Search results for: circulating tumor DNA (ctDNA)

Authors: Mahdieh Jajroudi

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Developing a pharmacokinetic model for the neuroendocrine tumors therapy agent 177Lu-DOTATATE in nude mice bearing AR42J rat pancreatic tumor to investigate and evaluate the behavior of the complex was the main purpose of this study. The utilization of compartmental analysis permits the mathematical differencing of tissues and organs to become acquainted with the concentration of activity in each fraction of interest. Biodistribution studies are onerous and troublesome to perform in humans, but such data can be obtained facilely in rodents. A physiologically based pharmacokinetic model for scaling up activity concentration in particular organs versus time was developed. The mathematical model exerts physiological parameters including organ volumes, blood flow rates, and vascular permabilities; the compartments (organs) are connected anatomically. This allows the use of scale-up techniques to forecast new complex distribution in humans' each organ. The concentration of the radiopharmaceutical in various organs was measured at different times. The temporal behavior of biodistribution of 177Lu labeled somatostatin analogues was modeled and drawn as function of time. Conclusion: The variation of pharmaceutical concentration in all organs is characterized with summation of six to nine exponential terms and it approximates our experimental data with precision better than 1%.

Keywords: biodistribution modeling, compartmental analysis, 177Lu labeled somatostatin analogues, neuroendocrine tumors

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Authors: Abdul Qadir Qadis, Satoru Goya, Minoru Yatsu, Yu-uki Yoshida, Toshihiro Ichijo, Shigeru Sato

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Bacterial probiotics are known to modulate the gut-associated lymphoid and epithelial tissue response to enhance the activities of intestinal and systemic immune system in human and animals. In cattle, the immune-stimulatory effects of probiotics have been evaluated during intestinal disorders. To investigate the effects of probiotic on the function of peripheral blood mononuclear cells, eight healthy Holstein calves (10 ± 3 weeks) were assigned to a 4 × 2 experimental design. The probiotic, consisting of Lactobacillus plantarum, Enterococcus faecium and Clostridium butyricum, was administered orally at 3.0 g/100 kg body weight to calves once daily for 5 consecutive days. Calves given no probiotic served as the control. In the treatment group, increases in numbers of CD282+ monocytes, CD3+ T-cells and CD4+, CD8+ and WC1+ γδ T- cell subsets were noted on day 7 post-placement compared to pre-dose day and the control group. Expression of interleukin-6, interferon-gamma and tumor necrosis factor-alpha was elevated in peripheral leukocytes on days 7 and 14. These results suggest that peripheral blood leukocytes in healthy calves may be stimulated via the gastrointestinal microbiota, which was increased by the oral probiotic treatment. The 5-day repeated administration of a bacterial probiotic may enhance cellular immune function in weaned calves.

Keywords: bacterial-probiotic, calf, interleukin, leukocyte

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Authors: Dominika Pihikova, Stefan Belicky, Tomas Bertok, Roman Sokol, Petra Kubanikova, Jan Tkac

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Since aberrant glycosylation is frequently accompanied by both physiological and pathological processes in a human body (cancer, AIDS, inflammatory diseases, etc.), the analysis of tumor-associated glycan patterns have a great potential for the development of novel diagnostic approaches. Moreover, altered glycoforms may assist as a suitable tool for the specificity and sensitivity enhancement in early-stage prostate cancer diagnosis. In this paper we discuss the construction and optimization of ultrasensitive sandwich biosensor platform employing lectin as glycan-binding protein. We focus on the immunoassay development, reduction of non-specific interactions and final glycoprofiling of human serum samples including both prostate cancer (PCa) patients and healthy controls. The fabricated biosensor was measured by label-free electrochemical impedance spectroscopy (EIS) with further lectin microarray verification. Furthermore, we analyzed different biosensor interfaces with atomic force microscopy (AFM) in nanomechanical mapping mode showing a significant differences in the altitude. These preliminary results revealing an elevated content of α-2,3 linked sialic acid in PCa patients comparing with healthy controls. All these experiments are important step towards development of point-of-care devices and discovery of novel glyco-biomarkers applicable in cancer diagnosis.

Keywords: biosensor, glycan, lectin, prostate cancer

Procedia PDF Downloads 372

Authors: Piamsiri Sawaisorn, Tienrat Tangchaikeeree, Waraporn Chan-On, Chaniya Leepiyasakulchai, Rachanee Udomsangpetch, Suradej Hongeng, Kulachart Jangpatarapongsa

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Human Vγ9Vδ2 T lymphocytes are regarded as promising effector cells for cancer immunotherapy since they have the ability to eliminate several tumor cells through non-peptide antigen recognition and non-major histocompatibility complex (MHC) restriction. An issue of recent interest is the capability to activate γδ T cells by use of a group of drugs, such as pamidronate, that cause accumulation of phosphoantigen which is recognized by γδ T cell receptors. Moreover, their antigen presenting cell-like phenotype and function have been confirmed in many clinical trials. In this study, Vγ9Vδ2 T cells derived from normal peripheral blood mononuclear cells were activated with pamidronate and the expanded Vγ9Vδ2 T cells can recognize and kill chronic myeloid leukemia (CML) cells treated with pamidronate through their cytotoxic activity. To support the strong role played by Vγ9Vδ2 T cells against cancer, we provide the evidence that Vγ9Vδ2 T cells activated with CML cell lysate antigen can efficiently express antigen presenting cell (APC) phenotype and function. In conclusion, pamidronate can be used in intentional activation of human Vγ9Vδ2 T cells and can increase the susceptibility of CML cells to cytotoxicity of Vγ9Vδ2 T cells. The activated Vγ9Vδ2 T cells by cancer cells lysate can show their APC characteristics, and so greatly increase the interest in exploring their therapeutic potential in hematologic malignancy.

