Search results for: vascular cells

Authors: Karla E. Sanchez-Cazares, Kim H. Parker, Jennifer H. Tweedy

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The purpose of this work is to develop a simple compartmental model of cerebral fluid balance including blood and cerebrospinal-fluid (CSF). At the first level the cerebral arteries and veins are modelled as bifurcating trees with constant scaling factors between generations which are connected through a homogeneous microcirculation. The arteries and veins are assumed to be non-rigid and the cross-sectional area, resistance and mean pressure in each generation are determined as a function of blood volume flow rate. From the mean pressure and further assumptions about the variation of wall permeability, the transmural fluid flux can be calculated. The results suggest the next level of modelling where the cerebral vasculature is divided into three compartments; the large arteries, the small arteries, the capillaries and the veins with effective compliances and permeabilities derived from the detailed vascular model. These vascular compartments are then linked to other compartments describing the different CSF spaces, the cerebral ventricles and the subarachnoid space. This compartmental model is used to calculate the distribution of fluid in the cranium. Known volumes and flows for normal conditions are used to determine reasonable parameters for the model, which can then be used to help understand pathological behaviour and suggest clinical interventions.

Keywords: cerebrovascular, compartmental model, CSF model, vascular network

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Authors: Lanlan Xiao, Yang Liu, Shuo Chen, Bingmei Fu

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Most cancer-related deaths are due to metastasis. Metastasis is a complex, multistep processes including the detachment of cancer cells from the primary tumor and the migration to distant targeted organs through blood and/or lymphatic circulations. During hematogenous metastasis, the emigration of tumor cells from the blood stream through the vascular wall into the tissue involves arrest in the microvasculature, adhesion to the endothelial cells forming the microvessel wall and transmigration to the tissue through the endothelial barrier termed as extravasation. The narrow slit between endothelial cells that line the microvessel wall is the principal pathway for tumor cell extravasation to the surrounding tissue. To understand this crucial step for tumor hematogenous metastasis, we used Dissipative Particle Dynamics method to investigate an individual cell passing through a narrow slit numerically. The cell membrane was simulated by a spring-based network model which can separate the internal cytoplasm and surrounding fluid. The effects of the cell elasticity, cell shape and cell surface area increase, and slit size on the cell transmigration through the slit were investigated. Under a fixed driven force, the cell with higher elasticity can be elongated more and pass faster through the slit. When the slit width decreases to 2/3 of the cell diameter, the spherical cell becomes jammed despite reducing its elasticity modulus by 10 times. However, transforming the cell from a spherical to ellipsoidal shape and increasing the cell surface area only by 3% can enable the cell to pass the narrow slit. Therefore the cell shape and surface area increase play a more important role than the cell elasticity in cell passing through the narrow slit. In addition, the simulation results indicate that the cell migration velocity decreases during entry but increases during exit of the slit, which is qualitatively in agreement with the experimental observation.

Keywords: dissipative particle dynamics, deformability, surface area increase, cell migration

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Authors: Nidal H. Abu-Zahra, Aruna P. Wanninayake

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Copper Oxide (CuO) is a p-type semiconductor with a band gap energy of 1.5 eV, this is close to the ideal energy gap of 1.4 eV required for solar cells to allow good solar spectral absorption. The inherent electrical characteristics of CuO nano particles make them attractive candidates for improving the performance of polymer solar cells when incorporated into the active polymer layer. The UV-visible absorption spectra and external quantum efficiency of P3HT/PC70BM solar cells containing different weight percentages of CuO nano particles showed a clear enhancement in the photo absorption of the active layer, this increased the power conversion efficiency of the solar cells by 24% in comparison to the reference cell. The short circuit current of the reference cell was found to be 5.234 mA/cm2 and it seemed to increase to 6.484 mA/cm2 in cells containing 0.6 mg of CuO NPs; in addition the fill factor increased from 61.15% to 68.0%, showing an enhancement of 11.2%. These observations suggest that the optimum concentration of CuO nano particles was 0.6 mg in the active layer. These significant findings can be applied to design high-efficiency polymer solar cells containing inorganic nano particles.

Keywords: copper oxide nanoparticle, UV-visible spectroscopy, polymer solar cells, P3HT/PCBM

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Authors: K. Barbaro, F. Di Egidio, A. Amaddeo, G. Lupoli, S. Eramo, G. Barraco, D. Amaddeo, C. Gallottini

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In this study, we wanted to evaluate the effects of nano-hydroxy apatite (NHA) on mesenchymal stem cells extracted from subcutaneous adipose tissue of the dog. The stem cells were divided into 6 experimental groups at different concentrations of NHA. The comparison was made with a control group of stem cell grown in standard conditions without NHA. After 1 week, the cells were fixed with 10% buffered formalin for 1 hour at room temperature and stained with Giemsa, measured at the inverted optical microscope. The morphological evaluation of the control samples and those treated showed that stem cells adhere to the substrate and proliferate in the presence of nanohydroxy apatite at different concentrations showing no detectable toxic effects.

