Search results for: inhibition of cancer cells
Commenced in January 2007
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Edition: International
Paper Count: 5431

Search results for: inhibition of cancer cells

4921 New Roles of Telomerase and Telomere-Associated Proteins in the Regulation of Telomere Length

Authors: Qin Yang, Fan Zhang, Juan Du, Chongkui Sun, Krishna Kota, Yun-Ling Zheng

Abstract:

Telomeres are specialized structures at chromosome ends consisting of tandem repetitive DNA sequences [(TTAGGG)n in humans] and associated proteins, which are necessary for telomere function. Telomere lengths are tightly regulated within a narrow range in normal human somatic cells, the basis of cellular senescence and aging. Previous studies have extensively focused on how short telomeres are extended and have demonstrated that telomerase plays a central role in telomere maintenance through elongating the short telomeres. However, the molecular mechanisms of regulating excessively long telomeres are unknown. Here, we found that telomerase enzymatic component hTERT plays a dual role in the regulation of telomeres length. We analyzed single telomere alterations at each chromosomal end led to the discoveries that hTERT shortens excessively long telomeres and elongates short telomeres simultaneously, thus maintaining the optimal telomere length at each chromosomal end for an efficient protection. The hTERT-mediated telomere shortening removes large segments of telomere DNA rapidly without inducing telomere dysfunction foci or affecting cell proliferation, thus it is mechanistically distinct from rapid telomere deletion. We found that expression of hTERT generates telomeric circular DNA, suggesting that telomere homologous recombination may be involved in this telomere shortening process. Moreover, the hTERT-mediated telomere shortening is required its enzymatic activity, but telomerase RNA component hTR is not involved in it. Furthermore, shelterin protein TPP1 interacts with hTERT and recruits it on telomeres to mediate telomere shortening. In addition, telomere-associated proteins, DKC1 and TCAB1 also play roles in this process. This novel hTERT-mediated telomere shortening mechanism not only exists in cancer cells, but also in primary human cells. Thus, the hTERT-mediated telomere shortening is expected to shift the paradigm on current molecular models of telomere length maintenance, with wide-reaching consequences in cancer and aging fields.

Keywords: aging, hTERT, telomerase, telomeres, human cells

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4920 Antibacterial Potentials of the Leaf Extracts of Siam Weed (Chromolaena odorata) on Wound Isolates

Authors: M. E. Abalaka, O. A. Falusi, M. Galadima, D. Damisa

Abstract:

The antimicrobial activity of aqueous, ethanolic and methanolic extracts of Chromolaena odorata (Siam weed) was evaluated against four wound isolates: Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumoniae at the concentrations of 200mg/ml, 100mg/ml, 50mg/ml and 25mg/ml respectively. S. aureus and E. coli showed high susceptibility to the various extracts than the other test isolates. The aqueous extract showed activity against Staphylococcus aureus with a mean diameter of zone of inhibition of 16 ± 3.00 at concentration of 200mg/ml and as low as 8 ± 0.00 at concentration of 25mg/ml; E. coli showed susceptibility with a mean diameter of zone of inhibition of 18 ± 2.00 and 10 ± 0.00 at a concentration of 200mg/ml and 25mg/ml respectively. Pseudomonas aeruginosa and Klebsiella pneumoniae were resistant to the aqueous extract. Methanol extract showed activity against Staphylococcus aureus with a mean diameter of zone of inhibition at 28 ± 4.00 and 12 ± 2.30 at a concentration of 200mg/ml and 25mg/ml respectively; while E. coli was susceptible with mean diameter of zone of inhibition of 18 ± 2.00 and as low as 12 ± 0.00 at a concentration of 200mg/ml and 50mg/ml respectively, Pseudomonas aeruginosa showed considerable susceptibility with mean diameter of zone of inhibition of 13 ± 1.00 and 12 ± 0.00 at a concentration of 200mg/ml and 100mg/ml respectively. The ethanol extract showed activity against S. aureus with a mean diameter zone of inhibition of 15 ± 2.00 and 9 ± 0.00 at a concentration of 200mg/ml and 25mg/ml respectively: E. coli showed susceptibility with a mean diameter zone of inhibition of 20 ± 4.00 and 13 ± 2.00 at a concentration of 200mg/ml and 25mg/ml respectively. Pseudomonas aeruginosa showed considerable susceptibility with a mean diameter zone of inhibition of 13 ± 1.00 and 9 ± 0.00 at a concentration of 200mg/ml and 100mg/ml respectively. The results above indicate the efficacy and potency of the crude extracts of Chromolaena odorata leaf on the tested wound isolates.

Keywords: antibacterial, Chromolaena odorata, leaf extracts, test isolates

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4919 A Review of Effective Gene Selection Methods for Cancer Classification Using Microarray Gene Expression Profile

Authors: Hala Alshamlan, Ghada Badr, Yousef Alohali

Abstract:

Cancer is one of the dreadful diseases, which causes considerable death rate in humans. DNA microarray-based gene expression profiling has been emerged as an efficient technique for cancer classification, as well as for diagnosis, prognosis, and treatment purposes. In recent years, a DNA microarray technique has gained more attraction in both scientific and in industrial fields. It is important to determine the informative genes that cause cancer to improve early cancer diagnosis and to give effective chemotherapy treatment. In order to gain deep insight into the cancer classification problem, it is necessary to take a closer look at the proposed gene selection methods. We believe that they should be an integral preprocessing step for cancer classification. Furthermore, finding an accurate gene selection method is a very significant issue in a cancer classification area because it reduces the dimensionality of microarray dataset and selects informative genes. In this paper, we classify and review the state-of-art gene selection methods. We proceed by evaluating the performance of each gene selection approach based on their classification accuracy and number of informative genes. In our evaluation, we will use four benchmark microarray datasets for the cancer diagnosis (leukemia, colon, lung, and prostate). In addition, we compare the performance of gene selection method to investigate the effective gene selection method that has the ability to identify a small set of marker genes, and ensure high cancer classification accuracy. To the best of our knowledge, this is the first attempt to compare gene selection approaches for cancer classification using microarray gene expression profile.

