Search results for: inhibition of cancer cells

Authors: Angela O. Ugwu, Sunday Ocheni

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Background: Cancer-associated thrombosis (CAT) is a cause of morbidity and mortality among cancer patients. Several risk factors for developing venous thromboembolism (VTE) also coexist with cancer patients, such as chemotherapy and immobilization, thus contributing to the higher risk of VTE in cancer patients when compared to non-cancer patients. This study aimed to determine if there is any correlation between levels of some inflammatory cytokines/haematological parameters and Khorana scores of newly diagnosed chemotherapy naïve ambulatory cancer patients (CNACP). Methods: This was a cross-sectional analytical study carried out from June 2021 to May 2022. Eligible newly diagnosed cancer patients 18 years and above (case group) were enrolled consecutively from the adult Oncology Clinics of the University of Nigeria Teaching Hospital, Ituku/Ozalla (UNTH). The control group was blood donors at UNTH Ituku/Ozalla, Enugu blood bank, and healthy members of the Medical and Dental Consultants Association of Nigeria (MDCAN), UNTH Chapter. Blood samples collected from the participants were assayed for IL-6, TNF-Alpha, and haematological parameters such as haemoglobin, white blood cell count (WBC), and platelet count. Data were entered into an Excel worksheet and were then analyzed using Statistical Package for Social Sciences (SPSS) computer software version 21.0 for windows. A P value of < 0.05 was considered statistically significant. Results: A total of 200 participants (100 cases and 100 controls) were included in the study. The overall mean age of the participants was 47.42 ±15.1 (range 20-76). The sociodemographic characteristics of the two groups, including age, sex, educational level, body mass index (BMI), and occupation, were similar (P > 0.05). Following One Way ANOVA, there were significant differences between the mean levels of interleukin-6 (IL-6) (p = 0.036) and tumor necrotic factor-α (TNF-α) (p = 0.001) in the three Khorana score groups of the case group. Pearson’s correlation analysis showed a significant positive correlation between the Khorana scores and IL-6 (r=0.28, p = 0.031), TNF-α (r= 0.254, p= 0.011), and PLR (r= 0.240, p=0.016). The mean serum levels of IL-6 were significantly higher in CNACP than in the healthy controls [8.98 (8-12) pg/ml vs. 8.43 (2-10) pg/ml, P=0.0005]. There were also significant differences in the mean levels of the haemoglobin (Hb) level (P < 0.001)); white blood cell (WBC) count ((P < 0.001), and platelet (PL) count (P = 0.005) between the two groups of participants. Conclusion: There is a significant positive correlation between the serum levels of IL-6, TNF-α, and PLR and the Khorana scores of CNACP. The mean serum levels of IL-6, TNF-α, PLR, WBC, and PL count were significantly higher in CNACP than in the healthy controls. Ambulatory cancer patients with high-risk Khorana scores may benefit from anti-inflammatory drugs because of the positive correlation with inflammatory cytokines. Recommendations: Ambulatory cancer patients with 2 Khorana scores may benefit from thromboprophylaxis since they have higher Khorana scores. A multicenter study with a heterogeneous population and larger sample size is recommended in the future to further elucidate the relationship between IL-6, TNF-α, PLR, and the Khorana scores among cancer patients in the Nigerian population.

Keywords: thromboprophylaxis, cancer, Khorana scores, inflammatory cytokines, haematological parameters

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Authors: Chih-Wei Chao, Jiashing Yu

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Microfluidic devices have recently emerged as promising tools for the fabrication of scaffolds for cell culture. To mimic the natural circumstances of organism for cells to grow, here we present three-dimensional (3D) scaffolds fabricated by microfluidics for cells cultivation. This work aims at investigating the behavior in terms of the viability and the proliferation capability of rat H9c2 cardiomyocytes in the gelatin 3D scaffolds by fluorescent images.

Keywords: microfluidic device, H9c2, tissue engineering, 3D scaffolds

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Authors: Larisa Gheber

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Mitosis is an essential process by which duplicated genetic information is transmitted from mother to daughter cells. Incorrect chromosome segregation during mitosis can lead to genetic diseases, chromosome instability and cancer. This process is mediated by a dynamic microtubule-based intracellular structure, the mitotic spindle. One of the major factors that govern the mitotic spindle dynamics are the kinesin-5 biological nano motors that were believed to move unidirectionally on the microtubule filaments, using ATP hydrolysis, thus performing essential functions in mitotic spindle dynamics. Surprisingly, several reports from our and other laboratories have demonstrated that some kinesin-5 motors are bi-directional: they move in minus-end direction on the microtubules as single-molecules and can switch directionality under a number of conditions. These findings broke a twenty-five-years old dogma regarding kinesin directionality (1, 2). The mechanism of this bi-directional motility and its physiological significance remain unclear. To address this unresolved problem, we apply an interdisciplinary approach combining live cell imaging, biophysical single molecule, and structural experiments to examine the activity of these motors and their mutated variants in vivo and in vitro. Our data shows that factors such as protein phosphorylation (3, 4), motor clustering on the microtubules (5, 6) and structural elements (7, 8) regulate the bi-directional motility of kinesin motors. We also show, using Cryo-EM, that bi-directional kinesin motors obtain non-canonical microtubule binding, which is essential to their special motile properties and intracellular functions. We will discuss the implication of these findings to mechanism bi-directional motility and physiological roles in mitosis.

Keywords: mitosis, cancer, kinesin, microtubules, biochemistry, biophysics

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Authors: Magdalena Kowalska, Weronika Rupik

