Search results for: tumor necrosis factor-related apoptosis-inducing ligand

Authors: D. Pradhan, G. Tripathy, S. Pradhan

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Objectives: Imperviousness gainst estrogen treatments is a noteworthy reason for infection backslide and mortality in estrogen receptor alpha (ERα)- positive breast diseases. Tamoxifen or estrogen withdrawal builds the reliance of breast malignancy cells on INT3 flagging. Here, we researched the commitment of Quercetin and INT3 motioning in endocrine-safe breast tumor cells. Methods: We utilized two models of endocrine treatments safe (ETR) breast tumor: Tamoxifen-safe (TamR) and long haul estrogen-denied (LTED) MCF7 cells. We assessed the transitory and intrusive limit of these cells by Transwell cells. Articulation of epithelial to mesenchymal move (EMT) controllers and in addition INT3 receptors and targets were assessed by constant PCR and western smudge investigation. Besides, we tried in-vitro hostile to Quercetin monoclonal Antibodies (mAbs) and Gamma Secretase Inhibitors (GSIs) as potential EMT inversion remedial specialists. At last, we created stable Quercetin overexpressing MCF7 cells and assessed their EMT components and reaction to Tamoxifen. Results: We found that ETR cells procured an Epithelial to Mesenchymal move (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we distinguished more elevated amount of INT3 however lower levels of INT1 and INT3 proposing a change to motioning through distinctive INT3 receptors after obtaining of resistance. Against Quercetin monoclonal antibodies and the GSI PF03084014 were powerful in obstructing the Quercetin/INT3 pivot and in part repressing the EMT process. As a consequence of this, cell relocation and attack were weakened and the immature microorganism like populace was essentially decreased. Hereditary hushing of Quercetin and INT3 prompted proportionate impacts. At long last, stable overexpression of Quercetin was adequate to make MCF7 lethargic to Tamoxifen by INT3 initiation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives intrusive conduct. Hostile to Quercetin mAbs and GSI PF03084014 lessen articulation of EMT particles decreasing cell obtrusiveness. Quercetin overexpression instigates Tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and INT3 warrants further clinical Correlation as substantial restorative methodologies in endocrine-safe breast.

Keywords: endocrine, epithelial, mesenchymal, INT3, quercetin, MCF7

Procedia PDF Downloads 291

Authors: B. Medani Amna, M. A. Elbadwi Samia, E. Amin Ahmed

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Variable plants present in nature are used by simple rural and urban people, researchers and drug manufacturers for medicinal purposes. Garad is one of the most commonly used in Sudan for both treatment and prophylaxis of infections in the respiratory, urinogenital tracts and the skin. Water exctracts from Acacia nilotica bods were used in this very experiment to test for their toxicity to Nubian goats at two dose rates under proper experimental conditions. The clinical, pathological, haematological and biological changes in Nubian goats given daily oral doses of 1 and 5 g/kg body weight of Acacia nilotica to two groups of test goats. The goats of the control group were undosed with Acacia nilotica.Other than the dose co-related mortality rates, the clinical signs were observed to be salivation, staggered gait, intermittent loss of voice and low appetite. On histopathological testing, the main lesions were hepatic centrolobular necrosis and fatty changes associated with the significant changes in GGT and ALP are indicating hepatic dysfunction.Renal malfunction is indicated by haemorrhages in addition to the change in the urea concentration. The congested, haemorrhagic, emphysematous, edematous and cyanotic lungs may contribute to the development of dyspnea. Acacia nilotica poisoning may lead to an immunosuppression pointed out by the lymphocyte infiltration. On evaluation of the above results, Acacia nilotica was considered toxic to Nubian goats at the above mentioned doses. Future work for Acacia nilotica was forwarded and practical implications of the result were highlighted.

Keywords: Acaia nilotica, toxicity data, Nubian goats, Garad

Procedia PDF Downloads 443

Authors: Angelis P. Barlampas

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PURPOSE: The purpose of this paper is to demonstrate the important role of taking an appropriate and detailed history, in order to reach the best possible diagnostic conclusion. MATERIAL: A patient presented to the emergency department due to the sudden onset of continuous abdominal pain, during the last hour and with the clinical symptoms of an acute abdomen. During the clinical examination, signs of peritoneal irritation and diffuse abdominal tenderness were found. The rest of the clinical and laboratory tests did not reveal anything important. From the reported medical history, nothing of note was found, except for the report of a large liver cyst, for which he was advised not to take any further action, except from regular ultrasound examination . METHOD: A computed tomography examination was performed after per os administration of gastrografin, which revealed a hyperdense ascitic effusion, similar in density to that of gastrografin within the intestinal tract. The presence of a large cyst of the left hepatic lobe was confirmed, contacting and pushing against the stomach. In the area of the contact between the liver cyst and the pylorus, there were extraluminal air bubbles and local opacity of the peritoneal fat, with a small hyperdense effusion. Result : The above, as well as the absence of a history of stomach ulcer or recent trauma, or other pathology, argue in favor of acute pyloric perforation, due to mural necrosis, in response to chronic external pressure from the pre-existing large liver cyst.

Keywords: perforation, stomach, large liver cyst, CT abdomen, acute abdominal pain, intraperitoneal leakage, constrast leakage

Procedia PDF Downloads 74

Authors: Azzam H., Abousamra N. K., Wafa A. A., Hafez M. M., El-Gilany A. H.