Keywords: gene selection, feature selection, cancer classification, microarray, gene expression profile

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4918 Experienced Chronic Sorrow in Mothers of Children with Cancer: A Phenomenological Study

Authors: Nikfarid Lida, Maryam Rassouli, Leili Borimnejad, Hamid Alavi Majd

Abstract:

Purpose: Chronic sorrow is experienced by mothers of children with cancer. It is a multidimensional concept and is experienced by mothers in different ways depends on their various contexts. Little is known about the concept of chronic sorrow in mothers of children with cancer living in Iran. This study aimed to clarify the concept and explain lived experiences of chronic sorrow in Iranian mothers of children with cancer. Methods: In this hermeneutic phenomenological study, 8 mothers of children with cancer participated in semi structured in-depth interviews about their experiences of chronic sorrow. Interviews continued until data saturation was reached. All interviews were recorded, transcribed, analyzed, and interpreted using 7 steps of the Dickelman et al’s phenomenological approach. Results: Three main themes emerged from mothers’ experiences of chronic sorrow related to child’s cancer. These main themes were ‘climbing up shaky rocks,’ ‘fear and hope,’ and ‘continuous role changing.’ Each of these themes consisted of several subthemes. Conclusion: There are similarities in experiencing chronic sorrow by mothers of children with chronic diseases in different societies. However some experiences are unique in Iranian mothers of children with cancer.

Keywords: cancer, children, mothers, Iran, phenomenology

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4917 Management Potentialities Of Rice Blast Disease Caused By Magnaporthe Grisae Using New Nanofungicides Derived From Chitosan

Authors: Abdulaziz Bashir Kutawa, Khairulmazmi Ahmad, Mohd Zobir Hussein, Asgar Ali, Mohd Aswad Abdul Wahab, Amara Rafi, Mahesh Tiran Gunasena, Muhammad Ziaur Rahman, Md Imam Hossain, Syazwan Afif Mohd Zobir

Abstract:

Various abiotic and biotic stresses have an impact on rice production all around the world. The most serious and prevalent disease in rice plants, known as rice blast, is one of the major obstacles to the production of rice. It is one of the diseases that has the greatest negative effects on rice farming globally, the disease is caused by a fungus called Magnaporthe grisae. Since nanoparticles were shown to have an inhibitory impact on certain types of fungus, nanotechnology is a novel notion to enhance agriculture by battling plant diseases. Utilizing nanocarrier systems enables the active chemicals to be absorbed, attached, and encapsulated to produce efficient nanodelivery formulations. The objectives of this research work were to determine the efficacy and mode of action of the nanofungicides (in-vitro) and in field conditions (in-vivo). Ionic gelation method was used in the development of the nanofungicides. Using the poisoned media method, the synthesized agronanofungicides' in-vitro antifungal activity was assessed against M. grisae. The potato dextrose agar (PDA) was amended in several concentrations; 0.001, 0.005, 0.01, 0.025, 0.05, 0.1, 0.15, 0.20, 0.25, 0.30, and 0.35 ppm for the nanofungicides. Medium with the only solvent served as a control. Every day, mycelial growth was measured, and PIRG (percentage inhibition of radial growth) was also computed. Every day, mycelial growth was measured, and PIRG (percentage inhibition of radial growth) was also computed. Based on the results of the zone of inhibition, the chitosan-hexaconazole agronanofungicide (2g/mL) was the most effective fungicide to inhibit the growth of the fungus with 100% inhibition at 0.2, 0.25, 0.30, and 0.35 ppm, respectively. Then followed by carbendazim analytical fungicide that inhibited the growth of the fungus (100%) at 5, 10, 25, 50, and 100 ppm, respectively. The least were found to be propiconazole and basamid fungicides with 100% inhibition only at 100 ppm. The scanning electron microscope (SEM), confocal laser scanning microscope (CLSM), and transmission electron microscope (TEM) were used to study the mechanisms of action of the M. grisae fungal cells. The results showed that both carbendazim, chitosan-hexaconazole, and HXE were found to be the most effective fungicides in disrupting the mycelia of the fungus, and internal structures of the fungal cells. The results of the field assessment showed that the CHDEN treatment (5g/L, double dosage) was found to be the most effective fungicide to reduce the intensity of the rice blast disease with DSI of 17.56%, lesion length (0.43 cm), DR of 82.44%, AUDPC of 260.54 Unit2, and PI of 65.33%, respectively. The least treatment was found to be chitosan-hexaconazole-dazomet (2.5g/L, MIC). The usage of CHDEN and CHEN nanofungicides will significantly assist in lessening the severity of rice blast in the fields, increasing output and profit for rice farmers.

Keywords: chitosan, hexaconazole, disease incidence, and magnaporthe grisae

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4916 Using Econometric Methods to Explore Obesity Stigma and Avoidance of Breast and Cervical Cancer Screening

Authors: Stephanie A. Schauder, Gosia Sylwestrzak

Abstract:

Overweight and obese women report avoiding preventive care due to fear of weight-related bias from medical professionals. Gynecological exams, due to their sensitive and personally invasive nature, are especially susceptible to avoidance. This research investigates the association between body mass index (BMI) and screening rates for breast and cervical cancer using claims data from 1.3 million members of a large health insurance company. Because obesity is associated with increased cancer risk, screenings for these cancers should increase as BMI increases. However, this paper finds that the distribution of cancer screening rates by BMI take an inverted U-shape with underweight and obese members having the lowest screening rates. For cervical cancer screening, those in the target population with a BMI of 23 have the highest screening rate at 68%, while Obese Class III members have a screening rate of 50%. Those in the underweight category have a screening rate of 58%. This relationship persists even after controlling for health and demographic covariates in regression analysis. Interestingly, there is no association between BMI and BRCA (BReast CAncer gene) genetic testing. This is consistent with the narrative that stigma causes avoidance because genetic testing does not involve any assessment of a person’s body. More work must be done to determine how to increase cancer screening rates in those who may feel stigmatized due to their weight.