Keywords: nano-hydroxy apatite, adipose mesenchymal stem cells, dog, morphological evaluation

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Authors: Ferreira RC, Simons HZ, Thompson WS, Cutler AJ, Dopico XC, Smyth DJ, Mashar M, Schuilenburg H, Walker NM, Dunger DB, Wallace C, Todd JA, Wicker LS, Pekalski ML

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Type 1 diabetes is caused by autoimmune destruction of insulin-secreting beta cells in the pancreas. T cells are known to play an important role in this immune-mediated destruction; however, there is no general consensus regarding alterations in cytokine production or T cell subsets in peripheral blood of patients with type 1 diabetes. Using polychromatic flow cytometry of peripheral blood mononuclear cells (PBMCs), we assessed production of the proinflammatory cytokines IL-21, IFN-γ and IL-17 by memory CD4 T effector (Teff) cells in 69 patients with type 1 diabetes and 61 healthy donors. We found a 21.9% (95% CI 5.8, 40.2; p = 3.9 × 10(-3)) higher frequency of IL-21(+) CD45RA(-) memory CD4(+) Teffs in patients with type 1 diabetes (geometric mean 5.92% [95% CI 5.44, 6.44]) compared with healthy donors (geometric mean 4.88% [95% CI 4.33, 5.50]). In a separate cohort of 30 patients with type 1 diabetes and 32 healthy donors, we assessed the frequency of circulating T follicular helper (Tfh) cells in whole blood. Consistent with the increased production of IL-21, we also found a 14.9% increase in circulating Tfh cells in the patients with type 1 diabetes (95% CI 2.9, 26.9; p = 0.016). Analysis of IL-21 production by PBMCs from a subset of 46 of the 62 donors immunophenotyped for Tfh showed that frequency of Tfh cells was associated with the frequency of IL-21+ cells (r2 = 0.174, p = 0.004). These results indicate that increased IL-21 production is likely to be an aetiological factor in the pathogenesis of type 1 diabetes that could be considered as a potential therapeutic target.

Keywords: T follicular helper cell, IL-21, IL-17, type 1 diabetes

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Authors: Natasha Petrovska, Mirjana Pavlovic, Maria M. Larrondo-Petrie

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Neural stem cells (NSCs) are multi-potent, self-renewing cells that generate new neurons. Three subtypes of NSCs can be separated regarding the stages of NSC lineage: quiescent neural stem cells (qNSCs), activated neural stem cells (aNSCs) and neural progenitor cells (NPCs), but their gene expression signatures are not utterly understood yet. Single-cell examinations have started to elucidate the complex structure of NSC populations. Nevertheless, there is a lack of thorough molecular interpretation of the NSC lineage heterogeneity and an increasing need for tools to analyze and improve the efficiency and correctness of single-cell sequencing data. Feature selection and ordering can identify and classify the gene expression signatures of these subtypes and can discover novel subpopulations during the NSCs activation and differentiation processes. The aim here is to review the implementation of the feature selection technique on NSC subtypes and the classification techniques that have been used for the identification of gene expression signatures.

Keywords: feature selection, feature similarity, neural stem cells, genes, feature selection methods

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Authors: Ratna Farida Soenarto, Anas Alatas, Made Ryan Kharmayani

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Background: Conventional ultrafiltration (CUF) system was shown to be helpful in reducing anti-inflammatory mediators for patients who underwent open heart surgery. Additionally, modified ultrafiltration (MUF) has been shown to reduce anti-inflammatory mediators further while reducing interstitial fluid volume at the same time. However, there has been minimal data concerning the efficacy of combining both ultrafiltration methods. This study aims to compare inflammation marker, vascular resistance, and cardiac index on CUF+MUF patients with CUF only patients undergoing open heart surgery. Method: This is a single blind randomized controlled trial on patients undergoing open heart surgery between June 2021 - October 2021 in CiptoMangunkusumo National Referral Hospital and Jakarta Heart Hospital. Patients wererandomized using block randomization into modified ultrafiltration following conventional ultrafiltration (CUF+MUF) and conventional ultrafiltration (CUF) only. Outcome assessed in this study were 24-hoursinterleukin-6 levels, systemic vascular resistance (SVR), pulmonary vascular resistance (PVR), and cardiac index. Results: A total of 38patients were included (19 CUF+MUF and 19 CUF subjects). There was no difference in postoperative IL-6 level between groups (p > 0.05).No difference in PVR was observed between groups.Higher difference in SVR was observed in CUF+MUF group (-646 vs. -261dyn/s/cm-5, p < 0.05). Higher cardiac index was observed on CUF+MUF group (0.93 vs. 0.48, p < 0.05). Conclusion: Patients undergoing open heart surgery with modified ultrafiltration following conventional ultrafiltration had similar systemic inflammatory response and better cardiac response than those having conventional ultrafiltration.

Keywords: open-heart, CUF, MUF, SVR, PVR, IL-6

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Authors: Premkumar Vincent, Hyeok Kim, Jin-Hyuk Bae

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Organic solar cells have high potential which enables these to absorb much weaker light than 1-sun in indoor environment. They also have several practical advantages, such as flexibility, cost-advantage, and semi-transparency that can have superiority in indoor solar energy harvesting. We investigate organic solar cells based on poly(3-hexylthiophene) (P3HT) and indene-C60 bisadduct (ICBA) for indoor application while Finite Difference Time Domain (FDTD) simulations were run to find the optimized structure. This may provide the highest short-circuit current density to acquire high efficiency under indoor illumination.