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Platelet activation occurs in peripheral blood of patients with rheumatic mitral stenosis (MS) and atrial fibrillation (AF) and could be related to abnormal thrombogenesis. The CD40/CD40 ligand (CD40L) which reflects platelet activation, mediate a central role in thrombotic diseases. However, the role of CD40/CD40L system in rheumatic MS with or without AF remains unclear. Expressions of CD40 on monocytes and CD40L on platelets were determined by whole blood flow cytometry and serum levels of soluble CD40L were measured by enzyme-linked immunosorbent assay in group 1 (19 patients with MS) and group 2 (20 patients with MS and AF) compared to group 3 (10 controls). Patients with groups 1 and 2 had a significant increase in expression of CD40 on monocytes (P1 and P2 = 0.000) and serum levels of sCD40L (P1 = 0.014 and P2 = 0.033, respectively), but nonsignificant increase in expression of CD40L on platelets (P1 = 0.109 and P2 = 0.060, respectively) as compared to controls. There were no significant difference in all the parameters in group 1 compared to group 2. Correlation analysis demonstrated that there was a significant direct relationship between the severity of MS and serum levels of sCD40L (r = -0.469, p = 0.043). In conclusion, rheumatic MS patients with or without AF had upregulation of the CD40/CD40L system as well as elevated sCD40L levels. The levels of sCD40L had a significantly direct relationship with the severity of MS and it was the stenotic mitral valve, not AF, that had a significant impact on platelet activation.

Keywords: CD40, CD40L, mitral stenosis, atrial fibrillation

Procedia PDF Downloads 75

Authors: Cahit Demetgul, Sahin Bayraktar, Neslihan Beyazit

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Metalloenzymes are enzyme proteins containing metal ions, which are directly bound to the protein or to enzyme-bound nonprotein components. One of the major metalloenzymes that play a key role in oxidation reactions is catechol oxidase, which shows catecholase activity i.e. oxidation of a broad range of catechols to quinones through the four-electron reduction of molecular oxygen to water. Studies on the model compounds mimicking the catecholase activity are very useful and promising for the development of new, more efficient bioinspired catalysts, for in vitro oxidation reactions. In this study, a new tetradentate asymmetrical Schiff-base and its Cu(II) complex were synthesized by condensation of 4-nitro-1,2-phenylenediamine with 6-formyl-7-hydroxy-5-methoxy-2-methylbenzopyran-4-one and by using an appropriate Cu(II) salt, respectively. The prepared compounds were characterized by elemental analysis, FT-IR, NMR, UV-Vis and magnetic susceptibility. The catecholase-mimicking activity of the new Schiff Base Cu(II) complex was performed for the oxidation of 3,5-di-tert-butylcatechol (3,5-DTBC) in methanol at 25 °C, where the electronic spectra were recorded at different time intervals. The yield of the quinone (3,5-DTBQ) was determined from the measured absorbance at 400 nm of the resulting solution. The compatibility of catalytic reaction with Michaelis-Menten kinetics was also investigated. In conclusion, we have found that our new Schiff Base Cu(II) complex presents a significant capacity to catalyze the oxidation reaction of the catechol to o-quinone.

Keywords: catecholase activity, Michaelis-Menten kinetics, Schiff base, transition metals

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Authors: Qian Zhao

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With global increasing demand for phosphorus and intensively depleting reserves, it is urgent need to explore innovative approaches towards capturing phosphate from sewage, which is also an effective way to reduce phosphate contamination and avoid eutrophication of water bodies. In the present article, the superparamagnetic nano-sorbents containing Fe₃O₄ core and hafnium-modified MgAl/MgFe layered double hydroxides shell (abbreviated as MgAlHf-NP and MgFeHf-NP) was developed using a simple and low-cost synthesis protocol. The obtained Hf-coated nano-materials showed well-defined crystal structure and sufficient saturation magnetization and exhibited higher adsorption capacity for phosphate. Meanwhile, high selectivity was also confirmed since coexisting foreign anions and biomacromolecules showed little competitive effect on phosphate adsorption. The enhancement via doping with Hf should be explained by the stronger ligand complexation built by the pair of hard acid Hf ion and hard base phosphate that matched up the bonding preferences. Sufficient OH⁻ concentration and clear pH shift during the desorption/regeneration allowed for regeneration rate of higher than 90% after 5 cycles of adsorption desorption. This article attempts to provide a competitive candidate for phosphate-capture, which is highly effective, easily separable and repeatedly usable.

Keywords: phosphate recovery, nanoparticles, superparamagnetic, adsorption, reusability

Procedia PDF Downloads 123

Authors: S. Woźniak, J. Rybka, T. Paszkowski, P. Milart

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A 30-year-old patient, who was pregnant for her second 9 weeks, was admitted to the hospital due to a suspected incomplete miscarriage. A fetal egg was found in the uterine cavity near the mouth of the fallopian tube. The patient was qualified for dilatation and curettage. The histopathological examination revealed fragments of the trophoblast. Two months later, the patient was re-admitted to the hospital due to vaginal bleeding and elevated levels of beta-hCG. Additional tests were performed. An intramural pregnancy was suspected. The patient was qualified for embolization of the uterine arteries and then treatment with methotrexate. Three weeks later, during a routine gynecological examination, a detached tumor 4 cm in diameter was found in the vagina. The material was sent for histopathological examination, which showed the presence of trophoblastic cells.

Keywords: ectopic pregnancy, intramural pregnancy, uterine artery embolization, methotrexate

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Authors: Vinai K. Singh

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In Neural Network-based Learning techniques, there are several models of Convolutional Networks. Whenever the methods are deployed with large datasets, only then can their applicability and appropriateness be determined. Clinical and pathological pictures of lobular carcinoma are thought to exhibit a large number of random formations and textures. Working with such pictures is a difficult problem in machine learning. Focusing on wet laboratories and following the outcomes, numerous studies have been published with fresh commentaries in the investigation. In this research, we provide a framework that can operate effectively on raw photos of various resolutions while easing the issues caused by the existence of patterns and texturing. The suggested approach produces very good findings that may be used to make decisions in the diagnosis of cancer.