Keywords: cancer screening, cervical cancer, breast cancer, weight stigma, avoidance of care

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4915 Comparative in silico and in vitro Study of N-(1-Methyl-2-Oxo-2-N-Methyl Anilino-Ethyl) Benzene Sulfonamide and Its Analogues as an Anticancer Agent

Authors: Pamita Awasthi, Kirna, Shilpa Dogra, Manu Vatsal, Ritu Barthwal

Abstract:

Doxorubicin, also known as adriamycin, is an anthracycline class of drug used in cancer chemotherapy. It is used in the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute leukemias, breast cancer, lung cancer, endometrium cancer and ovary cancers. It functions via intercalating DNA and ultimately killing cancer cells. The major side effects of doxorubicin are hair loss, myelosuppression, nausea & vomiting, oesophagitis, diarrhoea, heart damage and liver dysfunction. The minor modifications in the structure of compound exhibit large variation in the biological activity, has prompted us to carry out the synthesis of sulfonamide derivatives. Sulfonamide is an important feature with broad spectrum of biological activity such as antiviral, antifungal, diuretics, anti-inflammatory, antibacterial and anticancer activities. Structure of the synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilino-ethyl)benzene sulfonamide confirmed by proton nuclear magnetic resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools to assure the position of all protons and hence stereochemistry of the molecule. Further we have reported the binding potential of synthesized sulfonamide analogues in comparison to doxorubicin drug using Auto Dock 4.2 software. Computational binding energy (B.E.) and inhibitory constant (Ki) has been evaluated for the synthesized compound in comparison of doxorubicin against Poly (dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences. The in vitro cytotoxic study against human breast cancer cell lines confirms the better anticancer activity of the synthesized compound over currently in use anticancer drug doxorubicin. The IC50 value of the synthesized compound is 7.12 µM where as for doxorubicin is 7.2 µ.

Keywords: Doxorubicin, auto dock, in silco, in vitro

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4914 Investigation of the Excitotoxicity Pathways in Neuroblastoma Cells

Authors: Merve Colak, Gizem Donmez Yalcin

Abstract:

Glutamate has many neurological functions in the central nervous system and is found at high concentrations in the brain. Increased levels of glutamate in the neuronal space are toxic, causing neuron damage and death. This is called glutamate-induced excitotoxicity. Excitotoxicity is among the causes of many neurological diseases such as trauma, cerebral ischemia, epilepsy, Parkinson's Disease, Alzheimer's Disease. Since neuroblastoma cells are known to be excitotoxic, we propose that excitotoxicity can be studied in neuroblastoma cells. Excitotoxicity can be induced using kainic acid in neuroblastoma cells. Measuring the secretion of glutamate, excitotoxicity can be analyzed in neuroblastoma cells.

Keywords: glutamate, excitotoxicity, kainic acid, Sirt4

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4913 Estimation of Serum Levels of Calcium and Inorganic Phosphorus in Breast Cancer Patients

Authors: Safa Safdar

Abstract:

Breast cancer is a type of cancer which is developed by the formation of a tumor on the breast. This tumor invades and causes different electrolyte imbalance. The present study was designed to measure the serum calcium and inorganic phosphorous levels and to check the frequency of hypercalcemia and hypophosphatemia in breast cancer patients. Serum calcium and phosphorous levels of fifty breast cancer women of 18-70 years of age group and fifty healthy women of same age group were measured by using semi-automated chemistry analyzer ( Humalyzer 3000, Human, Germany ). Significant variation in these levels was observed. The mean calcium value in BC patients was higher 9.398 mg/dl as compared to controls which were 8.694 mg/dl. Whereas the mean value of inorganic phosphorus level was lower 4.060 mg/dl in BC patients as compared to controls having 4.456 mg/dl. In this study, the frequency of hypercalcemia in Breast cancer patients was 10% i.e. only 10 out of 50 Breast cancer patients were suffering from hypercalcemia. Whereas the frequency of hypophosphatemia in this study was only 2 % i.e. only 1 out of 50 patients was suffering from hypophosphatemia. Thus it is concluded that there is a significant change in serum calcium and inorganic phosphorous levels in Breast cancer patients as the disease progresses. So, this study will be helpful for the clinicians to maintain serum calcium and phosphorous levels in Breast cancer patients and also preventing them from further complications.

Keywords: serum analysis, calcium, inorganic phosphorus, hpercalcemia hypophosphatemia

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4912 Mathematical Modeling of Bi-Substrate Enzymatic Reactions in the Presence of Different Types of Inhibitors

Authors: Rafayel Azizyan, Valeri Arakelyan, Aram Gevorgyan, Varduhi Balayan, Emil Gevorgyan

Abstract:

Currently, mathematical and computer modeling are widely used in different biological studies to predict or assess behavior of such complex systems as biological ones. This study deals with mathematical and computer modeling of bi-substrate enzymatic reactions, which play an important role in different biochemical pathways. The main objective of this study is to represent the results from in silico investigation of bi-substrate enzymatic reactions in the presence of uncompetitive inhibitors, as well as to describe in details the inhibition effects. Four models of uncompetitive inhibition were designed using different software packages. Particularly, uncompetitive inhibitor to the first [ES1] and the second ([ES1S2]; [FS2]) enzyme-substrate complexes have been studied. The simulation, using the same kinetic parameters for all models allowed investigating the behavior of reactions as well as determined some interesting aspects concerning influence of different cases of uncompetitive inhibition. Besides that shown, that uncompetitive inhibitors exhibit specific selectivity depending on mechanism of bi-substrate enzymatic reaction.

Keywords: mathematical modeling, bi-substrate enzymatic reactions, reversible inhibition

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4911 Malignancy in Venous Thromboembolism

Authors: Naser Shagerdi Esmaeli, Mohsen Hamidpour

Abstract:

Purposes: The activation of coagulation in patients with cancer contributes significantly to morbidity and mortality rates and may play a fundamental role in the host response to growing tumor’s. Patients with cancer are clearly at high risk for the development of venous thromboembolism (VTE), particularly during chemotherapy and surgery. This situation is aggravated by the use of venous access catheters and possibly growth factors. Methods: Data derived from large, randomized, controlled trials have been used to determine the true incidence of this complication of cancer and its treatment. The incidence based on the analyses of these randomized controlled trials varies from 1% for limited stage patients with breast cancer treated with tamoxifen to 60% for patients with any type of cancer who are subjected to orthopedic surgery and do not receive prophylactic therapy. Results: In view of the morbidity and mortality attributable to VTE in cancer, widespread utilization of prophylactic anticoagulation therapy, which has proven safe and effective in a variety of situations, should be considered. While migratory thrombophlebitis is a clear indicator of an underlying neoplasm, the risk of cancer in patients with the more typical form of VTE has been the subject of intense debate over recent years. Conclusion: Some investigators have suggested that the relative risk of being diagnosed with occult cancer within six months of an episode of VTE (particularly recurrent VTE) could be up to 10-fold. However, the cost-effectiveness of aggressive screening for cancer in patients with VTE has not yet been defined adequately.

