Search results for: Kynurenine pathway
492 Auditory Profile Function in Hypothyroidism
Authors: Mrunal Phatak, Suvarna Raut
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Introduction: Thyroid hormone is important for the normal function of the auditory system. Hearing impairment can occur insidiously in subclinical hypothyroidism. The present study was undertaken with the aims of evaluating audiological tests like tuning fork tests, pure tone audiometry, brainstem evoked auditory potentials (BAEPs), and auditory reaction time (ART) in hypothyroid women and in age and sex matched controls so as to evaluate the effect of thyroid hormone on hearing. The objective of the study was to investigate hearing status by the audiological profile in hypothyroidism (group 1) and healthy controls ( group 2) to compare the audiological profile between these groups and find the correlation of levels of TSH, T3, and T4 with the above parameters. Material and methods: A total sample size of 124 women in the age group of 30 to 50 years was recruited and divided into the Cases group comprising of 62 newly diagnosed hypothyroid women and the Control group having 62 women with normal thyroid profile. Otoscopic examination, tuning fork tests, Pure tone audiometry tests (PTA). Brain Stem Auditory Evoked Potential (BAEP) and Auditory Reaction Time (ART) were done in both ears, i.e. total 248 ears of all subjects. Results: By BAEPs, hearing impairment was detected in total 64 ears (51.61%). A significant increase was seen in Wave V latency, IPL I-V, and IPL III-V, and the decrease was seen in the amplitude of Wave I and V in both the ears in cases. Positive correlation of Wave V latency of Right and Left ears is seen with TSH levels (p < 0.001) and a negative correlation with T3 (>0.05) and with T4 (p < 0.01). Negative correlation of wave V amplitude of Right and Left ears is seen with TSH levels (p < 0.001), and a significant positive correlation is seen with T3 and T4. Pure tone audiometry parameters showed hearing impairment of conductive (31.29%), sensorineural (36.29%), as well as the mixed type (15.32%). Hearing loss was mild in 65.32% of ears and moderate in 17.74% of ears. Pure tone averages (PTA) were significantly increased in cases than in controls in both the ears. Significant positive correlation of PTA of Right and Left ears is seen with TSH levels (p<0.05). Negative correlation with T3 and T4 is seen. A significant increase in HF ART and LF ART is seen in cases as compared to controls. Positive correlation of ART of high frequency and low frequency is seen with TSH levels and a negative correlation with T3 and T4 (p > 0.05). Conclusion: The abnormal BAEPs in hypothyroid women suggest an impaired central auditory pathway. BAEP abnormalities are indicative of a nonspecific injury in the bulbo-ponto-mesencephalic centres. The results of auditory investigations suggest a causal relationship between hypothyroidism and hearing loss. The site of lesion in the auditory pathway is probably at several levels, namely, in the middle ear and at cochlear and retrocochlear sites. Prolonged ART also suggests the impairment in central processing mechanisms. The results of the present study conclude that the probable reason for hearing impairment in hypothyroidism may be delayed impulse conduction in acoustic nerve up to the level of the midbrain (IPL I-V, III-V), particularly inferior colliculus (wave V). There is also impairment in central processing mechanisms, as shown by prolonged ART.Keywords: deafness, pure tone audiometry, brain stem auditory evoked potential, hyopothyroidism
Procedia PDF Downloads 132491 Non-Steroidal Microtubule Disrupting Analogues Induce Programmed Cell Death in Breast and Lung Cancer Cell Lines
Authors: Marcel Verwey, Anna M. Joubert, Elsie M. Nolte, Wolfgang Dohle, Barry V. L. Potter, Anne E. Theron
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A tetrahydroisoquinolinone (THIQ) core can be used to mimic the A,B-ring of colchicine site-binding microtubule disruptors such as 2-methoxyestradiol in the design of anti-cancer agents. Steroidomimeric microtubule disruptors were synthesized by introducing C'2 and C'3 of the steroidal A-ring to C'6 and C'7 of the THIQ core and by introducing a decorated hydrogen bond acceptor motif projecting from the steroidal D-ring to N'2. For this in vitro study, four non-steroidal THIQ-based analogues were investigated and comparative studies were done between the non-sulphamoylated compound STX 3450 and the sulphamoylated compounds STX 2895, STX 3329 and STX 3451. The objective of this study was to investigate the modes of cell death induced by these four THIQ-based analogues in A549 lung carcinoma epithelial cells and metastatic breast adenocarcinoma MDA-MB-231 cells. Cytotoxicity studies to determine the half maximal growth inhibitory concentrations were done using spectrophotometric quantification via crystal violet staining and lactate dehydrogenase (LDH) assays. Microtubule integrity and morphologic changes of exposed cells were investigated using polarization-optical transmitted light differential interference contrast microscopy, transmission electron microscopy and confocal microscopy. Flow cytometric quantification was used to determine apoptosis induction and the effect that THIQ-based analogues have on cell cycle progression. Signal transduction pathways were elucidated by quantification of the mitochondrial membrane integrity, cytochrome c release and caspase 3, -6 and -8 activation. Induction of autophagic cell death by the THIQ-based analogues was investigated by morphological assessment of fluorescent monodansylcadaverine (MDC) staining of acidic vacuoles and by quantifying aggresome formation via flow cytometry. Results revealed that these non-steroidal microtubule disrupting analogues inhibited 50% of cell growth at nanomolar concentrations. Immunofluorescence microscopy indicated microtubule depolarization and the resultant mitotic arrest was further confirmed through cell cycle analysis. Apoptosis induction via the intrinsic pathway was observed due to depolarization of the mitochondrial membrane, induction of cytochrome c release as well as, caspase 3 activation. Potential involvement of programmed cell death type II was observed due to the presence of acidic vacuoles and aggresome formation. Necrotic cell death did not contribute significantly, indicated by stable LDH levels. This in vitro study revealed the induction of the intrinsic apoptotic pathway as well as possible involvement of autophagy after exposure to these THIQ-based analogues in both MDA-MB-231- and A549 cells. Further investigation of this series of anticancer drugs still needs to be conducted to elucidate the temporal, mechanistic and functional crosstalk mechanisms between the two observed programmed cell deaths pathways.Keywords: apoptosis, autophagy, cancer, microtubule disruptor
