, Kristina Hellman, Anders Sundin, Lennart Blomqvist

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Background: Patients diagnosed with locally advanced cervical carcinoma are treated with definitive concomitant chemo-radiotherapy. Treatment failure occurs in 30-50% of patients with very poor prognoses. The treatment is standardized with risk for both over-and undertreatment. Consequently, there is a great need for biomarkers able to predict therapy outcomes to allow for individualized treatment. Aim: To explore the role of T2- and diffusion-weighted magnetic resonance imaging (MRI) for early prediction of therapy outcome and the optimal time point for assessment. Methods: A pilot study including 15 patients with cervical carcinoma stage IIB-IIIB (FIGO 2009) undergoing definitive chemoradiotherapy. All patients underwent MRI four times, at baseline, 3 weeks, 5 weeks, and 12 weeks after treatment started. Tumour size, size change (∆size), visibility on diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) and change of ADC (∆ADC) at the different time points were recorded. Results: 7/15 patients relapsed during the study period, referred to as "poor prognosis", PP, and the remaining eight patients are referred to "good prognosis", GP. The tumor size was larger at all time points for PP than for GP. The ∆size between any of the four-time points was the same for PP and GP patients. The sensitivity and specificity to predict prognostic group depending on a remaining tumor on DWI were highest at 5 weeks and 83% (5/6) and 63% (5/8), respectively. The combination of tumor size at baseline and remaining tumor on DWI at 5 weeks in ROC analysis reached an area under the curve (AUC) of 0.83. After 12 weeks, no remaining tumor was seen on DWI among patients with GP, as opposed to 2/7 PP patients. Adding ADC to the tumor size measurements did not improve the predictive value at any time point. Conclusion: A large tumor at baseline MRI combined with a remaining tumor on DWI at 5 weeks predicted a poor prognosis.

Keywords: chemoradiotherapy, diffusion-weighted imaging, magnetic resonance imaging, uterine cervical carcinoma

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