Search results for: healthy with induced pain
2470 Exploring the Influence of Culture on Dietary Practices and Ethnic Inequality in Health among Migrant Nigerians in the UK
Authors: Babatunde Johnson
Abstract:
The rate of diseases and death from preventable diseases among ethnic minority groups is high when compared with the wider white population in the UK. This can be due in part to the diet consumed and various cultural reasons. Changes in dietary practices and the health of ethnic minority groups can be caused by the adoption of food practices of the host culture after migration (acculturation) and generational differences among migrants. However, understanding how and why these changes occur is limited due to the challenges of data collection in research. This research utilizes the interpretive phenomenological approach, coupled with Bourdieu’s theory used as the conceptual framework, and seeks an in-depth understanding of how adult immigrant Nigerians in the UK interpret their experience of the influence of ethnic and prevailing cultures on their dietary practice. Recruiting participants from a close-knit community, such as the Nigerian population in the UK, can be complex and problematic and is determined by the accessibility to the community. Although complex, the researcher leveraged the principles of Patient and Public Involvement (PPI) in gaining access to participants within the Nigerian community. This study emphasizes the need for a culturally tailored and community-centered approach to interventions geared toward the reduction of ethnic health inequality in the UK other than the existing practice, which focuses on better healthy eating through the improvement of skills and knowledge about food groups.Keywords: culture, dietary practice, ethnic minority, health inequality
Procedia PDF Downloads 922469 Effect of Two Bouts of Eccentric Exercise on Knee Flexors Changes in Muscle-Tendon Lengths
Authors: Shang-Hen Wu, Yung-Chen Lin, Wei-Song Chang, Ming-Ju Lin
Abstract:
This study investigated whether the repeated bout effect (RBE) of knee flexors (KF) eccentric exercise would be changed in muscle-tendon lengths. Eight healthy university male students used their KF of non-dominant leg and performed a bout of 60 maximal isokinetic (30°/s) eccentric contractions (MaxECC1). A week after MaxECC1, all subjects used the same KF to perform a subsequent bout of MaxECC2. Changes in maximal isokinetic voluntary contraction torque (MVC-CON), muscle soreness (SOR), relaxed knee joint angle (RANG), leg circumference (CIR), and ultrasound images (UI; muscle-tendon length and muscle angle) were measured before, immediately after, 1-5 days after each bout. Two-way ANOVA was used to analyze all the dependent variables. After MaxECC1, all the dependent variables (e.g. MVC-CON: ↓30%, muscle-tendon length: ↑24%, muscle angle: ↑15%) showed significantly change. Following MaxECC2, all the above dependent variables (e.g. MVC-CON:↓21%, tendon length: ↑16%, muscle angle: ↑6%) were significantly smaller than those of MaxECC1. These results of this study found that protective effect conferred by MaxECC1 against MaxECC2, and changes in muscle damage indicators, muscle-tendon length and muscle angle following MaxECC2 were smaller than MaxECC1. Thus, the amount of shift of muscle-tendon length and muscle angle was related to the RBE.Keywords: eccentric exercise, maximal isokinetic voluntary contraction torque, repeated bout effect, ultrasound
Procedia PDF Downloads 3342468 Evaluation of Beam Structure Using Non-Destructive Vibration-Based Damage Detection Method
Authors: Bashir Ahmad Aasim, Abdul Khaliq Karimi, Jun Tomiyama
Abstract:
Material aging is one of the vital issues among all the civil, mechanical, and aerospace engineering societies. Sustenance and reliability of concrete, which is the widely used material in the world, is the focal point in civil engineering societies. For few decades, researchers have been able to present some form algorithms that could lead to evaluate a structure globally rather than locally without harming its serviceability and traffic interference. The algorithms could help presenting different methods for evaluating structures non-destructively. In this paper, a non-destructive vibration-based damage detection method is adopted to evaluate two concrete beams, one being in a healthy state while the second one contains a crack on its bottom vicinity. The study discusses that damage in a structure affects modal parameters (natural frequency, mode shape, and damping ratio), which are the function of physical properties (mass, stiffness, and damping). The assessment is carried out to acquire the natural frequency of the sound beam. Next, the vibration response is recorded from the cracked beam. Eventually, both results are compared to know the variation in the natural frequencies of both beams. The study concludes that damage can be detected using vibration characteristics of a structural member considering the decline occurred in the natural frequency of the cracked beam.Keywords: concrete beam, natural frequency, non-destructive testing, vibration characteristics
Procedia PDF Downloads 1162467 Rationally Designed Dual PARP-HDAC Inhibitor Elicits Striking Anti-leukemic Effects
Authors: Amandeep Thakur, Yi-Hsuan Chu, Chun-Hsu Pan, Kunal Nepali
Abstract:
The transfer of ADP-ribose residues onto target substrates from nicotinamide adenine dinucleotide (NAD) (PARylation) is catalyzed by Poly (ADP-ribose) polymerases (PARPs). Amongst the PARP family members, the DNA damage response in cancer is majorly regulated by PARP1 and PARP2. The blockade of DNA repair by PARP inhibitors leads to the progression of DNA single-strand breaks (induced by some triggering factors) to double-strand breaks. Notably, PARP inhibitors are remarkably effective in cancers with defective homologous recombination repair (HRR). In particular, cancer cells with BRCA mutations are responsive to therapy with PARP inhibitors. The aforementioned requirement for PARP inhibitors to be effective confers a narrow activity spectrum to PARP inhibitors, which hinders their clinical applicability. Thus, the quest to expand the application horizons of PARP inhibitors beyond BRCA mutations is the need of the hour. Literature precedents reveal that HDAC inhibition induces BRCAness in cancer cells and can broaden the therapeutic scope of PARP inhibitors. Driven by such disclosures, dual inhibitors targeting both PARP and HDAC enzymes were designed by our research group to extend the efficacy of PARP inhibitors beyond BRCA-mutated cancers to cancers with induced BRCAness. The design strategy involved the installation of Veliparib, an investigational PARP inhibitor, as a surface recognition part in the HDAC inhibitor pharmacophore model. The chemical architecture of veliparib was deemed appropriate as a starting point for the generation of dual inhibitors by virtue of its size and structural