Procedia PDF Downloads 253490 Integrating RAG with Prompt Engineering for Dynamic Log Parsing and Anomaly Detections
Authors: Liu Lin Xin
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With the increasing complexity of systems, log parsing and anomaly detection have become crucial for maintaining system stability. However, traditional methods often struggle with adaptability and accuracy, especially when dealing with rapidly evolving log content and unfamiliar domains. To address these challenges, this paper proposes approach that integrates Retrieval Augmented Generation (RAG) technology with Prompt Engineering for Large Language Models, applied specifically in LogPrompt. This approach enables dynamic log parsing and intelligent anomaly detection by combining real-time information retrieval with prompt optimization. The proposed method significantly enhances the adaptability of log analysis and improves the interpretability of results. Experimental results on several public datasets demonstrate the method's superior performance, particularly in scenarios lacking training data, where it significantly outperforms traditional methods. This paper introduces a novel technical pathway for log parsing and anomaly detection, showcasing the substantial theoretical value and practical potential.Keywords: log parsing, anomaly detection, RAG, prompt engineering, LLMs
Procedia PDF Downloads 33489 Colocalization Analysis to Understand Yttrium Uptake in Saxifraga paniculata Using Complementary Imaging Technics
Authors: Till Fehlauer, Blanche Collin, Bernard Angeletti, Andrea Somogyi, Claire Lallemand, Perrine Chaurand, Cédric Dentant, Clement Levard, Jerome Rose
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Over the last decades, yttrium (Y) has gained importance in high-tech applications. It is an essential part of alloys and compounds used for lasers, displays, or cell phones, for example. Due to its chemical similarities with the lanthanides, Y is often considered a rare earth element (REE). Despite their increased usage, the environmental behavior of REEs remains poorly understood. Especially regarding their interactions with plants, many uncertainties exist. On the one hand, Y is known to have a negative effect on root development and germination, but on the other hand, it appears to promote plant growth at low concentrations. In order to understand these phenomena, a precise knowledge is necessary about how Y is absorbed by the plant and how it is handled once inside the organism. Contradictory studies exist, stating that due to a similar ionic radius, Y and the other REEs might be absorbed through Ca²⁺-channels, while others suspect that Y has a shared pathway with Al³⁺. In this study, laser ablation coupled ICP-MS, and synchrotron-based micro-X-ray fluorescence (µXRF, beamline Nanoscopium, SOLEIL, France) have been used in order to localize Y within the plant tissue and identify associated elements. The plant used in this study is Saxifraga paniculata, a rugged alpine plant that has shown an affinity for Y in previous studies (in prep.). Furthermore, Saxifraga paniculata performs guttation, which means that it possesses phloem sap secreting openings on the leaf surface that serve to regulate root pressure. These so-called hydathodes could provide special insights in elemental transport in plants. The plants have been grown on Y doped soil (500mg/kg DW) for four months. The results showed that Y was mainly concentrated in the roots of Saxifraga paniculata (260 ± 85mg/kg), and only a small amount was translocated to the leaves (10 ± 7.8mg/kg). µXRF analysis indicated that within the root transects, the majority of Y remained in the epidermis and hardly penetrated the stele. Laser ablation coupled ICP-MS confirmed this finding and showed a positive correlation in the roots between Y, Fe, Al, and to a lesser extent Ca. In the stem transect, Y was mainly detected in a hotspot of approximately 40µm in diameter situated in the endodermis area. Within the stem and especially in the hotspot, Y was highly colocalized with Al and Fe. Similar-sized Y hotspots have been detected in/on the leaves. All of them were strongly colocalized with Al and Fe, except for those situated within the hydathodes, which showed no colocalization with any of the measured elements. Accordingly, a relation between Y and Ca during root uptake remains possible, whereas a correlation to Fe and Al appears to be dominant in the aerial parts, suggesting common storage compartments, the formation of complexes, or a shared pathway during translocation.Keywords: laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), Phytoaccumulation, Rare earth elements, Saxifraga paniculata, Synchrotron-based micro-X-ray fluorescence, Yttrium
Procedia PDF Downloads 148488 High-Intensity, Short-Duration Electric Pulses Induced Action Potential in Animal Nerves
Authors: Jiahui Song, Ravindra P. Joshi
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The use of high-intensity, short-duration electric pulses is a promising development with many biomedical applications. The uses include irreversible electroporation for killing abnormal cells, reversible poration for drug and gene delivery, neuromuscular manipulation, and the shrinkage of tumors, etc. High intensity, short-duration electric pulses result in the creation of high-density, nanometer-sized pores in the cellular membrane. This electroporation amounts to localized modulation of the transverse membrane conductance, and effectively provides a voltage shunt. The electrically controlled changes in the trans-membrane conductivity could be used to affect neural traffic and action potential propagation. A rat was taken as the representative example in this research. The simulation study shows the pathway from the sensorimotor cortex down to the spinal motoneurons, and effector muscles could be reversibly blocked by using high-intensity, short-duration electrical pulses. Also, actual experimental observations were compared against simulation predictions.Keywords: action potential, electroporation, high-intensity, short-duration
Procedia PDF Downloads 269487 Optimization of a Cone Loudspeaker Parameter of Design Parameters by Analysis of a Narrow Acoustic Sound Pathway
Authors: Yue Hu, Xilu Zhao, Takao Yamaguchi, Manabu Sasajima, Yoshio Koike, Akira Hara
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This study tried optimization of design parameter of a cone loudspeaker unit as an example of the high flexibility of the products design. We developed an acoustic analysis software program that considers the impact of damping caused by air viscosity. In sound reproduction, it is difficult to each design the parameter of the loudspeaker. To overcome the limitation of the design problem in practice, this paper proposes a new an acoustic analysis algorithm to optimize design the parameter of the loudspeaker. The material character of cone paper and the loudspeaker edge was the design parameter, and the vibration displacement of the cone paper was the objective function. The results of the analysis were compared with the predicted value. They had high accuracy to the predicted value. These results suggest that, though the parameter design is difficult by experience and intuition, it can be performed comparatively easily using the optimization design by the developed acoustic analysis software.Keywords: air viscosity, loudspeaker, cone paper, edge, optimization