Keywords: indoor solar cells, indoor light harvesting, organic solar cells, P3HT:ICBA, renewable energy

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Authors: S. Jaramillo, Y. Montoya, W. Agudelo, J. Bustamante

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Cardiovascular diseases (CVD) are related to affectations of the heart and blood vessels, within these are pathologies such as coronary or peripheral heart disease, caused by the narrowing of the vessel wall (atherosclerosis), which is related to the accumulation of Low-Density Lipoproteins (LDL) in the arterial walls that leads to a progressive reduction of the lumen of the vessel and alterations in blood perfusion. Currently, the main therapeutic strategy for this type of alteration is drug treatment with statins, which inhibit the enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), responsible for modulating the rate of cholesterol production and other isoprenoids in the mevalonate pathway. This enzyme induces the expression of LDL receptors in the liver, increasing their number on the surface of liver cells, reducing the plasma concentration of cholesterol. On the other hand, when the blood vessel presents stenosis, a surgical procedure with vascular implants is indicated, which are used to restore circulation in the arterial or venous bed. Among the materials used for the development of vascular implants are Dacron® and Teflon®, which perform the function of re-waterproofing the circulatory circuit, but due to their low biocompatibility, they do not have the ability to promote remodeling and tissue regeneration processes. Based on this, the present research proposes the development of a hydrolyzed collagen and polyethylene oxide electrospun membrane reinforced with medium and high-intensity statins, so that in future research it can favor tissue remodeling processes from its microarchitecture.

Keywords: atherosclerosis, medium and high-intensity statins, microarchitecture, electrospun membrane

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Authors: Rostika Flora, Muhammad Zulkarnain, Syokumawena

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Background: Aerobic physical exercises are recommended to keep body fit and healthy although physical exercises themselves can increase body metabolism and oxygen and can lead into tissue hypoxia. Oxygen pressure can serve as Vascular Endhothelial Growth Factor (VEGF) regulator. Hypoxia increases gene expression of VEGF through ascendant regulation of HIF-1. VEGF is involved in regulating angiogenesis process. Aerobic physical exercises can increase the concentration of VEGF in brain and enables angiogenesis process. We have investigated the influence of aerobic physical exercise to the VGEF concentration of wistar rat’s brain. Methods: This was experimental study using post test only control group design. Independent t-test was used as statistical test. The samples were twenty four wistar rat (Rattus Norvegicus) which were divided into four groups: group P1 (control group), group P2 (treatment group with once-a-week exercise), group P3 (treatment group with three time-a-week exercise), and group P4 (treatment group with seven time-a-week exercise). Group P2, P3, and P4 were treated with treadmil with speed of 20 m/minute for 30 minutes. The concentration of VEGF was determined by ELISA. Results: There was a significant increase of VEGF in treatment group compared with control one (<0.05). The maximum increase was found in group P2 (129.02±64.49) and the minimum increase was in group P4 (96.98±11.20). Conclusion: The frequency of aerobic physical exercises influenced the concentration of Vascular Endhothelial Growth Factor (VEGF) of brain tissue of Rattus Norvegicus.

Keywords: brain tissue, hypoxia, physical exercises, vascular endhothelial growth factor

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Authors: Gehan ElAkabawy

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Background: Diabetes mellitus causes severe deteriorations of almost all the organs and systems of the body, as well as significant damage to the oral cavity. The oral changes are mainly related to salivary glands dysfunction characterized by hyposalivation and xerostomia, which significantly reduce diabetic patients’ quality of life. Human dental pulp stem cells represent a promising source for cell-based therapies, owing to their easy, minimally invasive surgical access, and high proliferative capacity. It was reported that the trophic support mediated by dental pulp stem cells can rescue the functional and structural alterations of damaged salivary glands. However, potential differentiation and paracrine effects of human dental pulp stem cells in diabetic-induced parotid gland damage have not been previously investigated. Our study aimed to investigate the therapeutic effects of intravenous transplantation of human dental pulp stem cells (hDPSCs) on parotid gland injury in a rat model of streptozotocin (STZ)-induced type 1 diabetes. Methods: Thirty Sprague-Dawley male rats were randomly categorised into three groups: control, diabetic (STZ), and transplanted (STZ+hDPSCs). hDPSCs or vehicle was injected into the tail vein 7 days after STZ injection. The fasting blood glucose levels were monitored weekly. A glucose tolerance test was performed, and the parotid gland weight, salivary flow rate, oxidative stress indices, parotid gland histology, and caspase-3, vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen (PCNA) expression in parotid tissues were assessed 28 days post-transplantation. Results: Transplantation of hDPSCs downregulated blood glucose, improved the salivary flow rate, and reduced oxidative stress. The cells migrated to, survived, and differentiated into acinar, ductal, and myoepithelial cells in the STZ-injured parotid gland. Moreover, they downregulated the expression of caspase-3 and upregulated the expression of VEGF and PCNA, likely exerting pro-angiogenetic and antiapoptotic effects and promoting endogenous regeneration. In addition, the transplanted cells enhanced the parotid nitric oxide (NO) -tetrahydrobiopterin (BH4) pathway. Conclusions: Our results show that hDPSCs can migrate to and survive within the STZ-injured parotid gland, where they prevent its functional and morphological damage by restoring normal glucose levels, differentiating into parotid cell populations, and stimulating paracrine-mediated regeneration. Thus, hDPSCs may have therapeutic potential in the treatment of diabetes-induced parotid gland injury.