Keywords: γδ T lymphocytes, antigen-presenting cells, chronic myeloid leukemia, cancer, immunotherapy

Procedia PDF Downloads 186

Authors: Dalia O. Saleha, Gehad A. Abdel Jaleela, Sally W. Al-Awdana

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Diabetes mellitus (DM) is known to exacerbate cerebral ischemic injury. The present study aimed to investigate the anti-oxidant and anti-inflammatory effects of oral supplementation of melatonin (MLN) on cerebral injury caused by middle cerebral artery occlusion and reperfusion (MCAO/Re) in streptozotocin (STZ)-induced hyperglycemic rats. Hyperglycemia was induced by a single injection of STZ (55mg/kg; i.p.), six weeks later the cerebral injury was induced by MCAO/Re. Twenty-four hours after the MCAO/Re the MLN (10 mg/kg) was injected for 14 consecutive days. Results of the present study revealed that MCAO/Re in STZ-induced hyperglycemia in rats causes an increase in the oxidative stress biomarkers; it increased brain lipid peroxidation (measured as malondialdehyde; MDA) and brain level of nitric oxide (NO). Moreover, MCAO/Reproduces a prominent increase in the brain inflammatory markers viz. interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis nuclear factor-alpha (TNF-α). Oral treatment of MCAO/Re in STZ-induced hyperglycemic rats with MLN (10 mg/kg) for two weeks restored the brain levels of MDA, GSH, NO, IL-6, IL-1β and the TNF-α. MLN succeeded to suppress the exacerbation of damage in the brain of hyperglycemic rats. These results suggest that daily intake of MLN attenuates the exacerbation of cerebral ischemic injury in a diabetic state, which may be attributed to anti-oxidant and anti-inflammatory effects in the brain.

Keywords: melatonin, brain injury, cerebral ischemia/reperfusion, hyperglycemia, rats

Procedia PDF Downloads 157

Authors: Hsin-Lien Lin, Ju-Hui Fu

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Dendritic cells (DCs) are the major professional antigen-presenting cells for the development of optimal T-cell immunity. DCs can be used as pharmacological targets to screen novel biological modifiers for the treatment of harmful immune responses, such as transplantation rejection. Dryopteris crassirhizoma Nakai (Aspiadaceae) is used for traditional herbal medicine in the region of East Asia. The root of this fern plant has been listed for treating inflammatory diseases. Dryocrassin is the tetrameric phlorophenone component derived from Dryopteris. Here, we tested the immunomodulatory potential of dryocrassin on lipopolysaccharide (LPS)-stimulated activation of mouse bone marrow-derived DCs in vitro and in skin allograft transplantation in vivo. Results demonstrated that dryocrassin reduced the secretion of tumor necrosis factor-α, interleukin-6, and interleukin-12p70 by LPS-stimulated DCs. The expression of LPS-induced major histocompatibility complex class II, CD40, and CD86 on DCs was also blocked by dryocrassin. Moreover, LPS-stimulated DC-elicited allogeneic T-cell proliferation was lessened by dryocrassin. In addition, dryocrassin inhibited LPS-induced activation of IϰB kinase, JNK/p38 mitogen-activated protein kinase, as well as the translocation of NF-ϰB. Treatment with dryocrassin obviously diminished 2,4-dinitro-1-fluorobenzene- induced delayed-type hypersensitivity and prolonged skin allograft survival. Dryocrassin may be one of the potent immunosuppressive agents for transplant rejection through the destruction of DC maturation and function.

Keywords: dryocrassin, dendritic cells, immunosuppression, skin allograft

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Authors: Mai M. Farid, Ximeng Yang, Tomoharu Kuboyama, Yuna Inada, Chihiro Tohda

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Intro: Trigonella foenum-graecum (Fenugreek), from Fabaceae family is a well-known plant traditionally used as food and medicine. Many pharmacological effects of Trigonella foenum- graecum seeds extract (TF extract) were evaluated such as anti-diabetic, anti-tumor and anti-dementia effects using in vivo models. Regarding the anti-dementia effects of TF extract, diabetic rats, aluminum chloride-induced amnesia rats and scopolamine-injected mice were used previously for evaluation, which are not well established as Alzheimer’s disease models. In addition, those previous studies, active constituents in TF extract for memory function were not identified. Method: This study aimed to clarify the effect of TF extract on Alzheimer’s disease model, 5XFAD mouse that overexpresses mutated APP and PS1 genes and determine the major active constituent in the brain after oral intake of TF extract. Results: Trigonelline was detected in the cerebral cortex of 5XFAD mice after 24 hours of oral administration of TF extract by LC-MS/MS. Oral administration of TF extract for 17 days improved object location memory in 5XFAD mice. Conclusion: These results suggest that TF extract and its active constituents could be an expected therapeutic candidate for Alzheimer’s disease.

Keywords: Alzheimer's disease, LC-MS/MS, memory recovery, Trigonella foenum-graecum Seeds, 5XFAD mice

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Authors: Muhtasim Shafi Kader, Fizar Ahmed, Annesha Acharjee

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Machine learning and data mining are crucial in health care, as well as medical information and detection. Machine learning approaches are now being utilized to improve awareness of a variety of critical health issues, including diabetes detection, neuron cell tumor diagnosis, COVID 19 identification, and so on. Parkinson’s disease is basically a disease for our senior citizens in Bangladesh. Parkinson's Disease indications often seem progressive and get worst with time. People got affected trouble walking and communicating with the condition advances. Patients can also have psychological and social vagaries, nap problems, hopelessness, reminiscence loss, and weariness. Parkinson's disease can happen in both men and women. Though men are affected by the illness at a proportion that is around partial of them are women. In this research, we have to get out the accurate ML algorithm to find out the disease with a predictable dataset and the model of the following machine learning classifiers. Therefore, nine ML classifiers are secondhand to portion study to use machine learning approaches like as follows, Naive Bayes, Adaptive Boosting, Bagging Classifier, Decision Tree Classifier, Random Forest classifier, XBG Classifier, K Nearest Neighbor Classifier, Support Vector Machine Classifier, and Gradient Boosting Classifier are used.