Procedia PDF Downloads 401486 Oncogenic Role of MicroRNA-346 in Human Non-Small Cell Lung Cancer by Regulation of XPC/ERK/Snail/E-Cadherin Pathway
Authors: Cheng-Cao Sun, Shu-Jun Li, De-Jia Li
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Determinants of growth and metastasis in cancer remain of great interest to define. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. Here, we report the definition of miR-346 as an oncogenic microRNA that facilitates non-small cell lung cancer (NSCLC) cell growth and metastasis. XPC, an important DNA damage recognition factor in nucleotide excision repair was defined as a target for down-regulation by miR-346, functioning through direct interaction with the 3'-UTR of XPC mRNA. Blocking miR-346 by an antagomiR was sufficient to inhibit NSCLC cell growth and metastasis, an effect that could be phenol-copied by RNAi-mediated silencing of XPC. In vivo studies established that miR-346 overexpression was sufficient to promote tumor growth by A549 cells in xenografts mice, relative to control cells. Overall, our results defined miR-346 as an oncogenic miRNA in NSCLC, the levels of which contributed to tumor growth and invasive aggressiveness.Keywords: microRNA-346, miR-346, XPC, non-small cell lung cancer, oncogenesis
Procedia PDF Downloads 312485 Excitation and Active Control of Charge Density Waves at Degenerately Doped PN++ Junctions
Authors: R. K. Vinnakota, D. A. Genov, Z. Dong, A. F. Briggs, L. Nordin, S. R. Bank, D. Wasserman
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We present a semiconductor-based plasmonic electro-optic modulator based on excitation and active control of surface plasmon polaritons (SPPs) at the interface of degenerately doped In₀.₅₃Ga₀.₄₇As pn++ junctions. Set of devices, which we refer to as a surface plasmon polariton diode (SPPD), are fabricated and characterized electrically and optically. Optical characterization predicts far-field voltage-aided reflectivity modulation for mid-IR wavelengths. Numerical device characterizations using a self-consistent electro-optic multiphysics model have been performed to confirm the experimental findings were predicting data rates up to 1Gbits/s and 3dB bandwidth as high as 2GHz. Our findings also show that decreasing the device dimensions can potentially lead to data rates of more than 50Gbits/s, thus potentially providing a pathway toward fast all-semiconductor-based plasmotronic devices.Keywords: plasmonics, optoelectronics, PN junctions, surface plasmon polaritons
Procedia PDF Downloads 111484 Empowering Youth-Led Cooperatives for Sustainable Development: A Pathway to Inclusive Growth in Malawi
Authors: Ulemu Maseko
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In Malawi, empowering youth-led cooperatives is a pivotal strategy for fostering sustainable development and nurturing inclusive growth. The study delves into the pressing need to understand the impact and potential of youth-led cooperatives in driving socio-economic progress within the country. Through a mixed-methods approach encompassing qualitative interviews, surveys, and case studies, this research investigates the role of these cooperatives in promoting entrepreneurship, community engagement, and sustainable practices among young individuals. The results underscore the significant contribution of youth-led cooperatives towards economic empowerment and social inclusion in Malawi, highlighting their capacity to address local challenges effectively. The study concludes that supporting and investing in youth-led cooperatives is imperative for advancing sustainable development goals and achieving inclusive growth. Recommendations include tailored support mechanisms, capacity-building programs, and strategic partnerships to enhance the resilience and scalability of youth-led cooperative initiatives in Malawi.Keywords: youth-led cooperatives, sustainable development, Malawi, empowerment
Procedia PDF Downloads 23483 Exposure to Tactile Cues Does Not Influence Spatial Navigation in 129 S1/SvLm Mice
Authors: Rubaiyea Uddin, Rebecca Taylor, Emily Levesque
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The hippocampus, located in the limbic system, is most commonly known for its role in memory and spatial navigation (as cited in Brain Reward and Pathways). It maintains an especially important role in specifically episodic and declarative memory. The hippocampus has also recently been linked to dopamine, the reward pathway’s primary neurotransmitter. Since research has found that dopamine also contributes to memory consolidation and hippocampal plasticity, this neurotransmitter is potentially responsible for contributing to the hippocampus’s role in memory formation. In this experiment we tested to see the effect of tactile cues on spatial navigation for eight different mice. We used a radial arm that had one designated “reward” arm containing sucrose. The presence or absence of bedding was our tactile cue. We attempted to see if the memory of that cue would enhance the mice’s memory of having received the reward in that arm. The results from our study showed there was no significant response from the use of tactile cues on spatial navigation on our 129 mice. Tactile cues therefore do not influence spatial navigation.Keywords: mice, radial arm maze, memory, spatial navigation, tactile cues, hippocampus, reward, sensory skills, Alzheimer's, neuro-degenerative diseases
Procedia PDF Downloads 688482 The Analgesic Effect of Electroacupuncture in a Murine Fibromyalgia Model
Authors: Bernice Jeanne Lottering, Yi-Wen Lin