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The pancreas is an important organ present in all vertebrate species. It contains two different tissues, exocrine and endocrine, that act as two glands in one. The development and differentiation of the pancreas in reptiles is poorly known in comparison to other vertebrates. Therefore, the aim of this study was to investigate the particular steps concerning the differentiation of the pancreas in the grass snake (Natrix natrix) embryos. For this, histological methods (including hematoxylin and eosin, and Heidenhain's AZAN staining), transmission electron microscopy and three-dimensional (3D) reconstructions from serial paraffin sections were used. The results of this study indicated that the first step of pancreas development in Natrix was the connection of the two pancreatic buds: dorsal and ventral one. Then, duct walls in both buds started to be remodeled from the multilayered to single-layered epithelium. This remodeling started in the dorsal bud and was simultaneously with the differentiation of the duct lumens which occurred by the cavition. During this process, the cells that had no contact with the mesenchyme underwent cell death named anoikis. These findings indicated that the walls of ducts in the embryonic pancreas of the grass snake were initially formed by the abundant principal and single endocrine cells. Later the basal and goblet cells differentiated. Among the endocrine cells, as the first the B and A cells differentiated, then the D and PP cells. The next step of the pancreatic development was the withdrawing of the endocrine cells from the duct walls to form the pancreatic islets. The endocrine cells and islets were found only in the dorsal part of the pancreas in Natrix embryos what is different than in other vertebrate species. The islets were formed mainly by the A cells. Simultaneously, with the differentiation of the endocrine pancreas, the acinar tissue started to differentiate. The source of the acinar cells were pancreatic ducts similar as in other vertebrates. The acini formation began at the proximal part of the pancreas and went towards the caudal direction. Differentiating pancreatic ducts developed into the branched system that can be divided into extralobular, intralobular, and intercalated ducts, similarly as in other vertebrate species. However, the pattern of branching was different. In conclusions, particular steps of the pancreas differentiation in the grass snake were different than in other vertebrates. It can be supposed that these differences are related to the specific topography of the snake’s internal organs and their taxonomy position. All specimens used in the study were captured according to the Polish regulations concerning the protection of wild species. Permission was granted by the Local Ethics Commission in Katowice (41/2010; 87/2015) and the Regional Directorate for Environmental Protection in Katowice (WPN.6401.257.2015.DC).

Keywords: embryogenesis, organogenesis, pancreas, Squamata

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Authors: Dan Yan, Yunuo Zhang, Yuhan Huang, Weijie Ouyang

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The cornea serves as a vital protective barrier for the eye; however, it is prone to injury and damage that can disrupt corneal epithelium and nerves, triggering inflammation. Therefore, understanding the biological effects and molecular mechanisms involved in corneal wound healing and identifying drugs targeting these pathways is crucial for researchers in this field. This study aimed to investigate the therapeutic potential of progranulin (PGRN) in treating corneal injuries. Our findings demonstrated that PGRN significantly enhanced corneal wound repair by accelerating corneal re-epithelialization and re-innervation. In vitro experiments with cultured epithelial cells and trigeminal ganglion cells further revealed that PGRN stimulated corneal epithelial cell proliferation and promoted axon growth in trigeminal ganglion cells. Through RNA-sequencing (RNA-seq) analysis and other experimental techniques, we discovered that PGRN exerted its healing effects by modulating the Wnt signaling pathway, which played a critical role in repairing epithelial cells and promoting axon regeneration in trigeminal neurons. Importantly, our study highlighted the anti-inflammatory properties of PGRN by inhibiting the NF-κB signaling pathway, leading to decreased infiltration of macrophages. In conclusion, our findings underscored the potential of PGRN in facilitating corneal wound healing by promoting corneal epithelial cell proliferation, trigeminal ganglion cell axon regeneration, and suppressing ocular inflammation. These results suggest that PGRN could potentially expedite the healing process and improve visual outcomes in patients with corneal injuries.

Keywords: cornea, wound healing, progranulin, corneal epithelial cells, trigeminal ganglion cells

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Authors: Okhee Woo

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Purpose: The aim of this study is to evaluate 2-year cumulative effective radiation dose and cumulative organ dose on regular follow-up computed tomography (CT) scans in patients with breast cancer and to establish personalized low-dose CT protocol. Methods and Materials: A retrospective study was performed on the patients with breast cancer who were diagnosed and managed consistently on the basis of routine breast cancer follow-up protocol between 2012-01 and 2016-06. Based on ICRP (International Commission on Radiological Protection) 103, the cumulative effective radiation doses of each patient for 2-year follow-up were analyzed using the commercial radiation management software (Radimetrics, Bayer healthcare). The personalized effective doses on each organ were analyzed in detail by the software-providing Monte Carlo simulation. Results: A total of 3822 CT scans on 490 patients was evaluated (age: 52.32±10.69). The mean scan number for each patient was 7.8±4.54. Each patient was exposed 95.54±63.24 mSv of radiation for 2 years. The cumulative CT radiation dose was significantly higher in patients with lymph node metastasis (p = 0.00). The HER-2 positive patients were more exposed to radiation compared to estrogen or progesterone receptor positive patient (p = 0.00). There was no difference in the cumulative effective radiation dose with different age groups. Conclusion: To acknowledge how much radiation exposed to a patient is a starting point of management of radiation exposure for patients with long-term CT follow-up. The precise and personalized protocol, as well as iterative reconstruction, may reduce hazard from unnecessary radiation exposure.

Keywords: computed tomography, breast cancer, effective radiation dose, cumulative organ dose

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Authors: Pegah Safavi, Mehdi Zehtabian, Mohammad Amin Mosleh-Shirazi

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Cancer is one of the leading causes of death in the world. Radiation therapy is one of the main choices for cancer treatment. Intensity-modulated radiation therapy is a new type of radiation therapy technique available for vital structures such as the parathyroid glands. It is very important to check the accuracy of the delivered IMRT treatment because any mistake may lead to more complications for the patient. This paper describes an experiment to determine the accuracy of a dose measured by EBT3 film. To test this method, the EBT3 film on the head and neck of the Rando phantom was irradiated by an IMRT device and the irradiation was repeated twice. Finally, the dose designed by the irradiation system was compared with the dose measured by the EBT3 film. Using this criterion, the accuracy of the EBT3 film was evaluated. When using this criterion, a 95% agreement was reached between the planned treatment and the measured values.

Keywords: EBT3, phantom, accuracy, cancer, IMRT

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Authors: Amena Omer Syeda, Harita Shyam

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Background: Anorexia a common symptom among patients with prolonged illness leading to anorexia-cachexia syndrome with a prevalence rate of 70%. In order to provide effective health care and better response to treatment, appetite should be assessed on admission and then periodically for earlier nutrition intervention. Functional Assessment of Anorexia/Cachexia Therapy (FAACT) appetite scale is 12 questions, patient-rated, symptom specific measure for appetite, and distress from anorexia. It assigns a score ranging from 0 (worst response) to 4 (best response). Therefore, proposing a total score of ≤24 may be sufficient to make a diagnosis of anorexia. Objectives: To assess the FAACT scale by co-relating the scores with the Nutritional intake and BMI of Cancer Patients. Methods: The FAACT scores of 100 cancer in-patients receiving chemotherapy or radiation as treatment, their 24-hour calorie and protein intake and BMI were recorded. The data was then statistically analyzed. Results: The calorie and protein intake and FAACT scores both showed a significant positive co-relation (p<0.001), inferring that the patients with a FAACT score of ≤24 where not meeting their calorie as well as protein requirements, hence rightly categorizing them as anorexic. The co-relation between BMI and FAACT scores showed a weak co-relation and was not statistically significant (p > 0.05).The FAACT scale thus is not sensitive to distinguish patients being under-weight, normal weight or obese. Conclusion: The FAACT scale helps in providing better palliative and nutritional care as it correctly assessed anorexia /cachexia in cancer patients and co-related significantly with their nutrient intake.