Keywords: lobular carcinoma, convolutional neural networks (CNN), deep learning, histopathological imagery scans

Procedia PDF Downloads 114

Authors: Trevor E. Davis, Isaac Cassar, Yi-Kai Lo, Wentai Liu

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This study models the use of transcutaneous electrical nerve stimulation on skin with a disk electrode in order to simulate tissue damage. The current density distribution above a disk electrode is known to be a dynamic and non-uniform quantity that is intensified at the edges of the disk. The non-uniformity is subject to change through using various electrode geometries or stimulation methods. One of these methods known as edge-retarded stimulation has shown to reduce this edge enhancement. Though progress has been made in modeling the behavior of a disk electrode, little has been done to test the validity of these models in simulating the actual heat transfer from the electrode. This simulation uses finite element software to couple the injection of current from a disk electrode to heat transfer described by the Pennesbioheat transfer equation. An example application of this model is studying an experimental form of stimulation, known as edge-retarded stimulation. The edge-retarded stimulation method will reduce the current density at the edges of the electrode. It is hypothesized that reducing the current density edge enhancement effect will, in turn, reduce temperature change and tissue damage at the edges of these electrodes. This study tests this hypothesis as a demonstration of the capabilities of this model. The edge-retarded stimulation proved to be safer after this simulation. It is shown that temperature change and the fraction of tissue necrosis is much greater in the square wave stimulation. These results bring implications for changes of procedures in transcutaneous electrical nerve stimulation and transcutaneous spinal cord stimulation as well.

Keywords: bioheat transfer, electrode, neuroprosthetics, TENS, transcutaneous stimulation

Procedia PDF Downloads 216

Authors: Zohar Manber, Ran Elkon

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Accumulation of somatic mutations (SMs) in the genome is a major driving force of cancer development. Most SMs in the tumor's genome are functionally neutral; however, some cause damage to critical processes and provide the tumor with a selective growth advantage (termed cancer driver mutations). Current research on functional significance of SMs is mainly focused on finding alterations in protein coding sequences. However, the exome comprises only 3% of the human genome, and thus, SMs in the noncoding genome significantly outnumber those that map to protein-coding regions. Although our understanding of noncoding driver SMs is very rudimentary, it is likely that disruption of regulatory elements in the genome is an important, yet largely underexplored mechanism by which somatic mutations contribute to cancer development. The expression of most human genes is controlled by multiple enhancers, and therefore, it is conceivable that regulatory SMs are distributed across different enhancers of the same target gene. Yet, to date, most statistical searches for regulatory SMs have considered each regulatory element individually, which may reduce statistical power. The first challenge in considering the cumulative activity of all the enhancers of a gene as a single unit is to map enhancers to their target promoters. Such mapping defines for each gene its set of regulating enhancers (termed "set of regulatory elements" (SRE)). Considering multiple enhancers of each gene as one unit holds great promise for enhancing the identification of driver regulatory SMs. However, the success of this approach is greatly dependent on the availability of comprehensive and accurate enhancer-promoter (E-P) maps. To date, the discovery of driver regulatory SMs has been hindered by insufficient sample sizes and statistical analyses that often considered each regulatory element separately. In this study, we analyzed more than 2,500 whole-genome sequence (WGS) samples provided by The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) in order to identify such driver regulatory SMs. Our analyses took into account the combinatorial aspect of gene regulation by considering all the enhancers that control the same target gene as one unit, based on E-P maps from three genomics resources. The identification of candidate driver noncoding SMs is based on their recurrence. We searched for SREs of genes that are "hotspots" for SMs (that is, they accumulate SMs at a significantly elevated rate). To test the statistical significance of recurrence of SMs within a gene's SRE, we used both global and local background mutation rates. Using this approach, we detected - in seven different cancer types - numerous "hotspots" for SMs. To support the functional significance of these recurrent noncoding SMs, we further examined their association with the expression level of their target gene (using gene expression data provided by the ICGC and TCGA for samples that were also analyzed by WGS).

Keywords: cancer genomics, enhancers, noncoding genome, regulatory elements

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Authors: Karthikeyan M., Paul M. J.

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This abstract describes a case of central pancreatectomy (CP) for a 50-year-old woman with a neuroendocrine tumor in the mid-body of the pancreas. CP, a parenchyma-sparing surgical option, preserves the distal pancreas and spleen, reducing the risk of pancreatic endocrine and exocrine insufficiency compared to traditional resections. The patient, initially misdiagnosed with transient ischemic attack, presented with hypoglycemic symptoms and was found to have a pancreatic lesion. Post-operative results were positive, with a reduction in pancreatic drain volume and normalization of blood sugar levels. This case highlights CP's efficacy in treating centrally located pancreatic lesions while maintaining pancreatic function.

Keywords: central pancreatectomy without anastomosis, no endocrine deficiency on follow-op, less post-op hospital stay, less post-op complications

Procedia PDF Downloads 27

Authors: Sandeep Mohindra

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Since 2013, the authors have operated on 568 cases of pituitary tumors through the trans-sphenoidal route, using the binostril approach. The distribution included 486 cases of non-functioning pituitary tumors, 24 cases of Growth hormone(GH) secreting tumors(acromegaly), and 28 cases of adrenocorticotrophic(ACTH) secreting tumors(Cushing's Disease). The authors utilized neuro-navigation for 18 cases, and all belonged to the functional tumor category. Complications included ICA injury in 2 cases, fatal meningitis in 5 cases, while CSF leak required repair in 28 cases. Satisfactory excision was noted in 512 cases, while recurrence/residual required repeat surgery in 32 cases. Authors conclude that trans sphenoidal route remains the best and optimal way of managing sellar tumors, especially pituitary adenomas.