Keywords: venous thromboembolism, malignancy, cancer, tumor, heparin

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4910 Antioxidants: Some Medicinal Plants in Indian System of Medicine Work as Anti-cervical Cancer

Authors: Kamini Kaushal

Abstract:

Medicinal plants of Ayurveda are effective in the treatment of cervical cancer. The aim of this paper is to assess anti cancerous activities of these medicinal plants against cancer. Most of the medicinal plants in Ayurveda are using to treat cervical cancer as name of disease as treatment of YONI VYAPADA. The selected plants has been studied scientifically in India and evidence based written since Vedic era. The compilation results showed potential anti cervical cancer activity of the tested plants. There plants are remaining under the dark due to lack of awareness, lack of popularity and barrier of language. Now this is the time to eye opener regarding the classical text and clinical evidences, so that we can give the hope to world's affected women from this disease. World is waiting for such type of remedy which is having zero side effects, low cost and effective.

Keywords: anti cancerous, cervical cancer, ayurveda, medicinal plants, scientific study, classical text

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4909 Identification of Disease Causing DNA Motifs in Human DNA Using Clustering Approach

Authors: G. Tamilpavai, C. Vishnuppriya

Abstract:

Studying DNA (deoxyribonucleic acid) sequence is useful in biological processes and it is applied in the fields such as diagnostic and forensic research. DNA is the hereditary information in human and almost all other organisms. It is passed to their generations. Earlier stage detection of defective DNA sequence may lead to many developments in the field of Bioinformatics. Nowadays various tedious techniques are used to identify defective DNA. The proposed work is to analyze and identify the cancer-causing DNA motif in a given sequence. Initially the human DNA sequence is separated as k-mers using k-mer separation rule. The separated k-mers are clustered using Self Organizing Map (SOM). Using Levenshtein distance measure, cancer associated DNA motif is identified from the k-mer clusters. Experimental results of this work indicate the presence or absence of cancer causing DNA motif. If the cancer associated DNA motif is found in DNA, it is declared as the cancer disease causing DNA sequence. Otherwise the input human DNA is declared as normal sequence. Finally, elapsed time is calculated for finding the presence of cancer causing DNA motif using clustering formation. It is compared with normal process of finding cancer causing DNA motif. Locating cancer associated motif is easier in cluster formation process than the other one. The proposed work will be an initiative aid for finding genetic disease related research.

Keywords: bioinformatics, cancer motif, DNA, k-mers, Levenshtein distance, SOM

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4908 Detection of Lymphedema after Breast Cancer in Yucatecan Women

Authors: Olais A. Ingrid, Peraza G. Leydi, Estrella C. Damaris

Abstract:

Breast cancer is the most common among women worldwide; the different treatments can bring sequels that directly affect the quality of life, such as lymphedema. The objective was to determine if there is presence of lymphedema secondary to breast cancer in Yucatecan women. It was an observational, analytical, cross-sectional study, 92 women were included who met the following criteria: women with surgical treatment for unilateral: breast cancer, aged between 25 and 65 years old, minimum 6 weeks after unilateral breast surgery and have completed any type of chemotherapy or adjuvant radiotherapy treatment for breast cancer. The evaluation was through indirect measurement volume by circometry to determine the presence of lymphedema. 23% of women had lymphedema grade I. It related to the presence of some of the symptoms like stiffness, swelling, decreased range of motion and feeling of heaviness in the arm of the operated side of the breast. It is important to determine the presence of lymphedema to perform physical therapy treatment.

Keywords: breast cancer, lymphedema, physical therapy, Yucatan

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4907 Impacts of CuO, TiO2, SiO2 Nanoparticles on Biological Phosphorus Removal

Authors: H. Shiu, M.S. Lu, Y.P. Tsai

Abstract:

This study explored the impacts of CuO, TiO2, SiO2 nanoparticles on biological phosphorus removal. Experimental results showed that the phosphorus removal ability of phosphorus accumulating organism (PAO) was initially inhibited when CuO nanoparticle concentration was 5 mgl-1. The inhibition of phosphorus removal for 1000 mgl-1 of TiO2 with sunlight was higher than without sunlight case. The inhibition of phosphorus removal began at 500 mgl-1 SiO2 nanoparticle concentration. Inhibition became apparent when SiO2 nanoparticle concentration was up to 1000 mgl-1.

Keywords: nano copper oxide, nano titanium dioxide, nano silica, enhanced biological phosphate removal

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4906 The MicroRNA-2110 Suppressed Cell Proliferation and Migration Capacity in Hepatocellular Carcinoma Cells

Authors: Pelin Balcik Ercin

Abstract:

Introduction: ZEB transcription factor family member ZEB2, has a role in epithelial to mesenchymal transition during development and metastasis. The altered circulating extracellular miRNAs expression is observed in diseases, and extracellular miRNAs have an important role in cancer cell microenvironment. In ChIP-Seq study, the expression of miR-2110 was found to be regulated by ZEB2. In this study, the effects of miR2110 on cell proliferation and migration of hepatocellular carcinoma (HCC) cells were examined. Material and Methods: SNU398 cells transfected with mimic miR2110 (20nM) (HMI0375, Sigma-Aldrich) and negative control miR (HMC0002, Sigma-Aldrich). MicroRNA isolation was accomplished with miRVANA isolation kit according to manufacturer instructions. cDNA synthesis was performed expression, respectively, and calibrated with Ct of controls. The real-time quantitative PCR (RT-qPCR) reaction was performed using the TaqMan Fast Advanced Master Mix (Thermo Sci.). Ct values of miR2110 were normalized to miR-186-5p and miR16-5p for the intracellular gene. Cell proliferation analysis was analyzed with the xCELLigence RTCA System. Wound healing assay was analyzed with the ImageJ program and relative fold change calculated. Results: The mimic-miR-2110 transfected SNU398 cells nearly nine-fold (log2) more miR-2110 expressed compared to negative control transfected cells. The mimic-miR-2110 transfected HCC cell proliferation significantly inhibited compared to the negative control cells. Furthermore, miR-2110-SNU398 cell migration capacity was relatively four-fold decreased compared to negative control-miR-SNU398 cells. Conclusion: Our results suggest the miR-2110 inhibited cell proliferation and also miR-2110 negatively affect cell migration compared to control groups in HCC cells. These data suggest the complexity of microRNA EMT transcription factors regulation. These initial results are pointed out the predictive biomarker capacity of miR-2110 in HCC.