Keywords: appetite, cachexia, cancer, malnutrition

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Authors: Elena Filova, Ondrej Kaplan, Marie Markova, Helena Dragounova, Roman Matejka, Eduard Brynda, Lucie Bacakova

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Decellularized vessels have been evaluated as small-diameter vascular prostheses. Reseeding autologous cells onto decellularized tissue prior implantation should prolong prostheses function and make them living tissues. Suitable cell types for reseeding are both endothelial cells and bone marrow-derived stem cells, with a capacity for differentiation into smooth muscle cells upon mechanical loading. Endothelial cells assure antithrombogenicity of the vessels and MSCs produce growth factors and, after their differentiation into smooth muscle cells, they are contractile and produce extracellular matrix proteins as well. Fibrin is a natural scaffold, which allows direct cell adhesion based on integrin receptors. It can be prepared autologous. Fibrin can be modified with bound growth factors, such as basic fibroblast growth factor (FGF-2) and vascular endothelial growth factor (VEGF). These modifications in turn make the scaffold more attractive for cells ingrowth into the biological scaffold. The aim of the study was to prepare thin surface-attached fibrin assemblies with bound FGF-2 and VEGF, and to evaluate growth and differentiation of bone marrow-derived mesenchymal stem cells on the fibrin (Fb) assemblies. Following thin surface-attached fibrin assemblies were prepared: Fb, Fb+VEGF, Fb+FGF2, Fb+heparin, Fb+heparin+VEGF, Fb+heparin+FGF2, Fb+heparin+FGF2+VEGF. Cell culture poly-styrene and glass coverslips were used as controls. Human MSCs (passage 3) were seeded at the density of 8800 cells/1.5 mL alpha-MEM medium with 2.5% FS and 200 U/mL aprotinin per well of a 24-well cell culture. The cells have been cultured on the samples for 6 days. Cell densities on day 1, 3, and 6 were analyzed after staining with LIVE/DEAD cytotoxicity/viability assay kit. The differentiation of MSCs is being analyzed using qPCR. On day 1, the highest density of MSCs was observed on Fb+VEGF and Fb+FGF2. On days 3 and 6, there were similar densities on all samples. On day 1, cell morphology was polygonal and spread on all sample. On day 3 and 6, MSCs growing on Fb assemblies with FGF2 became apparently elongated. The evaluation of expression of genes for von Willebrand factor and CD31 (endothelial cells), for alpha-actin (smooth muscle cells), and for alkaline phosphatase (osteoblasts) is in progress. We prepared fibrin assemblies with bound VEGF and FGF-2 that supported attachment and growth of mesenchymal stem cells. The layers are promising for improving the ingrowth of MSCs into the biological scaffold. Supported by the Technology Agency of the Czech Republic TA04011345, and Ministry of Health NT11270-4/2010, and BIOCEV – Biotechnology and Biomedicine Centre of the Academy of Sciences and Charles University” project (CZ.1.05/1.1.00/02.0109), funded by the European Regional Development Fund for their financial supports.

Keywords: fibrin assemblies, FGF-2, mesenchymal stem cells, VEGF

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Authors: Behnaz Sohani, Sahand Shahalinezhad, Amir Rahmani, Aliyu Aliyu

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Recently, medical imaging and specifically medical image processing is becoming one of the most dynamically developing areas of medical science. It has led to the emergence of new approaches in terms of the prevention, diagnosis, and treatment of various diseases. In the process of diagnosis of lung cancer, medical professionals rely on computed tomography (CT) scans, in which failure to correctly identify masses can lead to incorrect diagnosis or sampling of lung tissue. Identification and demarcation of masses in terms of detecting cancer within lung tissue are critical challenges in diagnosis. In this work, a segmentation system in image processing techniques has been applied for detection purposes. Particularly, the use and validation of a novel lung cancer detection algorithm have been presented through simulation. This has been performed employing CT images based on multilevel thresholding. The proposed technique consists of segmentation, feature extraction, and feature selection and classification. More in detail, the features with useful information are selected after featuring extraction. Eventually, the output image of lung cancer is obtained with 96.3% accuracy and 87.25%. The purpose of feature extraction applying the proposed approach is to transform the raw data into a more usable form for subsequent statistical processing. Future steps will involve employing the current feature extraction method to achieve more accurate resulting images, including further details available to machine vision systems to recognise objects in lung CT scan images.

Keywords: lung cancer detection, image segmentation, lung computed tomography (CT) images, medical image processing

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Authors: Urvi Panwar, Kanchan Mishra, Kanjaksha Ghosh, ShankerLal Kothari

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Background: Day-by-day the increasing prevalence of neurodegenerative diseases have become a global issue to manage them by medical sciences. The adult neural stem cells are rare and require an invasive and painful procedure to obtain it from central nervous system. Mesenchymal stem cell (MSCs) therapies have shown remarkable application in treatment of various cell injuries and cell loss. MSCs can be derived from various sources like adult tissues, human bone marrow, umbilical cord blood and cord tissue. MSCs have similar proliferation and differentiation capability, but the human umbilical cord-derived mesenchymal stem cells (hUCMSCs) are proved to be more beneficial with respect to cell procurement, differentiation to other cells, preservation, and transplantation. Material and method: Human umbilical cord is easily obtainable and non-controversial comparative to bone marrow and other adult tissues. The umbilical cord can be collected after delivery of baby, and its tissue can be cultured using explant culture method. Cell culture medium such as DMEMF12+10% FBS and DMEMF12+Neural growth factors (bFGF, human noggin, B27) with antibiotics (Streptomycin/Gentamycin) were used to culture and differentiate mesenchymal stem cells into neural cells, respectively. The characterisations of MSCs were done with Flow Cytometer for surface markers CD90, CD73 and CD105 and colony forming unit assay. The differentiated various neural cells will be characterised by fluorescence markers for neurons, astrocytes, and oligodendrocytes; quantitative PCR for genes Nestin and NeuroD1 and Western blotting technique for gap43 protein. Result and discussion: The high quality and number of MSCs were isolated from human umbilical cord via explant culture method. The obtained MSCs were differentiated into neural cells like neurons, astrocytes and oligodendrocytes. The differentiated neural cells can be used to treat neural injuries and neural cell loss by delivering cells by non-invasive administration via cerebrospinal fluid (CSF) or blood. Moreover, the MSCs can also be directly delivered to different injured sites where they differentiate into neural cells. Therefore, human umbilical cord is demonstrated to be an inexpensive and easily available source for MSCs. Moreover, the hUCMSCs can be a potential source for neural cell therapies and neural cell regeneration for neural cell injuries and neural cell loss. This new way of research will be helpful to treat and manage neural cell damages and neurodegenerative diseases like Alzheimer and Parkinson. Still the study has a long way to go but it is a promising approach for many neural disorders for which at present no satisfactory management is available.

