Search results for: cellular automaton

Authors: Harish Rajak, Kamlesh Raghuwanshi

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Histone deacetylase (HDAC) are promising target for cancer treatment. The panobinostat (Farydak; Novartis; approved by USFDA in 2015) and chidamide (Epidaza; Chipscreen Biosciences; approved by China FDA in 2014) are the novel HDAC inhibitors ratified for the treatment of patients with multiple myeloma and peripheral T cell lymphoma, respectively. On the other hand, two other HDAC inhibitors, Vorinostat (SAHA; approved by USFDA in 2006) and Romidepsin (FK228; approved by USFDA in 2009) are already in market for the treatment of cutaneous T-cell lymphoma. Several hydroxamic acid based HDAC inhibitors i.e., belinostat, givinostat, PCI24781 and JNJ26481585 are in clinical trials. HDAC inhibitors consist of three pharmacophoric features - an aromatic cap group, zinc binding group (ZBG) and a linker chain connecting cap group to ZBG. Herein, we report synthesis, characterization and biological evaluation of HDAC inhibitors possessing substituted isatin moiety as cap group which recognize the surface of active enzyme pocket and thiosemicarbazide moiety incorporated as linker group responsible for connecting cap group to ZBG (hydroxamic acid). Several analogues were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells with GI50 values in the micro molar range. Some of the compounds exhibited promising results in vitro antiproliferative studies. Attempts were also made to establish the structure activity relationship among synthesized HDAC inhibitors.

Keywords: HDAC inhibitors, hydroxamic acid derivatives, isatin derivatives, antiproliferative activity, docking

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Authors: Mojtaba Mirmontazemi, Habibollah Dadgar

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Bone is the most common metastasis site in some advanced malignancies, such as prostate and breast cancer. Bone metastasis generally indicates fewer prognostic factors in these patients. Different radiological and molecular imaging modalities are used for detecting bone lesions. Molecular imaging including computed tomography, magnetic resonance imaging, planar bone scintigraphy, single-photon emission tomography, and positron emission tomography as noninvasive visualization of the biological occurrences has the potential to exact examination, characterization, risk stratification and comprehension of human being diseases. Also, it is potent to straightly visualize targets, specify clearly cellular pathways and provide precision medicine for molecular targeted therapies. These advantages contribute implement personalized treatment for each patient. Currently, NaF PET/CT has significantly replaced standard bone scintigraphy for the detection of bone metastases. On one hand, 68Ga-PSMA PET/CT has gained high attention for accurate staging of primary prostate cancer and restaging after biochemical recurrence. On the other hand, FDG PET/CT is not commonly used in osseous metastases of prostate and breast cancer as well as its usage is limited to staging patients with aggressive primary tumors or localizing the site of disease. In this article, we examine current studies about FDG, NaF, and PSMA PET/CT images in bone metastases diagnostic utility and assess response to treatment in patients with breast and prostate cancer.

Keywords: skeletal metastases, fluorodeoxyglucose, sodium fluoride, molecular imaging, precision medicine, prostate cancer (68Ga-PSMA-11)

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Authors: Farideh K. Khosroushahi, Serkan Erdal, Mucip Geni̇şel

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Soil salinity is one of the major abiotic stress factors that restricts arable land and reduces crop productivity worldwide. High salt concentration adversely affects plant growth and development inducing water deficit, ionic toxicity, nutrient imbalance, and lead to oxidative stress. Although the stimulating role of mammalian sex hormones on various biological and biochemical processes under normal and stress condition have been proven, there is no study regarding with these hormone's effect on modulation of the alternative respiration pathway and AOX gene expression. In this study, changes in alternative respiration pathway in leaves of maize seedlings under salinity and the possible modulating effect of estrogen on these changes were investigated. Maize seedlings were grown in a hydroponic media for 11 days and then were exposed to salt stress for 3 days after being sprayed estrogen. The data obtained from oxygen consumption revealed that salt stress elevated cellular respiration value in the leaves. In addition, a marked increase was observed at alternative respiration level in salt-stressed seedlings. Compared to salt application alone, supplementation with estrogen resulted in a significant rise in alternative oxidase (AOX) activities. Similarly, while salt stress caused to rise in expressions of AOX gene compared to control seedlings, estrogen application resulted in further activation of these genes’ expression compared to stressed-seedlings alone. These data revealed that mitigating role of estrogen against the detrimental effects of salt stress is linked to modulation of alternative respiration pathway.

Keywords: alternative oxidase, estrogen, Ssalt stress, AOX, maize

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Authors: Sahar Essa, Hussain A. Safar, Raj Raghupathy

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Human cytomegalovirus (CMV) continues to be a source of severe complications in immunologically immature and immunocompromised hosts. Effective CMV vaccines that help diminish CMV disease in transplant patients and avoid congenital infection are of great importance. Though the exact roles of defense mechanisms are unidentified, viral-specific antibodies and cytokine responses are known to be involved in controlling CMV infections. CMV envelope glycoprotein B (UL55/gB), matrix proteins (UL83/pp65, UL99/pp28, UL32/pp150), and assembly protein UL80a/pp38 are known to be targets of antiviral immune responses. We immunized mice intraperitoneally with these five CMV-related proteins (commercial) for their ability to induce specific antibody responses (in-house immunoassay) and cytokine production (commercial assay) in a mouse model. We observed a significant CMV-antigen-specific antibody response to pp38 and pp65 (E/C ˃2.0, p˂0.001). Mice immunized with pp38 had significantly higher concentrations of GM-CSF, IFN-α, IL-2 IL-4, IL-5, and IL-17A (p˂0.05). Mice immunized with pp65 showed significantly higher concentrations of GM-CSF, IFN-γ, IL-2 IL-4, IL-10, IL-12, IL-17A, and TNF-α. Th1 to Th2 cytokines ratios revealed a Th1 cytokine bias in mice immunized with pp38, pp65, pp150, and gB. We suggest that stimulation with multiple CMV-related proteins, which include pp38, pp65, and gB antigens, will allow both humoral and cellular immune responses to be efficiently activated, thus serving as appropriate CMV antigens for future vaccines.

