Search results for: adjuvant induced arthritis

Authors: Rachel Shukrun, Szilvia Baron, Victoria Fidel, Anna Shusterman, Osnat Sher, Netanya Kollender, Dror Levin, Yair Peled, Yair Gortzak, Yoav Ben-Shahar, Revital Caspi, Sagi Gordon, Michal Manisterski, Ronit Elhasid

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Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescent. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared to those with local disease. High NETs formation at diagnosis predicted poor response to neo-adjuvant chemotherapy, relapse, and death from disease (P < .05). NETs formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared to pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NETs formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.

Keywords: Ewing sarcoma, tumor microenvironment, neutrophil, neutrophil extracellular traps (NETs), prognosis

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Authors: Arieh Moussaieff, Bénédicte Elena-Herrmann, Yaakov Nahmias, Daniel Aberdam

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Differentiation of pluripotent stem cells is a slow process, marked by the gradual loss of pluripotency factors over days in culture. While the first few days of differentiation show minor changes in the cellular transcriptome, intracellular signaling pathways remain largely unknown. Recently, several groups demonstrated that the metabolism of pluripotent mouse and human cells is different from that of somatic cells, showing a marked increase in glycolysis previously identified in cancer as the Warburg effect. Here, we sought to identify the earliest metabolic changes induced at the first hours of differentiation. High-resolution NMR analysis identified 35 metabolites and a distinct, gradual transition in metabolism during early differentiation. Metabolic and transcriptional analyses showed the induction of glycolysis toward acetate and acetyl-coA in pluripotent cells, and an increase in cholesterol biosynthesis during early differentiation. Importantly, this metabolic pathway regulated differentiation of human and mouse embryonic stem cells. Acetate delayed differentiation preventing differentiation-induced histone de-acetylation in a dose-dependent manner. Glycolytic inhibitors upstream of acetate caused differentiation of pluripotent cells, while those downstream delayed differentiation. Our data suggests that a rapid loss of glycolysis in early differentiation down-regulates acetate and acetyl-coA production, causing a loss of histone acetylation and concomitant loss of pluripotency. It demonstrate that pluripotent stem cells utilize a novel metabolism pathway to maintain pluripotency through acetate/acetyl-coA and highlights the important role metabolism plays in pluripotency and early differentiation of stem cells.

Keywords: pluripotency, metabolomics, epigenetics, acetyl-coA

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Authors: Tella Toluwani, Adegbegi Ademuyiwa, Musei Chiedu, Adekunle Odola, Ayangbenro Ayansina, Adaramoye Oluwatosin

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Dithiocarbamates are very useful biological agents with antioxidant properties. Diclofenac (DIC) is a non-steroidal analgesic, anti-inflammatory, and antipyretic agent. The use of diclofenac has been linked with reproductive toxicity/damage. The purpose of this study is (i) To investigate the therapeutic potential of diisopropyldithiocarbamate sodium salt (Na(i-Pr₂dtc)) and vitamin E (VIT E) against diclofenac induced toxicity in the testes of male Wistar rats. (ii) To investigate the effect of (Na(i-Pr₂dtc)) and vitamin E on ameliorating damage done to the testes through histological analysis of the testes. Thirty-six (36) male Wistar rats were used for the experiment, they were divided into six (6) groups, the animals in group 1 served as control, animals in groups 2, 3, 4, 5 and 6 received DIC only, DIC and (Na(i-Pr₂dtc)), DIC and VIT E, (Na(i-Pr₂dtc) only and VIT E only respectively. A single dose of 100 mg/kg body weight of DIC was administered to male Wistar rats, while 30 mg/kg body weight of (Na(i-Pr₂dtc)) was used to treat both normal and DIC treated animals, control animals were treated with the vehicle, after 24 hrs of treatment the animals were euthanized and the testes were removed for analysis. The treatment of rats with Na(i-Pr₂dtc) significantly restored catalase (CAT) activity depressed by diclofenac. (Na(i-Pr₂dtc)) also restored glutathione levels reduced by DIC treatment and this was also accompanied by reduced lipid peroxidation (LPO) level. VIT E significantly restored superoxide dismutase (SOD) activity when compared with DIC only treated animals. Photomicrographs of testes from (Na(i-Pr₂dtc)) treated rats showed seminiferous epithelium with no lesions. We conclude that (Na(i-Pr₂dtc)) has an antioxidant effect, which might be related to the dose and duration of administration.

Keywords: diisopropyldithiocarbamate sodium salt, diclofenac, vitamin E, testes

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Authors: S. Noreen, S. Ahmad

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Salinity is one of the most important environmental factors that limit the production of crop plants to the greatest proportion than any other ones. Salt-induced changes in growth, pigment concentration, water status, malondialdehydes (MDA) and H₂O₂ content, enzymatic and non-enzymatic antioxidants, Na⁺, K⁺ content and yield attributes were examined in the glasshouse on ten pea (Pisum Sativum L.) accessions, namely ‘13240’, ‘18302’, ‘19666’, ‘19700’, ‘19776’, ‘19785’, ‘19788’, ‘20153’, ‘20155’, ‘26719’ were subjected to non-stress (0 mM NaCl) and salt stress (100 mM and150 mM NaCl) in pots containing sand medium. The results showed that salt stress at level150 mM substantially reduced biomass production, leaf water status, pigment concentration (chlorophyll ‘a’, ‘b’, ‘carotenoid content’ total chlorophyll), K⁺ content, quantum yield and yield attributes as compared to plants treated with 100 mM NaCl. Antioxidant enzymes, Catalase (CAT), Peroxidase (POD), Superoxide dismutase (SOD) and Ascorbate peroxidase (APX), proline content, total soluble protein, total amino acids, Malondialdehyde content (MDA), Hydrogen peroxide (H₂O₂) content and Na⁺ uptake markedly enhanced due to the influence of salt stress. On the basis of analyses (expressed as percent of control), of 10 accessions of pea plant, two were ranked as salt tolerant namely (‘19666’, ‘20153’), four were moderately tolerant namely (‘19700’, ‘19776’, ‘19785’, ‘20155’), and three were salt sensitive namely (‘13240’, ‘18302’, ‘26719’) at 150 mM NaCl level.

Keywords: antioxidant enzymes, ion uptake, pigment concentration, salt stress, yield attributes

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Authors: Omer Altaf, Liam Wotherspoon, Rolando Orense

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The Wairau Plains are located in the north-east of the South Island of New Zealand in the region of Marlborough. The region is cut by many active crustal faults such as the Wairau, Awatere, and Clarence faults, which give rise to frequent seismic events. This paper presents the preliminary results of the overall project in which liquefaction-induced ground damage maps are developed in the Wairau Plains based on the Ministry of Business, Innovation and Employment NZ guidance. A suite of maps has been developed in relation to the level of details that was available to inform the liquefaction hazard mapping. Maps at the coarsest level of detail make use of regional geologic information, applying semi-quantitative criteria based on geological age, design peak ground accelerations and depth to the water table. The next level of detail incorporates higher resolution surface geomorphologic characteristics to better delineate potentially liquefiable and non-liquefiable deposits across the region. The most detailed assessment utilised CPT sounding data to develop ground damage response curves for areas across the region and provide a finer level of categorisation of liquefaction vulnerability. Linking these with design level earthquakes defined through NZGS guidelines will enable detailed classification to be carried out at CPT investigation locations, from very low through to high liquefaction vulnerability. To update classifications to these detailed levels, CPT investigations in geomorphic regions are grouped together to provide an indication of the representative performance of the soils in these areas making use of the geomorphic mapping outlined above.