Keywords: naive bayes, adaptive boosting, bagging classifier, decision tree classifier, random forest classifier, XBG classifier, k nearest neighbor classifier, support vector classifier, gradient boosting classifier

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Authors: Deok Hyun Han

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Objective: To explore outcomes of UventaTM metallic ureteral stent between malignant and benign ureteral obstruction. Methods: We reviewed the medical records of 90 consecutive patients who underwent Uventa stent placement for benign or malignant ureteral obstruction from December 2009 to June 2013. We evaluated the clinical outcomes, complications, and reasons and results for unexpected stent removals. Results: The median follow-up was 10.7 (0.9 – 41) months. From a total of 125 ureter units, there were 24 units with benign obstructions and 101 units with malignant obstructions. Initial technical successes were achieved in all patients. The overall success rate was 70.8% with benign obstructions and 84.2% with malignant obstructions. The major reasons for treatment failure were stent migration (12.5%) in benign and tumor progression (11.9%) in malignant obstructions. The overall complication rate was similar between benign and malignant obstructions (58.3% and 42.6%), but severe complications, which are Clavien grade 3 or more, occurred in 41.7% of benign and 6.9% of malignant obstructions. The most common complications were stent migration (25.0%) in benign obstructions and persistent pain (14.9%) in malignant obstructions. The stent removal was done in 16 units; nine units that were removed by endoscopy and seven units were by open surgery. Conclusions: In malignant ureteral obstructions, the Uventa stent showed favorable outcomes with high success rate and acceptable complication rate. However, in benign ureteral obstructions, overall success rate and complication rate were less favorable. Malignant ureteral obstruction seems to be appropriate indication of Uventa stent placement. However, in chronic diffuse benign ureteral obstructions the decision of placement of Uventa stent has to be careful.

Keywords: cause, complication, ureteral obstruction, metal stent

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Authors: Razieh Zareia, Hassan ZMB, Darush Moslemic, Amrollah Mostafa-Zaded

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Introduction: Shark is a murine organism and its cartilage has antitumor peptides to prevent angiogenesis, at least, in vitro. The purpose of our research was to evaluate the immune-effectiveness on imbalance between IL-23/IL-17 axis, as an inflammatory pathway and TGF/Foxp3 T regulatory as a inhibitory pathway of commercial shark cartilage that is available as a non-common dietary supplement in IRAN. Materials and Methods: First investigated an imbalanced supernatant of cytokines exist in patients with gastric cancer by ELISA. Associated with cytokines measuring such as IL-23, IL-17, TGF-β, IL-4, and γ-IFN, then flow cytometry was employed to determine whether the peripheral blood mononuclear cells such as CD4+CD25+Foxp3highT regulatory cells in patients with gastric cancer were changed correspondingly. Results: The simultaneously presented up-regulation IL-17A indicated, at least cytokine level without changing in TGF-β amount or CD4+CD25+Foxp3 T regulatory cells, that there are not a direct correlation between IL-23/IL-17 axis and Treg/TGF-β pathway in patients with gastric cancer treated by shark cartilage, but IL-23 was not expressed differentially in this group. So, accompany these changes, an imbalance between Th1 immunity (γ-IFN production) and TH2 immunity (IL-4 secretion) evaluated in patients with gastric cancer treated by shark cartilage. Conclusion: On the basis of results, we propose that shark cartilage, by reducing IL-4, decreasing IL-17 a central cytokine in angiogenesis and increasing γ-IFN amplify anti-tumor immune responses in patients with gastric cancer.

Keywords: IL-23/IL17 axis, TGF-β/CD4+CD25+Foxp3high T regulatory pathway, γ-IFN, IL-4, shark cartilage, gastric cancer

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Authors: Majid Khan

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Introduction: In this era of microsurgery, free flap holds a remarkable spot in reconstructive surgery. A free flap is well suited for composite defects as it provides sufficient and well-vascularized tissue for coverage. We report our experience with the use of the free flaps for the reconstruction of composite defects. Methods: This is a retrospective case series (chart review) of patients who underwent reconstruction of composite defects with a free flap at Aga Khan University Hospital, Karachi (Pakistan) from January 01, 2015, to December 31, 2019. Data were collected for patient demographics, size of the defect, size of flap, recipient vessels, postoperative complications, and outcome of the free flap. Results: Over this period, 532 free flaps are included in this study. The overall success rate is 95.5%. The mean age of the patient was 44.86 years. In 532 procedures, there were 448 defects from tumor ablation of head and neck cancer. The most frequent free flap was the anterolateral thigh flap in 232 procedures. In this study, the risk factor hypertension (p=0.004) was found significant for wound dehiscence, preop radiation/chemotherapy (p=0.003), and malnutrition (p=0.005) were found significant for fistula formation. Malnutrition (p=0.02) and use of vein grafts (p=0.025) were significant factors for flap failure. Conclusion: Free tissue transfer is a reliable option for the reconstruction of large and composite defects. Hypertension, malnutrition, and preoperative radiotherapy can cause significant morbidity.

Keywords: free flap, free flap failure, risk factors for flap failure, free flap outcome

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Authors: Peri Harish Kumar, Sai Sharan Dwarka, Tajbinder Singh Bains, Suneet John Joseph, Chaitanya Kiran, Sambhu Dutta, Sarah Makram, Mohamed Sayed Zaazouee, Alaa Ahmed Elshanbary

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Objective: To identify cancer and non-cancer causes of death in hepatocellular carcinoma (HCC) patients over different time periods after diagnosis and to compare the mortality risk of each cause in HCC patients with the general population. Methods: In this retrospective cohort study, data of 67,637 HCC patients from 1975 to 2016 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. We investigated the association between different causes of death and the following variables: age, race, tumor stage at diagnosis, and treatment (surgery, chemotherapy, and radiotherapy); each according to the periods of <1 year, 1-5 years, 5-10 years, and >10 years following the diagnosis. Standardized mortality ratios (SMRs) and their 95% confidence intervals (CIs) were calculated for cancer and non-cancer deaths in each of the mentioned periods following diagnosis. Results: Data of 67,637 patients, of whom 50,571 patients died during the follow-up period, were analyzed. Most deaths were due to HCC itself (35,535, 70.3%), followed by other cancers (3,983, 7.9%). Common causes of non-cancer mortality included infectious and parasitic diseases including HIV (2,823 patients, SMR=105.68, 95% CI: 101.82-109.65), chronic liver disease (2,719 patients, SMR=76.56, 95% CI: 73.71,79.5), and heart diseases (1,265 patients, SMR=2.26, 95% CI: 2.14-2.39), with higher mortality risk in HCC patients than in the general population. Conclusion: Cancers stand for most deaths in patients with HCC. Besides, infectious, and parasitic diseases including HIV represent the commonest non-cancer cause of mortality.