Keywords: cytomegalovirus, UL99/pp28, UL80a/pp38, UL83/pp65, UL32/pp150, UL55/gB, CMV-antigen-specific antibody, CMV antigen-specific cytokine responses

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Authors: Shutchapol Chopvitayakun

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Nowadays, especially for the last 5 years, mobile devices, mobile applications and mobile users, through the deployment of wireless communication and mobile phone cellular network, all these components are growing significantly bigger and stronger. They are being integrated into each other to create multiple purposes and pervasive deployments into every business and non-business sector such as education, medicine, traveling, finance, real estate and many more. Objective of this study was to develop a mobile application for seniors or last-year students who enroll the internship program at each tertiary school (undergraduate school) and do onsite practice at real field sties, real organizations and real workspaces. During the internship session, all students as the interns are required to exercise, drilling and training onsite with specific locations and specific tasks or may be some assignments from their supervisor. Their work spaces are both private and government corporates and enterprises. This mobile application is developed under schema of a transactional processing system that enables users to keep daily work or practice log, monitor true working locations and ability to follow daily tasks of each trainee. Moreover, it provides useful guidance from each intern’s advisor, in case of emergency. Finally, it can summarize all transactional data then calculate each internship cumulated hours from the field practice session for each individual intern.

Keywords: internship, mobile application, Android OS, smart phone devices, mobile transactional processing system, guidance and monitoring, tertiary education, senior students, model view controller (MVC)

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Authors: Hyo-Min Kim, Seokjin Ham, Mi-Joung Yoo, Minseon Kim, Tae-Young Roh

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The gastrointestinal (GI) tract of most animals, including murine, is highly compartmentalized epithelia which also provide distinct different functions of its own tissue. Nevertheless, these epithelia share certain characteristics that enhance immune responses to infections and maintain the barrier function of the intestine. GI tract epithelia also undergo regeneration not only in homeostatic conditions but also in a response to the damage. A full turnover of the murine gastrointestinal epithelium occurs every 4-5 day, a process that is regulated and maintained by a minor population of Lgr5+ adult stem cell that commonly conserved in the bottom of crypts through GI tract. Maintenance of the stem cell is somehow regulated by epigenetic factors according to recent studies. Chromatin vacancy, remodelers, histone variants and histone modifiers could affect adult stem cell fate. In this study, Lgr5-EGFP reporter mouse was used to take advantage of exploring the epigenetic dynamics among Lgr5 positive mutual stem cell in GI tract. Cells were isolated by fluorescence-activated cell sorting (FACS), gene expression levels, chromatin accessibility changes and histone modifications were analyzed. Some notable chromatin structural related epigenetic variants were detected. To identify the overall cell-cell interaction inside the stem cell niche, an extensive genome-wide analysis should be also followed. According to the results, nevertheless, we expected a broader understanding of cellular niche maintaining stem cells and epigenetic barriers through conserved stem cell in GI tract. We expect that our study could provide more evidence of adult stem cell plasticity and more chances to understand each stem cell that takes parts in certain organs.

Keywords: adult stem cell, epigenetics, LGR5 stem cell, gastrointestinal tract

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Authors: Shifu Hu, Qiong Yu, Wei Xia, Changhong Zhu

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Background: P38α MAPK, which is a member of the canonical MAPK family, is activated in response to various extracellular stresses and plays a role in multiple cellular processes. It is well known that p38α MAPK play vital roles in oocyte maturation, but the localization and functional roles of p38α MAPK during the meiotic maturation of rat oocytes remain unknown. Study Design: In this study, western-blot and immunofluorescent staining were used to investigate the expression and subcellular localization of p38α MAPK during the meiotic maturation of rat oocytes. SB203580, a specific inhibitor of p38α MAPK, was used to study the roles of p38α MAPK in the meiotic cell cycle of rat oocytes. Results: The results found that p38α MAPK phosphorylation (p-p38α MAPK, indicative of p38α MAPK activation) was low at the germinal vesicle (GV) stage, increased 3 h after germinal vesicle breakdown (GVBD), and maintained its maximum at MI (metaphase I) or M II (metaphase II). The p-p38α MAPK mainly accumulated in the germinal vesicle and had no obvious expression in the nucleus. From GVBD to M II, p-p38α MAPK was distributed in the cytoplasm around either the chromosomes or the spindle. We used SB203580, an inhibitor of p38α MAPK, to investigate the possible functional role of p38α MAPK during rat oocyte meiotic maturation. Treatment of GV stage oocytes with 20 μM SB203580 blocked p-p38α MAPK activity, and the spindles appeared abnormal. Additionally, the rate of GVBD after 3h of culture with 20 μM SB203580 (58.8%) was significantly inhibited compared with the control (82.5%, p < 0.05), and the polar body extrusion rate after 12 h of culture with SB203580 was also significantly decreased compared with the control (40.1 vs. 73.3%, p < 0.05). Conclusions: These data indicate that p38α MAPK may play a vital role in rat oocyte meiotic maturation.

Keywords: meiotic maturation, oocyte, p38α MAPK, spindle

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Authors: Bernard L. Middleton, Susan P. Cosgrove

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There is an immediate need for alternative anti-herpetic treatment options effective for both primary infections and reoccurring reactivations of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Alternatives currently approved for the purposes of clinical administration includes antivirals and a reduced set of nucleoside analogues. The present article tests a treatment based on a systemic understanding of how the herpes virus affects cell inhibition and breakdown and targets different phases of the viral cycle, including the entry stage, reproductive cross mutation, and cell-to-cell infection. The treatment consisted of five immunotherapeutic core compounds (5CC), which were hypothesized to be capable of neutralizing human monoclonal antibodies. The tested 5CC were noted as being functional in the application of eliminating the DNA synthesis of herpes viral interferon (IFN) - induced cellular antiviral response. They were here found to neutralize antiviral reproduction by blocking cell-to-cell infection. The activity of the 5CC was tested on RC-37 in vitro using an assay plaque reduction and in vivo against HSV-1 and HSV-2. The 50% inhibitory concentration (IC50) of 5CC was 0.0009% for HSV-1 plaque formation and 0.0008% for HSV-2 plaque formation. Further tests were performed to evaluate the susceptibility of HSV-1 and HSV-2 to anti-herpetic drugs in Vero cells after virus entry. There were high-level markers of the 5CC virucidal activity in the viral suspension of HSV-1 and HSV-2. These concentrations of the 5CC are nontoxic and reduced plaque formation by 98.2% for HSV-1 and 93.0% for HSV-2. Virus HSV-1 and HSV-2 titers were reduced significantly by 5CC to the point of being negative, ranging 0.01–0.09 in 72%. The results concluded the 5CC as being an effective treatment option for the herpes simplex virus.