Keywords: bone marrow, cell therapy, explant culture method, flow cytometer, human umbilical cord, mesenchymal stem cells, neurodegenerative diseases, neuroprotective, regeneration

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Authors: Han-Wei Shih, Yao-Nan Wang, Ko-Tung Chang, Lung-Ming Fu

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A multi-channel cell growth real-time monitor and evaluation system using charge-coupled device (CCD) sensors with 40X lens integrating a NI LabVIEW image processing program is proposed and demonstrated. The LED light source control of monitor system is utilizing 8051 microprocessor integrated with NI LabVIEW software. In this study, the same concentration RAW264.7 cells growth rate and morphology in four different culture conditions (DMEM, LPS, G1, G2) were demonstrated. The real-time cells growth image was captured and analyzed by NI Vision Assistant every 10 minutes in the incubator. The image binarization technique was applied for calculating cell doubling time and cell division index. The cells doubling time and cells division index of four group with DMEM, LPS, LPS+G1, LPS+G2 are 12.3 hr,10.8 hr,14.0 hr,15.2 hr and 74.20%, 78.63%, 69.53%, 66.49%. The image magnification of multi-channel CCDs cell real-time monitoring system is about 100X~200X which compares with the traditional microscope.

Keywords: charge-coupled device (CCD), RAW264.7, doubling time, division index

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Authors: Maryam Kiani

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Non-precious electrocatalysts play a crucial role in the oxygen reduction reaction (ORR) for regenerative fuel cells and rechargeable metal-air batteries. To enhance ORR activity, La (a less active element) is added to modify the activity of Ni. This addition increases the surface contents of Ni2+, N, and S species in LaNi/N-S-C, while still maintaining a substantial specific surface area and hierarchical porosity. Therefore, the additional La is essential for the successful ORR process.In addition, the presence of extra La in the LaNi/N-S-C electrocatalyst enhances the efficiency of charge transfer and improves the surface acid-base characteristics, facilitating the adsorption of oxygen molecules during the ORR process. As a result, this superior and desirable electrocatalyst exhibits significantly enhanced ORR bifunctional activity. In fact, its ORR activity is comparable to that of the 20 wt% Pt/C.

Keywords: fuel cells, batteries, dual-doped carbon black, ORR

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Authors: Hossein Rassi, Marjan Moradi Fard, Masoud Houshmand

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Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia (CIN) and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, HPV18, p53 codon 72 polymorphism, miR-146a rs2910164 polymorphism

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Authors: Tansa Nisan Gunerhan

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Dementia comes in different forms, including Alzheimer's disease. The most common dementia diagnosis among elderly individuals is Alzheimer's disease. On average, for patients with Alzheimer’s, life expectancy is around 4-8 years after the diagnosis; however, expectancy can go as high as twenty years or more, depending on the shrinkage of the brain. Normally, along with aging, the brain shrinks at some level but doesn’t lose a vast amount of neurons. However, Alzheimer's patients' neurons are destroyed rapidly; hence problems with loss of memory, communication, and other metabolic activities begin. The toxic changes in the brain affect the stability of the neurons. Beta-amyloid and tau are two proteins that are believed to play a role in the development of Alzheimer's disease through their toxic changes. Beta-amyloid is a protein that is produced in the brain and is normally broken down and removed from the body. However, in people with Alzheimer's disease, the production of beta-amyloid increases, and it begins to accumulate in the brain. These plaques are thought to disrupt communication between nerve cells and may contribute to the death of brain cells. Tau is a protein that helps to stabilize microtubules, which are essential for the transportation of nutrients and other substances within brain cells. In people with Alzheimer's disease, tau becomes abnormal and begins to accumulate inside brain cells, forming neurofibrillary tangles. These tangles disrupt the normal functioning of brain cells and may contribute to their death, forming amyloid plaques which are deposits of a protein called amyloid-beta that build up between nerve cells in the brain. The accumulation of amyloid plaques and neurofibrillary tangles in the brain is thought to contribute to the shrinkage of brain tissue. As the brain shrinks, the size of the brain may decrease, leading to a reduction in brain volume. Brain atrophy in Alzheimer's disease is often accompanied by changes in the structure and function of brain cells and the connections between them, leading to a decline in brain function. These toxic changes that accumulate can cause symptoms such as memory loss, difficulty with thinking and problem-solving, and changes in behavior and personality.

Keywords: Alzheimer, amyloid-beta, brain atrophy, neuron, shrinkage

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Authors: R. Gharari, N. Kojouri, R. Hosseini Aghdam, E. Alibeigi, B. Salmasian

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In this research, the WWER1000/V446 (a PWR Russian type reactor) is chosen as the case study. It is assumed that radioactive materials that release into the environment are more than allowable limit due to a complete failure of the ventilation system (reactor stack). In the following, the HOTSPOT and the RASCAL computational codes have been used and coupled with a developed program using MATLAB software to evaluate Total effective dose equivalent (TEDE) and cancer risk according to the BEIR equations for various human organs. In addition, effects of the containment spray system and climate conditions on the TEDE have been investigated. According to the obtained results, there is an inverse correlation between the received dose and the wind speed; the amount of the TEDE for wind speed 2 m/s and is more than wind speed for 14 m/s during the class A of the climate (2.168 and 0.444 mSv, respectively). Also, containment spray system can effect and reduce the amount of the fission products and TEDE. Furthermore, the probability of the cancer risk for women is more than men, and for children is more than adults. In addition, a specific emergency zonal planning is proposed. Results are promising in which the site selection of the WWER1000/V446 were considered safe for the public in this situation.