Keywords: dental pulp stem cells, diabetes, streptozotocin, parotid gland

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Authors: Kamila Dus-Szachniewicz, Artur Bednarkiewicz, Katarzyna Gdesz-Birula, Slawomir Drobczynski

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In modern oncology hyperthermia (HT) is defined as a controlled tumor heating. HT treatment temperatures range between 40–48 °C and can selectively damage heat-sensitive cancer cells or limit their further growth, usually with minimal injury to healthy tissues. Despite many advantages, conventional whole-body and regional hyperthermia have clinically relevant side effects, including cardiac and vascular disorders. Additionally, the lack of accessibility of deep-seated tumor sites and impaired targeting micrometastases renders HT less effective. It is believed that above disadvantages can significantly overcome by the application of biofunctionalized microparticles, which can specifically target tumor sites and become activated by an external stimulus to provide a sufficient cellular response. In our research, the unique optical tweezers system have enabled capturing the silica microparticles, primary cells and tumor spheroids in highly controllable and reproducible environment to study the impact of localized heat stimulation on normal and pathological cell and within multicellular tumor spheroid. High throughput spheroid model was introduced to better mimic the response to HT treatment on tumors in vivo. Additionally, application of local heating of tumor spheroids was performed in strictly controlled conditions resembling tumor microenvironment (temperature, pH, hypoxia, etc.), in response to localized and nonhomogeneous hyperthermia in the extracellular matrix, which promotes tumor progression and metastatic spread. The lack of precise control over these well- defined parameters in basic research leads to discrepancies in the response of tumor cells to the new treatment strategy in preclinical animal testing. The developed approach enables also sorting out subclasses of cells, which exhibit partial or total resistance to therapy, in order to understand fundamental aspects of the resistance shown by given tumor cells in response to given therapy mode and conditions. This work was funded by the National Science Centre (NCN, Poland) under grant no. UMO-2017/27/B/ST7/01255.

Keywords: cancer spheroids, hyperthermia, microparticles, optical tweezers

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Authors: Lie-Sian Yap, Ming-Chien Yang

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This study demonstrated a novel injectable hydrogel scaffold composing of Pluronic F127, carboxymethyl hexanoyl chitosan (CA) and glutaraldehyde (GA) for encapsulating human fetal osteoblastic cells (hFOB) 1.19. The hydrogel was prepared by mixing F127 and GA in CA solution at 4°C. The mechanical properties and cytotoxicity of this hydrogel were determined through rheological measurements and MTT assay, respectively. After encapsulation process, the hFOB 1.19 cells morphology was examined using fluorescent and confocal imaging. The results indicated that the Tgel of this system was around 30°C, where sol-gel transformation occurred within 90s and F127/CA/GA gel was able to remain intact in the medium for more than 1 month. In vitro cell culture assay revealed that F127/CA/GA hydrogels were non-cytotoxic. Encapsulated hFOB 1.19 cells not only showed the spherical shape and formed colonies, but also reduced their size. Moreover, the hFOB 1.19 cells showed that cells remain alive after the encapsulation process. Based on these results, these F127/CA/GA hydrogels can be used to encapsulate cells for tissue engineering applications.

Keywords: carboxymethyl hexanoyl chitosan, cell encapsulation, hFOB 1.19, Pluronic F127

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Authors: Piyaporn Buaklang, Narisa Kengtrong Bordeerat

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The use of nanoparticles is increasing worldwide and there are many nanotech-based daily products available in the market. The toxicity of nanoparticles results from their extremely small size which can be transported easily into the blood stream and other organs. We aimed to study the genotoxicity of two nanoparticles, Titanium dioxide (TiO2-NPs) and Zinc oxide (ZnO-NPs), in TK6 cells by micronucleus assay. The cells were tested at 8, 24, and 48 hours after exposed to 0.10, 0.25, 0.50 and 1.00 µg/mL of TiO2-NPs particles size < 25 nm and < 100 nm and to ZnO-NPs at 1, 10, 50, and 100 µg/mL, particles size < 50 nm and < 100 nm. At 24 hours of incubation transmission electron microscope (TEM) revealed that the nanoparticles TiO2-NPs at 1.00 µg/mL and ZnO-NPs at 10 µg/mL were able to be taken into the cells and induced the production of increasing amount of micronucleus in dose-dependent manner. The effect of the two nanoparticles on chromosome aberration indicated that TiO2-NPs and ZnO-NPs are genotoxic. In addition, the toxicity of TiO2-NPs was found to be 10 times more toxic than ZnO-NPs after 24 hours exposure. Analysis showed that the TiO2-NPs induced formation of micronucleus was both time and dose dependent, whereas the genotoxicity of ZnO-NPs was only dose dependent. In conclusion, TiO2-NPs and ZnO-NPs were able to transport through the cells membrane and directly genotoxic to TK6 cells in dose-dependent manner.

Keywords: nanoparticles, genotoxicity, human lymphoblast cells (TK6), micronucleus

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Authors: Daniel Thompson, Sophie Cerutti, Muhammad Peerbux, Hansraj Bookun

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Introduction: Diabetic nephropathy is the leading cause end stage renal failure in Australia, responsible for 36% of cases. Patients who require dialysis may be suitable for haemodialysis through an arteriovenous fistula (AVF), and preoperatively careful planning is required to select suitable vessels for a long-lasting fistula that provides suitable dialysis access. Due to high levels of vascular disease in diabetic patients, we sought to investigate whether there is a difference in the types of autologous AVFs created for diabetic patients in renal failure compared to their non-diabetic counterparts. Method: Data was collected from the Australasian Vascular Audit, for all vascular surgery completed at St. Vincent’s Hospital Melbourne between 2011-2020. Patients were selected by operative type, creation of AVF, and compared in two groups, diabetic patients and patients without diabetes. Chi-squared test was utilised to determine significance. Results: Data analysis is ongoing and will be complete with updated abstract in time for the conference. Discussion: Diabetic nephropathy is the cause for roughly a third of end stage renal failure in Australia. Diabetic patients present with a unique set of challenges when it comes to dialysis access due to increased risk of peripheral vascular disease and arterial calcification. Care must be taken in the creation of fistulas to minimise complications and increase the chance of long-lasting access. Our study investigates the difference in autologous AVFs between diabetics and non-diabetics, and results may be used to influence location of fistula creation. Further research may be used to investigate patency rates of fistulas in diabetics vs non-diabetics which would further influence treatment decisions.