Keywords: synergy pharmaceuticals, herpes treatment, herpes cure, synergy pharmaceuticals treatment

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Authors: Byron Joseph A. Hallar, Annjeannette Alain D. Galang, Maria Visitacion N. Gumabay

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The widespread adoption and increasing proliferation of smartphones that started during the first decade of the twenty-first century have enabled their users to communicate and access information in ways that were merely thought of as possibilities in the few years before the smartphone revolution. A product of the convergence of the cellular phone and portable computer, the smartphone provides an additional important function that used to be the exclusive domain of desktop-bound computers and portable computers: Web Browsing. For increasing numbers of users, the smartphone and allied devices such as tablet computers have become their first and often their only means of accessing the World Wide Web. This has led to the development of websites that cater to the needs of the new breed of smartphone-carrying web users. The smaller size of smartphones as compared with conventional computers has provided unique challenges to web interface designers. The smaller screen size and touchscreen interface have made it much more difficult to read and navigate through web pages that were in most part designed for traditional desktop and portable computers. Although increasing numbers of websites now provide an alternate website formatted for smartphones, problems with ease of use, reliability and usability still remain. This study focuses on the identification of the problems associated with smartphone web interfaces, the compliance with accepted standards of user-oriented web interface design, the strategies that could be utilized to ensure the design of user-centric web interfaces for smartphones, and the identification of the current trends and developments related to user-centric web interface design intended for the consumption of smartphone users.

Keywords: human-computer interaction, user-centered design, web interface, mobile, smartphone

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Authors: Jang kyun Cho, Jeong-dong Lee

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The advent of the Internet, mobile communications, and social network services has stimulated social interactions among consumers, allowing people to affect one another’s innovation adoptions by exchanging information more frequently and more quickly. Previous diffusion models, such as the Bass model, however, face limitations in reflecting such recent phenomena in society. These models are weak in their ability to model interactions between agents; they model aggregated-level behaviors only. The agent based model, which is an alternative to the aggregate model, is good for individual modeling, but it is still not based on an economic perspective of social interactions so far. This study assumes the presence of social utility from other consumers in the adoption of innovation and investigates the effect of individual interactions on innovation diffusion by developing a new model called the interaction-based diffusion model. By comparing this model with previous diffusion models, the study also examines how the proposed model explains innovation diffusion from the perspective of economics. In addition, the study recommends the use of a small-world network topology instead of cellular automata to describe innovation diffusion. This study develops a model based on individual preference and heterogeneous social interactions using utility specification, which is expandable and, thus, able to encompass various issues in diffusion research, such as reservation price. Furthermore, the study proposes a new framework to forecast aggregated-level market demand from individual level modeling. The model also exhibits a good fit to real market data. It is expected that the study will contribute to our understanding of the innovation diffusion process through its microeconomic theoretical approach.

Keywords: innovation diffusion, agent based model, small-world network, demand forecasting

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Authors: Shabnam Monadizadeh, Charles Kibert, Jiaxuan Li, Janghoon Woo, Ashish Asutosh, Samira Roostaei, Maryam Kouhirostami

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A significant share of the technology that has emerged over the past several decades produces electromagnetic field (EMF) radiation. Communications devices, household appliances, industrial equipment, and medical devices all produce EMF radiation with a variety of frequencies, strengths, and ranges. Some EMF radiation, such as Extremely Low Frequency (ELF), Radio Frequency (RF), and the ionizing range have been shown to have harmful effects on human health. Depending on the frequency and strength of the radiation, EMF radiation can have health effects at the cellular level as well as at brain, nervous, and cardiovascular levels. Health authorities have enacted regulations locally and globally to set critical values to limit the adverse effects of EMF radiation. By introducing a more comprehensive field of EMF radiation study and practice, architects and designers can design for a safer electromagnetic (EM) indoor environment, and, as building and construction specialists, will be able to monitor and reduce EM radiation. This paper identifies the nature of EMF radiation in the built environment, the various EMF radiation sources, and its human health effects. It addresses European and US regulations for EMF radiation in buildings and provides a preliminary action plan. The challenges of developing measurement protocols for the various EMF radiation frequency ranges and determining the effects of EMF radiation on building occupants are discussed. This paper argues that a mature method for measuring EMF radiation in building environments and linking these measurements to human health impacts occupant health should be developed to provide adequate safeguards for human occupants of buildings for future research.

Keywords: biological affection, electromagnetic field, building regulation, human health, healthy building, clean construction

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Authors: Faezah Shekh Abdullah, Mohd. Azizuddin Mohd. Yussof, Komathy Thiagarajan, Hasnoorina Husin, Noor Azreena Abd Aziz

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Polycystic ovary syndrome has been associated with multiple disorders such as endocrine disorder, metabolic syndrome, infertility, and endometrial cancer. Women with polycystic ovary syndrome (PCOS) are anticipated to develop three times more chances for endometrial cancer than women without PCOS. This study, therefore, was conducted to determine the association between polycystic ovary syndrome and endometrial cancer and to determine the cervical cytology features of PCOS. Patients attending the Subfertility Clinic of the National Population and Family Development Board were recruited and examined physically by medical practitioners. They were categorized into two groups; i) the PCOS group if they met Rotterdam Criteria 2004 and ii) the control group if they did not meet Rotterdam Criteria 2004. Cervical sampling was done on all patients via the Liquid-Based Cytology (LBC) method in the pre-and post-subfertility treatment. A total of 167 patients participated in the study, of which 79 belonged to the PCOS group and 88 to the control group. The findings showed no cervical and endometrial cancer cases in both groups. The Liquid-Based Cytology results in the PCOS group displayed more cases with cellular changes, i.e., benign inflammation, atrophic smear and Candida sp. infection. To conclude, no association was found between polycystic ovary syndrome and endometrial cancer. A more holistic study with a higher number of participants can further determine the association between endometrial cancer and PCOS. Furthermore, a longer duration between LBC pre- and post-subfertility treatment should be implied to observe changes in the cervical cells.