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Introduction: Chronic pain has a definitive lack of objective parameters in the measurement and treatment efficacy of diseases such as Fibromyalgia (FM). Persistent widespread pain and generalized tenderness are the characteristic symptoms affecting a large majority of the global population, particularly females. This disease has indicated a refractory tendency to conventional treatment ventures, largely resultant from a lack of etiological and pathogenic understanding of the disease development. Emerging evidence indicates that the central nervous system (CNS) plays a critical role in the amplification of pain signals and the neurotransmitters associated therewith. Various stimuli have been found to activate the channels existent on nociceptor terminals, thereby actuating nociceptive impulses along the pain pathways. The transient receptor potential vanalloid 1 (TRPV1) channel functions as a molecular integrator for numerous sensory inputs, such as nociception, and was explored in the current study. Current intervention approaches face a multitude challenges, ranging from effective therapeutic interventions to the limitation of pathognomonic criteria resultant from incomplete understanding and partial evidence on the mechanisms of action of FM. It remains unclear whether electroacupuncture (EA) plays an integral role in the functioning of the TRPV1 pathway, and whether or not it can reduce the chronic pain induced by FM. Aims: The aim of this study was to explore the mechanisms underlying the activation and modulation of the TRPV1 channel pathway in a cold stress model of FM applied to a murine model. Furthermore, the effect of EA in the treatment of mechanical and thermal pain, as expressed in FM was also to be investigated. Methods: 18 C57BL/6 wild type and 6 TRPV1 knockout (KO) mice, aged 8-12 weeks, were exposed to an intermittent cold stress-induced fibromyalgia-like pain model, with or without EA treatment at ZusanLi ST36 (2Hz/20min) on day 3 to 5. Von Frey and Hargreaves behaviour tests were implemented in order to analyze the mechanical and thermal pain thresholds on day 0, 3 and 5 in control group (C), FM group (FM), FM mice with EA treated group (FM + EA) and FM in KO group. Results: An increase in mechanical and thermal hyperalgesia was observed in the FM, EA and KO groups when compared to the control group. This initial increase was reduced in the EA group, which directs focus at the treatment efficacy of EA in nociceptive sensitization, and the analgesic effect EA has attenuating FM associated pain. Discussion: An increase in the nociceptive sensitization was observed through higher withdrawal thresholds in the von Frey mechanical test and the Hargreaves thermal test. TRPV1 function in mice has been scientifically associated with these nociceptive conduits, and the increased behaviour test results suggest that TRPV1 upregulation is central to the FM induced hyperalgesia. This data was supported by the decrease in sensitivity observed in results of the TRPV1 KO group. Moreover, the treatment of EA showed a decrease in this FM induced nociceptive sensitization, suggesting TRPV1 upregulation and overexpression can be attenuated by EA at bilateral ST36. This evidence compellingly implies that the analgesic effect of EA is associated with TRPV1 downregulation.Keywords: fibromyalgia, electroacupuncture, TRPV1, nociception
Procedia PDF Downloads 139481 Evaluation of the Environmental Risk from the Co-Deposition of Waste Rock Material and Fly Ash
Authors: A. Mavrikos, N. Petsas, E. Kaltsi, D. Kaliampakos
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The lignite-fired power plants in the Western Macedonia Lignite Center produce more than 8 106 t of fly ash per year. Approximately 90% of this quantity is used for restoration-reclamation of exhausted open-cast lignite mines and slope stabilization of the overburden. The purpose of this work is to evaluate the environmental behavior of the mixture of waste rock and fly ash that is being used in the external deposition site of the South Field lignite mine. For this reason, a borehole was made within the site and 86 samples were taken and subjected to chemical analyses and leaching tests. The results showed very limited leaching of trace elements and heavy metals from this mixture. Moreover, when compared to the limit values set for waste acceptable in inert waste landfills, only few excesses were observed, indicating only minor risk for groundwater pollution. However, due to the complexity of both the leaching process and the contaminant pathway, more boreholes and analyses should be made in nearby locations and a systematic groundwater monitoring program should be implemented both downstream and within the external deposition site.Keywords: co-deposition, fly ash, leaching tests, lignite, waste rock
Procedia PDF Downloads 238480 Anomalous Course of Left Ovarian Vein Associated with Pelvic Congestion Syndrome
Authors: Viyango Pandian, Kumaresh Athiyappan
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Pelvic congestion Syndrome (PCS) is usually seen in multiparous women who give history of chronic dull-aching pelvic pain. We report a case of a 17 year old unmarried female, who presented with acute onset of chronic dull-aching abdominal pain in the left iliac fossa, which particularly increased during menstruation and was finally diagnosed to be pelvic congestion syndrome. On ultrasonography, multiple tortuous and dilated veins were observed in the left adnexa. Both ovaries appeared normal in size, volume and echotexture. Computed tomography (CT) angiography was performed to precisely delineate the venous pathway and to assess any associated abnormality; which showed a dilated and tortuous left ovarian vein with an anomalous course around the left kidney and draining into the left renal vein. Clinical parameters and hormonal levels were within normal limits. This is a rare case of anomalous course of left ovarian vein associated with pelvic congestion syndrome.Keywords: anomalous course of ovarian vein, computed tomography, pelvic congestion syndrome, ultrasonography
Procedia PDF Downloads 418479 Theoretical and Experimental Study on the NO Reduction by H₂ over Char Decorated with Ni at low Temperatures
Authors: Kaixuan Feng, Ruixiang Lin, Yuyan Hu, Yuheng Feng, Dezhen Chen, Tongcheng Cao
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In this study, we propose a reaction system for the low-temperature reduction of NO by H₂ on carbon-based materials decorated with 5%wt. Ni. This cost-effective catalyst system efficiently utilizes pyrolysis carbon-based materials and waste hydrogen. Additionally, it yields environmentally friendly products without requiring extra heat sources in practical SCR devices. Density functional theory elucidates the mechanism of NO heterogeneous reduction by H₂ on Ni-decorated char surfaces. Two distinct reaction paths were identified, one involving the intermediate product N₂O and the other not. These pathways exhibit different rate-determination steps and activation energies. Kinetic analysis indicates that the N₂O byproduct pathway has a lower activation energy. Experimental results corroborate the theoretical findings. Thus, this research enhances our mechanistic understanding of the NO-H₂ reaction over char and offers insights for optimizing catalyst design in low-temperature NO reduction.Keywords: char-based catalysis, NO reduction, DFT study, heterogeneous reaction, low-temperature H₂-reduction
Procedia PDF Downloads 79478 Synthesis and Anti-Inflammatory Activity of Pyrazol-3-yl Thiazole 4-Carboxylic Acid Derivatives Targeting Enzyme in the Leukotriene Pathway
Authors: Shweta Sinha, Mukesh Doble, Manju S. L.