flexibility. A validatory docking study was conducted at the outset to predict the binding mode of the designed dual modulatory chemical architectures. Subsequently, the designed chemical architectures were synthesized via a multistep synthetic route and evaluated for antitumor efficacy. Delightfully, one compound manifested impressive anti-leukemic effects (HL-60 cell lines) mediated via dual inhibition of PARP and class I HDACs. The outcome of the western blot analysis revealed that the compound could downregulate the expression levels of PARP1 and PARP2 and the HDAC isoforms (HDAC1, 2, and 3). Also, the dual PARP-HDAC inhibitor upregulated the protein expression of the acetyl histone H3, confirming its abrogation potential for class I HDACs. In addition, the dual modulator could arrest the cell cycle at the G0/G1 phase and induce autophagy. Further, polymer-based nanoformulation of the dual inhibitor was furnished to afford targeted delivery of the dual inhibitor at the cancer site. Transmission electron microscopy (TEM) results indicate that the nanoparticles were monodispersed and spherical. Moreover, the polymeric nanoformulation exhibited an appropriate particle size. Delightfully, pH-sensitive behavior was manifested by the polymeric nanoformulation that led to selective antitumor effects towards the HL-60 cell lines. In light of the magnificent anti-leukemic profile of the identified dual PARP-HDAC inhibitor, in-vivo studies (pharmacokinetics and pharmacodynamics) are currently being conducted. Notably, the optimistic findings of the aforementioned study have spurred our research group to initiate several medicinal chemistry campaigns to create bifunctional small molecule inhibitors addressing PARP as the primary target.Keywords: PARP inhibitors, HDAC inhibitors, BRCA mutations, leukemia
Procedia PDF Downloads 322466 Thymoquinone Prevented the Development of Symptoms in Animal Model of Parkinson’s Disease
Authors: Kambiz Hassanzadeh, Seyedeh Shohreh Ebrahimi, Shahrbanoo Oryan, Arman Rahimmi, Esmael Izadpanah
Abstract:
Parkinson’s disease is one of the most prevalent neurodegenerative diseases which occurs in elderly. There are convincing evidences that oxidative stress has an important role in both the initiation and progression of Parkinson’s disease. Thymoquinone (TQ) is shown to have antioxidant and anti-inflammatory properties in invitro and invivo studies. It is well documented that TQ acts as a free radical scavenger and prevents the cell damage. Therefore this study aimed to evaluate the effect of TQ on motor and non-motor symptoms in animal model of Parkinson’s disease. Male Wistar rats (10-12 months) received rotenone (1mg/kg/day, sc) to induce Parkinson’s disease model. Pretreatment with TQ (7.5 and 15 mg/kg/day, po) was administered one hour before the rotenone injection. Three motor tests (rotarod, rearing and bar tests) and two non-motor tests (forced swimming and elevated plus maze) were performed for behavioral assessment. Our results indicated that TQ significantly ameliorated the rotenone-induced motor dysfunction in rotarod and rearing tests also it could prevent the non-motor dysfunctions in forced swimming and elevated plus maze tests. In conclusion we found that TQ delayed the Parkinson's disease induction by rotenone and this effect might be related to its proved antioxidant effect.Keywords: Parkinson's disease, thymoquinone, motor and non-motor symptoms, neurodegenerative disease
Procedia PDF Downloads 5512465 Clinical Outcomes After Radiological Management of Varicoceles
Authors: Eric Lai, Sarah Lorger, David Eisinger, Richard Waugh
Abstract:
Introduction: Percutaneous embolization of varicoceles has shown similar outcomes to surgery. However, there are advantages of radiological intervention as patients are not exposed to general anaesthesia, experience a quicker recovery and face a lower risk of major complications. Radiological interventions are also preferable after a failed surgical approach. We evaluate clinical outcomes of percutaneous embolization at a tertiary hospital in Sydney, Australia. Methods: Retrospective case series without a control group from a single site (Royal Prince Alfred Hospital, Sydney, Australia). A data search was performed on the interventional radiology database with the word “varicocele” between February 2017 and March 2022. 62 patients were identified. Each patient file was reviewed and included in the study if they met the inclusion criteria. Results: A total of 56 patients were included. 6 patients were excluded as they did not receive intervention after the initial diagnostic venography. Technical success was 100%. Complications were seen in 3 patients (5.3%). The complications included post-procedural pain and fever, venous perforation with no clinical adverse outcome, and a mild allergic reaction to contrast. Recurrence occurred in 3 patients (5.6%), all of whom received a successful second procedure. DISCUSSION: This study demonstrates comparable rates of technical success, complication rate and recurrence to other studies in the literature. When compared to surgical outcomes, the results were also similar. The main limitation is multiple patients lack long-term follow-up beyond 1 year, resulting in potential underestimation of the recurrence rate. Conclusion: Percutaneous embolization of varicocele is a safe alternative to surgical intervention.Keywords: varicocele, interventional radiology, urology, radiology
Procedia PDF Downloads 762464 Synthesis of New Analogs of IPS-339, and Study of Their Cardiovascular in Dogs
Authors: Elham Zarenezhad, Ali Zarenezhad, Mehdi Mardkhoshnood
Abstract:
We described the synthesis and biological study of O-oxime ethers having a-amino acid residues as new analogs of IPS-339. In this synthesis, the reaction of fluorene O-oxime with epichlorohydrin or epibromohydrin afforded the corresponding O-oxime ether adducts. The N-alkylation of valine amino acid with O-oxime ether adducts led to the synthesis of new analogs of IPS-339. The cardiovascular properties of the compound have been studied. In this regard, six clinically healthy same sex mongrel dogs were examined. The dogs were randomly divided into 3 groups of two members. 1 groups received 2 mg kg-1 body weight of compound (2-(3-(9H-fluoren-9-ylideneaminooxy)-2- hydroxypropylamino)-3-methylbutanoic acid) intravenously, whereas group 2 and 3 received only DMSO–water (distil.) and propranolol (Inderal) (2 mg kg-1), respectively. The electrocardiograph (ECG) was recorded with lead II. The recording was run successively by 5 min time interval on each dog before, simultaneously, and after compound infusion. Data after administration were taken from normal sinus beats that were closely related to the arrhythmias whenever they occurred. In general, no detectable arrhythmia was observed in all ECG records regardless of increasing the heart rate that likely caused by stress origin from invasive procedure just after infusion. Compound diminished the heart rate during study especially at 20th minute compared to propranolol as a reference drug. Compound (2-(3-(9H-fluoren-9-ylideneaminooxy)-2- hydroxypropylamino)-3-methylbutanoic acid) was the most effective compound with remarkable ability in declining of the heart rate.Keywords: electrocardiograph (ECG), cardiovascular, IPS-339, dogs