Keywords: endometrial cancer, liquid-based cytology, PCOS, polycystic ovary syndrome

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Authors: Yingxiao Ye, Christopher Doehring, Angelos Georghiou, Hugh Robinson, Phebe Vayanos

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Human development is a threat to biodiversity, and conservation organizations (COs) are purchasing land to protect areas for biodiversity preservation. However, COs have limited budgets and thus face hard prioritization decisions that are confounded by uncertainty in future human land use. This research proposes a data-driven sequential planning model to help COs choose land parcels that minimize the uncertain human impact on biodiversity. The proposed model is robust to uncertain development, and the sequential decision-making process is adaptive, allowing land purchase decisions to adapt to human land use as it unfolds. The cellular automata model is leveraged to simulate land use development based on climate data, land characteristics, and development threat index from NASA Socioeconomic Data and Applications Center. This simulation is used to model uncertainty in the problem. This research leverages state-of-the-art techniques in the robust optimization literature to propose a computationally tractable reformulation of the model, which can be solved routinely by off-the-shelf solvers like Gurobi or CPLEX. Numerical results based on real data from the Jaguar in Central and South America show that the proposed method reduces conservation loss by 19.46% on average compared to standard approaches such as MARXAN used in practice for biodiversity conservation. Our method may better help guide the decision process in land acquisition and thereby allow conservation organizations to maximize the impact of limited resources.

Keywords: data-driven robust optimization, biodiversity conservation, uncertainty simulation, adaptive sequential planning

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Authors: Abdolrasoul Daneshjoo, Fatemeh Akbari Ghara

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Background and Purpose: Obesity is an increasing factor in cardiovascular disease and serum levels of cellular adhesion molecule. It plays an important role in predicting risk for coronary artery disease. The purpose of this research was to study the effect of eight weeks moderate intensity interval training and curcumin intake on ICAM-1 & VCAM-1 levels of menopausal fat rats. Materials and methods: in this study, 28 Wistar Menopausal fat rats aged 6-8 weeks with an average weight of 250-300 (gr) were randomly divided into four groups: control, curcumin supplement, moderate intensity interval training and moderate intensity interval training + curcumin supplement. (7 rats each group). The training program was planned as 8 weeks and 3 sessions per week. Each session consisted of 10 one-min sets with 50 percent intensity and the 2-minutes interval between sets in the first week. Subjects started with 14 meters per minute, and 2 (m/min) was added to increase their speed weekly until the speed of 28 (m/min) in the 8th week. Blood samples were taken 48 hours after the last training session, and ICAM-1 A and VCAM-1 levels were measured. SPSS software, one-way analysis of variance (ANOVA) and Pearson correlation coefficient were used to assess the results. Results: The results showed that eight weeks of training and taking curcumin had significant effects on ICAM-1 levels of the rats (p ≤ 0.05). However, it had no significant effect on VCAM-1 levels in menopausal obese rates (p ≥ 0.05). There was no significant correlation between the levels of ICAM-1 and VCAM-1 in eight weeks training and taking curcumin. Conclusion: Implementation of moderate intensity interval training and the use of curcumin decreased ICAM-1 significantly.

Keywords: curcumin, interval training , ICMA, VCAM

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Authors: Do Khanh Vy, Vuong Cat Khanh, Osamu Ohneda

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During atherosclerosis (AS) progression, perivascular adipose tissue-derived mesenchymal stem cells (PVAT-MSCs) are exposed to the hypoxic environment due to the oxygenic deprivation which might influence the adipose tissue-derived mesenchymal stem cells (AT-MSCs) function. Additionally, it has been reported that the angiogenic ability of subcutaneous AT-MSCs (SAT-MSCs) was impaired in the AS patients. However, up to now, the effects of AS on the characteristics and function of PVAT-MSCs have not been clarified yet. In the present study, we analyzed the AS microenvironment effects on the characteristics and function of AT-MSCs. We found that there was no significant difference in cellular morphology and differentiation ability between SAT-MSCs and PVAT-MSCs in AS patients. However, the proliferation of AS-derived PVAT-MSCs was less than those of AS-derived SAT-MSCs. Importantly, the migration of AS-derived PVAT-MSCs was faster than AS-derived SAT-MSCs. Of note, AS-derived PVAT-MSCs showed the upregulation of SDF1, which is related to the homing, and VEGF, which is related to the angiogenesis compared to those of AS-derived SAT-MSCs. Consistent with these results, AS-derived PVAT-MSCs showed the higher ability to recruit EPCs and ECs than AS-derived SAT-MSCs. In addition, EPCs and ECs which cultured in the presence of AS-derived PVAT-MSC conditioned medium showed the higher angiogenic function of the tube formation compared to those cultured in AS-derived SAT-MSC conditioned medium. This result suggests that the higher paracrine effects of AS-derived PVAT-MSCs support the angiogenic function of the target cells. Our data showed the different characteristics and functions of AT-MSCs derived from different sources of tissues. Under the AS microenvironment, it seems that the characteristics and functions of PVAT-MSCs might reflect the progression of AS. Further study will be necessary to clarify the mechanism in the future.

Keywords: atherosclerosis, mesenchymal stem cells, perivascular adipose tissue, subcutaneous adipose tissue

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Authors: Muhammad Muzamil Khan, Asadullah Madni, Nina Filipczek, Jiayi Pan, Nayab Tahir, Hassan Shah, Vladimir Torchilin

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Lipid-polymer hybrid nanoparticles (LPHNP) are delivery systems for controlled drug delivery at tumor sites. The superior biocompatible properties of lipid and structural advantages of polymer can be obtained via this system for controlled drug delivery. In the present study, cisplatin-loaded lipid-chitosan hybrid nanoparticles were formulated by the single step ionic gelation method based on ionic interaction of positively charged chitosan and negatively charged lipid. Formulations with various chitosan to lipid ratio were investigated to obtain the optimal particle size, encapsulation efficiency, and controlled release pattern. Transmission electron microscope and dynamic light scattering analysis demonstrated a size range of 181-245 nm and a zeta potential range of 20-30 mV. Compatibility among the components and the stability of formulation were demonstrated with FTIR analysis and thermal studies, respectively. The therapeutic efficacy and cellular interaction of cisplatin-loaded LPHNP were investigated using in vitro cell-based assays in A2780/ADR ovarian carcinoma cell line. Additionally, the cisplatin loaded LPHNP exhibited a low toxicity profile in rats. The in-vivo pharmacokinetics study also proved a controlled delivery of cisplatin with enhanced mean residual time and half-life. Our studies suggested that the cisplatin-loaded LPHNP being a promising platform for controlled delivery of cisplatin in cancer therapy.

