Search results for: egfr inhibitors

Authors: A. Kherraf, M. Bouziane, L. Azzouzi, R. Habbal

Abstract:

Introduction: Hypocalcaemia is a rare cause of heart failure. We report the clinical case of a young patient with reversible dilated cardiomyopathy secondary to hypocalcaemia in the context of hyperparathyroidism. Clinical case: We report the clinical case of a 23-year-old patient with a history of thyroidectomy for papillary thyroid carcinoma 3 years previously, who presented to the emergency room with a progressive onset dyspnea and edema of the lower limbs. Clinical examination showed hypotension at 90/70 mmHg, tachycardia at 102 bpm, and edema of the lower limbs. The ECG showed a regular sinus rhythm with a prolonged corrected QT interval to 520ms. The chest x-ray showed cardiomegaly. Echocardiography revealed dilated cardiomyopathy with biventricular dysfunction and a left ventricular ejection fraction of 45%, as well as moderate mitral insufficiency by restriction of the posterior mitral leaflet, moderate tricuspid insufficiency, and a dilated inferior vena cava with a pulmonary arterial pressure estimated at 46 mmHg. Blood tests revealed severe hypocalcemia at 38 mg / l with normal albumin and thyroxine levels, as well as hyperphosphatemia and increased TSH. The patient received calcium intake and vitamin D supplementation and was treated with beta blockers, ACE inhibitors, and diuretics with good progress and progressive normalization of cardiac function. Discussion: The cardiovascular manifestations of hypocalcaemia usually appear with deeply low serum calcium levels. This can lead to hypotension, arrhythmias, ventricular fibrillation, prolonged QT interval, or even heart failure. Heart failure is a rare and serious complication of hypocalcemia but most often characterized by complete normalization of myocardial function after treatment. The etiology of the hypocalcaemia, in this case, was probably related to accidental parathyroid removal during thyroidectomy. This is why careful monitoring of calcium levels is recommended after surgery. Conclusion: Hypocalcemic heart failure is rare but reversible heart disease. Systematic monitoring of serum calcium should be performed in all patients after thyroid surgery to avoid any complications related to hypoparathyroidism.

Keywords: hypocalcemia, heart failure, thyroid surgery, hypoparathyroidism

Procedia PDF Downloads 143

Authors: Gizachew Mulugeta Manahelohe, Khidmet Safarovich Shikhaliev

Abstract:

There has been a significant surge in interest in the synthesis of heterocyclic compounds that contain hydroquinoline fragments. This surge can be attributed to the broad range of pharmaceutical and industrial applications that these compounds possess. The present study provides a comprehensive account of the synthesis of both linear and fused heterocyclic systems that incorporate hydroquinoline fragments. Furthermore, the pharmacological activity spectra of the synthesized compounds were assessed using the in silico method, employing the prediction of activity spectra of substances (PASS) program. Hydroquinoline nitriles 7 and 8 were prepared through the reaction of the corresponding hydroquinolinecarbaldehyde using a hydroxylammonium chloride/pyridine/toluene system and iodine in aqueous ammonia under ambient conditions, respectively. 2-Phenyl-1,3-oxazol-5(4H)-ones 9a,b and 10a,b were synthesized via the condensation of compounds 5a,b and 6a,b with hippuric acid in acetic acid in 30–60% yield. When activated, 7-methylazolopyrimidines 11a and b were reacted with N-alkyl-2,2,4-trimethyl-1,2,3,4-tetrahydroquinoline-6-carbaldehydes 6a and b, and triazolo/pyrazolo[1,5-a]pyrimidin-6-yl carboxylic acids 12a and b were obtained in 60–70% yield. The condensation of 7-hydroxy-1,2,3,4-tetramethyl-1,2-dihydroquinoline 3 h with dimethylacetylenedicarboxylate (DMAD) and ethyl acetoacetate afforded cyclic products 16 and 17, respectively. The condensation reaction of 6-formyl-7-hydroxy-1,2,2,4-tetramethyl-1,2-dihydroquinoline 5e with methylene-active compounds such as ethyl cyanoacetate/dimethyl-3-oxopentanedioate/ethyl acetoacetate/diethylmalonate/Meldrum’s acid afforded 3-substituted coumarins containing dihydroquinolines 19 and 21. Pentacyclic coumarin 22 was obtained via the random condensation of malononitrile with 5e in the presence of a catalytic amount of piperidine in ethanol. The biological activities of the synthesized compounds were assessed using the PASS program. Based on the prognosis, compounds 13a, b, and 14 exhibited a high likelihood of being active as inhibitors of gluconate 2-dehydrogenase, as well as possessing antiallergic, antiasthmatic, and antiarthritic properties, with a probability value (Pa) ranging from 0.849 to 0.870. Furthermore, it was discovered that hydroquinoline carbonitriles 7 and 8 tended to act as effective progesterone antagonists and displayed antiallergic, antiasthmatic, and antiarthritic effects (Pa = 0.276–0.827). Among the hydroquinolines containing coumarin moieties, compounds 17, 19a, and 19c were predicted to be potent progesterone antagonists, with Pa values of 0.710, 0.630, and 0.615, respectively.

Keywords: heterocyclic compound, hydroquinoline, Vilsmeier–Haack formulation, quinolone

Procedia PDF Downloads 42

Authors: Gulsharat A. Baigonakova, Ekaterina S. Marchenko, Venera R. Luchsheva

Abstract:

The preferred materials for bone grafting are titanium-nickel alloys. They have a porous, permeable structure similar to that of bone tissue, can withstand long-term physiological stress in the body, and retain the scaffolding function for bone tissue ingrowth. Despite the excellent functional properties of these alloys, there is a possibility of post-operative infectious complications that prevent the newly formed bone tissue from filling the spaces created in a timely manner and prolong the rehabilitation period of patients. In order to minimise such consequences, it is necessary to use biocompatible materials capable of simultaneously fulfilling the function of a long-term functioning implant and an osteoreplacement carrier saturated with drugs. Methods to modify the surface by saturation with bioactive substances, in particular macrocyclic compounds, for the controlled release of drugs, biologically active substances, and cells are becoming increasingly important. This work is dedicated to the functionalisation of the surface of porous titanium nickelide by the deposition of macrocyclic compounds in order to provide titanium nickelide with antibacterial activity and accelerated osteogenesis. The paper evaluates the effect of macrocyclic compound deposition methods on the continuity, structure, and cytocompatibility of the surface properties of porous titanium nickelide. Macrocyclic compounds were deposited on the porous surface of titanium nickelide under the influence of various physical effects. Structural research methods have allowed the evaluation of the surface morphology of titanium nickelide and the nature of the distribution of these compounds. The method of surface functionalisation of titanium nickelide influences the size of the deposited bioactive molecules and the nature of their distribution. The surface functionalisation method developed has enabled titanium nickelide to be deposited uniformly on the inner and outer surfaces of the pores, which will subsequently enable the material to be uniformly saturated with various drugs, including antibiotics and inhibitors. The surface-modified porous titanium nickelide showed high biocompatibility and low cytotoxicity in in vitro studies. The research was carried out with financial support from the Russian Science Foundation under Grant No. 22-72-10037.

Keywords: biocompatibility, NiTi, surface, porous structure

Procedia PDF Downloads 83

Authors: Dugeree Otgongerel, Kyong Jin Cho, Yu-Han Kim, Sangmee Ahn Jo

Abstract:

Excessive activation of glutamate receptor is thought to be involved in retinal ganglion cell (RGC) death after ischemia- reperfusion damage. Glutamate carboxypeptidase II (GCPII) is an enzyme responsible for the synthesis of glutamate. Several studies showed that inhibition of GCPII prevents or reduces cellular damage in brain diseases. Thus, in this study, we examined the expression of GCPII in rat retina and the role of GCPII in acute high IOP ischemia-reperfusion damage of eye by using a GCPII inhibitor, 2-(phosphonomethyl) pentanedioic acid (2-PMPA). Animal model of ischemia-reperfusion was induced by raising the intraocular pressure for 60 min and followed by reperfusion for 3 days. Rats were randomly divided into four groups: either intra-vitreous injection of 2-PMPA (11 or 110 ng per eye) or PBS after ischemia-reperfusion, 2-PMPA treatment without ischemia-reperfusion and sham-operated normal control. GCPII immunoreactivity in normal rat retina was detected weakly in retinal nerve fiber layer (RNFL) and retinal ganglionic cell layer (RGL) and also inner plexiform layer (IPL) and outer plexiform layer (OPL) strongly where are co-stained with an anti-GFAP antibody, suggesting that GCPII is expressed mostly in Muller and astrocytes. Immunostaining with anti-BRN antibody showed that ischemia- reperfusion caused RGC death (31.5 %) and decreased retinal thickness in all layers of damaged retina, but the treatment of 2-PMPA twice at 0 and 48 hour after reperfusion blocked these retinal damages. GCPII level in RNFL layer was enhanced after ischemia-reperfusion but was blocked by PMPA treatment. This result was confirmed by western blot analysis showing that the level of GCPII protein after ischemia- reperfusion increased by 2.2- fold compared to control, but this increase was blocked almost completely by 110 ng PMPA treatment. Interestingly, GFAP immunoreactivity in the retina after ischemia- reperfusion followed by treatment with PMPA showed similar pattern to GCPII, increase after ischemia-reperfusion but reduction to the normal level by PMPA treatment. Our data demonstrate that increase of GCPII protein level after ischemia-reperfusion injury is likely to cause glial activation and/or retinal cell death which are mediated by glutamate, and GCPII inhibitors may be useful in treatment of retinal disorders in which glutamate excitotoxicity is pathogenic.