Keywords: epithelial to mesenchymal transition, EMT, hepatocellular carcinoma cells, micro-RNA-2110, ZEB2

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4905 Cancer Burden and Policy Needs in the Democratic Republic of the Congo: A Descriptive Study

Authors: Jean Paul Muambangu Milambo, Peter Nyasulu, John Akudugu, Leonidas Ndayisaba, Joyce Tsoka-Gwegweni, Lebwaze Massamba Bienvenu, Mitshindo Mwambangu Chiro

Abstract:

In 2018, non-communicable diseases (NCDs) were responsible for 48% of deaths in the Democratic Republic of Congo (DRC), with cancer contributing to 5% of these deaths. There is a notable absence of cancer registries, capacity-building activities, budgets, and treatment roadmaps in the DRC. Current cancer estimates are primarily based on mathematical modeling with limited data from neighboring countries. This study aimed to assess cancer subtype prevalence in Kinshasa hospitals and compare these findings with WHO model estimates. Methods: A retrospective observational study was conducted from 2018 to 2020 at HJ Hospitals in Kinshasa. Data were collected using American Cancer Society (ACS) questionnaires and physician logs. Descriptive analysis was performed using STATA version 16 to estimate cancer burden and provide evidence-based recommendations. Results: The results from the chart review at HJ Hospitals in Kinshasa (2018-2020) indicate that out of 6,852 samples, approximately 11.16% were diagnosed with cancer. The distribution of cancer subtypes in this cohort was as follows: breast cancer (33.6%), prostate cancer (21.8%), colorectal cancer (9.6%), lymphoma (4.6%), and cervical cancer (4.4%). These figures are based on histopathological confirmation at the facility and may not fully represent the broader population due to potential selection biases related to geographic and financial accessibility to the hospital. In contrast, the World Health Organization (WHO) model estimates for cancer prevalence in the DRC show different proportions. According to WHO data, the distribution of cancer types is as follows: cervical cancer (15.9%), prostate cancer (15.3%), breast cancer (14.9%), liver cancer (6.8%), colorectal cancer (5.9%), and other cancers (41.2%) (WHO, 2020). Conclusion: The data indicate a rising cancer prevalence in DRC but highlight significant gaps in clinical, biomedical, and genetic cancer data. The establishment of a population-based cancer registry (PBCR) and a defined cancer management pathway is crucial. The current estimates are limited due to data scarcity and inconsistencies in clinical practices. There is an urgent need for multidisciplinary cancer management, integration of palliative care, and improvement in care quality based on evidence-based measures.

Keywords: cancer, risk factors, DRC, gene-environment interactions, survivors

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4904 Survival Analysis of Identifying the Risk Factors of Affecting the First Recurrence Time of Breast Cancer: The Case of Tigray, Ethiopia

Authors: Segen Asayehegn

Abstract:

Introduction: In Tigray, Ethiopia, next to cervical cancer, breast cancer is one of the most common cancer health problems for women. Objectives: This article is proposed to identify the prospective and potential risk factors affecting the time-to-first-recurrence of breast cancer patients in Tigray, Ethiopia. Methods: The data were taken from the patient’s medical record that registered from January 2010 to January 2020. The study considered a sample size of 1842 breast cancer patients. Powerful non-parametric and parametric shared frailty survival regression models (FSRM) were applied, and model comparisons were performed. Results: Out of 1842 breast cancer patients, about 1290 (70.02%) recovered/cured the disease. The median cure time from breast cancer is found at 12.8 months. The model comparison suggested that the lognormal parametric shared a frailty survival regression model predicted that treatment, stage of breast cancer, smoking habit, and marital status significantly affects the first recurrence of breast cancer. Conclusion: Factors like treatment, stages of cancer, and marital status were improved while smoking habits worsened the time to cure breast cancer. Recommendation: Thus, the authors recommend reducing breast cancer health problems, the regional health sector facilities need to be improved. More importantly, concerned bodies and medical doctors should emphasize the identified factors during treatment. Furthermore, general awareness programs should be given to the community on the identified factors.

Keywords: acceleration factor, breast cancer, Ethiopia, shared frailty survival models, Tigray

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4903 hsa-miR-1204 and hsa-miR-639 Prominent Role in Tamoxifen's Molecular Mechanisms on the EMT Phenomenon in Breast Cancer Patients

Authors: Mahsa Taghavi

Abstract:

In the treatment of breast cancer, tamoxifen is a regularly prescribed medication. The effect of tamoxifen on breast cancer patients' EMT pathways was studied. In this study to see if it had any effect on the cancer cells' resistance to tamoxifen and to look for specific miRNAs associated with EMT. In this work, we used continuous and integrated bioinformatics analysis to choose the optimal GEO datasets. Once we had sorted the gene expression profile, we looked at the mechanism of signaling, the ontology of genes, and the protein interaction of each gene. In the end, we used the GEPIA database to confirm the candidate genes. after that, I investigated critical miRNAs related to candidate genes. There were two gene expression profiles that were categorized into two distinct groups. Using the expression profile of genes that were lowered in the EMT pathway, the first group was examined. The second group represented the polar opposite of the first. A total of 253 genes from the first group and 302 genes from the second group were found to be common. Several genes in the first category were linked to cell death, focal adhesion, and cellular aging. Two genes in the second group were linked to cell death, focal adhesion, and cellular aging. distinct cell cycle stages were observed. Finally, proteins such as MYLK, SOCS3, and STAT5B from the first group and BIRC5, PLK1, and RAPGAP1 from the second group were selected as potential candidates linked to tamoxifen's influence on the EMT pathway. hsa-miR-1204 and hsa-miR-639 have a very close relationship with the candidates genes according to the node degrees and betweenness index. With this, the action of tamoxifen on the EMT pathway was better understood. It's important to learn more about how tamoxifen's target genes and proteins work so that we can better understand the drug.