Keywords: cisplatin, lipid-polymer hybrid nanoparticle, chitosan, in vitro cell line study

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Authors: Shadia Al-Bahlani, Khadija Al-Bulushi, Zuweina Al-Hadidi, Buthaina Al-Dhahl, Nadia Al-Abri

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Breast cancer is the most common cancer in women worldwide. Triple-Negative Breast Cancer (TNBC) is an aggressive type of breast cancer, which is defined by the absence of Estrogen (ER), Progesterone (PR) and human epidermal growth factor (Her-2) receptors. The calpain system plays an important role in many cellular processes including apoptosis, necrosis, cell signaling and proliferation. However, the role of calpain in cisplatin (CDDP)-induced apoptosis in TNBC cells is not fully understood. Here, TNBC (MDA-MB231) cells were treated with different concentration of CDDP (0, 20 & 40 µM) and calpain activation and apoptosis were measured by western blot and Hoechst Stain respectively. In addition, calpain modulation by either activation and/or inhibition and its effect on CDDP-induced apoptosis were assessed by the same above approaches. Our findings showed that CDDP induced endoplasmic reticulum stress and thus Calcium release and subsequently activate calpain α-fodrin cleavage indicated by the increase in GRP78 and Calmodulin protein expression and respectively in MDA-MB231 cells. It also induced apoptosis as measured by Hoechst stain and caspase-12 cleavage. Calpain activation by both Cyclopiazonic acid and Thapsigargin showed similar effect and enhanced the sensitivity of these cells to CDDP treatment. On the other hand, calpain inhibition by either specific siRNA and/or exogenous inhibitor (Calpeptin) had an adverse effect where it attenuated calpain activation and thus CDDP- induced apoptosis in these cells. Altogether, these findings suggested that calpain activation play an essential role in sensitizing the TNBC cells to CDDP-induced apoptosis. This might lead to the discovery of novel treatment to over this aggressive type of breast cancer.

Keywords: calpain, cisplatin, apoptosis, breast cancer

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Authors: Vaishali D. Khairnar

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The main aim is to provide lower-latency and highly reliable communication facilities for vehicles in the automobile industry; vehicle-to-everything (V2X) communication basically intends to increase expressway road security and its effectiveness. The Ultra-Reliable Low-Latency Communications (URLLC) algorithm and cellular networks are applied in combination with Mobile Broadband (MBB). This is particularly used in express way safety-based driving applications. Expressway vehicle drivers (humans) will communicate in V2X systems using the sixth-generation (6G) communication systems which have very high-speed mobility features. As a result, we need to determine how to ensure reliable and consistent wireless communication links and improve the quality to increase channel gain, which is becoming a challenge that needs to be addressed. To overcome this challenge, we proposed a unique multi-user scheduling algorithm for ultra-massive multiple-input multiple-output (MIMO) systems using 6G. In wideband wireless network access in case of high traffic and also in medium traffic conditions, moreover offering quality-of-service (QoS) to distinct service groups with synchronized contemporaneous traffic on the highway like the Mumbai-Pune expressway becomes a critical problem. Opportunist MAC (OMAC) is a way of proposing communication across a wireless communication link that can change in space and time and might overcome the above-mentioned challenge. Therefore, a multi-user scheduling algorithm is proposed for MIMO systems using a cross-layered MAC protocol to achieve URLLC and high reliability in V2X communication.

Keywords: ultra-reliable low latency communications, vehicle-to-everything communication, multiple-input multiple-output systems, multi-user scheduling algorithm

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

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

Keywords: pluripotency, metabolomics, epigenetics, acetyl-coA

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Authors: Renata Rank Miranda, Arandi Ginane Bezerra, Ciro Alberto Oliveira Ribeiro, Marco AntôNio Ferreira Randi, Carmen Lúcia Voigt, Lilian Skytte, Kaare Lund Rasmussen, Francisco Filipak Neto, Frank Kjeldsen

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Synergetic and antagonistic effects of drugs are well-known concerns in pharmacological assessments of dose and toxicity. Similar approach should be used in assessing cellular uptake and cytotoxicity of nanoparticles. Since nanoparticles are released into the aquatic environment they may interact with existing xenobiotics. Here we used biochemical assays and quantitative proteomics to assess the cytotoxicity of silver nanoparticles (AgNP) when human hepatoma HepG2 cells were co-exposed to 2 nm AgNP together with either Cd2+ or Hg2+ ions. Time-course experiments (2h, 4h, and 24h) were conducted to assess the first response to the exposure studies. The general trend was that a synergetic toxicological response was observed in cells exposed to both AgNP and Cd2+ or Hg2+, with AgNP and Cd2+ being more toxic. This was observed by a significant increase in the ROS and superoxide level of >35% in the case of AgNP+Cd2+ compared to the sum of responses of AgNP and Cd2+, individually. Metabolic activity and viability also dropped more for AgNP+Cd2+ (>10%) than for AgNP and Cd2+ combined. We used inductively coupled plasma mass spectrometry to investigate if AgNP facilitates larger influx of toxic metal ions into HepG2 cells. Only Hg2+ ions was found to be more efficiently engulfed as the concentration of Hg2+ was found 2.8 times larger compared to exposure experiments with only Hg2+. This effect was not observed for Cd2+. We now continue with deep proteomics studies to obtain wider details on the mechanism of the toxicity related to AgNP, Cd2+, and AgNP+Cd2+, respectively.