Keywords: glutamate carboxypepptidase II, glutamate excitotoxicity, ischemia-reperfusion, retinal ganglion cell

Procedia PDF Downloads 340

Authors: Don Anushka Sandaruwan Elvitigala, P. D. S. U. Wickramasinghe, Jehee Lee

Abstract:

Cystatins are a large superfamily of proteins which act as reversible inhibitors of cysteine proteases. Papain proteases and cysteine cathepsins are predominant substrates of cystatins. Cystatin superfamily can be further clustered into three groups as Stefins, Cystatins, and Kininogens. Among them, stefines are also known as family 1 cystatins which harbors cystatin Bs and cystatin As. In this study, a homologue of family one cystatins more close to cystatin Bs was identified from Korean black rockfish (Sebastes schlegeli) using a prior constructed cDNA (complementary deoxyribonucleic acid) database and designated as RfCyt1. The full-length cDNA of RfCyt1 consisted of 573 bp, with a coding region of 294 bp. It comprised a 5´-untranslated region (UTR) of 55 bp, and 3´-UTR of 263 bp. The coding sequence encodes a polypeptide consisting of 97 amino acids with a predicted molecular weight of 11kDa and theoretical isoelectric point of 6.3. The RfCyt1 shared homology with other teleosts and vertebrate species and consisted conserved features of cystatin family signature including single cystatin-like domain, cysteine protease inhibitory signature of pentapeptide (QXVXG) consensus sequence and N-terminal two conserved neighboring glycine (⁸GG⁹) residues. As expected, phylogenetic reconstruction developed using the neighbor-joining method showed that RfCyt1 is clustered with the cystatin family 1 members, in which more closely with its teleostan orthologues. An SYBR Green qPCR (quantitative polymerase chain reaction) assay was performed to quantify the RfCytB transcripts in different tissues in healthy and immune stimulated fish. RfCyt1 was ubiquitously expressed in all tissue types of healthy animals with gill and spleen being the highest. Temporal expression of RfCyt1 displayed significant up-regulation upon infection with Aeromonas salmonicida. Recombinantly expressed RfCyt1 showed concentration-dependent papain inhibitory activity. Collectively these findings evidence for detectable protease inhibitory and immunity relevant roles of RfCyt1 in Sebastes schlegeli.

Keywords: Sebastes schlegeli, family 1 cystatin, immune stimulation, expressional modulation

Procedia PDF Downloads 136

Authors: Amina Omer, Ikram Elsiddig

Abstract:

Arctostaphylos uvaursi is a plant of the family Ericaceae, it’s used in skin care products mostly for its depigmenting action, due to the presence of hydroquinones that are well known inhibitors of tyrosinase, an enzyme involved in melanin biosynthesis in humans. The main hydroquinone found within the A. uvaursi is arbutin, which is found with varying percentage within the plant depending on the season, and area from which the plant is harvested. An in vitro experiment has shown that the arbutin found within the bearberry leaf extract inhibited the biosynthesis of melanin in human melanoma cells and in three-dimensional human skin model. Madurella mycetomatis is filamentous fungus that causes the fungal form of mycetoma known as eumycetoma, with existing anti-fungals and surgery, only 35% of people living eumycetoma are treated, M. mycetomatis has been found to shield itself against the antifungal therapy through the production of melanin decreasing the effectiveness of the therapy, therefore there is a need for a new and more effective therapy. The aim of the study was to investigate and compare the effect of arbutin powder and aqueous extract of A. uvaursi containing arbutin on the biosynthesis of melanin by M. mycetomatis. The experiment was carried out by culturing M. mycetomatis on minimal media composed of 2% agar, 15 mM glucose, 10 mM MgSO4, 29.4 mM KH2PO4, 13 mM glycin and 80mg/l gentamicin, the media was supplied with different concentration of arbutin solution (5, 25 50,and 75mg) and aqueous extract of A. uvaursi to contain arbutin with concentrations (5, 25 50,and 75mg), the plates were incubated for two month and the result was observed by the naked eye. The results revealed that the arbutin powder had an inhibitory effect on melanin synthesis by M. mycetomatis that correlated with its established inhibitory effect on melanin synthesis in humans. The inhibitory effect of arbutin on melanin synthesis by M. mycetomatis was found to be dose dependent. A. uvaursi aqueous leaf extract containing arbutin was also found to decrease melanin production by M. mycetomatis, however plates containing high concentrations of aqueous extract couldn’t be assessed for its melanin inhibitory effect due to the high content of carbohydrates in the extract that promoted the growth of fungi Asperigullus niger rendering the plates unsuitable for visual inspection. In conclusion inhibition of melanin synthesis was observed on the arbutin powder as well as the aqueous extract containing arbutin. A. uvaursi is known to exhibit anti-inflammatory activity, which can aid in wound healing that is beneficial in the chronic inflammation caused by M. mycetomatis.

Keywords: arbutin, arctostaphylos, Madurella, melanin

Procedia PDF Downloads 170

Authors: Akterono Budiyati, Gita Kusumo, Teguh Putra, Fritzie Rexana, Antonius Kurniawan, Aru Sudoyo, Ahmad Utomo, Andi Utama

Abstract:

The presence of the programmed death ligand-1 (PD-L1) has been used in multiple clinical trials and approved as biomarker for selecting patients more likely to respond to immune checkpoint inhibitors. However, the expression of PD-L1 is regulated in different ways, which leads to a different significance of its presence. Positive PD-L1 within tumors may result from two mechanisms, induced PD-L1 expression by T-cell presence or genetic mechanism that lead to constitutive PD-L1 expression. Amplification of PD-L1 genes was found as one of genetic mechanism which causes an increase in PD-L1 expression. In case of colorectal cancer (CRC), targeting immune checkpoint inhibitor has been recommended for patients with microsatellite instable (MSI). Although the correlation between PD-L1 expression and MSI status has been widely studied, so far the precise mechanism of PD-L1 gene activation in CRC patients, particularly in MSI population have yet to be clarified. In this present study we have profiled 61 archived formalin fixed paraffin embedded CRC specimens of patients from Medistra Hospital, Jakarta admitted in 2010 - 2016. Immunohistochemistry was performed to measure expression of PD-L1 in tumor cells as well as MSI status using antibodies against PD-L1 and MMR (MLH1, MSH2, PMS2 and MSH6), respectively. PD-L1 expression was measured on tumor cells with cut off of 1% whereas loss of nuclear MMR protein expressions in tumor cells but not in normal or stromal cells indicated presence of MSI. Subset of PD-L1 positive patients was then assessed for copy number variations (CNVs) using single Tube TaqMan Copy Number Assays Gene CD247PD-L1. We also observed KRAS mutation to profile possible genetic mechanism leading to the presence or absence of PD-L1 expression. Analysis of 61 CRC patients revealed 15 patients (24%) expressed PD-L1 on their tumor cell membranes. The prevalence of surface membrane PD-L1 was significantly higher in patients with MSI (87%; 7/8) compared to patients with microsatellite stable (MSS) (15%; 8/53) (P=0.001). Although amplification of PD-L1 gene was not found among PD-L1 positive patients, low-level amplification of PD-L1 gene was commonly observed in MSS patients (75%; 6/8) than in MSI patients (43%; 3/7). Additionally, we found 26% of CRC patients harbored KRAS mutations (16/61), so far the distribution of KRAS status did not correlate with PD-L1 expression. Our data suggest genetic mechanism through amplification of PD-L1 seems not to be the mechanism underlying upregulation of PD-L1 expression in CRC patients. However, further studies are warranted to confirm the results.