Keywords: hepatocellular carcinoma, seer, causes of death, mortality

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Authors: Noora Al Muftah, Reda Rawi, Richard Thompson, Halima Bensmail

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Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers of response to targeted agents. There is an urgent need to identify biomarkers that predict which patients with are most likely to respond to treatment. Systematic efforts to correlate tumor mutational data with biologic dependencies may facilitate the translation of somatic mutation catalogs into meaningful biomarkers for patient stratification. To identify genomic features associated with drug sensitivity and uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we have screened and integrated a panel of several hundred cancer cell lines from different databases, mutation, DNA copy number, and gene expression data for hundreds of cell lines with their responses to targeted and cytotoxic therapies with drugs under clinical and preclinical investigation. We found mutated cancer genes were associated with cellular response to most currently available Glioma cancer drugs and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.

Keywords: cancer, gene network, Lasso, penalized regression, P-values, unbiased estimator

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Authors: Gehan A. Hegazy, Hesham N. Mustafa, Sally A. El Awdan, Marawan AbdelBaset

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Doxorubicin (DOX) is a chemotherapeutic agent used for the treatment of different cancers and its clinical usage is hindered by the oxidative injury-related cardiotoxicity. This work aims to declare if the harmful effects of DOX on the heart can be alleviated with the use of Coenzyme Q10 (CoQ10) or L-carnitine. The study was performed on seventy-two female Wistar albino rats divided into six groups, 12 animals each: Control group; DOX group (10 mg/kg); CoQ10 group (200 mg/kg); L-carnitine group (100 mg/kg); DOX + CoQ10 group; DOX + L-carnitine group. CoQ10 and L-carnitine treatment orally started five days before a single dose of 10 mg/kg DOX that injected intraperitoneally (IP) then the treatment continued for ten days. At the end of the study, serum biochemical parameters of cardiac damage, oxidative stress indices, and histopathological changes were investigated. CoQ10 or L-carnitine showed noticeable effects in improving cardiac functions evidenced reducing serum enzymes as serum interleukin-1 beta (IL-1), tumor necrosis factor alpha (TNF-), leptin, lactate dehydrogenase (LDH), Cardiotrophin-1, Troponin-I and Troponin-T. Also, alleviate oxidative stress, decrease of cardiac Malondialdehyde (MDA), Nitric oxide (NO) and restoring cardiac reduced glutathione levels to normal levels. Both corrected the cardiac alterations histologically and ultrastructurally. With visible improvements in -SMA, vimentin and eNOS immunohistochemical markers. CoQ10 or L-carnitine supplementation improves the functional and structural integrity of the myocardium.

Keywords: CoQ10, doxorubicin, L-Carnitine, cardiotoxicity

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Authors: Ahmed Borg, Elsa Aristodemou, Attia Attia

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Well control involves managing the circulating drilling fluid within the wells and avoiding kicks and blowouts as these can lead to losses in human life and drilling facilities. Current practices for good control incorporate predictions of pressure losses through computational models. Developing a realistic hydraulic model for a good control problem is a very complicated process due to the existence of a complex multiphase region, which usually contains a non-Newtonian drilling fluid and the miscibility of formation gas in drilling fluid. The current approaches assume an inaccurate flow fluid model within the well, which leads to incorrect pressure loss calculations. To overcome this problem, researchers have been considering the more complex two-phase fluid flow models. However, even these more sophisticated two-phase models are unsuitable for applications where pressure dynamics are important, such as in managed pressure drilling. This study aims to develop and implement new fluid flow models that take into consideration the miscibility of fluids as well as their non-Newtonian properties for enabling realistic kick treatment. furthermore, a corresponding numerical solution method is built with an enriched data bank. The research work considers and implements models that take into consideration the effect of two phases in kick treatment for well control in conventional drilling. In this work, a corresponding numerical solution method is built with an enriched data bank. Software STARCCM+ for the computational studies to study the important parameters to describe wellbore multiphase flow, the mass flow rate, volumetric fraction, and velocity of each phase. Results showed that based on the analysis of these simulation studies, a coarser full-scale model of the wellbore, including chemical modeling established. The focus of the investigations was put on the near drill bit section. This inflow area shows certain characteristics that are dominated by the inflow conditions of the gas as well as by the configuration of the mud stream entering the annulus. Without considering the gas solubility effect, the bottom hole pressure could be underestimated by 4.2%, while the bottom hole temperature is overestimated by 3.2%. and without considering the heat transfer effect, the bottom hole pressure could be overestimated by 11.4% under steady flow conditions. Besides, larger reservoir pressure leads to a larger gas fraction in the wellbore. However, reservoir pressure has a minor effect on the steady wellbore temperature. Also as choke pressure increases, less gas will exist in the annulus in the form of free gas.