Keywords: dialysis, diabetes, renal access, fistula

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Authors: Parcha Sreenivasa Rao, P. Lakshmi

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Diabetes Mellitus is metabolic disorder, characterized by high glucose levels in the blood due to one of the reason i.e., the death of β cells. The lack of β cells leads to the reduced insulin levels. The β cell death generally occurs due to apoptosis induced by the several cytokines. IL-1β, IFN- ϒ and TNF –α cytokines that are generally cause apoptosis to the β cell. The nutrient based apoptosis is generally seen with high glucose and free fatty acids. It is also noted that the β cell death triggered by Fas ligand and its receptor Fas at the surface of the activated CD8+ T- lymphocytes. Reports also reveal that the β cell apoptosis is under control of the transcription factors NF-kB and STAT- 1. The arresting or opposing of the β cell apoptosis can be overcome by the different growth factors like GLP-1, growth hormone, prolactin, VEGF, Dipeptidyl peptidase-4, Vildagliptin, suberoylanilidehydroxamic acid, trichistatin-A, XIAP, Bcl-2, FGF-21. Present investigation explains antiapoptotic property of the β cells derived from the mesenchymal stem cells of umbilical cord.

Keywords: stem cells, umblical cord, diabetes, apoptosis

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Authors: Jerome G. Chandraseelan, Samuel M. D. Oliveira, Antti Häkkinen, Sofia Startceva, Andre S. Ribeiro

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We used live E. coli containing synthetic genetic oscillators to study how the degree of synchrony between the genetic circuits of sister cells changes with temperature. We found that both the mean and the variability of the degree of synchrony between the fluorescence signals from sister cells are affected by temperature. Also, while most pairs of sister cells were found to be highly synchronous in each condition, the number of asynchronous pairs increased with increasing temperature, which was found to be due to disruptions in the oscillations. Finally we provide evidence that these disruptions tend to affect multiple generations as opposed to individual cells. These findings provide insight in how to design more robust synthetic circuits and in how cell division can affect their dynamics.

Keywords: repressilator, robustness, synchrony, synthetic biology

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Authors: Kevin Zhao, Norman J. Horing

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A methodology for cells sorting and circulating tumor cell detection and discrimination is presented in this paper. The technique is based on Dielectrophoresis and microfluidic device theory. Specifically, the sorting of the cells is realized by adjusting the relation among the sedimentation forces, the drag force provided by the fluid, and the Dielectrophortic force that is relevant to the bias voltage applied on the device. The relation leads to manipulation of the elevation of the cells of the same kind to a height by controlling the bias voltage. Once the cells have been lifted to a position next to the bottom of the cell collection channel, the buffer fluid flashes them into the cell collection channel. Repeated elevation of the cells leads to a complete sorting of the cells in the sample chamber. A proof-of-principle example is presented which verifies the feasibility of the methodology.

Keywords: cell sorter, CTC cell, detection and discrimination, dielectrophoresisords, simulation

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Authors: Kamsiah Jaarin, Yusof Kamisah, Faizah Othman Nurul Akmal Muhammad, Zakiah Jubri, Qodriyah Mohd Saad, Srijit Das

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Forty (40) normotensive adult male Sprague-Dawley rats aged three months weighing 180-200 g were divided into 4 groups with 10 rats per group: (1) normotensive control; (2) hypertensive rats; (3) hypertensive rats treated with Nigella sativa (2.5 ml/kg/day); and (4) hypertensive rats treated with nicardipine (5 mg/kg/day). After acclimatization, the hypertensive rats of the group 2, 3 and 4 were induced to be hypertensive by giving NW–nitro-L-arginine methyl ester (L-NAME; 30 mg/kg/day) in their drinking water for consecutive 7 days. After one week, rats in the group 3 were given a daily oral dose of 2.5 ml/kg/day of Nigella sativa (NS) by oral gavage. Rats in the group 4 were given nicardipine (5 mg/kg/day) via oral gavages. All rats in this study received L-NAME continuously throughout the treatment duration. The blood pressure will be measured pre-treatment and weekly for 8 weeks using power lab. Blood was taken before and at the end of study for measurement of nitric oxide. At the end of 8 weeks, the rats are sacrificed and descending thoracic aorta was disserted for measurement of vascular reactivity, and intracellular adhesion molecules (ICAM-1) and vascular cell adhesion molecules (VCAM-1). Nigella sativa reduced both systolic and diastolic BP compared to control and L-name group. The BP lowering effect of NS was comparable to nicardipine a calcium antagonist. The blood pressure lowering effect of NS was accompanied with an increasing relaxation response to nitroprusside and acetylcholine and reducing vasoconstriction response to epinephrine. L-NAME and nicardipine on the other hand, reduced plasma nitric oxide concentration. In contrast, NS increased NO concentration. However, Nigella sativa had no significant effect on aortic VCAM- 1 and ICAM-1 expression. In conclusion; Nigella sativa oil reduces both systolic and diastolic blood pressure in L-NAME treated rats. The antihypertensive effect of NS was comparable to nicardipine. The BP lowering effect may be mediated via stimulating nitric oxide release from vascular endothelium.