Keywords: colorectal cancer, gene amplification, microsatellite instable, programmed death ligand-1

Procedia PDF Downloads 222

Authors: Yogesh Rai, Saurabh Singh, Sanjay Pandey, Dhananjay K. Sah, B. G. Roy, B. S. Dwarakanath, Anant N. Bhatt

Abstract:

One of the most common signatures of highly malignant gliomas is their capacity to metabolize more glucose to lactic acid than normal brain tissues, even under normoxic conditions (Warburg effect), indicating that aerobic glycolysis is constitutively upregulated through stable genetic or epigenetic changes. However, oxidative phosphorylation (OxPhos) is also required to maintain the mitochondrial membrane potential for tumor cell survival. In the process of tumorigenesis, tumor cells during fastest growth rate exhibit both high glycolytic and high OxPhos. Therefore, metabolically reprogrammed cancer cells with combination of both aerobic glycolysis and altered OxPhos develop a robust metabolic phenotype, which confers a selective growth advantage. In our study, we grew the high glycolytic BMG-1 (glioma) cells with continuous exposure of mitochondrial uncoupler 2, 4, dinitro phenol (DNP) for 10 passages to obtain a phenotype of high glycolysis with enhanced altered OxPhos. We found that OxPhos modified BMG (OPMBMG) cells has similar growth rate and cell cycle distribution but high mitochondrial mass and functional enzymatic activity than parental cells. In in-vitro studies, OPMBMG cells showed enhanced invasion, proliferation and migration properties. Moreover, it also showed enhanced angiogenesis in matrigel plug assay. Xenografted tumors from OPMBMG cells showed reduced latent period, faster growth rate and nearly five folds reduction in the tumor take in nude mice compared to BMG-1 cells, suggesting that robust metabolic phenotype facilitates tumor formation and growth. OPMBMG cells which were found radio-resistant, showed enhanced radio-sensitization by 2-DG as compared to the parental BMG-1 cells. This study suggests that metabolic reprogramming in cancer cells enhances the potential of migration, invasion and proliferation. It also strengthens the cancer cells to escape the death processes, conferring resistance to therapeutic modalities. Our data also suggest that combining metabolic inhibitors like 2-DG with conventional therapeutic modalities can sensitize such metabolically aggressive cancer cells more than the therapies alone.

Keywords: 2-DG, BMG, DNP, OPM-BMG

Procedia PDF Downloads 226

Authors: Tejinder Singh Sidhu

Abstract:

Hot corrosion has been recognized as a severe problem in steam-powered electricity generation plants and industrial waste incinerators as it consumes the material at an unpredictably rapid rate. Consequently, the load-carrying ability of the components reduces quickly, eventually leading to catastrophic failure. The inability to either totally prevent hot corrosion or at least detect it at an early stage has resulted in several accidents, leading to loss of life and/or destruction of infrastructures. A number of countermeasures are currently in use or under investigation to combat hot corrosion, such as using inhibitors, controlling the process parameters, designing a suitable industrial alloy, and depositing protective coatings. However, the protection system to be selected for a particular application must be practical, reliable, and economically viable. Due to the continuously rising cost of the materials as well as increased material requirements, the coating techniques have been given much more importance in recent times. Coatings can add value to products up to 10 times the cost of the coating. Among the different coating techniques, thermal spraying has grown into a well-accepted industrial technology for applying overlay coatings onto the surfaces of engineering components to allow them to function under extreme conditions of wear, erosion-corrosion, high-temperature oxidation, and hot corrosion. In this study, the hot corrosion performances of Ni-20Cr and Cr₃C₂-NiCr coatings developed by High Velocity Oxy-Fuel (HVOF) process have been studied. The coatings were developed on a Fe-based superalloy, and experiments were performed in an actual industrial environment of a coal-fired boiler. The cyclic study was carried out around the platen superheater zone where the temperature was around 1000°C. The study was conducted for 10 cycles, and one cycle was consisting of 100 hours of heating followed by 1 hour of cooling at ambient temperature. Both the coatings deposited on Fe-based superalloy imparted better hot corrosion resistance than the uncoated one. The Ni-20Cr coated superalloy performed better than the Cr₃C₂-NiCr coated in the actual working conditions of the coal fired boiler. It is found that the formation of chromium oxide at the boundaries of Ni-rich splats of the coating blocks the inward permeation of oxygen and other corrosive species to the substrate.

Keywords: hot corrosion, coating, HVOF, oxidation

Procedia PDF Downloads 83

Authors: Anna Rudzińska, Katarzyna Szklener, Pola Juchaniuk, Anna Rodzajweska, Katarzyna Machulska-Ciuraj, Monika Rychlik- Grabowska, Michał łOziński, Agnieszka Kolak-Bruks, SłAwomir Mańdziuk

Abstract:

Introduction: Immune checkpoint inhibition (ICI) belongs to the modern forms of anti-cancer treatment. Due to the constant development and continuous research in the field of ICI, many aspects of the treatment are yet to be discovered. One of the less researched aspects of ICI treatment is the influence of the adverse effects on the treatment success rate. It is suspected that adverse events in the course of the ICI treatment indicate a better response rate and correlate with longer progression-free- survival. Methodology: The research was conducted with the usage of the documentation of the Department of Clinical Oncology and Chemotherapy. Data of the patients with a lung cancer diagnosis who were treated between 2019-2022 and received ICI treatment were analyzed. Results: Out of over 133 patients whose data was analyzed, the vast majority were diagnosed with non-small cell lung cancer. The majority of the patients did not experience adverse effects. Most adverse effects reported were classified as grade 1 or grade 2 according to CTCAE classification. Most adverse effects involved skin, thyroid and liver toxicity. Statistical significance was found for the adverse effect incidence and overall survival (OS) and progression-free survival (PFS) (p=0,0263) and for the time of toxicity onset and OS and PFS (p<0,001). The number of toxicity sites was statistically significant for prolonged PFS (p=0.0315). The highest OS was noted in the group presenting grade 1 and grade 2 adverse effects. Conclusions: Obtained results confirm the existence of the prolonged OS and PFS in the adverse-effects-charged patients, mostly in the group presenting mild to intermediate (Grade 1 and Grade 2) adverse effects and late toxicity onset. Simultaneously our results suggest a correlation between treatment response rate and the toxicity grade of the adverse effects and the time of the toxicity onset. Similar results were obtained in several similar research conducted - with the proven tendency of better survival in mild and moderate toxicity; meanwhile, other studies in the area suggested an advantage in patients with any toxicity regardless of the grade. The contradictory results strongly suggest the need for further research on this topic, with a focus on additional factors influencing the course of the treatment.

Keywords: adverse effects, immunotherapy, lung cancer, PD-1/PD-L1 inhibitors

Procedia PDF Downloads 91

Authors: Ali Kamal M. Sami, Safa Almukhtar, Alaa Al-Krush, Ismael Hama-Amin Akha Weas, Ruqaya Ahmed Alqais

Abstract:

Introduction and Objectives Lower urinary tract symptoms (LUTS) are common among men with benign prostatic hyperplasia (BPH). The combination of 5 alpha-reductase inhibitors and alpha-blockers has been used as a conservative treatment of male LUTS secondary to BPH. Nanotechnology structured water magnalife is a type of water that is produced by modulators and specific frequency and energy fields that transform ordinary water into this Nanowater. In this study, we evaluated the use of Nano-water with the conservative treatment and to see if it improves the outcome and gives better results in those patients with LUTS/BPH. Material and methods For a period of 3 months, 200 men with International Prostate Symptom Score (IPSS)≥13, maximum flow rate (Qmax)≤ 15ml/s, and prostate volume > 30 and <80 ccs were randomly divided into two groups. Group A 100 men were given Nano-water with the (tamsulosindutasteride) and group B 100 men were given ordinary bottled water with the (tamsulosindutasteride). The water bottles were unlabeled and were given in a daily dose of 20ml/kg body weight. Dutasteride 0.5mg and tamsulosin 0.4 mg daily doses. Both groups were evaluated for the IPSS, Qmax, Residual Urine (RU), International Index of Erectile Function–Erectile Function (IIEF-EF) domain at the beginning (baseline data), and at the end of the 3 months. Results Of the 200 men with LUTS who were included in this study, 193 men were followed, and 7 men dropped out of the study for different reasons. In group A which included 97 men with LUTS, IPSS decreased by 16.82 (from 20.47 to 6.65) (P<0.00001) and Qmax increased by 5.73 ml/s (from 11.71 to 17.44) (P<0.00001) and RU <50 ml in 88% of patients (P<0.00001) and IIEF-EF increased to 26.65 (from 16.85) (P<0.00001). While in group B, 96 men with LUTS, IPSS decreased by 8.74(from 19.59 to 10.85)(P<0.00001) and Qmax increased by 4.67 ml/s(from 10.74 to 15.41)(P<0.00001), RU<50 ml in 75% of patients (P<0.00001), and IIEF-EF increased to 21(from 15.87)(P<0.00001). Group A had better results than group B. IPSS in group A decreased to 6.65 vs 10.85 in group B(P<0.00001), also Qmax increased to 17.44 in group A vs 15.41 in group B(P<0.00001), group A had RU <50 ml in 88% of patients vs 75% of patients in group B(P<0.00001).Group A had better IIEF-EF which increased to 26.65 vs 21 in group B(P<0.00001). While the differences between the baseline data of both groups were statistically not significant. Conclusion The use of nanotechnology structured water magnalife gives a better result in terms of LUTS and scores in patients with BPH. This combination is showing improvements in IPSS and even in erectile function in those men after 3 months.