Keywords: pituitary, adenoma, trans-sphenoidal, endonasal, neuronavigation

Procedia PDF Downloads 43

Authors: Amina Ben Abla, Sylvie Changotade, Geraldine Rohman, Guilhem Boeuf, Cyrine Dridi, Ahmed Elmarjou, Florence Dufour, Didier Lutomski, Abdellatif Elm’semi

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Understanding cell adhesion and interaction with the extracellular matrix is essential for biomedical and biotechnological applications, including the development of biomaterials. In recent years, numerous biomaterials have emerged and were used in the field of tissue engineering. Nevertheless, the lack of interaction of biomaterials with cells still limits their bio-integration. Thus, the design of bioactive biomaterials to improve cell attachment and proliferation is of growing interest. In this study, bio-functionalized material was developed combining a synthetic polymer scaffold surface with selected domains of type III human fibronectin (FNIII-DOM) to promote cell adhesion and proliferation. Bioadhesive ligand includes cell-binding domains of human fibronectin, a major ECM protein that interacts with a variety of integrins cell-surface receptors, and ECM proteins through specific binding domains were engineered. FNIII-DOM was produced in bacterial system E. coli in 5L fermentor with a high yield level reaching 20mg/L. Bioactivity of the produced fragment was validated by studying cellular adhesion of human cells. The adsorption and immobilization of FNIII-DOM onto the polymer scaffold were evaluated in order to develop an innovative biomaterial.

Keywords: biomaterials, cellular adhesion, fibronectin, tissue engineering

Procedia PDF Downloads 127

Authors: Fereydoon Bondarian, Samira Shaygan

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Today, many nutritionists recommend the consumption of plants, fruits, and vegetables to provide the antioxidants needed by the body because the use of plant antioxidants usually causes fewer side effects and better treatment. Natural antioxidants increase the power of plasma antioxidants and reduce the incidence of some diseases, such as cancer. Bad lifestyles and environmental factors play an important role in increasing the incidence of cancer. In this study, different extracts of white teas taken from two types of tea available in Iran (clone 100 and Chinese hybrid) due to the presence of a hydroxyl functional group in their structure to inhibit free radicals and anticancer properties, using 3 aqueous, methanolic and aqueous-methanolic methods were used. The total polyphenolic content was calculated using the Folin-Ciocalcu method, and the percentage of inhibition and trapping of free radicals in each of the extracts was calculated using the DPPH method. With the help of high-performance liquid chromatography, a small amount of each catechin in the tea samples was obtained. Clone 100 white tea was found to be the best sample of tea in terms of all the examined attributes (total polyphenol content, antioxidant properties, and individual amount of each catechin). The results showed that aqueous and aqueous-methanolic extracts of Clone 100 white tea have the highest total polyphenol content with 27.59±0.08 and 36.67±0.54 (equivalent gallic acid per gram dry weight of leaves), respectively. Due to having the highest level of different groups of catechin compounds, these extracts have the highest property of inhibiting and trapping free radicals with 66.61±0.27 and 71.74±0.27% (mg/l) of the extracted sample against ascorbic acid). Using the MTT test, the inhibitory effect of clone 100 white tea extract in inhibiting the growth of HCT-116 colon cancer cells was investigated and the best time and concentration treatments were 500, 150 and 1000 micrograms in 8, 16 and 24 hours, respectively. To investigate gene expression changes, selected genes, including tumorigenic genes, proto-oncogenes, tumor suppressors, and genes involved in apoptosis, were selected and analyzed using the real-time PCR method and in the presence of concentrations obtained for white tea. White tea extract at a concentration of 1000 μg/ml 3 times 16, 8, and 24 hours showed the highest growth inhibition in cancer cells with 53.27, 55.8, and 86.06%. The concentration of 1000 μg/ml aqueous extract of white tea under 24-hour treatment increased the expression of tumor suppressor genes compared to the normal sample.

Keywords: catechin, gene expression, suppressor genes, colon cell line

Procedia PDF Downloads 37

Authors: Milica Karadzic, Lidija Jevric, Sanja Podunavac-Kuzmanovic, Strahinja Kovacevic, Sinisa Markov, Aleksandar Okljesa, Andrea Nikolic, Marija Sakac, Katarina Penov Gasi

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This study considered the microbiological activity determination and molecular docking study for selected steroid derivatives of biomedical importance. Minimal inhibitory concentration (MIC) was determined for steroid derivatives against Staphylococcus aureus using macrodilution method. Some of the investigated steroid derivatives express bacteriostatic effect against Staphylococcus aureus. Molecular docking approaches are the most widely used techniques for predicting the binding mode of a ligand. Molecular docking study was done for steroid derivatives for androgen receptor negative prostate cancer cell line (PC-3) toward Human Cytochrome P450 CYP17A1. The molecules that had the smallest experimental IC50 values confirmed their ability to dock into active place using suitable molecular docking procedure. The binding disposition of those molecules was thoroughly investigated. Microbiological analysis and molecular docking study were conducted with aim to additionally characterize selected steroid derivatives for future investigation regarding their biological activity and to estimate the binding-affinities of investigated derivatives. This article is based upon work from COST Action (TD1305), supported by COST (European Cooperation and Science and Technology).

Keywords: binding affinity, minimal inhibitory concentration, molecular docking, pc-3 cell line, staphylococcus aureus, steroids

Procedia PDF Downloads 345

Authors: Samar Rabah

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Background: Incense woods are special kind of trees called Agarwood, which characterized by good smelling odors and many medical benefits. Incense smoke is heavily used in Saudi Arabia although comprehensive studies of its effects on health are limited. The present study demonstrated lung ultrastructure changes of mice after exposure and cessation to Incense smoke. Eighty mice are divided equally into four groups, three groups are exposed to different concentrations of Incense smoke (2, 4 and 6 gm) for three months, while the fourth group is control one. At the end of each month, lungs of five animals from each group are gathered, while the last five animals from each group are kept for another 60 days without exposure to the Incense smoke to allow for recovery. Results: Transmission electron microscope investigations of all exposed groups showed hypertrophy and hyperplasia in Clara Cells and some an enlargement of the macrophage to the point that it fills a large part of the alveolar lumen. Scanning electron microscope marks presence of mucus materials attached to the epithelial bronchioles. After prevention of exposure to the Incense smoke for 60 days, necrosis and degeneration in some cells of epithelial bronchioles, fibrosis of peribronchial, thickening in alveolar walls and aggregation of lymphoid cells were demonstrated. Conclusion: Based on the above findings and other related studies (not published), we conclude that exposure to Incense smoke causes harmful effects due to sever changes in pulmonary ultrastructure, such effects do not disappear even when Incense smoke inhalation was stopped. Therefore, we recommend that Incense smoke should use only in open places to reduce its harms.