Procedia PDF Downloads 3492463 Characteristics of GaAs/InGaP and AlGaAs/GaAs/InAlGaP Npn Heterostructural Optoelectronic Switches
Authors: Der-Feng Guo
Abstract:
Optoelectronic switches have attracted a considerable attention in the semiconductor research field due to their potential applications in optical computing systems and optoelectronic integrated circuits (OEICs). With high gains and high-speed operations, npn heterostructures can be used to produce promising optoelectronic switches. It is known that the bulk barrier and heterostructure-induced potential spike act important roles in the characteristics of the npn heterostructures. To investigate the effects of bulk barrier and potential spike heights on the optoelectronic switching of the npn heterostructures, GaAs/InGaP and AlGaAs/GaAs/InAlGaP npn heterostructural optoelectronic switches (HSOSs) have been fabricated in this work. It is seen that the illumination decreases the switching voltage Vs and increases the switching current Is, and thus the OFF state is under dark and ON state under illumination in the optical switching of the GaAs/InGaP HSOS characteristics. But in the AlGaAs/GaAs/InAlGaP HSOS characteristics, the Vs and Is present contrary trends, and the OFF state is under illumination and ON state under dark. The studied HSOSs show quite different switching variations with incident light, which are mainly attributed to the bulk barrier and potential spike heights affected by photogenerated carriers.Keywords: bulk barrier, heterostructure, optoelectronic switch, potential spike
Procedia PDF Downloads 2412462 In silico Analysis towards Identification of Host-Microbe Interactions for Inflammatory Bowel Disease Linked to Reactive Arthritis
Authors: Anukriti Verma, Bhawna Rathi, Shivani Sharda
Abstract:
Reactive Arthritis (ReA) is a disorder that causes inflammation in joints due to certain infections at distant sites in the body. ReA begins with stiffness, pain, and inflammation in these areas especially the ankles, knees, and hips. It gradually causes several complications such as conjunctivitis in the eyes, skin lesions in hand, feet and nails and ulcers in the mouth. Nowadays the diagnosis of ReA is based upon a differential diagnosis pattern. The parameters for differentiating ReA from other similar disorders include physical examination, history of the patient and a high index of suspicion. There are no standard lab tests or markers available for ReA hence the early diagnosis of ReA becomes difficult and the chronicity of disease increases with time. It is reported that enteric disorders such as Inflammatory Bowel Disease (IBD) that is inflammation in gastrointestinal tract namely Crohn’s Disease (CD) and Ulcerative Colitis (UC) are reported to be linked with ReA. Several microorganisms are found such as Campylobacter, Salmonella, Shigella and Yersinia causing IBD leading to ReA. The aim of our study was to perform the in-silico analysis in order to find interactions between microorganisms and human host causing IBD leading to ReA. A systems biology approach for metabolic network reconstruction and simulation was used to find the essential genes of the reported microorganisms. Interactomics study was used to find the interactions between the pathogen genes and human host. Genes such as nhaA (pathogen), dpyD (human), nagK (human) and kynU (human) were obtained that were analysed further using the functional, pathway and network analysis. These genes can be used as putative drug targets and biomarkers in future for early diagnosis, prevention, and treatment of IBD leading to ReA.Keywords: drug targets, inflammatory bowel disease, reactive arthritis, systems biology
Procedia PDF Downloads 2772461 The Effect of β-Cryptoxanthin on Testicular Ischemia-Reperfusion Injury in a Rat Model: Evidence from Testicular Histology
Authors: Kianoush Mohammadnejad, Rahim Mohammadi, Ali Soleimanzadeh, Ali Shalizar Jalai, Farshid Sareafzadeh Rezaei
Abstract:
Testicular torsion and detorsion are significant clinical issues for infertile men. Torsion of the spermatic cord is an emergency condition resulting from the rotation of the testis and epididymis around the axis of the spermatic cord. A rat testis model was used to assess the effects of β-cryptoxanthin on ischemia-reperfusion injury. Twenty healthy male Wistar rats were included and randomized into four investigational groups (n = 5): Group SHAM: In this group, midline incision of the scrotum was performed, and the testicles were taken out for 2 hours with a 720-degree rotation. Group ISCHEMIA: In this group, a midline incision of the scrotum was performed, and the testicles were taken out and underwent ischemia for 2 hours with a 720-degree rotation. Group IS/REP/Oil: In this group, a midline scrotum cut was performed the testicles were taken out, and ischemia was created for 2 hours with a 720-degree rotation and at the end of ischemia 100 µL of corn oil (β-cryptoxanthin solvent) was injected intraperitoneally. Group IS/REP/CRPTXNTN 2.5: The same as group IS/REP/Oil as well as intraperitoneal administration of 100 µL of β-cryptoxanthin (2.5 µg/kg) at the end of ischemia. In all groups, the testes were returned back to the scrotum and, after 60 days, were dissected out and removed for histopathological analyses. β-cryptoxanthin at the dose of 2.5 µg/kg significantly improved histologic indices compared to other treatment groups (p<0.05). β-cryptoxanthin could be helpful in minimizing ischemia-reperfusion injury in testicular tissue exposed to ischemia.Keywords: beta-cryptoxanthin, testis, Ischemia-reperfusion, Intraperitoneal
Procedia PDF Downloads 262460 Atomic Absorption Spectroscopic Analysis of Heavy Metals in Cancerous Breast Tissues among Women in Jos, Nigeria
Authors: Opeyemi Peter Idowu
Abstract:
Breast cancer is prevalent in northern Nigerian women, most especially in Jos, Plateau State, owing to anthropogenic activities such as solid earth mineral mining as far back as 1904. In this study, atomic absorption spectrometry was used to determine the concentration of eight heavy metals (Cd, As, Cr, Cu, Fe, Pb, Ni, and Zn) in cancerous and non-cancerous breast tissues of Jos Nigerian Women. The levels of heavy metals ranged from 1.08 to 29.34 mg/kg, 0.29 to 10.76 mg/kg, 0.35 to 51.93 mg/kg, 5.15 to 62.93 mg/kg, 11.64 to 51.10 mg/kg, 0.42 to 83.16 mg/kg, 2.08 to 43.07 mg/kg and 1.67 to 71.53 mg/kg for Cd, As, Cr, Cu, Fe, Pb, Ni and Zn respectively. Using MATLAB R2016a, significant differences (tᵥ = 0.0041 - 0.0317) existed between the levels of all the heavy metals in cancerous and non-cancerous breast tissues except Fe. At 0.01 level of significance, a positive significant correlation existed between Pb and Fe, Pb and Cu, Pb and Fe, Ni and Fe, Cr and Pb, as well as Ni and Cr (r = 0.583 – 0.998) in cancerous breast tissues. Using ANOVA, significant differences also occurred in the levels of these heavy metals in cancerous breast tissues (p = 1.910510×10⁻²⁶). The relatively high levels of the cancer-induced heavy metals (Cd, As, Cr, and Pb) compared with control indicated contamination or exposure to heavy metals, which could be the major cause of cancer in these female subjects. This was evidence of contamination as a result of exposure by ingestion, inhalation, or other means to one anthropogenic activity of the other. Therapeutic measures such as gastric lavage, ascorbic acid consumption, and divalent cation treatment are all effective ways to manage heavy metal toxicity in the subjects to lower the risk of breast cancer.Keywords: breast cancer, heavy metals, spectroscopy, bio-accumulation
Procedia PDF Downloads 392459 Dynamic Cardiac Mitochondrial Proteome Alterations after Ischemic Preconditioning
Authors: Abdelbary Prince, Said Moussa, Hyungkyu Kim, Eman Gouda, Jin Han
Abstract:
We compared the dynamic alterations of mitochondrial proteome of control, ischemia-reperfusion (IR) and ischemic preconditioned (IPC) rabbit hearts. Using 2-DE, we identified 29 mitochondrial proteins that were differentially expressed in the IR heart compared with the control and IPC hearts. For two of the spots, the expression patterns were confirmed by Western blotting analysis. These proteins included succinate dehydrogenase complex, Acyl-CoA dehydrogenase, carnitine acetyltransferase, dihydrolipoamide dehydrogenase, Atpase, ATP synthase, dihydrolipoamide succinyltransferase, ubiquinol-cytochrome c reductase, translation elongation factor, acyl-CoA dehydrogenase, actin alpha, succinyl-CoA Ligase, dihydrolipoamide S-succinyltransferase, citrate synthase, acetyl-Coenzyme A dehydrogenase, creatine kinase, isocitrate dehydrogenase, pyruvate dehydrogenase, prohibitin, NADH dehydrogenase (ubiquinone) Fe-S protein, enoyl Coenzyme A hydratase, superoxide dismutase [Mn], and 24-kDa subunit of complex I. Interestingly, most of these proteins are associated with the mitochondrial respiratory chain, antioxidant enzyme system, and energy metabolism. The results provide clues as to the cardioprotective mechanism of ischemic preconditioning at the protein level and may serve as potential biomarkers for detection of ischemia-induced cardiac injury.Keywords: ischemic preconditioning, mitochondria, proteome, cardioprotection
Procedia PDF Downloads 3542458 Apoptosis Inducing Potential of Onosma Bracteata Wall. in Mg-63 Human Osteosarcoma Cells via cdk2/Cyclin E Pathway
Authors: Ajay Kumar, Satwinderjeet Kaur
Abstract:
Onosma bracteata Wall. (Boraginaceae), is known to be a medicinal plant, useful in the treatment of body swellings, abdominal pain and urinary calculi, etc. The present study focused on the radical scavenging and cancer growth inhibitory properties of isolates from O. bracteata. Obea fraction demonstrated noticeable free radical scavenging ability along with antiproliferative activity in human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung cancer A549 cell lines using MTT assay with GI50 values of 88.56, 101.61 and 112.7 μg/ml, respectively. The scanning electron and confocal microscopy studies showed morphological alterations including nuclear condensation and formation of apoptotic bodies in osteosarcoma MG-63 cells. Obea fraction in osteosarcoma MG-63 cells augmented the reactive oxygen species (ROS) level and decreased the mitochondrial membrane potential. Flow cytometry analysis revealed the Obea treated cells to be arrested in the G0/G1 phase in a dose dependent manner supported by the observed increase in the early apoptotic cell population. Western blotting analysis showed that the expression of p-NF-kB, COX-2, p-Akt, and Bcl-xL decreased whereas, the expression of GSK-3β, p53, caspase-3 and caspase-9 proteins increased. The downregulation of Bcl-2, Cyclin E, CDK2 and mortalin gene expression and upregulation of p53 genes was unfolded in RT-qPCR studies. The presence of catechin, kaempferol, Onosmin A and epicatechin, as revealed in high-performance liquid chromatography (HPLC) studies, contributes towards the chemopreventive potential of O. bracteata which can be tapped for chemotherapeutic use.Keywords: apoptosis, confocal microscopy, HPLC, mitochondria membrane potential, reactive oxygen species
Procedia PDF Downloads 1402457 Growth of Nitella in Response to Cesium Exposure: Implication for Phytoremediation
Authors: Harun Rashid, Keerthi S. S. Atapaththu, Takashi Asaeda
Abstract:
Cesium (Cs) induced growth and stress response of Nitella were studied after exposure to four concentration of the metal; i.e. 0 (control), 0.001, 0.01, and 0.1 ppm Cs in growth media. Each treatment with three replicates were randomly allocated to 12 glass beakers in a complete randomize design and the experiment was continued for 30 days. At the end of the experiment, shoot length, cesium content, total chlorophyll, and plant stress response were compared. Anti-oxidant enzyme activities (peroxidase, catalase, and ascorbic peroxidase) and the concentration of H2O2 were measured to check plant stress. The longest shoot was found in control treatment (0 ppm Cs) and the shoot length of plants exposed to 0.001 ppm was statistically similar to that of control. Concentration of cesium in plants grown at 0.001, 0.01, and 0.1 ppm were significantly higher than those in control treatments. The antioxidant enzymes activities of plants exposed to cesium were significantly higher than those grown without any Cs (control). An elevated level of H2O2 concentration was also observed in former groups of plants. Further, the reduction in chlorophyll concentration and chlorophyll fluorescence in response to cesium exposure indicated the chronically damaged photosynthetic efficiency in cesium stressed Nitella.Keywords: antioxidant enzymes, cesium, growth, Nitella, oxidative stress
Procedia PDF Downloads 4322456 Capnography for Detection of Return of Spontaneous Circulation Pseudo-Pea
Authors: Yiyuan David Hu, Alex Lindqwister, Samuel B. Klein, Karen Moodie, Norman A. Paradis
Abstract:
Introduction: Pseudo-Pulseless Electrical Activity (p-PEA) is a lifeless form of profound cardiac shock characterized by measurable cardiac mechanical activity without clinically detectable pulses. Patients in pseudo-PEA carry different prognoses than those in true PEA and may require different therapies. End-tidal carbon dioxide (ET-CO2) is a reliable indicator of the return of spontaneous circulation (ROSC) in ventricular fibrillation and true-PEA but has not been studied p-PEA. Hypothesis: ET-CO2 can be used as an independent indicator of ROSC in p-PEA resuscitation. Methods: 30kg female swine (N = 14) under intravenous anesthesia were instrumented with aortic and right atrial micromanometer pressure. ECG and ET-CO2 were measured continuously. p-PEA was induced by ventilation with 6% oxygen in 94% nitrogen and was defined as a systolic Ao less than 40 mmHg. The statistical relationships between ET-CO2 and ROSC are reported. Results: ET-CO2 during resuscitation strongly correlated with ROSC (Figure 1). Mean ET-CO2 during p-PEA was 28.4 ± 8.4, while mean ET-CO2 in ROSC for 100% O2 cohort was 42.2 ± 12.6 (p < 0.0001), mean ET-CO2 in ROSC for 100% O2 + CPR was 33.0 ± 15.4 (p < 0.0001). Analysis of slope was limited to one minute of resuscitation data to capture local linearity; assessment began 10 seconds after resuscitation started to allow the ventilator to mix 100% O2. Pigs who would recover with 100% O2 had a slope of 0.023 ± 0.001, oxygen + CPR had a slope of 0.018 ± 0.002, and oxygen + CPR + epinephrine had a slope of 0.0050 ± 0.0009. Conclusions: During resuscitation from porcine hypoxic p-PEA, a rise in ET-CO2 is indicative of ROSC.Keywords: ET-CO2, resuscitation, capnography, pseudo-PEA
Procedia PDF Downloads 1942455 Emotion Processing Differences Between People
Authors: Elif Unveren, Ozlem Bozkurt
Abstract:
Emotion processing happens when someone has a negative, stressful experience and gets over it in time, and it is a different experience for every person. As to look into emotion processing can be categorised by intensity, awareness, coordination, speed, accuracy and response. It may vary depending on people’s age, sex and conditions. Each emotion processing shows different activation patterns in different brain regions. Activation is significantly higher in the right frontal areas. The highest activation happens in extended frontotemporal areas during the processing of happiness, sadness and disgust. Those emotions also show widely disturbed differences and get produced earlier than anger and fear. For different occasions, listed variables may have less or more importance. A borderline personality disorder is a condition that creates an unstable personality, sudden mood swings and unpredictability of actions. According to a study that was made with healthy people and people who had BPD, there were significant differences in some categories of emotion processing, such as intensity, awareness and accuracy. According to another study that was made to show the emotional processing differences between puberty and was made for only females who were between the ages of 11 and 17, it was perceived that for different ages and hormone levels, different parts of the brain are used to understand the given task. Also, in the different study that was made for kids that were between the age of 4 and 15, it was observed that the older kids were processing emotion more intensely and expressing it to a greater extent. There was a significant increase in fear and disgust in those matters. To sum up, we can say that the activity of undertaking negative experiences is a unique thing for everybody for many different reasons.Keywords: age, sex, conditions, brain regions, emotion processing
Procedia PDF Downloads 882454 Refinement of Existing Benzthiazole lead Targeting Lysine Aminotransferase in Dormant Stage of Mycobacterium tuberculosis
Authors: R. Reshma srilakshmi, S. Shalini, P. Yogeeswari, D. Sriram
Abstract:
Lysine aminotransferase is a crucial enzyme for dormancy in M. tuberculosis. It is involved in persistence and antibiotic resistance. In present work, we attempted to develop benzthiazole derivatives as lysine aminotransferase inhibitors. In our attempts, we also unexpectedly arrived at an interesting compound 21 (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)thiophen-2-yl)benzoic acid which even though has moderate activity against persistent phase of mycobacterium, it has significant potency against active phase. In the entire series compound 22 (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)thiophen-2-yl)isophthalic acid emerged as potent molecule with LAT IC50 of 2.62 µM. It has a significant log reduction of 2.9 and 2.3 fold against nutrient starved and biofilm forming mycobacteria. It was found to be inactive in MABA assay and M.marinum induced zebra fish model. It is also devoid of cytotoxicity. Compound 22 was also found to possess bactericidal effect which is independent of concentration and time. It was found to be effective in combination with Rifampicin in 3D granuloma model. The results are very encouraging as the hit molecule shows activity against active as well as persistent forms of tuberculosis. The identified hit needs further more pharmacokinetic and dynamic screening for development as new drug candidate.Keywords: benzothiazole, latent tuberculosis, LAT, nutrient starvation
Procedia PDF Downloads 3322453 Sainte Sophie Landfill: Field-Scale Assessment of Municipal Solid Waste Mechanical Characteristics
Authors: Wameed Alghazali, Shawn Kenny, Paul J. Van Geel
Abstract:
Settlement of municipal solid waste (MSW) in landfills can be represented by mechanical settlement, which is instantaneous and time-dependent creep components, and biodegradation-induced settlement. Mechanical settlement is governed by the physical characteristics of MSW and the applied overburden pressure. Several research studies used oedometers and different size compression cells to evaluate the primary and mechanical creep compression indices/ratios. However, MSW is known for its heterogeneity, which means data obtained from laboratory testing are not necessary to be a good representation of the mechanical response observed in the field. Furthermore, most of the laboratory tests found in the literature were conducted on shredded samples of MSW to obtain specimens that are suitable for the testing setup. It is believed that shredding MSW samples changes the physical and mechanical properties of the waste. In this study, settlement field data was collected during the filling stage of Ste. Sophie landfill was used to estimate the primary and mechanical creep compression ratios. The field results from Ste. Sophie landfill indicated that both the primary and mechanical creep compression ratios of MSW are not constants but decrease with the increase in the applied vertical stress.Keywords: mechanical creep compression ratio, municipal solid waste, primary compression ratio, stress level
Procedia PDF Downloads 1002452 Frequency of Polymorphism of Mrp1/Abcc1 And Mrp2/Abcc2 in Healthy Volunteers of the Center Savannah (Colombia)
Authors: R. H. Bustos, L. Martinez, J. García, F. Suárez
Abstract:
MRP1 (Multi-drug resistance associated protein 1) and MRP2 (Multi-drug resistance associated protein 2) are two proteins belonging to the transporters of ABC (ATP-Binding Cassette). These transporter proteins are involved in the efflux of several biological drugs and xenobiotic and also in multiple physiological, pathological and pharmacological processes. Evidence has been found that there is a correlation among different polymorphisms found and their clinical implication in the resistance to antiepileptic, chemotherapy and anti-infectious drugs. In our study, exonic regions of MRP1/ABCC1 y MRP2/ABCC2 were studied in the Colombian population, specifically in the region of the central Savannah (Cundinamarca) to determinate SNP (Single Nucleotide Polymorphisms) and determinate its allele frequency and its genomics frequency. Results showed that for our population, SNP are found that have been previously reported for MRP1/ABCC1 (rs200647436, rs200624910, rs150214567) as well as for MRP2/ABCC2 (rs2273697, rs3740066, rs142573385, rs17216212). In addition, 13 new SNP were identified. Evidences show an important clinic correlation for polymorphisms rs3740066 and rs2273697. The study object population displays genetic variability as compared to the one reported in other populations.Keywords: ATP-binding cassette (ABCC), Colombian population, multidrug-resistance protein (MRP), pharmacogenetic, single nucleotide polymorphism (SNP)
Procedia PDF Downloads 3262451 Cloning and Expression of Human Interleukin 15: A Promising Candidate for Cytokine Immunotherapy
Authors: Sadaf Ilyas
Abstract:
Recombinant cytokines have been employed successfully as potential therapeutic agent. Some cytokine therapies are already used as a part of clinical practice, ranging from early exploratory trials to well established therapies that have already received approval. Interleukin 15 is a pleiotropic cytokine having multiple roles in peripheral innate and adaptive immune cell function. It regulates the activation, proliferation and maturation of NK cells, T-cells, monocytes/macrophages and granulocytes, and the interactions between them thus acting as a bridge between innate and adaptive immune responses. Unraveling the biology of IL-15 has revealed some interesting surprises that may point toward some of the first therapeutic applications for this cytokine. In this study, the human interleukin 15 gene was isolated, amplified and ligated to a TA vector which was then transfected to a bacterial host, E. coli Top10F’. The sequence of cloned gene was confirmed and it showed 100% homology with the reported sequence. The confirmed gene was then subcloned in pET Expression system to study the IPTG induced expression of IL-15 gene. Positive expression was obtained for number of clones that showed 15 kd band of IL-15 in SDS-PAGE analysis, indicating the successful strain development that can be studied further to assess the potential therapeutic intervention of this cytokine in relevance to human diseases.Keywords: Interleukin 15, pET expression system, immune therapy, protein purification
Procedia PDF Downloads 4162450 Right Cerebellar Stroke with a Right Vertebral Artery Occlusion Following an Embolization of the Right Glomus Tympanicum Tumor
Authors: Naim Izet Kajtazi
Abstract:
Context: Although rare, glomus tumor (i.e., nonchromaffin chemodectomas and paragan¬gliomas) is the most common middle ear tumor, with female predominance. Pre-operative embolization is often required to devascularize the hypervascular tumor for better surgical outcomes. Process: A 35-year-old female presented with episodes of frequent dizziness, ear fullness, and right ear tinnitus for 12 months. Head imaging revealed a right glomus tympanicum tumor. She underwent pre-operative endovascular embolization of the glomus tympanicum tumor with surgical, cyanoacrylate-based glue. Immediately after the procedure, she developed drowsiness and severe pain in the right temporal region. Further investigations revealed a right cerebellar stroke in the posterior inferior cerebellar artery territory. She was treated with intravenous heparin, followed by one year of oral anticoagulation. With rehabilitation, she significantly recovered from her post embolization stroke. However, the tumor was resected at another institution. Ten years later, follow-up imaging indicated a gradual increase in the size of the glomus jugulare tumor, compressing the nearby critical vascular structures. She subsequently received radiation therapy to treat the residual tumor. Outcome: Currently, she has no neurological deficit, but her mild dizziness, right ear tinnitus, and hearing impairment persist. Relevance: This case highlights the complex nature of these tumors, which often bring challenges to the patients as well as treatment teams. The multi-disciplinary team approach is necessary to tailor the management plan for individual tumors. Although embolization is a safe procedure, careful attention and thoughtful anatomic knowledge regarding dangerous anastomosis are essential to avoid devastating complications. Complications occur due to encountered vessel anomalies and new anastomoses formed during the gluing and changes in hemodynamics.Keywords: stroke, embolization, MRI brain, cerebral angiogram
Procedia PDF Downloads 742449 Baseline CD4 Positive T Lymphocytes Counts among HIV Sero-Positive Patients Attending Benue State University Teaching Hospital, Makurdi, Nigeria
Authors: S. I. Nwadioha, M. S. Odimayo, G. T. A. Jombo, E. O. P. Nwokedi
Abstract:
Aims and Objectives: To determine the baseline CD4 positive T lymphocytes count of HIV/AIDS treatment naïve adults clients presenting for the first time treatment in Benue State University Teaching Hospital. Subjects and Methods: A total of 700 subjects age between 18 years to 70 years, were recruited for the study, comprising 600 HIV sero-positive patients and 100 healthy controls in Benue State University Teaching Hospital, Makurdi from 2013 to 2014. The CD4 counts of the subjects were evaluated using a Partec flow cytometer. Results: CD4 count of 200-299 cells/μl peaked with 25% (n=150/600)[control; 0%( n= 0/100)]. The study also showed that 44% (266/600) of HIV subjects had acquired immunodeficiency syndrome as defined by low CD4 counts below 200 cells/μl. Seventy-five per cent (n=451/600)of our patients would require to be placed on antiretroviral therapy with CD4 count of less than 350 cells/μl. At CD4 350 baseline criterion, age group 20-29 years had the highest demand 35%(160/451) for ARV followed by age groups 30-39 and 40-49 years with 28%(128/451) and 22%(98/451) respectively. Conclusion: There is a high prevalence of acquired immunodeficiency syndrome as defined by CD4 counts below 200 cells/μl, among the young active productive age group. The strict adopting of the ART WHO 2010 scale- up criteria doubles the number of the HIV clients that would qualify for ART with its attendant health benefits on the long run.Keywords: CD4 counts, HIV patients, young age group, Nigeria
Procedia PDF Downloads 3332448 Overall Function and Symptom Impact of Self-Applied Myofascial Release in Adult Patients With Fibromyalgia. A Seven-Week Pilot Study
Authors: Domenica Tambasco, Riina Bray, Sophia Jaworski, Gillian Grant, Celeste Corkery