Keywords: nano water, lower urinary tract symptoms, benign prostatic hypertrophy, erectile dysfunction

Procedia PDF Downloads 71

Authors: M. F. Perez, Ysmael Verde, B. Escobar, R. Barbosa, J. C. Cruz

Abstract:

Reinforced concrete is one of the most important materials in the construction industry. However, in recent years the durability of concrete structures has been a worrying problem, mainly due to corrosion of reinforcing steel; the consequences of corrosion in all cases lead to shortening of the life of the structure and decrease in quality of service. Since the emergence of this problem, they have implemented different methods or techniques to reduce damage by corrosion of reinforcing steel in concrete structures; as the use of polymeric materials as coatings for the steel rod, spiked inhibitors of concrete during mixing, among others, presenting different limitations in the application of these methods. Because of this, it has been used a method that has proved effective, cathodic protection. That is why due to the properties attributed to carbon nanotubes (CNT), these could act as cathodic corrosion protection. Mounting a three-electrode electrochemical cell, carbon steel as working electrode, saturated calomel electrode (SCE) as the reference electrode, and a graphite rod as a counter electrode to close the system is performed. Samples made were subjected to a cycling process in order to compare the results in the corrosion performance of a coating composed of CNT and the others based on an anticorrosive commercial painting. The samples were tested at room temperature using an electrolyte consisting NaCl and NaOH simulating the typical pH of concrete, ranging from 12.6 to 13.9. Three test samples were made of steel rod, white, with commercial anticorrosive paint and CNT based coating; delimiting the work area to a section of 0.71 cm2. Tests cyclic voltammetry and linear voltammetry electrochemical spectroscopy each impedance of the three samples were made with a window of potential vs SCE 0.7 -1.7 a scan rate of 50 mV / s and 100 mV / s. The impedance values were obtained by applying a sine wave of amplitude 50 mV in a frequency range of 100 kHz to 100 MHz. The results obtained in this study show that the CNT based coating applied to the steel rod considerably decreased the corrosion rate compared to the commercial coating of anticorrosive paint, because the Ecorr was passed increase as the cycling process. The samples tested in all three cases were observed by light microscopy throughout the cycling process and micrographic analysis was performed using scanning electron microscopy (SEM). Results from electrochemical measurements show that the application of the coating containing carbon nanotubes on the surface of the steel rod greatly increases the corrosion resistance, compared to commercial anticorrosive coating.

Keywords: anticorrosive, carbon nanotubes, corrosion, steel

Procedia PDF Downloads 477

Authors: Philippa Saunders, Claire Fletcher

Abstract:

INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive the expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signaling remains a key driver of growth. Androgen deprivation therapy (ADT) is, therefore, a first-line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signaling inhibitors, respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIAL AND METHOD: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.

Keywords: microRNA, androgen deprivation therapy, Enzalutamide, abiraterone, patient-derived xenograft

Procedia PDF Downloads 143

Authors: Dounyazad Sour

Abstract:

This research examines international doctoral students’ reflections on their journey and experiences of studying for a PhD in the UK. Since the early 1990s, the international students’ number in the UK has increased. The significant contribution of these international students to the cultural and academic diversity of the UK universities’ doctoral programmes is widely acknowledged. The substantial fees these students bring to British Higher Education institutions is also much appreciated. The rationale for undertaking this study grew from personal experience of studying in the UK. Through membership in different groups both online and, when regulations permitted it, face to face social groups, it quickly became apparent that among all students, there were both shared and individual experiences of struggles and triumphs. This insight led to the decision to investigate these matters in greater detail. This in-depth qualitative interpretative study, inspired by a phenomenological approach, offers fresh insights into academic, social and cultural experiences of international PhD students in the UK. Data collection was carried out in the UK over a period of three months, deploying focus groups, individual semi-structured interviews, and images selected by participants that represent their feelings towards their experiences. The ten participants are attending different UK universities, studying a range of disciplines and have diverse backgrounds. Interviews and discussions took place in the participants' preferred languages; Arabic, English and French. The analysis shows that the participants had experienced two types of shock: negative and positive. Negative shocks, which have seen considerable attention in the field of international students’ experiences, relate to unexpected incidents that happened to the participants in relation to their interactions with others: people from different backgrounds and people from the same background. This impacted their experience negatively through experiencing feelings of anxiety, stress, low self-esteem and xenophobia, all these hindering factors contribute to make international students struggle to adapt to the new environment. Positive shocks, which have remained largely under-researched in the field of international students’ experiences, refer to all the positive occurrences that participants experienced. For instance, a shop assistant saying: “do you need any help, honey?” which brought a sense of belonging, feeling home, safety, and satisfaction to the respondents, and made their experiences less challenging. This investigation will offer insights into the PhD international students’ experiences and shed new light on the shocks that can work as facilitators, rather than as inhibitors.

Keywords: international students, PhD journey, phenomenological approach, positive shock

Procedia PDF Downloads 188

Authors: Wei-Ju Huang, Hung-Pin Hsu

Abstract:

[Background] In congestive heart failure (CHF), it has always been the principle of clinical treatment to control the water retention mechanism in the body to prevent excessive fluid retention. Early control of sympathetic nerves, Renin-Angiotensin-Aldosterone system (RAA system, RAAS), or strengthening of Atrial Natriuretic Peptide (ANP) was the point. In RAA system, related hormones, such as angiotensin, or enzymes in the pathway, such as ACE-I, can be used with corresponding inhibitors to reduce water content.[Aim] In recent years, clinical studies have pointed out that if different mechanisms are combined, the control effect seems to be better. For example, recent studies showed that ENTRESTO, a combination of Sacubitril and Valsartan, is a good new drug for CHF. Sacubitril is a prodrug. After activation, it can inhibit neprilysin and act as a neprilysin inhibitor (ARNI) to reduce the breakdown of natriuretic peptides(ANP). Valsartan is a kind of angiotensin receptor blocker (ARB), both of which are used to treat heart failure at the same time, have excellent curative effects.[Materials and Methods] Considering the side effects of this drug, coughing and a few cases of diarrhea were observed. However, the effect of this drug on the patient's intestinal tract has not been confirmed. On the other hand, studies have pointed out that ANP supplement can improve the CHF and increase the inhibitory effect on cancer cells. Therefore, the purpose of this study is to use a special microbial detection method to prove that whether oral drugs have an effect on microorganisms.The experimental method uses Nissui Compact Dry to observe the situation in different types of microorganisms. After the drug is dissolved in water, it is implanted in a petri dish, and the presence of different microorganisms is detected through different antibody reactions to confirm whether the drug has some toxicology in the gut.[Results and Discussion]From the above experimental results, it can be known that among the effects of Sacubitril and Valsartan on the basic microbial flora of the human body, low doses had no significant effect on Escherichia coli or intestinal bacteria. If Sacubitril or Valsartan with a high concentration of 3mg/ml is used alone or under the stimulation of a high concentration of the two drugs, it has a significant inhibitory effect on Escherichia coli. However, in terms of the effect on intestinal bacteria, high concentration of Sacubitril has a more significant inhibitory effect on intestinal bacteria, while high concentration of Valsartan has a less significant inhibitory effect on intestinal bacteria. The inhibitory effect of the combination of the two drugs on intestinal bacteria is also less significant.[Conclusion]The results of this study can be used as a further reference for the possible side effects of the clinical use of Sacubitril and Valsartan on the intestinal tract of patients,

Keywords: sacubitril, valsartan, entresto, congestive heart failure (CHF)