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Pyrazole scaffold is an important group of compound in heterocyclic chemistry and is found to possess numerous uses in chemistry. Pyrazole derivatives are also known to possess important biological activities including antitumor, antimicrobial, antiviral, antifungal, anticancer and anti-inflammatory. Inflammation is associated with pain, allergy and asthma. Leukotrienes are mediators of various inflammatory and allergic disorders. 5-Lipoxygenase (5-LOX) is an important enzyme involved in the biosynthesis of leukotrienes and metabolism of arachidonic acid (AA) and thus targeted for anti-inflammation. In vitro inhibitory activity of pyrazol-3-yl thiazole 4-carboxylic acid derivatives is tested against enzyme 5-LOX. Most of these compounds exhibit good inhibitory activity against this enzyme. Binding mode study of these compounds is determined by computational tool. Further experiments are being done to understand the mechanism of action of these compounds in inhibiting this enzyme. To conclude, these compounds appear to be a promising target in drug design against 5-LOX.Keywords: inflammation, inhibition, 5-lipoxygenase, pyrazole
Procedia PDF Downloads 244477 Anti-Melanogenic Effect of Fisetin through Activating Connective Tissue Growth Factor in vivo Mice Model
Authors: Ryeong-Hyeon Kim, Ah-Reum Lee, Seong-Soo Roh, Gyo-Nam Kim
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Appropriate regulation of melanogenesis is important for the management of skin pigmentation-related disease. Although several beneficial effects of fisetin (3,7,3’,4’-tetrahydroxyflavone) have been reported, the precise role and molecular mechanisms of fisetin in skin health both remain unclear. Here, we induced melanogenesis of HRM2 mice (n=7/group) by UVB irradiation for 20 days. UVB-induced HRM2 mice showed that the significantly increased melanin accumulation, however, fisetin treatment (25mg and 50mg/kg of body weight) dose-dependently and significantly inhibits UVB-induced melanogenesis. In line with this, fisetin treatment effectively down-regulated m RNA and expression levels of tyrosinase, TRP2, and MITF. In addition, our inhibitor assay revealed the down-regulated melanogenic marker genes by fisetin treatment were mediated with connective tissue growth factor (CCN2)/TGF-β signaling pathway. Useful information is provided for development of functional foods using fisetin for skin health.Keywords: connective tissue growth factor, fisetin, melanogenesis, skin, TGF-beta
Procedia PDF Downloads 236476 Enhancement Dynamic Cars Detection Based on Optimized HOG Descriptor
Authors: Mansouri Nabila, Ben Jemaa Yousra, Motamed Cina, Watelain Eric
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Research and development efforts in intelligent Advanced Driver Assistance Systems (ADAS) seek to save lives and reduce the number of on-road fatalities. For traffic and emergency monitoring, the essential but challenging task is vehicle detection and tracking in reasonably short time. This purpose needs first of all a powerful dynamic car detector model. In fact, this paper presents an optimized HOG process based on shape and motion parameters fusion. Our proposed approach mains to compute HOG by bloc feature from foreground blobs using configurable research window and pathway in order to overcome the shortcoming in term of computing time of HOG descriptor and improve their dynamic application performance. Indeed we prove in this paper that HOG by bloc descriptor combined with motion parameters is a very suitable car detector which reaches in record time a satisfactory recognition rate in dynamic outside area and bypasses several popular works without using sophisticated and expensive architectures such as GPU and FPGA.Keywords: car-detector, HOG, motion, computing time
Procedia PDF Downloads 323475 The 10,000 Fold Effect of Retrograde Neurotransmission, a New Concept for Stroke Revival: Use of Intracarotid Sodium Nitroprusside
Authors: Vinod Kumar
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Background: Tissue Plasminogen Activator (tPA) showed a level 1 benefit in acute stroke (within 3-6 hrs). Intracarotid sodium nitroprusside (ICSNP) has been studied in this context with a wide treatment window, fast recovery and affordability. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a)Retrograde Neurotransmission (acute cases): 1)Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2)Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b)Vasospasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c)Long-Term Potentıatıon (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Des’gn: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat stroke cases. Case-control prospective study. Mater’als And Methods: The experimental population included 82 stroke patients (10 patients were given control treatments without superfusion or with 5% dextrose superfusion, and 72 patients comprised the ICSNP group). The mean time for superfusion was 9.5 days post-stroke. Pre- and post-ICSNP status was monitored by NIHSS, MRI and TCD. Results: After 90 seconds in the ICSNP group, the mean change in the NIHSS score was a decrease of 1.44 points, or 6.55%; after 2 h, there was a decrease of 1.16 points; after 24 h, there was an increase of 0.66 points, 2.25%, compared to the control-group increase of 0.7 points, or 3.53%; at 7 days, there was an 8.61-point decrease, 44.58%, compared to the control-group increase of 2.55 points, or 22.37%; at 2 months in ICSNP, there was a 6.94-points decrease, 62.80%, compared to the control-group decrease of 2.77 points, or 8.78%. TCD was documented and improvements were noted. Conclusions: ICSNP is a swift-acting drug in the treatment of stroke, acting within 90 seconds on day 9.5 post-stroke with a small decrease after 24 hours. The drug recovers from this decrease quickly.Keywords: brain infarcts, intracarotid sodium nitroprusside, perforators, vasodilatıons, retrograde transmission, the 10, 000-fold effect
Procedia PDF Downloads 307474 Fertility Transition in Sub-Saharan Africa: The Role Family Planning Programs
Authors: Vincent Otieno, Alfred Agwanda, Anne Khasakhala