Keywords: hazard, liquefaction, mapping, seismicity

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Authors: N. F. Hamid, A. Kipar, J. Stewart, D. J. Antoine, B. K. Park, D. P. Williams

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Acetaminophen (APAP) is a widely used analgesic that is safe at therapeutic doses. The mouse model of APAP has been extensively used for studies on pathogenesis and intervention of drug induced liver injury based on the CytP450 mediated formation of N-acetyl-p-benzo-quinoneimine and, more recently, as model for mechanism based biomarkers. Delay of the fasted CD1 mice to rebound to the basal level of hepatic GSH compare to fed mice is reported in this study. Histologically, 15 hours fasted mice prior to APAP treatment leading to overall more intense cell loss with no evidence of apoptosis as compared to non-fasted mice, where the apoptotic cells were clearly seen on cleaved caspase-3 immunostaining. After 15 hours post APAP administration, hepatocytes underwent stage of recovery with evidence of mitotic figures in fed mice and return to completely no histological difference to control at 24 hours. On the contrary, the evidence of ongoing cells damage and inflammatory cells infiltration are still present on fasted mice until the end of the study. To further measure the regenerative capacity of the hepatocytes, the inflammatory mediators of cytokines that involved in the progression or regression of the toxicity like TNF-α and IL-6 in liver and spleen using RT-qPCR were also included. Yet, quantification of proliferating cell nuclear antigen (PCNA) has demonstrated the time for hepatic regenerative in fasted is longer than that to fed mice. Together, these data would probably confirm that fasting prior to APAP treatment does not only modulate liver injury, but could have further effects to delay subsequent regeneration of the hepatocytes.

Keywords: acetaminophen, liver, proliferating cell nuclear antigen, regeneration, apoptosis

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Authors: Guram Adamashvili

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Surface plasmon polariton is a surface optical wave which undergoes a strong enhancement and spatial confinement of its wave amplitude near an interface of two-dimensional layered structures. Phosphorene (single-layer black phosphorus) and other two-dimensional anisotropic phosphorene-like materials are recognized as promising materials for potential future applications of surface plasmon polariton. A theory of an optical breather of self-induced transparency for surface plasmon polariton propagating in monolayer or few-layer phosphorene is developed. A theory of an optical soliton of self-induced transparency for surface plasmon polariton propagating in monolayer or few-layer phosphorene have been investigated earlier Starting from the optical nonlinear wave equation for surface TM-modes interacting with a two-dimensional layer of atomic systems or semiconductor quantum dots and a phosphorene monolayer (or other two-dimensional anisotropic material), we have obtained the evolution equations for the electric field of the breather. In this case, one finds that the evolution of these pulses become described by the damped Bloch-Maxwell equations. For surface plasmon polariton fields, breathers are found to occur. Explicit relations of the dependence of breathers on the local media, phosphorene anisotropic conductivity, transition layer properties and transverse structures of the SPP, are obtained and will be given. It is shown that the phosphorene conductivity reduces exponentially the amplitude of the surface breather of SIT in the process of propagation. The direction of propagation corresponding to the maximum and minimum damping of the amplitude are assigned along the armchair and zigzag directions of black phosphorus nano-film, respectively. The most rapid damping of the intensity occurs when the polarization of breather is along the armchair direction.

Keywords: breathers, nonlinear waves, solitons, surface plasmon polaritons

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Authors: Fangfang Wang, Fan Qu

Abstract:

Polycystic ovary syndrome (PCOS), the most common endocrinopathy among women of reproductive age, is characterized by ovarian dysfunction, hyperandrogenism and reduced fecundity. The aim of this study is to investigate whether the circadian disruption is involved in pathogenesis of PCOS in androgen-induced animal model. We established a rat model of PCOS using single subcutaneous injection with testosterone propionate on the ninth day after birth, and confirmed their PCOS-like phenotypes with vaginal smears, ovarian hematoxylin and eosin (HE) staining and serum androgen measurement. The control group rats received the vehicle only. Gene expression was detected by real-time quantitative PCR. (1) Compared with control group, PCOS model rats of 10-week group showed persistently keratinized vaginal cells, while all the control rats showed at least two consecutive estrous cycles. (2) Ovarian HE staining and histological examination showed that PCOS model rats of 10-week group presented many cystic follicles with decreased numbers of granulosa cells and corpora lutea in their ovaries, while the control rats had follicles with normal layers of granulosa cells at various stages of development and several generations of corpora lutea. (3) In the 10-week group, serum free androgen index was notably higher in PCOS model rats than controls. (4) Disturbed mRNA expression patterns of core clock genes were found in ovaries of PCOS model rats of 10-week group. Abnormal expression of key genes associated with circadian rhythm in ovary may be one of the mechanisms for ovarian dysfunction in PCOS model rats induced by androgen.

Keywords: polycystic ovary syndrome, androgen, animal model, circadian disruption

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Authors: Bin Shi, Mouhab Meshreki, Grégoire Bazin, Helmi Attia

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Large monolithic components are widely used in the aerospace industry in order to reduce airplane weight. Milling is an important operation in manufacturing of the monolithic parts. More than 90% of the material could be removed in the milling operation to obtain the final shape. This results in low rigidity and post-machining distortion. The post-machining distortion is the deviation of the final shape from the original design after releasing the clamps. It is a major challenge in machining of the monolithic parts, which costs billions of economic losses every year. Three sources are directly related to the part distortion, including initial residual stresses (RS) generated from previous manufacturing processes, machining-induced RS and thermal load generated during machining. A finite element model was developed to simulate a milling process and predicate the post-machining distortion. In this study, a rolled-aluminum plate AA7175 with a thickness of 60 mm was used for the raw block. The initial residual stress distribution in the block was measured using a layer-removal method. A stress-mapping technique was developed to implement the initial stress distribution into the part. It is demonstrated that this technique significantly accelerates the simulation time. Machining-induced residual stresses on the machined surface were measured using MTS3000 hole-drilling strain-gauge system. The measured RS was applied on the machined surface of a plate to predict the distortion. The predicted distortion was compared with experimental results. It is found that the effect of the machining-induced residual stress on the distortion of a thick plate is very limited. The distortion can be ignored if the wall thickness is larger than a certain value. The RS generated from the thermal load during machining is another important factor causing part distortion. Very limited number of research on this topic was reported in literature. A coupled thermo-mechanical FE model was developed to evaluate the thermal effect on the plastic deformation of a plate. A moving heat source with a feed rate was used to simulate the dynamic cutting heat in a milling process. When the heat source passed the part surface, a small layer was removed to simulate the cutting operation. The results show that for different feed rates and plate thicknesses, the plastic deformation/distortion occurs only if the temperature exceeds a critical level. It was found that the initial residual stress has a major contribution to the part distortion. The machining-induced stress has limited influence on the distortion for thin-wall structure when the wall thickness is larger than a certain value. The thermal load can also generate part distortion when the cutting temperature is above a critical level. The developed numerical model was employed to predict the distortion of a frame part with complex structures. The predictions were compared with the experimental measurements, showing both are in good agreement. Through optimization of the position of the part inside the raw plate using the developed numerical models, the part distortion can be significantly reduced by 50%.