Keywords: TEDE, total effective dose equivalent, RASCAL and HOTSPOT codes, BEIR equations, cancer risk

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Authors: S. Maleczek, K. Drabczyk, L. Bogdan, A. Iwan

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It is known that for industrial applications using solar panel constructed from silicon solar cells require high-efficiency performance. One of the main problems in solar panels is different mechanical and structural defects, causing the decrease of generated power. To analyse defects in solar cells, various techniques are used. However, the thermal imaging is fast and simple method for locating defects. The main goal of this work was to analyze defects in constructed flexible silicon photovoltaic modules via thermal imaging and electroluminescence method. This work is realized for the GEKON project (No. GEKON2/O4/268473/23/2016) sponsored by The National Centre for Research and Development and The National Fund for Environmental Protection and Water Management. Thermal behavior was observed using thermographic camera (VIGOcam v50, VIGO System S.A, Poland) using a DC conventional source. Electroluminescence was observed by Steinbeis Center Photovoltaics (Stuttgart, Germany) equipped with a camera, in which there is a Si-CCD, 16 Mpix detector Kodak KAF-16803type. The camera has a typical spectral response in the range 350 - 1100 nm with a maximum QE of 60 % at 550 nm. In our work commercial silicon solar cells with the size 156 × 156 mm were cut for nine parts (called single solar cells) and used to create photovoltaic modules with the size of 160 × 70 cm (containing about 80 single solar cells). Flexible silicon photovoltaic modules on polyamides or polyester fabric were constructed and investigated taking into consideration anomalies on the surface of modules. Thermal imaging provided evidence of visible voltage-activated conduction. In electro-luminescence images, two regions are noticeable: darker, where solar cell is inactive and brighter corresponding with correctly working photovoltaic cells. The electroluminescence method is non-destructive and gives greater resolution of images thereby allowing a more precise evaluation of microcracks of solar cell after lamination process. Our study showed good correlations between defects observed by thermal imaging and electroluminescence. Finally, we can conclude that the thermographic examination of large scale photovoltaic modules allows us the fast, simple and inexpensive localization of defects at the single solar cells and modules. Moreover, thermographic camera was also useful to detection electrical interconnection between single solar cells.

Keywords: electro-luminescence, flexible devices, silicon solar cells, thermal imaging

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Authors: Basuki Supartono

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Introduction: Diabetic wound risks limb amputation, and the healing remains challenging. Chronic Hyperglycemia caused the insufficient inflammatory response and impaired ability of the cells to regenerate. Tissue Engineering Technique is mandatory. Methods: Tissue engineering (TE)-based therapy Utilizing mononuclear cells, plasma rich platelets, and collagen applied on the damaged tissue Results: TE technique resulting in acceptable outcomes. The wound healed completely in 2 months. No adverse effects. No allergic reaction. No morbidity and mortality Discussion: TE-based therapy utilizing mononuclear cells, plasma rich platelets, and collagen are safe and comfortable to fix damaged tissues. These components stop the chronic inflammatory process and increase cells' ability for regeneration and restoration of damaged tissues. Both of these allow the wound to regenerate and heal. Conclusion: TE-based therapy is safe and effectively treats unhealed diabetic lesion.

Keywords: diabetic foot lesion, tissue engineering technique, wound healing, stemcells

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Authors: Adeniyi Onasanya, Maher Elshakankiri

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In recent years, the Internet of Things (IoT) has constituted a driving force of modern technological advancement, and it has become increasingly common as its impacts are seen in a variety of application domains, including healthcare. IoT is characterized by the interconnectivity of smart sensors, objects, devices, data, and applications. With the unprecedented use of IoT in industrial, commercial and domestic, it becomes very imperative to harness the benefits and functionalities associated with the IoT technology in (re)assessing the provision and positioning of healthcare to ensure efficient and improved healthcare delivery. In this research, we are focusing on two important services in healthcare systems, which are cancer care services and business analytics/cloud services. These services incorporate the implementation of an IoT that provides solution and framework for analyzing health data gathered from IoT through various sensor networks and other smart devices in order to improve healthcare delivery and to help health care providers in their decision-making process for enhanced and efficient cancer treatment. In addition, we discuss the wireless sensor network (WSN), WSN routing and data transmission in the healthcare environment. Finally, some operational challenges and security issues with IoT-based healthcare system are discussed.

Keywords: IoT, smart health care system, business analytics, (wireless) sensor network, cancer care services, cloud services

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Authors: Jung-Feng Hsieh, Chu Ze Chen

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Curcumin is the main active compound of turmeric that can inhibit the activities of α-glucosidase and xanthine oxidase (XO). α-Glucosidase and XO inhibitors are widely used to treat patients with diabetes mellitus and gout, respectively; therefore, the objective of this research was to evaluate the inhibitory activities of curcumin and its analogs against α-glucosidase and XO. Our results demonstrated that CM-F had the strongest antioxidant activity with a half-maximal effective concentration (EC50) of 9.39 ± 0.16 μM, which was superior to vitamin E (EC50=17.03 ± 0.09 μM). CM-F also exhibited potent inhibitory activity against XO with an IC50 value of 6.14 ± 0.38 μM and enzyme kinetic results revealed competitive inhibition of XO. We also found that CM-1 and CM-2 inhibited α-glucosidase with IC50 values of 21.06 ± 0.92 μM and 5.95 ± 0.09 μM, respectively, and kinetic studies indicated that both CM-1 and CM-2 are mixed competitive inhibitors of α-glucosidase. Furthermore, docking simulation identified five hydrogen bonds between XO and CM-F; however, only one and two hydrogen bonds are involved in CM-1 and CM-2 binding to α-glucosidase, respectively. Accordingly, curcumin and its analogs have the potential to be used in the treatment of patients with diabetes mellitus and gout.