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Among the neo-Malthusian adherents, it is believed that rapid population growth strain countries’ capacity and performance. Fertility have however decelerated in most of the countries in the recent past. Scholars have concentrated on wide range of factors associated with fertility majorly at the national scale with some opining that analysis of trends and differentials in the various fertility parameters have been discussed extensively. However, others believe that considerably less attention has been paid to the fertility preference- a pathway through which various variables act on fertility. The Sub-Saharan African countries’ disparities amid almost similarities in policies is a cause of concern to demographers. One would point at the meager synergies that have been focused on the fertility preference as well, especially at the macro scale. Using Bongaarts reformulation of Easterlin and Crimmins (1985) conceptual scheme, the understanding of the current transition based on the fertility preference in general would help to provide explanations to the observed latest dynamics. This study therefore is an attempt to explain the current fertility transition through women’s fertility preference. Results reveal that indeed fertility transition is on course in most of the sub-Saharan countries with huge disparities in fertility preferences and its implementation indices.Keywords: fertility preference, the degree of implementation index, sub-Saharan Africa, transition
Procedia PDF Downloads 243473 The 10,000 Fold Effect of Retrograde Neurotransmission: A New Concept for Cerebral Palsy Revival by the Use of Nitric Oxide Donars
Authors: V. K. Tewari, M. Hussain, H. K. D. Gupta
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Background: Nitric Oxide Donars (NODs) (intrathecal sodium nitroprusside (ITSNP) and oral tadalafil 20mg post ITSNP) has been studied in this context in cerebral palsy patients for fast recovery. This work proposes two mechanisms for acute cases and one mechanism for chronic cases, which are interrelated, for physiological recovery. a) Retrograde Neurotransmission (acute cases): 1) Normal excitatory impulse: at the synaptic level, glutamate activates NMDA receptors, with nitric oxide synthetase (NOS) on the postsynaptic membrane, for further propagation by the calcium-calmodulin complex. Nitric oxide (NO, produced by NOS) travels backward across the chemical synapse and binds the axon-terminal NO receptor/sGC of a presynaptic neuron, regulating anterograde neurotransmission (ANT) via retrograde neurotransmission (RNT). Heme is the ligand-binding site of the NO receptor/sGC. Heme exhibits > 10,000-fold higher affinity for NO than for oxygen (the 10,000-fold effect) and is completed in 20 msec. 2) Pathological conditions: normal synaptic activity, including both ANT and RNT, is absent. A NO donor (SNP) releases NO from NOS in the postsynaptic region. NO travels backward across a chemical synapse to bind to the heme of a NO receptor in the axon terminal of a presynaptic neuron, generating an impulse, as under normal conditions. b) Vasopasm: (acute cases) Perforators show vasospastic activity. NO vasodilates the perforators via the NO-cAMP pathway. c) Long-Term Potentiation (LTP): (chronic cases) The NO–cGMP-pathway plays a role in LTP at many synapses throughout the CNS and at the neuromuscular junction. LTP has been reviewed both generally and with respect to brain regions specific for memory/learning. Aims/Study Design: The principles of “generation of impulses from the presynaptic region to the postsynaptic region by very potent RNT (10,000-fold effect)” and “vasodilation of arteriolar perforators” are the basis of the authors’ hypothesis to treat cerebral palsy cases. Case-control prospective study. Materials and Methods: The experimental population included 82 cerebral palsy patients (10 patients were given control treatments without NOD or with 5% dextrose superfusion, and 72 patients comprised the NOD group). The mean time for superfusion was 5 months post-cerebral palsy. Pre- and post-NOD status was monitored by Gross Motor Function Classification System for Cerebral Palsy (GMFCS), MRI, and TCD studies. Results: After 7 days in the NOD group, the mean change in the GMFCS score was an increase of 1.2 points mean; after 3 months, there was an increase of 3.4 points mean, compared to the control-group increase of 0.1 points at 3 months. MRI and TCD documented the improvements. Conclusions: NOD (ITSNP boosts up the recovery and oral tadalafil maintains the recovery to a well-desired level) acts swiftly in the treatment of CP, acting within 7 days on 5 months post-cerebral palsy either of the three mechanisms.Keywords: cerebral palsy, intrathecal sodium nitroprusside, oral tadalafil, perforators, vasodilations, retrograde transmission, the 10, 000-fold effect, long-term potantiation
Procedia PDF Downloads 362472 Investigation into the Role of Leadership in the Management of Digital Transformation for Small and Medium Enterprises
Authors: Francesco Coraci, Abdul-Hadi G. Abulrub
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Digital technology is transforming the landscape of the industrial sector at a precedential level by connecting people, processes, and machines in real-time. It represents the means for a new pathway to achieve innovative, dynamic competitive advantages, deliver unique customers’ values, and sustain critical relationships. Thus, success in a constantly changing environment is governed by the ability of an organization to revolutionize their business models, deliver innovative solutions, and capture values from big data analytics and insights. Businesses need to re-strategize operations and develop extra capabilities to cope with the necessity for additional flexibility and agility. The traditional “command and control” leadership style is structurally and operationally incompatible with the digital era. In this paper, the authors discuss how transformational leaders can act as a glue in the social, organizational context, which is crucial to enable the workforce and develop a psychological attachment to the digital vision.Keywords: internet of things, strategy, change leadership, dynamic competitive advantage, digital transformation
Procedia PDF Downloads 129471 New Quinazoline Derivative Induce Cytotoxic Effect against Mcf-7 Human Breast Cancer Cell
Authors: Maryam Zahedi Fard, Nazia Abdul Majid, Hapipah Mohd Ali, Mahmood Ameen Abdulla