Keywords: tamoxifen, breast cancer, bioinformatics analysis, EMT, miRNAs

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4902 Improving Cell Type Identification of Single Cell Data by Iterative Graph-Based Noise Filtering

Authors: Annika Stechemesser, Rachel Pounds, Emma Lucas, Chris Dawson, Julia Lipecki, Pavle Vrljicak, Jan Brosens, Sean Kehoe, Jason Yap, Lawrence Young, Sascha Ott

Abstract:

Advances in technology make it now possible to retrieve the genetic information of thousands of single cancerous cells. One of the key challenges in single cell analysis of cancerous tissue is to determine the number of different cell types and their characteristic genes within the sample to better understand the tumors and their reaction to different treatments. For this analysis to be possible, it is crucial to filter out background noise as it can severely blur the downstream analysis and give misleading results. In-depth analysis of the state-of-the-art filtering methods for single cell data showed that they do, in some cases, not separate noisy and normal cells sufficiently. We introduced an algorithm that filters and clusters single cell data simultaneously without relying on certain genes or thresholds chosen by eye. It detects communities in a Shared Nearest Neighbor similarity network, which captures the similarities and dissimilarities of the cells by optimizing the modularity and then identifies and removes vertices with a weak clustering belonging. This strategy is based on the fact that noisy data instances are very likely to be similar to true cell types but do not match any of these wells. Once the clustering is complete, we apply a set of evaluation metrics on the cluster level and accept or reject clusters based on the outcome. The performance of our algorithm was tested on three datasets and led to convincing results. We were able to replicate the results on a Peripheral Blood Mononuclear Cells dataset. Furthermore, we applied the algorithm to two samples of ovarian cancer from the same patient before and after chemotherapy. Comparing the standard approach to our algorithm, we found a hidden cell type in the ovarian postchemotherapy data with interesting marker genes that are potentially relevant for medical research.

Keywords: cancer research, graph theory, machine learning, single cell analysis

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4901 Benzimidazole as Corrosion Inhibitor for Heat Treated 6061 Al-SiCp Composite in Acetic Acid

Authors: Melby Chacko, Jagannath Nayak

Abstract:

6061 Al-SiCp composite was solutionized at 350 °C for 30 minutes and water quenched. It was then underaged at 140 °C (T6 treatment). The aging behaviour of the composite was studied using Rockwell B hardness measurement. Corrosion behaviour of the underaged sample was studied in different concentrations of acetic acid and at different temperatures. Benzimidazole at different concentrations was used for the inhibition studies. Inhibition efficiency of benzimidazole was calculated for different experimental conditions. Thermodynamic parameters were found out which suggested benzimidazole is an efficient inhibitor and it adsorbed onto the surface of composite by mixed adsorption where chemisorption is predominant.

Keywords: 6061 Al-SiCp composite, T6 treatment, corrosion inhibition, chemisorption

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4900 Factors Contributing to Delayed Diagnosis and Treatment of Breast Cancer and Its Outcome in Jamhoriat Hospital Kabul, Afghanistan

Authors: Ahmad Jawad Fardin

Abstract:

Over 60% of patients with breast cancer in Afghanistan present late with advanced stage III and IV, a major cause for the poor survival rate. The objectives of this study were to identify the contributing factors for the diagnosis and treatment delay and its outcome. This cross-sectional study was conducted on 318 patients with histologically confirmed breast cancer in the oncology department of Jamhoriat hospital, which is the first and only national cancer center in Afghanistan; data were collected from medical records and interviews conducted with women diagnosed with breast cancer, linear regression and logistic regression were used for analysis. Patient delay was defined as the time from first recognition of symptoms until first medical consultation and doctor form first consultation with a health care provider until histological confirmation of breast cancer. The mean age of patients was 49.2+_ 11.5years. The average time for the final diagnosis of breast cancer was 8.5 months; most patients had ductal carcinoma 260.7 (82%). Factors associated with delay were low education level 76% poor socioeconomic and cultural conditions 81% lack of cancer center 73% lack of screening 19%. The stage distribution was as follows stage IV 4 22% stage III 44.4% stage II 29.3% stage I 4.3%. Complex associated factors were identified to delayed the diagnosis of breast cancer and increased adverse outcomes consequently. Raising awareness and education in women, the establishment of cancer centers and providing accessible diagnosis service and screening, training of general practitioners; required to promote early detection, diagnosis and treatment.

Keywords: delayed diagnosis and poor outcome, breast cancer in Afghanistan, poor outcome of delayed breast cancer treatment, breast cancer delayed diagnosis and treatment in Afghanistan

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4899 Effect of Serine/Threonine Kinases on Autophagy Mechanism

Authors: Ozlem Oral, Seval Kilic, Ozlem Yedier, Serap Dokmeci, Devrim Gozuacik

Abstract:

Autophagy is a degradation pathway, activating under stress conditions. It digests macromolecules, such as abnormal proteins and long-lived organelles by engulfing them and by subsequent delivery of the cargo to lysosomes. The members of the phospholipid-dependent serine/threonine kinases, involved in many signaling pathways, which are necessary for the regulation of cellular metabolic activation. Previous studies implicate that, serine/threonine kinases have crucial roles in the mechanism of many diseases depend on the activated and/or inactivated signaling pathway. Data indicates, the signaling pathways activated by serine/threonine kinases are also involved in activation of autophagy mechanism. However, the information about the effect of serine/threonine kinases on autophagy mechanism and the roles of these effects in disease formation is limited. In this study, we investigated the effect of activated serine/threonine kinases on autophagic pathway. We performed a commonly used autophagy technique, GFP-LC3 dot formation and by using microscopy analyses, we evaluated promotion and/or inhibition of autophagy in serine/threonine kinase-overexpressed fibroblasts as well as cancer cells. In addition, we carried out confocal microscopy analyses and examined autophagic flux by utilizing the differential pH sensitivities of RFP and GFP in mRFP-GFP-LC3 probe. Based on the shRNA-library based screening, we identified autophagy-related proteins affected by serine/threonine kinases. We further studied the involvement of serine/threonine kinases on the molecular mechanism of newly identified autophagy proteins and found that, autophagic pathway is indirectly controlled by serine/threonine kinases via specific autophagic proteins. Our data indicate the molecular connection between two critical cellular mechanisms, which have important roles in the formation of many disease pathologies, particularly cancer. This project is supported by TUBITAK-1001-Scientific and Technological Research Projects Funding Program, Project No: 114Z836.