Keywords: modelling, monolithic parts, optimization, post-machining distortion, residual stresses

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Authors: Gyaltsen Dakpa, K. J. Senthil Kumar, Nai-Wen Tsao, Sheng-Yang Wang

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Context: Coronavirus disease 2019 (COVID-19) is a severe respiratory illness caused by the SARS-CoV-2 virus. One of the hallmarks of COVID-19 is a change in metabolism, which can lead to increased severity and mortality. The mechanism of SARS-CoV-2-mediated perturbations of metabolic pathways has yet to be fully understood. Research Aim: This study aimed to investigate the metabolic alteration caused by SARS-CoV-2 spike protein in Phorbol 12-myristate 13-acetate (PMA)-induced human monocytes (THP-1) and to examine the regulatory effect of natural compounds like Antcins A on SARS-CoV-2 spike protein-induced metabolic alteration. Methodology: The study used a combination of proton nuclear magnetic resonance (1H-NMR) and MetaboAnalyst 5.0 software. THP-1 cells were treated with SARS-CoV-2 spike protein or control, and the metabolomic profiles of the cells were compared. Antcin A was also added to the cells to assess its regulatory effect on SARS-CoV-2 spike protein-induced metabolic alteration. Findings: The study results showed that treatment with SARS-CoV-2 spike protein significantly altered the metabolomic profiles of THP-1 cells. Eight metabolites, including glycerol-phosphocholine, glycine, canadine, sarcosine, phosphoenolpyruvic acid, glutamine, glutamate, and N, N-dimethylglycine, were significantly different between control and spike-protein treatment groups. Antcin A significantly reversed the changes in these metabolites. In addition, treatment with antacid A significantly inhibited SARS-CoV-2 spike protein-mediated up-regulation of TLR-4 and ACE2 receptors. Theoretical Importance The findings of this study suggest that SARS-CoV-2 spike protein can cause significant metabolic alterations in THP-1 cells. Antcin A, a natural compound, has the potential to reverse these metabolic alterations and may be a potential candidate for developing preventive or therapeutic agents for COVID-19. Data Collection: The data for this study was collected from THP-1 cells that were treated with SARS-CoV-2 spike protein or a control. The metabolomic profiles of the cells were then compared using 1H-NMR and MetaboAnalyst 5.0 software. Analysis Procedures: The metabolomic profiles of the THP-1 cells were analyzed using 1H-NMR and MetaboAnalyst 5.0 software. The software was used to identify and quantify the cells' metabolites and compare the control and spike-protein treatment groups. Questions Addressed: The question addressed by this study was whether SARS-CoV-2 spike protein could cause metabolic alterations in THP-1 cells and whether Antcin A can reverse these alterations. Conclusion: The findings of this study suggest that SARS-CoV-2 spike protein can cause significant metabolic alterations in THP-1 cells. Antcin A, a natural compound, has the potential to reverse these metabolic alterations and may be a potential candidate for developing preventive or therapeutic agents for COVID-19.

Keywords: SARS-CoV-2-spike, ¹H-NMR, metabolomics, antcin-A, taiwanofungus camphoratus

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Authors: Mohammad Jamalabadi, Noemi Zabari, Lukasz Bratasz

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Panel paintings -complex multi-layer structures consisting of wood support and a paint layer composed of a preparatory layer of gesso, paints, and varnishes- are among the category of cultural objects most vulnerable to relative humidity fluctuations and frequently found in museum collections. The current environmental specifications in museums have been derived using the criterion of crack initiation in an undamaged, usually new gesso layer laid on wood. In reality, historical paintings exhibit complex crack patterns called craquelures. The present paper analyses the structural response of a paint layer with a virtual network of rectangular cracks under environmental loadings using a three-dimensional model of a panel painting. Two modes of loading are considered -one induced by one-dimensional moisture response of wood support, termed the tangential loading, and the other isotropic induced by drying shrinkage of the gesso layer. The superposition of the two modes is also analysed. The modelling showed that minimum distances between cracks parallel to the wood grain depended on the gesso stiffness under the tangential loading. In spite of a non-zero Poisson’s ratio, gesso cracks perpendicular to the wood grain could not be generated by the moisture response of wood support. The isotropic drying shrinkage of gesso produced cracks that were almost evenly spaced in both directions. The modelling results were cross-checked with crack patterns obtained on a mock-up of a panel painting exposed to a number of extreme environmental variations in an environmental chamber.

Keywords: fracture saturation, surface cracking, paintings on wood, wood panels

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Authors: Harukuni Tokuda, Takanari Arai, Xu FengHao, Nobutaka Suzuki

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In our continuous search for anti-tumor promoting, chemopreventive active potency from natural source material, a kind of healthy tea, Gromwell seed (Coix lachryma-jobi) ext., and including compounds Monoolein and Trilinolein have been screened using the in vitro synergistic assay indicated by inhibitory effects on the induction of Epstein-Barr virus early antigen (EBV-EA) by TPA. In assay, Gromwell seed aqueous extract and hot aqueous extract exhibited the potential inhibitory effects on EBV-EA activation without strong cytotoxicity on Raji cells. In our experimental system, the inhibitory effects of both Gromwell extracts and compounds were greater than that of beta-carotene, which is known anti-tumor promoting agent and/or chemopreventive agent. These compounds were evaluated for their in vitro inhibitory effect on EBV-EA activation induced by TPA. The percentages of the inhibition of TPA-induced EBV-EA activation for these materials were 60% and 30% at concentration 100 μg. Based on the results obtained in vitro, we studied the inhibitory effect of compounds, in an in vivo two-stage carcinogenesis test of mouse skin papilloma using DMBA as an initiator and TPA as a potential promoter. The control animals showed a 100% incidence of papilloma at 20 weeks after DMBA-TPA tumor promotion, while treatment with compounds reduced the percentage of number of tumor to 60 % after 20 weeks. Results from in vitro and in vivo studies showing chemopreventive activity against TPA promoting stage and these data support the effective potency of carcinogenic stage in clinical evaluation of integrative oncology.

Keywords: gromwell seed, medicinal plant, chemoprevention, pharmaceutical medicine

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Authors: Abazar Ghorbani, W. M. Wishwajith W. Kandegama, Seyed Mehdi Razavi, Moxian Chen

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The roles of hydrogen sulfide (H₂S) and melatonin (MT) as gasotransmitters in plants are widely recognised. Nevertheless, the precise nature of their involvement in defensive reactions remains uncertain. This study investigates the impact of the ML-H2S interaction on tomato plants exposed to vanadium (V) toxicity, focusing on synthesising secondary metabolites and V metal sequestration. The treatments applied in this study included a control (T1), V stress (T2), MT+V (T3), MT+H2S+V (T4), MT+hypotaurine (HT)+V (T5), and MT+H2S+HT+V (T6). These treatments were administered: MT (150 µM) as a foliar spray pre-treatment (3X), HT treatment (0.1 mM, an H2S scavenger) as root immersion for 12 hours as pre-treatments, and H2S (NaHS, 0.2 mM) and V (40 mg/L) treatments added to the Hoagland solution for 2 weeks. Results demonstrate that ML and H2S+ML treatments alleviate V toxicity by promoting the transcription of key genes (ANS, F3H, CHS, DFR, PAL, and CHI) involved in phenolic and anthocyanin biosynthesis. Moreover, they decreased V uptake and accumulation and enhanced the transcription of genes involved in glutathione and phytochelatin synthesis (GSH1, PCS, and ABC1), leading to V sequestration in roots and protection against V-induced damage. Additionally, ML and H2S+ML treatments optimize chlorophyll metabolism, and increase internal H2S levels, thereby promoting tomato growth under V stress. The combined treatment of ML+H2S shows superior effects compared to ML alone, suggesting synergistic/interactive effects between these two substances. Furthermore, inhibition of the beneficial impact of ML+H2S and ML treatments by HT, an H2S scavenger, underscores the significant involvement of H₂S in the signaling pathway activated by ML during V toxicity. Overall, these findings suggest that ML requires the presence of endogenous H₂S to mitigate V-induced adverse effects on tomato seedlings.