Keywords: Incense smoke, lungs, ultrastructure of lungs, Agarwood

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Authors: Ilya B. Tsyrlov, Dmitry Y. Oshchepkov

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A computational search for dioxin response elements (DREs) in genes of proteins comprising the Ah receptor (AhR) cytosolic core complex was performed by highly efficient tool SITECON. Eventually, the following number of new DREs in 5’flanking region was detected by SITECON: one in AHR gene, five in XAP2, eight in HSP90AA1, and three in HSP90AB1 genes. Numerous DREs found in genes of AhR and AhR cytosolic complex members would shed a light on potential mechanisms of expression, the stoichiometry of unliganded AhR core complex, and its degradation vs biosynthesis dynamics resulted from treatment of target cells with the AhR most potent ligand, 2,3,7,8-TCDD. With human viruses, reduced susceptibility to TCDD of geneencoding HIV-1 P247 was justified by the only potential DRE determined in gag gene encoding HIV-1 P24 protein, whereas the regulatory region of CMV genes encoding IE gp/UL37 has five potent DRE, 1.65 kb/UL36 – six DRE, pp65 and pp71 – each has seven DRE, and pp150 – ten DRE. Also, from six to eight DRE were determined with SITECON in the regulatory region of HSV-1 IE genes encoding tegument proteins, UL36 and UL37, and of UL19 gene encoding bindingglycoprotein C (gC). So, TCDD in the low picomolar range may activate in human cells AhR: Arnt transcription pathway that triggers CMV and HSV-1 reactivation by binding to numerous promoter DRE within immediate-early (IE) genes UL37 and UL36, thus committing virus to the lytic cycle.

Keywords: dioxin response elements, Ah receptor, AhR: Arnt transcription pathway, human and viral genes

Procedia PDF Downloads 91

Authors: Le Nguyen Binh, Luong Xuan Binh, Le Van Tuan, Tran Binh Duong, Truong Nguyen Khanh Hung, Do Le Hoang Son, Pham Quang Vinh, Hoang Quoc Huy, Nguyen Bach, Nguyen Quoc Khanh Le, Jiunn Horng Kang

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Introduction: Traumatic hip dislocation is an emergency in young adult which can cause avascular necrosis of femoral head or osteoarthritis of hip joint. The reasons for these may be the loose body of bony or chondral fragments, which are difficult to be detected on CT scan or MRI. In those cases, Hip arthroscopy may be the method of choice for diagnosis and treatment of loose bodies in hip joint after traumatic dislocation. Methods: A case report is performed. A 55-year-old male patient was under hip arthroscopy to retrieve the loose body in the right hip joint. Results: The patient’s hip was reduced under anesthesia in the opeation room. Xray and CT scan post-reduction showed that his right hip was wide and a small fragment of femoral head (< 5mm) locking inside the joint. A hip arthroscopy was done to take the fragment out. Post-operation, the patient went under rehabilition. After 6 months, he can walk with full-weight bearing; no further dislocaion was noted, and the Harris score was 84 points. Conclusions: Although acute traumatic injury of hip joint is usually treated with open surgeries, these methods have many drawbacks, such as soft tissue destruction, blood-loss,….Despite its technical requirement, hip arthroscopy is less invasive and effective treatment. Therefore, it may be an alternative treatment for a traumatic hip injury and can be applied frequently in the near future.

Keywords: hip dislocation, hip arthroscopy, hip osteoarthritis, acute hip trauma

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Authors: Iulianna Taritsa, Kuldeep Neote, Eric Fossel

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Lysosome-induced immunogenic cell death (LIICD) is a powerful mechanism of targeting cancer cells that kills circulating malignant cells and primes the host’s immune cells against future remission. Current immunotherapies for cancer are limited in preventing recurrence – a gap that can be bridged by training the immune system to recognize cancer neoantigens. Lysosomal leakage can be induced therapeutically to traffic antigens from dying cells to dendritic cells, which can later present those tumorigenic antigens to T cells. Previous research has shown that oxidative agents administered in the tumor microenvironment can initiate LIICD. We generated a fusion protein between an oxidative agent known as xanthine oxidase (XO) and a mini-antibody specific for EGFR/HER2-sensitive breast tumor cells. The anti-EGFR single domain antibody fragment is uniquely sourced from llama, which is functional without the presence of a light chain. These llama micro-antibodies have been shown to be better able to penetrate tissues and have improved physicochemical stability as compared to traditional monoclonal antibodies. We demonstrate that the fusion protein created is stable and can induce early markers of immunogenic cell death in an in vitro human breast cancer cell line (SkBr3). Specifically, we measured overall cell death, as well as surface-expressed calreticulin, extracellular ATP release, and HMGB1 production. These markers are consensus indicators of ICD. Flow cytometry, luminescence assays, and ELISA were used respectively to quantify biomarker levels between treated versus untreated cells. We also included a positive control group of SkBr3 cells dosed with doxorubicin (a known inducer of LIICD) and a negative control dosed with cisplatin (a known inducer of cell death, but not of the immunogenic variety). We looked at each marker at various time points after cancer cells were treated with the XO/antibody fusion protein, doxorubicin, and cisplatin. Upregulated biomarkers after treatment with the fusion protein indicate an immunogenic response. We thus show the potential for this fusion protein to induce an anticancer effect paired with an adaptive immune response against EGFR/HER2+ cells. Our research in human cell lines here provides evidence for the success of the same therapeutic method for patients and serves as the gateway to developing a new treatment approach against breast cancer.