Procedia PDF Downloads 67

Authors: Mantas Sriubas, Kristina Bockute, Darius Virbukas, Giedrius Laukaitis

Abstract:

In this work, the doped TiO2 (dopants – Ca, Mg) was investigated. The comparison between the physical vapour deposition methods as electron beam vapour deposition and magnetron sputtering was performed and the structural and electrical properties of the formed thin films were investigated. Thin films were deposited on different type of substrates: SiO2, Alloy 600 (Fe-Ni-Cr) and Al2O3 substrates. The structural properties were investigated using Ambios XP-200 profilometer, scanning electron microscope (SEM) Hitachi S-3400N, X-ray energy-dispersive spectroscope (EDS) Quad 5040 (Bruker AXS Microanalysis GmbH), X-ray diffractometer (XRD) D8 Discover (Bruker AXS GmbH) with glancing angles focusing geometry in a 20 – 70° range using the Cu Kα1 λ = 0.1540562 nm radiation). The impedance spectroscopy measurements were performed using Probostat® (NorECs AS) measurement cell in the frequency range from 10-1-106 Hz under reducing and oxidizing conditions in temperature range of 200 °C to 1200 °C. The investigation of the e-beam deposited Ca and Mg doped-TiO2 thin films shows that the thin films are dense without any visible pores and cavities and the thin films grow in zone T according Barna-Adamik SZM. Substrate temperature was kept 600 °C during the deposition and Ts/Tm ≈ 0.32 (substrate temperature (Ts) and coating material melting temperature (Tm)). The surface diffusion is high however, the grain boundary migration is strongly limited at this temperature. This means that structure is inhomogeneous and the columnar structure is mostly visible in the upper part of the films. According to XRD, the increasing of the Ca dopants’ concentration increases the crystallinity of the formed thin films and the crystallites size increase linearly and Ca dopants act as prohibitors. Thin films are comprised of anatase TiO2 phase with an exception of 2 % Ca doped TiO2, where a small peak of Ca arise. In the case of Mg doped-TiO2 the intensities of the XRD peaks decreases with increasing Mg molar concentration. It means that there are less diffraction planes of the particular orientation in thin films with higher impurities concentration. Thus, the crystallinity decreases with increasing Mg concentration and Mg dopants act as inhibitors. The impedance measurements show that the dopants changed the conductivity of the formed thin films. The conductivity varies from 10-3 S/cm to 10-4 S/cm at 800 °C under wet reducing conditions. The microstructure of the magnetron sputtered thin TiO2 films is different comparing to the thin films deposited using e-beam deposition therefore influencing other structural and electrical properties.

Keywords: electrical properties, electron beam deposition, magnetron sputtering, microstructure, titanium dioxide

Procedia PDF Downloads 296

Authors: Nigatu Tadesse, Li Juan, Liuhong Ming

Abstract:

Gastric cancer (GC) is the fifth most common and fourth deadly cancer in the world with limited treatment options at late advanced stage in which surgical therapy is not recommended with chemotherapy remain as the mainstay of treatment. However, the occurrence of chemoresistance as well as intera-tumoral and inter-tumoral heterogeneity of response to targeted and immunotherapy underlined a clear unmet treatment need in gastroenterology. Several molecular and cellular alterations ascribed for chemo resistance in GC including cancer stem cells (CSC) and tumor microenvironment (TME) remodeling. Cancer cells including CSC bears higher metabolic demand and major changes in TME involves alterations of gut microbiota interacting with nutrients metabolism. Metabolic upregulation in lipids, carbohydrates, amino acids, fatty acids biosynthesis pathways identified as a common hall mark in GC. Metabolic addiction to methionine metabolism occurs in many cancer cells to promote the biosynthesis of S-Adenosylmethionine (SAM), a universal methyl donor molecule for high rate of transmethylation in GC and promote cell proliferation. Targeting methionine metabolism found to promotes chemo-sensitivity with treatment non-heterogeneity. Methionine restriction (MR) promoted the arrest of cell cycle at S/G2 phase and enhanced downregulation of GC cells resistance to apoptosis (including ferroptosis), which suggests the potential of synergy with chemotherapies acting at S-phase of the cell cycle as well as inducing cell apoptosis. Accumulated evidences showed both the biogenesis as well as intracellular metabolism of exogenous methionine could be safe and effective target for therapy either alone or in combination with chemotherapies. This review article provides an over view of the upregulation in methionine biosynthesis pathway and the molecular signaling through the PI3K/Akt/mTOR-c-MYC axis to promote metabolic reprograming through activating the expression of L-type aminoacid-1 (LAT1) transporter and overexpression of Methionine adenosyltransferase 2A(MAT2A) for intercellular metabolic conversion of exogenous methionine to SAM in GC, and the potential of targeting with novel therapeutic agents such as methioninase (METase), Methionine adenosyltransferase 2A (MAT2A), c-MYC, methyl like transferase 16 (METTL16) inhibitors that are currently under clinical trial development stages and future perspectives.

Keywords: gastric cancer, methionine metabolism, pi3k/akt/mtorc1-c-myc axis, gut microbiota, MAT2A, c-MYC, METTL16, methioninase

Procedia PDF Downloads 48

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

Abstract:

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

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

Procedia PDF Downloads 305

Authors: Md. Fazlul Karim, Ashik Sharfaraz, Aysha Ferdoushi

Abstract:

Background: Computational medicinal chemistry approaches are used for designing and identifying new drug-like molecules, predicting properties and pharmacological activities, and optimizing lead compounds in drug development. SIRT7, a nicotinamide adenine dinucleotide (NAD+)-dependent deacylase which regulates aging, is an emerging target for cancer therapy with mounting evidence that SIRT7 downregulation plays important roles in reversing cancer phenotypes and suppressing tumor growth. Activation or altered expression of SIRT7 is associated with the progression and invasion of various cancers, including liver, breast, gastric, prostate, and non-small cell lung cancer. Objectives: The goal of this work was to identify potent and selective bioactive candidate inhibitors of SIRT7 by in silico screening of small molecule compounds obtained from Nigella sativa (N. sativa). Methods: SIRT7 structure was retrieved from The Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB), and its active site was identified using CASTp and metaPocket. Molecular docking simulation was performed with PyRx 0.8 virtual screening software. Drug-likeness properties were tested using SwissADME and pkCSM. In silico toxicity was evaluated by Osiris Property Explorer. Bioactivity was predicted by Molinspiration software. Antitumor activity was screened for Prediction of Activity Spectra for Substances (PASS) using Way2Drug web server. Molecular dynamics (MD) simulation was carried out by Desmond v3.6 package. Results: A total of 159 bioactive compounds from the N. Sativa were screened against the SIRT7 enzyme. Five bioactive compounds: chrysin (CID:5281607), pinocembrin (CID:68071), nigellidine (CID:136828302), nigellicine (CID:11402337), and epicatechin (CID:72276) were identified as potent SIRT7 anti-cancer candidates after docking score evaluation and applying Lipinski's Rule of Five. Finally, MD simulation identified Chrysin as the top SIRT7 anti-cancer candidate molecule. Conclusion: Chrysin, which shows a potential inhibitory effect against SIRT7, can act as a possible anti-cancer drug candidate. This inhibitor warrants further evaluation to check its pharmacokinetics and pharmacodynamics properties both in vitro and in vivo.

Keywords: SIRT7, antitumor, molecular docking, molecular dynamics simulation

Procedia PDF Downloads 79

Authors: Alon Cohen, Jeffrey Kantor, Shalom Levy

Abstract:

Technology adoption models are extensively used in the literature to explore drivers and inhibitors affecting the adoption of Computer Assisted Audit Techniques and Tools (CAATTs). Further studies from recent years suggested additional factors that may affect technology adoption by CPA firms. However, the adoption of CAATTs by financial auditors differs from the adoption of technologies in other industries. This is a result of the unique characteristics of the auditing process, which are expressed in the audit risk elements and the risk-based auditing approach, as encoded in the auditing standards. Since these audit risk factors are not part of the existing models that are used to explain technology adoption, these models do not fully correspond to the specific needs and requirements of the auditing domain. The overarching objective of this qualitative research is to fill the gap in the literature, which exists as a result of using generic technology adoption models. Followed by a pretest and based on semi-structured in-depth interviews with 16 Israeli CPA firms of different sizes, this study aims to reveal determinants related to audit risk factors that influence the adoption of CAATTs in audits and proposes a new modeling approach for the successful adoption of CAATTs. The findings emphasize several important aspects: (1) while large CPA firms developed their own inner guidelines to assess the audit risk components, other CPA firms do not follow a formal and validated methodology to evaluate these risks; (2) large firms incorporate a variety of CAATTs, including self-developed advanced tools. On the other hand, small and mid-sized CPA firms incorporate standard CAATTs and still need to catch up to better understand what CAATTs can offer and how they can contribute to the quality of the audit; (3) the top management of mid-sized and small CPA firms should be more proactive and updated about CAATTs capabilities and contributions to audits; and (4) All CPA firms consider professionalism as a major challenge that must be constantly managed to ensure an optimal CAATTs operation. The study extends the existing knowledge of CAATTs adoption by looking at it from a risk-based auditing approach. It suggests a new model for CAATTs adoption by incorporating influencing audit risk factors that auditors should examine when considering CAATTs adoption. Since the model can be used in various audited scenarios and supports strategic, risk-based decisions, it maximizes the great potential of CAATTs on the quality of the audits. The results and insights can be useful to CPA firms, internal auditors, CAATTs developers and regulators. Moreover, it may motivate audit standard-setters to issue updated guidelines regarding CAATTs adoption in audits.