Keywords: multiphase flow, well- control, STARCCM+, petroleum engineering and gas technology, computational fluid dynamic

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Authors: Omnia M. Kandil, Noha M. F. Hassan, Doaa Sedky, Hatem A. Shalaby, Heba M. Ashry, Nadia M. T. Abu El Ezz, Sahar M. Kandeel, Mohamed S. Abdelfattah Ying L, Ebtesam M. Al-Olayan

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The aim of the present study was to determine the prevalence of bovine cysticercosis in both cattle and buffaloes in Egypt and to assess the cysticidal efficacy of Balanites aegyptiacafruits (B. aegyptiaca) and Moringa oleiferaseeds (M. oleifera) extracts in experimentally infected mice. The study detected the level of tumor necrosis factor (TNF-α) to monitor the immune and inflammatory responses of experimentally infected mice. Through meat inspection, a total number of 2125 male bovines, 2 to 5 years old (1125 cattle and 1000 buffaloes) were examined at official abattoirs in Cairo Governorate. The prevalence of the disease among bovine was 7.8%, (6.31% of cattle and 9.5% of buffaloes). A decrease in the number of cysticerci was found in all treated mice groups, and up to 88% reduction was achieved in the B. aegyptiaca-treated group; higher than that was recorded in both M. oleifera (72.23%) and albendazole-treated ones (80.56%). Postmortem findings proved that M. oleifera and B. aegyptiaca reduced cysticerci numbers comparable to a commercial anthelmintic. The study showed a significant decrease (P<0.001) in TNF-α levels after treatment with Balanites and Moringa extracts, compared with the untreated control and the albendazole-treated groups.

Keywords: prevalence, bovine cysticercossis, extracts, mice

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Authors: Chia-Yen Lee, Hao-Jen Wang, Jhih-Hao Lai

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In recent years, infrared (IR) imaging has been considered as a potential tool to assess the efficacy of chemotherapy and early detection of breast cancer. Regions of tumor growth with high metabolic rate and angiogenesis phenomenon lead to the high temperatures. Observation of differences between the heat maps in long term is useful to help assess the growth of breast cancer cells and detect breast cancer earlier, wherein the multi-time infrared image alignment technology is a necessary step. Representative feature points detection and matching are essential steps toward the good performance of image registration and quantitative analysis. However, there is no clear boundary on the infrared images and the subject's posture are different for each shot. It cannot adhesive markers on a body surface for a very long period, and it is hard to find anatomic fiducial markers on a body surface. In other words, it’s difficult to detect and match features in an IR sequence images. In this study, automated feature detection and matching algorithms with two type of automatic feature points (i.e., vascular branch points and modified Harris corner) are developed respectively. The preliminary results show that the proposed method could identify the representative feature points on the IR breast images successfully of 98% accuracy and the matching results of 93% accuracy.

Keywords: Harris corner, infrared image, feature detection, registration, matching

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Authors: Sarim Ahmad

Abstract:

The Single Cell Gel Electrophoresis Assay (SCGE, known as comet assay) is a potential, uncomplicated, sensitive and state-of-the-art technique for quantitating DNA damage at individual cell level and repair from in vivo and in vitro samples of eukaryotic cells and some prokaryotic cells, being popular in its widespread use in various areas including human biomonitoring, genotoxicology, ecological monitoring and as a tool for research into DNA damage or repair in different cell types in response to a range of DNA damaging agents, cancer risk and therapy. The method involves the encapsulation of cells in a low-melting-point agarose suspension, lysis of the cells in neutral or alkaline (pH > 13) conditions, and electrophoresis of the suspended lysed cells, resulting in structures resembling comets as observed by fluorescence microscopy; the intensity of the comet tail relative to the head reflects the number of DNA breaks. The likely basis for this is that loops containing a break lose their supercoiling and become free to extend towards the anode. This is followed by visual analysis with staining of DNA and calculating fluorescence to determine the extent of DNA damage. This can be performed by manual scoring or automatically by imaging software. The assay can, therefore, predict an individual’s tumor sensitivity to radiation and various chemotherapeutic drugs and further assess the oxidative stress within tumors and to detect the extent of DNA damage in various cancerous and precancerous lesions of oral cavity.

Keywords: comet assay, single cell gel electrophoresis, DNA damage, early detection test

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Authors: Yun-Tsuen Chen, Shih-Ting Huang, Pi-Fen Cheng, Yu-Ting Su, Joffrey Hsu, Hui-Zhu Chen

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Acute intestinal obstruction is one of the differentials of acute abdomen and requires timely alleviation of intestinal distention and abdominal pain to avoid perforation, intra-abdominal infection, and peritonitis. Investigation to identify the cause of obstruction will direct treatment planning and allow for more effective management. In this study, we present a 71-year-old female presenting with symptoms of acute intestinal obstruction for five days. After extensive history taking, physical exam, medical imaging, and pathology, the patient was diagnosed with colon cancer with lung metastasis and acute intestinal obstruction. The patient was placed on nil per os status with intravenous fluid support, intravenous antibiotics, and a decompression nasogastric tube was placed. The patient received decompression with colostomy creation surgery. After assessing the patient’s clinical condition and tumor staging, a multidisciplinary healthcare team created an individualized treatment plan, which included plans to prepare the patient for home self-care and maintain good mental health with regular monitoring in the clinic setting. This case demonstrates the importance of early diagnosis, effective treatment, and a multidisciplinary approach to the management of acute intestinal obstruction secondary to colon cancer.

Keywords: acute intestinal obstruction, colostomy surgery, metastatic colon cancer, multidisciplinary healthcare team