Keywords: autophagy, GFP-LC3 dot formation assay, serine/threonine kinases, shRNA-library screening

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4898 Higher Freshwater Fish and Sea Fish Intake Is Inversely Associated with Liver Cancer in Patients with Hepatitis B

Authors: Maomao Cao

Abstract:

Background and aims While the association between higher consumption of fish and lower liver cancer risk has been confirmed, however, the association between specific fish intake and liver cancer risk remains unknown. We aimed to identify the association between specific fish consumption and the risk of liver cancer. Methods: Based on a community-based seropositive hepatitis B cohort involving 18404 individuals, face to face interview was conducted by a standardized questionnaire to acquire baseline information. Three common fish types in this study were analyzed, including freshwater fish, sea fish, and small fish (shrimp, crab, conch, and shell). All participants received liver cancer screening, and possible cases were identified by CT or MRI. Multivariable logistic models were applied to estimate the odds ratio (OR) and 95% confidence intervals (CI). Multivariate multiple imputations were utilized to impute observations with missing values. Results: 179 liver cancer cases were identified. Consumption of freshwater fish and sea fish at least once a week had a strong inverse association with liver cancer risk compared with the lowest intake level, with an adjusted OR of 0.53 (95% CI, 0.38-0.75) and 0.38 (95% CI, 0.19-0.73), respectively. This inverse association was also observed after the imputation. There was no statistically significant association between intake of small fish and liver cancer risk (OR=0.58, 95%, CI 0.32-1.08). Conclusions: Our findings suggest that consumption of freshwater fish and sea fish at least once a week could reduce liver cancer risk.

Keywords: cross-sectional study, fish intake, liver cancer, risk factor

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4897 Antimicrobial Peptide Produced by Lactococcus garvieae with a Broad Inhibition Spectrum

Authors: Hai Chi, Ibrahim Mehmeti, Kirill Ovchinnikov, Hegle Holo, Ingolf F. Nes, Dzung B. Diep

Abstract:

By using a panel of multiple indicator strains of different bacterial species and genera, we screened a large collection of bacterial isolates (over 1800 isolates) derived from raw milk, for bacteriocin producers with broad inhibition spectra (BIS). Fourteen isolates with BIS were identified, and by 16S rDNA sequencing they were found to belong to Lactococcus garvieae (10 isolates) and Enterococcus feacalis (4 isolates). Further analysis of the ten L. garvieae isolates revealed that they were very similar, if not identical, to each other in metabolic and genetic terms: they had the same fermentation profile on different types of sugars, repetitive sequence-based PCR (rep-PCR) DNA pattern as well as they all had the same inhibition profile towards over 50 isolates of different species. The bacteriocin activity from one of the L. garvieae isolates was assessed further. The bacteriocin which was termed garvicin KS, was found to be heatstable and proteinase-labile and its inhibition spectrum contained many distantly related genera of Firmicutes, comprising most lactic acid bacteria (LAB) as well as problematic species of Bacillus, Listeria, Streptococcus and Staphylococcus and their antibiotic resistant derivatives (e.g. VRE, MRSA). Taken together, the results indicate that this is a potent bacteriocin from L. garvieae and that its very broad inhibition spectrum can be a very useful property for use in food preservation as well as in infection treatments caused by gram-positive pathogens and their antibiotic-derivatives.

Keywords: bacteriocin, lactic acid bacteria, Lactococcus garvieae, antibiotics resistance

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4896 Computational Analysis of Potential Inhibitors Selected Based on Structural Similarity for the Src SH2 Domain

Authors: W. P. Hu, J. V. Kumar, Jeffrey J. P. Tsai

Abstract:

The inhibition of SH2 domain regulated protein-protein interactions is an attractive target for developing an effective chemotherapeutic approach in the treatment of disease. Molecular simulation is a useful tool for developing new drugs and for studying molecular recognition. In this study, we searched potential drug compounds for the inhibition of SH2 domain by performing structural similarity search in PubChem Compound Database. A total of 37 compounds were screened from the database, and then we used the LibDock docking program to evaluate the inhibition effect. The best three compounds (AP22408, CID 71463546 and CID 9917321) were chosen for MD simulations after the LibDock docking. Our results show that the compound CID 9917321 can produce a more stable protein-ligand complex compared to other two currently known inhibitors of Src SH2 domain. The compound CID 9917321 may be useful for the inhibition of SH2 domain based on these computational results. Subsequently experiments are needed to verify the effect of compound CID 9917321 on the SH2 domain in the future studies.

Keywords: nonpeptide inhibitor, Src SH2 domain, LibDock, molecular dynamics simulation

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4895 Sexual Quality of Life in Women with Gynecological Cancer

Authors: Hatice Kahyaoglu Sut, Serap Unsar, Seda Kurt

Abstract:

The aim of this study is to investigate sexual quality of life in women with gynecological cancer. This cross-sectional study was conducted on 37 women with gynecological cancer and 39 control women (in menopausal term) at the Gynecooncology and Menopause Clinics of Trakya University Medical Faculty between January and July 2015. Women who had sexual active and willing to participate in the study filled an information form inquiring socio-demographic characteristics and Sexual Quality of Life Questionnaire-Female (SQLQ-F). Data were analyzed by Mann-Whitney-U test and Kruskal-Wallis test. The average age of the women was 52.7 ± 7.6 (51.2 ± 8.7 in women with gynecological cancer, 54.3 ± 6.0 in controls). The SQOL-F scores in women with gynecologic cancer (60.8 ± 22.4) was lower than controls (63.5 ± 20.7), however, there was no statistically significant difference (p = 0.759). Women with gynecological cancer who had vaginal dryness and pain during sexual intercourse (45.7 ± 21.3) were lower SQOL-F total score than control group (66.0 ± 21.7) (p = 0.014). The SQOL-F scores in women who took chemotherapy treatment (55.7 ± 17.8) were lower than in women who had not chemotherapy treatment (86.8 ± 16.6) (p = 0.005). In conclusion, taking chemotherapy treatment and occurring vaginal dryness and pain complaints during sexual intercourse in women with gynecological cancer reduces sexual quality of life. Therefore, sexual quality of life in women with gynecological cancer should be evaluated, and they should be supported in order to improve their sexual quality of life.