Keywords: vanadium toxicity, secondary metabolites, vanadium sequestration, h2s-melatonin crosstalk

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Authors: Ramasamy Tamizhselvi, Leema George, Madhav Bhatia

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We have earlier shown that mouse pancreatic acinar cells produce hydrogen sulfide (H2S) and play a role in the pathogenesis of acute pancreatitis. This study is to determine the effect of H2S on TLR4 mediated innate immune signaling in acute pancreatitis via substance P (SP). Male Swiss mice were treated with hourly intraperitoneal injection of caerulein (50μg/kg) for 10 hour. DL-propargylglycine (PAG) (100 mg/kg i.p.), an inhibitor of H2S formation was administered 1h after the induction of acute pancreatitis. Pancreatic acinar cells from male Swiss mice were incubated with or without caerulein (10–7 M for 60 min) and CP-96345 (NK1R inhibitor). To better understand the effect of H2S in inflammation, acinar cells were stimulated with caerulein after addition of H2S donor, NaHS. In addition, caerulein treated pancreatic acinar cells were pretreated with PAG (30 µM), for 1h. H2S inhibitor, PAG, eliminated TLR4, IRAK4, TRAF6 and NF-kB levels in an in vitro and in vivo model of caerulein-induced acute pancreatitis. PPTA gene deletion reduced TLR4, MyD88, IRAK4, TRAF6, adhesion molecules and NF-kB in caerulein treated pancreatic acinar cells whereas administration of NaHS resulted in further rise in TLR4 and NF-kB levels in caerulein treated pancreatic acinar cells. In addition, acini isolated from mice and treated with PPTA gene receptor NK1R antagonist CP96345 did not exhibit further increase in TLR4, IRAK4, TRAF6, adhesion molecules and NF-kB levels after NaHS pretreatment. The present findings show for the first time that in acute pancreatitis, H2S up-regulates TLR4 pathway and NF-kB via substance P.

Keywords: preprotachykinin-A gene, H2S, TLR4, acute pancreatitis

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Authors: Arfan Ali, Idrees Ahmad Nasir

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The critical evaluation of tolerance in tomato plants against the induced saline soil were assessed by transcript analysis of genes coding for products potentially involved in stress tolerance. A reverse transcriptase PCR experiment was performed with Hsp90-1, MT2, and GR1like protein genes using RNA isolated from different tissues of tomato plants. Four strains of Bacillus magisterium were inoculated with 100 Mm & 200 Mm concentrations of salt. Eleven treatments each ten replica pots were installed in green house experiment and the parameters taken into account were morphological (length, weight, number of leaves, leaf surface area), chemical (anthocyanin, chlorophyll-a, chlorophyll-b, carotenoids) and biological (gene expression). Results bare a response i.e. highest response of MT2 like gene was at 24 hpi and the highest levels of GR1 like protein transcript accumulation were detected at 36 hpi. The chemical and morphological parameters at diverse salt concentrations bequeath superlative response amongst strains which candidly flank on Zm7 and Zm4. Therefore, Bacillus magisterium Zm7 strains and somehow Zm4 strain can be used in saline condition to make plants tolerant. The overall performance of strains Zm7, Zm6, and Zm4 was found better for all studied traits under salt stress conditions. Significant correlations among traits root length, shoot length, number of leaves, leaf surface area, carotenoids, anthocyanin, chlorophyll-a and chlorophyll-b were found and suggested that the salt tolerance in tomato may be improved through the use of PGPR strains.

Keywords: Bacillus magisterium, gene expression glutathione reductase, metallothionein, PGPR, Rhizobacteria, saline

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Authors: Ahmed M. Kabel, Maaly A. Abd Elmaaboud

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Scleroderma is one of the connective tissue disorders characterized by skin and systemic fibrosis. Its pathogenesis involves multiple interrelated processes of autoimmunity, vasculopathy, inflammation, and oxidative stress. This study was a trial to explore the possible ameliorative effects of sodium valproate on an experimental model of skin fibrosis induced by bleomycin. Forty male BALB/c mice were divided into four equal groups as follows: control group; bleomycin group; bleomycin + sodium valproate group, and sodium valproate group. Mice were assessed for their body weight every four days throughout the whole study. Skin tissues were used to evaluate the oxidative stress parameters, transforming growth factor beta 1 (TGF-β1), tumor necrosis factor alpha (TNF-α), interleukin 15, and mammalian target of rapamycin (mTOR). Skin fibrosis was evaluated by measuring dermal thickness and staining the skin tissues with Masson trichrome stain. Also, the skin tissues were immunostained with alpha smooth muscle actin (α-SMA). Administration of sodium valproate to bleomycin-treated mice resulted in the restoration of the body weight with a significant decrease in the dermal thickness, amelioration of oxidative stress, suppression of TGF-β1 and mTOR expression, and significant reduction of the percentage of α-SMA immunostaining and the proinflammatory cytokine levels compared to mice treated with bleomycin alone. In conclusion, sodium valproate has an antifibrotic effect on skin fibrosis which may represent a beneficial therapeutic modality for the management of scleroderma.

Keywords: scleroderma, bleomycin, sodium valproate, skin fibrosis

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Authors: Nura Khattab, Fayad Al-Haimus, Teruko Kishibe, Netanel Krugliak, Melissa McGowan, Brodie Nolan

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Trauma-induced coagulopathy remains a significant contributor to mortality in severely injured patients. Fibrinogen is essential for early hemostasis and is recognized as the first coagulation factor to fall below critical levels, compromising the coagulation cascade. Early administration of fibrinogen concentrate may be feasible and effective to prevent coagulopathy. We conducted this scoping review to characterize the existing quantity of literature, and to explore the usage of prehospital fibrinogen concentrate products in improving clinical outcomes in trauma patients. Methods: A search strategy was developed in consultation with an information specialist. We searched MEDLINE, Embase, Cochrane, and Scopus from inception to May 6th 2024. English studies evaluating prehospital/military usage of fibrinogen concentrate in trauma patients were included. Studies were assessed by three independent reviewers for meeting inclusion and exclusion criteria. Reference lists of included articles were reviewed to identify additional studies meeting inclusion criteria. Clinical endpoints regarding fibrinogen concentrate were extracted and synthesized. Results: The literature search returned 1301 articles with seven studies meeting the inclusion criteria. Five studies (71%) were conducted in civilian settings and two studies (29%) were conducted in military settings. Of the included studies, three (43%) utilized a randomized control trial. We identified seven outcomes that compared varying concentrations of fibrinogen or fibrinogen concentrate to a placebo group. The outcomes included overall mortality, death from hemorrhage, thromboembolic events, clotting time, maximum clot firmness, clot stability at ER admission, and fibrinogen concentration at ER admission. Apart from thromboembolic events, all other reported outcomes showed statistically significant differences in group comparisons, determined using p values. The four (57%) non-clinical studies underscored the robustness, practicality, and degree of fibrinogen concentrate utilization in military environments and retrieval services. Conclusion: Preliminary research suggests that prehospital fibrinogen concentrate administration in traumatic bleeding patients is both feasible and effective, improving mortality and clotting parameters. While implementing a time-saving and proactive approach with fibrinogen holds potential for enhancing trauma care, the current evidence is limited. Further studies in this novel field are warranted.