Keywords: curcumin, α-glucosidase, inhibitor, xanthine oxidase

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Authors: Petnamnueng Dettipponpong, Shuen E. Chen

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Heat stress is known to have negative effects on reproductive functions, such as follicular development and ovulation. This study aimed to investigate the specific effects of heat stress on steroid hormone secretion of ovarian follicle cells, particularly in relation to the expression of Apolipoprotein B (ApoB) and microsomal triglyceride transfer protein (MTP). The aim of the study was to understand the impact of heat stress on steroid hormone secretion in ovarian follicle cells and to explore the role of ApoB and MTP in this process. Primary granulosa and theca cells were collected from follicles and cultured under heat stress conditions (42 °C) for various time periods. Controls were maintained under normal conditions (37.5 °C ). The culture medium was collected at different time points to measure levels of progesterone and estradiol using ELISA kits. ApoB and MTP expression levels were analyzed using homemade antibodies and western blot. Data were assessed by a one-way ANOVA comparison test with Duncan’s new multiple-range test. Results were expressed as mean±S.E. Difference was considered significant at P<0.05. The results showed that heat stress significantly increased progesterone secretion in granulosa cells, with the peak observed after 13 hours of recovery under thermoneutral conditions. Estradiol secretion by theca cells was not affected. Heat stress also had a significant negative effect on granulosa cell viability. Additionally, the expression of ApoB and MTP was found to be differentially regulated by heat stress. ApoB expression in theca cells was transiently promoted, while ApoB expression in granulosa cells was consistently suppressed. MTP expression increased after 5 hours of recovery in both cell types. These findings suggest a mechanism by which chicken follicle cells export cellular lipids as very low-density lipoprotein (VLDL) in response to thermal stress. These contribute to our understanding of the role of ApoB and MTP steroidogenesis and lipid metabolism under heat stress conditions. The study involved the collection of primary granulosa and theca cells, culture under different temperature conditions, and analysis of the culture medium for hormone levels using ELISA kits. ApoB and MTP expression levels were assessed using homemade antibodies and western blot. This study aimed to address the effects of heat stress on steroid hormone secretion in ovarian follicle cells, as well as the role of ApoB and MTP in this process. The study demonstrates that heat stress stimulates steroidogenesis in granulosa cells, affecting progesterone secretion. ApoB and MTP expression were found to be differentially regulated by heat stress, indicating a potential mechanism for the export of cellular lipids in response to thermal stress.

Keywords: heat stress, granulosa cells, theca cells, steroidogenesis, chicken, apolipoprotein B, microsomal triglyceride transfer protein

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Authors: Dalila Bouamra, Chekib Arslane Baki, Abdelhamid Bouchebour, Fatiha Koussa, Amel Benamara, Seoussen Kada

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The activity of methanolic extract from Anacyclus pyrethrum was evaluated using λ-carrageenan 1% induced paw edema in Wistar Albinos rats. The oral administration of 200 mg/kg, 400 mg/kg and 600 mg/kg, body weight of methanolic extract, one hour before induction of inflammation, exerted a significant inhibition effect of 47%, 57% and 62% respectively after 4h λ-carrageenan treatment and highly significant inhibition effect of 57%, 66% and 75% respectively after 8h λ-carrageenan treatment, compared to non treated group (100%) and that treated with aspirin, a standard anti-inflammatory drug. On the other hand, the effect of the plant extract on stomach was macroscopically and microscopically studied. The plant extract has an impact on the loss ratio of granulocytes that have invaded the stomach after a period of inflammation at a dose of 600 mg/kg body weight.

Keywords: inflammation, Anacyclus pyrethrum, gastritis, Wistar Albinos rats

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Authors: Ya-Ting Chuang, Krystle Leung, Ya-Jen Chang, Rosemarie H. DeKruyff, Paul B. Savage, Richard Cruse, Christophe Benoit, Dirk Elewaut, Nicole Baumgarth, Dale T. Umetsu

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We examined characteristics of a Natural Killer T (NKT) cell subpopulation that developed during influenza infection in neonatal mice, and that suppressed the subsequent development of allergic asthma in a mouse model. This NKT cell subset expressed CD38 but not CD4, produced IFN-γ, but not IL-17, IL-4 or IL-13, and inhibited the development of airway hyperreactivity (AHR) through contact-dependent suppressive activity against helper CD4 T cells. The NKT subset expanded in the lungs of neonatal mice after infection with influenza, but also after treatment of neonatal mice with a Th1-biasing α-GalCer glycolipid analogue, Nu-α-GalCer. These results suggest that early/neonatal exposure to infection or to antigenic challenge can affect subsequent lung immunity by altering the profile of cells residing in the lung and that some subsets of NKT cells can have direct inhibitory activity against CD4+ T cells in allergic asthma. Importantly, our results also suggest a potential therapy for young children that might provide protection against the development of asthma.

Keywords: NKT subset, asthma, airway hyperreactivity, hygiene hypothesis, influenza

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Authors: Hashaam Akhtar

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IFNλR1 and IL10R2 collectively construct a heterodimer, which is an acknowledged functional receptor for all type III interferons (IFNs). Expression of IFNλR1 is highly tissue specific, which can help in making type III IFNs a drug of choice as comparable to its analogue, type I IFNs, for treating hepatitis C in the near future. Although, expression of IFNλR1 also varies with the concentration of type I IFNs, but in this study it was shown that the expression of IFNλR1 varies with the protein titers of IFN-α, IFN-λ3 and the newly discovered IFN-λ4. High dosage of IFN-α reduces the expression of IFNλR1 in HepG2 cells, which can affect the antiviral activity of type III IFNs in vivo. We premeditated an experimental strategy to differentiate monocytes into dendritic cells (DCs), type I and type II macrophages in vitro and quantified the expression of the IFNλR1 by qPCR. The exposure of newly discovered IFN-λ4 to macrophages and DCs also raised the expression of its own receptor, which shows that expression of IFN-λ4 protein in hepatitis C patient may augment type I treatment and help ease off viral titers. The results of this study may contribute in some understanding towards the mechanisms involved in the selective expression of IFNLR1 and exceptionalities associated with the receptor.