Keywords: nanotoxicology, silver nanoparticles, proteomics, human cell line

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Authors: Yi-Hui Lai, Chih-Hsiang Yang, Li-Chung Hsu

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The inflammasome is a protein complex that modulates caspase-1 activity, resulting in proteolytic cleavage of proinflammatory cytokines such as IL-1β and IL-18, into their bioactive forms. It has been shown that the inflammasomes play a crucial role in the clearance of pathogenic infection and tissue repair. However, dysregulated inflammasome activation contributes to a wide range of human diseases such as cancers and auto-inflammatory diseases. Yet, regulation of NLRP3 inflammasome activation remains largely unknown. We discovered a novel DEAD box protein, whose biological function has not been reported, not only negatively regulates NLRP3 inflammasome activation by interfering NLRP3 inflammasome assembly and cellular localization but also mitigate pyroptosis upon pathogen evasion. The DEAD-box protein is the first DEAD-box protein gets involved in modulation of the inflammasome activation. In our study, we found that caspase-1 activation and mature IL-1β production were largely enhanced upon LPS challenge in the DEAD box-containing protein- deleted THP-1 macrophages and bone marrow-derived macrophages (BMDMs). In addition, this DEAD box-containing protein migrates from the nucleus to the cytoplasm upon LPS stimulation, which is required for its inhibitory role in NLRP3 inflammasome activation. The DEAD box-containing protein specifically interacted with the LRR motif of NLRP3 via its DEAD domain. Furthermore, due to the crucial role of the NLRP3 LRR domain in the recruitment of NLRP3 to mitochondria and binding to its adaptor ASC, we found that the interaction of NLRP3 and ASC was downregulated in the presence of the DEAD box-containing protein. In addition to the mechanical study, we also found that this DEAD box protein protects host cells from inflammasome-triggered cell death in response to broad-ranging pathogens such as Candida albicans, Streptococcus pneumoniae, etc., involved in nosocomial infections and severe fever shock. Collectively, our results suggest that this novel DEAD box molecule might be a key therapeutic strategy for various infectious diseases.

Keywords: inflammasome, inflammation, innate immunity, pyroptosis

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Authors: Gyati Shilakari Asthana, Abhay Asthana, Dharm Veer Kohli, Suresh Prasad Vyas

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Purpose: The therapeutic potential of oligonucleotide (ODN) is primarily dependent upon its safe and efficient delivery to specific cells overcoming degradation and maximizing cellular uptake in vivo. The present study is focused to design low molecular weight chitosan nanoconstructs to meet the requirements of safe and effectual delivery of ODNs. LMW-chitosan is a biodegradable, water soluble, biocompatible polymer and is useful as a non-viral vector for gene delivery due to its better stability in water. Methods: LMW chitosan ODN nanoparticles (CHODN NPs) were formulated by self-assembled method using various N/P ratios (moles ratio of amine groups of CH to phosphate moieties of ODNs; 0.5:1, 1:1, 3:1, 5:1, and 7:1) of CH to ODN. The developed CHODN NPs were evaluated with respect to gel retardation assay, particle size, zeta potential and cytotoxicity and transfection efficiency. Results: Complete complexation of CH/ODN was achieved at the charge ratio of 0.5:1 or above and CHODN NPs displayed resistance against DNase I. On increasing the N/P ratio of CH/ODN, the particle size of the NPs decreased whereas zeta potential (ZV) value increased. No significant toxicity was observed at all CH concentrations. The transfection efficiency was increased on increasing N/P ratio from 1:1 to 3:1, whereas it was decreased with further increment in N/P ratio upto 7:1. Maximum transfection of CHODN NPs with both the cell lines (Raw 267.4 cells and Hela cells) was achieved at N/P ratio of 3:1. The results suggest that transfection efficiency of CHODN NPs is dependent on N/P ratio. Conclusion: Thus the present study states that LMW chitosan nanoparticulate carriers would be acceptable choice to improve transfection efficiency in vitro as well as in vivo delivery of oligonucleotide.

Keywords: LMW-chitosan, chitosan nanoparticles, biocompatibility, cytotoxicity study, transfection efficiency, oligonucleotide

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Authors: N. Rajendra Prasad

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Resveratrol (RSV), a grape phytochemical, has drawn greater attention because of its beneficial ef-fects against cancer. However, RSV has some draw-backs such as unstabilization, poor water solubility and short biological half time, which limit the utili-zation of RSV in medicine, food and pharmaceutical industries. In this study, we have encapsulated RSV in gelatin nanoparticles (GNPs) and studied its anti-cancer efficacy in NCI-H460 lung cancer cells. SEM and DLS studies have revealed that the prepared RSV-GNPs possess spherical shape with a mean diameter of 294 nm. The successful encapsulation of RSV in GNPs has been achieved by the cross-linker glutaraldehyde probably through Schiff base reaction and hydrogen bond interaction. Spectrophotometric analysis revealed that the max-imum of 93.6% of RSV has been entrapped in GNPs. In vitro drug release kinetics indicated that there was an initial burst release followed by a slow and sustained release of RSV from GNPs. The prepared RSV-GNPs exhibited very rapid and more efficient cellular uptake than free RSV. Further, RSV-GNPs treatment showed greater antiproliferative efficacy than free RSV treatment in NCI-H460 cells. It has been found that greater ROS generation, DNA damage and apoptotic incidence in RSV-GNPs treated cells than free RSV treatment. Erythrocyte aggregation assay showed that the prepared RSV-GNPs formulation elicit no toxic response. HPLC analysis revealed that RSV-GNPs was more bioavailable and had a longer half-life than free RSV. Hence, GNPs carrier system might be a promising mode for controlled delivery and for improved therapeutic index of poorly water soluble RSV.