Keywords: gynecological cancer, quality of life, sexuality, women

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4894 Common Regulatory Mechanisms Reveals Links between Aberrant Glycosylation and Biological Hallmarks in Cancer

Authors: Jahanshah Ashkani, Kevin J. Naidoo

Abstract:

Glycosylation is the major posttranslational modification (PTM) process in cellular development. In tumour development, it is marked by structural alteration of carbohydrates (glycans) that is the result of aberrant glycosylation. Altered glycan structures affect cell surface ligand-receptor interactions that interfere with the regulation of cell adhesion, migration, and proliferation. The resulting changes in glycan biosynthesis pathways originate from altered expression of glycosyltransferases and glycosidases. While the alteration in glycosylation patterns is a recognized “hallmark of cancer”, the influential overview of the biology of cancer proposes eight hallmarks with no explicit suggestion to connectivity with glycosylation. Recently, we have discovered a connection between the glycosyltransferase gene expression and cancer type and subtype. Here we present an association between aberrant glycosylation and the biological hallmarks of breast cancer by exploring the common regulatory mechanisms at the genomic scale. The result of this study bridges the glycobiological and biological pathways that are accepted hallmarks of cancer by connecting their common regulatory pathways. This is an impetus for further investigation as target therapies of breast cancer are very likely to be uncovered from this.

Keywords: aberrant glycosylation, biological hallmarks, breast cancer, regulatory mechanism

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4893 Children Asthma; The Role of Molecular Pathways and Novel Saliva Biomarkers Assay

Authors: Seyedahmad Hosseini, Mohammadjavad Sotoudeheian

Abstract:

Introduction: Allergic asthma is a heterogeneous immuno-inflammatory disease based on Th-2-mediated inflammation. Histopathologic abnormalities of the airways characteristic of asthma include epithelial damage and subepithelial collagen deposition. Objectives: Human bronchial epithelial cell genome expression of TNF‑α, IL‑6, ICAM‑1, VCAM‑1, nuclear factor (NF)‑κB signaling pathways up-regulate during inflammatory cascades. Moreover, immunofluorescence assays confirmed the nuclear translocation of NF‑κB p65 during inflammatory responses. An absolute LDH leakage assays suggestedLPS-inducedcells injury, and the associated mechanisms are co-incident events. LPS-induced phosphorylation of ERKand JNK causes inflammation in epithelial cells through inhibition of ERK and JNK activation and NF-κB signaling pathway. Furthermore, the inhibition of NF-κB mRNA expression and the nuclear translocation of NF-κB lead to anti-inflammatory events. Likewise, activation of SUMF2 which inhibits IL-13 and reduces Th2-cytokines, NF-κB, and IgE levels to ameliorate asthma. On the other hand, TNFα-induced mucus production reduced NF-κB activation through inhibition of the activation status of Rac1 and IκBα phosphorylation. In addition, bradykinin B2 receptor (B2R), which mediates airway remodeling, regulates through NF-κB. Bronchial B2R expression is constitutively elevated in allergic asthma. In addition, certain NF-κB -dependent chemokines function to recruit eosinophils in the airway. Besides, bromodomain containing 4 (BRD4) plays a significant role in mediating innate immune response in human small airway epithelial cells as well as transglutaminase 2 (TG2), which is detectable in saliva. So, the guanine nucleotide-binding regulatory protein α-subunit, Gα16, expresses a κB-driven luciferase reporter. This response was accompanied by phosphorylation of IκBα. Furthermore, expression of Gα16 in saliva markedly enhanced TNF-α-induced κB reporter activity. Methods: The applied method to form NF-κB activation is the electromobility shift assay (EMSA). Also, B2R-BRD4-TG2 complex detection by immunoassay method within saliva with EMSA of NF-κB activation may be a novel biomarker for asthma diagnosis and follow up. Conclusion: This concept introduces NF-κB signaling pathway as potential asthma biomarkers and promising targets for the development of new therapeutic strategies against asthma.

Keywords: NF-κB, asthma, saliva, T-helper

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4892 Produced Water Treatment Using Novel Solid Scale Inhibitors Based on Silver Tungstate Loaded Kit-6: Static and Modeling Evaluation

Authors: R. Hosny, Mahmoud F. Mubarak, Heba M. Salem, Asmaa A. Abdelrahman

Abstract:

Oilfield scaling is a major problem in the oil and gas industry. Scale issues cost the industry millions of dollars in damage and lost production every year. One of the main causes of global production decline is scale. In this study, solid scale inhibitors based on silver tungstate loaded KIT-6 were synthesized and evaluated in both static and scale inhibition modeling. The silver tungstate loaded KIT-6 catalysts were synthesized via a simple impregnated method using 3D mesoporous KIT-6 as support. The synthesized materials were characterized using wide and low XRD, N2 adsorption–desorption analysis, TGA analysis, and FTIR, SEM, and XPS analysis. The scale inhibition efficiency of the synthesized materials was evaluated using a static scale inhibition test. The results of this study demonstrate the potential application of silver tungstate-loaded KIT-6 solid scale inhibitors for the oil and gas industry. The results of this study will contribute to the development of new and innovative solid scale inhibitors based on silver tungstate-loaded KIT-6. The inhibition efficiency of the scale inhibitor increases, and calcite scale inhibitor decreases with increasing pH (2 to8), it proposes that the scale inhibitor was more effective under alkaline conditions. An inhibition efficiency of 99% on calcium carbonate can be achieved at the optimal dosage of 7.5 ppm at 55oC, indicating that the scale inhibitor exhibits a relatively good inhibition performance on calcium carbonate. The use of these materials can potentially lead to more efficient and cost-effective solutions for scaling inhibition in various industrial processes.

Keywords: produced water treatment, solid scale inhibitors, calcite, silver tungestate, 3 D mesoporous KIT-6, oilfield scales, adsorption

Procedia PDF Downloads 144