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New quinazoline schiff base 3-(5-bromo-2-hydroxy-3-methoxybenzylideneamino)-2-(5-bromo-2-hydroxy-3-methoxyphenyl)-2,3-dihydroquinazolin-4(1H)-one was investigated for anticancer activity against MCF-7 human breast cancer cell line with involved mechanism of apoptosis. The compound demonstrated a remarkable antiproliferative effect, with an IC50 value of 3.41 ± 0.34, after 72 hours of treatment. Morphological apoptotic features in treated MCF-7 cells were observed by AO/PI staining. Furthermore, treated MCF-7 cells subjected to apoptosis death, as exhibited by perturbation of mitochondrial membrane potential and cytochrome c release as well as increase in ROS generation. We also found activation of caspases 3/7 and -9. Moreover, acute toxicity test demonstrated the nontoxic nature of the compound in mice. Our results showed the selected compound significantly induce apoptosis in MCF-7 cells via intrinsic pathway, which might be considered as a potent candidate for further in vivo and clinical breast cancer studies.Keywords: antiproliferative effect, MCF-7 human breast cancer cell line, apoptosis, caspases
Procedia PDF Downloads 532470 Synthesis, Characterization and in vitro DNA Binding and Cleavage Studies of Cu(II)/Zn(II) Dipeptide Complexes
Authors: A. Jamsheera, F. Arjmand, D. K. Mohapatra
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Small molecules binding to specific sites along DNA molecule are considered as potential chemotherapeutic agents. Their role as mediators of key biological functions and their unique intrinsic properties make them particularly attractive therapeutic agents. Keeping in view, novel dipeptide complexes Cu(II)-Val-Pro (1), Zn(II)-Val-Pro (2), Cu(II)-Ala-Pro (3) and Zn(II)-Ala-Pro (4) were synthesized and thoroughly characterized using different spectroscopic techniques including elemental analyses, IR, NMR, ESI–MS and molar conductance measurements. The solution stability study carried out by UV–vis absorption titration over a broad range of pH proved the stability of the complexes in solution. In vitro DNA binding studies of complexes 1–4 carried out employing absorption, fluorescence, circular dichroism and viscometric studies revealed the binding of complexes to DNA via groove binding. UV–vis titrations of 1–4 with mononucleotides of interest viz., 5´-GMP and 5´-TMP were also carried out. The DNA cleavage activity of the complexes 1 and 2 were ascertained by gel electrophoresis assay which revealed that the complexes are good DNA cleavage agents and the cleavage mechanism involved a hydrolytic pathway. Furthermore, in vitro antitumor activity of complex 1 was screened against human cancer cell lines of different histological origin.Keywords: dipeptide Cu(II) and Zn(II) complexes, DNA binding profile, pBR322 DNA cleavage, in vitro anticancer activity
Procedia PDF Downloads 349469 Collision Induced Dissociation of Transition Metal Fluoride Complexes and the Multiply Charged Anions
Authors: Ruqia Nazir, Robin Perutz
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Collision-induced dissociation (CID) can be used to study the intrinsic properties of ions in the gas phase.1 Decay pathways of transition metal difluoride complexes of titanium, zirconium, hafnium, and ruthenium were studied by CID in an ESI-Ion trap mass spectrometer. Furthermore, the decay pathways of multiply charged anions (MCAs) of titanium and zirconium were also studied. The CID results are illustrated by the behaviour of (Cp*)₂TiF₂, which initially forms the ions [M-F-]⁺, [M+Na]⁺, and [M+K]⁺. The [(Cp*₂)TiF⁺ ion decays on resonant excitation to lose HF forming [Cp*(C₅Me₄CH₂)Ti]⁺ (Figure). The other major ion, [(Cp*)₂TiF₂+Na]⁺, decays on resonant excitation with production of [(Cp*)₂TiF₂]⁺ and [C₅Me₄CH₂]⁺. We also report the behaviour of Cp₂MF₂ (M = Zr, Hf) and Ru(PMe₃)₄F₂. The decay pathway of the multiply charged anions (MCAs), notably TiF₆²⁻ and ZrF₆²⁻ was concluded to be ionic fragmentation with loss of F⁻ rather than electron detachment.Keywords: collision induced dissociation, transition metal difluoride comolexes, multiply charged anions, mass spectrometry
Procedia PDF Downloads 107468 Sport Facilities and Social Change: European Funds as an Opportunity for Urban Regeneration
Authors: Lorenzo Maiorino, Fabio Fortuna, Giovanni Panebianco, Marco Sanzari, Gabriella Arcese, Valerio Maria Paolozzi
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It is well known that sport is a factor of social cohesion and the breaking down of barriers between people. From this point of view, the aim is to demonstrate how, through the (re)generation of sustainable structures, it is possible to give life to a new social, cultural, and economic pathway, where possible, in peripheral areas with problems of abandonment and degradation. The aim of this paper is, therefore, to study realities such as European programs and funds and to highlight the ways in which planning can be used to respond to critical issues such as urban decay, abandonment, and the mitigation of social differences. For this reason, the analysis will be carried out through the Multiannual Financial Framework (MFF) package, the Next Generation EU, the Recovery and Resilience Facility (RRF), the Cohesion Fund, the European Social Fund, and other managed funds. The procedure will rely on sources and data of unquestionable origin, and the relation to the object of study in question will be highlighted. The project lends itself to be ambitious and exploring a further aspect of the sports theme, which, as we know, is one of the foundations for a healthy society.Keywords: sport, social inclusion, urban regeneration, sports facilities, European funds
Procedia PDF Downloads 225467 The Effects of Androgen Receptor Mutation on Cryptorchid Testes in 46, XY Female
Authors: Ihtisham Bukhari
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In the current study, we enrolled a 46, XY phenotypically female patient bearing testes in her inguinal canal. DNA sequencing of the AR gene detected a missense mutation C.1715A > G (p. Y572C) in exon 2 which is already known to cause Complete androgen insensitivity syndrome (CAIS). We further studied the effects of this mutation on the testicular histopathology of the patient. No spermatocytes were seen in the surface spreading of testicular tissues while H&E staining showed that seminiferous tubules predominantly have only Sertoli cells. To confirm this meiotic failure is likely due to the current AR mutation we performed mRNA expression of genes associated with AR pathway, expression and location of the associated proteins in testicular tissues. Western blot and real-time PCR data showed that the patient had high levels of expression of AMH, SOX9, and INNB in testis. Tubules were stained with SOX9 and AMH which revealed Sertoli cell maturation arrest. Therefore, we suggest that AR mutation enhances AMH expression which ultimately leads to failure in the maturation of Sertoli cells and failure in spermatogenesis.Keywords: androgen receptor, spermatogenesis, infertility, Sertoli cell only syndrome