Keywords: IFNLR1, Interferon Lambda 4 (IFN-λ4), Mononuclear Phagocyte Cells (MPCs), expression

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Authors: Astrid Tannert, Anuradha Ramoji, Christina Ebert, Frederike Gladigau, Lorena Tuchscherr, Jürgen Popp, Ute Neugebauer

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Staphylococcus aureus is a facultative intracellular pathogen, which by entering host cells may evade immunologic host response as well as antimicrobial treatment. In that way, S. aureus can cause persistent intracellular infections which are difficult to treat. Depending on the strain, S. aureus may persist at different intracellular locations like the phagolysosome. The first barrier invading pathogens from the blood stream that they have to cross are the endothelial cells lining the inner surface of blood and lymphatic vessels. Upon proceeding from an acute to a chronic infection, intracellular pathogens undergo certain biochemical and structural changes including a deceleration of metabolic processes to adopt for long-term intracellular survival and the development of a special phenotype designated as small colony variant. In this study, the endothelial cell line Ea.hy 926 was used as a model for acute and chronic S. aureus infection. To this end, Ea.hy 926 cells were cultured on QIAscout™ Microraft Arrays, a special graded cell culture substrate that contains around 12,000 microrafts of 200 µm edge length. After attachment to the substrate, the endothelial cells were infected with GFP-expressing S. aureus for 3 weeks. The acute infection and the development of persistent bacteria was followed by confocal laser scanning microscopy, scanning the whole Microraft Array for the presence and for detailed determination of the intracellular location of fluorescent intracellular bacteria every second day. After three weeks of infection representative microrafts containing infected cells, cells with protruded infections and cells that did never show any infection were isolated and fixed for Raman micro-spectroscopic investigation. For comparison, also microrafts with acute infection were isolated. The acquired Raman spectra are correlated with the fluorescence microscopic images to give hints about a) the molecular alterations in endothelial cells during acute and chronic infection compared to non-infected cells, and b) metabolic and structural changes within the pathogen when entering a mode of persistence within host cells. We thank Dr. Ruth Kläver from QIAGEN GmbH for her support regarding QIAscout technology. Financial support by the BMBF via the CSCC (FKZ 01EO1502) and from the DFG via the Jena Biophotonic and Imaging Laboratory (JBIL, FKZ PO 633/29-1, BA 1601/10-1) is highly acknowledged.

Keywords: correlative image analysis, intracellular infection, pathogen-host adaption, Raman micro-spectroscopy

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Authors: Azzeddine Abdelalim, Fatiha Rogti

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The degradation phenomenon in polymer solar cells (PCSs) has not been clearly explained yet. In fact, there are many causes that show up and influence these cells in a variety of ways. Also, there has been a growing concern over this degradation in the photovoltaic community. One of the main variables deciding PSCs photovoltaic output is defect states. In this research, devices modeling is carried out to analyze the multiple effects of degradation by applying high defect states (HDS) on ideal PSCs, mainly poly(3-hexylthiophene) (P3HT) absorber layer. Besides, a comparative study is conducted between P3HT and other PSCs by a simulation program called Solar Cell Capacitance Simulator (SCAPS). The adjustments to the defect parameters in several absorber layers explain the effect of HDS on the total output properties of PSCs. The performance parameters for HDS, quantum efficiency, and energy band were therefore examined. This research attempts to explain the degradation process of PSCs and the causes of their low efficiency. It was found that the defects often affect PSCs performance, but defect states have a little effect on output when the defect level is less than 1014cm-3, which gives similar performance values with P3HT cells when these defects is about 1019cm-3. The high defect states can cause up to 11% relative reduction in conversion efficiency of ideal P3HT. In the center of the band gap, defect states become more noxious. This approach is for one of the degradation processes potential of PSCs especially that use fullerene derivative acceptors.

Keywords: degradation, high defect states, polymer solar cells, SCAPS-1D

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Authors: Maria E. V. Amarante, Carolina L. Cerdeira, Julia V. Cortes, Fiorita G. L. Mundim

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Basal cell carcinoma (BCC) is the most prevalent type of skin cancer in humans. It arises from the basal cells of the epidermis and cutaneous appendages. The role of sunlight exposure as a risk factor for BCC is very well defined due to its power to influence genetic mutations, in addition to having a suppressor effect on the skin immune system. Despite showing low metastasis and mortality rates, the tumor is locally infiltrative, aggressive, and destructive. Considering the high prevalence rate of this carcinoma and the importance of early detection, a retrospective study was carried out in order to correlate the clinical data available on BBC, characterize it epidemiologically, and thus enable effective prevention measures for the population. Data on the period from January 2015 to December 2019 were collected from the medical records of patients registered at one pathology service located in the southeast region of Brazil, known as SVO, which delivers skin biopsy results. The study was aimed at correlating the variables, sex, age, and subtypes found. Data analysis was performed using the chi-square test at a nominal significance level of 5% in order to verify the independence between the variables of interest. Fisher's exact test was applied in cases where the absolute frequency in the cells of the contingency table was less than or equal to five. The statistical analysis was performed using the R® software. Ninety-three basal cell carcinoma were analyzed, and its frequency in the 31-to 45-year-old age group was 5.8 times higher in men than in women, whereas, from 46 to 59 years, the frequency was found 2.4 times higher in women than in men. Between the ages of 46 to 59 years, it should be noted that the sclerodermiform subtype appears more than the solid one, with a difference of 7.26 percentage points. Reversely, the solid form appears more frequently in individuals aged 60 years or more, with a difference of 8.57 percentage points. Among women, the frequency of the solid subtype was 9.93 percentage points higher than the sclerodermiform frequency. In males, the same percentage difference is observed, but sclerodermiform is the most prevalent subtype. It is concluded in this study that, in general, there is a predominance of basal cell carcinoma in females and in individuals aged 60 years and over, which demonstrates the tendency of this tumor. However, when rarely found in younger individuals, the male gender prevailed. The most prevalent subtype was the solid one. It is worth mentioning that the sclerodermiform subtype, which is more aggressive, was seen more frequently in males and in the 46-to 59-year-old range.

Keywords: basal cell carcinoma, epidemiology, sclerodermiform basal cell carcinoma, skin cancer, solar radiation, solid basal cell carcinoma

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Authors: Jemini Vyas, Oluwatobi Adeyoe, Jenny Branagan, Chandran Tanabalan, Aakash Pai

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Introduction: Radical prostatectomy and radiotherapy are both viable options for the treatment of localised prostate cancer. Over the years medicine has evolved towards a patient-centred approach. Patient decision-making is not motivated by clinical outcomes alone. Geographical location and ease of access to treating clinician are contributory factors. With the development of robotic surgery, prostatectomy has been centralised into tertiary centres. This has impacted on the distances that patients and their families are expected to travel. Methods: A single centre retrospective study was undertaken over a five-year period. All patients with localised prostate cancer, undergoing radical radiotherapy or prostatectomy were collected pre-centralisation. This was compared to the total number undergoing these treatments post centralisation. Results: Pre-centralisation, both radiotherapy and prostatectomy groups had to travel a median of less than five miles for treatment. Post-centralisation of pelvic surgery, prostatectomy patients had to travel a median of more than 40 miles, whilst travel distance for the radiotherapy group was unchanged. In the post centralisation cohort, there was a 63% decline in the number of patients undergoing radical prostatectomy per month from a mean of 5.1 to 1.9. The radical radiotherapy group had a concurrent 41% increase in patient numbers with a mean increase from 13.3 to 18.8 patients per month. Conclusion: Choice of radical treatment in localised prostate cancer is based on multiple factors. This study infers that local availability can influence choice of radical treatment. It is imperative that efforts are made to maintain accessibility to all viable options for prostate cancer patients, so that patient choice is not compromised.