Keywords: fibrinogen concentrate, prehospital, military, trauma, trauma-induced coagulopathy

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Authors: Bassant M. M. Ibrahim, Doha H. Abou Baker, Ahmed Abd Elghafour

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Excessive exposure to heavy metals contributes to the occurrence of deleterious health problems that affect vital organs like the brain, liver, kidneys, and heart. The use of natural products that have antioxidant capabilities may contribute to the protection of these organs. In the present study, the essential oil of summer savory (Satureja hortensis) was used to evaluate its protective effects against lead acetate induced damaging effect on rats’ vital organs, due to its high contents of carvacrol, y-terpinene, and p-cymene. Forty female Wister Albino rats were classified into five equal groups, the 1st served as normal group, the 2nd served as positive control group was given lead acetate (60 mg/kg) intra-peritoneal (IP), the third to fifth groups were treated with calcium disodium (EDTA) as chelating agent and summer savory essential oil in doses of (50 and 100mg/kg) respectively. All treatments were given IP concomitant with lead acetate for ten successive days. At the end of the experiment duration electrocardiogram (ECG), an open field test for the evaluation of psychological state, rotarod test as for the evaluation of locomotor coordination ability as well as anti-inflammatory and oxidative stress biomarkers in serum and histopathology of vital organs were performed. The investigations in this study show that the protective effect of high dose of summer savory essential oil is more than the low dose and that the essential oil of summer savory is a promising agent that can contribute to the protection of vital organs against the hazardous damaging effects of lead acetate.

Keywords: brain, heart, kidneys, lead acetate, liver, protective, summer savory

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Authors: Dong-Gyu Leem, Ji-Sun Shin, Sang Yoon Choi, Kyung-Tae Lee

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In this study, we focused on the anti-proliferative effects of panaxydol, a C17 polyacetylenic compound derived from Panax ginseng roots, against various human cancer cells. We treated with panaxydol to various cancer cells and panaxydol treatment was found to significantly inhibit the proliferation of human lung cancer cells (A549) and human pancreatic cancer cells (AsPC-1 and MIA PaCa-2), of which AsPC-1 cells were most sensitive to its treatment. DNA flow cytometric analysis indicated that panaxydol blocked cell cycle progression at the G1 phase in A549 cells, which accompanied by a parallel reduction of protein expression of cyclin-dependent kinase (CDK) 2, CDK4, CDK6, cyclin D1 and cyclin E. CDK inhibitors (CDKIs), such as p21CIP1/WAF1 and p27KIP1, were gradually upregulated after panaxydol treatment at the protein levels. Furthermore, panaxydol induced the activation of p53 in A549 cells. In addition, panaxydol also induced apoptosis of AsPC-1 and MIA PaCa-2 cells, as shown by accumulation of subG1 and apoptotic cell populations. Panaxydol triggered the activation of caspase-3, -8, -9 and the cleavage of poly (ADP-ribose) polymerase (PARP). Reduction of mitochondrial transmembrane potential by panaxydol was determined by staining with dihexyloxacarbocyanine iodide. Furthermore, panaxydol suppressed the levels of anti-apoptotic proteins, XIAP and Bcl-2, and increased the levels of proapoptotic proteins, Bax and Bad. In addition, panaxydol inhibited the activation of Akt and extracellular signal-regulated kinase (ERK) and activated the p38 mitogen-activated protein kinase kinase (MAPK). Our results suggest that panaxydol is an anti-tumor compound that causes p53-mediated cell cycle arrest and apoptosis via mitochondrial apoptotic pathway in various cancer cells.

Keywords: apoptosis, cancer, G1 arrest, panaxydol

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Authors: Rashmi Ranade, Neelu Joshi

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Barleria prionitis L. is a well explored Indian medicinal plant valued for its stem and leaf which forms an important ingredient of many Ayurvedic formulations. It is used for the treatment of various disorders like toothache, bleeding gums, strengthening gums, whooping cough, inflammation, arthritis, enlargement of scrotum and sciatica etc. The plant is propagated vegetatively through stem cuttings. Frequent harvesting of this plant has led to the shortage of planting material, and it has acquired the status of vulnerable plant species. Plant tissue culture technology offers a very good alternative for propagation and conservation of such plant species. The present investigation was undertaken to develop in vitro regeneration protocol for B. prionitis L. via callus organogenesis pathway. Stem and leaf explants were used for this purpose. Different media and plant growth regulators were optimized to develop the protocol. The problem of phenol secretion and browning and in vitro cultures at the establishment phase was successfully curbed with the usage of antibrowning agents such as ascorbic acid and activated charcoal. Optimum shoot multiplication was achieved by the use of liquid media and incorporation of silver nitrate and TIBA (triiodobenzoic acid) into the media. High percent rooting (76%) was observed on WPM media supplemented with IBA (2.0 mg/l), IAA (0.5 mg/l), GA3(0.5) and activated charcoal(500 mg/l). The rooted plantlets were subjected to in vitro hardening on sterile potting mix (soil:farmyard manure:compost; 1:2:1) and acclimatized under greenhouse conditions. Around 85% survival of plantlets was recorded upon acclimatization. This lab scale protocol would be tested for in vitro scaling up production of B. prionitis L.