Keywords: audit risk, CAATTs, financial auditing, information technology, technology adoption models

Procedia PDF Downloads 67

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

Abstract:

Anti-estrogen treatment resistant is a noteworthy reason for disease relapse and mortality in estrogen receptor alpha (ERα)- positive breast cancers. Tamoxifen or estrogen withdrawal increases the dependance of breast malignancy cells on INT3 signaling. Here, we researched the contribution of Quercetin and INT3 signaling in endocrine resistant breast cancer cells. Methods: We utilized two models of endocrine therapies resistant (ETR-) breast cancer: tamoxifen-resistant (TamR) and long term estrogen-deprived (LTED) MCF7 cells. We assessed the migratory and invasive limit of these cells by Transwell assay. Expression of epithelial to mesenchymal transition (EMT) controllers and in addition INT3 receptors and targets were assessed by real-time PCR and western blot analysis. Besides, we tried in vitro anti-Quercetin monoclonal antibodies (mAbs) and gamma secretase inhibitors (GSIs) as potential EMT reversal therapeutic agents. At last, we created stable Quercetin over expessing MCF7 cells and assessed their EMT features and response to tamoxifen. Results:We found that ETR cells acquired an epithelial to mesenchymal transition (EMT) phenotype and showed expanded levels of Quercetin and INT3 targets. Interestingly, we detected higher level of INT3 however lower levels of INT31 and INT32 proposing a switch to targeting through distinctive INT3 receptors after obtaining of resistance. Anti-Quercetin monoclonal antibodies and the GSI PF03084014 were effective in obstructing the Quercetin/INT3 axis and in part inhibiting the EMT process. As a consequence of this, cell migration and invasion were weakened and the stem cell like population was considerably decreased. Genetic hushing of Quercetin and INT3 prompted proportionate impacts. Finally, stable overexpression of Quercetin was adequate to make MCF7 lethargic to tamoxifen by INT3 activation. Conclusions: ETR cells express abnormal amounts of Quercetin and INT3, whose actuation eventually drives invasive conduct. Anti-Quercetin mAbs and GSI PF03084014 lessen expression of EMT molecules decreasing cellular invasiveness. Quercetin overexpression instigates tamoxifen resistance connected to obtaining of EMT phenotype. Our discovering propose that focusing on Quercetin and/or INT3 warrants further clinical assessment as substantial therapeutic methodologies in endocrine-resistant breast cancer.

Keywords: quercetin, INT3, mesenchymal transition, MCF7 breast cancer cells

Procedia PDF Downloads 311

Authors: Harald Lindorfer, Bettina Frauz, Dietmar Ramhold

Abstract:

Next to the well-known inhibitors in anaerobic digestion like ammonia, antibiotics or disinfectants, the number of process failures connected with mould growth in the feedstock increased significantly in the last years. It was assumed that mycotoxins are the cause of the negative effects. The financial damage to plants associated with these process failures is considerable. The aim of this study was to find a way of predicting the failures and furthermore strategies for a fast process recovery. In a first step, mould-contaminated feedstocks causing process failures in full-scale digesters were sampled and analysed on mycotoxin content. A selection of these samples was applied to biological inhibition tests. In this test, crystalline cellulose is applied in addition to the feedstock sample as standard substrate. Affected digesters were also sampled and analytical process data as well as operational data of the plants were recorded. Additionally, different mycotoxin substances, Deoxynivalenol, Zearalenon, Aflatoxin B1, Mycophenolic acid and Citrinin, were applied as pure substances to lab-scale digesters, individually and in various combinations, and effects were monitored. As expected, various mycotoxins were detected in all of the mould-contaminated samples. Nevertheless, inhibition effects were observed with only one of the collected samples, after applying it to an inhibition test. With this sample, the biogas yield of the standard substrate was reduced by approx. 20%. This result corresponds with observations made on full-scale plants. However, none of the tested mycotoxins applied as pure substance caused a negative effect on biogas production in lab scale digesters, neither after application as individual substance nor in combination. The recording of the process data in full-scale plants affected by process failures in most cases showed a severe accumulation of fatty acids alongside a decrease in biogas production and methane concentration. In the analytical data of the digester samples, a typical distribution of fatty acids with exceptionally high acetic acid concentrations could be identified. This typical fatty acid pattern can be used as a rapid identification parameter pointing to the cause of the process troubles and enable a fast implication of countermeasures. The results of the study show that more attention needs to be paid to feedstock storage and feedstock conservation before their application to anaerobic digesters. This is all the more important since first studies indicate that the occurrence of mycotoxins will likely increase in Europe due to the ongoing climate change.

Keywords: Anaerobic digestion, Biogas, Feedstock conservation, Fungal mycotoxins, Inhibition, process failure

Procedia PDF Downloads 130

Authors: Teresa Sarmento de Beires, Sofia Padilha, Pedro Arantes, Joana Ribeiro, Andreia Eiras

Abstract:

Background: Trichotillomania is a psychiatric condition that is very challenging to treat, with no first-line medications approved by any medical agency. It is defined as a recurrent compulsive habit of pulling out one's own hair, usually from the scalp and eyebrows area, but it can also affect eyelashes or any other hair-bearing area. N-acetylcysteine, a glutamate modulator, has been studied as a possible treatment for several psychiatric and neurological disorders, considering its role in attenuating pathophysiological processes responsible for compulsive behaviors and, therefore, trichotillomania. Objective: This study aims to determine the efficacy of N-acetylcysteine in the treatment of adults with trichotillomania. Methodology: The authors researched guidelines, standards of clinical guidance, systematic reviews, meta-analyses, and randomized clinical trials, published in the last 20 years using the MeSH terms: "Trichotillomania” and “N-acetylcysteine” in the following databases: PubMed, Cochrane library, National Guideline Clearing House, National Institute of Health and Care Excellence (NICE), Canadian Medical Association Practice Guidelines and Database of Abstracts of Reviews of Effectiveness (DARE). The Strength of Recommendation Taxonomy (SORT) Scale, from the American Family Physician, was used to evaluate the level of evidence and assign the strength of recommendation. Results: The research found fifteen articles, among which only three were eligible according to the inclusion criteria: 1. systematic review and 2. meta-analyses. There was evidence of a probable beneficial effect of N-acetylcysteine on treatment response and reduction of trichotillomania symptom severity in adults, with moderate certainty in the effect estimate. There was no evidence of effectiveness with the use of inositol, antioxidants, naltrexone, or selective serotonin reuptake inhibitors (SSRIs) in the treatment of adults with trichotillomania. Clomipramine and Olanzapine showed potential treatment benefits, with low certainty. N-acetylcysteine had the least severe side effect profile in adults compared with the other potentially beneficial pharmacological treatments. Conclusion: Evidence points towards the effectiveness of N-acetylcysteine in the treatment of adults with trichotillomania, which exhibits a good tolerability profile with minimal adverse effects. Therefore, the authors attribute a level of evidence 2, the strength of recommendation B, to the prescription of N-acetylcysteine in the treatment of adults suffering from trichotillomania (SORT analysis). Further investigation is needed in order to extract high-quality conclusions from the meta-analysis.