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Authors: M. Moncef Khaddar

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This paper focuses mainly on a contextualized understanding of ‘autocratic authoritarianism’ in Tunisia without approaching its peculiarities in reference to the ideal type of capitalist-liberal democracy but rather analysing it as a Tunisian ‘civilian dictatorship’. This is reminiscent, to some extent, of the French ‘colonial authoritarianism’ in parallel with the legacy of the traditional formal monarchic absolutism. The Tunisian autocratic political system is here construed as a state manufactured nationalist-populist authoritarianism associated with a de facto presidential single party, two successive autocratic presidents and their subservient autocratic elites who ruled with an iron fist the de-colonialized ‘liberated nation’ that came to be subjected to a large scale oppression and domination under the new Tunisian Republic. The diachronic survey of Tunisia’s autocratic authoritarian system covers the early years of autocracy, under the first autocratic president Bourguiba, 1957-1987, as well as the different stages of its consolidation into a police-security state under the second autocratic president, Ben Ali, 1987-2011. Comparing the policies of authoritarian regimes, within what is identified synchronically as a bi-cephalous autocratic system, entails an in-depth study of the two autocrats, who ruled Tunisia for more than half a century, as modern adaptable autocrats. This is further supported by an exploration of the ruling authoritarian autocratic elites who played a decisive role in shaping the undemocratic state-society relations, under the 1st and 2nd President, and left an indelible mark, structurally and ideologically, on Tunisian polity. Emphasis is also put on the members of the governmental and state-party institutions and apparatuses that kept circulating and recycling from one authoritarian regime to another, and from the first ‘founding’ autocrat to his putschist successor who consolidated authoritarian stability, political continuity and autocratic governance. The reconfiguration of Tunisian political life, in the post-autocratic era, since 2011 will be analysed. This will be scrutinized, especially in light of the unexpected return of many high-profile figures and old guards of the autocratic authoritarian apparatchiks. How and why were, these public figures, from an autocratic era, able to return in a supposedly post-revolutionary moment? Finally, while some continue to celebrate the putative exceptional success of ‘democratic transition’ in Tunisia, within a context of ‘unfinished revolution’, others remain perplexed in the face of a creeping ‘oligarchic transition’ to a ‘hybrid regime’, characterized rather by elites’ reformist tradition than a bottom-up genuine democratic ‘change’. This latter is far from answering the 2010 ordinary people’s ‘uprisings’ and ‘aspirations, for ‘Dignity, Liberty and Social Justice’.

Keywords: authoritarianism, autocracy, democratization, democracy, populism, transition, Tunisia

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Authors: Maha Z. Rizk, Sami A. Fattah, Heba M. Darwish, Sanaa A. Ali, Mai O. Kadry

Abstract:

The increasing use of nanomaterials in consumer and industrial products has aroused global concern regarding their fate in biological systems resulting in demand for parallel risk assessment. The objective of this study is investigating either the effect of individual or combined doses of idebenone, carnosine and vitamin E on amelioration of some biochemical indices of nano sized titanium dioxide (TiO2 NPS) induced metabolic disorders in mice liver. TiO2-NPS was administered in an oral dose of 150 mg/kg for consecutive 14 days followed by oral daily doses of the aforementioned antioxidants for 1 month. TiO2-NPS induced a significant elevation in serum level of ALT and AST, hepatic inflammatory markers (tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6)) and increased the percent of DNA damage which was assessed by COMET assay in addition to the apoptotic marker Caspase-3. Moreover, mRNA gene expression observed by RT-PCR showed a significant overexpression in nuclear factor relation-2 (Nrf2), nuclear factor kappa beta (NF-Kβ) and the apoptotic factor (bax), and a significant down-regulation in the antiapoptotic factor (bcl2) level. In conclusion, idebenone, carnosine and vitamin E ameliorated the deviated parameters with a variable degree with the most pronounced role in alleviating the hazardous effect of TiO2 NPS toxicity following the combination regimen.

Keywords: idebenone, carnosine, vitamin E, TiO2 NPS, caspase-3, NrF2, NF-KB

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Authors: Danni Cheng

Abstract:

Purpose:Surgicallyinclusive treatment(SIT)isthemajor treatment fororopharyngealsquamouscellcarcinoma (OPSCC) in Eastern countries, while nonsurgical treatments(NSTs) are the priority treatment in Western countries. The preferred treatmentsforOPSCC patients remaindebated. Methods:Atotalof 153 consecutive OPSCC casesdiagnosed between 2009 and 2019inWCH, and 15,400 OPSCC cases from SEER database (2000-2017) were obtained. Clinical characteristics, treatments, and survival outcomes were retrospectively collected. We conductedKaplan-Meier curves univariate and multivariate analysis to compare the prognosis of OPSCC patients in WCH, SEER Asian, and SEER all ethnic population by different treatment modalities,HPVstatus, ages, and TNM stages. Results: The 5-year overall survival rate was 59% in WCH, 64% in the SEER all ethnic and 67% in SEER Asian group. In both univariate and multivariate analysis, SIT was observed as a consistent benefit factor for OPSCC patients in all three populations when classified by genders, tumor stages, and HPV status. Patients who underwent SIT had significantly better survival outcomes than those who received NSTsin WCH, SEER Asian, and SEER all ethnic groups. HPV positive status was the beneficial factor of OPSCC patients in all three groups. Besides, male patients had worse survival outcomes in both WCH and SEER Asian group, whereas male patients had better outcomes in the SEER all ethnic group. Conclusion: In contrast to nowadaysNSTs are the first-line therapiesfor OPSCC, our ten-year real-world data and SEER data indicated that OPSCC patients who underwent SIT had better prognosis than NSTs.

Keywords: OPSCC, survival outcome, SEER, treatment modalities

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Authors: Matthias Haenisch, Katharina Hermann, Marc Godau, Verena Weidner

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Over the past two decades, international music education has been characterized by a growing interest in informal learning for formal contexts and a "compositional turn" that has moved from closed to open forms of composing. This change occurs under social and technological conditions that permeate 21st-century musical practices. This forms the background of Musical Communities in the (Post)Digital Age (MusCoDA), a four-year joint research project of the University of Erfurt (UE) and the University of Education Karlsruhe (PHK), funded by the German Federal Ministry of Education and Research (BMBF). Both explore songwriting processes as an example of collective creativity in (post)digital communities, one in formal and the other in informal learning contexts. Collective songwriting will be studied from a network perspective, that will allow us to view boundaries between both online and offline as well as formal and informal or hybrid contexts as permeable and to reconstruct musical learning practices. By comparing these songwriting processes, possibilities for a pedagogical-didactic interweaving of different educational worlds are highlighted. Therefore, the subproject of the University of Erfurt investigates school music lessons with the help of interviews, videography, and network maps by analyzing new digital pedagogical and didactic possibilities. In the first step, the international literature on songwriting in the music classroom was examined for design development. The analysis focused on the question of which methods and practices are circulating in the current literature. Results from this stage of the project form the basis for the first instructional design that will help teachers in planning regular music classes and subsequently reconstruct musical learning practices under these conditions. In analyzing the literature, we noticed certain structural methods and concepts that recur, such as the Building Blocks method and the pre-structuring of the songwriting process. From these findings, we developed a deck of cards that both captures the current state of research and serves as a method for design development. With this deck of cards, both teachers and students themselves can plan their individual songwriting lessons by independently selecting and arranging topic, structure, and action cards. In terms of science communication, music educators' interactions with the card game provide us with essential insights for developing the first design. The overall goal of MusCoDA is to develop an empirical model of collective musical creativity and learning and an instructional design for teaching music in the postdigital age.