Keywords: Nigella sativa, ICAM, VCAM, blood pressure, vascular reactivity

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Authors: Akbar Esmaeili, Fateme Dadashi

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Bismuth can increase radiation and reduce the dose of radiotherapy. On the other hand, hyaluronic acid plays a role in healing damaged cells, and melittin has been used to destroy cancer cells. This research aims to destroy eye cancer cells and accelerate the recovery of damaged healthy cells during treatment. In this research, we used this nanoparticle, the sol-gel method. According to the optimization process that was carried out, we obtained the optimal value of the desired variables for the manufacture of nanoparticles. The advantage of doing this is reducing the amount of medicine used, as a result of reducing the number of side effects during the treatment and using melittin as an anti-eye cancer drug and the presence of hyaluronic acid to accelerate the recovery of cells, as well as coating the bismuth nanoparticle with chitosan to increase the half-life of the nanoparticle and prevent its adhesion.

Keywords: synthesis, nanoparticles, coated, cancer

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Authors: Shamill Amedot Udonwa, Phyllis S. Y. Chong, Lim S. L. Julia, Wee-Joo Chng

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In this paper, we investigated how PRL-3 expression in H929 and U266 cells affects the efficacy of drug treatment. H929 and U266 cells were treated with Bortezomib (BTZ) of different concentrations, and it was observed that H929 cells were resistant to BTZ, while U266 cells were not viable. Investigations into how BTZ targets these cells were conducted, and it was observed that BTZ affects the PARP-Caspase3 pathway as well as PRL-3-Leo1 pathways. These pathways regulate cell proliferation and cell cycle, respectively. Hence, we are able to show the mechanism of how BTZ affects cells and also the role PRL-3 plays on downstream oncogenes such as cyclin-D1 and c-MYC. More importantly, this investigation into PRL-3 in BTZ resistance will be highly applicable in the future as the first clinical trials of PRL-3 antibody (PRL3-zumab) are ongoing at the National University Hospital, Singapore (NUHS). This would mean that understanding the mechanism of resistance through PRL-3, which has yet to be studied, will demonstrate the potential of PRL-3 in developing novel strategies to improve the treatment of MM.

Keywords: drug resistance, hematology, multiple myeloma, oncogene

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Authors: Nurul Amziah Md Yunus, Izhal Abdul Halin, Nasri Sulaiman, Noor Faezah Ismail, Nik Hasniza Nik Aman

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Nanotechnology has become the world attention in various applications including the solar cells devices due to the uniqueness and benefits of achieving low cost and better performances of devices. Recently, thin film solar cells such as cadmium telluride (CdTe), copper-indium-gallium-diSelenide (CIGS), copper-zinc-tin-sulphide (CZTS), and dye-sensitized solar cells (DSSC) enhanced by nanotechnology have attracted much attention. Thus, a compilation of nanotechnology devices giving the progress in the solar cells has been presented. It is much related to nanoparticles or nanocrystallines, carbon nanotubes, and nanowires or nanorods structures.

Keywords: nanotechnology, nanocrystalline, nanowires, carbon nanotubes, nanorods, thin film solar cells

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Authors: Ramin Amirmardfar

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Throughout Necessary oxygen should be supplied for all cells of a mammal at any moment through blood to make it possible remain alive all cells the mammal’s body. In case a mammal’s bulk is large, there is a farther distance between cells in different tissues and mammals’ heart. Therefore red blood cells in bulky mammal’s body should be capable of conveying oxygen to farther distances. To make it practical, oxygen should be glued red blood cells tenaciously. In other words, cohesion strength of oxygen to red blood cell of bulky mammal’s blood should be much more than the same of small mammal’s blood. In mammal’s bodies, the controlling factor of amount of cohesion of oxygen to red blood cell, are organic phosphates (like DPG). The less DPG in red blood cells of a mammal, the more cohesion of oxygen to red blood cell (at the same rate). As much as oxygen is glued more tenacious to red blood cells, oxygen could been carried to farther distance and as much as oxygen could be conveyed to farther points of heart, bulk of mammal could be larger at the same rate.

Keywords: mammals size, animals size, organic phosphates, DPG, red blood cell, metabolism

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Authors: A. N. Gornostaeva, P. I. Bobyleva, E. R. Andreeva, L. B. Buravkova

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Multipotent mesenchymal stromal cells (MSCs) possess immunomodulatory properties. The effect of MSCs on the crucial cellular immunity compartment – T-cells is of a special interest. It is known that MSC tissue niche and expected milieu of their interaction with T- cells are characterized by low oxygen concentration, whereas the in vitro experiments usually are carried out at a much higher ambient oxygen (20%). We firstly evaluated immunomodulatory effects of MSCs on T-cells at tissue-related oxygen (5%) after interaction implied cell-to-cell contacts and paracrine factors only. It turned out that MSCs under reduced oxygen can effectively suppress the activation and proliferation of PHA-stimulated T-cells and can provoke decrease in the production of proinflammatory and increase in anti-inflammatory cytokines. In hypoxia some effects were amplified (inhibition of proliferation, anti-inflammatory cytokine profile shift). This impact was more evident after direct cell-to-cell interaction; lack of intercellular contacts could revoke the potentiating effect of hypoxia.