Keywords: prostate, prostatectomy, radiotherapy, centralisation

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Authors: Matthew Cardeiro, Amalia D. Ardeljan, Lexi Frankel, Dianela Prado Escobar, Catalina Molnar, Omar M. Rashid

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Introduction: Enterococci comprise the natural flora of nearly all animals and are ubiquitous in food manufacturing and probiotics. However, its role in the microbiome remains controversial. The gut microbiome has shown to play an important role in immunology and cancer. Further, recent data has suggested a relationship between gut microbiota and breast cancer. These studies have shown that the gut microbiome of patients with breast cancer differs from that of healthy patients. Research regarding enterococcus infection and its sequala is limited, and further research is needed in order to understand the relationship between infection and cancer. Enterococcus may prevent the development of breast cancer (BC) through complex immunologic and microbiotic adaptations following an enterococcus infection. This study investigated the effect of enterococcus infection and the incidence of BC. Methods: A retrospective study (January 2010- December 2019) was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database and conducted using a Humans Health Insurance Database. International Classification of Disease (ICD) 9th and 10th codes, Current Procedural Terminology (CPT), and National Drug Codes were used to identify BC diagnosis and enterococcus infection. Patients were matched for age, sex, Charlson Comorbidity Index (CCI), antibiotic treatment, and region of residence. Chi-squared, logistic regression, and odds ratio were implemented to assess the significance and estimate relative risk. Results: 671 out of 28,518 (2.35%) patients with a prior enterococcus infection and 1,459 out of 28,518 (5.12%) patients without enterococcus infection subsequently developed BC, and the difference was statistically significant (p<2.2x10⁻¹⁶). Logistic regression also indicated enterococcus infection was associated with a decreased incidence of BC (RR=0.60, 95% CI [0.57, 0.63]). Treatment for enterococcus infection was analyzed and controlled for in both enterococcus infected and noninfected populations. 398 out of 11,523 (3.34%) patients with a prior enterococcus infection and treated with antibiotics were compared to 624 out of 11,523 (5.41%) patients with no history of enterococcus infection (control) and received antibiotic treatment. Both populations subsequently developed BC. Results remained statistically significant (p<2.2x10-16) with a relative risk of 0.57 (95% CI [0.54, 0.60]). Conclusion & Discussion: This study shows a statistically significant correlation between enterococcus infection and a decrease incidence of breast cancer. Further exploration is needed to identify and understand not only the role of enterococcus in the microbiome but also the protective mechanism(s) and impact enterococcus infection may have on breast cancer development. Ultimately, further research is needed in order to understand the complex and intricate relationship between the microbiome, immunology, bacterial infections, and carcinogenesis.

Keywords: breast cancer, enterococcus, immunology, infection, microbiome

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Authors: Wei Xiao, Gangzhi Cai, Xingliang Qin, Hongyan Ren, Zaidong Hua, Zhe Zhu, Hongwei Xiao, Ximin Zheng, Jie Yao, Yanzhen Bi

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Myostatin (MSTN) is the master regulator of double muscling phenotype with overgrown muscle and decreased fatness in animals, but its action mode to regulate fat deposition remains to be elucidated. In this study a swin-specific pathway through which MSTN acts to regulate the fat deposition was deciphered. Deep sequenincing of the mRNA and miRNA of fat tissues of MSTN knockout (KO) and wildtype (WT) pigs discovered the positive correlation of myocyte enhancer factor 2C (MEF2C) and fat-inhibiting miR222 expression, and the inverse correlation of miR222 and stearoyl-CoA desaturase 5 (SCD5) expression. SCD5 is rodent-absent and expressed only in pig, sheep and cattle. Fatty acid spectrum of fat tissues revealed a lower percentage of oleoyl-CoA (18:1) and palmitoleyl CoA (16:1) in MSTN KO pigs, which are the catalyzing products of SCD5-mediated desaturation of steroyl CoA (18:0) and palmitoyl CoA (16:0). Blood metrics demonstrated a 45% decline of triglyceride (TG) content in MSTN KO pigs. In light of these observations we hypothesized that MSTN might act through MEF2C/miR222/SCD5 pathway to regulate desaturation of fatty acid as well as triglyceride synthesis in pigs. To this end, real-time PCR and Western blotting were carried out to detect the expression of the three genes stated above. These experiments showed that MEF2C expression was up-regulated by nearly 2-fold, miR222 up-regulated by nearly 3-fold and SCD5 down-regulated by nearly 50% in MSTN KO pigs. These data were consistent with the expression change in deep sequencing analysis. Dual luciferase reporter was then used to confirm the regulation of MEF2C upon the promoter of miR222. Ecotopic expression of MEF2C in preadipocyte cells enhanced miR222 expression by 3.48-fold. CHIP-PCR identified a putative binding site of MEF2C on -2077 to -2066 region of miR222 promoter. Electrophoretic mobility shift assay (EMSA) demonstrated the interaction of MEF2C and miR222 promoter in vitro. These data indicated that MEF2C transcriptionally regulates the expression of miR222. Next, the regulation of miR222 on SCD5 mRNA as well as its physiological consequences were examined. Dual luciferase reporter testing revealed the translational inhibition of miR222 upon the 3´ UTR (untranslated region) of SCD5 in preadipocyte cells. Transfection of miR222 mimics and inhibitors resulted in the down-regulation and up-regulation of SCD5 in preadipocyte cells respectively, consistent with the results from reporter testing. RNA interference of SCD5 in preadipocyte cells caused 26.2% reduction of TG, in agreement with the results of TG content in MSTN KO pigs. In summary, the results above supported the existence of a molecular pathway that MSTN signals through MEF2C/miR222/SCD5 to regulate the fat deposition in pigs. This swine-specific pathway offers potential molecular markers for the development and breeding of a new pig line with optimised fatty acid composition. This would benefit human health by decreasing the takeup of saturated fatty acid.

Keywords: fat deposition, MEF2C, miR222, myostatin, SCD5, pig

Procedia PDF Downloads 126