Keywords: resveratrol, coacervation, anticancer gelatin nanoparticles, lung cancer, controlled release

Procedia PDF Downloads 447

Authors: Rita Bagheri, Javed Ahmed, Humayra Bashir, M. Irfan Qureshi

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Agriculture lands suffer from a combination of stresses such as salinity and metal contamination including cadmium at the same time. Under such condition of multiple stresses, plant may exhibit unique responses different from the stress occurring individually. Thus, it would be interesting to investigate that how plant respond to combined stress at level of antioxidants and proteome expression, and identifying the proteins which are involved in imparting stress tolerance. With an approach of comparative proteomics and antioxidant analysis, present study investigates the response of Spinacia oleracea to salt (NaCl), cadmium (Cd), and their combination (NaCl+Cd) stress. Two-dimensional gel electrophoresis was used for resolving leaf proteome, and proteins of interest were identified using PDQuest software. A number of proteins expressed differentially, those indicated towards their roles in imparting stress tolerance, were digested by trypsin and analyzed on mass spectrometer for peptide mass fingerprinting (PMF). Data signals were then matched with protein databases using MASCOT. Results show that NaCl, Cd and both together (NaCl+Cd) induce oxidative stress which was highest in combined stress of Cd+NaCl. Correspondingly, the activities of enzymatic antioxidants viz., SOD, APX, GR and CAT, and non-enzymatic antioxidants had highest changes under combined stress compares to single stress over their respective controls. Among the identified proteins, several interesting proteins were identified that may be have role in Spinacia oleracia tolerance in individual and combinatorial stress of salt and cadmium. The functional classification of identified proteins indicates the importance and necessity of keeping higher ratio of defence and disease responsive proteins.

Keywords: Spinacia oleracea, Cd, salinity, proteomics, antioxidants, combinatorial stress

Procedia PDF Downloads 382

Authors: M. D. Asemoloye, S. G. Jonathan, A. Rafiq, O. J. Olawuyi, D. O. Adejoye

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Calmodulin is one of the intracellular calcium proteins that regulates large spectrum of enzymes and cellular functions including metabolism of cyclic nucleotides and glycogen. The potentials of calmodulin gene in fungi necessitates their genetic response and their strong cassette of enzyme secretions for pesticide degradation. Therefore, this study was carried out to investigate the ‘Transcriptomic’ response of calmodulin encoding genes in Talaromyces fungi in response to 2, 2-dichlorovinyl dimethyl phosphate (DDVP or Dichlorvos) an organophosphate pesticide and γ-Hexachlorocyclohexane (Lindane) an organochlorine pesticide. Fungi strains isolated from rhizosphere from grasses rhizosphere in pesticide polluted sites were subjected to percentage incidence test. Two most frequent fungi were further characterized using ITS gene amplification (ITS1 and ITS4 combinations), they were thereafter subjected to In-vitro DDVP and lindane tolerance tests at different concentrations. They were also screened for presence and expression of calmodulin gene (caM) using RT-PCR technique. The two Talaromyces strains had the highest incidence of 50-72% in pesticide polluted site, they were both identified as Talaromyces astroroseus asemoG and Talaromyces purpurogenum asemoN submitted in NCBI gene-bank with accession numbers KY488464 and KY488468 respectively. T. astroroseus KY488464 tolerated DDVP (1.23±0.023 cm) and lindane (1.11±0.018 cm) at 25 % concentration while T. purpurogenum KY488468 tolerated DDVP (1.33±0.061 cm) and lindane (1.54±0.077 cm) at this concentration. Calmodulin gene was detected in both strains, but RT-PCR expression of caM gene revealed at 900-1000 bp showed an under-expression of caM in T. astrorosues KY488464 but overexpressed in T. purpurogenum KY488464. Thus, the calmodulin gene response of these fungal strains to both pesticides could be considered in monitoring the potentials of fungal strains to pesticide tolerance and bioremediation of pesticide in polluted soil.

Keywords: Calmodulin gene, pesticide, RT-PCR, talaromyces, tolerance

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Authors: Gloria Pinilla, Jose Manuel Baena, Patricia Gálvez-Martín, Juan Antonio Marchad

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Cartilage is a dense connective tissue with limited self-repair properties. Currently, the therapeutic use of autologous or allogenic chondrocytes makes up an alternative therapy to the pharmacological treatment. The design of a bioprinted 3D cartilage with chondrocytes and biodegradable biomaterials offers a new therapeutic alternative able of bridging the limitations of current therapies in the field. We have developed an enhanced printing processes-Injection Volume Filling (IVF) to increase the viability and survival of the cells when working with high-temperature thermoplastics without the limitation of the scaffold geometry in contact with cells. We have demonstrated the viability of the printing process using chondrocytes for cartilage regeneration. This development will accelerate the clinical uptake of the technology and overcomes the current limitation when using thermoplastics as scaffolds. An alginate-based hydrogel combined with human chondrocytes (isolated from osteoarthritis patients) was formulated as bioink-A and the polylactic acid as bioink-B. The bioprinting process was carried out with the REGEMAT V1 bioprinter (Regemat 3D, Granada-Spain) through a IVF. The printing capacity of the bioprinting plus the viability and cell proliferation of bioprinted chondrociytes was evaluated after five weeks by confocal microscopy and Alamar Blue Assay (Biorad). Results showed that the IVF process does not decrease the cell viability of the chondrocytes during the printing process as the cells do not have contact with the thermoplastic at elevated temperatures. The viability and cellular proliferation of the bioprinted artificial 3D cartilage increased after 5 weeks. In conclusion, this study demonstrates the potential use of Regemat V1 for 3D bioprinting of cartilage and the viability of bioprinted chondrocytes in the scaffolds for application in regenerative medicine.

Keywords: cartilage regeneration, bioprinting, bioink, scaffold, chondrocyte

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Authors: Hye Kyung Kim, Myung-Gyou Kim, Kang-Hyun Leem

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The prickly pear cactus (Opuntia ficus-indica) has a global distribution and has been used for medicinal benefits such as artherosclerosis, diabetes, gastritis, and hyperglycemia. The prickly pear variety Opuntia ficus-indica var. Saboten (OFS) is widely cultivated in Cheju Island, the southwestern region of Korea, and used as a functional food. The present study investigated the effects of OFS on adipogenesis, lipolysis, glucose uptake, and glucose transporter (GLUT4) expression using preadipocyte 3T3-L1 cells. Adipogenesis was determined by preadipocyte differentiation and triglyceride accumulation assessed by Oil Red O staining. Lipolysis was determined as the rate of glycerol release. Insulin-stimulated glucose uptake and GLUT4 expression were measured using fluorescent glucose analogue, 2-NBDG, and ELISA, respectively. Quantitative real-time RT-PCR was performed to investigate the effects of OFS on the mRNA expression of peroxisome proliferator-activated receptor γ (PPARγ), a regulator of adipocyte differentiation. Ethanol extracts of OFS dose-dependently enhanced adipocyte differentiation and cellular triglyceride levels indicating the enhancement of the differentiation of preadipocytes into adipocytes. Insulin-stimulated glucose uptake and GLUT4 expression were also dose-dependently increased by OFS treatment. Furthermore, OFS treatment also increased the mRNA levels of PPARγ. These effects of OFS on adipocytes suggest that OFS is potentially beneficial for type 2 diabetes by due to its enhanced glucose uptake and balanced adipogenesis and lipolysis properties.