Keywords: card game, collective songwriting, community of practice, network, postdigital

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Authors: AliAkbar Hafezi, Jahanbakhsh Asadi, Majid Shahbazi, Alijan Tabarraei, Nader Mansour Samaei, Hamed Sheibak, Roghaye Gharaei

Abstract:

Background: Breast cancer is the most common cancer in women. In most cancer cells, apoptosis is blocked. As for the importance of apoptosis in cancer cell death and the role of different genes in its induction or inhibition, the search for compounds that can begin the process of apoptosis in tumor cells is discussed as a new strategy in anticancer drug discovery. The aim of this study was to investigate the effect of Naringenin (NGEN) on the apoptosis in the T47D cell line of breast cancer. Materials and Methods: In this experimental study in vitro, the T47D cell line of breast cancer was selected as a sample. The cells at 24, 48, and 72 hours were treated with doses of 20, 200, and 1000 µm of Naringenin. Then, the transcription levels of the genes involved in apoptosis, including Bcl-2, Bax, Caspase 3, Caspase 8, Caspase 9, P53, PARP-1, and FAS, were assessed using Real Time-PCR. The collected data were analyzed using IBM SPSS Statistics 24.0. Results: The results showed that Naringenin at doses of 20, 200, and 1000 µm in all three times of 24, 48, and 72 hours increased the expression of Caspase 3, P53, PARP-1 and FAS and reduced the expression of Bcl-2 and increased the Bax/Bcl-2 ratio, nevertheless in none of the studied doses and times, had not a significant effect on the expression of Bax, Caspase 8 and Caspase 9. Conclusion: This study indicates that Naringenin can reduce the growth of some cancer cells and cause their deaths through increased apoptosis and decreased anti-apoptotic Bcl-2 gene expression and, resulting in the induction of apoptosis via both internal and external pathways.

Keywords: apoptosis, breast cancer, naringenin, T47D cell line

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Authors: Shalini Menon, K. Girish Kumar

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Norepinephrine (NE) is one of the naturally occurring catecholamines which act both as a neurotransmitter and a hormone. Catecholamine levels are used for the diagnosis and regulation of phaeochromocytoma, a neuroendocrine tumor of the adrenal medulla. The development of simple, rapid and cost-effective sensors for NE still remains a great challenge. Herein, a dual-channel sensor has been developed for the determination of NE. A mixture of AgNO₃, NaOH, NH₃.H₂O and cetrimonium bromide in appropriate concentrations was taken as the working solution. To the thoroughly vortexed mixture, an appropriate volume of NE solution was added. After a particular time, the fluorescence and absorbance were measured. Fluorescence measurements were made by exciting at a wavelength of 400 nm. A dual-channel optical sensor has been developed for the colorimetric as well as the fluorimetric determination of NE. Metal enhanced fluorescence property of nanoparticles forms the basis of the fluorimetric detection of this assay, whereas the appearance of brown color in the presence of NE leads to colorimetric detection. Wide linear ranges and sub-micromolar detection limits were obtained using both the techniques. Moreover, the colorimetric approach was applied for the determination of NE in synthetic blood serum and the results obtained were compared with the classic high-performance liquid chromatography (HPLC) method. Recoveries between 97% and 104% were obtained using the proposed method. Based on five replicate measurements, relative standard deviation (RSD) for NE determination in the examined synthetic blood serum was found to be 2.3%. This indicates the reliability of the proposed sensor for real sample analysis.

Keywords: norepinephrine, colorimetry, fluorescence, silver nanoparticles

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Authors: Yasser Mahmoudi, Nader Karimi

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The present work examines analytically the effect internal heat generation on temperature fields in a channel partially-filled with a porous under local thermal non-equilibrium condition. The Darcy-Brinkman model is used to represent the fluid transport through the porous material. Two fundamental models (models A and B) represent the thermal boundary conditions at the interface between the porous medium and the clear region. The governing equations of the problem are manipulated, and for each interface model, exact solutions for the solid and fluid temperature fields are developed. These solutions incorporate the porous material thickness, Biot number, fluid to solid thermal conductivity ratio Darcy number, as the non-dimensional energy terms in fluid and solid as parameters. Results show that considering any of the two models and under zero or negative heat generation (heat sink) and for any Darcy number, an increase in the porous thickness increases the amount of heat flux transferred to the porous region. The obtained results are applicable to the analysis of complex porous media incorporating internal heat generation, such as heat transfer enhancement (THE), tumor ablation in biological tissues and porous radiant burners (PRBs).

Keywords: porous media, local thermal non-equilibrium, forced convection, heat transfer, exact solution, internal heat generation

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Authors: Soujanya Pasumarthi

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Inverse docking is a relatively new technique that has been used to identify potential receptor targets of small molecules. Our docking software package MDock is well suited for such an application as it is both computationally efficient, yet simultaneously shows adequate results in binding affinity predictions and enrichment tests. As a validation study, we present the first stage results of an inverse-docking study which seeks to identify potential direct targets of PRIMA-1. PRIMA-1 is well known for its ability to restore mutant p53's tumor suppressor function, leading to apoptosis in several types of cancer cells. For this reason, we believe that potential direct targets of PRIMA-1 identified in silico should be experimentally screened for their ability to inhibitcancer cell growth. The highest-ranked human protein of our PRIMA-1 docking results is oxidosqualene cyclase (OSC), which is part of the cholesterol synthetic pathway. The results of two followup experiments which treat OSC as a possible anti-cancer target are promising. We show that both PRIMA-1 and Ro 48-8071, a known potent OSC inhibitor, significantly reduce theviability of BT-474 breast cancer cells relative to normal mammary cells. In addition, like PRIMA-1, we find that Ro 48-8071 results in increased binding of mutant p53 to DNA in BT- 474cells (which highly express p53). For the first time, Ro 48-8071 is shown as a potent agent in killing human breast cancer cells. The potential of OSC as a new target for developing anticancer therapies is worth further investigation.