Keywords: MSCs, T-cells, activation, low oxygen, cell-to-cell interaction, immunosuppression

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Authors: Steven Robinson, Adriana Dager, Param Patel

Abstract:

Wandering spleen is a rare variant where there is abnormal development of the ligamentous peritoneal attachments of the spleen which normally anchor it in the left upper quadrant of the abdomen. Ligamentous abnormalities can be congenital, or acquired through pregnancy, injury, or iatrogenic causes. Absence or laxity of these ligaments allows migration of the spleen into ectopic portions of the abdomen, which is also associated with an elongated vascular pedicle. Incidence of wandering spleen is reported at less than 0.25% with a female to male ratio of approximately 6:1. The most common complication of a wandering spleen is torsion around its vascular pedicle which can lead to thrombosis and infarction. Torsion of a wandering spleen is a rare but important cause of an acute abdomen. Imaging, and specifically CT or ultrasound, is crucial in the diagnosis. We present a case of a torsed wandering spleen which was treated with splenectomy.

Keywords: Wandering Spleen, Torsion, Splenic Torsion, Spleen

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Authors: Emílie Kučerová, Tereza Veverková, Marina Morozovová, Eva Kudová, Jitka Viktorová

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The blood-brain barrier (BBB) is a key element regulating the transport of substances between the blood and the central nervous system (CNS). The BBB protects the CNS from potentially harmful substances and maintains a suitable environment for nervous activity in the CNS, but at the same time, it represents a significant obstacle to the entry of drugs into the CNS. Pharmacoresistant epilepsy is a form of epilepsy that cannot be suppressed using two (or more) appropriately chosen antiepileptic drugs. In many cases, pharmacoresistant epilepsy is characterized by an increased concentration of efflux pumps on the luminal sides of the endothelial cells that form the BBB and an increased number of drug-metabolizing enzymes in the BBB cells, thereby preventing the effective transport of antiepileptic drugs into the CNS. Currently, a number of scientific groups are focusing on the preparation and improvement of BBB models in vitro in order to study cell interactions or transport mechanisms. However, in pathological conditions such as pharmacoresistant epilepsy, there are changes in BBB structure, and current BBB models are insufficient for related research. Our goal is to develop a suitable BBB model for pharmacoresistant epilepsy in vitro and use it to test the transfer of potential antiepileptic drugs. This model is created by co-culturing immortalized human cerebral microvascular endothelial cells, human vascular pericytes and immortalized human astrocytes. The BBB in vitro is cultivated in the form of a 2D transwell model and the integrity of the barrier is verified by measuring transendothelial electrical resistance (TEER). From the current results, a contact cell arrangement with the cultivation of endothelial cells on the upper side of the insert and the co-cultivation of astrocytes and pericytes on the lower side of the insert is selected as the most promising for BBB model cultivation. The pharmacoresistance of the BBB model is achieved by long-term cultivation of endothelial cells in an increasing concentration of selected antiepileptic drugs, which should lead to increased production of efflux pumps and drug-metabolizing enzymes. The pharmacoresistant BBB model in vitro will be further used for the screening of substances that could act both as antiepileptics and at the same time as inhibitors of efflux pumps in endothelial cells. This project was supported by the Technology Agency of the Czech Republic (TACR), Personalized Medicine: Translational research towards biomedical applications, No. TN02000109 and by the Academy of Sciences of the Czech Republic (AS CR) – grant RVO 61388963.

Keywords: antiepileptic drugs, blood-brain barrier, efflux transporters, pharmacoresistance

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Authors: Kyungbae Pi, Kibeom Lee, Yongil Kim, Eun-Jung Lee

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Abnormal adipocyte growth, in terms of increased cell numbers and increased cell differentiation, is considered to be a major pathological feature of obesity. Thus, the inhibition of preadipocyte mitogenesis and differentiation could help prevent and suppress obesity. The aim of this study was to assess whether extracts from Weissella koreensis 521 cells isolated from kimchi could exert anti-adipogenic effects in 3T3-L1 cells (fat cells). Differentiating 3T3-L1 cells were treated with W. koreensis 521 cell extracts (W. koreensis 521_CE), and cell viability was assessed by MTT assays. At concentrations below 0.2 mg/ml, W. koreensis 521_CE did not exert any cytotoxic effect in 3T3-L1 cells. However, treatment with W. koreensis 521_CE significantly inhibited adipocyte differentiation, as assessed by morphological analysis and Oil Red O staining of fat. W. koreensis 521_CE treatment (0.2 mg/ml) also reduced lipid accumulation by 24% in fully differentiated 3T3-L1 adipocytes. These findings collectively indicate that Weissella koreensis 521 may help prevent obesity.