Keywords: apoptosis, breast cancer, immunogenic cell death, lysosome

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Authors: Lu Yang, Keng Po Lai

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Metformin, a well-known clinical drug against diabetes, is found with potential anti-diabetic and anti-obese benefits, as reported in increasing evidences. However, the current clinical and experimental investigations are not to reveal the detailed mechanisms of metformin-anti-obesity/hypertension. We have used the bioinformatics strategy, including network pharmacology and molecular docking methodology, to uncover the key targets and pathways of bioactive compounds against clinical disorders, such as cancers, coronavirus disease. Thus, in this report, the in-silico approach was utilized to identify the hug targets, pharmacological function, and mechanism of metformin against obesity and hypertension. The networking analysis identified 154 differentially expressed genes of obesity and hypertension, 21 interaction genes, and 6 hug genes of metformin treating hypertensive obesity. As a result, the molecular docking findings indicated the potent binding capability of metformin with the key proteins, including interleukin 6 (IL-6) and chemokine (C-C motif) Ligand 2 (CCL2), in hypertensive obesity. The metformin-exerted anti-hypertensive obesity action involved in metabolic regulation, inflammatory reaction. And the anti-hypertensive obesity mechanisms of metformin were revealed, including regulation of inflammatory and immunological signaling pathways for metabolic homeostasis in tissue and microenvironmental melioration in blood pressure. In conclusion, our identified findings with bioinformatics analysis have demonstrated the detailed hug and pharmacological targets, biological functions, and signaling pathways of metformin treating hypertensive obesity.

Keywords: metformin, obesity, hypertension, bioinformatics findings

Procedia PDF Downloads 102

Authors: Nidhi Chadha, A. K. Tiwari, Marilyn D. Milton, Anil K. Mishra

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Translocator protein (18 kDa) TSPO is highly expressed during microglia activation in neuroinflammation. Although a number of PET ligands have been developed for the visualization of activated microglia, one of the advantageous approaches is to develop potential optical imaging (OI) probe. Our study involves computational screening, synthesis and evaluation of TSPO ligand through various imaging modalities namely PET/SPECT/Optical. The initial computational screening involves pharmacophore modeling from the library designing having oxo-benzooxazol-3-yl-N-phenyl-acetamide groups and synthesis for visualization of efficacy of these compounds as multimodal imaging probes. Structure modeling of monomer, Ala147Thr mutated, parallel and anti-parallel TSPO dimers was performed and docking analysis was performed for distinct binding sites. Computational analysis showed pattern of variable binding profile of known diagnostic ligands and NBMP via interactions with conserved residues along with TSPO’s natural polymorphism of Ala147→Thr, which showed alteration in the binding affinity due to considerable changes in tertiary structure. Preliminary in vitro binding studies shows binding affinity in the range of 1-5 nm and selectivity was also certified by blocking studies. In summary, this skeleton was found to be potential probe for TSPO imaging due to ease in synthesis, appropriate lipophilicity and reach to specific region of brain.

Keywords: TSPO, molecular modeling, imaging, docking

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Authors: M. R. Haji Hajikolaei, A. A. Nikvand, A. R. Ghadrdan, M. Ghorbanpoor, B. Mohammadian

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This study was carried out on water buffalo for detection of Leptospira interrogans in kidney and urine and its relationship with serological findings. Blood, urine and kidney samples were taken immediately after slaughter from 353 water buffalos at Ahvaz abattoir in Khouzestan province, Iran. Sera were initially screened at serum dilution of 1:100 against seven live antigens of Leptospira interrogans: pomona, hardjo, ballum, icterohemorrhagiae, tarasovi, australis and grippotyphosa using the microscopic agglutination test (MAT) and sera with positive results were titrated against reacting antigens in serial twofold dilution from 1:100 to 1:800. The samples of kidney were embedded in paraffin wax and 5µm thick sections were stained routinely with Haematoxylin and Eosin (H&E). Polymerase chain reaction (PCR) examination was done on urine and kidney by using LipL32 gene primers. Antibodies against one or more serovars at dilution >:100 were detected in sera. The most frequent reactor was hardjo (56.2%), followed by pomona (52.3%), australis (9.8%), tarassovi (5.9%), grippotyphosa (4.5%) and icterohaemorrhagiae (3.9%). The L. interrogans were detected in 43 (12.2%) of examined buffaloes, so that 26 (8.2%) of kidney tissues, 14 (4.8%) of urine samples separately and 3 (0.84%) of both kidney and urine samples were positive in PCR. From 153 (43.3%) buffaloes with positive MAT, 24 cases were positive by PCR of kidney and/or urine samples, synchronously. Renal lesions such as interstitial nephritis, acute tubular necrosis (ATN), pyelonephritis, glomerolonephritis, renal fibrosis and hydronephrosis were found in 128 (36.3%) cases. Statistical analysis indicated that there was no significant association between results of MAT, PCR and interstitial nephritis.

Keywords: leptospiral infection, PCR, MAT, histopathology, river buffalo

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Authors: Frazer Kirk, Matthew Yong, Peter Williams, Andrie Strobel

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Pulmonary valve papillary fibroelastoma is an exceedingly rare pathology. The experience and literature regarding them are largely anecdotal and based on sporadic, single case reports. Throughout their known history, two features remain salient that they are classically asymptomatic and found incidentally. The demographic profile of those affected is unclear, as reports regarding those affected are mixed, and there is no clear gender or age predominance, although there is some suggestion of a predisposition to affect females. Nor has there been a well-structured epidemiological study of the entity. Interestingly they are becoming more common on peri-mortum examination. Here-after we describe our experience with a symptomatic presentation of pulmonary papillary fibroelastoma masquerading as a pulmonary embolism and its subsequent assessment and management, with intraoperative photography and echocardiography for reference.