Keywords: explant browning, liquid culture, micropropagation, shoot multiplication, phenolic secretion

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Authors: Priyanka Bhowmik, Subrata Majumdar, Debprasad Chattopadhyay

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Background: Cervical cancer is the third major cause of cancer in women and the second most frequent cause of cancer related deaths causing 300,000 deaths annually worldwide. Evasion of immune response by Human Papilloma Virus (HPV), the key contributing factor behind cancer and pre-cancerous lesions of the uterine cervix, makes immunotherapy a necessity to treat this disease. Objective: A Heat killed fraction of Mycobacterium indicus pranii (MIP), a non-pathogenic Mycobacterium has been shown to exhibit cytotoxic effects on different cancer cells, including human cervical carcinoma cell line HeLa. However, the underlying mechanisms remain unknown. The aim of this study is to decipher the mechanism of MIP induced HeLa cell death. Methods: The cytotoxicity of Mycobacterium indicus pranii against HeLa cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by annexin V and Propidium iodide (PI) staining. The assessment of reactive oxygen species (ROS) generation and cell cycle analysis were measured by flow cytometry. The expression of apoptosis associated genes was analyzed by real time PCR. Result: MIP could inhibit the proliferation of HeLa cell in a time and dose dependent manner but caused minor damage to normal cells. The induction of apoptosis was confirmed by the cell surface presentation of phosphatidyl serine, DNA fragmentation, and mitochondrial damage. MIP caused very early (as early as 30 minutes) transcriptional activation of p53, followed by a higher activation (32 fold) at 24 hours suggesting prime importance of p53 in MIP-induced apoptosis in HeLa cell. The up regulation of p53 dependent pro-apoptotic genes Bax, Bak, PUMA, and Noxa followed a lag phase that was required for the transcriptional p53 program. MIP also caused the transcriptional up regulation of Toll like receptor 2 and 4 after 30 minutes of MIP treatment suggesting recognition of MIP by toll like receptors. Moreover, MIP caused the inhibition of expression of HPV anti apoptotic gene E6, which is known to interfere with p53/PUMA/Bax apoptotic cascade. This inhibition might have played a role in transcriptional up regulation of PUMA and subsequently apoptosis. ROS was generated transiently which was concomitant with the highest transcription activation of p53 suggesting a plausible feedback loop network of p53 and ROS in the apoptosis of HeLa cells. Scavenger of ROS, such as N-acetyl-L-cysteine, decreased apoptosis suggesting ROS is an important effector of MIP induced apoptosis. Conclusion: Taken together, MIP possesses full potential to be a novel therapeutic agent in the clinical treatment of cervical cancer.

Keywords: cancer, mycobacterium, immunity, immunotherapy.

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Authors: Rashmi Shukla, Yamini Bhusan Tripathi

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Diabetic nephropathy (DN) is characterized as diabetic kidney disease which involves many pathways e.g. hyperactivated protein kinase c (PKC), polyol pathway, excess production of advanced glycation end product (AGEs) & free radical accumulation etc. All of them results to hypoxia followed by apoptosis of podocytes, glomerulosclerosis, extracellular matrix (ECM) accumulation and fibrosis resulting to irreversible changes in kidney. This is continuously rising worldwide and there are not enough specific drugs, to retard its progress. Due to increasing side effects of allopathic drugs, interest in herbal remedies is growing. Earlier, we have reported that PTY-2 (a phytomedicine, derived from Pueraria tuberosa Linn.) inhibits the accumulation of extracellular matrix (ECM) through activation of MMP-9. Present study exhibited the therapeutic potential of Pueraria tuberosa in the prevention of podocytes apoptosis and modulation of nephrin expression in streptozotocin (STZ) induced DN rats. DN rats were produced by maintaining persistent hyperglycemia for 8 weeks by intra-peritoneal injection of 55 mg/kg streptozotocin (STZ). These rats were randomly divided in 2 groups, i.e. DN control, and DN+ water extract of Pueraria tuberosa (PTW). One group of age-matched normal rats served as non-diabetic control (group-1), The STZ induced DN rats (group-2) and DN+PTW treated rats (group-3). The PTW was orally administered (0.3g/kg) daily to group-2 rats and drug vector (1 ml of 10% tween 20) in control rats. The treatments were continued for 20 days and blood and urine samples were collected. Rats were then sacrificed to investigate the expression Bcl2, Bax and nephroprotective protein i.e. nephrin in kidney glomerulus. The effect of PTW was evaluated, we have found that the PTW significantly(p < .001) reversed the raised serum urea, serum creatinine, urine protein and improved the creatinine clearance in STZ induce diabetic nephropathy in rats and also significantly(p < .001) prevented the rise in urine albumin excretion. The Western blot analysis of kidney tissue homogenate showed increased expression of Bcl2 in PTW treated rats. The RT-PCR showed the increased expression and accumulation of nephrin mRNA. The confocal photomicrographs also supported the reduction of Bax and a simultaneous increase in Bcl2 and nephrin in glomerular podocytes. Hence, our finding suggests that the nephroprotective role of PTW is mediated via restoration of nephrin thus prevents the podocytes apoptosis and ameliorates diabetic nephropathy. The clinical trial of PTW would prove to be a potential food supplement/ drug of alternative medicine for patients with diabetic nephropathy in early stage.

Keywords: Pueraria tuberosa, diabetic nephropathy, anti-apoptosis, nephrin

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Authors: Huma Shareef, Ghazala H. Rizwani, Ahsana Dar

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In traditional medicine Cardiospermum halicacabum L. (Sapindeaceae) is used against various ailments. In current investigation searching a new remedy that will available easily, non expensive, able to lower hypertension and standardize blood pressure, made us to develop an herbal medicine. Crude ethanol extract of C. halicacabum and its various fractions ethyl acetate and butanol showed a dose-dependent hypotensive effect in anaesthetized rats. The trachea was exposed and freed from connective tissue and incubated by cannula to facilitate spontaneous respiration. The right carotid artery and left jugular vein were cannulated with polyethylene tubing PE-50 for monitoring blood pressure changes via pressure transducer (Gould P23 ID) connected to a Grass model 79D polygraph and for i.v. injection, respectively. Drugs or the plant extracts were administered at a constant volume of 0.5 ml/kg, followed by injection of 0.2 ml of saline that flushed the cannula. Systolic, diastolic and mean arterial blood pressure (MABP) was measured in mm Hg and heart rate in beats/min. Ethanol extract of C. halicacabum showed a significant activity at 50 mg/kg dose. Ethyl acetate fraction (10, 20, 30, 40, and 50 mg/kg) induced dose dependent fall in systolic and diastolic blood pressure, heart rate of rats. At 10-30 mg/kg the hypotensive effect was non significantly reduced by 10 -15%. However, the extract at 40 mg/kg induced significant hypotensive effect calculated as 30.95±3.2% MABP and this effect persists till 50 mg/kg. The higher polar fraction (butanol) of the whole plant failed to produce any significant response against MABP at all the tested doses (10-50 mg/kg). C. halicacabum lowers blood pressure, exerts a dose-dependent hypotensive effect, can be used as hypotensor.

Keywords: cardiospermum halicacabum, calcium channel blocker, hypotensive, various extracts

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Authors: A. Newman-Tancredi, R. Depoortère, P. Gruca, E. Litwa, M. Lason, M. Papp