Keywords: trichotillomania, hair pulling, treatment, n-acetylcysteine

Procedia PDF Downloads 102

Authors: Danni Cheng

Abstract:

Background: Preclinical and epidemiological studies have reported potential protective effects of low-density lipoprotein cholesterol (LDL-C) lowering drugs on head and neck squamous cell cancer (HNSCC) survival, but the causality was not consistent. Genetic variants associated with LDL-C lowering drug targets can predict the effects of their therapeutic inhibition on disease outcomes. Objective: We aimed to evaluate the causal association of genetically proxied cholesterol-lowering drug targets and circulating lipid traits with cancer survival in HNSCC patients stratified by human papillomavirus (HPV) status using two-sample Mendelian randomization (MR) analyses. Method: Single-nucleotide polymorphisms (SNPs) in gene region of LDL-C lowering drug targets (HMGCR, NPC1L1, CETP, PCSK9, and LDLR) associated with LDL-C levels in genome-wide association study (GWAS) from the Global Lipids Genetics Consortium (GLGC) were used to proxy LDL-C lowering drug action. SNPs proxy circulating lipids (LDL-C, HDL-C, total cholesterol, triglycerides, apoprotein A and apoprotein B) were also derived from the GLGC data. Genetic associations of these SNPs and cancer survivals were derived from 1,120 HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) and 2,570 non-HPV-driven HNSCC patients in VOYAGER program. We estimated the causal associations of LDL-C lowering drugs and circulating lipids with HNSCC survival using the inverse-variance weighted method. Results: Genetically proxied HMGCR inhibition was significantly associated with worse overall survival (OS) in non-HPV-drive HNSCC patients (inverse variance-weighted hazard ratio (HR IVW), 2.64[95%CI,1.28-5.43]; P = 0.01) but better OS in HPV-positive OPSCC patients (HR IVW,0.11[95%CI,0.02-0.56]; P = 0.01). Estimates for NPC1L1 were strongly associated with worse OS in both total HNSCC (HR IVW,4.17[95%CI,1.06-16.36]; P = 0.04) and non-HPV-driven HNSCC patients (HR IVW,7.33[95%CI,1.63-32.97]; P = 0.01). A similar result was found that genetically proxied PSCK9 inhibitors were significantly associated with poor OS in non-HPV-driven HNSCC (HR IVW,1.56[95%CI,1.02 to 2.39]). Conclusion: Genetically proxied long-term HMGCR inhibition was significantly associated with decreased OS in non-HPV-driven HNSCC and increased OS in HPV-positive OPSCC. While genetically proxied NPC1L1 and PCSK9 had associations with worse OS in total and non-HPV-driven HNSCC patients. Further research is needed to understand whether these drugs have consistent associations with head and neck tumor outcomes.

Keywords: Mendelian randomization analysis, head and neck cancer, cancer survival, cholesterol, statin

Procedia PDF Downloads 99

Authors: Xiao Wang, Qinge Zhang

Abstract:

Background: This randomized, open-label study examined the therapeutic effects of computerized cognitive training (CCT) combined with selective serotonin reuptake inhibitors (SSRIs) on cognitive impairment among patients with late-life depression (LLD). Method: Study data were collected from May 5, 2021, to April 21, 2023. Outpatients who met diagnostic criteria for major depressive disorder according to the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria (i.e., a total score on the 17-item Hamilton Depression Rating Scale (HAMD-17) ≥ 18 and a total score on the Montreal Cognitive Assessment scale (MOCA) <26) were randomly assigned to receive up to 12 weeks of CCT and SSRIs treatment (n=57) or SSRIs and Control treatment (n=61). The primary outcome was the change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores from baseline to week 12 between the two groups. The secondary outcomes included changes in the HAMD-17 score, Hamilton Anxiety Scale (HAMA) score and Neuropsychiatric Inventory (NPI) score. Mixed model repeated measures (MMRM) analysis was performed on modified intention-to-treat (mITT) and completer populations. Results: The full analysis set (FAS) included 118 patients (CCT and SSRIs group, n=57; SSRIs and Control group, n =61). Over the 12-week study period, the reduction in the ADAS-cog total score was significant (P < 0.001) in both groups, while MMRM analysis revealed a significantly greater reduction in cognitive function (ADAS-cog total scores) from baseline to posttreatment in the CCT and SSRIs group than in the SSRI and Control group [(F (1,115) =13.65, least-squares mean difference [95% CI]: −2.77 [−3.73, −1.81], p<0.001)]. There were significantly greater improvements in depression symptoms (measured by the HAMD-17) in the CCT and SSRIs group than in the control group [MMRM, estimated mean difference (SE) between groups −3.59 [−5.02, −2.15], p < 0.001]. The least-squares mean changes in the HAMA scores and NPI scores between baseline and week 8 were greater in the CCT and SSRIs group than in the control group (all P < 0.05). There was no significant difference between groups on response rates and remission rates by using the last-observation-carried-forward (LOCF) method (all P > 0.05). The most frequent adverse events (AEs) in both groups were dry mouth, somnolence, and constipation. There was no significant difference in the incidence of adverse events between the two groups. Conclusions: CCT combined with SSRIs was efficacious and well tolerated in LLD patients with cognitive impairment.

Keywords: late-life depression, cognitive function, computerized cognitive training, SSRIs

Procedia PDF Downloads 52

Authors: Jeffrey A. Amelse

Abstract:

Many corporations aspire to become Net Zero Carbon Carbon Dioxide by 2035-2050. This paper examines what it will take to achieve those goals. Achieving Net Zero CO₂ requires an understanding of where energy is produced and consumed, the magnitude of CO₂ generation, and proper understanding of the Carbon Cycle. The latter leads to the distinction between CO₂ and biomass carbon sequestration. Short reviews are provided for prior technologies proposed for reducing CO₂ emissions from fossil fuels or substitution by renewable energy, to focus on their limitations and to show that none offer a complete solution. Of these, CO₂ sequestration is poised to have the largest impact. It will just cost money, scale-up is a huge challenge, and it will not be a complete solution. CO₂ sequestration is still in the demonstration and semi-commercial scale. Transportation accounts for only about 30% of total U.S. energy demand, and renewables account for only a small fraction of that sector. Yet, bioethanol production consumes 40% of U.S. corn crop, and biodiesel consumes 30% of U.S. soybeans. It is unrealistic to believe that biofuels can completely displace fossil fuels in the transportation market. Bioethanol is traced through its Carbon Cycle and shown to be both energy inefficient and inefficient use of biomass carbon. Both biofuels and CO₂ sequestration reduce future CO₂ emissions from continued use of fossil fuels. They will not remove CO₂ already in the atmosphere. Planting more trees has been proposed as a way to reduce atmospheric CO₂. Trees are a temporary solution. When they complete their Carbon Cycle, they die and release their carbon as CO₂ to the atmosphere. Thus, planting more trees is just 'kicking the can down the road.' The only way to permanently remove CO₂ already in the atmosphere is to break the Carbon Cycle by growing biomass from atmospheric CO₂ and sequestering biomass carbon. Sequestering tree leaves is proposed as a solution. Unlike wood, leaves have a short Carbon Cycle time constant. They renew and decompose every year. Allometric equations from the USDA indicate that theoretically, sequestrating only a fraction of the world’s tree leaves can get the world to Net Zero CO₂ without disturbing the underlying forests. How can tree leaves be permanently sequestered? It may be as simple as rethinking how landfills are designed to discourage instead of encouraging decomposition. In traditional landfills, municipal waste undergoes rapid initial aerobic decomposition to CO₂, followed by slow anaerobic decomposition to methane and CO₂. The latter can take hundreds to thousands of years. The first step in anaerobic decomposition is hydrolysis of cellulose to release sugars, which those who have worked on cellulosic ethanol know is challenging for a number of reasons. The key to permanent leaf sequestration may be keeping the landfills dry and exploiting known inhibitors for anaerobic bacteria.