Abstract:
Fibromyalgia is a chronic condition characterized by widespread musculoskeletal pain, fatigue, and reduced function. Management of symptoms include medications, physical treatments and mindfulness therapies. Myofascial Release is a modality that has been successfully applied in var-ious musculoskeletal conditions. However, to the author’s best knowledge, it is not yet recog-nized as a self-management therapy option in Fibromyalgia. In this study, we investigated whether Self-applied Myofascial Release (SMR) is associated with overall improved function and symptoms in Fibromyalgia. Methods: Eligible adult patients with a confirmed diagnosis of Fibromyalgia at Women’s College Hospital were recruited to SMR. Sessions ran for 1 hour once a week for 7 weeks, led by the same two Physiotherapists knowledgeable in this physical treat-ment modality. The main outcome measure was an overall impact score for function and symp-toms based on the validated assessment tool for Fibromyalgia, the Revised Fibromyalgia Impact Questionnaire (FIQR), measured pre and post-intervention. Both descriptive and analytical methods were applied and reported. Results: We analyzed results using a paired t-test to deter-mine if there was a statistically significant difference in mean FIQR scores between initial (pre-intervention) and final (post-intervention) scores. A clinically significant difference in FIQR was defined as a reduction in score by 10 or more points. Conclusions: Our pilot study showed that SMR appeared to be a safe and effective intervention for our Fibromyalgia participants and the overall impact on function and symptoms occurred in only 7 weeks. Further studies with larger sample sizes comparing SMR to other physical treatment modalities (such as stretching) in an RCT are recommended.Keywords: fibromyalgia, myofascial release, physical therapy, FIQR
Procedia PDF Downloads 782447 Distribution of HLA-DQA1 and HLA-DQB1 Alleles in Thais: Genetics Database Insight for COVID-19 Severity
Authors: Jinu Phonamontham
Abstract:
Coronavirus, also referred to as COVID-19, is a virus caused by the SARS-Cov-2 virus. The pandemic has caused over 10 million cases and 500,000 deaths worldwide through the end of June 2020. In a previous study, HLA-DQA1*01:02 allele was associated with COVID-19 disease (p-value = 0.0121). Furthermore, there was a statistical significance between HLA- DQB1*06:02 and COVID-19 in the Italian population by Bonferroni’s correction (p-value = 0.0016). Nevertheless, there is no data describing the distribution of HLA alleles as a valid marker for prediction of COVID-19 in the Thai population. We want to investigate the prevalence of HLA-DQA1*01:02 and HLA-DQB1*06:02 alleles that are associated with severe COVID-19 in the Thai population. In this study, we recruited 200 healthy Thai individuals. Genomic DNA samples were isolated from EDTA blood using Genomic DNA Mini Kit. HLA genotyping was conducted using the Lifecodes HLA SSO typing kits (Immucor, West Avenue, Stamford, USA). The frequency of HLA-DQA1 alleles in Thai population, consisting of HLA-DQA1*01:01 (27.75%), HLA-DQA1*01:02 (24.50%), HLA-DQA1*03:03 (13.00%), HLA-DQA1*06:01 (10.25%) and HLA-DQA1*02:01 (6.75%). Furthermore, the distributions of HLA-DQB1 alleles were HLA-DQB1*05:02 (21.50%), HLA-DQB1*03:01 (15.75%), HLA-DQB1*05:01 (14.50%), HLA-DQB1*03:03 (11.00%) and HLA-DQB1*02:02 (8.25%). Particularly, HLA- DQA1*01:02 (29.00%) allele was the highest frequency in the NorthEast group, but there was not significant difference when compared with the other regions in Thais (p-value = 0.4202). HLA-DQB1*06:02 allele was similarly distributed in Thai population and there was no significant difference between Thais and China (3.8%) and South Korea (6.4%) and Japan (8.2%) with p-value > 0.05. Whereas, South Africa (15.7%) has a significance with Thais by p-value of 0.0013. This study supports the specific genotyping of the HLA-DQA1*01:02 and HLA-DQB1*06:02 alleles to screen severe COVID-19 in Thai and many populations.Keywords: HLA-DQA1*01:02, HLA-DQB1*06:02, Asian, Thai population
Procedia PDF Downloads 1022446 Motivational Qualities of and Flow State Responses to Participant-Selected Music and Researcher-Selected Music
Authors: Nurul A. Hamzah, Tony Morris, Dan Van Der Westhuizen
Abstract:
Music listening can potentially promote the achievement of flow state during exercise. Selecting music for exercise should consider the motivational factors-internal factors (music tempo and musicality) and external factors (cultural impact and association). This study was a cross-over study which was designed to examine the motivational qualities of music (participant-selected music and researcher-selected music) and flow state responses during exercise accompanying with music. 17 healthy participants (M=30.2, SD=6.3 years old) were among low physical activity individuals. Participants completed two separate sessions of 30 minutes of moderate intensity exercise (40-60% of Heart Rate Reserve) while listening to music. Half the participants at random were assigned to exercise with participant-selected music first, and half were assigned to exercise with researcher-selected music first. Parameters including flow state responses (Flow State Scale-2) and motivational music rating (Brunel Music Rating Inventory-2) were administered immediately after the exercise. Results from this study showed that there were no significant differences for both flow state t(32)=0.00, p>0.05 and motivational music rating t(32)= .393, p>0.05 between exercise with participant-selected music and exercise with researcher-selected music. Listening to music either participant or researcher selected music could promote flow experience during exercise when music is perceived as motivational. Music tempo and music preference are factors that could influence individuals to enjoy exercise and improve the exercise performance.Keywords: motivational music, flow state, researcher-selected music, participant-selected music
Procedia PDF Downloads 3872445 Biologic Materials- Ecological Living Network
Authors: Ina Dajci
Abstract:
Biologic Materials presents groundbreaking transdisciplinary research aimed at fostering new collaborative models across the Built Environment, Forestry, and Agriculture sectors. This initiative seeks to establish innovative paradigms for local and global material flows by developing a biocompatible, regenerative material economy. The project focuses on creating materials derived from biowaste and silvicultural practices, ensuring the preservation of endangered indigenous and vernacular techniques through the integration of emerging biosciences. By utilizing biomaterials sourced from agricultural waste and forest byproducts, the initiative incorporates fabrication methods recognized by UNESCO as ‘intangible cultural heritage of humanity,’ which are currently at risk. The structural, mechanical, and environmental properties of these materials are enhanced through advanced CAD-CAM fabrication, along with energy-efficient biochemical and bacterial processes that promote healthy indigo coloration. Furthermore, the integration of AI technologies in species selection facilitates a novel partnership model, enabling designers to collaborate effectively with forest managers and silviculture practitioners. This collaborative approach not only optimizes the use of plant-based materials but also enhances biodiversity and climate resilience in regional ecosystems. Overall, this project embodies a holistic strategy for addressing environmental challenges while revitalizing traditional practices and fostering sustainable innovation.Keywords: material, architecture, culture, heritage, ecology, environment