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The N-methyl-D-aspartic acid (NMDA) receptor antagonist, ketamine, can elicit rapid-acting antidepressant (RAAD) effects in treatment-resistant patients, but it requires parenteral co-administration with a classical antidepressant under medical supervision. In addition, ketamine can also produce serious side effects that limit its long-term use, and there is much interest in identifying RAADs based on ketamine’s mechanism of action but with safer profiles. Ketamine elicits GABAergic interneuron inhibition, glutamatergic neuron stimulation, and, notably, activation of serotonin 5-HT1A receptors in the prefrontal cortex (PFC). Direct activation of the latter receptor subpopulation with selective ‘biased agonists’ may therefore be a promising strategy to identify novel RAADs and, consistent with this hypothesis, the prototypical cortical biased agonist, NLX-101, exhibited robust RAAD-like activity in the chronic mild stress model of depression (CMS). The present study compared the effects of a novel, selective 5-HT1A receptor-biased agonist, NLX-204, with those of ketamine and NLX-101. Materials and methods: CMS procedure was conducted on Wistar rats; drugs were administered either intraperitoneally (i.p.) or by bilateral intracortical microinjection. Ketamine: 10 mg/kg i.p. or 10 µg/side in PFC; NLX-204 and NLX-101: 0.08 and 0.16 mg/kg i.p. or 16 µg/side in PFC. In addition, interaction studies were carried out with systemic NLX-204 or NLX-101 (each at 0.16 mg/kg i.p.) in combination with intracortical WAY-100635 (selective 5-HT1A receptor antagonist; 2 µg/side) or muscimol (GABA-A receptor agonist, 12.5 ng/side). Anhedonia was assessed by CMS-induced decrease in sucrose solution consumption; anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), and cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Results: A single administration of NLX-204 was sufficient to reverse the CMS-induced deficit in sucrose consumption, similarly to ketamine and NLX-101. NLX-204 also reduced CMS-induced anxiety in the EPM and abolished CMS-induced NOR deficits. These effects were maintained (EPM and NOR) or enhanced (sucrose consumption) over a subsequent 2-week period of treatment. The anti-anhedonic response of the drugs was also maintained for several weeks Following treatment discontinuation, suggesting that they had sustained effects on neuronal networks. A single PFC administration of NLX-204 reversed deficient sucrose consumption, similarly to ketamine and NLX-101. Moreover, the anti-anhedonic activities of systemic NLX-204 and NLX 101 were abolished by coadministration with intracortical WAY-100635 or muscimol. Conclusions: (i) The antidepressant-like activity of NLX-204 in the rat CMS model was as rapid as that of ketamine or NLX-101, supporting targeting cortical 5-HT1A receptors with selective, biased agonists to achieve RAAD effects. (ii)The anti-anhedonic activity of systemic NLX-204 was mimicked by local administration of the compound in the PFC, confirming the involvement of cortical circuits in its RAAD-like effects. (iii) Notably, the effects of systemic NLX-204 and NLX-101 were abolished by PFC administration of muscimol, indicating that they act by (indirectly) eliciting a reduction in cortical GABAergic neurotransmission. This is consistent with ketamine’s mechanism of action and suggests that there are converging NMDA and 5-HT1A receptor signaling cascades in PFC underlying the RAAD-like activities of ketamine and NLX-204. Acknowledgements: The study was financially supported by NCN grant no. 2019/35/B/NZ7/00787.

Keywords: depression, ketamine, serotonin, 5-HT1A receptor, chronic mild stress

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Authors: Mrinal Mukherjee, Gargi Seal, Bitopan Mazumdar, Prakhar Agarwal

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The central sector of Palghat-Cauvery Shear zone Tamil Nadu, India, had been studied with reference to development, mode of occurrence, interrelationship and variation of structural elements. The litho assemblages of the study area include gneisses migmatites granites and bear signature of multistage deformation patterns. The early deformation D1 is characterized in migmatites and gneisses by the development of tight to isoclinal, recumbent to reclined folds within the compositional bands that are refolded subsequently to produce D2 deformation structures ranging from type-II to type-III superposed geometry. The granite, in general, is undeformed, save a few places where strong mylonitic foliation developed with stretching lineation on it. The D1-D2 structures of gneisses and migmatites were affected by a D3 stage- E-W trending shear zone (Palghat-Cauvery Shear zone) that dips steeply towards north. The shear zone is characterized by the development of mylonite zone with stretching lineation on foliation, shear band structures, modification of geometry and orientation of earlier folds and foliations within the shear zone and development of shear induced folds and foliations. Several anastomosing lenses of shear zones define the larger Palghat-Cauvery Shear zone. The orientation of the shear induced folds and foliations and deflections of earlier foliation and folds within the Palghat-Cauvery shear zone indicate an oblique-slip thrust-shear with north-towards-east sense of displacement. The E-W trending shear zone is further openly folded along N-S in the D4 stage of deformation.

Keywords: deformation, migmatites, mylonites, shear zones

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Authors: Aisling Eves, Andrew Pieri, Ross McLean, Nerys Forester

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Background: DCIS accounts for 20% of malignancies diagnosed by the breast screening programme and is primarily managed by surgical excision. There is variable guidance on defining excision margins, and adjuvant treatments vary widely. This study aimed to investigate the clinical outcomes for patients following surgical excision of small volume DCIS. Methods: This single-centreretrospective cohort study of 101 consecutive breast screened patients diagnosed with DCIS who underwent surgical excision. All patients diagnosed with DCIS had radiological abnormalities <15mm. Clinical, radiological, and histological data were collected from patients who had been diagnosed within a 5 year period, and ASCO guidelines for margin involvement of <2mm was used to guide the need for re-excision. Outcomes included re-excision rates, radiotherapy usage, and the presence of invasive cancer. Results: Breast conservation surgery was performed in 94.1% (n=95). Following surgical excision, 74(73.27%)patients had complete DCIS excision (>2mm margin), 4(4.0%) had margins 1-2mm, and 17(16.84%)had margins <1mm. The median size of DCIS in the specimen sample was 4mm. In 86% of patients with involved margins (n=18), the mammogram underestimated the DCIS size by a median of 12.5mm (range: 1-42mm). Of the patients with involved margins, 11(10.9%)had a re-excision, and 6 of these (50%) required two re-excisions to completely excise the DCIS. Post-operative radiotherapy was provided to 53(52.48%)patients. Four (3.97%) patients were found to have invasive ductal carcinoma on surgical excision, which was not present on core biopsy – all had high-grade DCIS. Recurrence of DCIS was seen in the same site during follow-up in 1 patient (1%), 1 year after their first DCIS diagnosis. Conclusion: Breast conservation surgery is safe in patients with DCIS, with low rates of re-excision, recurrence, and upstaging to invasive cancer. Furthermore, the median size of DCIS found in the specimens of patients who had DCIS fully removed in surgery was low, suggesting it may be possible that total removal through VAE was possible for these patients.

Keywords: surgical excision, breast conservation surgery, DCIS, Re-excision, radiotherapy, invasive cancer

Procedia PDF Downloads 133

Authors: Arindam Chowdhury, Andres Tremante, Mohammadtaghi Moravej, Bodhisatta Hajra, Ioannis Zisis, Peter Irwin

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Extreme wind events, such as hurricanes, have caused significant damage to buildings, resulting in losses worth millions of dollars. The roof of a building is most vulnerable to wind-induced damage due to the high suctions experienced by the roof in extreme wind conditions. Wind turbines fitted to buildings can help generate energy, but to our knowledge, their application to wind load mitigation is not well known. This paper presents results from an experimental study to assess the effect of small wind turbines (developed and patented by the first and second authors) on the wind loads on a low rise building roof. The tests were carried out for an open terrain at the Wall of Wind (WOW) experimental facility at Florida International University (FIU), Miami, Florida, USA, for three cases – bare roof, roof fitted with wind turbines placed closer to the roof edges, and roof with wind turbines placed away from the roof edges. Results clearly indicate that the presence of the wind turbines reduced the mean and peak pressure coefficients (less suction) on the roof when compared to the bare deck case. Furthermore, the peak pressure coefficients were found to be lower (less suction) when the wind turbines were placed closer to the roof, than away from the roof. Flow visualization studies using smoke and gravel clearly showed that the presence of the turbines disrupted the formation of vortices formed by cornering winds, thereby reducing roof suctions and preventing lift off of roof coverings. This study shows that the wind turbines besides generating wind energy, can be used for mitigating wind induced damage to the building roof. Future research must be directed towards understanding the effect of these wind turbines on other roof geometries (e.g. hip/gable) in different terrain conditions.