Keywords: Weissella koreensis 521, 3T3-L1 cells, adipocyte differentiation, obesity

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Authors: Daphne Meza, Louie Abejar, David A. Rubenstein, Wei Yin

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Endothelial cell (ECs) morphology and function is highly impacted by the mechanical stresses these cells experience in vivo. Any change in the mechanical environment can trigger pathological EC responses. A detailed understanding of EC morphological response and function upon subjection to individual and simultaneous mechanical stimuli is needed for advancement in mechanobiology and preventive medicine. To investigate this, a programmable device capable of simultaneously applying physiological fluid shear stress (FSS) and cyclic strain (CS) has been developed, characterized and validated. Its validation was performed both experimentally, through tracer tracking, and theoretically, through the use of a computational fluid dynamics model. The effectiveness of the device was evaluated through EC morphology changes under mechanical loading conditions. Changes in cell morphology were evaluated through: cell and nucleus elongation, cell alignment and junctional actin production. The results demonstrated that the combined FSS-CS stimulation induced visible changes in EC morphology. Upon simultaneous fluid shear stress and biaxial tensile strain stimulation, cells were elongated and generally aligned with the flow direction, with stress fibers highlighted along the cell junctions. The concurrent stimulation from shear stress and biaxial cyclic stretch led to a significant increase in cell elongation compared to untreated cells. This, however, was significantly lower than that induced by shear stress alone, indicating that the biaxial tensile strain may counteract the elongating effect of shear stress to maintain the shape of ECs. A similar trend was seen in alignment, where the alignment induced by the concurrent application of shear stress and cyclic stretch fell in between that induced by shear stress and tensile stretch alone, indicating the opposite role shear stress and tensile strain may play in cell alignment. Junctional actin accumulation was increased upon shear stress alone or simultaneously with tensile stretch. Tensile stretch alone did not change junctional actin accumulation, indicating the dominant role of shear stress in damaging EC junctions. These results demonstrate that the shearing-stretching device is capable of applying well characterized dynamic shear stress and tensile strain to cultured ECs. Using this device, EC response to altered mechanical environment in vivo can be characterized in vitro.

Keywords: cyclic stretch, endothelial cells, fluid shear stress, vascular biology

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Authors: Anjali Roy, Mirza S. Baig

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Atherosclerosis is a chronic inflammatory disease characterized by the formation of lipid rich plaque enriched with necrotic core, modified lipid accumulation, smooth muscle cells, endothelial cells, leucocytes and macrophages. Macrophage foam cells play a critical role in the occurrence and development of inflammatory atherosclerotic plaque. Foam cells are the fat-laden macrophages in the initial stage atherosclerotic lesion formation. Foam cells are an indication of plaque build-up, or atherosclerosis, which is commonly associated with increased risk of heart attack and stroke as a result of arterial narrowing and hardening. The mechanisms that drive atherosclerotic plaque progression remain largely unknown. Dissecting the molecular mechanism involved in process of macrophage foam cell formation will help to develop therapeutic interventions for atherosclerosis. To investigate the mechanism, we studied the role of nitric oxide synthase 1(NOS1)-mediated nitric oxide (NO) on low-density lipoprotein (LDL) uptake by bone marrow derived macrophages (BMDM). Using confocal microscopy, we found that incubation of macrophages with NOS1 inhibitor, TRIM (1-(2-Trifluoromethylphenyl) imidazole) or L-NAME (N omega-nitro-L-arginine methyl ester) prior to LDL treatment significantly reduces the LDL uptake by BMDM. Further, addition of NO donor (DEA NONOate) in NOS1 inhibitor treated macrophages recovers the LDL uptake. Our data strongly suggest that NOS1 derived NO regulates LDL uptake by macrophages and foam cell formation. Moreover, we also checked proinflammatory cytokine mRNA expression through real time PCR in BMDM treated with LDL and copper oxidized LDL (OxLDL) in presences and absences of inhibitor. Normal LDL does not evoke cytokine expression whereas OxLDL induced proinflammatory cytokine expression which significantly reduced in presences of NOS1 inhibitor. Rapid NOS-1-derived NO and its stable derivative formation act as signaling agents for inducible NOS-2 expression in endothelial cells, leading to endothelial vascular wall lining disruption and dysfunctioning. This study highlights the role of NOS1 as critical players of foam cell formation and would reveal much about the key molecular proteins involved in atherosclerosis. Thus, targeting NOS1 would be a useful strategy in reducing LDL uptake by macrophages at early stage of disease and hence dampening the atherosclerosis progression.

Keywords: atherosclerosis, NOS1, inflammation, oxidized LDL

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Authors: Dara Kutsyk, Olga Bondarenko, Mariya Sorochka

Abstract:

In 21-century type 2 diabetes (T2D) has become a global health and social problem in the whole world. The goal of treatment for patients with T2D is to prevent complications of diabetes - macrovascular diseases (heart disease, stroke, and peripheral vascular disease) and microvascular diseases (retinopathy, neuropathy and nephropathy). Nitric oxide (NO) plays an important role in maintaining vascular homeostasis. Loss of NO function is one of the earliest indicators of disease and its progression especially in patients with T2D. Aim: To compare NO level between patients with well and bad controlled glycemia in T2D. Methods: The study included 32 patients with T2D. The diagnosis of T2D was confirmed due to International Diabetes Federation (IDF) criteria 2015. Patients were divided into two groups: with well controlled glycaemia (HbA1c < 7%) and bad controlled glycaemia (HbA1c > 7%). The control group consists of 15 healthy subjects. Results: NO level in patients with T2D is significantly higher (27,2 ±3,1 µmol), compared to controls (18,86±0,9 µmol; p < 0,001). A significant difference in NO level was found between patients with bad controlled glycaemia (25,9±2,2 µmol) and well controlled glycaemia (28,7 ± 3,0 µmol; p<0,01). The study showed a moderate negative correlation between NO level and HbA1c (-0,399; р< 0,05). Conclusions: Production of NO is impaired in patients with T2D, especially with badly controlled glycaemia. With the increase in HbAc serum NO decreases. This can be the main target for prevention vascular complication in T2D.

Keywords: type 2 diabetes, glycated hemoglobin, nitric oxide, Diabetes mellitus

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