Keywords: cardiac tumor, pulmonary valve, fibroelastoma, cardiac surgery

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Authors: Mohamed F. Ahmed, Mabruka S. Elashheb, Fatma M. Ben Rabha

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This study aimed to determine the possible protective effects of L‐carnitine against gentamicin‐induced nephrotoxicity. Forty male albino rats were divided into 4 groups (10 rats each); Group 1: normal control, group 2: induced nephrotoxicity (gentamicin 50 mg/kg/day S.C; 8 days) , group 3: treated with L‐carnitine (40 mg/kg/d SC for 12 days) and group 4: treated with L‐carnitine 4 days before and for 8 days in concomitant with gentamicin. Gentamicin‐induced nephrotoxicity (group 2): caused significant increase in serum urea, creatinine, urinary N‐acetyl‐B‐D‐glucosaminidase (NAG), gamma glutamyl transpeptidase (GGT), urinary total protein and kidney tissue malondialdehyde (MDA) with significant decrease in serum superoxide dismutase (SOD), serum catalase and creatinine clearance and marked tubular necrosis in the proximal convoluted tubules with interruption in the basement membrane around the necrotic tubule compared to the normal control group. L‐carnitine 4 days before and for 8 days in concomitant with gentamicin (group 4) offered marked decrease in serum urea, serum creatinine, urinary NAG, urinary GGT, urinary proteins and kidney tissue MDA, with marked increase in serum SOD, serum catalase and creatinine clearance with marked improvement in the tubular damage compared to gentamicin‐induced nephrotoxicity group. L‐carnitine administered for 12 days produced no change in the above-mentioned parameters as compared to the normal control group. In conclusion: L‐carnitine could reduce most of the biochemical parameters and also improve the histopathological features of the kidney associated with gentamicin-induced nephrotoxicity.

Keywords: gentamicin, nephrotoxicity, L‐carnitine, kidney disease

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Authors: S. Bahrami, A. Rezaie, Z. Boroumand, S. Ghavami

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Neospora caninum is protozoan parasite which can cause a serious disease in dogs and cattle. It has been shown that birds may be a permissive intermediate host for N. caninum since parasite DNA has been detected in tissues from birds. It is showed that embryonated chicken egg can be used as an animal model for experimental infection. The aim of present study was to compare experimental infection of Neospora in chicken and pigeons embryonated eggs. An infection with N. caninum Nc1 isolate was conducted in chicken and pigeons embryonated eggs to evaluate LD50. After calculation of LD50, 2LD50 of tachyzoites were injected to eggs. Macroscopic changes of each embryo were noticed and to investigate the parasite distribution in tissues immunohistochemistry (IHC) and molecular methods were used. In the present study, histopathological changes were considered and sections to those used for histopathological examination including heart, liver, brain and chorioallantoic (CA) membrane were subjected to IHC, too. For PCR procedure, primer pair Np21/Np6 was used for amplification of the Nc5 gene. Pigeon's embryo showed more macroscopic changes than chicken embryo. A hemorrhage of the CA was the main grass lesion. All the infected tissues had histopathological changes. Microscopic examination of tissues revealed acute neosporosis due to hemorrhage, necrosis and infiltration of mononuclear inflammatory cells. Based on IHC and molecular results, the parasite aggregation in the heart was more predominant than in the other tissues. These results reinforce that there is genetic susceptibility to N. caninum in pigeons embryonated eggs like chickens embryonated eggs and provide new insights to research an inexpensive and available animal model for N. caninum.

Keywords: immunohistochemistry, Neospora caninum, PCR, pigeon embryonated egg

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Authors: S. A. Nirmal, J. M. Ingale, G. S. Asane, S. C. Pal, Subhash C. Mandal

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The present work was undertaken to determine the effects of Amaranthus roxburghianus Nevski. (Amaranthaceae) root alone and in combination with piperine in treating ulcerative colitis (UC) in mice. Swiss albino mice were divided into seven groups (n = 6). Standard group received prednisolone (5 mg/kg, i.p.). Treatment groups received hydroalcoholic extract of roots of A. roxburghianus (50 and 100 mg/kg, p.o.) and a combination of hydroalcoholic extract of roots of A. roxburghianus (50 and 100 mg/kg, p.o.) and piperine (5 mg/kg, p.o.). Ulcer index, colitis severity, myeloperoxidase (MPO), malondialdehyde and glutathione were estimated from blood and tissue. Column chromatography of the extract was done and purified fractions were analyzed by gas chromatography-mass spectroscopy (GC-MS). Treatment with the combination of hydroalcoholic extract of A. roxburghianus and piperine showed minimal ulceration, hemorrhage, necrosis and leucocyte infiltration by histopathological observation. Acetic acid increased MPO levels in blood and colon tissue to 355 U/mL and 385 U/mg, respectively. The combination of hydroalcoholic extract (100 mg/kg) and piperine (5 mg/kg) significantly decreased MPO in blood and tissue to 182 U/mL and 193 U/mg, respectively. Similarly, this combination significantly reduced MPO and increased glutathione levels in blood and tissue. Various phytoconstituents were detected by GC-MS. The combination of hydroalcoholic extract and piperine is effective in the treatment of UC and the effects are comparable with the standard drug prednisolone. 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl, eugenol and benzene, and 1-(1,5-dimethyl-4-hexenyl)-4-methyl are reported having analgesic, anti-inflammatory, and antioxidant properties; they may play a role in the biological activity of A. roxburghianus root.