Keywords: wall of wind, wind loads, wind turbine, building

Procedia PDF Downloads 249

Authors: Shashi Bala, Neha A. Chugh, Subhash C. Bansal, Mohal L. Garg, Ashwani Koul

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Purpose: The present study was designed to evaluate the radioprotective efficacy of Aloe vera from whole body X-ray exposure in rodents. Materials and Methods: For this purpose, after on week’s acclimatization, male balb/c mice procured from Central Animal House, Panjab University, Chandigarh (India), were divided into four groups: Group I mice served as control. Group II mice were orally administrated Aloe vera pulp extract (50 mg/ kg body weight) on alternate days for 30 days. Group III mice were subjected to whole body X-ray irradiation to cumulative dose of 2Gy (0.258Gy twice a day for four days in the last week). Group IV animals were pretreated with Aloe vera pulp extract on alternate days as in Group II and in the last week of the study, they were exposed to X-ray as in Group III. Results: Spleen of X-ray irradiated mice showed histopathological alterations accompanied with enhanced activity of lactate dehydrogenase (LDH) in serum. Elevated levels of reactive oxygen species (ROS), lipid peroxidation (LPO), enhanced activities in Glutathione based enzymes such as Glutathione peroxidase (GSH-Px), Glutathione reductase (GR), Catalase (CAT), Superoxide dismutase (SOD) associated with depletion in reduced Glutathione (GSH) concentration were observed after X-ray exposure in blood plasma and spleen.. Pro-inflammatory cytokines like tumor necrosis factors (TNF-α) and Inteleukin-6 (IL-6) levels were also found to be enhanced in serum of irradiated mice. Irradiation-induced significant elevation in Total leucocyte counts (TLC), neutrophil counts and decline in platelet counts, associated with unaltered levels of red blood cell counts (RBC’s) and haemoglobin (Hb) in various treatment groups. Clastogenic damage and apoptosis was also found to be increase in splenic tissue of X-ray exposed mice as assessed by micronucleus and TUNEL assay. However, X-ray irradiated animals administered with Aloe vera revealed significant improvement in levels of ROS/ LPO, LDH activity, and antioxidant mechanism. Aloe vera pretreated animals exhibited less severe damage, and early recovery in micronucleated cells, hematological parameters, apoptotic cells and inflammatory markers as compared to X-ray exposed mice. Conclusion: These results indicate that the radioprotective potential of Aloe vera against X-ray induced damage. This may be due to its free radical scavenging, antioxidant, anti-apoptotic and anti-inflammatory properties.

Keywords: aloe vera, antioxidant defense system, lactate dehydrogenase (LDH), micronucleus assay, x-ray

Procedia PDF Downloads 192

Authors: Izuddin Fahmy Abu, Mohamad Haiqal Nizar Mohamad, Muhammad Fattah Fazel, Renu Agarwal, Igor Iezhitsa, Nor Salmah Bakar, Henrik Franzyk, Ian Mellor

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Glaucoma is the global leading cause of irreversible blindness. Currently, the available treatment strategy only involves lowering intraocular pressure (IOP); however, the condition often progresses despite lowered or normal IOP in some patients. N-methyl-D-aspartate receptor (NMDAR) excitotoxicity often occurs in neurodegeneration-related glaucoma; thus it is a relevant target to develop a therapy based on neuroprotection approach. This study investigated the effects of Philanthotoxin-343 (PhTX-343), an NMDAR antagonist, on the neuroprotection of NMDA-induced glaucoma to alleviate visual impairments. Male Sprague-Dawley rats were equally divided: Groups 1 (control) and 2 (glaucoma) were intravitreally injected with phosphate buffer saline (PBS) and NMDA (160nM), respectively, while group 3 was pre-treated with PhTX-343 (160nM) 24 hours prior to NMDA injection. Seven days post-treatments, rats were subjected to visual behavior assessments and subsequently euthanized to harvest their retina and optic nerve tissues for histological analysis and determination of nitrosative stress level using 3-nitrotyrosine ELISA. Visual behavior assessments via open field, object, and color recognition tests demonstrated poor visual performance in glaucoma rats indicated by high exploratory behavior. PhTX-343 pre-treatment appeared to preserve visual abilities as all test results were significantly improved (p < 0.05). H&E staining of the retina showed a marked reduction of ganglion cell layer thickness in the glaucoma group; in contrast, PhTX-343 significantly increased the number by 1.28-folds (p < 0.05). PhTX-343 also increased the number of cell nuclei/100μm2 within inner retina by 1.82-folds compared to the glaucoma group (p < 0.05). Toluidine blue staining of optic nerve tissues showed that PhTX-343 reduced the degeneration changes compared to the glaucoma group which exhibited vacuolation overall sections. PhTX-343 also decreased retinal 3- nitrotyrosine concentration by 1.74-folds compared to the glaucoma group (p < 0.05). All results in PhTX-343 group were comparable to control (p > 0.05). We conclude that PhTX-343 protects against NMDA-induced changes and visual impairments in the rat model by reducing nitrosative stress levels.

Keywords: excitotoxicity, glaucoma, nitrosative stress , NMDA receptor , N-methyl-D-aspartate , philanthotoxin, visual behaviour

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Authors: Jinyoung Park, Eun Joo Song

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Introduction: Deubiquitinating enzymes (DUBs) are proteases that cleave ubiquitin or ubiquitin-like modifications on substrates. Deubiquitination could regulate cellular physiology, such as signal transduction, DNA damage and repair, and cell cycle progression. Although more than 100 DUBs are encoded in the human and the importance of DUBs has been realized, the functions of most DUBs are unknown. This study aims to identify the molecular mechanism by which deubiquitinating enzyme USP35 regulates cell cycle progression for the first time. Methods: USP35 RNAi was mainly used to identify the function of USP35 in cell cycle progression. To find substrates of USP35, we analyzed protein-protein interaction using LC-MS. Several biological methods, such as ubiquitination assay, cell synchronization, immunofluorescence, and immunoprecipitation assay were used to investigate the exact mechanism by which USP35 affects successful completion of mitosis. Results: USP35 knockdown caused not only reduction of mitotic cell number but also induction of mitotic cells with abnormal spindle formation. Actually, cell proliferation was decreased by USP35 knockdown. Interestingly, we found that loss of USP35 decreased the stability and expression of Aurora B, a member of chromosomal passenger complex (CPC), and the phosphorylation of its substrate. Indeed, USP35 interacted with Aurora B and deubiquitinated it. In addition, USP35 knockdown induced abnormal localization of Aurora B in mitotic cells. Finally, CDH1-mediated ubiquitination of Aurora B level was rescued by USP35 overexpression, but not inactive form of USP35, USP35 C450A. Discussion: Our findings suggest that USP35 regulates Aurora B-mediated mitotic spindle assembly and G2-M transition by blocking CDH1-induced degradation of Aurora B.

Keywords: USP35, HSP90, Aurora B, cell cycle progression

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