Keywords: carbon dioxide, net zero, sequestration, biomass, leaves

Procedia PDF Downloads 128

Authors: Allaire Eric, Hauet Pascal, Floresco Jean, Beley Sebastien, Sussman Helene, Virag Ronald

Abstract:

Background: Caverno-venous leakage (CVL) is devastating, although barely known disease, the first cause of major physical impairment in men under 25, and responsible for 50% of resistances to phosphodiesterase 5-inhibitors (PDE5-I), affecting 30 to 40% of users in this medication class. In this condition, too early blood drainage from corpora cavernosa prevents penile rigidity and penetration during sexual intercourse. The role of conservative surgery in this disease remains controversial. Aim: Assess complications and results of combined open surgery and embolization for CVL. Method: Between June 2016 and September 2021, 133 consecutive patients underwent surgery in our institution for CVL, causing severe erectile dysfunction (ED) resistance to oral medical treatment. Procedures combined vein embolization and ligation with microsurgical techniques. We performed a pre-and post-operative clinical (Erection Harness Scale: EHS) hemodynamic evaluation by duplex sonography in all patients. Before surgery, the CVL network was visualized by computed tomography cavernography. Penile EMG was performed in case of diabetes or suspected other neurological conditions. All patients were optimized for hormonal status—data we prospectively recorded. Results: Clinical signs suggesting CVL were ED since age lower than 25, loss of erection when changing position, penile rigidity varying according to the position. Main complications were minor pulmonary embolism in 2 patients, one after airline travel, one with Factor V Leiden heterozygote mutation, one infection and three hematomas requiring reoperation, one decreased gland sensitivity lasting for more than one year. Mean pre-operative pharmacologic EHS was 2.37+/-0.64, mean pharmacologic post-operative EHS was 3.21+/-0.60, p<0.0001 (paired t-test). The mean EHS variation was 0.87+/-0.74. After surgery, 81.5% of patients had a pharmacologic EHS equal to or over 3, allowing for intercourse with penetration. Three patients (2.2%) experienced lower post-operative EHS. The main cause of failure was leakage from the deep dorsal aspect of the corpus cavernosa. In a 14 months follow-up, 83.2% of patients had a clinical EHS equal to or over 3, allowing for sexual intercourse with penetration, one-third of them without any medication. 5 patients had a penile implant after unsuccessful conservative surgery. Conclusion: Open surgery combined with embolization for CVL is an efficient approach to CVL causing severe erectile dysfunction.

Keywords: erectile dysfunction, cavernovenous leakage, surgery, embolization, treatment, result, complications, penile duplex sonography

Procedia PDF Downloads 149

Authors: Susanne Shunnaq

Abstract:

During the past decade, an increasing number of higher education institutions in Oman have sought accreditation in an attempt to assure the quality of their programs. Sultan Qaboos University (SQU), the only public university in the country, has also been seeking accreditation. Hence, the university administration has been encouraging departments to evaluate their programs for development purposes. The Department of English, where 100% of the students are learners of English as a foreign language, already produced a self-study report that outlined the strength and weaknesses of the current program. The department came to the realization that due to a changing local and regional job market, transferrable communication skills are high in demand among stakeholders in the public and private sectors. Failure to equip English literature students, for example, with excellent verbal communicative skills in English may have detrimental effects for undergraduate job-seekers who have to compete for jobs in employment sectors with a predominantly English-speaking workforce. Ongoing extensive discussions about restructuring the current literature program by means of partially replacing literature courses with skills courses, hoping to produce higher quality graduates who are equipped with effective communication skills for local and regional markets, have sparked the idea for this research. The researcher, who is an American Literature specialist at SQU, has set out to investigate to what extent senior American literature students have been able to apply transferable communication skills in an advanced literature course. The study also attempts to unearth performance inhibitors and causes for communication breakdown. The primary data source for the study were audio-recordings of 6 in-class peer-group discussions in an advanced contemporary American literature course during the academic year 2016/2017. The significance of this research lies in the rarity of studies focusing on verbal communication skills in Omani higher education literature classrooms at a time when English programs are in the process of being re-visited and revamped both for accreditation purposes and for meeting job-market demands. The results showed a considerable variation in Omani students' verbal communicative abilities and English proficiency levels. The study also raises crucial questions and provides important recommendations for administrators and teachers alike who are in the process of restructuring English programs in the region and in non-English speaking countries worldwide.

Keywords: job-market, literature, Oman, tertiary education, oral communication skills

Procedia PDF Downloads 146

Authors: Zoi Konsoula

Abstract:

The increasing prevalence of Alzheimer’s disease (AD) and diabetes mellitus (DM) constitutes them major global health problems. Recently, the inhibition of key enzyme activity is considered a potential treatment of both diseases. Specifically, inhibition of acetylcholinesterase (AChE), the key enzyme involved in the breakdown of the neurotransmitter acetylcholine, is a promising approach for the treatment of AD, while inhibition of α-amylase retards the hydrolysis of carbohydrates and, thus, reduces hyperglycemia. Unfortunately, commercially available AChE and α-amylase inhibitors are reported to possess side effects. Consequently, there is a need to develop safe and effective treatments for both diseases. In the present study, pomegranate peel (PP) was extracted using various solvents of increasing polarity, while two extraction methods were employed, the conventional maceration and the ultrasound assisted extraction (UAE). The concentration of bioactive phytoconstituents, such as total phenolics (TPC) and total flavonoids (TFC) in the prepared extracts was evaluated by the Folin-Ciocalteu and the aluminum-flavonoid complex method, respectively. Furthermore, the anti-neurodegenerative and anti-hyperglycemic activity of all extracts was determined using AChE and α-amylase inhibitory activity assays, respectively. The inhibitory activity of the extracts against AChE and α-amylase was characterized by estimating their IC₅₀ value using a dose-response curve, while galanthamine and acarbose were used as positive controls, respectively. Finally, the kinetics of AChE and α-amylase in the presence of the most inhibitory potent extracts was determined by the Lineweaver-Burk plot. The methanolic extract prepared using the UAE contained the highest amount of phytoconstituents, followed by the respective ethanolic extract. All extracts inhibited acetylcholinesterase in a dose-dependent manner, while the increased anticholinesterase activity of the methanolic (IC₅₀ = 32 μg/mL) and ethanolic (IC₅₀ = 42 μg/mL) extract was positively correlated with their TPC content. Furthermore, the activity of the aforementioned extracts was comparable to galanthamine. Similar results were obtained in the case of α-amylase, however, all extracts showed lower inhibitory effect on the carbohydrate hydrolyzing enzyme than on AChE, since the IC₅₀ value ranged from 84 to 100 μg/mL. Also, the α-amylase inhibitory effect of the extracts was lower than acarbose. Finally, the methanolic and ethanolic extracts prepared by UAE inhibited both enzymes in a mixed (competitive/noncompetitive) manner since the Kₘ value of both enzymes increased in the presence of extracts, while the Vmax value decreased. The results of the present study indicate that PP may be a useful source of active compounds for the management of AD and DM. Moreover, taking into consideration that PP is an agro-industrial waste product, its valorization could not only result in economic efficiency but also reduce the environmental pollution.

Keywords: acetylcholinesterase, Alzheimer’s disease, α-amylase, diabetes mellitus, pomegranate

Procedia PDF Downloads 122

Authors: Rajeev Ravindran, Amit K. Jaiswal

Abstract:

Waste from the food-processing industry is produced in large amount and contains high levels of lignocellulose. Due to continuous accumulation throughout the year in large quantities, it creates a major environmental problem worldwide. The chemical composition of these wastes (up to 75% of its composition is contributed by polysaccharide) makes it inexpensive raw material for the production of value-added products such as biofuel, bio-solvents, nanocrystalline cellulose and enzymes. In order to use lignocellulose as the raw material for the microbial fermentation, the substrate is subjected to enzymatic treatment, which leads to the release of reducing sugars such as glucose and xylose. However, the inherent properties of lignocellulose such as presence of lignin, pectin, acetyl groups and the presence of crystalline cellulose contribute to recalcitrance. This leads to poor sugar yields upon enzymatic hydrolysis of lignocellulose. A pre-treatment method is generally applied before enzymatic treatment of lignocellulose that essentially removes recalcitrant components in biomass through structural breakdown. Present study is carried out to find out the best pre-treatment method for the maximum liberation of reducing sugars from spent coffee waste (SPW). SPW was subjected to a range of physical, chemical and physico-chemical pre-treatment followed by a sequential, combinatorial pre-treatment strategy is also applied on to attain maximum sugar yield by combining two or more pre-treatments. All the pre-treated samples were analysed for total reducing sugar followed by identification and quantification of individual sugar by HPLC coupled with RI detector. Besides, generation of any inhibitory compounds such furfural, hydroxymethyl furfural (HMF) which can hinder microbial growth and enzyme activity is also monitored. Results showed that ultrasound treatment (31.06 mg/L) proved to be the best pre-treatment method based on total reducing content followed by dilute acid hydrolysis (10.03 mg/L) while galactose was found to be the major monosaccharide present in the pre-treated SPW. Finally, the results obtained from the study were used to design a sequential lignocellulose pre-treatment protocol to decrease the formation of enzyme inhibitors and increase sugar yield on enzymatic hydrolysis by employing cellulase-hemicellulase consortium. Sequential, combinatorial treatment was found better in terms of total reducing yield and low content of the inhibitory compounds formation, which could be due to the fact that this mode of pre-treatment combines several mild treatment methods rather than formulating a single one. It eliminates the need for a detoxification step and potential application in the valorisation of lignocellulosic food waste.

Keywords: lignocellulose, enzymatic hydrolysis, pre-treatment, ultrasound

Procedia PDF Downloads 366