Keywords: inverse docking, in silico screening, protein-ligand interactions, molecular docking

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Authors: Thitima Plejai

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The practice in the operating room has been continually performed according to standards of services; however, undesirable incidents from surgical services are found such as surgical complications in the operating room. This participation action research aimed to develop practice guidelines for surgical safety management to reduce undesirable incidents from surgical services in the operating room of Songkhla Hospital. The target population was all 84 members of the multidisciplinary team who were involved in surgical services in the operating room consisting of 28 surgeons from five branches of surgery, 27 anesthetists and nurse anesthetists, and 29 surgical nurses. The data were collected through in-depth interviews, and non-participatory observations. The research instrument was tested by three experts, and the steps of the development consisted of four cycles, each consisting of assessment, planning, practice, practice reflection, and improvement until every step is practicable. The data were validated through triangulation research method, analyzed through content analysis and statistical analysis with number and percentage. The results of the development of practice guidelines surgical safety management to reduce undesirable incidents from surgical services could be concluded as follows. 1) The multidisciplinary team in surgery participated in the needs assessment for development of practice guidelines for surgical patient safety, and agreed on adapting the WHO Surgical Safety Checklists for use. 2) The WHO Surgical Safety Checklists was implemented, and meetings were held for the multidisciplinary team in surgery and the organizational risk committee to improve the practice guidelines to make them more practicable. 3) The multidisciplinary team consisting of surgeons from five branches of surgery, anesthetists, nurse anesthetists, surgical nurses, and the organizational risk committee announced policy on safety for surgical patients; the organizational risk committee designated the Surgical Safety Checklist as an instrument for surgical patient safety. The results of the safety management found that the surgical team members who could follow 100 percent of the guidelines were: professional nurses who checked patient identity and information before taking the patient to the operating room and kept complete records of data on the patients; surgical nurses who checked readiness of the patient before surgery; nurse anesthetists who assessed readiness before administering anesthetic drugs, and confirmed correctness of the patient; and circulating perioperative nurses who gave confirmation to the surgical team after completion of the surgery. The rates of undesirable incidents (surgical complications rates) before and after the implementation of the surgical safety management were 1.60 percent and 0.66 percent, respectively. The satisfaction of the surgery-related teams towards the use of the guidelines was 89 percent. The practice guidelines for surgical safety management to reduce undesirable incidents were taken as guidelines for surgical safety that the multidisciplinary team involved in the surgical process implemented correctly and in the same direction and clearly reduced undesirable incidents in surgical patients.

Keywords: practice guidelines, surgical safety management, reduce undesirable incidents, operating Room

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Authors: Shazia Mannan, Zunera Khalid, Hammad-Ul-Mubeen

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Wingless type Mouse mammary tumor virus (MMTV) Integration site-10B (Wnt10B) is an important member of the Wnt protein family that functions as cellular messenger in paracrine manner. Aberrant Wnt10B activity is the cause of several abnormalities including cancers of breast, cervix, liver, gastric tract, esophagus, pancreas as well as physiological problems like obesity, and osteoporosis. The objective of this study was to determine the possible inhibitors against aberrant expression of Wnt10B in order to prevent and treat the physiological disorders associated with it. Wnt10B3D structure was predicted by using comparative modeling and then analyzed by PROCHECK, Verify3D, and Errat. The model having 84.54% quality value was selected and acylated to satisfy the hydrophobic nature of Wnt10B. For search of inhibitors, virtual screening was performed on Natural Products (NP) database. The compounds were filtered and ligand-based screening was performed using the antagonist for mouse Wnt-3A. This resulted in a library of 272 unique compounds having most potent drug like activities for Wnt-4. Out of the 271 molecules analyzed three small molecules ZINC35442871, ZINC85876388, and ZINC00754234 having activity against Wnt4 abbarent expression were found common through docking experiment of Wnt10B. It is concluded that the three molecules ZINC35442871, ZINC85876388, and ZINC00754234 can be considered as lead compounds for performing further drug designing experiments against aberrant Wnt expressions.

Keywords: Wnt10B inhibitors, comparative computational studies, proto-oncogene, molecular docking

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Authors: Yonghwa Lee, Yoon Suk Kim, Yongsub Yi

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This study was to confirm the effects of anti-melanogenesis and anti-inflammatory effects from Opuntia humifusa fruit and stem extracts. A potent anti-oxidant activity was shown from the leaf extract at IC50 value of 38.33±1.07 μg/mL and fruit extract at IC50 value of 40.23±2.21 μg/mL by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Also, phenolic contents were confirmed total phenolic assay by high performance liquid chromatography (HPLC). Fraction of taxifolin from leaf extract was identified using HPLC and gas chromatography/mass spectrometry. The extracts of Opuntia humifusa fruit and stem were confirmed about toxicity effect in B16 F1 by cell viability. Melanin contents were decreased. Opuntia humifusa fruit and stem extracts had a positive effect of melanin synthesis inhibition for skin whitening. In investigating the anti-inflammatory activities of Opuntia humifusa, the results of cell viability indicated that taxifolin did not show cytotoxicity on RAW264.7 cells at 500 μM of concentration. The results show that taxifolin inhibited lipopolysaccharide (LPS)-induced production of Nitrite oxide (NO). In addition, taxifolin indicated the inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) -α and interleukin (IL) -6 productions by cytokine assay and cyclooxygenase (COX)-2 expression by western blot analysis, meaning that taxifolin had a significant anti-inflammatory effect. Our results suggested that taxifolin from Opuntia humifusa has anti-melanogenesis and anti-inflammatory activities.

Keywords: anti-melanogenesis, anti-inflammatory, Opuntia humifusa, taxifolin

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