Procedia PDF Downloads 232444 Scientific Insight Review of Corrosion Methods and Corrosion Control of Pre-Stressed Concrete Cylinder Pipes
Authors: Saad A. Bakheet, Ashraf A. Younees, Abdalsamia M. Falah
Abstract:
The main purpose of this study is to the occurrence of several failures in four-meter diameter pre-restressed concrete cylinder pipes, which transport a huge quantity of water from the Libyan Sahara Desert to the populated coastal area in the north. This study will help to address the problems related to corrosion of the pre-stressed concrete cylinder pipes and methods of controlling it. The methodologies used depended on reviewing the design and fabrication of pre-stressed concrete cylinder pipes and studying the cause of the corrosion, which resulted in the failure of the pre-stressed concrete cylinder pipe Man-Made River project in Libya. The chloride-induced corrosion penetrating through the mortar coat was the main reason for corrosion. The beginning of the occurrence of corrosion, its causes, and the mechanisms of its development in pre-stressed concrete pipes since 1937 have been reviewed and are continuing until now. Manufacturing technology control corrosion and all associated problems and technology to control it have been demonstrated, including variables during manufacture, the use of a modified coating, and cathodic protection systems. It has been revised and is still based on international standards. The development of these standards and the change in some of their technical contents reflect the world's interest in the problems of corrosion and the cost of maintenance and replacement.Keywords: PCCP corrosion, international standard, coating system, failure assessment
Procedia PDF Downloads 812443 Allele Frequency of HLA-DRB1* in Thai Population to Predict Factor for Severity of COVID-19 Infection
Authors: Siriniya Siribrahmanakul
Abstract:
Introduction:SARsCOVID-19 is rapidly spreading, and some people may exhibit severe symptoms. Mortality rate of 2.0–3.0% with COVID-19 infection atworldwide. Human leukocyte antigen (HLA), located on chromosome 6, consist of HLA class I and class II. HLA are used by the immune system to attach self-antigens. Previous studies, HLA-DRB1*01:01,HLA-DRB1*12:01and HLA-DRB1*14:04 were, showed significant difference with severe COVID-19 in the Chinese population by p-value < 0.05. Objective: We investigated the prevalence of HLA-DRB1 alleles associated with severe COVID-19 in Thai population. Materials and Methods:200 DNA samples were isolated from EDTA blood using the MagNAprue Compact Nucleic Acid Isolation kits.HLA-DRB1alleles were genotyped using sequence-specific oligonucleotides (PCR-SSOs). Results:The frequency of HLA-DRB1 alleles in Thai population wereHLA-DRB1*12:02 (15.75%), HLA-DRB1*15:02 (14.50%), HLA-DRB1*09:01 (11.50%), HLA-DRB1*07:01 (9.50%), HLA-DRB1*03:01,HLA-DRB1*05:01 (5.75%), HLA-DRB1*14:01 (5.50%), HLA-DRB1*16:02 (4.50%), HLA-DRB1*04:05 (4.00%), HLA-DRB1*14:03 (3.25%), HLA-DRB1*10:01 (2.25%) and HLA-DRB1*13:02 (2.00%). Particularly, HLA-DRB1*12:02 allele was the highest allele frequency presented in the four regions groups of Thai population. Furthermore, the HLA-DRB1* alleles associated with severe COVID-19, which consists ofHLA-DRB1*14:04(2.00 %) and HLA-DRB1*12:01(0.50%) in Thai population, whereas HLA-DRB1*01:01 allele was not found in this population. HLA-DRB1*14:04 and HLA-DRB1*12:01alleles were similarly distributed in four regions populations in Thailand (p-value > 0.05). The alleles frequencies of HLA-DRB1*14:04 and HLA-DRB1*12:01, which associated with severe COVID-19, had no significant differences between Thai population, South China population, South Africa population, and South Koreapopulation (p-value > 0.05). Conclusions: Particularly, this study has focused on allele frequency of HLA-DRB1*14:04in a healthy Thai population to evaluating their impact on the severe COVID-19. Furthermore, our research needs to be done in larger numbers of Thai patients.Keywords: HLA-DRB1, allele frequency, Thai population, COVID-19 marker
Procedia PDF Downloads 1372442 Cellular Mechanisms Involved in the Radiosensitization of Breast- and Lung Cancer Cells by Agents Targeting Microtubule Dynamics
Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron
Abstract:
Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization
Procedia PDF Downloads 2122441 The Transcriptional Regulation of Human LRWD1 through DNA Methylation
Authors: Yen-Ni Teng, Hsing-Yi Chen, Hsien-An Pan, Yung-Ming Lin, Hany A. Omar, Jui-Hsiang Hung
Abstract:
Leucine-rich repeats and WD repeat domain containing 1 (LRWD1) is highly expressed in the testes of healthy males. On the other hand, LRWD1 is significantly down-regulated in the testicular tissues of patients with severe spermatogenic defects. In our study, the downregulation of LRWD1 expression by shRNA caused a significant reduction of cell growth and mitosis and a noteworthy increase in the cell microtubule atrophy rate. Here, we used EMBOSS CpG plot analysis to explore the promoter region of LRWD1 gene. We found that CpG islands are located between positions -253 to +5 nucleotides upstream from the LRWD1 transcription start site. Luciferase reporter assay revealed that the hypermethylation of the LRWD1 promoter reduced the transcription activity in cells. In addition, quantitative methylation-specific PCR and immunostaining showed that the methylation inhibitor, 5-Aza-2'-deoxycytidine, increased LRWD1 promoter activity, LRWD1 mRNA, protein expression and cell viability. Whereas, the methylation activator, S-adenosylmethionine, caused opposite effects. The overexpression of p53 and Nrf2 in NT2/D1 cells increased LRWD1 promoter activity while 5-fluorodeoxyuridine decreased it. In conclusion, this study highlights evidence that the methylation status of LRWD1 promoter is associated with LRWD1 expression. Since the expression level of LRWD1 plays an important role in spermatogenesis, the methylation status of LRWD1 may serve as a novel molecular diagnostic or therapeutic approach in male's infertility.Keywords: LRWD1, DNA methylation, p53, Nrf2
Procedia PDF Downloads 153