Keywords: Amaranthus roxburghianus, ulcerative colitis, anti-inflammatory, ulcerative colitis

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Authors: Nitin Dwivedi, Jigna Shah

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Aim and objective of study: This article indicates a comparison among various generations of dendrimers, a dendrimer is a bioactive material has repetitively branched molecule and used for delivery of various therapeutic active agents. This debut report compares the effect various generations of PPI dendrimers for brain targeting and management of neurodegenerative disorders potential on single platform. This report involves the study of the various mechanism of synthesis ligand anchored various generations PPI dendrimers deliver the drug directly to the CNS, prove their effectiveness in the management of the various neurodegenerative disease. Material and Methods: The Memantine an anti-Alzheimer drug loaded in different generations (3.0G, 4.0G, and 5.0G) of PPI dendrimers which were synthesized were synthesized. The various studies investigate the effect of PPI dendrimers generation on different characteristic parameters i.e. synthesis procedure, drug loading, release behavior, hemolysis profile at different concentration, MRI study for determine the route drug from olfactory transfer, animal model study in vitro, as well as in vivo performance. The outcomes of the investigation indicate drug delivery benefit as well as superior biocompatibility of 4.0G PPI dendrimer over 3.0G and 5.0G dendrimer, respectively. Results and Conclusion: The above study indicate the superiority of in drug delivery system with maximum drug utilization and minimize the drug dose for neurodegenerative disorder over 5.0G PPI dendrimers. So, 4.0G PPI dendrimers are the safe formulations for the symptomatic treatment of the neurodegenerative disorder. The fifth-generation poly(propyleneimine) (PPI) dendrimers, inherent toxicity due to the presence of many peripheral cationic groups is the major issue that limits their applicability.

Keywords: Alzheimer disease, generation, memantine, PPI

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Authors: Gaurav Shinde, Sai Charan Gongiguntla, Prajwal Shirur, Ahmed Hambaba

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Health issues are significantly increasing, putting a substantial strain on healthcare services. This has accelerated the integration of machine learning in healthcare, particularly following the COVID-19 pandemic. The utilization of machine learning in healthcare has grown significantly. We introduce DeClEx, a pipeline that ensures that data mirrors real-world settings by incorporating Gaussian noise and blur and employing autoencoders to learn intermediate feature representations. Subsequently, our convolutional neural network, paired with spatial attention, provides comparable accuracy to state-of-the-art pre-trained models while achieving a threefold improvement in training speed. Furthermore, we provide interpretable results using explainable AI techniques. We integrate denoising and deblurring, classification, and explainability in a single pipeline called DeClEx.

Keywords: machine learning, healthcare, classification, explainability

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Authors: Zahra Heydari

Abstract:

Introduction: One of the major clinical issues is acute renal failure, which is caused by ischemia-reperfusion of the kidney and is associated with high mortality. Despite advances in this area, important issues such as tissue necrosis, cell apoptosis, and so on in damaged tissue are suggestive for more researches and study on this subject. Objective: Evaluation of the potential utility of Ezetimibe in reducing injuries and cell death induced by kidney ischemia/ reperfusion through inducing expression changes of different cellular pathways in adult Sprague-Dawley rats. Materials and methods: Forty rats weighing 180-200g were divided into 4 groups. For this purpose, the first right kidneys of the rats were removed during surgery. After 20 days, the left renal artery was closed with a soft clamp and reperfusion was performed. After 24 hours, blood samples were collected and sent to the laboratory with kidneys to measure bax and bcl-2 by Western blotting and histopathological tests. Results: Quantitative damage reviews of Kidney tissue indicates damage Acute and severe tubular lesions were observed in the ischemia group. Also, the amount of injury was significantly reduced in the treatment group. There was also a significant difference between the ischemia and sham groups. In general, the results show that a single dose of 1.2 mg/kg of ezetimibe can reduce the bax/ bcl-2 ratio compared to the ischemia group. In general, the results showed Ezetimibe is effective in reducing cell damage and death due to ischemia/ reperfusion after renal ischemia through changes in the expression of various cellular pathways in rats.

Keywords: acute renal failure, renal ischemia-reperfusion injury, ezetimibe, apoptosis

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Authors: Hu-Jiang Shi, Li-Juan Zhu

Abstract:

The implication of 5-hydroxytryptamine 2C receptor (5-HT2CR) in affective behaviors is a topic of debate, and the underlying mechanisms remain largely unclear. Here, we elucidate that the interaction between hippocampal neuronal nitric oxide synthase (nNOS) and carboxy-terminal PDZ ligand of nNOS (CAPON) contributes to the disruption of hippocampal excitation-inhibition (E/I) balance, which is responsible for the anxiety- and depressive-like behaviors caused by chronic stress-related 5-HT2CR signaling deficiency. In detail, activation or inhibition of 5-HT2CR by CP809101 or SB242084 modulates nNOS-CAPON interaction by influencing intracellular Ca²⁺ release. Notably, the dissociation of nNOS-CAPON abolishes SB242084-induced anxiety- and depressive-like behaviors, as well as the reduction in extracellular signal-regulated kinase (ERK)/cAMP-response element binding protein (CREB)/synapsin signaling and SNARE complex assembly. Furthermore, nNOS-CAPON blockers restore the impairments caused by SB242084, including the reduction in SNARE assembly-mediated γ-aminobutyric acid (GABA) vesicle release and a consequent shift of the E/I balance toward excitation in CA3 pyramidal neurons. Conclusively, our findings disclose the regulatory role of 5-HT2CR in anxiety- and depressive-like behaviors and highlight the hippocampal nNOS-CAPON coupling-triggered E/I imbalance as a pivotal cellular event underpinning the behavioral consequences of 5-HT2CR inhibition.

Keywords: 5-HT2CR, anxiety, depression, nNOS-CAPON coupling, excitation-inhibition balance, neurotransmitter release

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