Keywords: 3T3-L1 preadipocyte cell, adipogenesis, GLUT4, lipolysis, Opuntia ficus-indica var. Saboten, PPARγ, prickly pear cactus

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Authors: Afifa Hafidh, Hedia Chaabane

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This work mainly focused on the synthetic strategies and biological activities associated with pyrazoles. Pyrazole derivatives have been successfully synthesized by simple and facile method and studied for their antibacterial activity. These compounds were prepared from pyrazolic difunctional compounds as starting materials, by reaction with salicylic acid, paracetamol and thiosemicarbazide respectively. Structure of all the prepared compounds confirmation were proved using (FT-IR), (1H-NMR) and (13C-NMR) spectra in addition to melting points. The screening of the antimicrobial activity of the pyrazolic derivatives was examined against different microorganisms in the present study. They were screened for their antimicrobial activities against gram positive bacteria, gram negative bacteria and Candida albicans. The synthesized compounds were found to exhibit high antibacterial and antifungal efficiency against several tested bacterial strains, using agar diffusion method and filter paper disc-diffusion method. Ampicillin was used as positive control for all strains except Candida albicans for which Nystatin was used. The obtained results reveal that the antibacterial activity of some pyrazolic derivatives is comparable to that observed for the control samples (Ampicilin and Nystatin), suggesting a strong antibacterial activity. The analysis of these results shows that synthesized products react on the surfaces cell walls that are disrupted. When these products are in contact with the bacteria, they damage the membrane, leading to the perturbation of different cellular processes and then leakage of cytoplasm, resulting in the death of the cells. The results will be presented in details. The obtained products constitute effective antibacterial agents and important compounds for biological systems.

Keywords: salicylic acid, antimicrobial activities, antioxidant activity, paracetamol, pyrazole, thiosemicarbazide

Procedia PDF Downloads 173

Authors: Ouzid Yasmina, Aiche-Iratni Ghenima, Harchaoui Lina, Saadoun Noria, Houali Karim

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Medicinal plants are an important source of bioactive molecules with biological activities such as anticancer, antioxidant, anti-inflammatory, antibacterial, antimitotic.... These molecules include alkaloids, polyphenols and terpenes. The latter can be extracted by different solvents, namely: water, ethanol, methanol, butanol, acetone... This is why it seemed interesting to us to evaluate in vitro the antimitotic and genotoxic effect of these secondary metabolites contained in the aqueous extract of the leaves of Peganum harmala L. by the Allium cepa L. test on meristematic cells by calculating the mitotic parameters (The mitotic index, the aberration index and the limit value of cytotoxicity).A spectrophotometric determination of secondary metabolites, namely alkaloids and flavonoids in the aqueous extract of this essence, was performed. As a result, the alkaloid content is estimated to be 28.42 μg EC/mg extract, and the flavonoid content is 12.52 μg EQ/mg extract. The determination of the mitotic index revealed disturbances in cell division with a highly significant difference between the negative control (distilled water) and the different samples (aqueous extracts, colchicine and quecetin). The exposure of meristematic cells to our samples resulted in a large number of chromosomal, nuclear and cellular aberrations with an aberration index reaching 16.21±1.28% for the 4mg/ml aqueous extract and 11.71±3.32% for the 10mg/ml aqueous extract. The limit value of cytotoxicity revealed that our samples are sublethal on Allium cepa L. meristematic cells.

Keywords: allium cepa l., antimitotic and genotoxic effect, aqueous leaf extract, laghouat (algeria), peganum harmala l., secondary metabolites

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Authors: S. M. M. Syairah, M. H. Rajikin, A. R. Sharaniza

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Several embryonic cellular mechanism including cell cycle, growth and apoptosis are regulated by phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway. The goal of present study is to determine the effects of annatto (Bixa orellana)-derived δ-tocotrienol (δ-TCT) on the regulations of PI3K/Akt genes in murine morula. Twenty four 6-8 week old (23-25g) female balb/c mice were randomly divided into four groups (G1-G4; n=6). Those groups were subjected to the following treatments for 7 consecutive days: G1 (control) received tocopherol stripped corn oil, G2 was given 60 mg/kg/day of δ-TCT mixture (contains 90% delta & 10% gamma isomers), G3 was given 60 mg/kg/day of pure δ-TCT (>98% purity) and G4 received 60 mg/kg/day α-TOC. On Day 8, females were superovulated with 5 IU Pregnant Mare’s Serum Gonadotropin (PMSG) for 48 hours followed with 5 IU human Chorionic Gonadotropin (hCG) before mated with males at the ratio of 1:1. Females were sacrificed by cervical dislocation for embryo collection 48 hours post-coitum. About fifty morula from each group were used in the gene expression analyses using Affymetrix QuantiGene Plex 2.0 Assay. Present data showed a significant increase (p<0.05) in the average number (mean + SEM) of morula produced in G2 (26.0 + 0.45), G3 (23.0 + 0.63) and G4 (25.0 + 0.73) compared to control group (G1 – 16.0 + 0.63). This is parallel with the high expression of PDK1 gene with increase of 2.75-fold (G2), 3.07-fold (G3) and 3.59-fold (G4) compared to G1 (1.78-fold). From the present data, it can be concluded that supplementation with δ-TCT(s) and α-TOC induced high expression of PDK1 in G2-G4 which enhanced the PI3K/Akt signaling activity, resulting in the increased number of morula.

Keywords: delta-tocotrienol, embryonic development, nicotine, vitamin E

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