Procedia PDF Downloads 143466 Chemical Fingerprinting of the Ephedrine Pathway to Methamphetamine
Authors: Luke Andrighetto, Paul G. Stevenson, Luke C. Henderson, Jim Pearson, Xavier A. Conlan
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As pseudoephedrine, a common ingredient in cold and flu medications is closely monitored and restricted in Australia, alternative methods of accessing it are of interest. The impurities and by-products of every reaction step of pseudoephedrine/ephedrine and methamphetamine synthesis have been mapped in order to develop a chemical fingerprint based on synthetic route. Likewise, seized methamphetamine contains a combination of different cutting agents and starting materials. Therefore, in-silico optimised two-dimensional HPLC with DryLab® and OpenMS® software has been used to efficiently separate complex seizure samples. An excellent match between simulated and real separations was observed. Targeted separation of model compounds was completed with significantly reduced method development time. This study produced a two-dimensional separation regime that offers unprecedented separation power (separation space) while maintaining a rapid analysis time that is faster than those previously reported for gas chromatography, single dimension high performance liquid chromatography or capillary electrophoresis.Keywords: chemical fingerprint, ephedrine, methamphetamine, two-dimensional HPLC
Procedia PDF Downloads 459465 The Effect of Gibberellic Acid on Gamma-Aminobutyric Acid (GABA) Metabolism in Phaseolus Vulgaris L. Plant Exposed to Drought and Salt Stresses
Authors: Fazilet Özlem Çekiç, Seyda Yılmaz
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Salinity and drought are important environmental problems in the world and have negative effects on plant metabolism. Gamma-aminobutyric acid (GABA), four-carbon non-protein amino acid, is a significant component of the free amino acid pool. GABA is widely distributed in prokaryotic and eukaryotic organisms. Environmental stress factors increase GABA accumulation in plants. Our aim was to evaluate the effect of gibberellic acid (GA) on GABA metabolism system during drought and salt stress factors in Phaseolus vulgaris L. plants. GABA, Glutamate dehydrogenase (GDH) activity, chlorophyll, and lipid peroxidation (MDA) analyses were determined. According to our results we can suggest that GA play a role in GABA metabolism during salt and drought stresses in bean plants. Also GABA shunt is an important metabolic pathway and key signaling allowing to adapt to drought and salt stresses.Keywords: gibberellic acid, GABA, Phaseolus vulgaris L., salinity, drought
Procedia PDF Downloads 423464 Xeroderma Pigmentosum Group G: Gene Polymorphism and Risk of Breast Cancer
Authors: Malik SS, Masood N, Mubarik S, Khadim TM
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Introduction: Xeroderma pigmentosum group G (XPG) gene plays a crucial role in the correction of UV-induced DNA damage through nucleotide excision repair pathway. Single nucleotide polymorphisms in XPG gene have been reported to be associated with different cancers. Current case-control study was designed to evaluate the relationship between one of the most frequently found XPG (rs1047768 T>C) polymorphism and breast cancer risk. Methodology: A total of 200 individuals were screened for this polymorphism including 100 pathologically confirmed breast cancer cases and age-matched 100 controls. Genotyping was carried out using Tetra amplification-refractory mutation system (ARMS) PCR and results were confirmed by gel electrophoresis. Results: Conditional logistic regression analysis showed significant association between TC genotype (OR: 8.9, CI: 2.0 – 38.7) and increased breast cancer risk. Although homozygous CC genotype was more frequent in patients as compared to controls, but it was statistically non-significant (OR: 3.9, CI: 0.4 – 35.7). Conclusion: In conclusion, XPG (rs1047768 T>C) polymorphism may contribute towards increased risk of breast cancer but other polymorphisms may also be evaluated to elucidate their role in breast cancer.Keywords: XPG, breast cancer, NER, ARMS-PCR
Procedia PDF Downloads 188463 Characterization of Molecular Targets to Mediate Skin Itch and Inflammation
Authors: Anita Jäger, Andrew Salazar, Jörg von Hagen, Harald Kolmar
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In the treatment of individuals with sensitive and psoriatic skin, several inflammation and itch-related molecular and cellular targets have been identified, but many of these have yet to be characterized. In this study, we present two potential targets in the skin that can be linked to the inflammation and itch cycle. 11ßHSD1 is the enzyme responsible for converting inactive cortisone to active cortisol used to transmit signals downstream. The activation of the receptor NK1R correlates with promoting inflammation and the perception of itch and pain in the skin. In this study, both targets have been investigated based on their involvement in inflammation. The role of both identified targets was characterized based on the secretion of inflammation cytokine- IL6, IL-8, and CCL2, as well as phosphorylation and signaling pathways. It was found that treating skin cells with molecules able to inhibit inflammatory pathways results in the reduction of inflammatory signaling molecules secreted by skin cells and increases their proliferative capacity. Therefore, these molecular targets and their associated pathways show therapeutic potential and can be mitigated via small molecules. This research can be used for further studies in inflammation and itch pathways and can help to treat pathological symptoms.Keywords: inflammation, itch, signaling pathway, skin
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